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.

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.

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.

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.

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.

OBJECTIVE: To explore the clinical and genetic characteristics of a very early-onset inflammatory bowel disease (VEO-IBD) type 28 child with atypical clinical manifestations. METHODS: A VEO-IBD type 28 child with atypical clinical manifestations admitted to the Department of Neonatology, Children's Hospital Affiliated to Shandong University on November 5, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples of the child and his parents were collected for high-throughput sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 50-day-old male, had manifested bronchitis, ulcerative stomatitis, eczema and slightly loose stool. High-throughput sequencing revealed that he has harbored compound heterozygous variants of the IL-10RA gene, namely c.299T>G (p.V100G) and c.301C>T (p.R101W), which were inherited from his father and mother, respectively. Bioinformatic analysis showed that both variants have been recorded in the HGMD database, though the c.299T>G variant has not been included in the gnomAD, 1000 Genomes, ExAC and ESP6500 databases, while the c.301C>T variant has a low population frequency. Both variants were predicted to be deleterious by the online software including SIFT, PolyPhen-2 and Mutation Taster. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PS3+PM2_Supporting+PP3). CONCLUSION The c.299T>G and c.301C>T variants of the IL-10RA gene probably underlay the VEO-IBD type 28 in this child. Above finding has expanded the phenotypic spectrum of VEO-IBD type 28 due to variants of the IL-10RA gene and provided a reference for the clinical diagnosis of this disease.
Humans ; Child ; Male ; Computational Biology ; Diarrhea ; Gene Frequency ; Inflammatory Bowel Diseases/genetics* ; Mutation

Objective:To monitor the effects of intervention and management on the quality of life and the incidence of cardiovascular events in patients with chronic heart failure in the community setting.Methods:Based on questionnaire data, 200 patients with chronic heart failure in the community were randomly divided into an observation group and a control group, with 100 cases in each group.The control group was followed up for routine health information collection at home, while the observation group received standardized community intervention for patients with chronic heart failure.The awareness rate of heart failure, rate of patients receiving drug treatment, rate of standardized drug utilization, cardiac function, satisfaction with quality of life and incidence of cardiovascular events were compared between the two groups.Results:Scientific intervention for community-dwelling patients with chronic heart failure was able to significantly improve standardized drug usage and quality of life( P<0.05).Compared with the control group, patients in the observation group showed a significantly lower probability of cardiovascular events and more favorable results measured with parameters such as blood pressure, blood glucose and heart rate after intervention.Especially noteworthy was that the effective control rate of blood pressure in the observation group reached 72.4%, which was much higher than 45.9% in the control group( χ2=14.543, P<0.05), the effective control rate of blood glucose in the observation group reached 69.4%, which was much higher than 32.7% in the control group( χ2=12.588, P<0.05), and the effective control rate of heart rate in the observation group(80.6%)was much higher than in the control group(53.1%)( χ2=13.137, P<0.05).The observation group also had better results than the control group in quitting smoking, eating a low-salt, low-fat diet, and regularly measuring blood pressure, blood glucose and body fat percentage.The MNLF score in the control group(31.21±3.01)was higher than that in the observation group(22.66±2.87), and the difference was statistically significant( t=7.26, P<0.05).The LiHFe score in the control group(39.85±6.09)was lower than that in the observation group(71.36±4.32), and the difference was statistically significant( t=18.44, P<0.05).The observation group had lower readmission frequency(46.9% vs.29.6%)and incidence of cardiovascular events(56.1% vs.31.6%)than the control group and the difference was statistically significant( χ2=12.64, 15.01, both P<0.05). Conclusions:The establishment of community intervention and management for patients with chronic heart failure can significantly improve the awareness rate of heart failure, rate of drug treatment, rate of standardized drug usage, self-management ability and quality of life, and reduce the incidence of cardiovascular events.The practice should be promoted in communities.

This study reported the diagnosis and treatment of cytochrome P450 oxidoreductase deficiency (PORD) in a male infant. The patient was admitted to Children's Hospital Affiliated to Shandong University at the age of 38 days due to nasal obstruction and feeding difficulties presented at 10 d after birth, as well as less weight gain. Physical examination showed craniosynostoses, hand and foot deformities, and normal external genitalia. Laboratory examination revealed mildly elevated serum adrenocorticotrophic hormone and decreased level of baseline cortisol. A homozygous mutation of c.1370G>A(p.R457H) in POR gene was detected by whole-exome sequencing, which confirmed the diagnosis of PORD. Skeletal deformities complicated by external genital malformations and/or adrenocortical hormone abnormalities are important diagnostic indicators for PORD.