Primary biliary cholangitis （PBC） and Sjögren’s syndrome （SS） are both autoimmune disorders characterized by the involvement of epithelial tissue， and comorbidity of PBC and SS is often observed in clinical practice， suggesting that these two diseases may have common pathogeneses. Currently， there are still no specific targeted therapies for PBC and SS， and the therapeutic approach for systemic manifestations mainly relies on the treatment regimens for other autoimmune disorders. This article reviews the various potential therapeutic targets that have been clarified in the pathogenesis of PBC and SS and points out that targeted therapies for these two diseases can be developed based on the common immunopathological mechanism of PBC and SS， thereby providing valuable ideas for developing novel therapies.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Diarrhea is a common and frequent disease in clinical practice.Many factors cause diarrhea,and numerous research method with animal models of diarrhea have been explored.Despite this,drugs for the treatment of diarrhea in clinical practice are limited,and some existing drugs are only suitable for diarrhea caused by a single factor.Therefore,the construction and selection of appropriate animal models of diarrhea are not only important for in-depth studies of the pathogenesis,but are also effective means for the clinical screening and evaluation of drugs for comprehensively preventing and treating diarrhea.This article reviews the literature on the establishment and evaluation of animal models of functional,bacterial,viral,and symptomatic diarrhea,as well as progress of therapeutic drug research,to provide a reference for animal experimental research into the prevention and treatment of diarrhea.

Cellular force transducer plays a crucial role in normal development of the follicles,which consists of integrin,focal adhesion,signal pathways and cytoskeleton.In follicle development,cellular force transducer converts force stimulation into biochemical signal,and activates the signal pathways to make cytoskeleton respond to stimulation.This process promotes various biological functions of germ cells,such as migration,meiosis and ovulation.This review summarizes the mechanism of follicles'development from two aspects,the role of cellular force transducer in the development of follicles and the related signal pathways,so as to provide a new idea for the further study of follicle development.

Objective:To explore the risk factors of diabetic nephropathy in type 2 diabetes patients, establish a risk prediction model for diabetic nephropathy and provide scientific reference for the prevention and screening of diabetic nephropathy.Methods:Clinical data of 1 223 patients admitted at Department of Endocrinology, General Hospital of Ningxia Medical University from January 2018 to December 2022 were retrospectively collected. In the training set, LASSO regression analysis and 10-fold cross-validation were used to screen the optimal feature variables by RStudio 4.2.1 software, and then multivariate logistic regression analysis was used to determine the final predictors selected from LASSO regression to construct the risk prediction model and draw the nomogram diagram. The receiver operating characteristic curve, C-index, calibration curve, and Hosmer-Lemeshow test were used to assess the discrimination and accuracy of the model; and the decision curve analysis was used to assess the clinical validity of the model.Results:The multivariate logistic regression analysis showed that the duration of diabetes, glycosylated hemoglobin [odds ratio ( OR) = 1.14, 95% confidence interval ( CI): 1.05-1.24], serum creatinine ( OR = 1.02, 95% CI: 1.01-1.04), 25-(OH)-D ( OR = 0.97, 95% CI: 0.95-1.00) were the best predictors of diabetic nephropathy in patients with type 2 diabetes ( P < 0.05). The predictive model was constructed by plotting the nomogram graph based on the predictor variables. In the training cohort, the diabetic nephropathy risk model displayed medium predictive power with a C-index of 0.762 (95% CI: 0.734-0.790). Meanwhile, the risk model was also well validated in the validation set, where the C-index was 0.742 (95% CI: 0.689-0.790). Hosmer-Lemeshow test showed excellent degree of fit ( P = 0.108), and the results of the decision curve analysis showed that the prediction model could be clinically beneficial. Conclusion:The establishment of the risk prediction nomogram model provides clinicians with a more convenient and scientific method for early screening and prevention of diabetic nephropathies.

Objective:To explore the effect of nurse-led peer education on the disease knowledge, medication adherence, and fall efficacy of osteoporosis patients.Methods:From June 2022 to May 2023, convenience sampling was used to select 63 patients with osteoporosis who visited the Bone Metabolism Clinic of Peking Union Medical College Hospital as participants. The patients were divided into a control group ( n=32) and an observation group ( n=31) using a random number table method. Control group received conventional health education, while observation group was treated with nurse-led peer education on the basis of control group. The osteoporosis knowledge, medication adherence, and fall efficacy scores were compared between the two groups of patients before and after intervention. Results:Two cases were lost to follow-up in control group, one case was lost to follow-up in observation group, and ultimately 30 cases were included in both observation group and control group. Before intervention, there was no statistically significant difference in osteoporosis knowledge, medication adherence, and fall efficacy scores between the two groups of patients ( P>0.05). After intervention, observation group had higher scores in osteoporosis knowledge, medication adherence, and fall efficacy than control group, and the differences were statistically significant ( P<0.05) . Conclusions:Nurse-led peer education based on online platforms can improve the knowledge, medication compliance, and fall efficacy score of osteoporosis patients, and is worthy of promotion and application in health education for osteoporosis patients.

Objective:To explore the risk factors for lymphoproliferative disorders (PTLD) in children with thalassemia major (TM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:This was a retrospective case-control study.A total of 482 children with TM who underwent allo-HSCT at Shenzhen Children′s Hospital between January 2020 and December 2022 were selected and classified into the PTLD and non-PTLD groups according to the occurrence of PTLD.The risk factors for PTLD after allo-HSCT in children with TM were analyzed, and the diagnostic efficiency of relevant risk factors for PTLD was analyzed by receiver operating characteristic (ROC) curve.Results:A total of 25 out of 482 patients (5.2%, 25/482) developed PTLD about 114 (54-271) days after allo-HSCT.Among them, 12 cases (12/25, 48.0%) occurred within 100 days, and 22 cases (22/25, 88.0%) occurred within 1 year after allo-HSCT.Univariate analysis showed that there were significant differences in gender composition, type of transplant donor, number of natural killer cells and B lymphocytes in peripheral blood at 30 days after allo-HSCT, positive rate of plasma Epstein-Barr virus deoxyribonucleic acid (EBV-DNA) and incidence rate of acute graft-versus-host disease (aGVHD) between the 2 groups (all P<0.05).Multivariate Logistic regression analysis showed that female ( OR=3.196, 95% CI: 1.144-8.929), positive plasma EBV-DNA ( OR=17.523, 95% CI: 5.449-56.344) and aGVHD ( OR=3.156, 95% CI: 1.161-8.575) were independent risk factors for PTLD after allo-HSCT in TM children (all P<0.05).The ROC curve analysis showed that positive plasma EBV-DNA had an excellent accuracy in predicting the occurrence of PTLD after allo-HSCT (sensitivity was 0.796, specificity was 0.800, area under the curve was 0.803).If combined with aGVHD and gender, the area under the curve for the prediction of PTLD increased to 0.831. Conclusions:Female, positive plasma EBV-DNA and aGVHD are independent risk factors for PTLD after allo-HSCT in children with TM.It provides useful early warnings for the prediction and prevention of PTLD.

Objective:To evaluate and summarize the best evidence for exercise intervention in patients with hypertension, and to provide the basis for clinical medical workers to manage hypertension.Methods:We searched UpToDate, BMJ Best Practice, the Cochrane Library, the International Guideline Collaborative Network to collect guidelines, systematic evaluation, and evidence summary. The retrieval time was from database establishment to June 1st 2022. Two researchers independently conducted literature quality evaluation and extracted evidence from the included literature.Results:A total of 13 articles were included, including 10 guidelines, 1 expert consensus and 2 Meta analysis. A total of 23 pieces of best evidence were collected, mainly involving 8 aspects, including exercise principles, exercise assessment, exercise environment, pre-exercise preparation, exercise program, post-exercise collation, tracking and review, exercise compliance.Conclusions:Exercise has a positive effect on improving blood pressure in patients with hypertension. The suggestions summarized in this study can be tried to guide clinical practice.