Pharmacovigilance runs through the whole life cycle of drugs. This paper systematically sorts out the development course of pharmacovigilance in China， from the initial establishment of the adverse drug reaction reporting system to the gradual construction of a complete pharmacovigilance system aligned with international standards. It focuses on analyzing the evolutionary features of the organizational system， legal system and monitoring system during this process. On this basis， this paper further discusses the future development trends of pharmacovigilance in China. In general， remarkable progress has been achieved in both regulatory construction and practical implementation of China’s pharmacovigilance system. In the future， efforts should be continuously made to improve the pharmacovigilance system， such as accelerating the implementation of the “one-body with two-wings” working framework and strengthening the primary responsibility of marketing authorization holders. It is also necessary to cultivate and reserve professional talents and promote information-based construction， including optimizing the spontaneous reporting system and establishing active monitoring systems. These measures can provide more solid support for ensuring public drug safety and facilitating high-quality development of the pharmaceutical industry.

OBJECTIVES: To investigate the effect of orexin-A-mediated regulation of ionotropic glutamate receptors for promoting motor function recovery in rats with spinal cord injury (SCI). METHODS: Thirty-six newborn SD rats (aged 7-14 days) were randomized into 6 groups (n=6), including a normal control group, a sham-operated group, and 4 SCI groups with daily intrathecal injection of saline, DNQX, orexin-A, or orexin-A+DNQX for 3 consecutive days after PCI. Motor function of the rats were evaluated using blood-brain barrier (BBB) score and inclined plane test 1 day before and at 1, 3, and 7 days after SCI. For patch-clamp experiment, spinal cord slices from newborn rats in the control, sham-operated, SCI, and SCI+orexin groups were prepared, and ventral horn neurons were acutely isolated to determine the reversal potential and dynamic indicators of glutamate receptor-mediated currents under glutamate perfusion. RESULTS: At 3 and 7 days after SCI, the orexin-A-treated rats showed significantly higher BBB scores and grip tilt angles than those with other interventions. Compared with those treated with DNQX alone, the rats receiving the combined treatment with orexin and DNQX had significantly higher BBB scores and grip tilt angles on day 7 after PCI. In the patch-clamp experiment, the ventral horn neurons from SCI rat models exhibited obviously higher reversal potential and greater rise slope of glutamate current with shorter decay time than those from sham-operated and orexin-treated rats. CONCLUSIONS Orexin-A promotes motor function recovery in rats after SCI possibly by improving the function of the ionotropic glutamate receptors.
Animals ; Spinal Cord Injuries/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Receptors, Ionotropic Glutamate/metabolism* ; Recovery of Function/drug effects* ; Orexins/pharmacology* ; Male ; Female ; Animals, Newborn ; Neuropeptides/pharmacology* ; Intracellular Signaling Peptides and Proteins/pharmacology*

The passing of ethical review is a necessary conditions and prerequisite for the development of life science and medical research involving humans. At present, some medical and health institutions have no or insufficient ethical review capabilities. The lack of ethical review ability has become a bottleneck restricting the development of life science and medical research involving humans. According to documents such as Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Pharmaceutical and Medical Devices, Opinions on Strengthening the Ethical Governance of Science and Technology, institutions can entrust competent institutional ethics review committees or regional ethics review committees in writing to conduct ethical review. Entrustment ethical review provides a viable solution for institutions that need to carry out life science and medical research involving humans but do not have an ethics (review) committee or the ethics (review) committee is not competent to review. To conduct the entrustment ethical review, the entrustment between the principal and the trustee is required. According to The Measures for Ethical Review of Life Sciences and Medical Research Involving Humans, if medical and health institutions and their ethical review committees do not accept the formal entrustment to provide the ethical review opinions for other institutions, the local health authorities at or above the county level will impose administrative penalties and sanctions on the relevant institutions and personnel in accordance with the law. Signing the entrustment ethical review contract, implementing legal compliance entrusted ethical review to protect the rights and interests of the trustee and the principal, and protect the research participants.

Objective:To investigate the techniques used in blood flow control of Kimura laparoscopic spleen-preserving pancreatectomy (LSPDP).Methods:Forty·five patients with benign or low-grade malignant pancreatic diseases undergoing LSPDP at Huzhou Central Hospital from May 2014 to Oct 2021 were analyzed retrospectively. Patients were divided into splenic vascular flow control group ( n=22) and routine management group ( n=23). Results:There was no significant difference in gender, age, BMI, accompanying symptoms, hypertension, diabetes, lesion size and pathological diagnosis between the two groups (all P>0.05). A higher overall spleen preservation rate (90.9% vs. 52.2%, χ2=8.213, P=0.004), lower incidence of morbidity with Clavien grade ≥ Ⅱ (22.7% vs. 73.9%, χ2=9.911, P=0.002) and shorter postoperative hospital stay [(9.6±4.5) d vs. (14.3±6.6) d, t=2.447, P=0.008] were achieved in the vascular flow control group compared with those in the routine group. Conclusion:Splenic vascular flow control techniques improve the success rate of spleen preservation in laparoscopic distal pancreatectomy, reduce the postoperative complications and shorten the postoperative hospital stay.

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.

Objective:To explore the curative effect of synchronous bionic electrical stimulation in hyperbaric oxygen chamber on patients with sudden deafness（SD）and the changes in hemorheological indicators.Methods:A total of 128 SD outpatients and inpatients treated at the Hyperbaric Oxygen Department of the Sixth Medical Center of the Chinese PLA General Hospital from June 2020 to June 2021 were randomly divided into study group（70 cases treated with synchronous brain bionic electrical stimulator in hyperbaric oxygen chamber）and control group（58 cases given conventional hyperbaric oxygen therapy），respectively. The curative effects of the two groups were evaluated，and the hemorheological indicators，such as the whole blood（high-shear and low-shear）viscosity，plasma viscosity，and red blood cell aggregation，were analyzed by the automatic biochemical analyzer before and after treatment.Results:After two courses of treatments，the overall effective rate of the study group（88.57%）was significantly higher than that of the control group（79.31%），and the difference was statistically significant（ P<0.05）. After treatment，the whole blood（high-shear and low-shear）viscosities，plasma viscosity，and erythrocyte aggregation indicators of the two groups were significantly decreased compared with those before treatment（ P<0.05），and the above indicators in the study group were significantly lower than those in the control group（ P<0.05）. Conclusions:Synchronous brain bionic electrical stimulation in the hyperbaric oxygen chamber can improve the hemorheological indicators of the SD patients，reduce their blood hypercoagulability，and improve their hearing level and treatment effect. Hence，it is worth of clinical promotion.

Objective:To explore the curative effect of synchronous bionic electrical stimulation in hyperbaric oxygen chamber on patients with sudden deafness（SD）and the changes in hemorheological indicators.Methods:A total of 128 SD outpatients and inpatients treated at the Hyperbaric Oxygen Department of the Sixth Medical Center of the Chinese PLA General Hospital from June 2020 to June 2021 were randomly divided into study group（70 cases treated with synchronous brain bionic electrical stimulator in hyperbaric oxygen chamber）and control group（58 cases given conventional hyperbaric oxygen therapy），respectively. The curative effects of the two groups were evaluated，and the hemorheological indicators，such as the whole blood（high-shear and low-shear）viscosity，plasma viscosity，and red blood cell aggregation，were analyzed by the automatic biochemical analyzer before and after treatment.Results:After two courses of treatments，the overall effective rate of the study group（88.57%）was significantly higher than that of the control group（79.31%），and the difference was statistically significant（ P<0.05）. After treatment，the whole blood（high-shear and low-shear）viscosities，plasma viscosity，and erythrocyte aggregation indicators of the two groups were significantly decreased compared with those before treatment（ P<0.05），and the above indicators in the study group were significantly lower than those in the control group（ P<0.05）. Conclusions:Synchronous brain bionic electrical stimulation in the hyperbaric oxygen chamber can improve the hemorheological indicators of the SD patients，reduce their blood hypercoagulability，and improve their hearing level and treatment effect. Hence，it is worth of clinical promotion.

Objective To compare the effectiveness of surgical procedures (devascularization,shunt and combined shunt and devascularization) in treating recurrent variceal bleeding and other complications in patients with portal hypertension.Methods A systematic literature search was carried out on patients with portal hypertension,and a Meta-analysis was conducted using Revman 5.3 software to evaluate the effectiveness of different surgical procedures on recurrent esophageal variceal bleeding,hepatic encephalopathy,operative mortality and survival rates.Results A total of 24 trials were finally selected using predetermined inclusion criteria.Meta-analysis showed there was no significant difference among the three operations on operative mortality (P ＞ 0.05).The rebleeding rate of the combined group was significantly lower than the devascularization group (P ＜ 0.05).The encephalopathy rate of the combined group was significantly lower than the shunt group (P ＜ 0.05),and the 1-year and 3-year survival rates of the combined group were better than the devascularization group (both P ＜ 0.05),but there were no significant difference in the 5-year survival rates between these two groups (P ＞ 0.18).The 1-year and 3-year survival rates were not significantly different between the combined and the shunt groups (both P ＞ 0.05).Conclusions Combined shunt and devascularization had better therapeutic effectiveness than either devascularization alone or shunt alone in patients with portal hypertension with a high rebleeding risk.There were no significant difference among the three surgical procedures in operative mortality.The survival rates of combined surgery were significantly better than devascrlarization alone.

Objective:To investigate the relationship between the distance from the upper and lower resection margin and the gastric cancer patients with R0 resection and no distant metastasis.Methods:Retrospective analysis of 281 patients with gastric cancer in our hospital,the relationship between the age,sex,tumor size,tumor size,vascular invasion,lymph node metastasis,TNM stage,type of gastric cancer,tumor location and operation mode was analyzed.To compare the survival time of patients with different upper and lower margins.Results:The increase of the distance from upper resection margin was significantly related to the tumor size＞5 cm,TNM stage,type of gastric cancer,tumor location,and the difference was statistically significant(P＜0.05);The distance of lower resection margin was significantly correlated with tumor size＞5cm,vascular invasion,lymph node metastasis and TNM stage,type of gastric cancer,and the difference was statistically significant (P＜0.05);Themedian survival timein patientsof upper resection marginr□3cm with 48 months of the 5-year follow-up period was significantly higher than that in patients of the resection margin＞3cmwith 46 months (P＜0.001).Themedian survival timein patientsof lower resection margin□3cm with 45 months of the 5-year follow-up period was significantly higher than that in patients of the resection margin＞3cm with 44 months (P＜0.001).Conclusion:Gastric cancer postoperative upper and lower resection margin was significantly related with tumor size,TNM staging factors,and the median survival time of upper and lower resection margin＞5 cm was significantly lower than that of the resection margin3 cm.

Objective To evaluate the safety of Renaissance spine robot assisted system in spinal injury.Methods From March 2014 to May 2016,38 patients with spinal disease received spinal surgery assisted by spine robot system.They were 20 males and 18 females,with an average age of 42 years (range,from 12 to 69 years).There were 10 lumbar fractures,8 thoracic fractures and 20 spinal deformities.Pedicle screw implantation was conducted in 30 patients (PS group) and percutaneous vertebroplasty in 8 (PV group).One side was chosen randomly to use Mazor spine robot assisted system (assisted group) and the opposite side the conventional method (non-assisted group).The anteroposterior and lateral X-rays and CT scan of the lumbar and/or thoracic spine were performed in all patients after surgery.The precision of pedicle screws implantation in PS group was evaluated by the Abul-Kasimhierarchy grading system;location of the puncture trajectory,time used for puncture and radiation exposure time in PV group were evaluated.Results 208 pedicle screws were implanted in PS group,including 120 lumbar ones and 88 thoracic ones.For lumbar pedicle screw implantation,the excellent to good rate was 95.0％ (57/60) in the assisted group,significantly higher than that in the non-assisted group (80.0％,48/60) (P ＜ 0.05).For thoracic pedicle screw implantation,the excellent to good rate was 95.5％ (42/44) in the assisted group,significantly higher than that in the non-assisted group (77.3％,34/44) (P ＜ 0.05).There were 24 puncture trajectories in 8 patients in PV group,showing no pedicle penetration or cement leaking in any case.The mean time used for puncture was 5.5 ± 1.4 min in the assisted group,significantly shorter than that in the non-assisted group (17.8 ± 7.5 min) (P ＜ 0.05);the X-ray exposure time was 14.0 ± 4.0 s in the assisted group,significantly shorter than that in the non-assisted group (22.4 ± 6.0 s) (P ＜ 0.05).Conclusions Renaissance spine robot-assisted system deserves more clinical application,because in spinal surgery it can make pedicle screw implantation more precise and safer,and can reduce operation time and X-ray exposure time in percutaneous vertebroplasty.