BACKGROUND:Stem cells can promote nerve regeneration,repair damaged nerves,inhibit inflammation and apoptosis of nerve cells,and provide a new way for the treatment of Alzheimer's disease. OBJECTIVE:To make a bibliometrical analysis of the articles on stem cell therapy for Alzheimer's disease published internationally from 2004 to 2023,in order to reveal the research hotspot and trend of stem cell therapy for Alzheimer's disease. METHODS:From the Web of Science Core Collection database,by using Excel,VOSviewer,and Citespace software,the annual number of publications,countries,institutions,journals/co-cited journals,authors,and keywords of articles related to stem cells and Alzheimer's disease published from January 1,2004 to October 31,2023 were visually analyzed. RESULTS AND CONCLUSION:A total of 3 521 core papers were included,and the number of published papers increased year by year.The United States is the country with the most papers.Harvard Medical School is the most prolific institution.Maiese kenneth is the author with the most papers.International Journal of Molecular Sciences has the most papers in this field.The journal PLoS One published the most citations.At present,the field of stem cell therapy for Alzheimer's disease focuses on pathophysiological mechanism and animal experimental research,and"neurogenesis","oxidative stress","extracellular vesicles",and"mesenchymal stem cells"are the research trends in this field.Stem cell therapy for Alzheimer's disease has broad prospects.In the future,exchanges and cooperation between institutions and authors should be strengthened to further explore the main mechanism of stem cell therapy for Alzheimer's disease,solve possible clinical problems such as immune rejection,effectiveness,and safety,and further tap the potential of stem cells in the treatment of Alzheimer's disease.

Objective:To compare arthroscopic versus open Brostr?m-Gould repair of the anterior talofibular ligament (ATFL) in the treatment of chronic ankle instability (CAI) in young men undergoing high intensity exercise.Methods:A retrospective study was conducted to analyze the 61 young male patients with CAI undergoing high-intensity exercise who had been treated at Department of Trauma and Orthopedics, 947th Army Hospital of Chinese People’s Liberation Army from January 2016 to July 2020. Their age was (25.9±2.7) years and their disease duration (13.9±2.8) months. According to their different treatment methods, they were divided into an arthroscopic group ( n=26) in which their ATFL was repaired by arthroscopic Brostr?m-Gould surgery and a Brostr?m-Gould group ( n=35) in which their ATFL was repaired by open Brostr?m-Gould surgery. The 2 groups were compared in terms of operation time and intraoperative bleeding, as well as the ankle-hindfoot scores of American Orthopaedic Foot & Ankle Society (AOFAS), Karlsson ankle functional (KAF) scores and visual analogue scale (VAS) pain scores at postoperative 3, 6, 12, and 24 months. Results:There were no significant differences in the preoperative general data between the 2 groups, indicating comparability ( P > 0.05). The operation time [(35.8±3.9) min] and intraoperative bleeding [(6.6±2.6) mL] in the arthroscopic group were significantly less than those in the Brostr?m-Gould group [(52.1±4.6) min and (16.1±4.0) mL] ( P < 0.05). The AOFAS ankle-hindfoot scores and KAF scores in the arthroscopic group were significantly higher than those in the Brostr?m-Gould group at postoperative 3 and 6 months, but the AOFAS ankle-hindfoot score and KAF score at postoperative 24 months were significantly lower than those in the Brostr?m-Gould group ( P < 0.05). There was no statistically significant difference in AOFAS ankle-hindfoot score or KAF score between the 2 groups at postoperative 12 months, as well as in VAS pain scores at postoperative 3, 6, 12, and 24 months between the 2 groups ( P > 0.05). Conclusions:In young men undergoing high intensity exercise, compared with open Brostr?m-Gould surgery, arthroscopic Brostr?m-Gould surgery may lead to better clinical outcomes in a short-term (3 months after surgery). However, open Brostr?m-Gould surgery may result in better long-term efficacy than arthroscopic Brostr?m-Gould surgery (24 months after surgery).

The pathogenesis of immune-mediated liver injury is related to immune regulation disorders. In recent years, researchers have focused on the unique role of invariant natural killer T cells (iNKT cells) in immune-mediated liver injury. iNKT cells, a special subset of lymphocytes, are crucial for immune regulation by bridging innate and adaptive immunity. iNKT cells interact with various immune cells and possess strong immune regulatory capabilities, but their role is complex, potentially promoting liver injury or protecting the liver from damage. This article reviews the latest research progress on iNKT cells in immune-mediated liver injury and describes some factors that regulate immune liver injury by altering the expression of glycosphingolipids, such as liver X receptor and tumor progression site2. In addition, the research results are explored to assist in deepening the understanding of the mechanism of immune-mediated liver injury so as to provide new directions for the development of related treatment strategies.

BACKGROUND: Epoxyeicosatrienoic acids (EETs), which are metabolites of arachidonic acid catalyzed by cytochrome P450 epoxygenase, are degraded into inactive dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH). Many studies have revealed that sEH gene deletion exerts protective effects against diabetes. Vascular calcification is a common complication of diabetes, but the potential effects of sEH on diabetic vascular calcification are still unknown. METHODS: The level of aortic calcification in wild-type and Ephx2-/- C57BL/6 diabetic mice induced with streptozotocin was evaluated by measuring the aortic calcium content through alizarin red staining, immunohistochemistry staining, and immunofluorescence staining. Mouse vascular smooth muscle cell lines (MOVAS cells) treated with β-glycerol phosphate (0.01 mol/L) plus advanced glycation end products (50 mg/L) were used to investigate the effects of sEH inhibitors or sEH knockdown and EETs on the calcification of vascular smooth muscle cells, which was detected by Western blotting, alizarin red staining, and Von Kossa staining. RESULTS: sEH gene deletion significantly inhibited diabetic vascular calcification by increasing levels of EETs in the aortas of mice. EETs (especially 11,12-EET and 14,15-EET) efficiently prevented the osteogenic transdifferentiation of MOVAS cells by decreasing nidogen-2 (NID2) expression. Interestingly, suppressing sEH activity by small interfering ribonucleic acid or specific inhibitors did not block osteogenic transdifferentiation of MOVAS cells induced by β-glycerol phosphate and advanced glycation end products. NID2 overexpression significantly abolished the inhibitory effect of sEH gene deletion on diabetic vascular calcification. Moreover, NID2 overexpression mediated by adeno-associated virus 9 vectors markedly increased insulin-like growth factor 2 (IGF2) and phospho-ERK1/2 expression in MOVAS cells. Overall, sEH gene knockout inhibited diabetic vascular calcification by decreasing aortic NID2 expression and, then, inactivating the downstream IGF2-ERK1/2 signaling pathway. CONCLUSIONS sEH gene deletion markedly inhibited diabetic vascular calcification through repressed osteogenic transdifferentiation of vascular smooth muscle cells mediated by increased aortic EET levels, which was associated with decreased NID2 expression and inactivation of the downstream IGF2-ERK1/2 signaling pathway.
Animals ; Mice ; Vascular Calcification/metabolism* ; Mice, Inbred C57BL ; Epoxide Hydrolases/metabolism* ; Diabetes Mellitus, Experimental/genetics* ; Male ; Gene Deletion ; MAP Kinase Signaling System/genetics* ; Cell Line ; Immunohistochemistry ; Muscle, Smooth, Vascular/metabolism* ; Signal Transduction/genetics* ; Mice, Knockout

This study aims to investigate the isolate and identify of infectious bronchitis virus(IBV)in chickens,and study its genetic variation and pathogenicity.In 2023,two strains named CK/CH/HN/SQ202301 and CK/CH/HN/SQ202302 were obtained from suspected infectious bronchitis(IB)infected materials collected in a region of Henan Province,China.Further analysis showed that the two isolates belong to the G Ⅰ-13 and GⅥ genotypes,respectively.The cleavage sites of S protein were all RRSRR.The prediction of glycosylation sites showed that the two isolates had 18 and 12 N-glycosylation sites respectively,but no O-glycosylation site.Recombinant analysis shows that C2023-1 was a recombinant strain.Pathogenicity was assessed by infecting 1-day-old SPF chicks with the two isolates,and the results showed that C2023-1 strain infection could cause clini-cal symptoms such as depression and head shaking,as well as death in chicks,with a mortality rate of 37.5％.There were no clinical symptoms or deaths after infection with C2023-2 strain.Viral load test results showed that both isolates continued to detoxify until the 10th day,and had strong rep-lication capacity in the kidney,trachea and bursa of Fabricius.The results indicate significant differences in the genetic characteristics and pathogenicity of the two isolates due to their different genotypes.This study not only provides new epidemiological data on IB,which contributes to a bet-ter understanding of IBV's epidemiological features and control challenges,but also adds valuable bioinformatics resources for IBV by analyzing its variation mechanisms and biological information.

Objective To investigate the causal relationship between abnormal placental lipid metabolism and trophoblast dysfunction in patients with preeclampsia(PE),and to explore the regulatory effects of PPARγ on trophoblast function under hypoxic conditions.Methods Placental tissues were collected from 30 patients with PE and 30 individuals with normal pregnancies at the General Hospital of Ningxia Medical University between October 2020 and November 2021 for the analysis of lipid deposition.A rat model of PE was established,comprising a sham-operated(Sham)group and a reduced uterine perfusion pressure(Rupp)group,with six rats in each group(n=12 total).Human trophoblast cells(HTR-8/SVneo)were cultured in vitro and randomly assigned to four experimental groups:normoxic control,hypoxia,hypoxia+PPARγ agonist(Rosiglitazone),and hypoxia+PPARγ antagonist(T0070907).The expression levels of lipid metabolism-related genes and transcription factors(FASN,FABP4,PPARγ,LXRα)were assessed using RT-qPCR.Western blotting was performed to determine the protein expression levels of PPARγ.Cell migration and invasion capacities were evaluated using scratch wound healing and Transwell assays,respectively.Results Placental lipid deposition in the PE group was significantly higher than that in the control group,particularly in the Rupp model mice(P<0.001).Under hypoxic conditions,the expression levels of FASN and FABP4 were upregulated in trophoblast cells(P<0.001),whereas the expression of PPARγ and LXRα was downregulated(P<0.001).Furthermore,treatment with the PPARγ antagonist T0070907 exacerbated the inhibitory effects of hypoxia on cell function(P<0.001),significantly reducing cell invasion and migration capacity(P<0.001).Additional siRNA-mediated knockdown experiments confirmed that PPARγ deficiency further aggravated hypoxia-induced impairments in cell migration and invasion,and this detrimental effect could not be reversed by Rosiglitazone.Conclusions Abnormal placental lipid metabolism in PE is closely linked to PPARγ-mediated enhancement of lipid synthesis and metabolic dysregulation under hypoxic conditions,which may subsequently impair trophoblast invasion and migration.

Objective:To establish a machine learning-based risk prediction model for perimenopausal depressive symptoms and to identify associated risk factors.Methods:A total of 1 105 women aged 45 to 55 years were selected from the 2020 China Health and Retirement Longitudinal Study (CHARLS) dataset.Three machine learning algorithms, including Random Forest, XGBoost and Adaptive Boosting (AdaBoost), were employed to construct prediction models for perimenopausal depressive symptoms. Descriptive statistics and between-group comparisons were performed using SPSS 24.0.And Python 3.10 software was used to build the risk prediction model. Model performance was assessed using receiver operating characteristic (ROC) curves and calibration plots, and the optimal model was identified accordingly. The Shapley additive explanation (SHAP) algorithm was then used to analyze feature importance and the influence of each predictor on the outcome.Results:Among the 1 105 perimenopausal women, 671(60.7%)were categorized in the non-depressive group and 434 (39.3%) in the depressive group. The Random Forest model demonstrated the best overall predictive performance among the three machine learning models, achieving an area under the ROC curve (AUC) of 0.793 and a calibration error of 0.181. SHAP analysis revealed that annual household income was the strongest risk factor in the Random Forest model, with a relative importance of 0.048, followed by cognitive function(0.047), self-rated health status(0.046), life satisfaction(0.043), sleep duration(0.041).Conclusions:The Random Forest based model effectively predicts the risk of perimenopausal depressive symptoms. Annual household income, cognitive function, self-rated health, and life satisfaction are risk factors for depressive symptoms in perimenopausal women.

To verify whether the two B-cell epitopes Pep1 and Pep4 in the FAdV-4 WZ fiber can be used as candidate epitopes for multivalent epitope vaccines,epitopes Pep1 and Pep4 were tandemly linked with the chicken infectious bronchitis virus strain M41 S1 protein gene in different patterns,and a recombinant fusion plasmid was constructed and expressed in E.coli BL21(DE3).It was confirmed by Western blot and ELISA tests that all four expressed fusion proteins reacted specific-ally with anti-M41 whole virus serum and WZ strain anti-Fiber 2-knob protein serum.After purifi-cation and immunization of BALB/c mice,specific antibodies against the peptide epitopes were de-tected in mouse sera.The results showed that the Pep4 epitope induced a stronger immune re-sponse than the Pep1 epitope.When Pep1 was connected with the amino and carboxyl termini of the fusion protein,respectively,both resulted in the production of the same level of anti-Pep1 anti-bodies in the immunized animals,whereas when Pep4 was connected with the carboxyl terminus of the fusion protein,the immunized animals produced a higher level of anti-Pep4-specific antibodies.This research indicates that the B cell epitopes Pep1 and Pep4 of the reactive WZ strain Fiber 2,when conjugated with proteins to form fusion proteins,can enhance the immunogenicity of Pep1 and Pep4 without affecting the antigenicity of the carrier protein.This study provides technical support and serves as a reference for the design and development of a multivalent epitope vaccine for FAdV-4.

Objective:To investigate the current situation and correlation between mental health and stressors of new professional master's degree graduates in clinical medicine, and to provide empirical support for improving student mental health.Methods:An online questionnaire survey was conducted among 3 587 fresh graduate students with master's degree in clinical medicine from 65 training institutions in China. SPSS 26.0 was used to compare and analyze the measurement data. Descriptive statistics were used to analyze the mental health using Symptom Checklist-90 (SCL-90) and the current status of stressors. The influence factors and correlation between mental health and stressors were analyzed by means of differentiation analysis and correlation analysis.Results:The SCL-90 overall mean score as well as the scores of obsessive-compulsive symptoms, interpersonal sensitivity, depression, terror, anxious, psychoticism, and hostility of new professional master's degree graduates in clinical medicine were all higher than the national norm ( P<0.05). Among the participants, 58.21% (2 088/3 587) exhibited varying degrees of symptoms listed in the SCL-90. Students from families with low per capita income and low parental education level have more prominent psychological problems. The top three stressors perceived were job seeking, research tasks, and self-ability. Students with positive SCL-90 symptoms reported significantly higher perceived stress in all three stressor dimensions compared to their symptom-negative counterparts ( P<0.001), indicating a significant correlation between mental health status and stressors. Conclusions:The mental health status of new professional master's degree graduates in clinical medicine is concerning and warrants focused attention from educational authorities, academic institutions, and families.

Objective:To understand the graduation destination of newly graduated medical master's students in China and analyze their employment status.Methods:A questionnaire survey was conducted on 15 942 medical master's students who graduated in 2023. Descriptive analysis, χ2 test, and Kruskal-Wallis rank-sum test were used to understand the current situation and differences in the graduation destinations, employment units, job positions, and starting salaries of different types of medical master's graduates. Results:The employment rate of medical master's graduates was 58.21% (9 280/15 942). In terms of graduation destinations, male graduates, professional degree holders, graduates from non-"Double First-Class" universities, and nursing majors had a high proportion of confirmed employment units. Male graduates, academic degree holders, graduates from "Double First-Class" universities, and basic medical science majors had a high proportion pursuing further studies domestically. In terms of employment, the highest proportion of medical master's graduates worked in hospitals (84.92%, 6 495/7 648) and the lowest proportion worked in primary-level medical and healthcare institutions (1.02%, 78/7 648). The majority (78.07%, 5 971/7 648) held professional technical positions. Starting salaries were relatively low and ranged between 3 001 and 5 000 yuan/month, accounting for 30.99% (2 370/7 648).Conclusions:The employment rate of medical master's graduates is low, with concentrated employment units and job positions, and there is a lack of talents in primary medical institutions. Colleges and universities and education management departments should adopt policy-driven approaches to support key demographic groups and encourage employment in primary healthcare. Training programs should be timely adjusted in response to market demands and focus on cultivating the comprehensive quality and job competence of medical master's graduates. Additionally, student-centered approaches should be used to strengthen the employment guidance and career planning services.