1.Comprehensive Clinical Evaluation of Duliang Soft Capsules in Treatment of Migraine with Wind-cold Blood Stasis Syndrome
Xiaoxiao ZHAO ; Xuming ZHANG ; Junyu XI ; Zhenkai LU ; Fumei LIU ; Lianxin WANG ; Yuanyuan LI ; Yanming XIE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):223-232
ObjectiveTo comprehensively assess the clinical value of Duliang soft capsules in the treatment of migraine with wind-cold blood stasis syndrome, and to provide guidance for national medical decision-making, clinical drug promotion, and pharmaceutical services. MethodThe evaluation of Duliang soft capsules' clinical value was conducted in accordance with the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs (Trial Version, 2021) using a combination of qualitative and quantitative methods. Utilizing the CSC v2.0 software, this study conducted a comprehensive clinical evaluation of Duliang soft capsules across the "6+1" dimensions, including safety pre- and post-market launch, effectiveness in treating migraine, economy (cost-effectiveness), and innovation, suitability, accessibility, and traditional Chinese medicine (TCM) characteristics in both its technology and clinical applications. ResultSafety: Duliang soft capsules were found to have good safety based on evidence from known adverse reactions (spontaneous reporting system (SRS) data, literature data, etc.), pre-marketing toxicological research, and post-marketing drug monitoring. Effectiveness: A meta-analysis indicated that the combination of Duliang soft capsules and western medicine was more effective than Western medicine alone in the treatment of migraine. The product's effectiveness was rated as "Best" based on the quality and value of the evidence. Economy: Duliang soft capsules are moderately priced and categorized as a Type B medical insurance product. Economic research indicated that the combination of Western medicine and Duliang soft capsules was more cost-effective than Western medicine alone. The product's economy was rated as "Better". Innovation: Duliang soft capsules, with Angelicae Dahuricae Radix and Chuanxiong Rhizoma as the main components, hold one invention patent and have been awarded the China Patent Excellence Award. The pharmaceutical company has introduced innovative extraction (CO2 supercritical extraction technology) and formulation (soft capsule) processes. The product's innovation was rated as "Better". Suitability: A questionnaire survey on Duliang soft capsules showed that it was well-suited for both patients and healthcare professionals. The product received a comprehensive assessment of suitability through the "Evaluation of Chinese Patent Medicine Information Services". The product's suitability was rated as "Best". Accessibility: Duliang soft capsules are moderately priced, making them accessible and affordable. The product's accessibility was rated as "Good" based on evidence from these three aspects. TCM characteristics: The formulation of Duliang soft capsules can be traced back to WANG Qiu's Selected Formulas from the Praiseworthy Studio (Shi Zhai Bai Yi Xuan Fang) from the Song Dynasty, and it was documented in ZHANG Jiebin's The Complete Works of Zhang Jing-yue (Jing Yue Quan Shu) as "Duliangwan". The product has been extensively studied with over 2000 clinical cases since its market launch, and its TCM characteristics were rated as outstanding with sufficient evidence. ConclusionThe comprehensive clinical value evaluation of Duliang soft capsules demonstrated its high effectiveness, suitability, and accessibility, and outstanding TCM characteristics. The product's safety, economy, and innovation received good ratings. In summary, Duliang soft capsules exhibited significant clinical value and outstanding TCM characteristics, the evidence was sufficient, and the result was confirmed, providing crucial references for clinical decision-making and pharmaceutical management.
2.Clinical Comprehensive Evaluation of Zhichuanling Oral Liquid in Treatment of Asthma and Considerations for Cultivating High-value Patents
Shuo YANG ; Haiyan LI ; Yanming XIE ; Lianxin WANG ; Jingming CHENGFENG ; Xin CUI ; Lixun LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):208-216
ObjectiveThis study conducted a "6 + 1" clinical comprehensive evaluation of the existing research on Zhichuanling oral liquid (ZOL) in the treatment of asthma,so as to clarify the clinical advantages and precise clinical positioning of ZOL in the treatment of asthma, lay a foundation for further research and academic promotion of ZOL, and provide new directions for patent cultivation. MethodAn evaluation method featuring a qualitative and quantitative combination was used, which considered the dimensions of safety,effectiveness,economy,innovation,suitability,accessibility, and traditional Chinese medicine (TCM) characteristics. According to Expert Meeting Law, relevant weights were obtained through voting. CSC_v2.0 software was used to calculate each dimension and convert it into the corresponding grade score. ResultBased on the existing materials,① ZOL instruction indicates the adverse reactions,taboo, and notes. Multiple data of clinical research before and after marketing and spontaneous reporting system shows that ZOL has controllable risk and good safety. Safety is rated as B grade. ② Multiple data of clinical research before marketing, systematic evaluation of clinical effectiveness, and Meta-analysis shows that ZOL has good effectiveness and clinical significance. Effectiveness is rated as a B grade. ③ Analysis of the cost-effectiveness of ZOL combined with conventional treatment shows that the economy of the drug is good and rated as a B grade. ④ ZOL has better innovation, which is rated as an A grade. ⑤ ZOL can basically meet the clinical drug needs based on the result of the questionnaire survey and has good suitability, which is rated as a B grade. ⑥ ZOL has better accessibility, and accessibility is rated as A grade. ⑦ ZOL involves a rich theory of TCM but insufficient experience of human usage. It is thus rated as a C grade in terms of TCM characteristics. Based on the results of "6 + 1" dimension,the clinical comprehensive evaluation of ZOL in the treatment of asthma (cold syndrome and heat syndrome)is rated as B category. ConclusionZOL has good clinical value and outstanding innovation and accessibility in the treatment of asthma (cold syndrome and heat syndrome). It is recommended that ZOL be transformed into the relevant policy results of basic clinical drug management procedurally. At the same time,it is recommended to actively cultivate patents with TCM characteristics.
3.A Multicenter, Randomized, Double-blind, and Placebo-parallel Controlled Trial of Tibetan Medicine Ruyi Zhenbaowan in Treatment of Knee Osteoarthritis
Chunquan SUN ; Yanming XIE ; Jinghua GAO ; Weiheng CHEN ; Lianxin WANG ; Shangquan WANG ; Xiangdong TIAN ; Zujian XU ; Yuxin ZHENG ; Mingwang ZHOU ; Chungen LI ; Zhanwang XU ; Jiayi GUO ; Shuangqing DU ; Qigang CHEN ; Quan JI ; Zhiqiang BAI ; Jing XIAO ; Wanli QI ; Weiyi YANG ; Jingxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):57-67
ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan(RYZBW)in the treatment of initial and early knee osteoarthritis (KOA) through a prospective multicenter,randomized,double-blind,and placebo-parallel controlled trial. MethodFrom October 13th, 2021 to December 25th, 2021, 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital, Chinese Academy of Chinese Medical Sciences, and they were randomly divided into observation group and control group, with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education, and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks, and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score (WOMAC score), and the secondary outcome measures were the response rate of visual scale (VAS) pain score, WOMAC sub item scores (joint pain, joint stiffness, and joint function), quality of life (SF-12) score, and traditional Chinese medicine (TCM) syndrome score. Result(1) Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW, and the difference was statistically significant (P<0.05). There was no significant difference between the two groups in improving VAS score response rate, WOMAC function score, WOMAC stiffness score, SF12-PCS (quality of life-physical health) score, SF12-MCS (quality of life-mental health) score, and TCM syndrome score. (2) Subgroup analysis. ① In terms of VAS score response rate, the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of (4, 5], and the difference was statistically significant (P<0.05). ② In terms of TCM syndrome score, for subjects aged [56, 60] and [61, 65], the decrease in total TCM syndrome score in the observation group was better than that in the control group, and the difference was statistically significant (P<0.05). ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score, VAS score response rate, WOMAC pain score, WOMAC function score, and TCM syndrome score for patients with initial and early KOA, which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.
4.Expert consensus on the accurate diagnosis and treatment of acetabular fractures based on three-column classification (version 2023)
Ruipeng ZHANG ; Hongmin CAI ; Shicai FAN ; Gang LYU ; Yan ZHUANG ; Chengla YI ; Xiaodong GUO ; Longpo ZHENG ; Xianzhong MA ; Hua CHEN ; Dahui SUN ; Guanglin WANG ; Qishi ZHOU ; Weixu LI ; Wei FENG ; Zhangyuan LIN ; Xiaodong QIN ; Jiandong WANG ; Zhanying SHI ; Lianxin LI ; Guangyao LIU ; Shuquan GUO ; Ming LI ; Jianzhong GUAN ; Yingze ZHANG ; Zhiyong HOU
Chinese Journal of Trauma 2023;39(10):865-875
Accurate classification of the acetabular injuries and appropriate treatment plan are great challenges for orthopedic surgeons because of the irregular anatomical structure of the acetabulum and aggregation of important vessels and nerves around it. Letournel-Judet classification system has been widely applied to classify acetabular fractures. However, there are several limitations, including incomplete inclusion of fracture types, difficulty in understanding and insufficient guidance for surgical treatment, etc. Serious complications such as traumatic arthritis are common due to wrong classification and diagnosis and improper selection of surgical strategy, which brings a heavy burden to the society and families. Three-column classification, based on anatomic characteristics, has advantages of containing more fracture types and being easy to understand, etc. To solve the problems existing in the diagnosis and treatment process based on Letournel-Judet classification, achieve accurate diagnosis and treatment of patients with acetabular fractures, and obtain satisfactory prognosis, the Orthopedic Trauma Emergency Center of Third Hospital of Hebei Medical University and the Trauma Orthopedic Branch of the Chinese Orthopedic Association organized experts from relevant fields to formulate the Expert consensus on the accurate diagnosis and treatment of acetabular fractures based on three-column classification ( version 2023) in terms of principles of evidence-based medicine. Based on the three-column classification, 15 recommendations were proposed, covering the diagnosis, treatment, complication prevention and management, etc, so as to provide reference for accurate diagnosis and treatment of acetabular fractures.
5.Minimally invasive technique for tibial plateau bicondylar fracture repair using the double reverse traction repositor
Zhimeng ZHAO ; Fulin TAO ; Dawei WANG ; Lin LI ; Dongsheng ZHOU ; Lianxin LI
Chinese Journal of Orthopaedics 2023;43(22):1509-1516
Objective:To assess the efficacy of a minimally invasive technique for repairing tibial plateau bicondylar fractures utilizing the double reverse traction repositor.Methods:A retrospective analysis was performed of the data of 31 patients (Schatzker V 17 cases, Schatzker VI 14 cases) who had been admitted to trauma center of Shandong provincial hospital affiliated to Shandong first medical university for tibial plateau bicondylar fractures from January 2017 to January 2022. There were 21 males and 10 females, aged from 18 to 67 years (average, 32.4±6.5 years). The intervention strategy comprised the use of a double reverse traction repositor and was augmented by precise screw fixation. A comprehensive set of parameters were measured, including time interval between injury and operation, operation time, blood loss, hospital stay, fracture healing time, incision complications. Postoperative assessments were made immediately and at the 12-month mark, including the evaluation of articular step-off height, medial tibial plateau angle, and posterior tibial slope angle. The evaluation also included thTime interval between injury and operation ranged from 5 to 11 days, with an average of 6.1±1.3 days. The surgical procedures varied in length from 70 to 160 minutes, averaging at 109.2±15.6 minutes. The volume of blood loss was noted to be between 90 to 380 ml, averaging at 176.5±20.8 ml. Hospitalization spanned from 10 to 15 days, with an average stay of 12.2 ±0.8 days. Over a follow-up duration of 12 to 20 months, averaging at 13.5±1.1 months, all patients achieved fracture union within a period of 11 to 20 weeks, with an average time of 14.6±1.5 weeks. The postoperative articular step-off was recorded at 0.45±0.13 mm immediately after surgery and 0.58±0.21 mm at the one-year follow-up. Similarly, the medial tibial plateau angle and posterior tibial slope angle showed marginal changes from the immediate postoperative period to the 12-month evaluation. Knee joint mobility at the one-year mark ranged impressively from 0° to 135°, with an average of 125.6°±2.1°. Functional outcomes as reflected by Rasmussen scores ranged from 18 to 28 points, with an average of 25.4±1.7 points. Pain, as assessed by the VAS, had a low score range of 0 to 2 points, averaging at 0.7±0.2 points. Notably, there were no postoperative complications associated with the incisions, such as fat liquefaction, infection, skin necrosis, or exposure of internal fixations. Additionally, no cases of delayed union or fixation failure were observed. Six patients had traumatic arthritis 1 year after operation.Conclusion:The minimally invasive double reverse traction repositor technique for tibial plateau bicondylar fracture repair is effective, warranting its broader application in orthopedic surgery.
6.Application value of donor liver autologous portal venous blood rinse in orthotopic liver trans-plantation
Yafei GUO ; Zebin ZHU ; Hao ZHENG ; Ning WANG ; Zhijun XU ; Xuefeng LI ; Wei CAI ; Ruipeng SONG ; Jizhou WANG ; Dalong YIN ; Lianxin LIU ; Shugeng ZHANG
Chinese Journal of Digestive Surgery 2023;22(2):244-250
Objective:To investigate the application value of donor liver autologous portal venous blood rinse in orthotopic liver transplantation (OLT).Methods:The retrospective cohort study was conducted. The clinicopathological data of 35 pairs of donors and recipients who underwent OLT in the First Affiliated Hospital of University of Science and Technology of China from May 2018 to June 2019 were collected. Of the 35 donors, there were 31 males and 4 females, aged (48±9)years. Of the 35 recipients, there were 25 males and 10 females, aged (47±9)years. Of the 35 recipients, 16 recipients undergoing donor liver autologous portal venous blood rinse were allocated into the portal vein group, and 19 recipients undergoing donor liver albumin water rinse were allocated into the albumin group. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and compari-son between groups was analyzed using the t test. Measurement data of skewed distribution were represented as M(range). Count data were descried as absolute numbers, and comparison between groups was analyzed using the Fisher exact probability. Results:(1) Surgical situations. The anhepatic phase time and arterial blood Ca 2+ concentration within 5 minutes after reperfusion of the recipients were (52±12)minutes and (0.99±0.10)mmol/L in the portal vein group, versus (64±12)minutes and (1.05±0.07)mmol/L in the albumin group, showing significant differences in the above indicators between the two groups ( t=2.94, 2.22, P<0.05). The mean arterial pressure, arterial blood K +concentration and arterial blood pH within 5 minutes after reperfusion of the recipients were (70±24)mmHg (1 mmHg=0.133 kPa), (4.7±1.3)mmol/L and 7.27±0.06 in the portal vein group, versus (71±28)mmHg, (4.6±1.1)mmol/L and 7.30±0.07 in the albumin group, showing no significant difference in the above indicators between the two groups ( t=0.14, 0.30, 1.22, P>0.05). (2) Post-operative situations. Cases with post-reperfusion syndrome (PRS), cases with severe PRS of cardiac arrest, cases with primary graft nonfunction of the recipients were 6, 0, 2 in the portal vein group, versus 8, 1, 1 in the albumin group, showing no significant difference in the above indicators between the two groups ( P>0.05). Total bilirubin on postoperative day 7 of the recipients was (90±52)μmol/L in the portal vein group, versus (166±112)μmol/L in the albumin group, showing a significant difference between the two groups ( t=2.66, P<0.05). International normalized ratio on postoperative day 7, the highest alanine aminotransferase and aspartate aminotransferase within 7 days after operation of the recipients were 2.1±2.0, (1 952±2 813)IU/L and (3 944±6 673)IU/L in the portal vein group, versus 1.8±0.6, (1 023±1 014) IU/L and (2 005±2 910)IU/L in the albumin group, showing no significant difference in the above indicators between the two groups ( t=0.66, 1.23, 1.08, P>0.05). Recipients with hepatic artery complication and biliary complication were 1 and 2 in the portal vein group, versus 0 and 4 in the albumin group, showing no significant difference in the above indicators between the two groups ( P>0.05). There were 3 cases and 2 cases died during the perioperative period in the portal vein group and the albumin group, respectively. (3) Follow-up. Of the 35 recipients, 30 recipients were followed up for 534(range, 28?776)days after operation. During the follow-up, there were 3 patients with postoperative complications in the portal vein group including 2 cases died and 1 case recovered after sympto-matic treatment. There were 5 patients with postoperative complications in the albumin group including 1 case died and 4 cases recovered after symptomatic treatment. Up to the follow-up date, 11 patients in the portal vein group and 16 patients in the albumin group were in good condition. Conclusion:Rinse of the donor liver with autologous portal venous blood during liver transplantation can shorten the time of anhepatic phase, without increasing the occurrence of post-reperfusion syndrome, ischemia re-perfusion injury and biliary tract complications.
7.Chinese expert consensus on emergency surgery for severe trauma and infection prevention during corona virus disease 2019 epidemic (version 2023)
Yang LI ; Yuchang WANG ; Haiwen PENG ; Xijie DONG ; Guodong LIU ; Wei WANG ; Hong YAN ; Fan YANG ; Ding LIU ; Huidan JING ; Yu XIE ; Manli TANG ; Xian CHEN ; Wei GAO ; Qingshan GUO ; Zhaohui TANG ; Hao TANG ; Bingling HE ; Qingxiang MAO ; Zhen WANG ; Xiangjun BAI ; Daqing CHEN ; Haiming CHEN ; Min DAO ; Dingyuan DU ; Haoyu FENG ; Ke FENG ; Xiang GAO ; Wubing HE ; Peiyang HU ; Xi HU ; Gang HUANG ; Guangbin HUANG ; Wei JIANG ; Hongxu JIN ; Laifa KONG ; He LI ; Lianxin LI ; Xiangmin LI ; Xinzhi LI ; Yifei LI ; Zilong LI ; Huimin LIU ; Changjian LIU ; Xiaogang MA ; Chunqiu PAN ; Xiaohua PAN ; Lei PENG ; Jifu QU ; Qiangui REN ; Xiguang SANG ; Biao SHAO ; Yin SHEN ; Mingwei SUN ; Fang WANG ; Juan WANG ; Jun WANG ; Wenlou WANG ; Zhihua WANG ; Xu WU ; Renju XIAO ; Yang XIE ; Feng XU ; Xinwen YANG ; Yuetao YANG ; Yongkun YAO ; Changlin YIN ; Yigang YU ; Ke ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Gang ZHAO ; Xiaogang ZHAO ; Xiaosong ZHU ; Yan′an ZHU ; Changju ZHU ; Zhanfei LI ; Lianyang ZHANG
Chinese Journal of Trauma 2023;39(2):97-106
During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.
8.Single-dose AAV-based vaccine induces a high level of neutralizing antibodies against SARS-CoV-2 in rhesus macaques.
Dali TONG ; Mei ZHANG ; Yunru YANG ; Han XIA ; Haiyang TONG ; Huajun ZHANG ; Weihong ZENG ; Muziying LIU ; Yan WU ; Huan MA ; Xue HU ; Weiyong LIU ; Yuan CAI ; Yanfeng YAO ; Yichuan YAO ; Kunpeng LIU ; Shifang SHAN ; Yajuan LI ; Ge GAO ; Weiwei GUO ; Yun PENG ; Shaohong CHEN ; Juhong RAO ; Jiaxuan ZHAO ; Juan MIN ; Qingjun ZHU ; Yanmin ZHENG ; Lianxin LIU ; Chao SHAN ; Kai ZHONG ; Zilong QIU ; Tengchuan JIN ; Sandra CHIU ; Zhiming YUAN ; Tian XUE
Protein & Cell 2023;14(1):69-73
9.Epidemiological characteristics, diagnosis, treatment and prognosis of gallbladder cancer in China: a report of 6 159 cases
Xuheng SUN ; Yijun WANG ; Wei ZHANG ; Yajun GENG ; Yongsheng LI ; Tai REN ; Maolan LI ; Xu'an WANG ; Xiangsong WU ; Wenguang WU ; Wei CHEN ; Tao CHEN ; Min HE ; Hui WANG ; Linhua YANG ; Lu ZOU ; Peng PU ; Mingjie YANG ; Zhaonan LIU ; Wenqi TAO ; Jiayi FENG ; Ziheng JIA ; Zhiyuan ZHENG ; Lijing ZHONG ; Yuanying QIAN ; Ping DONG ; Xuefeng WANG ; Jun GU ; Lianxin LIU ; Yeben QIAN ; Jianfeng GU ; Yong LIU ; Yunfu CUI ; Bei SUN ; Bing LI ; Chenghao SHAO ; Xiaoqing JIANG ; Qiang MA ; Jinfang ZHENG ; Changjun LIU ; Hong CAO ; Xiaoliang CHEN ; Qiyun LI ; Lin WANG ; Kunhua WANG ; Lei ZHANG ; Linhui ZHENG ; Chunfu ZHU ; Hongyu CAI ; Jingyu CAO ; Haihong ZHU ; Jun LIU ; Xueyi DANG ; Jiansheng LIU ; Xueli ZHANG ; Junming XU ; Zhewei FEI ; Xiaoping YANG ; Jiahua YANG ; Zaiyang ZHANG ; Xulin WANG ; Yi WANG ; Jihui HAO ; Qiyu ZHANG ; Huihan JIN ; Chang LIU ; Wei HAN ; Jun YAN ; Buqiang WU ; Chaoliu DAI ; Wencai LYU ; Zhiwei QUAN ; Shuyou PENG ; Wei GONG ; Yingbin LIU
Chinese Journal of Digestive Surgery 2022;21(1):114-128
Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.
10.Clinical efficacy of avatrombopag combined with recombinant human thrombopoietin versus avatrombopag in the treatment of severe thrombocytopenia associated with chronic liver disease
Yongshuai WANG ; Sai ZHANG ; Lei LI ; Wei WANG ; Wei WANG ; Shenyu ZHANG ; Huachuan SONG ; Huanzhang YAO ; Ruipeng SONG ; Lianxin LIU ; Jizhou WANG
Chinese Journal of Digestive Surgery 2022;21(2):281-286
Objective:To investigate the clinical efficacy of avatrombopag combined with recombinant human thrombopoietin (rhTPO) versus avatrombopag in the treatment of severe thrombocytopenia associated with chronic liver disease.Methods:The retrospective cohort study was conducted. The clinical data of 56 patients with severe thrombocytopenia associated with chronic liver disease who were admitted to the First Affiliated Hospital of University of Science and Technology of China from May 2020 to October 2021 were collected. There were 36 males and 20 females, aged from 33 to 74 years, with a median age of 54 years. Of 56 patients, 21 cases undergoing treatment of avatrombopag combined with rhTPO were allocated into the combined treatment group and 35 cases undergoing treatment of avatrombopag were allocated into the monotherapy group. Observation indicators: (1) changes of platelet after treatment; (2) adverse drug reaction. Follow-up was conducted using outpatient examination and telephone interview to detect changes of platelet and effects of treatment within 2 weeks after treatment. The follow-up was up to October 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and compari-son between groups was analyzed using the chi-square test or Fisher exact probability. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Changes of platelet after treatment. The platelet level within 1 to 5 days and 6 to 10 days after treatment in the combined treatment group were (35±19)×10 9/L and (73±41)×10 9/L, respectively. The above indicators of the monotherapy group were (40±30)×10 9/L and (70±51)×10 9/L, respectively. There was no significant difference in change trends of platelet before and after treatment between the two groups ( Fgroup=0.30, P>0.05). There was a significant difference in platelet count before and after treatment between the two groups ( Ftime=59.96, P<0.05). There was no interaction effect in change trends of platelet between the two groups ( Finteraction=0.40, P>0.05). The effective rates were 66.67%(14/21) in the combination therapy group and 54.29%(19/35) in the monotherapy group. There was no significant difference in the effective rate between the two groups ( χ2=0.83, P>0.05). (2) Adverse drug reaction. Cases with headache, dizziness, blood transfusion reaction, hematuria, proteinuria, fever, abdominal pain, diarrhea, dyspepsia, fatigue, nausea or peripheral tissue edema were 2, 4, 1, 2, 2, 7, 10, 6, 8, 14, 12, 5 in the combined treatment group, versus 5, 8, 1, 3, 5, 7, 19, 11,20, 19, 14, 5 in the monotherapy group, respectively. There was no significant difference in cases with headache, dizziness, blood transfusion reaction, hematuria, proteinuria between the two groups ( P>0.05), and there was no significant difference in cases with fever, abdominal pain, diarrhea, dyspepsia, fatigue, nausea, peripheral tissue edema between the two groups ( χ2=1.24, 0.23, 0.05, 1.91, 0.83, 2.04, 0.81, P>0.05). Conclusion:Both of avatrombopag combined with rhTPO and monotherapy of avatrom-bopag can be used to promote the platelet level in patients with severe thrombocytopenia associated with chronic liver disease, and avatrombopag combined with rhTPO does not provide better clinical benefits compared with monotherapy avatrombopag.

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