Mo
heart-breaking star candidates also get the job
Jiang had been eliminated
test for three years with Tang Wei
Zhao sleepwalk
The annual Arts test
drama staged as scheduled, those carries into the North Star Dream shadow gate to take the exam in the play the children are undergoing a rigorous test after another. A few days ago, the Beijing Film Academy re-examination was announced 2556 candidates were eliminated in the second interview that does not appear on the list of candidates who tears the scene impressive. In fact, those big stars took part in the exams is not easy, a lot of stars when the examination is not smooth, and even some stars are only admitted to the examination of several years. Candidates need not be eliminated too sad, and then proceed to pack his mind, perhaps the next king.
arbitrary than the ability to have forgetten not
this year to compete with Beijing Film 学院表演系 4392 30 places, out of more than 99%, a record high of nearly five years, to battle through ranks, candidates must have some attractions, knowledge, Reiki, ability, like Less.
Jiang Qinqin scores first
Since it is a test, then the results should always be ranked first. Membership beauty Jiang Qinqin Chongqing contact with performing since childhood, 10 years old admitted to art school to learn Peking Opera in Chongqing, graduated from art school and then into the Peking Opera Troupe of Chongqing in 1992, 17-year-old Jiang Qinqin taken part in a Chongqing TV drama Guanyin, In 1994, the 19-year-old Jiang Qinqin apply for the Beijing Film Academy, Scores first in the country. Jiang Qinqin the case last year admitted to the Beijing Film Studio, Yang Zi, Zhang Yishan, this year's candidates weeks winter rain, similar to Wang Shasha, are first, the basis for entry to the show system performance. With this foundation is very important, can be mixed a Lianshu, but the key will be significantly reduced tension, easy to normal play.
Zhang Ziyi
reading forgetten
Zhang Ziyi who will always have is placing shares fearless children, as early as a student has been revealed. In 1996, the 17-year-old Zhang Ziyi as tired of practicing dance of life, decided to apply for professional performances, and the year before in the video game than the North entrance, so that Zhang Ziyi to set foot on the performing arts this way. Zhang Ziyi at the first test interview recited a song called second half, did not think Zhang Ziyi is very calm and said the words, The examination room to ensure the normal functioning of the primary conditions for good results, even when unexpected situations, but also such as Zhang Ziyi unruffled, confident, calm, with the ability, whether the examination room, the workplace or the international arena, are naturally invincible.
get the job do not give up than the persistence
mighty force in single, perseverance is a major factor beyond that, those who cry because they are out to candidates who should learn from the older generation, performing test system two or three times before the door into the great artist someone. And into the entertainment industry does not mean to be a star, mixed crew, but unfortunately still a long day.
test for three years with Tang Wei
pay attention to well-known contemporary entertainment as early as possible, but Tang Wei in 2007 with Tang Wei, who sit in the theater did not even test in two years, until in 2000 she was admitted to the Department of play when the director is already a 21-year-old Tang Wei, after graduating from high school in Hangzhou, Training received while training in film and television, and then came to Beijing to prepare comprehensive examinations play. To test review, Tang Wei rented a cottage in the next game, helped by friends only can afford to pay rent. Jiang Qinqin popular film and television at that time, Chen Derong type of beauty, temperament and unique soup only some far away from the public standards of beauty, for several years fallen off. Tang Wei adjust the concept of the third year, the director, Department of applicants before they get it.
Jiang had been eliminated
1979 years, after graduating from high school, applied for the Beijing Film Academy, Jiang Wen, he was out, sent the letter in encouraged him The next year, Jiang Wen has applied for the performances in the theater department, physical teacher and vocal teacher feel that he just passable in both areas, but there may be a place created to barely give a passing mark. Zhang Ren in the acting class the teacher was responsible for the recruitment of teachers, he strongly advocated to Jiang to stay. When Jiang recited the exam because of some Chekhov's Zhang that the actors, the other can make up for the shortcomings, but the humor can only rely on that. Jiang was in the theater department perform the youngest 80 classes a, Liping classmates there, Cong Shan, etc., but Jiang is one of the best results.
stupid people than luck from me
ability and perseverance, the high and low test scores and luck has a delicate relationship. There are always thousands of individual candidates who, fortunately, the door inexplicably rushed him to open. However, luck is only temporary, since they must depend on hard work.
Zhao sleepwalk
1996, the Beijing Film 学院表演系 Zhao Wei candidates, the examination room examination made taboo, lost ticket. Staff informed the examiner Cuixin Qin, Cui Zhao teacher mercilessly directly to leave. Rotation candidates in the examination room space, Cui Xinqin teachers to rest in the corridor, the corridor outside the examination room to see the side is sitting crying Zhao Wei, before we know this is the girl that lost ticket, and Zhao Wei pair of watery eyes suddenly moved Cui teacher. Cui then the Office of the teacher in charge of finding candidates who re-submit the request for the ticket Zhao Wei, in her repeated plea, the office responsible for personnel agreed to make an exception. Zhao Wei opportunity to regain test particularly well in the exam easily into the final
Yapeng unintentional
Yapeng stories are very classical play the comprehensive examinations. First test is a talent show, the teacher asked him to sing, play a comedy, a story, the result of a Yapeng said he will not, he is to accompany a friend to the exam. Teacher was furious that he ignored the examination rules. Yapeng to quickly sang Still vain forty-six Yapeng second interview, the teacher asked him if he know anything about sheet music, Yapeng readily say Wait until the teacher sat down to prepare for his piano accompaniment, the Yapeng changed to say Interview, the teacher asked him know anything about chess, went so far as to ask the teacher did not expect Yapeng, The teacher said do not know, Yapeng retorted,
The most important features than looks
If one that looks first test will be eliminated in 2500 there must be more than two people is much prettier than this girl. Although the general system of professional performing different, but the standard three face court five admissions system has never been the highest standards of performance.
Gong Li
bad teeth
1983 years, Gong Li graduated from high school, apply for Shandong Normal University, Qufu Normal University Art Department and Art Department successive defeat. Gong Li and apply for one year after the Art Department of Shandong College of Art and Art 学院表演系 Liberation Army, also lost out. After losing four times four tests, Gong Li by a friend, find the Jinan Military Region Song and Dance Ensemble Directed by avant-garde in Iraq much, much in Iraq help and encouragement, applied for the Central Academy of Drama. Gong Li in 1985, played in the examination room, a comedy show, However, Gong Li, a teacher found a Huya examiners, and examiners that the teeth can be sharp, Gong Li was actually pulled out the two eye teeth behind to retain the front. However, the cultural achievements and Gong Li, a difference of 11 points in the game, and ultimately the Ministry of Culture Arts Education Department through a special approval, an exception was in the theater admission.
Honglei body fat
Honglei spur of the moment decision to apply the current game, before the examination at the recommendation of the villagers saw the show Head of the Department, but was told At that time only a month away from the entrance, Honglei did not give up hope, diet and exercise, he just 31 days before the exam by 36 pounds. At that time, and other popular game show series Enrollment has been completed, leaving only less popular musical profession. Participate in performing the examination, the examiner asked the two people know each other temporarily play up, Honglei be arranged and a girl play up to the girl look just beautiful, just do not take the show. Did not expect the end of the examination, the examiner suddenly asked Honglei again. After the change a partner in the next 10 minutes performance time, the laughter. Honglei 25-year-old entered in the final game of the door.
Morning News reporter Wang Lin
Monday, February 28, 2011
Sunday, February 27, 2011
Pneumoperitoneum on what the implications of the body
Laparoscopic surgery is used most of pneumoperitoneum, abdominal swelling most commonly used medium is the C02, for those determined to pulmonary insufficiency, but also the use of helium (He) did abdominal swelling medium. Pneumoperitoneum low complication rate and serious level, in addition to the patient's own state, but also with the level of abdominal pressure gas, gas type, duration of pneumoperitoneum vary asked.
compartment syndrome refers to a limited dissection chamber volume, pressure, increased so that the chamber after the occurrence of tissues and organs of blood circulation disorder, and thus of functional and organic damage to a group of syndromes. is the most common clinical limb bone fascia compartment syndrome. peritoneal cavity as a separate room, under pressure in the pneumoperitoneum can occur that change the same.
normal intra-abdominal pressure and atmospheric pressure similar to the contents of any form of abdominal volume increase, can cause increased intra-abdominal pressure, the formation of abdominal compartment syndrome ( abdominal compartment syndrome, ACS), the most vulnerable organ system affected the cardiovascular system, respiratory system and kidneys, mainly as increased peripheral vascular resistance, reduced cardiac output, increased airway resistance, lung compliance, or even anoxia . peritoneal pathological changes than after decompression can often be reversed quickly, but are not limited to sexual ACS can cause fatal organ failure.
gas abdominal laparoscopic surgery in the automatic regulation of pneumoperitoneum and under strict monitoring of patients is rarely formed in the ACS, but the adaptive ability to regulate the body reduction for elderly patients or liver and kidney dysfunction associated with cardiopulmonary patients, laparoscopy in abdominal pressure to take the gas as low as possible is highly benefits.
a subcutaneous emphysema and gas embolism
(a) of the subcutaneous emphysema subcutaneous emphysema
the exact incidence and cause of the unknown. Kunming General Hospital, where the author of more than 8,000 cases of LC CCP appeared in 23 cases, were associated with significant hypercapnia, but all patients are closely monitored in the completion of surgery. retrospective analysis of these 23 patients during surgery and found that the following factors and subcutaneous emphysema occurrence of obvious relevance: ① the location of improper Veress needle to establish pneumoperitoneum gas was injected into the extraperitoneal space; ② casing surrounding the abdominal cavity into the subcutaneous tissue through C02; ③ repeated puncture needle or tube taper off the original puncture site, created in the abdominal wall to form multiple channel, C02 enter the skin through Chong Road; ④ with expander expansion of puncture or other methods (such as check except when the gallbladder), the abdominal wall and the casing of the reduction between the closed, gas from the the gap between the abdominal wall and the casing to the subcutaneous tissue diffusion; ⑤ intra-abdominal pressure is increased when the potential closure of the inguinal canal does not pass, the gas can leak into the subcutaneous tissue from the abdomen.
severe and widespread oppression of thoracic subcutaneous emphysema may be and upper respiratory tract, the lung compliance, increased airway resistance, severe hypoxemia or produce C02 accumulation. on the cardiovascular system can be expressed as emphysema local vascular compression, the late decline in emissions can be developed Zhixin , central venous pressure, mean arterial pressure and heart rate changes are also frequent.
mild subcutaneous emphysema little effect on the body, do not need special treatment. a serious and extensive subcutaneous emphysema because of the negative of cardiopulmonary effects must be closely monitored to do surgery, especially when patients are determined to pulmonary insufficiency. appropriate to reduce the intra-abdominal pressure, the anesthesiologist uses hyperventilation to poke holes at Extruded emphysema, all help to reduce the adverse emphysema effect and slow the spread of emphysema. difficult to correct because of subcutaneous emphysema caused by heart and lung function changes or hypercapnia, should be converted to open surgery, but this is rare.
an interesting phenomenon: the author subcutaneous emphysema, 23 cases occurred in the early cases, nearly 4,000 cases of post-LC has not been to see subcutaneous emphysema. As mentioned above caused by subcutaneous emphysema in a number of related factors can not be in nearly 4,000 cases of LC does not appear This can not help but gives rise to the following questions: whether the production of subcutaneous emphysema and some unknown other factors.
(b)
gas embolism gas embolism (hereinafter referred to as air embolism) is a rare complication of pneumoperitoneum , but its consequences are very serious, usually fatal. embolism may be the site of the right atrium, pulmonary artery, to a rare coronary and cerebral arteries. The exact incidence of air embolism can not be estimated, Cottin reported that a group of 1994 cases of laparoscopic surgery, air embolism occurred in 2 cases and lead to patient death, which is the highest known incidence of a group. inflatable gas species and the formation of air embolism should have between the exact probability of relevance. C02 As a high solubility of gases, as long as not a lot in a short time into the blood vessels, the possibility of the formation of air embolism is small. such as the use of helium inflated, because of its low solubility, only very small amount into the blood vessels, which the formation of air embolism can be fatal, it has been confirmed by experiments.
to the current lack of actual laparoscopic surgery carried out against the background of the formation mechanism of air embolism experimental study, suggesting the formation of the following ways: ① pneumoperitoneum strayed into the abdominal vein needle, large amounts of gas directly into the blood within a short time; ② tissue wound separation fracture or broken veins on a high-pressure gas into the portal circulation; ③ the gas dissolved in the blood as could be, like decompression sickness the formation of bubbles, is not yet certain.
the literature of many prevention of air embolism and intraoperative monitoring methods to do a lot of discussion, but the incidence of air embolism is very low, making it difficult to apply these measures in routine clinical patients, but the incidence of air embolism is unpredictable and almost impossible to determine so-called air embolism monitoring, preventive measures, in the present not much practical significance.
meaningful, perhaps, is how the existing emergency air embolism. The existing methods include: ① the immediate lifting of pneumoperitoneum, stop source of air embolism; ② left lateral position so that gas is not easy to enter the right ventricle; ③ rapid central venous catheter sucked out of the right atrium and right ventricle and pulmonary artery bubbles; ④ possible emergency air bubbles out of direct puncture of right atrium; ⑤ inhalation of pure Oxygen; ⑥ breathing underwent cardiac arrest cardiopulmonary resuscitation; ⑦ hyperbaric oxygen therapy.
Second, hypercapnia and respiratory acidosis
C02 pneumoperitoneum laparoscopic surgery can cause hypercapnia and respiratory acidosis, and this phenomenon has long been recognized by the industry, but mainly limited to the previous diagnostic laparoscopy and gynecological minor such do not seem to highlight the issue. With the significance.
study shows that: the intra-abdominal pressure associated with pneumoperitoneum may limit diaphragmatic movement, leading to reduced lung and possible tidal CO2 retention, and the resulting increase in P C02 can be caused by positive cardiac inotropic effect and the surrounding enhanced vasoconstriction. by supporting muscle relaxant drugs and positive pressure breathing intervention, a way to overcome the pneumoperitoneum on the impact of lung ventilation, the ventilation will not be any significant decline and the increase of P C02.
C02 pneumoperitoneum state whether there hypercapnia, respiratory acidosis often associated with the following factors:
1. pneumoperitoneum Ishizaki experiments showed that the pneumoperitoneum pressure 16mmHg or more, for 1 hour after pneumoperitoneum cardiac output that is significantly decreased peripheral vascular resistance increased significantly; intra-abdominal pressure in the 8 mmHg ~ 12 mmHg, the above changes is not obvious. intra-abdominal pressure is increased to the C02 has increased the dispersion of blood, if the additional decrease in cardiac output, and increased peripheral vascular resistance, the retention of blood in the C02 will be more obvious.
2. pneumoperitoneum Leighton found that the gas of choice: C02 pneumoperitoneum can produce respiratory acidosis animals, He does not have this pneumoperitoneum phenomenon. In addition, C02 absorption and tissue perfusion related to the time of hemorrhagic shock is often more severe hypercapnia.
3. pneumoperitoneum asked the length of the longer duration of pneumoperitoneum, peritoneal absorption of the C02 is also more.
4. subcutaneous emphysema and pneumothorax occurred in laparoscopic surgery such as subcutaneous emphysema or pneumothorax, often accompanied by more pronounced hypercapnia and acidosis.
5. anesthetic effects such as the former above, when the pneumoperitoneum laparoscopic surgery to muscle relaxants and positive pressure breathing supplementary intervention, it would be a way to correct or block the pneumoperitoneum on the impact of lung ventilation.
6. the body of the cardiopulmonary Wittgen compensatory ability of functional results have been widely cited. The study found that: LC preoperative patients with normal cardiopulmonary function can be well tolerated without the occurrence of C02 pneumoperitoneum and hypercapnia and acidosis; and cardiopulmonary dysfunction LC patients are prone to difficult surgery to correct the respiratory acidosis. of the result that: arterial blood gas analysis is pneumoperitoneum laparoscopic surgery better means of monitoring, and preoperative blood gas analysis and cardiopulmonary function assessment should be made to adapt LC Choose one of the screening criteria permit.
for the prevention of laparoscopic intraoperative hypercapnia and respiratory acidosis, in addition to preoperative surgical indication to grasp, but also during the operation proper monitoring, understanding pulse rate , oxygen saturation, pulmonary ventilation, airway pressure, blood gas analysis, PET C02 and other indicators of real change. in the event of hypercapnia, hyperventilation viable product from the body retention of C02, but the speed can not be too quickly, Otherwise, hypercapnia has been adapted to the respiratory, circulatory central hypercapnia due to sudden loss of stimulation, there will be the so-called and the sharp drop in blood pressure caused by coronary artery contraction and respiratory depression. a heavier degree of retention of C02 should be the end of surgery as soon as possible, completely eliminate the residual intra-abdominal C02, appropriate application of basic drugs. that can not correct the hypercapnia and respiratory acidosis, and must be converted to laparotomy.
three
shoulder pain shoulder pain after laparoscopic surgery is a very common symptom, its incidence can be as high as 35% to 60%. on the LC patients, even After becoming the most common but one of the major complaints. This symptom may be the incentive for intra-abdominal residual C02 caused by phrenic nerve stimulation, was noted when the patient semi-recumbent position to take the pain when the shoulder is often increased. If the above suggested the establishment of the net emission of surgery should be able to reduce the intra-abdominal postoperative C02 of shoulder pain, but unfortunately the practice is not entirely the case. on postoperative severe symptoms, can be symptomatic with salicylic acid drugs. Narchi Randomized comparative study: intraoperative use in the liver of local anesthetic diaphragm can significantly reduce postoperative shoulder pain patients.
four, arrhythmia
pneumoperitoneum state arrhythmia is not uncommon, but its exact The reason remains unclear, in addition to the surgeon's own state outside the pneumoperitoneum should also be an important incentive. have found that arrhythmia-prone of the pneumoperitoneum established in the initial period, and concluded that the establishment of the initial arrhythmia and pneumoperitoneum When the amount of traffic on C02. Whether or not this view is correct, considering the body's ability to adapt to the various organ systems, the timing of mobilization, then the establishment of pneumoperitoneum to low flow began, and then gradually increase to high traffic and high traffic maintain intraoperative pneumoperitoneum should be a principle must be followed. In addition, that the temperature of the C02 pneumoperitoneum also contributed to the possible causes of arrhythmia.
five, deep venous congestion and thrombosis
DVT is common complications after surgery. literature, more than 40 years of age are not common prophylactic anticoagulant treatment in patients after surgery, about 25% of the occurrence of DVT. vein angiography in patients after open cholecystectomy about 7% l0%, there may be DVT, pulmonary embolism rate of 0.4% to 0.7%. With 70% of DVT patients had no clinical manifestations, so the true incidence of DVT after surgery is difficult to estimate. laparoscopic surgery due to pneumoperitoneum intra-abdominal pressure on the lower extremity venous blood flow obstruction, combined with low pupil is sometimes used in the first position, suggesting that there should be higher than traditional surgical incidence of DVT, but there is still lack of convincing a large series of comparative results. small sample results obtained in different rooms of a completely different conclusions. Patel's research shows a high incidence of DVT after LC in open cholecystectomy, Kopanski the result was the opposite. causes of this phenomenon may be due to: ① hidden most of the clinical DVT; ② While there is venous congestion and laparoscopic hypercoagulable state, but a shorter operation time and more small to offset part of the impact of the trauma; ③ preventive measures taken to calculate the true incidence of rate greatly. Nevertheless, laparoscopic surgery of lower extremity venous stasis of blood flow is an indisputable fact remains, it is necessary to take appropriate disposal.
(b) the mechanism of thrombosis and prevention
1. thrombus formation mechanism
(1) venous stasis venous blood flow stasis, vascular wall endothelial damage and blood hypercoagulability is the three elements of venous thrombosis. gas abdominal pressure exceeds venous blood pressure, will lead to changes in hemodynamics, manifested as lower extremity vein dilation, blood flow slows, blood pressure increased.
Christen balloon pressure in vitro method of simulated abdominal laparoscopic pneumoperitoneum when the state of the multi-pulse Determination of volunteers Doppler femoral vein diameter and blood flow velocity changes. The results showed: air bag pressure can cause abdominal pressure associated with a significant increase of femoral vein diameter and blood flow slowed down. LC surgery in 11 mmHg ~ 13 mmHg abdominal pressure, the femoral vein diameter significantly increased pressure by 7.5mmHg increase to 15.5 mmHg, femoral vein flow velocity by 12.5cm / s down to 8.5cm/s.Beebe a study has reached the same conclusion. position state of pneumoperitoneum have significant effects on venous return. Ido measured by color Doppler in patients undergoing LC the right femoral vein blood flow changes, the results showed that with the increase of intra-abdominal pressure, blood flow velocity has slowed down, head high more obvious when low enough. When low pupil from scratch into a supine position, blood flow improved significantly, suggesting that LC surgery without first pupil will help alleviate the low status of venous stasis.
venous stasis due to blood viscosity higher degree and become risk factors for venous thrombosis. Intravenous increased pressure can lead to occurrence of micro-vascular endothelial tear (microtears), collagen fibers exposed, and induce coagulation.
(2) changes in blood coagulation research Caprini that, despite the use of elastic stockings, and intraoperative preventive measures such as lower limb compression device, but compared with the control group, LC postoperative day thrombelastography preoperative total index was still significantly elevated partial thromboplastin time (PTT) was significantly shorter in patients after LC shows that hypercoagulability. clotting mechanism to rely more on activation of coagulation factors, rather than the quantity and quality of platelets. Zhujiang Fan LC compared with OC and other patients with perioperative coagulation fibrinolytic system changes in some indicators. Based on the results of that: in terms of the stability of the blood alone, LC does not increase the risk of thrombotic complications.
2. the prevention of thrombosis in the majority of authors believe that laparoscopic surgery is currently , due to venous flow stasis, hypercoagulability and other factors, prone to thromboembolic complications, and should take preventive measures. A survey showed that .60% of North American surgeons to take the patients to accept preventive LC measures after DVT. specific ways, including: for the use of lower extremity venous stasis, intermittent compression devices and elastic stockings and other physical and hypercoagulable states for use of heparin and other anticoagulant drugs law.
(1) physical method in abdominal surgery Application of leg compression devices for prevention of postoperative DVT and pulmonary embolism has been shown to be effective measures. This device can periodically oppressed the lower leg and thigh of patients, and promote venous (sinus, especially in the calf muscles) and evacuation, to prevent vein dilation, while fibrinolytic plasminogen activation system. Although such measures can not be sure of venous pressure and blood flow have much impact, but to prevent vein dilation, activation of fibrinolytic system, major surgery on laparoscopic patients is beneficial. Christen found: in vitro balloon pressure to 50 mmHg abdominal pressure, the use of intermittent lower extremity compression devices can be effective in restoring pressure venous blood flow velocity, but can not change the shares vein diameter and pressure. Ido found: When the intra-abdominal pressure of 5 mmHg or less, the application of compression bandages to prevent venous stasis; and abdominal pressure was 10 mmHg or lower during the first pupil, pressure bandages can not play this types of preventive effect, suggesting that this method applies only without the establishment of pneumoperitoneum and changes in position of the open surgery, laparoscopic surgery but may be ineffective. pneumoperitoneum removed, the femoral vein blood velocity and cross-sectional area can quickly return to base value, so that venous stasis condition rapidly improved. Thus, repeated in laparoscopic surgery may be inflated and deflated in a way to prevent DVT.
(2) Drugs Act, the use of heparin in the conventional surgery can reduce the incidence of venous thrombosis. However, Kadm dar et al reported that even with heparin, the incidence of pulmonary embolism after surgery remains high (0.7%). The incidence of pulmonary embolism after laparoscopic surgery may be higher than the above figures. Beebe and other reports of heparin can be successfully combined with ergotamine in preventing postoperative venous thrombosis. heparin to prevent blood clot formation, ergotamine may cause venous contraction, reducing the vein diameter, thereby reducing the stimulation of connective tissue on the vein wall and vascular endothelial damage. Caprini taken comprehensive measures to prevent the occurrence of DVT after laparoscopic surgery: 2 hours before surgery until discharge system using a long elastic stockings (TED); intraoperative and early postoperative use in the legs stockings continuous pressure device (SCD); on the high-risk patients low-dose subcutaneous heparin 10000U / d, and adjust the dose to TEG index maintained at + / -2 between, until after 7 days to 30 days; after l week, 3 weeks, blood tests, respectively, to adjust the heparin dose. Following the above treatment, l00 l cases LC cases occurred only in patients with asymptomatic DVT. I believe that the use of elastic stockings, and intraoperative leg compression device, high-risk patients (old age, obesity, hypertension, etc.) subcutaneous heparin, Salvia oral tablets, intravenous infusion of dipyridamole and so can effectively prevent the occurrence of DVT after laparoscopic surgery.
six, abdominal internal organs ischemia
because of increased intra-abdominal pressure, abdominal organs (liver, kidney, stomach intestine, etc.) may be due to mechanical compression of blood flow and reduce the impact of neuroendocrine. pneumoperitoneum laparoscopy in intra-abdominal organs caused by decreased blood flow and function of the damage mechanisms include: ① splanchnic vascular mechanical compression; ② vessels plus pressure release material; ③ surgical position and vena cava blood pressure reduction caused by Huixin; ④ visceral blood flow after the lifting of pneumoperitoneum reperfusion; ⑤ oxygen free radicals and intestinal bacterial translocation; ⑥ C02 pneumoperitoneum to peritoneal The temperature dropped, the small blood vessels; ⑦ halothane and other anesthetics on visceral vascular contraction.
(a) and other liver function
Halevy observed spectrum of liver enzymes after LC change. of the 67 cases preoperative alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels were normal in patients with LC after 3 days of enzymatic observations, the results: AST increased in 53 patients (79% ), more than normal levels of l.8 times; ALT increased in 55 cases (82%) is 2.2 times the average preoperative; ALP increased in 36 cases (53%), but is normal; otherwise lO (14%) postoperative bilirubin. the enzyme index change and patient's age, narcotic drugs and surgery independent of time. All patients recovered uneventfully after surgery. authors speculate that these enzymes as indicators of possible mechanisms of change: ① abdominal increased pressure, liver blood flow; ② When isolated gallbladder squeeze liver enzyme release into the blood; ③ heat damage to the liver; ④ traction gallbladder dysfunction caused by extrahepatic bile duct, bile duct pressure increased; ⑤ hepatic vagus cystic artery was clipped; ⑥ small stones within the biliary excretion; ⑦ the comprehensive reasons.
the author of the 40 cases of LC in patients with liver function before and after surgery were observed, one of the following circumstances do not enter the list of observations: ① preoperative abnormal liver function; ② patients with chronic liver disease; ③ transfer surgery; ④ line before surgery ERCP; ⑤ intraoperative cholangiography was OK. Infarct: LC l before and after the first day, 3 days of serum total protein ( TP), albumin (A), globulin (G), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutamyl (base) transferase (GGT), total bile acid (TBA), the results can be seen: LC on postoperative day 1, patients with TP, G, TBA decreased significantly, ALT, AST, LHD, GGT and other indicators of liver enzymes increased significantly 3 days after surgery, liver enzyme indicators have declined, but still significant difference between preoperative and TP, A, G, TBA no recovery trend. more reason for the change of pressure with the change of pneumoperitoneum has important links. LC C02 used in the operation gas abdominal pressure is generally maintained at 1.5kPa ~ 2.0kPa (11.2mmHg ~ 15mmHg), such as intra-abdominal pressure in the short time to ask the rise in liver blood flow is more significant. pneumoperitoneum lifted, will result in the liver in rats. The deep meaning of changes in liver function is: With the broadening of the indications of laparoscopic surgery, laparoscopic surgery than some more complex or time-consuming LC longer for the liver function has been damage to such complex patients in laparoscopic surgery, the need to more fully consider the surgery in patients with liver function may be negative effects.
(b) changes in renal function related to pneumoperitoneum
renal function under There are many studies. Harman observed in intra-abdominal pressure of 20.25 mmHg, the renal blood flow and glomerular filtration rate values were based on only 21% and 23%, 55% increase in renal vascular resistance, renal venous pressure higher than the intra-abdominal pressure 0.75 mmHg ~ 2.25 mmHg. Although gas abdominal laparoscopic surgery is usually not more than l5 mmHg, intra-abdominal pressure on renal function but there is still some impact. Iwase et al renal function in patients after LC observation indicates high intra-abdominal pressure group (12mmHg) to show decline in renal function, and low gas abdominal group (3.97mmHg) is not present significant changes in renal function. of the view that LC temporary postoperative renal dysfunction is due to long abdominal pressure due to higher gas.
the exclusion of the original factors of renal dysfunction, the author of 40 patients with LC preoperative and postoperative renal function to do the survey, the results show on postoperative day 1 was significantly BUN down, cr was significantly increased, BUN / Cr decreased significantly after 3 days BUN / Cr compared with a further decrease on day 1, indicating that LC does pneumoperitoneum on renal function have an impact.
renal blood flow during pneumoperitoneum reduction is an important factor of renal function, the mechanism is multifaceted, including the impact of pneumoperitoneum pressure, neuroendocrine changes and so on. on chronic renal impairment, old age, hypertension, glucose mirage than patients in need purple complex laparoscopic renal function required special attention to the protection, if necessary, can be used without pneumoperitoneum laparoscopic surgery.
(c) intestinal ischemia, necrosis
pneumoperitoneum pressure to reduce visceral blood flow is a common However, intestinal ischemia, necrosis is very rare. According to the literature, it is mainly seen in the upper abdominal laparoscopic surgery. Elefsheriadis LC compared with OC patients of gastric pH value of the police. LC group was found to be significantly gastric pH, below 0C group, suggesting that when the gastric organization LC ischemia and hypoxia: Mirror posthumous shame generally love life and bowel necrosis within 1 week after surgery, mainly seen in elderly patients and Guangdong, the heart thing to Lei: diabetes mellitus and operation time longer patients to arterial thrombosis is more common, but venous thrombosis may also occur.
main clinical manifestations: sudden recovery process after abdominal pain, often accompanied by nausea, vomiting, some patients have diarrhea, systemic poisoning symptoms can be very quickly into a state of shock. then very difficult to diagnosis before surgery, the mortality can be as high as 70% to 90%. When the patients after sudden unexplained severe abdominal pain, consider this complication, if necessary can be used for angiography. Treatment measures include: Application vasodilators and anticoagulants, effective fluid resuscitation and timely laparotomy.
typical case: Female, 62 years old, due to cholecystitis and reflux esophagitis admission. has its own analogy hemolytic anemia with thrombocytopenic purpura, was treated with prednisone and other drugs. elective LC, the operation lasted 40min. l days after surgery the patient body in good condition and continue to give cortisone drugs. surgery 2 days after sudden severe abdominal pain, rapid pulse, abdominal plain film was normal. 3 days after surgery patients had abdominal distension, abnormal liver enzyme indices, the day of death. autopsies no biliary leakage, bleeding and infection, superior mesenteric artery thrombosis, Cooke's ligament necrosis of the small intestine and right colon.
laparoscopic surgery can also cause venous thrombosis. Valeri 12 cases of laparoscopic splenectomy patients, l cases of spontaneous thrombocytopenic purpura patients by color Doppler ultrasound and angiography had confirmed partial right portal vein and the left branch of complete thrombosis. 48h followed by a heparin anticoagulation (dicumaro1) 5 days of cold treatment, symptoms, liver enzyme levels back to normal. continue anticoagulant therapy l months, Doppler ultrasound showed patency of the portal vein has been completely restored. Klugewitz other reports l IC patients undergoing blood 24 hours after it occurred in patients 41 years old male: similar to acute inflammatory bowel disease, the high-dose heparin treatment 44 days after discharge, 6 months after the laparotomy found fully restore the integrity of intestinal mucosa.
view of this, the high-risk patients, such as older age, diabetes mellitus (blood coagulation at high state), hypertension, etc., preoperative administration of vasodilator drugs and the prophylactic use of anticoagulant drugs is necessary.
(d) adrenal hemorrhage and acute adrenal crisis
adrenal hemorrhage after surgery is a rare The risk of complications, due to non-specific clinical manifestations, diagnosis is often difficult, but as long as an understanding of this complication, Determination of blood glucocorticoid levels and abdominal CT, MRl seized apricot can confirm the diagnosis. Belmore has been reported a typical case:
male patients, aged 53, undergoing elective LC l days after surgery, was discharged in good condition because of the body. postoperative day 5 because of abdominal pain, systemic failure hospitalization. examination: body temperature 38.600C blood pressure 68.2 mmHg / 40.5 mmHg, moderate degree of dehydration, abdominal tenderness in the right upper quadrant as the weight, no muscle health and rebound tenderness, no back tenderness, decreased bowel sounds. hyponatremia 125mmoL / L, potassium 5.2mmoL / L, amylase l971U / L, diagnosed as acute pancreatitis. subsequent abdominal CT scan prompted both sides of the adrenal hemorrhage associated with renal infarction, serum cortisol l4mg / L. The final diagnosis: primary adrenal insufficiency. hormone replacement therapy given after 48h of symptoms improved, was discharged in good condition after .2 weeks after emergency re-admission in critical condition, and ultimately death, the cause of acute adrenal crisis may be lines.
Shuhou causes adrenal hemorrhage and adrenal stress response and vascular Special anatomy related. hypotension or other conditions (such as venous congestion, increased demand for stress hormones, etc.) adrenal venous pressure will rise, causing bleeding. when 90% of the adrenal cortex is destroyed, adrenal insufficiency can occur . Postoperative acute adrenal insufficiency nonspecific clinical manifestations make the diagnosis of this complication is often the experience-dependent, serum cortisol, CT, MRI scans both sides. adrenalectomy has confirmed significance. hormone replacement therapy is the treatment of adrenal cortex The only effective measure dysfunction.
seven, N20 anesthesia and the abdominal cavity caused by blasting the possibility of coagulation
early laparoscopic Zengyi N20 (nitrous oxide) the establishment of pneumoperitoneum due to coagulation may cause intra-abdominal CO2 blasting the use of foreign lines have been widely used inhaled anesthetic N20/02, N20 has a highly organized inter-diffuse, fast into the abdominal cavity. George found: inhalation of 66% N20/33% 02, 30min after the intraperitoneal anesthesia N20 concentration of up to 47%. bowel contains hydrogen (H2) and methane (CH4), the highest concentration reached 69% and 56%. In vitro studies have shown that 47% of the N20 can be 56% combustion CH4; 29% of the N20 68% can be combustion H2. surgery if bowel injury, bowel within the H2 and CH4 that spilled into the abdominal cavity, abdominal N20 in the combustion can be achieved under the blasting of the critical point, and finally by coagulation start burning H2 and CH4 explosion. The authors suggest that laparoscopic surgery, anesthesia should be reduced or completely avoid the use of N20 concentration of N20. currently although N20 anesthesia caused the relevant report blasting the abdominal cavity, but should arouse our vigilance. author of laparoscopic surgery hospital to CO2 pneumoperitoneum established, and a smoke free static N20 anesthesia, completely avoid the occurrence of these risks.
eight, intra-abdominal high concentration of carbon monoxide (C0) of the operating room pollution
C02 pneumoperitoneum the hypoxic environment caused intra-abdominal, the use of transurethral electrocoagulation organization, the organization is not completely oxidized to produce high concentrations of C0. electrocoagulation after 5mm, the average concentration of intra-abdominal C0 up to l2.32 (0.89 ~ 57.14) mmoL / L, has exceeded the allowable limit C0 concentration 1.25mmol / L 54 times. Beebe's research has not yet found that C0 levels in the blood of patients, but intraoperative conversion equipment gas leakage caused by abdominal surgery can cause indoor pollution C0, that is or inhalation of a small amount of C0 is also sufficient to endanger the health of operating room staff. Therefore, the operating room should have good ventilation, not in a poorly ventilated environment to work long hours.
nine, with no added temperature drops
temperature of C02 (C02 cylinders are common low-temperature C02) inflatable, or intraperitoneal C02 replacement can lead to excessive patient temperature drops, more common in infants and young children. Holland and other 26 cases /}, JL and 42 cases of laparoscopic surgery / I, JL laparotomy carried out a comparative study of temperature changes and found that the average body temperature of children dropped peritoneoscopy 0.69 ℃, and laparotomy only decreased 0.47 ℃, although not statistically significant, but the heat prompted laparoscopy loss may be more. So in pediatric laparoscopic surgery should be closely observed in the temperature changes, keep warm, not too low operating room temperature.
compartment syndrome refers to a limited dissection chamber volume, pressure, increased so that the chamber after the occurrence of tissues and organs of blood circulation disorder, and thus of functional and organic damage to a group of syndromes. is the most common clinical limb bone fascia compartment syndrome. peritoneal cavity as a separate room, under pressure in the pneumoperitoneum can occur that change the same.
normal intra-abdominal pressure and atmospheric pressure similar to the contents of any form of abdominal volume increase, can cause increased intra-abdominal pressure, the formation of abdominal compartment syndrome ( abdominal compartment syndrome, ACS), the most vulnerable organ system affected the cardiovascular system, respiratory system and kidneys, mainly as increased peripheral vascular resistance, reduced cardiac output, increased airway resistance, lung compliance, or even anoxia . peritoneal pathological changes than after decompression can often be reversed quickly, but are not limited to sexual ACS can cause fatal organ failure.
gas abdominal laparoscopic surgery in the automatic regulation of pneumoperitoneum and under strict monitoring of patients is rarely formed in the ACS, but the adaptive ability to regulate the body reduction for elderly patients or liver and kidney dysfunction associated with cardiopulmonary patients, laparoscopy in abdominal pressure to take the gas as low as possible is highly benefits.
a subcutaneous emphysema and gas embolism
(a) of the subcutaneous emphysema subcutaneous emphysema
the exact incidence and cause of the unknown. Kunming General Hospital, where the author of more than 8,000 cases of LC CCP appeared in 23 cases, were associated with significant hypercapnia, but all patients are closely monitored in the completion of surgery. retrospective analysis of these 23 patients during surgery and found that the following factors and subcutaneous emphysema occurrence of obvious relevance: ① the location of improper Veress needle to establish pneumoperitoneum gas was injected into the extraperitoneal space; ② casing surrounding the abdominal cavity into the subcutaneous tissue through C02; ③ repeated puncture needle or tube taper off the original puncture site, created in the abdominal wall to form multiple channel, C02 enter the skin through Chong Road; ④ with expander expansion of puncture or other methods (such as check except when the gallbladder), the abdominal wall and the casing of the reduction between the closed, gas from the the gap between the abdominal wall and the casing to the subcutaneous tissue diffusion; ⑤ intra-abdominal pressure is increased when the potential closure of the inguinal canal does not pass, the gas can leak into the subcutaneous tissue from the abdomen.
severe and widespread oppression of thoracic subcutaneous emphysema may be and upper respiratory tract, the lung compliance, increased airway resistance, severe hypoxemia or produce C02 accumulation. on the cardiovascular system can be expressed as emphysema local vascular compression, the late decline in emissions can be developed Zhixin , central venous pressure, mean arterial pressure and heart rate changes are also frequent.
mild subcutaneous emphysema little effect on the body, do not need special treatment. a serious and extensive subcutaneous emphysema because of the negative of cardiopulmonary effects must be closely monitored to do surgery, especially when patients are determined to pulmonary insufficiency. appropriate to reduce the intra-abdominal pressure, the anesthesiologist uses hyperventilation to poke holes at Extruded emphysema, all help to reduce the adverse emphysema effect and slow the spread of emphysema. difficult to correct because of subcutaneous emphysema caused by heart and lung function changes or hypercapnia, should be converted to open surgery, but this is rare.
an interesting phenomenon: the author subcutaneous emphysema, 23 cases occurred in the early cases, nearly 4,000 cases of post-LC has not been to see subcutaneous emphysema. As mentioned above caused by subcutaneous emphysema in a number of related factors can not be in nearly 4,000 cases of LC does not appear This can not help but gives rise to the following questions: whether the production of subcutaneous emphysema and some unknown other factors.
(b)
gas embolism gas embolism (hereinafter referred to as air embolism) is a rare complication of pneumoperitoneum , but its consequences are very serious, usually fatal. embolism may be the site of the right atrium, pulmonary artery, to a rare coronary and cerebral arteries. The exact incidence of air embolism can not be estimated, Cottin reported that a group of 1994 cases of laparoscopic surgery, air embolism occurred in 2 cases and lead to patient death, which is the highest known incidence of a group. inflatable gas species and the formation of air embolism should have between the exact probability of relevance. C02 As a high solubility of gases, as long as not a lot in a short time into the blood vessels, the possibility of the formation of air embolism is small. such as the use of helium inflated, because of its low solubility, only very small amount into the blood vessels, which the formation of air embolism can be fatal, it has been confirmed by experiments.
to the current lack of actual laparoscopic surgery carried out against the background of the formation mechanism of air embolism experimental study, suggesting the formation of the following ways: ① pneumoperitoneum strayed into the abdominal vein needle, large amounts of gas directly into the blood within a short time; ② tissue wound separation fracture or broken veins on a high-pressure gas into the portal circulation; ③ the gas dissolved in the blood as could be, like decompression sickness the formation of bubbles, is not yet certain.
the literature of many prevention of air embolism and intraoperative monitoring methods to do a lot of discussion, but the incidence of air embolism is very low, making it difficult to apply these measures in routine clinical patients, but the incidence of air embolism is unpredictable and almost impossible to determine so-called air embolism monitoring, preventive measures, in the present not much practical significance.
meaningful, perhaps, is how the existing emergency air embolism. The existing methods include: ① the immediate lifting of pneumoperitoneum, stop source of air embolism; ② left lateral position so that gas is not easy to enter the right ventricle; ③ rapid central venous catheter sucked out of the right atrium and right ventricle and pulmonary artery bubbles; ④ possible emergency air bubbles out of direct puncture of right atrium; ⑤ inhalation of pure Oxygen; ⑥ breathing underwent cardiac arrest cardiopulmonary resuscitation; ⑦ hyperbaric oxygen therapy.
Second, hypercapnia and respiratory acidosis
C02 pneumoperitoneum laparoscopic surgery can cause hypercapnia and respiratory acidosis, and this phenomenon has long been recognized by the industry, but mainly limited to the previous diagnostic laparoscopy and gynecological minor such do not seem to highlight the issue. With the significance.
study shows that: the intra-abdominal pressure associated with pneumoperitoneum may limit diaphragmatic movement, leading to reduced lung and possible tidal CO2 retention, and the resulting increase in P C02 can be caused by positive cardiac inotropic effect and the surrounding enhanced vasoconstriction. by supporting muscle relaxant drugs and positive pressure breathing intervention, a way to overcome the pneumoperitoneum on the impact of lung ventilation, the ventilation will not be any significant decline and the increase of P C02.
C02 pneumoperitoneum state whether there hypercapnia, respiratory acidosis often associated with the following factors:
1. pneumoperitoneum Ishizaki experiments showed that the pneumoperitoneum pressure 16mmHg or more, for 1 hour after pneumoperitoneum cardiac output that is significantly decreased peripheral vascular resistance increased significantly; intra-abdominal pressure in the 8 mmHg ~ 12 mmHg, the above changes is not obvious. intra-abdominal pressure is increased to the C02 has increased the dispersion of blood, if the additional decrease in cardiac output, and increased peripheral vascular resistance, the retention of blood in the C02 will be more obvious.
2. pneumoperitoneum Leighton found that the gas of choice: C02 pneumoperitoneum can produce respiratory acidosis animals, He does not have this pneumoperitoneum phenomenon. In addition, C02 absorption and tissue perfusion related to the time of hemorrhagic shock is often more severe hypercapnia.
3. pneumoperitoneum asked the length of the longer duration of pneumoperitoneum, peritoneal absorption of the C02 is also more.
4. subcutaneous emphysema and pneumothorax occurred in laparoscopic surgery such as subcutaneous emphysema or pneumothorax, often accompanied by more pronounced hypercapnia and acidosis.
5. anesthetic effects such as the former above, when the pneumoperitoneum laparoscopic surgery to muscle relaxants and positive pressure breathing supplementary intervention, it would be a way to correct or block the pneumoperitoneum on the impact of lung ventilation.
6. the body of the cardiopulmonary Wittgen compensatory ability of functional results have been widely cited. The study found that: LC preoperative patients with normal cardiopulmonary function can be well tolerated without the occurrence of C02 pneumoperitoneum and hypercapnia and acidosis; and cardiopulmonary dysfunction LC patients are prone to difficult surgery to correct the respiratory acidosis. of the result that: arterial blood gas analysis is pneumoperitoneum laparoscopic surgery better means of monitoring, and preoperative blood gas analysis and cardiopulmonary function assessment should be made to adapt LC Choose one of the screening criteria permit.
for the prevention of laparoscopic intraoperative hypercapnia and respiratory acidosis, in addition to preoperative surgical indication to grasp, but also during the operation proper monitoring, understanding pulse rate , oxygen saturation, pulmonary ventilation, airway pressure, blood gas analysis, PET C02 and other indicators of real change. in the event of hypercapnia, hyperventilation viable product from the body retention of C02, but the speed can not be too quickly, Otherwise, hypercapnia has been adapted to the respiratory, circulatory central hypercapnia due to sudden loss of stimulation, there will be the so-called and the sharp drop in blood pressure caused by coronary artery contraction and respiratory depression. a heavier degree of retention of C02 should be the end of surgery as soon as possible, completely eliminate the residual intra-abdominal C02, appropriate application of basic drugs. that can not correct the hypercapnia and respiratory acidosis, and must be converted to laparotomy.
three
shoulder pain shoulder pain after laparoscopic surgery is a very common symptom, its incidence can be as high as 35% to 60%. on the LC patients, even After becoming the most common but one of the major complaints. This symptom may be the incentive for intra-abdominal residual C02 caused by phrenic nerve stimulation, was noted when the patient semi-recumbent position to take the pain when the shoulder is often increased. If the above suggested the establishment of the net emission of surgery should be able to reduce the intra-abdominal postoperative C02 of shoulder pain, but unfortunately the practice is not entirely the case. on postoperative severe symptoms, can be symptomatic with salicylic acid drugs. Narchi Randomized comparative study: intraoperative use in the liver of local anesthetic diaphragm can significantly reduce postoperative shoulder pain patients.
four, arrhythmia
pneumoperitoneum state arrhythmia is not uncommon, but its exact The reason remains unclear, in addition to the surgeon's own state outside the pneumoperitoneum should also be an important incentive. have found that arrhythmia-prone of the pneumoperitoneum established in the initial period, and concluded that the establishment of the initial arrhythmia and pneumoperitoneum When the amount of traffic on C02. Whether or not this view is correct, considering the body's ability to adapt to the various organ systems, the timing of mobilization, then the establishment of pneumoperitoneum to low flow began, and then gradually increase to high traffic and high traffic maintain intraoperative pneumoperitoneum should be a principle must be followed. In addition, that the temperature of the C02 pneumoperitoneum also contributed to the possible causes of arrhythmia.
five, deep venous congestion and thrombosis
DVT is common complications after surgery. literature, more than 40 years of age are not common prophylactic anticoagulant treatment in patients after surgery, about 25% of the occurrence of DVT. vein angiography in patients after open cholecystectomy about 7% l0%, there may be DVT, pulmonary embolism rate of 0.4% to 0.7%. With 70% of DVT patients had no clinical manifestations, so the true incidence of DVT after surgery is difficult to estimate. laparoscopic surgery due to pneumoperitoneum intra-abdominal pressure on the lower extremity venous blood flow obstruction, combined with low pupil is sometimes used in the first position, suggesting that there should be higher than traditional surgical incidence of DVT, but there is still lack of convincing a large series of comparative results. small sample results obtained in different rooms of a completely different conclusions. Patel's research shows a high incidence of DVT after LC in open cholecystectomy, Kopanski the result was the opposite. causes of this phenomenon may be due to: ① hidden most of the clinical DVT; ② While there is venous congestion and laparoscopic hypercoagulable state, but a shorter operation time and more small to offset part of the impact of the trauma; ③ preventive measures taken to calculate the true incidence of rate greatly. Nevertheless, laparoscopic surgery of lower extremity venous stasis of blood flow is an indisputable fact remains, it is necessary to take appropriate disposal.
(b) the mechanism of thrombosis and prevention
1. thrombus formation mechanism
(1) venous stasis venous blood flow stasis, vascular wall endothelial damage and blood hypercoagulability is the three elements of venous thrombosis. gas abdominal pressure exceeds venous blood pressure, will lead to changes in hemodynamics, manifested as lower extremity vein dilation, blood flow slows, blood pressure increased.
Christen balloon pressure in vitro method of simulated abdominal laparoscopic pneumoperitoneum when the state of the multi-pulse Determination of volunteers Doppler femoral vein diameter and blood flow velocity changes. The results showed: air bag pressure can cause abdominal pressure associated with a significant increase of femoral vein diameter and blood flow slowed down. LC surgery in 11 mmHg ~ 13 mmHg abdominal pressure, the femoral vein diameter significantly increased pressure by 7.5mmHg increase to 15.5 mmHg, femoral vein flow velocity by 12.5cm / s down to 8.5cm/s.Beebe a study has reached the same conclusion. position state of pneumoperitoneum have significant effects on venous return. Ido measured by color Doppler in patients undergoing LC the right femoral vein blood flow changes, the results showed that with the increase of intra-abdominal pressure, blood flow velocity has slowed down, head high more obvious when low enough. When low pupil from scratch into a supine position, blood flow improved significantly, suggesting that LC surgery without first pupil will help alleviate the low status of venous stasis.
venous stasis due to blood viscosity higher degree and become risk factors for venous thrombosis. Intravenous increased pressure can lead to occurrence of micro-vascular endothelial tear (microtears), collagen fibers exposed, and induce coagulation.
(2) changes in blood coagulation research Caprini that, despite the use of elastic stockings, and intraoperative preventive measures such as lower limb compression device, but compared with the control group, LC postoperative day thrombelastography preoperative total index was still significantly elevated partial thromboplastin time (PTT) was significantly shorter in patients after LC shows that hypercoagulability. clotting mechanism to rely more on activation of coagulation factors, rather than the quantity and quality of platelets. Zhujiang Fan LC compared with OC and other patients with perioperative coagulation fibrinolytic system changes in some indicators. Based on the results of that: in terms of the stability of the blood alone, LC does not increase the risk of thrombotic complications.
2. the prevention of thrombosis in the majority of authors believe that laparoscopic surgery is currently , due to venous flow stasis, hypercoagulability and other factors, prone to thromboembolic complications, and should take preventive measures. A survey showed that .60% of North American surgeons to take the patients to accept preventive LC measures after DVT. specific ways, including: for the use of lower extremity venous stasis, intermittent compression devices and elastic stockings and other physical and hypercoagulable states for use of heparin and other anticoagulant drugs law.
(1) physical method in abdominal surgery Application of leg compression devices for prevention of postoperative DVT and pulmonary embolism has been shown to be effective measures. This device can periodically oppressed the lower leg and thigh of patients, and promote venous (sinus, especially in the calf muscles) and evacuation, to prevent vein dilation, while fibrinolytic plasminogen activation system. Although such measures can not be sure of venous pressure and blood flow have much impact, but to prevent vein dilation, activation of fibrinolytic system, major surgery on laparoscopic patients is beneficial. Christen found: in vitro balloon pressure to 50 mmHg abdominal pressure, the use of intermittent lower extremity compression devices can be effective in restoring pressure venous blood flow velocity, but can not change the shares vein diameter and pressure. Ido found: When the intra-abdominal pressure of 5 mmHg or less, the application of compression bandages to prevent venous stasis; and abdominal pressure was 10 mmHg or lower during the first pupil, pressure bandages can not play this types of preventive effect, suggesting that this method applies only without the establishment of pneumoperitoneum and changes in position of the open surgery, laparoscopic surgery but may be ineffective. pneumoperitoneum removed, the femoral vein blood velocity and cross-sectional area can quickly return to base value, so that venous stasis condition rapidly improved. Thus, repeated in laparoscopic surgery may be inflated and deflated in a way to prevent DVT.
(2) Drugs Act, the use of heparin in the conventional surgery can reduce the incidence of venous thrombosis. However, Kadm dar et al reported that even with heparin, the incidence of pulmonary embolism after surgery remains high (0.7%). The incidence of pulmonary embolism after laparoscopic surgery may be higher than the above figures. Beebe and other reports of heparin can be successfully combined with ergotamine in preventing postoperative venous thrombosis. heparin to prevent blood clot formation, ergotamine may cause venous contraction, reducing the vein diameter, thereby reducing the stimulation of connective tissue on the vein wall and vascular endothelial damage. Caprini taken comprehensive measures to prevent the occurrence of DVT after laparoscopic surgery: 2 hours before surgery until discharge system using a long elastic stockings (TED); intraoperative and early postoperative use in the legs stockings continuous pressure device (SCD); on the high-risk patients low-dose subcutaneous heparin 10000U / d, and adjust the dose to TEG index maintained at + / -2 between, until after 7 days to 30 days; after l week, 3 weeks, blood tests, respectively, to adjust the heparin dose. Following the above treatment, l00 l cases LC cases occurred only in patients with asymptomatic DVT. I believe that the use of elastic stockings, and intraoperative leg compression device, high-risk patients (old age, obesity, hypertension, etc.) subcutaneous heparin, Salvia oral tablets, intravenous infusion of dipyridamole and so can effectively prevent the occurrence of DVT after laparoscopic surgery.
six, abdominal internal organs ischemia
because of increased intra-abdominal pressure, abdominal organs (liver, kidney, stomach intestine, etc.) may be due to mechanical compression of blood flow and reduce the impact of neuroendocrine. pneumoperitoneum laparoscopy in intra-abdominal organs caused by decreased blood flow and function of the damage mechanisms include: ① splanchnic vascular mechanical compression; ② vessels plus pressure release material; ③ surgical position and vena cava blood pressure reduction caused by Huixin; ④ visceral blood flow after the lifting of pneumoperitoneum reperfusion; ⑤ oxygen free radicals and intestinal bacterial translocation; ⑥ C02 pneumoperitoneum to peritoneal The temperature dropped, the small blood vessels; ⑦ halothane and other anesthetics on visceral vascular contraction.
(a) and other liver function
Halevy observed spectrum of liver enzymes after LC change. of the 67 cases preoperative alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels were normal in patients with LC after 3 days of enzymatic observations, the results: AST increased in 53 patients (79% ), more than normal levels of l.8 times; ALT increased in 55 cases (82%) is 2.2 times the average preoperative; ALP increased in 36 cases (53%), but is normal; otherwise lO (14%) postoperative bilirubin. the enzyme index change and patient's age, narcotic drugs and surgery independent of time. All patients recovered uneventfully after surgery. authors speculate that these enzymes as indicators of possible mechanisms of change: ① abdominal increased pressure, liver blood flow; ② When isolated gallbladder squeeze liver enzyme release into the blood; ③ heat damage to the liver; ④ traction gallbladder dysfunction caused by extrahepatic bile duct, bile duct pressure increased; ⑤ hepatic vagus cystic artery was clipped; ⑥ small stones within the biliary excretion; ⑦ the comprehensive reasons.
the author of the 40 cases of LC in patients with liver function before and after surgery were observed, one of the following circumstances do not enter the list of observations: ① preoperative abnormal liver function; ② patients with chronic liver disease; ③ transfer surgery; ④ line before surgery ERCP; ⑤ intraoperative cholangiography was OK. Infarct: LC l before and after the first day, 3 days of serum total protein ( TP), albumin (A), globulin (G), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutamyl (base) transferase (GGT), total bile acid (TBA), the results can be seen: LC on postoperative day 1, patients with TP, G, TBA decreased significantly, ALT, AST, LHD, GGT and other indicators of liver enzymes increased significantly 3 days after surgery, liver enzyme indicators have declined, but still significant difference between preoperative and TP, A, G, TBA no recovery trend. more reason for the change of pressure with the change of pneumoperitoneum has important links. LC C02 used in the operation gas abdominal pressure is generally maintained at 1.5kPa ~ 2.0kPa (11.2mmHg ~ 15mmHg), such as intra-abdominal pressure in the short time to ask the rise in liver blood flow is more significant. pneumoperitoneum lifted, will result in the liver in rats. The deep meaning of changes in liver function is: With the broadening of the indications of laparoscopic surgery, laparoscopic surgery than some more complex or time-consuming LC longer for the liver function has been damage to such complex patients in laparoscopic surgery, the need to more fully consider the surgery in patients with liver function may be negative effects.
(b) changes in renal function related to pneumoperitoneum
renal function under There are many studies. Harman observed in intra-abdominal pressure of 20.25 mmHg, the renal blood flow and glomerular filtration rate values were based on only 21% and 23%, 55% increase in renal vascular resistance, renal venous pressure higher than the intra-abdominal pressure 0.75 mmHg ~ 2.25 mmHg. Although gas abdominal laparoscopic surgery is usually not more than l5 mmHg, intra-abdominal pressure on renal function but there is still some impact. Iwase et al renal function in patients after LC observation indicates high intra-abdominal pressure group (12mmHg) to show decline in renal function, and low gas abdominal group (3.97mmHg) is not present significant changes in renal function. of the view that LC temporary postoperative renal dysfunction is due to long abdominal pressure due to higher gas.
the exclusion of the original factors of renal dysfunction, the author of 40 patients with LC preoperative and postoperative renal function to do the survey, the results show on postoperative day 1 was significantly BUN down, cr was significantly increased, BUN / Cr decreased significantly after 3 days BUN / Cr compared with a further decrease on day 1, indicating that LC does pneumoperitoneum on renal function have an impact.
renal blood flow during pneumoperitoneum reduction is an important factor of renal function, the mechanism is multifaceted, including the impact of pneumoperitoneum pressure, neuroendocrine changes and so on. on chronic renal impairment, old age, hypertension, glucose mirage than patients in need purple complex laparoscopic renal function required special attention to the protection, if necessary, can be used without pneumoperitoneum laparoscopic surgery.
(c) intestinal ischemia, necrosis
pneumoperitoneum pressure to reduce visceral blood flow is a common However, intestinal ischemia, necrosis is very rare. According to the literature, it is mainly seen in the upper abdominal laparoscopic surgery. Elefsheriadis LC compared with OC patients of gastric pH value of the police. LC group was found to be significantly gastric pH, below 0C group, suggesting that when the gastric organization LC ischemia and hypoxia: Mirror posthumous shame generally love life and bowel necrosis within 1 week after surgery, mainly seen in elderly patients and Guangdong, the heart thing to Lei: diabetes mellitus and operation time longer patients to arterial thrombosis is more common, but venous thrombosis may also occur.
main clinical manifestations: sudden recovery process after abdominal pain, often accompanied by nausea, vomiting, some patients have diarrhea, systemic poisoning symptoms can be very quickly into a state of shock. then very difficult to diagnosis before surgery, the mortality can be as high as 70% to 90%. When the patients after sudden unexplained severe abdominal pain, consider this complication, if necessary can be used for angiography. Treatment measures include: Application vasodilators and anticoagulants, effective fluid resuscitation and timely laparotomy.
typical case: Female, 62 years old, due to cholecystitis and reflux esophagitis admission. has its own analogy hemolytic anemia with thrombocytopenic purpura, was treated with prednisone and other drugs. elective LC, the operation lasted 40min. l days after surgery the patient body in good condition and continue to give cortisone drugs. surgery 2 days after sudden severe abdominal pain, rapid pulse, abdominal plain film was normal. 3 days after surgery patients had abdominal distension, abnormal liver enzyme indices, the day of death. autopsies no biliary leakage, bleeding and infection, superior mesenteric artery thrombosis, Cooke's ligament necrosis of the small intestine and right colon.
laparoscopic surgery can also cause venous thrombosis. Valeri 12 cases of laparoscopic splenectomy patients, l cases of spontaneous thrombocytopenic purpura patients by color Doppler ultrasound and angiography had confirmed partial right portal vein and the left branch of complete thrombosis. 48h followed by a heparin anticoagulation (dicumaro1) 5 days of cold treatment, symptoms, liver enzyme levels back to normal. continue anticoagulant therapy l months, Doppler ultrasound showed patency of the portal vein has been completely restored. Klugewitz other reports l IC patients undergoing blood 24 hours after it occurred in patients 41 years old male: similar to acute inflammatory bowel disease, the high-dose heparin treatment 44 days after discharge, 6 months after the laparotomy found fully restore the integrity of intestinal mucosa.
view of this, the high-risk patients, such as older age, diabetes mellitus (blood coagulation at high state), hypertension, etc., preoperative administration of vasodilator drugs and the prophylactic use of anticoagulant drugs is necessary.
(d) adrenal hemorrhage and acute adrenal crisis
adrenal hemorrhage after surgery is a rare The risk of complications, due to non-specific clinical manifestations, diagnosis is often difficult, but as long as an understanding of this complication, Determination of blood glucocorticoid levels and abdominal CT, MRl seized apricot can confirm the diagnosis. Belmore has been reported a typical case:
male patients, aged 53, undergoing elective LC l days after surgery, was discharged in good condition because of the body. postoperative day 5 because of abdominal pain, systemic failure hospitalization. examination: body temperature 38.600C blood pressure 68.2 mmHg / 40.5 mmHg, moderate degree of dehydration, abdominal tenderness in the right upper quadrant as the weight, no muscle health and rebound tenderness, no back tenderness, decreased bowel sounds. hyponatremia 125mmoL / L, potassium 5.2mmoL / L, amylase l971U / L, diagnosed as acute pancreatitis. subsequent abdominal CT scan prompted both sides of the adrenal hemorrhage associated with renal infarction, serum cortisol l4mg / L. The final diagnosis: primary adrenal insufficiency. hormone replacement therapy given after 48h of symptoms improved, was discharged in good condition after .2 weeks after emergency re-admission in critical condition, and ultimately death, the cause of acute adrenal crisis may be lines.
Shuhou causes adrenal hemorrhage and adrenal stress response and vascular Special anatomy related. hypotension or other conditions (such as venous congestion, increased demand for stress hormones, etc.) adrenal venous pressure will rise, causing bleeding. when 90% of the adrenal cortex is destroyed, adrenal insufficiency can occur . Postoperative acute adrenal insufficiency nonspecific clinical manifestations make the diagnosis of this complication is often the experience-dependent, serum cortisol, CT, MRI scans both sides. adrenalectomy has confirmed significance. hormone replacement therapy is the treatment of adrenal cortex The only effective measure dysfunction.
seven, N20 anesthesia and the abdominal cavity caused by blasting the possibility of coagulation
early laparoscopic Zengyi N20 (nitrous oxide) the establishment of pneumoperitoneum due to coagulation may cause intra-abdominal CO2 blasting the use of foreign lines have been widely used inhaled anesthetic N20/02, N20 has a highly organized inter-diffuse, fast into the abdominal cavity. George found: inhalation of 66% N20/33% 02, 30min after the intraperitoneal anesthesia N20 concentration of up to 47%. bowel contains hydrogen (H2) and methane (CH4), the highest concentration reached 69% and 56%. In vitro studies have shown that 47% of the N20 can be 56% combustion CH4; 29% of the N20 68% can be combustion H2. surgery if bowel injury, bowel within the H2 and CH4 that spilled into the abdominal cavity, abdominal N20 in the combustion can be achieved under the blasting of the critical point, and finally by coagulation start burning H2 and CH4 explosion. The authors suggest that laparoscopic surgery, anesthesia should be reduced or completely avoid the use of N20 concentration of N20. currently although N20 anesthesia caused the relevant report blasting the abdominal cavity, but should arouse our vigilance. author of laparoscopic surgery hospital to CO2 pneumoperitoneum established, and a smoke free static N20 anesthesia, completely avoid the occurrence of these risks.
eight, intra-abdominal high concentration of carbon monoxide (C0) of the operating room pollution
C02 pneumoperitoneum the hypoxic environment caused intra-abdominal, the use of transurethral electrocoagulation organization, the organization is not completely oxidized to produce high concentrations of C0. electrocoagulation after 5mm, the average concentration of intra-abdominal C0 up to l2.32 (0.89 ~ 57.14) mmoL / L, has exceeded the allowable limit C0 concentration 1.25mmol / L 54 times. Beebe's research has not yet found that C0 levels in the blood of patients, but intraoperative conversion equipment gas leakage caused by abdominal surgery can cause indoor pollution C0, that is or inhalation of a small amount of C0 is also sufficient to endanger the health of operating room staff. Therefore, the operating room should have good ventilation, not in a poorly ventilated environment to work long hours.
nine, with no added temperature drops
temperature of C02 (C02 cylinders are common low-temperature C02) inflatable, or intraperitoneal C02 replacement can lead to excessive patient temperature drops, more common in infants and young children. Holland and other 26 cases /}, JL and 42 cases of laparoscopic surgery / I, JL laparotomy carried out a comparative study of temperature changes and found that the average body temperature of children dropped peritoneoscopy 0.69 ℃, and laparotomy only decreased 0.47 ℃, although not statistically significant, but the heat prompted laparoscopy loss may be more. So in pediatric laparoscopic surgery should be closely observed in the temperature changes, keep warm, not too low operating room temperature.
Thursday, February 24, 2011
Shaping the perspective of IBM's life sciences market in China
Zhuanzhai Note: The following quote from IBM's announcement of a White Paper on China's pharmaceutical market, we can understand from the perspective of the IT companies to look at the Chinese pharmaceutical market, I believe there will be inspired.
Life science market in China has become even the engine of global development. even in this financial turmoil, because of strong consumer demand, China's pharmaceutical and medical device market is still maintained double-digit growth every year. China should focus on the concerns of long-term life sciences market development potential. China life sciences market is undergoing a revolutionary change, the most compelling next three years, governments at all levels will be invested in the new health reform 850 billion yuan (about 125 billion U.S. dollars), the healthcare enterprises that is undoubtedly a golden opportunity. Meanwhile, the Chinese government will also aim to create a more transparent and regulated health care market environment. This white paper the main market structure will change and the impact of related enterprises discussed:
1. to improve health insurance coverage to a wider audience can enjoy affordable health care services: pharmaceuticals and medical equipment to stimulate growth in consumption.
2. to provide a more efficient health services: urban primary care system and the establishment of rural health care system to promote a new generation of consumer groups, causing changes in channel structure, and thus on the ability of companies with new operational requirements.
3. to establish and implement national essential drug list drugs online public bidding in order to strengthen drug sales and use regulation.
the Chinese government is committed to promoting the pharmaceutical industry innovation, promote China's pharmaceutical enterprises to enhance competitiveness, thus forming a new pattern of life science market. We believe that this is R & D resources and innovative ways to promote the integration of medicine. When R & D (R & D) the market is full of vitality, will attract more investment; and increased investment will lead to further promote the sound development of pharmaceutical R & D market. China in recent years pharmaceutical manufacturing practices (GMP) and drug quality management specification (GSP) of the revised standards to improve the quality of medicines, but also on pharmaceutical manufacturing and distribution companies set higher requirements. With the further integration of the pharmaceutical industry, a group of weak competitiveness of enterprises will be eliminated, the pharmaceutical industry The access threshold will become higher. In short, we hope that China's life sciences industry will become increasingly mature and more competitive in the international market.
this white paper to the China life sciences companies to the rapid development of and full of success in the market change to provide practical insight into the views. We recommend that companies should follow the following three key operational capabilities to enhance:
b innovation: the development of domestic technology industries and government support for the opportunity to strengthen R & D capacity . through cooperation with external institutions to enhance research and development capabilities, by developing internal talent and manage projects to enhance internal management capabilities.
b production quality: high-quality products is not only the pharmaceutical companies marketing differentiation in the embodiment, it is which pharmaceutical companies first condition of existence. companies must improve productivity, reduce operating costs to achieve supply chain operational excellence.
b sales, marketing and distribution: business channels and by strengthening logistics management, so that more consumers can easily buy high-quality drugs. Therefore, strategies to expand sales channels and strengthen sales force management is the key to future business run-off market. Pharmaceutical manufacturers and pharmaceutical distribution enterprises to be more closely together to enhance overall operational efficiency. the definition of life sciences market
defined our extensive coverage of the life sciences market throughout the health of ecosystems and life sciences ecosystem, the main enterprise (organization), as shown in Figure 1. these companies in the medical field engaged in pharmaceuticals, medical devices and diagnostic tests and other content related to business activities, through innovation (R & D), manufacturing, marketing and distribution of the whole process, and ultimately commitment to patients and provide consumers with better health services. < br> When the slowdown in other industries, China's life sciences market is undoubtedly a bright spot in the global economy. Chinese medicine market because of its huge development potential and attracted much attention. Chinese brand prescription and non prescription drugs (OTC) 1997 years market size of only 37 million, while 2010 is expected to reach 220-250 billion U.S. dollars. expected in 2009 China's pharmaceutical market will reach an annual growth rate of 25%, higher than in other emerging markets growth rate of 15% and much higher in developed countries, about 5% of the market growth rate of .3 is the world's attention even more is expected in 2020 to 220 billion U.S. dollars is expected in the market, second only to the United States the world's second largest pharmaceutical market in China .4
The current health care reform and the Government to establish more innovative and competitive industry initiatives, will promote China's booming life sciences market. When corporate exposure in a more orderly, more regulated market environment, to better meet patient needs demand responsibility, and gradually become a global market leader.
health care reform on China's Life Sciences Industry in China is
health system reform its huge investment In 2009 an unprecedented 1 month, the State Council announced the next two years will be 850 billion yuan investment in the health sector (about 125 billion U.S. dollars), and provide residents with high-quality, affordable health services .5 expects the investment will in the life sciences market, pharmaceutical, medical equipment manufacturing and pharmaceutical distribution and other enterprises have a significant impact.
more people can enjoy affordable health services means that the increase in health care spending, resulting in the demand for drugs and medical equipment rose
health reform One of the main objectives is to solve China's population and of coverage due to lack of medical problems. in recent years in the medical security system in China has made remarkable progress in 2010, various types of health insurance will cover more than 90% of urban and rural residents, Through the implementation of the national basic medical insurance, basic medical insurance for urban residents and the new rural cooperative medical care (referred to NCMS), a wide range of urban and rural residents to improve health insurance coverage. 6
new group health insurance coverage is not only broader, and that the government increased subsidies for individual insurance. For example, the government medical insurance for urban residents per person per year subsidy from the standard 80 yuan to 120 yuan, the new rural cooperative subsidy from the standard 40 yuan per person per year to 120. Government subsidies increase the number of each individual concerned may not, but taking into account the total number of health insurance coverage is very large, this initiative will profoundly affect the total consumption expenditure on health. Analysts predict that by 2011 to increase coverage for health care reform pharmaceutical market brought about expansion will reach 1650-3330 one hundred million yuan .7 There is no doubt the next two years to improve health insurance coverage will promote pharmaceutical sales.
more efficient health service system will change the life of existing scientific institutions channel, product and customer portfolio
reverse city doctors, hospital beds, medical facilities, etc.), the inequality. 8 China's current urban medical service system of medical resources from the hospital too focused on high-end will be referred to a hospital for further treatment.
This marks the existing health service system, patients are mainly concentrated in large urban hospitals would be a dramatic change in status. The new model, the main function of the high-end hospitals is the treatment incurable diseases, serious illness serious illness, teaching and research, large-scale clinical trials and medical research. can be expected, the high-end hospital resource utilization will gradually decline, such as out-patient share from the current 80% to 50%. midrange Hospitals will also be divided, some hospitals with better conditions will be transformed into the top three hospitals, in part poor efficiency, small-scale hospitals, may be converted into community health centers or other services.
With the establishment of urban primary care health system, the number of community health services will grow rapidly. Community health services provided at a lower price treatment of common diseases, preventive health and disease control services, to provide economic and convenient health services. From 2007 to 2010, China will in all level and above the county level cities and in the establishment of 40,000 urban community health services. The goal is 3-10 per million inhabitants, or by district offices and the establishment of a number of health centers community health service stations .9
rapid emergence of health services will be at the basis of medical institutions and medical market enterprises (such as manufacturers of generic drugs, basic medical equipment manufacturers and pharmaceutical distribution business) have a profound impact. Community health services institutions were established, and will be produced in a certain period of significant recruitment and training needs of qualified medical personnel; medical device manufacturers will usher in a new market demand, expected funding for community health for 30% of institution-building will be used to purchase basic medical equipment . Meanwhile, the commonly used drugs, especially generics sales will go up.
three-tier health service system in rural development, life sciences sector will face new customers and channels
will establish a new rural health services in three system so that minor illnesses within the village of rural residents, serious illness not counties. county hospital will become a regional treatment center, the main provider of basic health services and specialist disease clinics, while rural health facilities will also provide training and operational staff and technical guidance . Since the 3 years beginning in 2009, the central key support around 2000 county hospital building, so that each county at least one county-level hospitals to standardize the level of .10
basic community health agencies and similar organizations in the development of rural health for pharmaceutical companies, medical device manufacturers and medical distribution companies to bring new channels and markets. community and the rise of the two major markets in rural areas, will have sales of drugs, types and significant impact on the current channel structure.
strengthen drug sale and use of regulatory, operational requirements of life science institutions change
content as part of new health care reform, medical reform led to widespread popular attention and discussion, especially in drug procurement, drug distribution and so on. Although the drug sales and use implementation details have not yet released, but the new medical reform plan is certain, will strengthen the transparency of drug sales and use, to reduce the total cost of health care services (Figure 3) .11
to control medical costs is a key initiative to establish national Drugs List, based on types and brands of drugs into three categories, each set different types of pharmaceutical reimbursement. A majority of medicines covered by basic drugs, from state subsidies received full reimbursement of the insurance sector, B medicines for a certain reimbursement ratio, C medicines to be paid at their own expense. local governments have increased in the B class directory and remove the flexibility of 5% of drugs. National Drug List will be given the highest guiding price of each drug, and the final price tenders by local governments through decision.
health reform under the new policy, all community health agencies all use the essential drugs list in the variety of other medical and health institutions such as tertiary hospitals should give priority to use the directory prescription drugs .12 In addition, there are some on the use of essential drugs List of proposals to lower drug costs, such as retail pharmacies to buy drugs in the base directory will be included in the scope of reimbursement. The overall objective is to full competition by encouraging the market to further reduce drug prices.
Another important reform is the provincial government for the establishment of centralized procurement of drugs for profit platform, state-owned non-profit medical institutions must all participate in centralized drug purchasing. implementing web-based centralized procurement and online bidding, procurement process to improve health care transparency of the Drug. the provincial government to establish a scientific evaluation of drug procurement methods gradually increase the weights of different elements, such as drug quality, price, service and reputation, and other elements of pharmaceutical manufacturers. Meanwhile, to encourage medical institutions Biaozhun Hua prescription drugs to improve health care quality and regulate the behavior of prescribing part of .13
local governments such as Guangdong have tried to make some reforms. This requires pharmaceutical companies and distribution companies to enhance the quality and cost control. pharmaceutical distribution market will be affected, the next 80% of the essential drugs will be directly delivered to the community or rural health facilities medical institutions, which will encourage the use of large regional and national circulation circulation commercial business, giving rise to the integration of pharmaceutical distribution market. 14
China's health reforms will change the existing channels and customer segments
Chinese medical and health Life sciences companies will bring reform to market changes and opportunities. pharmaceutical companies, especially manufacturers of generic drugs, medical equipment manufacturers, vaccine manufacturers will benefit from increased public expenditure on basic health services and health insurance coverage expansion initiatives have been interests. National Essential Drugs List in 50% of Chinese patent medicines, the Chinese manufacturers are also expected to benefit from.
bring health care reform and pharmaceutical channel structure changes in the consumer market segments. estimated that about 20% of the drugs transferred from the hospital market to the third terminal market, the third terminal market is outside of the hospital pharmacies and retail pharmacies sell drugs directly to consumers terminals, such as community health agencies, clinics, health care centers. 15
us noted that health care reform will promote the formation of three major market segments, companies in every market segment for marketing, sales and distribution activities, will need to build the operational capabilities of differentiation (see Figure 4).
basic State Drugs List, drug procurement and other measures to increase the public bidding of drug sales and use of supervision, but also pharmaceutical companies and distribution companies put forward higher requirements. companies need to enhance the pharmaceutical, medical equipment sales and distribution of the transparency of the process and control at the same time, product pricing, market entry, medical claims, etc., need to be strengthened with the government, social insurance institutions relationship management.
create a more competitive and innovative life science market in China
life science industry's competitiveness and innovation is growing. The Chinese government is taking important measures to encourage innovation, improve industry standards, and continuously improve the industrial environment. This is consistent with the national support for domestic companies to extend high-end value chain, engaged in high value-added innovation programs, to enhance local enterprises in China and the global competitiveness of the overall objective.
efforts to promote innovation and to in the global life sciences industry shows great potential for development, the Chinese government to establish bio-pharmaceutical industry as the pillar industry of China in 2020 .16 biomedical industry will account for gross domestic product (GDP) of 4%. bio-industry development, fifteen planning Chinese enterprises encouraged to develop new drugs in 2010 .19 The specific objectives of:
b build 10-20 new drug incubator 8-10
b form drug development alliance
b cultivate a number of chemical drugs , Chinese medicine and biological medicine big business
b 2008-2010 investment budget of 6.6 billion years (about 96 million U.S. dollars)
b completed clinical study of 30 new drugs, for 1-2 innovations with intellectual property rights drugs can be completed or substantially completed in developed countries clinical trials
b 20-30 items and strive to break through the development of innovative drug research key technologies, including chemical medicine, Chinese medicine and biotechnology drug development and quality control of new drugs that the special will
implemented in two tranches, the first establishment of a special group of enterprises the main incubator of innovative drug research center .2008, Beijing Pharmaceutical Group, North China Pharmaceutical, Shijiazhuang Pharmaceutical Group, Zhejiang Medical Group, Tianjin Tasly Group, Jiangsu Hengrui Medicine and other six companies short-listed the first national technology research, innovative drug research and development, new drug research and development of technology platform and other projects.
created a major new drug is one of the special importance of the domestic R & D R & D focus on key areas. For example, specific for the 10 categories (species ) seriously endangers the health of the people of the major disease drug research, standardization of traditional Chinese medicine to strengthen the field of biological agents in the lead. to establish state-level enterprise research center, will help to focus funds and resources to high-potential Chinese enterprises. aware of multinational corporations expensive drug development model is not suitable for China, Chinese companies try to to attract talent, and leading academic institutions and biotechnology companies to form strategic alliances, and many other challenges, but also is becoming a popular innovative multinational territory.
recognized life sciences industry has to attract high value-added manufacturing and the promotion of local employment development potential, local governments have to build a large pharmaceutical industrial park. For example, Tianjin aims to biopharmaceutical R & D base, limited production. At present, around the emergence of highly competitive industrial park, the country is said about 14 Medical Park, the United States only 16. However, there is a lot of multinational companies has completed investments in R & D base, and mainly concentrated in Beijing and Shanghai.
in promoting innovation in local government also play a key role. Figure 5 shows, across different policy to concentrate resources to promote biomedical innovation.
enhance and strengthen the GxP standards, pharmaceutical companies and distribution companies to improve the competitive threshold
China is the implementation and revision of medicines management specification standards that affect the development of drugs to the sales process from all aspects. in research and development, China adopted the International Drug Clinical Practice (GCP) and medical laboratory practice (GLP), mainly used in contract R & D outsourcing (CRO) and other R & D R & D institutions and multinational agencies. China's current Good Manufacturing Practices (GMP) and drug management quality management practices (GSP) with different standards in Europe and America, but the Chinese government has set standards revised and improved to meet the national security and quality requirements. as the Chinese government to improve standards of GMP and GSP, pharmaceutical companies and distribution companies the threshold will be increased competition, which will likely trigger a new round of industry shuffling.
GMP standards to improve the pharmaceutical the operational efficiency of enterprises, higher current requirements of GMP standards in the execution of
when, in fact, expanded the scope of review and improve a request for review in 2004 did not shut down the 1800 GMP standard pharmaceutical enterprises, these enterprises are due to lack of funds and human resources and shut down production. This incident has greatly enhanced the quality awareness of pharmaceutical companies, and to promote the adjustment of industrial structure.
government implemented in 2010 the latest GMP standards to improve the Chinese pharmaceutical companies the level of product quality and competitiveness. The focus of the revised GMP by GMP review and improve the quality control of pharmaceutical companies and software management requirements to ensure business compliance with the management of drug registration and recall regulations. The main changes include :
b pharmaceutical companies apply for GMP certification, to assess their compliance with medication supervision, registration and recall of the Ordinance
b pharmaceutical companies to perform an annual quality inspection and is responsible for the recall of substandard products
b improve drug quality assurance, design validation and change control requirements such as filing a new concept. The current requirements of GMP standards for pharmaceutical companies only on the main production steps and processes for archiving key areas, while the new standards may be required to record and archive products before distribution to the pharmaceutical distribution companies in the entire production process 21
revised GMP standards will encourage enterprises to improve the new drug safety requirements of the pharmaceutical manufacturing enterprises to improve the effectiveness of the system. To meet the new standard for the traceability of product recalls , pharmaceutical companies need to work closely with pharmaceutical distribution companies to ensure the visibility of the process of drug distribution.
China for drug export pharmaceutical companies, for the following national and international quality standards is essential to invest. domestic pharmaceutical companies to upgrade from the production of pharmaceutical raw materials to finished products exported to seek more value-added drug development, the prerequisite is to improve the standards and compliance to meet international standards. At present, less than 20 pharmaceutical companies in China by the EU's European cGMP standards Zhejiang China Sea just got finished a pharmaceutical drug exports to the U.S. certification. Huahai 2007 domestic production of finished products will be successfully exported to the U.S. FDA drug certification, is a milestone in the history of the pharmaceutical industry.
a generic how companies successfully finished drug exports to the U.S. case
Ltd. Zhejiang Huahai start in 1989, is a leading pharmaceutical companies, the main raw material medicine, the company exports to over 30 countries and regions. In 2007, an anti-HIV drugs Huahai received U.S. FDA approval, became the first production by the U.S. FDA approved anti-HIV drugs business. HUAHAI FDA-approved and put the whole application process is painful and enormous: from the beginning of the planning, preparation documents to the FDA field investigations, the whole application process took 5 years to spend more than 1 billion yuan. but the benefits are huge. of course, have to wait until China Sea in May 2012 to patent expiration in the U.S. pharmaceutical exports to the United States. When certification from the FDA to Hua Hailiang after the green light, which not only make the Chinese sea approval from other countries access to drugs easier, but also improves the China Sea and other international pharmaceutical giants capacity. 2008 Merck China Sea by the United States medicine in China, designated as OEM (OEM) of the pharmaceutical companies .22
pharmaceutical quality management specification revision (GSP) standards, will accelerate the maturity of pharmaceutical distribution industry in China released a new version of GSP
comments draft, which will pharmaceutical companies and medical distribution companies, higher demands. excerpt may change the terms of the:
b more stringent regulatory measures: the illegal drug business enterprises to strengthen the punishment, such as suspension, revocation GSP certificate and business license drugs.
b stressed that traceability: new coverage for drugs purchased computer information systems, storage, marketing and other business aspects of all of the requirements of the quality control process in order to achieve the management of the flow of drugs and so on, and the control of sources of procurement of medicines to make strict rules.
b strengthen the management of pharmaceutical distribution companies: the in warehousing of 15,000 square meters area of not less than .23
new GSP, once implemented, will promote the pharmaceutical distribution industry, the acceleration of change. In the past few years, the Chinese pharmaceutical distribution industry has experienced a regional expansion to drive industry consolidation. current China circulation market of the top three market share close to 20%, although with the United States and Japan accounted for 95% of the top three, respectively, compared to 65% of the market share gap between the obvious, but it will be a key turning point in the industry. new changes in GSP requiring companies to have better infrastructure, more efficient operational processes and systems to ensure compliance with government regulations. This may require the implementation of product traceability system and pharmaceutical electronic resume (e-pedigree) and other solutions in the process of production and circulation effective management of medicines. the threshold will increase competition in the industry, some small businesses can not meet the standards could face closure or consolidation.
In short, we expect more innovative enterprises with domestic and competitiveness, China will become more prosperous life science industry shown in Figure 6. multinationals also benefit from their R & D in China and outsourcing manufacturing to find more opportunities for cooperation.
prescription should change: recommendations for life sciences companies to
In the rapidly changing market environment to be successful, life sciences companies need to build and strengthen the three core operational capability: innovation, product quality and sales, marketing and distribution.
innovation: enterprises should strengthen the research capacity to seize this golden opportunity for development
enterprises will continue to strengthen in the short term R & D activities. In addition to the above-mentioned innovative activities of domestic enterprises, multinational pharmaceutical companies grow in accordance with market conditions may still continue to increase R & D (R & D) investment. Enterprise The innovation will be more complex, particularly the exploratory stage in the product.
when China gradually developed into a major global pharmaceutical industry, innovation centers, companies will generally face two major challenges. First, the establishment and strengthening of internal capacity, which can be through talent recruitment, retention and management of projects to be realized, the competition for talent in the pharmaceutical industry, the two centers will focus on the Beijing-Shanghai is particularly intense. The second is to expand through collaboration with external R & D capacity, which is carried out within the current industry model innovation and effective general trend, but also the capacity required for the global R & D institutions. IBM to a recent survey showed that two thirds of the CEO believe that the life sciences staff skills will lead to major changes in the next three years the major companies will face different .24 Challenge Summary Figure 7.
domestic companies choose different strategies can be used to develop its innovative model
domestic generic pharmaceutical companies to innovative drugs from the changes need to gradually build echelon personnel, expertise and access to capital. We the development of its innovative model of domestic enterprises have made different strategic choices.
b hybrid model: low-cost advantage of China to provide outsourcing services for third parties to obtain the funds required for research activities. Hisun ceremony on the adoption of the United States the company produced its own research and development of tuberculosis drugs to raise funds.
b form a strategic alliance: strategic alliances with multinational corporations, academic institutions to establish licensing partnerships to develop profitable product mix, and eventually enter the international market. North China Pharmaceutical new drug development company, Yunnan Institute of Microbiology and the German Institute for Natural Products HKI strategic alliance for cancer drug research.
b into the branded generics market: Simcere to take strategy, the successful introduction of only two edaravone injection, one of the generic product than the deposit (Bicun).
b to expand export markets: the breakdown of generic drug products into export markets, such as the China Sea in addition to the U.S. FDA approved the export of anti-HIV drugs, in early 2008 and successfully exported products to the European preparations.
b Find China has a unique advantage of new market: Focus on domestic and international markets Biosimiliars unregulated commercial development. Such products contain interference factors, growth factors erythropoietin, human insulin, erythropoietin and other growth factors, the production of such drugs Dragon Pharmaceutical company, Toho Pharmaceutical, etc..
multinational enterprises should make full use of China's growing research and development capabilities, increased global sales channels and accelerate time to market
the past few years, many multinational companies have invested heavily in China to establish R & D center. taking into account the importance of the Chinese market and China's potential for innovation, multinational corporations should take the initiative to explore the innovation base in China increased R & D pipeline, clinical trials take full advantage of China's leading CRO capabilities and improve speed to market, accelerate product development.
multinational partners to implement effective strategies bio: 25
b based on the advantages: multinational research and development in China team should actively seek partners in China, including leading research institutions, biotechnology companies, and establish the ideal partner to seek win-win good reputation
b: to understand the unique demands of R & D institutions in China, such as academic research scientists to provide a more influential position
b appropriate alliance management: when partners began to work with global teams, to promote interaction with partners to reduce unnecessary conflicts, a leading multinational has entered
areas of strength in China, hoping to mine from the traditional Chinese medicine infectious diseases, biological agents in the drug, and using the Chinese hepatitis, cancer and other major diseases, population-based participation in global research and development.
manufacturing quality: companies must transform their manufacturing capacity in order to achieve more efficient, lower operating costs and better compliance when the GMP standard production
improve manufacturing quality and compliance to pharmaceutical companies is no longer a differentiation advantage, and become a prerequisite. If properly managed, high-quality harmony manufacturing not only will not increase the regulatory cost of doing business, on the contrary, higher productivity and lower operating costs will bring more business value.
leading pharmaceutical companies should have the following prerequisites in order to improve compliance and improve product quality:
b familiar with compliance requirements, wanting to enter the international market, it is particularly important: If Chinese enterprises want to enter the U.S. market, you need to be familiar with federal law CFR21 requirements and provisions of 210 (the current drug production, processing, packaging or preservation of production management practices) and operate. For example, they will need to consider how to meet the requirements of electronic batch records
b establish an effective quality management processes and systems: through the establishment of systems (including processes, facilities, etc. ) is particularly important to improve the quality, rather than focus only on a single product
b consider the quality of delivery to complete the organization and personnel readiness
b using the appropriate, integrated IT systems to support document management, change control and real-time risk management, integrated IT system can also improve management efficiency, control and improve product quality and traceability
b cooperate with the FDA: FDA sought and established offices in China, the cooperation between
from a strategic, tactical and technical aspects of a structured method of examining:
b strategy: risk assessment, identify failures, production risks and the underlying causes of income. This can help companies sort, to develop and identify best course of action to reduce risk program.
b tactics: the use of science, systems and technology to ensure product and process quality, and product product quality, efficacy and safety.
sales, marketing and distribution: to improve the channels and logistics management can help companies improve operational breadth, accuracy, economy, timely response and security
how to provide more reliable , higher quality and safer drugs are life sciences companies are facing challenges. in addition to the extension of an effective channel strategy and sales force management, pharmaceutical companies and medical distribution companies need to work closely with the effective management of channels and logistics.
the complexity of the Chinese market in sales and marketing at the right time to do, the correct information and data is passed to the right people is challenging. For example, enterprises in the new situation to be successful, needs and national, local Government to establish a solid relationship. marketing major hospitals in addition to the traditional objects of professional doctors, pharmaceutical companies gave the health care reform has brought primary health care work in the new target customers. The community health care and rural health facilities and clinics for the working characteristics of is very different.
enterprises are facing a major challenge is how to cost advantage in the two communities and rural areas to expand into new markets, the main consideration is shown in Figure 8.
to meet the market demand for these dynamic , Life Science Enterprise ...
Life science market in China has become even the engine of global development. even in this financial turmoil, because of strong consumer demand, China's pharmaceutical and medical device market is still maintained double-digit growth every year. China should focus on the concerns of long-term life sciences market development potential. China life sciences market is undergoing a revolutionary change, the most compelling next three years, governments at all levels will be invested in the new health reform 850 billion yuan (about 125 billion U.S. dollars), the healthcare enterprises that is undoubtedly a golden opportunity. Meanwhile, the Chinese government will also aim to create a more transparent and regulated health care market environment. This white paper the main market structure will change and the impact of related enterprises discussed:
1. to improve health insurance coverage to a wider audience can enjoy affordable health care services: pharmaceuticals and medical equipment to stimulate growth in consumption.
2. to provide a more efficient health services: urban primary care system and the establishment of rural health care system to promote a new generation of consumer groups, causing changes in channel structure, and thus on the ability of companies with new operational requirements.
3. to establish and implement national essential drug list drugs online public bidding in order to strengthen drug sales and use regulation.
the Chinese government is committed to promoting the pharmaceutical industry innovation, promote China's pharmaceutical enterprises to enhance competitiveness, thus forming a new pattern of life science market. We believe that this is R & D resources and innovative ways to promote the integration of medicine. When R & D (R & D) the market is full of vitality, will attract more investment; and increased investment will lead to further promote the sound development of pharmaceutical R & D market. China in recent years pharmaceutical manufacturing practices (GMP) and drug quality management specification (GSP) of the revised standards to improve the quality of medicines, but also on pharmaceutical manufacturing and distribution companies set higher requirements. With the further integration of the pharmaceutical industry, a group of weak competitiveness of enterprises will be eliminated, the pharmaceutical industry The access threshold will become higher. In short, we hope that China's life sciences industry will become increasingly mature and more competitive in the international market.
this white paper to the China life sciences companies to the rapid development of and full of success in the market change to provide practical insight into the views. We recommend that companies should follow the following three key operational capabilities to enhance:
b innovation: the development of domestic technology industries and government support for the opportunity to strengthen R & D capacity . through cooperation with external institutions to enhance research and development capabilities, by developing internal talent and manage projects to enhance internal management capabilities.
b production quality: high-quality products is not only the pharmaceutical companies marketing differentiation in the embodiment, it is which pharmaceutical companies first condition of existence. companies must improve productivity, reduce operating costs to achieve supply chain operational excellence.
b sales, marketing and distribution: business channels and by strengthening logistics management, so that more consumers can easily buy high-quality drugs. Therefore, strategies to expand sales channels and strengthen sales force management is the key to future business run-off market. Pharmaceutical manufacturers and pharmaceutical distribution enterprises to be more closely together to enhance overall operational efficiency. the definition of life sciences market
defined our extensive coverage of the life sciences market throughout the health of ecosystems and life sciences ecosystem, the main enterprise (organization), as shown in Figure 1. these companies in the medical field engaged in pharmaceuticals, medical devices and diagnostic tests and other content related to business activities, through innovation (R & D), manufacturing, marketing and distribution of the whole process, and ultimately commitment to patients and provide consumers with better health services. < br> When the slowdown in other industries, China's life sciences market is undoubtedly a bright spot in the global economy. Chinese medicine market because of its huge development potential and attracted much attention. Chinese brand prescription and non prescription drugs (OTC) 1997 years market size of only 37 million, while 2010 is expected to reach 220-250 billion U.S. dollars. expected in 2009 China's pharmaceutical market will reach an annual growth rate of 25%, higher than in other emerging markets growth rate of 15% and much higher in developed countries, about 5% of the market growth rate of .3 is the world's attention even more is expected in 2020 to 220 billion U.S. dollars is expected in the market, second only to the United States the world's second largest pharmaceutical market in China .4
The current health care reform and the Government to establish more innovative and competitive industry initiatives, will promote China's booming life sciences market. When corporate exposure in a more orderly, more regulated market environment, to better meet patient needs demand responsibility, and gradually become a global market leader.
health care reform on China's Life Sciences Industry in China is
health system reform its huge investment In 2009 an unprecedented 1 month, the State Council announced the next two years will be 850 billion yuan investment in the health sector (about 125 billion U.S. dollars), and provide residents with high-quality, affordable health services .5 expects the investment will in the life sciences market, pharmaceutical, medical equipment manufacturing and pharmaceutical distribution and other enterprises have a significant impact.
more people can enjoy affordable health services means that the increase in health care spending, resulting in the demand for drugs and medical equipment rose
health reform One of the main objectives is to solve China's population and of coverage due to lack of medical problems. in recent years in the medical security system in China has made remarkable progress in 2010, various types of health insurance will cover more than 90% of urban and rural residents, Through the implementation of the national basic medical insurance, basic medical insurance for urban residents and the new rural cooperative medical care (referred to NCMS), a wide range of urban and rural residents to improve health insurance coverage. 6
new group health insurance coverage is not only broader, and that the government increased subsidies for individual insurance. For example, the government medical insurance for urban residents per person per year subsidy from the standard 80 yuan to 120 yuan, the new rural cooperative subsidy from the standard 40 yuan per person per year to 120. Government subsidies increase the number of each individual concerned may not, but taking into account the total number of health insurance coverage is very large, this initiative will profoundly affect the total consumption expenditure on health. Analysts predict that by 2011 to increase coverage for health care reform pharmaceutical market brought about expansion will reach 1650-3330 one hundred million yuan .7 There is no doubt the next two years to improve health insurance coverage will promote pharmaceutical sales.
more efficient health service system will change the life of existing scientific institutions channel, product and customer portfolio
reverse city doctors, hospital beds, medical facilities, etc.), the inequality. 8 China's current urban medical service system of medical resources from the hospital too focused on high-end will be referred to a hospital for further treatment.
This marks the existing health service system, patients are mainly concentrated in large urban hospitals would be a dramatic change in status. The new model, the main function of the high-end hospitals is the treatment incurable diseases, serious illness serious illness, teaching and research, large-scale clinical trials and medical research. can be expected, the high-end hospital resource utilization will gradually decline, such as out-patient share from the current 80% to 50%. midrange Hospitals will also be divided, some hospitals with better conditions will be transformed into the top three hospitals, in part poor efficiency, small-scale hospitals, may be converted into community health centers or other services.
With the establishment of urban primary care health system, the number of community health services will grow rapidly. Community health services provided at a lower price treatment of common diseases, preventive health and disease control services, to provide economic and convenient health services. From 2007 to 2010, China will in all level and above the county level cities and in the establishment of 40,000 urban community health services. The goal is 3-10 per million inhabitants, or by district offices and the establishment of a number of health centers community health service stations .9
rapid emergence of health services will be at the basis of medical institutions and medical market enterprises (such as manufacturers of generic drugs, basic medical equipment manufacturers and pharmaceutical distribution business) have a profound impact. Community health services institutions were established, and will be produced in a certain period of significant recruitment and training needs of qualified medical personnel; medical device manufacturers will usher in a new market demand, expected funding for community health for 30% of institution-building will be used to purchase basic medical equipment . Meanwhile, the commonly used drugs, especially generics sales will go up.
three-tier health service system in rural development, life sciences sector will face new customers and channels
will establish a new rural health services in three system so that minor illnesses within the village of rural residents, serious illness not counties. county hospital will become a regional treatment center, the main provider of basic health services and specialist disease clinics, while rural health facilities will also provide training and operational staff and technical guidance . Since the 3 years beginning in 2009, the central key support around 2000 county hospital building, so that each county at least one county-level hospitals to standardize the level of .10
basic community health agencies and similar organizations in the development of rural health for pharmaceutical companies, medical device manufacturers and medical distribution companies to bring new channels and markets. community and the rise of the two major markets in rural areas, will have sales of drugs, types and significant impact on the current channel structure.
strengthen drug sale and use of regulatory, operational requirements of life science institutions change
content as part of new health care reform, medical reform led to widespread popular attention and discussion, especially in drug procurement, drug distribution and so on. Although the drug sales and use implementation details have not yet released, but the new medical reform plan is certain, will strengthen the transparency of drug sales and use, to reduce the total cost of health care services (Figure 3) .11
to control medical costs is a key initiative to establish national Drugs List, based on types and brands of drugs into three categories, each set different types of pharmaceutical reimbursement. A majority of medicines covered by basic drugs, from state subsidies received full reimbursement of the insurance sector, B medicines for a certain reimbursement ratio, C medicines to be paid at their own expense. local governments have increased in the B class directory and remove the flexibility of 5% of drugs. National Drug List will be given the highest guiding price of each drug, and the final price tenders by local governments through decision.
health reform under the new policy, all community health agencies all use the essential drugs list in the variety of other medical and health institutions such as tertiary hospitals should give priority to use the directory prescription drugs .12 In addition, there are some on the use of essential drugs List of proposals to lower drug costs, such as retail pharmacies to buy drugs in the base directory will be included in the scope of reimbursement. The overall objective is to full competition by encouraging the market to further reduce drug prices.
Another important reform is the provincial government for the establishment of centralized procurement of drugs for profit platform, state-owned non-profit medical institutions must all participate in centralized drug purchasing. implementing web-based centralized procurement and online bidding, procurement process to improve health care transparency of the Drug. the provincial government to establish a scientific evaluation of drug procurement methods gradually increase the weights of different elements, such as drug quality, price, service and reputation, and other elements of pharmaceutical manufacturers. Meanwhile, to encourage medical institutions Biaozhun Hua prescription drugs to improve health care quality and regulate the behavior of prescribing part of .13
local governments such as Guangdong have tried to make some reforms. This requires pharmaceutical companies and distribution companies to enhance the quality and cost control. pharmaceutical distribution market will be affected, the next 80% of the essential drugs will be directly delivered to the community or rural health facilities medical institutions, which will encourage the use of large regional and national circulation circulation commercial business, giving rise to the integration of pharmaceutical distribution market. 14
China's health reforms will change the existing channels and customer segments
Chinese medical and health Life sciences companies will bring reform to market changes and opportunities. pharmaceutical companies, especially manufacturers of generic drugs, medical equipment manufacturers, vaccine manufacturers will benefit from increased public expenditure on basic health services and health insurance coverage expansion initiatives have been interests. National Essential Drugs List in 50% of Chinese patent medicines, the Chinese manufacturers are also expected to benefit from.
bring health care reform and pharmaceutical channel structure changes in the consumer market segments. estimated that about 20% of the drugs transferred from the hospital market to the third terminal market, the third terminal market is outside of the hospital pharmacies and retail pharmacies sell drugs directly to consumers terminals, such as community health agencies, clinics, health care centers. 15
us noted that health care reform will promote the formation of three major market segments, companies in every market segment for marketing, sales and distribution activities, will need to build the operational capabilities of differentiation (see Figure 4).
basic State Drugs List, drug procurement and other measures to increase the public bidding of drug sales and use of supervision, but also pharmaceutical companies and distribution companies put forward higher requirements. companies need to enhance the pharmaceutical, medical equipment sales and distribution of the transparency of the process and control at the same time, product pricing, market entry, medical claims, etc., need to be strengthened with the government, social insurance institutions relationship management.
create a more competitive and innovative life science market in China
life science industry's competitiveness and innovation is growing. The Chinese government is taking important measures to encourage innovation, improve industry standards, and continuously improve the industrial environment. This is consistent with the national support for domestic companies to extend high-end value chain, engaged in high value-added innovation programs, to enhance local enterprises in China and the global competitiveness of the overall objective.
efforts to promote innovation and to in the global life sciences industry shows great potential for development, the Chinese government to establish bio-pharmaceutical industry as the pillar industry of China in 2020 .16 biomedical industry will account for gross domestic product (GDP) of 4%. bio-industry development, fifteen planning Chinese enterprises encouraged to develop new drugs in 2010 .19 The specific objectives of:
b build 10-20 new drug incubator 8-10
b form drug development alliance
b cultivate a number of chemical drugs , Chinese medicine and biological medicine big business
b 2008-2010 investment budget of 6.6 billion years (about 96 million U.S. dollars)
b completed clinical study of 30 new drugs, for 1-2 innovations with intellectual property rights drugs can be completed or substantially completed in developed countries clinical trials
b 20-30 items and strive to break through the development of innovative drug research key technologies, including chemical medicine, Chinese medicine and biotechnology drug development and quality control of new drugs that the special will
implemented in two tranches, the first establishment of a special group of enterprises the main incubator of innovative drug research center .2008, Beijing Pharmaceutical Group, North China Pharmaceutical, Shijiazhuang Pharmaceutical Group, Zhejiang Medical Group, Tianjin Tasly Group, Jiangsu Hengrui Medicine and other six companies short-listed the first national technology research, innovative drug research and development, new drug research and development of technology platform and other projects.
created a major new drug is one of the special importance of the domestic R & D R & D focus on key areas. For example, specific for the 10 categories (species ) seriously endangers the health of the people of the major disease drug research, standardization of traditional Chinese medicine to strengthen the field of biological agents in the lead. to establish state-level enterprise research center, will help to focus funds and resources to high-potential Chinese enterprises. aware of multinational corporations expensive drug development model is not suitable for China, Chinese companies try to to attract talent, and leading academic institutions and biotechnology companies to form strategic alliances, and many other challenges, but also is becoming a popular innovative multinational territory.
recognized life sciences industry has to attract high value-added manufacturing and the promotion of local employment development potential, local governments have to build a large pharmaceutical industrial park. For example, Tianjin aims to biopharmaceutical R & D base, limited production. At present, around the emergence of highly competitive industrial park, the country is said about 14 Medical Park, the United States only 16. However, there is a lot of multinational companies has completed investments in R & D base, and mainly concentrated in Beijing and Shanghai.
in promoting innovation in local government also play a key role. Figure 5 shows, across different policy to concentrate resources to promote biomedical innovation.
enhance and strengthen the GxP standards, pharmaceutical companies and distribution companies to improve the competitive threshold
China is the implementation and revision of medicines management specification standards that affect the development of drugs to the sales process from all aspects. in research and development, China adopted the International Drug Clinical Practice (GCP) and medical laboratory practice (GLP), mainly used in contract R & D outsourcing (CRO) and other R & D R & D institutions and multinational agencies. China's current Good Manufacturing Practices (GMP) and drug management quality management practices (GSP) with different standards in Europe and America, but the Chinese government has set standards revised and improved to meet the national security and quality requirements. as the Chinese government to improve standards of GMP and GSP, pharmaceutical companies and distribution companies the threshold will be increased competition, which will likely trigger a new round of industry shuffling.
GMP standards to improve the pharmaceutical the operational efficiency of enterprises, higher current requirements of GMP standards in the execution of
when, in fact, expanded the scope of review and improve a request for review in 2004 did not shut down the 1800 GMP standard pharmaceutical enterprises, these enterprises are due to lack of funds and human resources and shut down production. This incident has greatly enhanced the quality awareness of pharmaceutical companies, and to promote the adjustment of industrial structure.
government implemented in 2010 the latest GMP standards to improve the Chinese pharmaceutical companies the level of product quality and competitiveness. The focus of the revised GMP by GMP review and improve the quality control of pharmaceutical companies and software management requirements to ensure business compliance with the management of drug registration and recall regulations. The main changes include :
b pharmaceutical companies apply for GMP certification, to assess their compliance with medication supervision, registration and recall of the Ordinance
b pharmaceutical companies to perform an annual quality inspection and is responsible for the recall of substandard products
b improve drug quality assurance, design validation and change control requirements such as filing a new concept. The current requirements of GMP standards for pharmaceutical companies only on the main production steps and processes for archiving key areas, while the new standards may be required to record and archive products before distribution to the pharmaceutical distribution companies in the entire production process 21
revised GMP standards will encourage enterprises to improve the new drug safety requirements of the pharmaceutical manufacturing enterprises to improve the effectiveness of the system. To meet the new standard for the traceability of product recalls , pharmaceutical companies need to work closely with pharmaceutical distribution companies to ensure the visibility of the process of drug distribution.
China for drug export pharmaceutical companies, for the following national and international quality standards is essential to invest. domestic pharmaceutical companies to upgrade from the production of pharmaceutical raw materials to finished products exported to seek more value-added drug development, the prerequisite is to improve the standards and compliance to meet international standards. At present, less than 20 pharmaceutical companies in China by the EU's European cGMP standards Zhejiang China Sea just got finished a pharmaceutical drug exports to the U.S. certification. Huahai 2007 domestic production of finished products will be successfully exported to the U.S. FDA drug certification, is a milestone in the history of the pharmaceutical industry.
a generic how companies successfully finished drug exports to the U.S. case
Ltd. Zhejiang Huahai start in 1989, is a leading pharmaceutical companies, the main raw material medicine, the company exports to over 30 countries and regions. In 2007, an anti-HIV drugs Huahai received U.S. FDA approval, became the first production by the U.S. FDA approved anti-HIV drugs business. HUAHAI FDA-approved and put the whole application process is painful and enormous: from the beginning of the planning, preparation documents to the FDA field investigations, the whole application process took 5 years to spend more than 1 billion yuan. but the benefits are huge. of course, have to wait until China Sea in May 2012 to patent expiration in the U.S. pharmaceutical exports to the United States. When certification from the FDA to Hua Hailiang after the green light, which not only make the Chinese sea approval from other countries access to drugs easier, but also improves the China Sea and other international pharmaceutical giants capacity. 2008 Merck China Sea by the United States medicine in China, designated as OEM (OEM) of the pharmaceutical companies .22
pharmaceutical quality management specification revision (GSP) standards, will accelerate the maturity of pharmaceutical distribution industry in China released a new version of GSP
comments draft, which will pharmaceutical companies and medical distribution companies, higher demands. excerpt may change the terms of the:
b more stringent regulatory measures: the illegal drug business enterprises to strengthen the punishment, such as suspension, revocation GSP certificate and business license drugs.
b stressed that traceability: new coverage for drugs purchased computer information systems, storage, marketing and other business aspects of all of the requirements of the quality control process in order to achieve the management of the flow of drugs and so on, and the control of sources of procurement of medicines to make strict rules.
b strengthen the management of pharmaceutical distribution companies: the in warehousing of 15,000 square meters area of not less than .23
new GSP, once implemented, will promote the pharmaceutical distribution industry, the acceleration of change. In the past few years, the Chinese pharmaceutical distribution industry has experienced a regional expansion to drive industry consolidation. current China circulation market of the top three market share close to 20%, although with the United States and Japan accounted for 95% of the top three, respectively, compared to 65% of the market share gap between the obvious, but it will be a key turning point in the industry. new changes in GSP requiring companies to have better infrastructure, more efficient operational processes and systems to ensure compliance with government regulations. This may require the implementation of product traceability system and pharmaceutical electronic resume (e-pedigree) and other solutions in the process of production and circulation effective management of medicines. the threshold will increase competition in the industry, some small businesses can not meet the standards could face closure or consolidation.
In short, we expect more innovative enterprises with domestic and competitiveness, China will become more prosperous life science industry shown in Figure 6. multinationals also benefit from their R & D in China and outsourcing manufacturing to find more opportunities for cooperation.
prescription should change: recommendations for life sciences companies to
In the rapidly changing market environment to be successful, life sciences companies need to build and strengthen the three core operational capability: innovation, product quality and sales, marketing and distribution.
innovation: enterprises should strengthen the research capacity to seize this golden opportunity for development
enterprises will continue to strengthen in the short term R & D activities. In addition to the above-mentioned innovative activities of domestic enterprises, multinational pharmaceutical companies grow in accordance with market conditions may still continue to increase R & D (R & D) investment. Enterprise The innovation will be more complex, particularly the exploratory stage in the product.
when China gradually developed into a major global pharmaceutical industry, innovation centers, companies will generally face two major challenges. First, the establishment and strengthening of internal capacity, which can be through talent recruitment, retention and management of projects to be realized, the competition for talent in the pharmaceutical industry, the two centers will focus on the Beijing-Shanghai is particularly intense. The second is to expand through collaboration with external R & D capacity, which is carried out within the current industry model innovation and effective general trend, but also the capacity required for the global R & D institutions. IBM to a recent survey showed that two thirds of the CEO believe that the life sciences staff skills will lead to major changes in the next three years the major companies will face different .24 Challenge Summary Figure 7.
domestic companies choose different strategies can be used to develop its innovative model
domestic generic pharmaceutical companies to innovative drugs from the changes need to gradually build echelon personnel, expertise and access to capital. We the development of its innovative model of domestic enterprises have made different strategic choices.
b hybrid model: low-cost advantage of China to provide outsourcing services for third parties to obtain the funds required for research activities. Hisun ceremony on the adoption of the United States the company produced its own research and development of tuberculosis drugs to raise funds.
b form a strategic alliance: strategic alliances with multinational corporations, academic institutions to establish licensing partnerships to develop profitable product mix, and eventually enter the international market. North China Pharmaceutical new drug development company, Yunnan Institute of Microbiology and the German Institute for Natural Products HKI strategic alliance for cancer drug research.
b into the branded generics market: Simcere to take strategy, the successful introduction of only two edaravone injection, one of the generic product than the deposit (Bicun).
b to expand export markets: the breakdown of generic drug products into export markets, such as the China Sea in addition to the U.S. FDA approved the export of anti-HIV drugs, in early 2008 and successfully exported products to the European preparations.
b Find China has a unique advantage of new market: Focus on domestic and international markets Biosimiliars unregulated commercial development. Such products contain interference factors, growth factors erythropoietin, human insulin, erythropoietin and other growth factors, the production of such drugs Dragon Pharmaceutical company, Toho Pharmaceutical, etc..
multinational enterprises should make full use of China's growing research and development capabilities, increased global sales channels and accelerate time to market
the past few years, many multinational companies have invested heavily in China to establish R & D center. taking into account the importance of the Chinese market and China's potential for innovation, multinational corporations should take the initiative to explore the innovation base in China increased R & D pipeline, clinical trials take full advantage of China's leading CRO capabilities and improve speed to market, accelerate product development.
multinational partners to implement effective strategies bio: 25
b based on the advantages: multinational research and development in China team should actively seek partners in China, including leading research institutions, biotechnology companies, and establish the ideal partner to seek win-win good reputation
b: to understand the unique demands of R & D institutions in China, such as academic research scientists to provide a more influential position
b appropriate alliance management: when partners began to work with global teams, to promote interaction with partners to reduce unnecessary conflicts, a leading multinational has entered
areas of strength in China, hoping to mine from the traditional Chinese medicine infectious diseases, biological agents in the drug, and using the Chinese hepatitis, cancer and other major diseases, population-based participation in global research and development.
manufacturing quality: companies must transform their manufacturing capacity in order to achieve more efficient, lower operating costs and better compliance when the GMP standard production
improve manufacturing quality and compliance to pharmaceutical companies is no longer a differentiation advantage, and become a prerequisite. If properly managed, high-quality harmony manufacturing not only will not increase the regulatory cost of doing business, on the contrary, higher productivity and lower operating costs will bring more business value.
leading pharmaceutical companies should have the following prerequisites in order to improve compliance and improve product quality:
b familiar with compliance requirements, wanting to enter the international market, it is particularly important: If Chinese enterprises want to enter the U.S. market, you need to be familiar with federal law CFR21 requirements and provisions of 210 (the current drug production, processing, packaging or preservation of production management practices) and operate. For example, they will need to consider how to meet the requirements of electronic batch records
b establish an effective quality management processes and systems: through the establishment of systems (including processes, facilities, etc. ) is particularly important to improve the quality, rather than focus only on a single product
b consider the quality of delivery to complete the organization and personnel readiness
b using the appropriate, integrated IT systems to support document management, change control and real-time risk management, integrated IT system can also improve management efficiency, control and improve product quality and traceability
b cooperate with the FDA: FDA sought and established offices in China, the cooperation between
from a strategic, tactical and technical aspects of a structured method of examining:
b strategy: risk assessment, identify failures, production risks and the underlying causes of income. This can help companies sort, to develop and identify best course of action to reduce risk program.
b tactics: the use of science, systems and technology to ensure product and process quality, and product product quality, efficacy and safety.
sales, marketing and distribution: to improve the channels and logistics management can help companies improve operational breadth, accuracy, economy, timely response and security
how to provide more reliable , higher quality and safer drugs are life sciences companies are facing challenges. in addition to the extension of an effective channel strategy and sales force management, pharmaceutical companies and medical distribution companies need to work closely with the effective management of channels and logistics.
the complexity of the Chinese market in sales and marketing at the right time to do, the correct information and data is passed to the right people is challenging. For example, enterprises in the new situation to be successful, needs and national, local Government to establish a solid relationship. marketing major hospitals in addition to the traditional objects of professional doctors, pharmaceutical companies gave the health care reform has brought primary health care work in the new target customers. The community health care and rural health facilities and clinics for the working characteristics of is very different.
enterprises are facing a major challenge is how to cost advantage in the two communities and rural areas to expand into new markets, the main consideration is shown in Figure 8.
to meet the market demand for these dynamic , Life Science Enterprise ...
Wednesday, February 23, 2011
The story of two men
The story of two people
1
03 in the summer, I fallen off to another school after the repeat.
A classroom door, I found a space to sit down casually, Wang Leyan podium that a big deal than I After many years of female teachers, to cool the room and looked at the group of students will be my She wore a very simple m at least the group I have seen fancy dress who want much more simple. black hair scattered on the back, a face is not beautiful, it can not be said to be handsome. Somehow, I seen so many beautiful women, never have heart like this feeling, perhaps her momentum that comes out of it. I do not know exactly hh
Today is the first day of school, I sat in the classroom, and others chat with other people in conversation, I learned today there was a man into my classes, I heard that was a say Although the class leader, but did not want his big dealings hh
2
day at school was really boring, can often call with former brothers to talk, chat, and it is nothing to do to only play on the computer. days to the disappearance of such a day, and I mm to sink day by day I have always sink to the bottom, just do not know what the bottom is the following, plenty of time now anyway, why not try it. I was surprised that she, then thin , turned out to be squad leader, in possession of this class of hand and foot, and not thinking too much different, she's learning is very good, helpful people, optimistic, cheerful, maybe these are her class when the class leader and will rule oral reasons to be convinced.
In this class, except me, the passing rate is 100 ℅, is the focus of the class of cultivation, the president of my uncle had perhaps I can take this excellent learning environment , to get rid of bad habits. But now, I pull this class in the hind legs, is really ridiculous hh
he was really angry, why do I have to help him, but he 拒人于千里之外, in the end why? In fact, he is not stupid, I can from his notebooks that he wrote some poetry notebooks and writing, usually in the dark for Beijing, it is sad, very touching. did not think his writing could be so good, will be interpretation in the dark so thoroughly, looked like he was living in the dark background. But when I asked him, he said it was copied, not written by him. But I do not believe, I know it must be written by him, Only he can write such sad article. may be why he did not learn it? why I have so many fans, her body seemed to be surrounded by fog, do not allow others to see him, recognize him. Why? I have To uncover this mystery.
3
past few nights I have been following her and protect her. Why should I protect her? I do not know. just unconscious, a school to follow her footsteps . the brain constantly diverted away sent a signal to his feet refused to move, followed her, until she return home safely, into the house, only to settle down.
these days, she seems to mean to me , ran to my side from time to time to chat with me. have asked several times on my laptop who wrote that article, I said almost spilled the beans, but I did not tell her. I just told her This is a site I can see, that to write well, to copy down, and told her that the people writing these articles is the person named purgatory, and told her the URL of the site. and told her best Do not go, that site is too dark, and log off to one of those things is something with dark colors, though touching, but it is easier to teach bad. I do not want to harm her. Actually, I did not tell her, hell is my screen name, I opened that site also, which is what I wrote. I do not want to tell her that, a I loved the people, I still retain most of the secrets hidden in the words, but only a few, very little of the important secrets for others to explore. read my articles know that I used a word: A I do not want others to know this character, hh, do not insist.
Today I chat with him, I found that he was concerned forlorn, he seems not to want to let people know the secret, that he did not want to let others know him. how to solve this big mystery, the head What a mess. Fortunately, however, he told me a website URL, but also told me some stories of purgatory. I feel very sad, though this hell, but let people think it is an interesting person.
successful landing site at 11:12 I had no idea where the hell the whole image, the main color is gray, and the background picture for the hell map, it is the name for hell, I first call up purgatory of some public information and found his 14-year-old began some articles posted in some forums, aged 16, opened the site, the site of more than 200 articles on writing, two novellas, poetry, more than 60 first, is a very talented good people. I picked up an article called would anyone write such sad words to. woman's sixth sense told me that the hell is he, only he could write such sad words, and only he can understand the pain of life. do not know why, I always have so many thoughts in my brain waves.
the plane, I lay in bed, my mind there is always a mist shrouded the man, but always blind to see, but I know that figure is that he He waved at me hiding behind the mist, waving to me to open that layer of mist, Barbara's understand him, understand him.
whispered sound asleep.
4
I finally began to seriously lectures, and only because I found that I had liked her, but she grades are so good, and I, results are so poor, so that results, how can I convince her tell the truth, I want to shorten the distance between us, so I started to seriously lectures, doing problem seriously. I discovered that something so easy on the books, the original title is not a difficult task to do, how I had no discovery? Maybe I never had one lesson on it seriously. night I still followed her, were delivered to her door, is planning to leave, did not expect to be rushed to a boy, took her hand link, seems very happy to see her faint, tried to shake his hand, but if Shuaibu Diao, evidently be very severe noisy. I am very angry, his hands clenched into a hammer and would like to rush to , but I did not. I slowly pulled out his cellphone and dialed the familiar number, dial, I just say I hung up the place, the cooperation of our past experience, I know he'll understand. I rely on In the wall, staring at them quarrel, and finally, she shake him off and ran into the house. and he, had been there for a while, the left.
then I heard the motor sound, I sneered the voice, said: soon caught up with him, and two vehicles stuck in his face, I slowly get off, sneered, waving an iron bar, he looked at me scared E, trembling and asked: ; the person next to me said: After the sound, we get away vehicle, leaving him a man, lying on the ground groaning in pain.
papers issued today, did not think he's such a good test, really can not, by definition, only a few worse than me points, his success became the focus of the whole school year, in fact, he is the one focus, not that is rebellious, but now is good.
go home at night, just about to enter the house, who thought that the very discussion of evil men said he liked me, but also holding my hand, so disgusting, the fought, I saw him. he quietly against the wall, took out his mobile to say what they immediately hung up, I think he come back to help me free, but he did not, he just quietly against the wall, from beginning to end, I suddenly felt his heart hurts, and why? heart is so painful. Is just because he saw that I was someone else not come to my rescue pestering and heartache. or, I like him? not, how did I like him, his thoughts a mess, I hard a walk away, rushed into the house.
water, how will my face water. No, not water, and tears. may be why I cry, why?
out the window, voices sounded loud vehicle, I went out the window, saw him riding on a motor vehicle, took root iron. speeding away. he going to do, why take the iron bar, is it not in the mood to fight hh
homework, had to go online, the website successfully log in purgatory, the election of the chapter called man purgatory. came to the school to see him properly seated, it seems that no matter, my peace of mind settle down, back seat, the guy did not come to class last night, listening to the teacher says he has been playing, and who more than a dozen fractures , not 度过危险期. I know he did it, did not think he should so bold, will not be because of me. If it is because of me. Then I really became a sinner.
5
I told my uncle that I want to move, in her rented house neighborhood. I do not want her to hurt anymore, since I like him, they should protect her. I was a special situation of the people, found a woman, would wholeheartedly must make her happy.
moving things downstairs sound really annoying, noisy, I can not read. can only see the watch.
in a pile of furniture, there is a familiar figure in the busy is his, would be his. Did he want to move up here, how could. I went with him hello, asked: Q. Who wrote it, this time he told me he wrote, purgatory is his screen name. I was surprised, although I have prepared, but through his mouth to say, was very surprised. I asked him if he does not publish a book, he said, not going to, later do not know, really strange, but he was a strange man.
me the mystery is slowly being opened, which is hidden in numerous small mystery, so that I'm dizzy. But good news is, I know him the addition of some, I believe that sooner or later I will solve these mysteries one by one, completely understand the inner world of the man he was, I'm confident.
6
I declare to her, she just said no reaction in the test and then go ahead. how to do, if she does not like me, then I do not this time around the effort in vain. Even so, I did not force her, I just say that you carefully consider it, the test to the test, waited so long, not bad these days.
brothers party, I brought her in the bar, I asked her, is the second time you to such a place, and she nodded. brothers have come, the second with a smile said to me, the last time you had for her ah. I described to her said: brothers, by the age, I'm the oldest, the second is called tiger blood, the third is called Tiger, youngest son called passionate tiger, white tiger called Five. lane black friends told us to Fab Five. of endurance, if you can not stand, do not fight back, you just say, he grocery store will not appear once in front of you, this is the special situation of the characteristics of hh drink a lot more than words can Can Can, and she has been sitting there, drinking orange juice, watching our noisy, like an angel watching her followers gathered.
late, casual gatherings I drove her, and flying in the street with, and occasionally from promising a mirror, so pure, so beautiful, as if an angel came down. Perhaps she is an angel, to save my people in the dark.
he declare to me, and so excited, but I did not immediately say yes, then I say that in the examination, he agreed, he told me good, then I understand, tolerate, and I know he really likes me. but I can now say yes. because I had on the parents said that in the exam, I will not fall in love. Perhaps it is very unfair to him, but it can be said to give him a test, try him I love how deep in the end.
he took me to join his fraternity. cold Tiger, blood tiger, tiger, passionate tiger, white tiger, black Fab Five. I could have fixed and black sitting in the same Fab Five on the table, spread out, people will think I'm bad. forget it, just happy like, why should others are saying.
impressed me most is the white tiger, he is so white, so quiet, is simply a pale-faced scholar how could Fab Five process is linked with the black is really baffling. Maybe they have some extraordinary experience. so they will go together, but unfortunately the hero hero.
in their conversation, I know that they are abandoned by their families, and later by their foster parent shelter, and he is lost in the subway by their parents, two or three in the subway station alone at the age of 1 month of life, so miserable. No wonder his character is so cold, the original is the human loss of confidence. send him articles on the site could be so similar, did not he write the secret is in the article, no wonder he wrote, and then worry about writing dark, in the original may not be his personal experience, what a poor people, then I want to look good to these articles to enhance his understanding. with my character to change his cold, and I believe I can do.
party scattered, and I boarded his vehicle, he Zhang car wings are affixed stickers black tiger, so handsome. my hands holding his head on his back, receiving came from the temperature of his back, feeling good.
7
short and long 3 days in the test was over at last, I finally liberated, and finally you can easily play. Since her confession, I have not played easy, and now finally have the chance. I My hand, and looked up at the land surface right for fear of hitting people. busy almost easy music. Time with ears blowing in the wind and I looked up and down the Department of flies by, we knew we stay away from the city.
appear in front of a van, blocking my way, I know ill intent, get back to her, run, do not look back, I have other brothers phone number, you just call the tiger blood. I will finish phone secretly into her hands. that almost all people in the car down, I whispered before running for about 20m, turn the front, see the car they want, with the go, while looking out the back looking mirror, the side pedal to the metal. in a corner, I put her thrown into the grass, walk alone. A few minutes later, no oil tank, and I was forced to stop vehicles, out of hiding cars in the bar, waiting for them back the vehicle, almost half a minute later, they caught up with me. I dragged an iron bar left and right cut, I do not know how long, who know only a few fractures, continuous blood flow. Finally, I lay a pool of blood, loss of consciousness.
in the test after he invited me to drag racing, sitting in his Tiger on, feel the feeling of the wind whistling from the ear, his broad back of the upload to the warmth, I feel I'm so happy. heard him say a meteor shower tonight, he took me to see, so romantic. did not think like a person is so happy.
lying on his back, closed eyes, let the hair floating freely back and feel the warm wind howls from the ear, made me sleepy.
suddenly stop the car, I was awakened to see parked in front of van, the car went down a lot of people who took the iron bar, I'm scared, holding him tightly.
he gently asked me to run, I called in the blood of the tiger, and inserted into a mobile phone my hands. from the mirror after looking to see that he may calm, calm almost cruel. I do not know how to do. Then he engine car, and rushed toward them, knocking down two, we break loose. I had I thought we could escape, I did not expect he turned his head towards them to go, and after 1 hit, I was afraid to move for the tight close your eyes, ear and growing, I felt he was fierce throttle, speed. Although in this case, he did not nervous, calm, unusual calm, no wonder the tiger is called cold, not quite sure how the president and his principal has a relationship.
I was thinking about when Di Hu ears suddenly came to him, run. I did not react from time to time, people have dropped in the grass, who was a rock to draw a few road wound, it hurts. and so I opened my eyes, he was in another a corner disappeared, with both the disappearance of the van that bike in the corner. I'm busy out phone, find the blood of the tiger's phone number. phone to get through, I'm anxious to tell him the situation and leave the cold tiger direction. hung up the phone After I climbed highway in the direction toward the cold to chase the tiger away.
I do not know throw a few somersault, feet have been numb pain. I finally caught up with them. and he does not fall in the blood , motionless, blood tiger they were busy people with the name on the van, no one to help him stop the bleeding, I rushed to hand hold the wound, the tears kept on dropping, and his blood melt in a go, flow hard road hh
8
I slowly opened my eyes, a sight Cancan clear. She flutter in my bed, sleep in very familiar face looming round after round of tears, she seemed very tired, So let her get some sleep much. I looked at her sleeping quietly, motionless.
she woke up and saw I looked at her face turned to red, red, cute. She suddenly ran out a while, come in a bunch of people, in animated conversation, keep me from Hao Fan. can not ignore them I had to bite the bullet, and they talk. are finally gone, leaving only Under her four brothers and foster parent. I'm inside, they said, you go out, I want to talk to her alone. They left the room only me and her. I calmly told her Road, the last time you do not mean to think about it? is not taken into account, when I do not exist, forget me. she was surprised and asked him why? me, do not ask, to the site at night, I will tell you everything. she was gone , crying bitterly. My heart hurts, and I did not want to hurt her, but she followed me there will not be happy. for her good, I only have to do.
year later, I'm all good. Blood Tiger told those guys I finally found the whereabouts of, and is cold man. the day, we bring along troops, into the wind the nest, the one that turned upside down, we go.
I and return to independence, the secret firmly buried in the bottom of my heart.
I understand that the bottom of the following is purgatory.
he slept more than five days, finally woke up. I had to say to him I promised him. But he said No, he did not want me there before. how is it possible, I'm so sad, I did not expect to be abandoned is so uncomfortable.
night I went to site, he posted an article on its website a new composition , entitled Purgatory and the site concerned.
Postscript: two stories to this end, after the story, I do not know whether there will be, They result, it is the way he did not know, she did not know, I do not know. I think no one would know. let the god of marriage to busy. we can not help them. Perhaps, he and she, never goodbye, perhaps, They soon married. What can not do, is not it!
1
03 in the summer, I fallen off to another school after the repeat.
A classroom door, I found a space to sit down casually, Wang Leyan podium that a big deal than I After many years of female teachers, to cool the room and looked at the group of students will be my She wore a very simple m at least the group I have seen fancy dress who want much more simple. black hair scattered on the back, a face is not beautiful, it can not be said to be handsome. Somehow, I seen so many beautiful women, never have heart like this feeling, perhaps her momentum that comes out of it. I do not know exactly hh
Today is the first day of school, I sat in the classroom, and others chat with other people in conversation, I learned today there was a man into my classes, I heard that was a say Although the class leader, but did not want his big dealings hh
2
day at school was really boring, can often call with former brothers to talk, chat, and it is nothing to do to only play on the computer. days to the disappearance of such a day, and I mm to sink day by day I have always sink to the bottom, just do not know what the bottom is the following, plenty of time now anyway, why not try it. I was surprised that she, then thin , turned out to be squad leader, in possession of this class of hand and foot, and not thinking too much different, she's learning is very good, helpful people, optimistic, cheerful, maybe these are her class when the class leader and will rule oral reasons to be convinced.
In this class, except me, the passing rate is 100 ℅, is the focus of the class of cultivation, the president of my uncle had perhaps I can take this excellent learning environment , to get rid of bad habits. But now, I pull this class in the hind legs, is really ridiculous hh
he was really angry, why do I have to help him, but he 拒人于千里之外, in the end why? In fact, he is not stupid, I can from his notebooks that he wrote some poetry notebooks and writing, usually in the dark for Beijing, it is sad, very touching. did not think his writing could be so good, will be interpretation in the dark so thoroughly, looked like he was living in the dark background. But when I asked him, he said it was copied, not written by him. But I do not believe, I know it must be written by him, Only he can write such sad article. may be why he did not learn it? why I have so many fans, her body seemed to be surrounded by fog, do not allow others to see him, recognize him. Why? I have To uncover this mystery.
3
past few nights I have been following her and protect her. Why should I protect her? I do not know. just unconscious, a school to follow her footsteps . the brain constantly diverted away sent a signal to his feet refused to move, followed her, until she return home safely, into the house, only to settle down.
these days, she seems to mean to me , ran to my side from time to time to chat with me. have asked several times on my laptop who wrote that article, I said almost spilled the beans, but I did not tell her. I just told her This is a site I can see, that to write well, to copy down, and told her that the people writing these articles is the person named purgatory, and told her the URL of the site. and told her best Do not go, that site is too dark, and log off to one of those things is something with dark colors, though touching, but it is easier to teach bad. I do not want to harm her. Actually, I did not tell her, hell is my screen name, I opened that site also, which is what I wrote. I do not want to tell her that, a I loved the people, I still retain most of the secrets hidden in the words, but only a few, very little of the important secrets for others to explore. read my articles know that I used a word: A I do not want others to know this character, hh, do not insist.
Today I chat with him, I found that he was concerned forlorn, he seems not to want to let people know the secret, that he did not want to let others know him. how to solve this big mystery, the head What a mess. Fortunately, however, he told me a website URL, but also told me some stories of purgatory. I feel very sad, though this hell, but let people think it is an interesting person.
successful landing site at 11:12 I had no idea where the hell the whole image, the main color is gray, and the background picture for the hell map, it is the name for hell, I first call up purgatory of some public information and found his 14-year-old began some articles posted in some forums, aged 16, opened the site, the site of more than 200 articles on writing, two novellas, poetry, more than 60 first, is a very talented good people. I picked up an article called would anyone write such sad words to. woman's sixth sense told me that the hell is he, only he could write such sad words, and only he can understand the pain of life. do not know why, I always have so many thoughts in my brain waves.
the plane, I lay in bed, my mind there is always a mist shrouded the man, but always blind to see, but I know that figure is that he He waved at me hiding behind the mist, waving to me to open that layer of mist, Barbara's understand him, understand him.
whispered sound asleep.
4
I finally began to seriously lectures, and only because I found that I had liked her, but she grades are so good, and I, results are so poor, so that results, how can I convince her tell the truth, I want to shorten the distance between us, so I started to seriously lectures, doing problem seriously. I discovered that something so easy on the books, the original title is not a difficult task to do, how I had no discovery? Maybe I never had one lesson on it seriously. night I still followed her, were delivered to her door, is planning to leave, did not expect to be rushed to a boy, took her hand link, seems very happy to see her faint, tried to shake his hand, but if Shuaibu Diao, evidently be very severe noisy. I am very angry, his hands clenched into a hammer and would like to rush to , but I did not. I slowly pulled out his cellphone and dialed the familiar number, dial, I just say I hung up the place, the cooperation of our past experience, I know he'll understand. I rely on In the wall, staring at them quarrel, and finally, she shake him off and ran into the house. and he, had been there for a while, the left.
then I heard the motor sound, I sneered the voice, said: soon caught up with him, and two vehicles stuck in his face, I slowly get off, sneered, waving an iron bar, he looked at me scared E, trembling and asked: ; the person next to me said: After the sound, we get away vehicle, leaving him a man, lying on the ground groaning in pain.
papers issued today, did not think he's such a good test, really can not, by definition, only a few worse than me points, his success became the focus of the whole school year, in fact, he is the one focus, not that is rebellious, but now is good.
go home at night, just about to enter the house, who thought that the very discussion of evil men said he liked me, but also holding my hand, so disgusting, the fought, I saw him. he quietly against the wall, took out his mobile to say what they immediately hung up, I think he come back to help me free, but he did not, he just quietly against the wall, from beginning to end, I suddenly felt his heart hurts, and why? heart is so painful. Is just because he saw that I was someone else not come to my rescue pestering and heartache. or, I like him? not, how did I like him, his thoughts a mess, I hard a walk away, rushed into the house.
water, how will my face water. No, not water, and tears. may be why I cry, why?
out the window, voices sounded loud vehicle, I went out the window, saw him riding on a motor vehicle, took root iron. speeding away. he going to do, why take the iron bar, is it not in the mood to fight hh
homework, had to go online, the website successfully log in purgatory, the election of the chapter called man purgatory. came to the school to see him properly seated, it seems that no matter, my peace of mind settle down, back seat, the guy did not come to class last night, listening to the teacher says he has been playing, and who more than a dozen fractures , not 度过危险期. I know he did it, did not think he should so bold, will not be because of me. If it is because of me. Then I really became a sinner.
5
I told my uncle that I want to move, in her rented house neighborhood. I do not want her to hurt anymore, since I like him, they should protect her. I was a special situation of the people, found a woman, would wholeheartedly must make her happy.
moving things downstairs sound really annoying, noisy, I can not read. can only see the watch.
in a pile of furniture, there is a familiar figure in the busy is his, would be his. Did he want to move up here, how could. I went with him hello, asked: Q. Who wrote it, this time he told me he wrote, purgatory is his screen name. I was surprised, although I have prepared, but through his mouth to say, was very surprised. I asked him if he does not publish a book, he said, not going to, later do not know, really strange, but he was a strange man.
me the mystery is slowly being opened, which is hidden in numerous small mystery, so that I'm dizzy. But good news is, I know him the addition of some, I believe that sooner or later I will solve these mysteries one by one, completely understand the inner world of the man he was, I'm confident.
6
I declare to her, she just said no reaction in the test and then go ahead. how to do, if she does not like me, then I do not this time around the effort in vain. Even so, I did not force her, I just say that you carefully consider it, the test to the test, waited so long, not bad these days.
brothers party, I brought her in the bar, I asked her, is the second time you to such a place, and she nodded. brothers have come, the second with a smile said to me, the last time you had for her ah. I described to her said: brothers, by the age, I'm the oldest, the second is called tiger blood, the third is called Tiger, youngest son called passionate tiger, white tiger called Five. lane black friends told us to Fab Five. of endurance, if you can not stand, do not fight back, you just say, he grocery store will not appear once in front of you, this is the special situation of the characteristics of hh drink a lot more than words can Can Can, and she has been sitting there, drinking orange juice, watching our noisy, like an angel watching her followers gathered.
late, casual gatherings I drove her, and flying in the street with, and occasionally from promising a mirror, so pure, so beautiful, as if an angel came down. Perhaps she is an angel, to save my people in the dark.
he declare to me, and so excited, but I did not immediately say yes, then I say that in the examination, he agreed, he told me good, then I understand, tolerate, and I know he really likes me. but I can now say yes. because I had on the parents said that in the exam, I will not fall in love. Perhaps it is very unfair to him, but it can be said to give him a test, try him I love how deep in the end.
he took me to join his fraternity. cold Tiger, blood tiger, tiger, passionate tiger, white tiger, black Fab Five. I could have fixed and black sitting in the same Fab Five on the table, spread out, people will think I'm bad. forget it, just happy like, why should others are saying.
impressed me most is the white tiger, he is so white, so quiet, is simply a pale-faced scholar how could Fab Five process is linked with the black is really baffling. Maybe they have some extraordinary experience. so they will go together, but unfortunately the hero hero.
in their conversation, I know that they are abandoned by their families, and later by their foster parent shelter, and he is lost in the subway by their parents, two or three in the subway station alone at the age of 1 month of life, so miserable. No wonder his character is so cold, the original is the human loss of confidence. send him articles on the site could be so similar, did not he write the secret is in the article, no wonder he wrote, and then worry about writing dark, in the original may not be his personal experience, what a poor people, then I want to look good to these articles to enhance his understanding. with my character to change his cold, and I believe I can do.
party scattered, and I boarded his vehicle, he Zhang car wings are affixed stickers black tiger, so handsome. my hands holding his head on his back, receiving came from the temperature of his back, feeling good.
7
short and long 3 days in the test was over at last, I finally liberated, and finally you can easily play. Since her confession, I have not played easy, and now finally have the chance. I My hand, and looked up at the land surface right for fear of hitting people. busy almost easy music. Time with ears blowing in the wind and I looked up and down the Department of flies by, we knew we stay away from the city.
appear in front of a van, blocking my way, I know ill intent, get back to her, run, do not look back, I have other brothers phone number, you just call the tiger blood. I will finish phone secretly into her hands. that almost all people in the car down, I whispered before running for about 20m, turn the front, see the car they want, with the go, while looking out the back looking mirror, the side pedal to the metal. in a corner, I put her thrown into the grass, walk alone. A few minutes later, no oil tank, and I was forced to stop vehicles, out of hiding cars in the bar, waiting for them back the vehicle, almost half a minute later, they caught up with me. I dragged an iron bar left and right cut, I do not know how long, who know only a few fractures, continuous blood flow. Finally, I lay a pool of blood, loss of consciousness.
in the test after he invited me to drag racing, sitting in his Tiger on, feel the feeling of the wind whistling from the ear, his broad back of the upload to the warmth, I feel I'm so happy. heard him say a meteor shower tonight, he took me to see, so romantic. did not think like a person is so happy.
lying on his back, closed eyes, let the hair floating freely back and feel the warm wind howls from the ear, made me sleepy.
suddenly stop the car, I was awakened to see parked in front of van, the car went down a lot of people who took the iron bar, I'm scared, holding him tightly.
he gently asked me to run, I called in the blood of the tiger, and inserted into a mobile phone my hands. from the mirror after looking to see that he may calm, calm almost cruel. I do not know how to do. Then he engine car, and rushed toward them, knocking down two, we break loose. I had I thought we could escape, I did not expect he turned his head towards them to go, and after 1 hit, I was afraid to move for the tight close your eyes, ear and growing, I felt he was fierce throttle, speed. Although in this case, he did not nervous, calm, unusual calm, no wonder the tiger is called cold, not quite sure how the president and his principal has a relationship.
I was thinking about when Di Hu ears suddenly came to him, run. I did not react from time to time, people have dropped in the grass, who was a rock to draw a few road wound, it hurts. and so I opened my eyes, he was in another a corner disappeared, with both the disappearance of the van that bike in the corner. I'm busy out phone, find the blood of the tiger's phone number. phone to get through, I'm anxious to tell him the situation and leave the cold tiger direction. hung up the phone After I climbed highway in the direction toward the cold to chase the tiger away.
I do not know throw a few somersault, feet have been numb pain. I finally caught up with them. and he does not fall in the blood , motionless, blood tiger they were busy people with the name on the van, no one to help him stop the bleeding, I rushed to hand hold the wound, the tears kept on dropping, and his blood melt in a go, flow hard road hh
8
I slowly opened my eyes, a sight Cancan clear. She flutter in my bed, sleep in very familiar face looming round after round of tears, she seemed very tired, So let her get some sleep much. I looked at her sleeping quietly, motionless.
she woke up and saw I looked at her face turned to red, red, cute. She suddenly ran out a while, come in a bunch of people, in animated conversation, keep me from Hao Fan. can not ignore them I had to bite the bullet, and they talk. are finally gone, leaving only Under her four brothers and foster parent. I'm inside, they said, you go out, I want to talk to her alone. They left the room only me and her. I calmly told her Road, the last time you do not mean to think about it? is not taken into account, when I do not exist, forget me. she was surprised and asked him why? me, do not ask, to the site at night, I will tell you everything. she was gone , crying bitterly. My heart hurts, and I did not want to hurt her, but she followed me there will not be happy. for her good, I only have to do.
year later, I'm all good. Blood Tiger told those guys I finally found the whereabouts of, and is cold man. the day, we bring along troops, into the wind the nest, the one that turned upside down, we go.
I and return to independence, the secret firmly buried in the bottom of my heart.
I understand that the bottom of the following is purgatory.
he slept more than five days, finally woke up. I had to say to him I promised him. But he said No, he did not want me there before. how is it possible, I'm so sad, I did not expect to be abandoned is so uncomfortable.
night I went to site, he posted an article on its website a new composition , entitled Purgatory and the site concerned.
Postscript: two stories to this end, after the story, I do not know whether there will be, They result, it is the way he did not know, she did not know, I do not know. I think no one would know. let the god of marriage to busy. we can not help them. Perhaps, he and she, never goodbye, perhaps, They soon married. What can not do, is not it!
Subscribe to:
Posts (Atom)