Objective:To investigate the role of the IgG subtypes (IgG1 and IgG2a) in anti-glycoprotein (GP) Ⅰbα antibody-induced platelet clearance.Methods:Venous blood was collected from healthy volunteers, and platelets were separated. The phagocytosis of human platelets by human acute monocytic leukemia cells (THP-1 cells) induced by different anti-GPⅠbα antibodies (AN51, AK2, HIP1, TM60, VM16d, WM23, and SZ2) was detected by flow cytometry. The effects of the AN51 full-length antibody, F (ab') 2, and Fab fragments on platelet phagocytosis by THP-1 cells were detected by flow cytometry. Then, the Fc blocking antibody 2.4G2 and normal rat IgG2a or IgG1 were injected into C57BL/6J mice via the posterior ocular vein, and their effects on platelet reduction induced by R300 were detected by a hematology analyzer. Results:Compared with IgG1, the IgG2a subtype of anti-GPⅠbα antibodies induced the phagocytosis of platelets by THP-1 cells in vitro ( P<0.05). In contrast to the AN51 full-length antibody, neither AN51 F (ab') 2 nor the Fab fragment could induce THP-1 cells to phagocytose platelets ( P<0.05). Compared with the control group, anti-mouse GPⅠbα R300-induced thrombocytopenia in mice was reduced at 2, 4, and 6 h after the injection of Fc blocking antibody 2.4G2 ( P<0.05). Similarly, R300-induced thrombocytopenia in mice was reduced at 2, 4, and 6 h after the injection of rat IgG2a ( P<0.05) . Conclusion:IgG2a plays an important role in anti-GPⅠbα-induced clearance.

Objective:To investigate the role of the IgG subtypes (IgG1 and IgG2a) in anti-glycoprotein (GP) Ⅰbα antibody-induced platelet clearance.Methods:Venous blood was collected from healthy volunteers, and platelets were separated. The phagocytosis of human platelets by human acute monocytic leukemia cells (THP-1 cells) induced by different anti-GPⅠbα antibodies (AN51, AK2, HIP1, TM60, VM16d, WM23, and SZ2) was detected by flow cytometry. The effects of the AN51 full-length antibody, F (ab') 2, and Fab fragments on platelet phagocytosis by THP-1 cells were detected by flow cytometry. Then, the Fc blocking antibody 2.4G2 and normal rat IgG2a or IgG1 were injected into C57BL/6J mice via the posterior ocular vein, and their effects on platelet reduction induced by R300 were detected by a hematology analyzer. Results:Compared with IgG1, the IgG2a subtype of anti-GPⅠbα antibodies induced the phagocytosis of platelets by THP-1 cells in vitro ( P<0.05). In contrast to the AN51 full-length antibody, neither AN51 F (ab') 2 nor the Fab fragment could induce THP-1 cells to phagocytose platelets ( P<0.05). Compared with the control group, anti-mouse GPⅠbα R300-induced thrombocytopenia in mice was reduced at 2, 4, and 6 h after the injection of Fc blocking antibody 2.4G2 ( P<0.05). Similarly, R300-induced thrombocytopenia in mice was reduced at 2, 4, and 6 h after the injection of rat IgG2a ( P<0.05) . Conclusion:IgG2a plays an important role in anti-GPⅠbα-induced clearance.

Surgical position is very important in upper urinary calculi surgery.The correct surgical position can provide a good surgical field of view,shorten the operation time,reduce the incidence of complications,and ensure the safety of patients'airway and comfort.Endoscopic surgery is the preferred treatment for kidney and ureteral stones.As the traditional position causes higher recurrence rate and more complications,more positions have been experimented.This article reviews the application and therapeutic effects of different surgical positions in percutaneous nephrolithotomy(PCNL),retrograde intrarenal flexible ureteroscopic lithotripsy(RIRS)as well as their combined use,and summarizes the advantages and disadvantages for clinical reference.

BACKGROUND: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. RESULTS: Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. CONCLUSION: Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. TRIAL REGISTRATION Chictr.org, ChiCTR2000039799.
Humans ; Quality of Life ; China ; Arthritis, Rheumatoid/drug therapy* ; Piperidines/therapeutic use* ; Treatment Outcome ; Antirheumatic Agents/therapeutic use* ; Pyrroles/therapeutic use*

Objective To investigate the changes and clinical significance of bile acid spectrum levels in patients with early non-alcoholic fatty liver disease(NAFLD).Methods A total of 149 patients with early NAFLD(NAFLD group)and 140healthy controls(healthy group)who underwent physical examinations at the Physical Examination Center,the Fourth Affiliated Hospital of Zhejiang Uni-versity School of Medicine from July 2021 to February 2022 were selected,and liver function test,bile acid spectrum detection and con-trolled attenuation parameter test were performed on all patients,the differences in liver function and bile acid spectrum between the two groups were compared,and the risk factors of early NAFLD and the efficacy of bile acid subgroups in diagnosing early NAFLD were ana-lyzed.Results The levels of aspartate transaminase(AST),alanine aminotransferase(ALT),and γ-glutamyl transpeptidase(r-GT)in the NAFLD group were higher than those in the healthy group(P<0.05).cholic acid(CA),glycocholic acid(GCA),tauro-cholic acid(TCA),glycodeoxycholic acid(GDCA),chenodeoxycholic acid(CDCA),glycochenodeoxycholic acid(GCDCA),tauro-chenodeoxycholic acid(TCDCA),glycineursodeoxycholic acid(GUDCA),tauroursodeoxycholic acid(TUDCA)and taurolithocholic acid(TLCA)were higher than those in the healthy group(P<0.05),and the level of lithocholic acid(LCA)was lower than the healthy group(P<0.05);Logistic regression analysis showed that AST,GCA,TCA,CDCA,GCDCA,TCDCA,GUDCA and TLCA were inde-pendent risk factors in NAFLD patients;receiver operating characteristic curve shows that AST,GCA,TCA,CDCA,GCDCA,TCDCA,GUDCA and TLCA could predict the occurrence of NAFLD to a certain extent,among which AST had the best comprehensive prediction effect(AUC =0.750),and GCA had the highest sensitivity(77.2%),and TLCA had the strongest specificity(88.6%);the levels of GCA and TCA in the severe group were significantly higher than those in the mild group(P<0.05),the concentration of serum TCA in-creased gradually increased with the aggravation of NAFLD severity,and there was a linear correlation between them(r = 0.52,P<0.05).Conclusion The bile acid spectrum components of patients with early NAFLD was changed,mainly primary bile acids and con-jugated bile acids.The level of TCA can not only predict the occurrence of NAFLD to a certain extent,but also has a positive correlation with the severity of NAFLD,which is expected to become a serological marker of NAFLD.

Objective:To investigate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with maintenance hemodialysis (MHD) in Jiangsu province during SARS-CoV-2 pandemic in China from December 7, 2022 to January 27, 2023, and to analyze the influencing factors of all-cause death.Methods:It was a multi-center cross-sectional investigation. Structured questionnaire was used to collect patient information by medical staff of each hemodialysis center (room) as investigators. Part of the demography data and laboratory examination data came from the Jiangsu Province Hemodialysis Data Information System. MHD patients from hemodialysis centers (rooms) at all levels of medical institutions and independent hemodialysis institutions in Jiangsu province during the outbreak of SARS-CoV-2 infection were included, and the clinical characteristics and all-cause mortality of confirmed and suspected cases of SARS-CoV-2 infection were analyzed.Results:Questionnaire surveys and data analysis on 57 278 patients in 407 hemodialysis centers (rooms) were completed, accounting for 90.41% of the total number of MHD patients (63 357 cases) in Jiangsu province during the same period. There were 24 038 cases (41.97%) of SARS-CoV-2 infection and 14 805 cases (25.85%) of suspected infection, which were widely distributed in all dialysis centers in Jiangsu province. After clinical classification of 38 843 confirmed and suspected SARS-CoV-2 infection cases, 3 662 cases were severe and critical cases, accounting for 9.43% of the infected and suspected cases. Among the patients who had completed the questionnaires, there were 1 812 all-cause deaths, with an all-cause mortality rate of 3.16%. Multivariate logistic regression analysis showed that elderly (taking ≤50 years as a reference, 51-59 years: OR=1.583, 95% CI 1.279-1.933, P=0.001; 60-69 years: OR=3.972, 95% CI 3.271-4.858, P<0.001; 70-79 years: OR=7.236, 95% CI 5.917-8.698, P<0.001; ≥80 years: OR=11.738, 95% CI 9.459-14.663, P<0.001), male ( OR=1.371, 95% CI 1.229-1.529, P<0.001), and co-infection with hepatitis B virus (HBV) (positive serum HBV surface antigen, OR=0.629, 95% CI 0.484-0.817, P<0.001) were independent influencing factors for all cause mortality. Receiver-operating characteristic curve analysis showed that the area under the curve for male, age and current HBV infection prediction of all-cause death was 0.529 ( P<0.001), 0.724 ( P<0.001) and 0.514 ( P=0.042), respectively, and the cut-off value for age prediction of all-cause death was 65.5 years old. Compared with patients without HBV infection, MHD patients with HBV infection significantly reduced the proportion of severe and critically ill patients, all-cause hospitalizations and all cause deaths when infected with SARS-CoV-2 (4.99% vs. 6.41%, χ2=6.136, P=0.013; 8.90% vs. 11.44%, χ2=11.662, P<0.001; 2.01% vs. 3.37%, χ2=10.713, P=0.001, respectively). Conclusion:The MHD patients in Jiangsu province are susceptible to SARS-CoV-2. Elderly age and male gender are independent risk factors for death in MHD patients during the epidemic, while the HBV infection may be a protective factor for death of MHD patients infected with SARS-CoV-2.

The study is designed to explore new methods of evaluation for teachers′ comprehensive ability in general medicine. In the whole education process of resident aiming at general practitioner (GP) residency post competency, the authors made comprehensive evaluation of GP faculty, and created a comprehensive GP faculty evaluation model of result orientation. The efforts aim at exploring and introducing faculty evaluation methods and promoting education quality, in order to develop outstanding GP residents of strong post competency.

Objective: To investigate the effects of Tim-3 on osteoclast-like cell (OLC) formation and bone resorption induced by peripheral blood mononuclear cells (PBMCs). Methods: The expression levels of Tim-3 in of rheumatoid arthritis (RA) patients and healthy controls were detected by flow cytometry. The OLCs were induced by human PBMCs in vitro. The expression levels of tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK) and matrix metalloproteinase 9 (MMP9) mRNAs in the formation of OLCs were detected by real-time quantitative PCR. The morphology of OLCs was observed by Wright′s staining and G-actin staining, and the number of OLCs was counted by TRAP staining. The number and area of bone resorption pits in OLCs were detected by the Corning Osteo Assay Surface. Results: The expression levels of Tim-3 in PBMCs of RA patients ([77.31±10.66]%) were significantly higher than that of healthy controls ([51.72±16.69]%, t=7.593, P＜0.01). When PBMCs with different Tim-3 levels were induced into OLCs, the area of bone resorption pits in the high Tim-3 level group ([1.054±0.085] S/mm 2 ) were significantly lower than those in the intermediate Tim-3 level group ([1.889±0.053] S/mm 2 ) and the low Tim-3 level group ([2.763±0.066] S/mm 2 , F=9.318, P＜0.05). Conclusion Tim-3 may negatively regulate the bone resorption of OLCs.

Objective To evaluate the effect of " elite small class" training mode in capacity building for general practitioners in Yiwu city. Methods The Fourth Affiliated Hospital of Zhejiang University School of Medicine worked with Yiwu Health Bureau, and held the first training class for general practitioners from December 6th in 2018 to April 5th in 2019.The mode of " elite small-class" was adopted. Theoretical assessment was carried out for trainees before and after the training and discussion was conducted after the training. Descriptive analysis of quantitative data and thematic analysis of qualitative data were carried out. Results The trainees′theoretical performance had been significantly improved after 4 months of theoretical learning and clinical rotation.The average score of the theoretical performance was increased from 66.94 to 72.59. Conclusions It was preliminarily found that the " elite small-class" training mode was suitable for the training of general practitioners in rural areas.Government support and trainee selection are key to training outcomes.

The fourth affiliated hospital of Zhejiang university is responsible for training general practitioners in view of the basics of local general practitioners and the characteristics of chronic and frequently-occurring diseases in Yiwu city. This program is carried out relying on the high-quality faculty of medical alliances within Zhejiang university, and funded by the municipal government of Yiwu. The "4+6"training program is designed to elevate the competence of primary general practitioners. Such training fit the overall medical level of general practitioners, enhances people′s trust of general practitioners and the rate of diagnosis at primary level.