OBJECTIVE To confirm the therapeutic effect of Jintiange capsules on osteoarthritis(OA) and the potential mechanism of synovial mesenchymal stem cell exosomes(SMSC-Exos) and articular chondrocytes(ACs) in the treatment of OA based on high-throughput sequencing technology. METHODS Type Ⅱ collagenase-induced OA rats were used for efficacy verification through general behavioral observation, bipedal balance difference experiment, mechanical foot reflex threshold, Micro-CT observation, and Safranin O-Fast Green staining. SMSCs and ACs were cultured in suitable concentration of drug-containing serum, and mRNA sequencing was performed on ACs in the control, model, and Jintiange capsules groups, as well as miRNA sequencing on SMSC-Exos. Differential expressed mRNAs and miRNAs were screened and target genes were predicted. The common differential expressed genes between SMSC and ACs were obtained by intersecting the differential expressed genes, and a miRNA-mRNA regulatory network was constructed using Cytoscape software. The expression trend analysis of common differential expressed genes was conducted, as well as the correlation analysis between differential expressed gene mRNA and miRNA, Micro-CT efficacy indicators, and differential expressed gene mRNA. RESULTS Under the pathological state of OA, the expression of miRNA-23a-3p, miRNA-342-3p, miRNA-146b-5p, miRNA-501-3p, and miRNA-214-3p were down-regulated, while miRNA-222-3p, miRNA-30e-3p, miRNA-676-3p, and miRNA-192-5p were up-regulated (P<0.05). The expressions of these miRNAs were significantly reversed after intervention with drug-containing serum of Jintiange capsules. There was a certain correlation between Micro-CT efficacy indicators, mRNA and miRNA. CONCLUSION Jintiange capsule has obvious efficacy in the treatment of OA, and its mechanism may be related to the promotion of SMSC-Exos targeting ACs to transport miRNA and then regulate Serpinb10, Ntn1, Il1b, Tgm2, Megf10, Il11, Cd40, Slc15a3, Pou2f2 and other genes.

Objective:Correct chest compression posture (CCP) is an important basis for high-quality cardiopulmonary resuscitation, but the research on CCP was still very limited. In this study, a new automatic analysis model was developed to achieve the purpose of objectification, standardization and automation of CCP monitoring.Methods:A total of 15 participants, including 11 professionals and 4 nonprofessionals, were recruited to participate in the field experiment. The video data were recorded simultaneously with zed cameras in the front and 45-degree sides. All participants performed 120 consecutive external chest compression operations on the Smartman CPR simulator. Three experts annotated the videos independently. An intelligent algorithm was used to extract human bone points for subsequent analysis and model development. The chi-square test was used to compare the rates of the professional and nonprofessional groups.Results:The results showed that problems with wrists, fingers, center of body weight and elbow bending had the highest incidence. Through 28 800 sets of standard human skeleton point coordinate data, we obtained a reasonable range of arm angles of 169.24°- 180.00° for the left arm and 168.49°-180.00° for the right arm. By the same method, the reasonable range of the center of gravity angle is 0.00°-18.46°. Based on these results, a new chest compression posture detection model based on a dual ZED camera was developed, which can accurately identify CCP errors (accuracy 91.31%; sensitivity 80.16%; specificity 93.53%).Conclusions:This study innovatively proposed an objective evaluation method for CCP. Moreover, a new chest compression posture detection model based on a dual ZED camera was developed, which can accurately identify CCP errors to achieve automation and standardization of quality control in CPR training.

Objective:To explore the effects of standard meal and treadmill exercise test on body surface gastrointestinal electrogram in healthy subjects, and to provide more evidence for the clinical application of gastrointestinal electrogram.Methods:From January to June 2021, a total of 100 healthy asymptomatic volunteers underwent gastrointestinal electrogram after fasting, standard meal and treadmill exercise test. After the subjects fasted for more than 8 hours, the gastrointestinal electrogram was performed after the subjects were lying flat, quiet, and breathing steadily, electrodes were placed on the the body surface projection positions of the gastric body, the lesser curvature, the greater curvature, the antrum, the ascending colon, the transverse colon, the descending colon, and the rectum. The fasting gastrointestinal electrogram was recorded for 6 min. Then lay for 5 to 10 min after the standard meal (100 g bread, 250 mL milk), the postprandial gastrointestinal electrogram was recorded for 6 min. And lay for 5 to 10 min after treadmill exercise test, then the postexercise gastrointestinal electrogram was recorded for 6 min. The frequency and amplitude of gastrointestinal electrogram waveforms of the three time points were compared, and the percentage of gastrointestinal electrical rhythm disorder, and slow wave frequency instability coefficient were also compared. Stratified analysis of gastric motility was performed according to age, sex and body mass index. Paired t-test, Pearson Chi-squared test, continuity correction Chi-squared test, Fisher′s exact method and Speraman correlation were used for statistical analysis. Results:The standard meal did not obviously affect the mean frequency of the gastric electrocardiogram, however the mean amplitude of gastric electrocardiogram significantly increased after standard meal compared with that of fasting, especially in the electrodes placed at lesser curvature((148.5±8.7) μV vs.(113.2±5.0)μV ), greater curvature((176.3±11.3) μV vs.(126.1±7.3) μV), and antrum((161.8±10.6) μV vs.(117.6±4.91) μV), and the differences were statistically significant( t=4.63, 4.63 and 3.99, all P< 0.001). There were no significant changs in rhythm and stability of the gastric electrocardiogram. The mean frequency of intestinal electrograms at the ascending colon, the transverse colon, the descending colon, and the rectum decreased after the standard meal compared with that of fasting ((10.8±0.2) count per minute(cpm) vs.(11.5±0.2) cpm, (10.5±0.2) cpm vs.(11.2±1.6) cpm, (10.9±0.2) cpm vs.(11.7±0.2) cpm, (11.1±0.2) cpm vs.(11.8±0.2) cpm), and the differences were statistically significant ( t=3.82, 4.55, 4.39, and 3.98, all P<0.001); the mean amplitude of the ascending colon, the transverse colon, and the rectum increased compared with that of fasting ((129.8±6.1) μV vs. (110.9±6.4) μV, (119.6±4.1) μV vs. (101.3±4.7) μV, (124.1±4.6) μV vs. (106.2±5.7) μV), and the differences were statistically significant ( t=2.62, 3.76, and 3.16; P=0.010, <0.001, =0.002); and the number of leads with enteroelectric rhythm disorder increased (398 vs. 389, the total number of leads is 400), and the difference was statistically significant( χ2=7.31, P=0.026). The mean frequency of gastric electricity after treadmill exercise in electrode placed at antrum increased compared with that after standard meal ((3.4±0.4) cpm vs.(3.3±0.3) cpm), and the differences were statistically significant( t=2.45, P=0.016), and the mean amplitude of gastric electricity in electrodes placed at gastric body, lesser curvature and antrum increased compared with those after standard meal((160.2±8.6) μV vs. (133.9±6.4) μV, (178.1±10.0) μV vs. (148.5±8.7) μV, (202.5±10.2) μV vs. (161.8±10.6) μV), and the differences were statistically significant ( t=2.30, 2.35, and 2.48; P=0.024, 0.021, and 0.015). Treadmill exercise affected the rhythm and stability of gastric electricity, and the number of electrodes with instable and abnormal coefficient frequency slow-wave significantly increased (25 vs. 1, the total number of electrodes is 400), and the difference was statistically significant( χ2=22.90, P<0.001). There was no significant change in the mean frequency of the colonic electricity after treadmill exercise compared with that after standard meal, however the mean amplitude of intestinal electrical waveform at the ascending colon, the transverse colon, the descending colon, and the rectum increased compared with those after standard meal((171.2±8.4) μV vs. (129.8±6.1) μV, (166.1±7.7) μV vs. (119.6±4.1) μV, (147.2±7.2) μV vs. (121.1±4.9) μV, (149.6±7.3) μV vs. (124.1±4.6) μV), and the differences were statistically significant( t=3.51, 5.49, 3.09, and 2.83; P=0.001, <0.001, =0.003, and=0.006), which affected the rhythm and stability of the colonic electricity, and the number of electrodes with instable and abnormal coefficient frequency slow-wave significantly increased (10 vs. 3, the total number of electrodes is 400, χ2=4.04, P=0.040). Gender was correlated with mean frequency of gastric electricity after standrdmeal and treadmill exercise test and mean amplitude of fasting and standard postprandial gastric electricity( r=0.242, -0.272, 0.286, 0.242; P=0.015, 0.006, 0.004, 0.015), and with mean amplitude of fasting and standard postprandial electricity( r=0.225, 0.460; P=0.024, <0.001). Age was only associated with mean frequency of fasting gastric electricity( r=-0.214, P=0.033). Body mass index was correlated with mean gastric electrical amplitude after fasting, standard meal and treadmill exercise( r=-0.347, -0.260, -0.211; P<0.001, =0.009, =0.036), as well as with the mean gastric electricity frequency after treadmill exercise ( r=0.242, P=0.016). Body mass index was correlated with the mean amplitude and frequency of fasting and standard postprandial intestinal electricity ( r=-0.261, -0.296, -0.400, -0.286; P=0.009, =0.003, < 0.001, =0.003). In the healthy volunteers with female gender and body mass index < 24 kg/m 2, there were statistically significant differences in the changes of gastric motility after standard meal (Fisher′s exact method, P=0.022 and 0.024). Conclusion:Both standard meal and treadmill exercise test affect gastrointestinal electrical activity, and exercise caused more changes in gastrointestinal electrical activity than standard meal.

Objective:To compare results of four glycosylated hemoglobin A1c (HbA1c) detection methods and to evaluate the uncertainty of HbA1C results in clinical laboratory, and to provide method for clinical laboratory on the evaluation of uncertainty.Methods:According to the four uncertainty evaluation methods, which were recommended by "CNAS-TRL-001, the evaluation and expression of measurement uncertainty in medical laboratory", the relative and absolute uncertainty of low, medium and high HbA1c in 33 clinical laboratories measured in 2019 and 35 clinical laboratories measured in 2020 was evaluated by more than 6 months of internal quality control (IQC) data, trueness verification and external quality assessment (EQA) data. The four uncertainty evaluation methods were: IQC data and trueness verification data (method 1), only trueness verification data (method 2), IQC and EQA data (method 3) and only EQA data (method 4). The related statistical methods used in this analysis were Friedman and Wilcoxon signed rank test.Results:For method 1, the median range of relative and absolute uncertainty of low, medium and high HbA1c detection in 2019 and 2020 ranged from 4.21% to 9.24% and from 0.27% to 0.64%, respectively. Compared to method 1, the relative and absolute uncertainties obtained by method 2 were smaller, and the differences were statistically significant ( P<0.016 7, P<0.05). Compared to method 1, the relative uncertainties obtained by method 3 and method 4 were smaller, except for the high concentration of HbA1c level in 2020. Among the 6 pairs of comparisons (low, medium and high HbA1c in 2019 and 2020), there were 3 pairs (high HbA1c in 2019, low and medium HbA1c in 2020) and 2 pairs (low and high HbA1c in 2020) of differences with statistical significance (all P<0.016 7). Conclusion:The uncertainty evaluation of HbA1c detection in clinical laboratory should be evaluated based on IQC and trueness verification data.

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 establish the donor bank for local region and distinguish the donors based on the past blood donation frequency and blood donation type, so as to improve the application efficiency of platelet bank. 【Methods】 1) According to the donation type and frequency of blood donors, the blood donors who had joined China Marrow Donor Program(CMDP)in our center from 2011 to 2020 were screened and classified. They are classified as reserve donors, prospective donors, and active donors. The donors, who met the selection conditions of active donors, were enrolled from all apheresis donors in 2020 to expand the local platelet bank. 2) In 2020, 739 blood donors who met the conditions of active donors were screened(including donors who had entered CMDP), and their HLA-A/B loci were detected by HLA high-resolution genotyping, and HPA was detected by Q-PCR genotyping. 3) The compatible platelets provided by three types of donors in 2021 were calculated. 【Results】 1) Taiyuan platelet bank, composed of donors with different previous donation experiences, had been constructed, including 739 active donors, 3840 prospective donors and 18 715 reserve donors. The composition ratio of ABO blood groups among three types of donors was found to be similar via chi square test; there were more male than female in three groups. 2) In 2021, the ratio of the average redonation by active donors in the platelet bank to the regular donation by the general donors was 14.4∶3.98. 3) Of the 142 compatible platelets, supplied to PTR patients in 2021, 83.8% of them came from the redonation of active donors after registration in the bank, and 9.9% and 6.3% from prospective donors and reserve donors, respectively. 4) In 2021, 28.1% of the stored pheresis platalets in our center had HLA typing data, and 54.2% of compatible platelets were retrieved from the inventory, which timely met the needs of clinical patients. 【Conclusion】 Integrating resources and distinguishing the activity degree of donors in platelet bank can reduce the cost of bank building and improve the application efficiency of the platelet bank.

Objective:To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China.Methods:This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to Ⅰ, whereas 1 059 (30.02%) in stage Ⅱ to Ⅲ, 1 874 (53.12%) in stage Ⅳ, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed.Results:Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn′t be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage ⅣB tumor without surgery was 5.4%, and for patients with stage ⅣB tumor underwent palliative surgery was 4.7%.Conclusions:More than half GBC patients in China are diagnosed in stage Ⅳ.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.

Objective:To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China.Methods:This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to Ⅰ, whereas 1 059 (30.02%) in stage Ⅱ to Ⅲ, 1 874 (53.12%) in stage Ⅳ, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed.Results:Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn′t be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage ⅣB tumor without surgery was 5.4%, and for patients with stage ⅣB tumor underwent palliative surgery was 4.7%.Conclusions:More than half GBC patients in China are diagnosed in stage Ⅳ.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.

Objective To investigate therapeutic effect of the low dose clomiphene treatment of idiopathic oligoasthenospermia and effect on sperm epididymal protein level 4.Methods183 cases of idiopathic oligoasthenospermia were divided into three groups, vitamin group of 61 patients were given vitamin E,clomiphene group(61 cases)treated with low dose clomiphene, combined group of 61 patients were given low dose clomiphene and vitamin E, lasted for 12 weeks.Semen volume, sperm density, sperm motility, sperm survival rate and sperm reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), human epididymis protein 4 (HE4), follicle stimulating hormone, luteinizing hormone, testosterone concentration were observed before and after treatment.After treatment, the patients were followed up for 1 year, the observation of the natural pregnancy rate after treatment.ResultsSperm density, sperm survival rate and sperm and a A+B grade sperm in the clomiphene group were significantly higher comparedwith the vitamin group (P< 0.05), sperm density, sperm survival rate and sperm and a A+B grade sperm in the combined group were significantly increasedcompared with clomiphene group and vitamin group (P< 0.05),levels of HE4 after treatment was significantly lower compared with before treatment (P< 0.05), And the difference between the three groups were statistically significant (P< 0.05).Follicle stimulating hormone, luteinizing hormone, testosterone in clomiphene group and combined group after treatment, were significantly increased compared with before treatment (P< 0.05), and the combined group had no statistically difference compared with clomiphene group.The pregnancy rate in 1 year of vitamin group, clomiphene group and combined group were 24.59%, 42.62% and 62.29% (P< 0.05).ConclusionClomiphene treatment of idiopathic asthenospermia is better than vitamin E, the combination of the two has a synergistic effect.

Patients with nonvalvular atrial fibrillation are the high-risk population of ischemic stroke.Anticoagulation therapy is mainly used to prevent the occurrence of stroke in clinical practice.However,there are some difficulties in the conventional administration of oral anticoagulant warfarin because of some restrictions.There are a number of novel oral anticoagulants with promising data for the prevention of stroke in nonvalvular atrial fibrillation,such as direct thrombin inhibitor and coagulant factor X a inhibitor.