BACKGROUND:Extracellular vesicles mediate intercellular signal transduction through the proteins,nucleic acids,and lipids they carry,thereby influencing the function of target cells.This vesicle-mediated communication mechanism is involved in regulating female reproductive development.OBJECTIVE:To summarize and analyze the regulatory roles of extracellular vesicle-mediated intercellular communication in female reproductive development.METHODS:A search was conducted in the PubMed database using the search terms"extracellular vesicles,exosomes,reproduction,maternal-embryo communication,maternal-fetal crosstalk,embryo implantation,endometrium,oviduct,follicle."The initial screening was carried out by reading the titles and abstracts of the literature,and then the literature with poor relevance to the research purpose,outdated content,and duplication was excluded according to the inclusion and exclusion criteria.Ultimately,69 relevant articles were included for comprehensive analysis.RESULTS AND CONCLUSION:Extracellular vesicles play a crucial role in key processes of female reproductive development,from folliculogenesis to implantation.(1)Extracellular vesicles mediate intercellular communication within the follicle,particularly the interactions between oocytes and follicular cells,which are essential for follicle development and maturation.(2)Extracellular vesicles and their contents facilitate interactions between the embryo and the fallopian tube,influencing the trajectory of embryonic development.(3)Extracellular vesicles and their contents promote implantation by mediating bidirectional communication between the embryo and the endometrium.Uterine-derived extracellular vesicles regulate processes such as embryo adhesion,invasion,and decidualization,while embryo-derived extracellular vesicles modulate endometrial receptivity,convey embryonic signals,and adjust the endometrial microenvironment.Studying the roles of extracellular vesicles in female reproductive development can provide valuable insights into the mechanisms of infertility and support the development of new therapeutic strategies.

BACKGROUND:Low temperatures have detrimental effects on the human cardiovascular system,with a higher prevalence of hypertension and related cardiovascular diseases,especially among people living in cold climates.Transient receptor potential M8(TRPM8)is often recognized as a physiological sensor of environmental cold,and glutamate receptor-3(GLR-3)/glutamate receptor ionotropic,kainate 2(GluK2)is also cold-sensitive.However,the specific molecular mechanisms of cold-associated TRPM8 and GLR-3/GluK2 in regulating hypertension remain puzzling.OBJECTIVE:Through a review of the literature in this field,to find out the general pattern of TRPM8 and GLR-3/GluK2 in regulating the body's cold response,as well as the specific mechanism of action in hypertension,thereby providing a theoretical basis for subsequent research on the treatment of hypertension based on cold-stimulation-related targets,and further expanding the new ideas and methods for the treatment of hypertension.METHODS:We searched,reviewed and screened the relevant literature on"cold stimulation,TRPM8,GLR-3/GluK2 and hypertension"to lay the theoretical foundation for the analysis of the whole article.Comparative analysis method,through reading and analyzing the obtained literature,comparing the similarities and differences between the literature,was performed to provide reasonable theoretical support for the argument.Through further comparative analysis of the literature,the relationship between the relevant indicators was clarified,and the ideas were clarified for the analysis of the full text.RESULTS AND CONCLUSION:(1)TRPM8 can be activated by cold and mainly mediates cool temperature perception in mammals.Its activation can trigger neurogenic inflammatory response and indirectly affect the inflammatory process.Abnormal TRPM8 signal can lead to excessive activation of immune cells,which is significantly associated with the occurrence and development of hypertension.(2)The activation threshold of GLR-3/GluK2 is lower than that of TRPM8,which may preferentially respond to noxious cold stimulation rather than ordinary cool temperature.In cold environment,GLR-3/GluK2 activation enhances sympathetic nerve excitability by regulating interneuron signal transduction and causes peripheral vascular constriction.Long-term effects can lead to increased peripheral vascular resistance.To conclude,TRPM8 and GLR-3/GluK2 are involved in the interaction of the nerve-immune-vascular system by sensing different cold stimuli.Abnormal TRPM8 signaling indirectly promotes the progression of hypertension through inflammation and immune dysregulation,while GLR-3/GluK2 directly exacerbates vascular constriction and resistance by enhancing sympathetic nerve activity.The combination of the two factors may constitute the key molecular mechanism of the occurrence and development of hypertension in cold environment,and provide a potential target for the intervention of cold-related cardiovascular diseases.

BACKGROUND:Extracellular vesicles mediate intercellular signal transduction through the proteins,nucleic acids,and lipids they carry,thereby influencing the function of target cells.This vesicle-mediated communication mechanism is involved in regulating female reproductive development.OBJECTIVE:To summarize and analyze the regulatory roles of extracellular vesicle-mediated intercellular communication in female reproductive development.METHODS:A search was conducted in the PubMed database using the search terms"extracellular vesicles,exosomes,reproduction,maternal-embryo communication,maternal-fetal crosstalk,embryo implantation,endometrium,oviduct,follicle."The initial screening was carried out by reading the titles and abstracts of the literature,and then the literature with poor relevance to the research purpose,outdated content,and duplication was excluded according to the inclusion and exclusion criteria.Ultimately,69 relevant articles were included for comprehensive analysis.RESULTS AND CONCLUSION:Extracellular vesicles play a crucial role in key processes of female reproductive development,from folliculogenesis to implantation.(1)Extracellular vesicles mediate intercellular communication within the follicle,particularly the interactions between oocytes and follicular cells,which are essential for follicle development and maturation.(2)Extracellular vesicles and their contents facilitate interactions between the embryo and the fallopian tube,influencing the trajectory of embryonic development.(3)Extracellular vesicles and their contents promote implantation by mediating bidirectional communication between the embryo and the endometrium.Uterine-derived extracellular vesicles regulate processes such as embryo adhesion,invasion,and decidualization,while embryo-derived extracellular vesicles modulate endometrial receptivity,convey embryonic signals,and adjust the endometrial microenvironment.Studying the roles of extracellular vesicles in female reproductive development can provide valuable insights into the mechanisms of infertility and support the development of new therapeutic strategies.

BACKGROUND:Low temperatures have detrimental effects on the human cardiovascular system,with a higher prevalence of hypertension and related cardiovascular diseases,especially among people living in cold climates.Transient receptor potential M8(TRPM8)is often recognized as a physiological sensor of environmental cold,and glutamate receptor-3(GLR-3)/glutamate receptor ionotropic,kainate 2(GluK2)is also cold-sensitive.However,the specific molecular mechanisms of cold-associated TRPM8 and GLR-3/GluK2 in regulating hypertension remain puzzling.OBJECTIVE:Through a review of the literature in this field,to find out the general pattern of TRPM8 and GLR-3/GluK2 in regulating the body's cold response,as well as the specific mechanism of action in hypertension,thereby providing a theoretical basis for subsequent research on the treatment of hypertension based on cold-stimulation-related targets,and further expanding the new ideas and methods for the treatment of hypertension.METHODS:We searched,reviewed and screened the relevant literature on"cold stimulation,TRPM8,GLR-3/GluK2 and hypertension"to lay the theoretical foundation for the analysis of the whole article.Comparative analysis method,through reading and analyzing the obtained literature,comparing the similarities and differences between the literature,was performed to provide reasonable theoretical support for the argument.Through further comparative analysis of the literature,the relationship between the relevant indicators was clarified,and the ideas were clarified for the analysis of the full text.RESULTS AND CONCLUSION:(1)TRPM8 can be activated by cold and mainly mediates cool temperature perception in mammals.Its activation can trigger neurogenic inflammatory response and indirectly affect the inflammatory process.Abnormal TRPM8 signal can lead to excessive activation of immune cells,which is significantly associated with the occurrence and development of hypertension.(2)The activation threshold of GLR-3/GluK2 is lower than that of TRPM8,which may preferentially respond to noxious cold stimulation rather than ordinary cool temperature.In cold environment,GLR-3/GluK2 activation enhances sympathetic nerve excitability by regulating interneuron signal transduction and causes peripheral vascular constriction.Long-term effects can lead to increased peripheral vascular resistance.To conclude,TRPM8 and GLR-3/GluK2 are involved in the interaction of the nerve-immune-vascular system by sensing different cold stimuli.Abnormal TRPM8 signaling indirectly promotes the progression of hypertension through inflammation and immune dysregulation,while GLR-3/GluK2 directly exacerbates vascular constriction and resistance by enhancing sympathetic nerve activity.The combination of the two factors may constitute the key molecular mechanism of the occurrence and development of hypertension in cold environment,and provide a potential target for the intervention of cold-related cardiovascular diseases.

Objective To investigate the clinical efficacy of minimally invasive mitral valvuloplasty (MVP) in the treatment of infective endocarditis (IE) with mitral regurgitation (MR). Methods A retrospective analysis was conducted on the clinical data of patients who underwent MVP for IE with MR at the Department of Cardiovascular Surgery in Zhongshan Hospital, Fudan University from 2016 to 2020. Patients were divided into two groups based on the surgical incision: those with a right mini-thoracotomy were classified as a minimally invasive surgery (MIS) group, and those with a median sternotomy (MS) were classified as an MS group. All patients had isolated mitral valve involvement. Perioperative data were analyzed, and mid- to long-term outcomes were compared between the two groups. Results A total of 86 patients were included, with 40 in the MIS group [22 males and 18 females, with a mean age of (39.78±15.36) years ranging from 14 to 75 years] and 46 in the MS group [27 males and 19 females, with a mean age of (49.94±16.13) years ranging from 14 to 71 years]. The patients in the MIS group were relatively younger (P=0.004) with better preoperative cardiac function (P=0.004). There was no statistical difference in preoperative fever, gender, or comorbidities between the two groups (P>0.05). The MIS group had shorter postoperative ventilation times, less postoperative 24-hour drainage, less blood transfusion, and shorter total hospital stays compared to the MS group (P＜0.05). There was no statistical difference in cardiopulmonary bypass times or ICU stays between the two groups (P>0.05). The perioperative complication rates and mortality rates were not significantly different between the two groups (P>0.05). Follow-up was conducted for 11-92 months, with a mean duration of (49±19) months and an overall follow-up rate of 91.9%. During the follow-up, 3 patients in each group required reoperation for mitral valve issues, with no statistical difference in incidence (7.5% vs. 6.5%, P=0.691). There were no warfarin-related complications, recurrences, or deaths in either group during follow-up. Multivariate regression analysis identified age, preoperative cardiac function, and surgeon experience as influencing factors for the choice of surgical approach. Conclusion Minimally invasive MVP for IE with MR is relatively safe in the perioperative period and shows significant efficacy, with clear mid- to long-term outcomes. It is recommended for younger patients with better preoperative cardiac function and when performed by surgeons with extensive experience in mitral valvuloplasty.

Objective: To systematically evaluate the performance of machine learning (ML) models in predicting non suicidal self injury (NSSI) behavior among adolescents, providing an evidence based foundation for the development of clinically applicable risk assessment tools. Methods: A comprehensive search was conducted in PubMed, Embase, Web of Science, CNKI, and Wanfang databases for relevant studies from their inception to July 21, 2025. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to evaluate the methodological quality of the included studies. Stata 18 software was used to calculate the area under the receiver operating characteristic curve (AUC) of the models, and publication bias assessment, sensitivity analysis, and Egger s test were performed. Results: The total of 12 studies (42 prediction models) involving 58 070 adolescents were included. There were 15 machine learning algorithms in total, among which Random Forest, Logistic Regression, XGBoost, and Support Vector Machines were the most frequently utilized. The most common predictors were gender (female), family function, depression, emotion regulation, and age. All 12 included studies exhibited a high risk of bias. The pooled AUC was 0.80 (95% CI =0.78-0.82), although heterogeneity was substantial ( I 2=95.8%, P <0.01). Sensitivity analysis confirmed the robustness of these findings (no overlap in 95% CI ), while Egger s test indicated the presence of publication bias ( P <0.05). Conclusions Machine learning demonstrates potential in the risk prediction of adolescent NSSI, but existing models have a high risk of bias. Future research should focus on improving methodological quality and optimizing model reliability through rigorous external validation.

Objective: To investigate the current status of screening myopia and anxiety symptoms and associated factors among junior and senior high school students in Beijing, so as to provide evidence for myopia prevention and control and the improvement of mental health among adolescents. Methods: From September to November 2024, a total of 17 245 junior high schools, general senior high schools and vocational high schools from 16 districts in Beijing were enrolled by stratified cluster sampling method. Questionnaire surveys and vision screening were conducted to collect data on anxiety symptom and screening diagnosed myopia. The Chi square test was used to analyze the co-occurrence of myopia and anxiety symptoms, and binary Logistic regression analysis was adopted to explore the related factors of the co-occurrence. Results: The overall detection rate of cooccurrence screening myopia and anxiety symptoms among Beijing junior and senior high school students was 6.00%. The detection rate was higher in females ( 7.15 %) than in males (4.90%), higher in urban areas (6.65%) than in suburban areas (5.41%), and higher in general senior high school students (7.61%) than in vocational high school students (6.46%) and junior high school students (4.65%). All differences were statistically significant ( χ 2=38.49, 11.66, 54.88, all P <0.01). Binary Logistic regression analysis showed that female gender ( OR =1.43), general senior high school ( OR =1.60), vocational high school ( OR =1.59), daily sugar sweetened beverage intake ( OR =1.66), participation in academic extracurricular classes in preschool ( OR =1.30), electronic screen use for more than 2 hours per day ( OR =1.21), and insufficient sleep ( OR =2.41) were associated with an increased risk of co-occurring screening diagnosed myopia and anxiety symptoms (all P <0.05). Conclusions The co-occurrence of screening diagnosed of myopia and anxiety symptoms among junior and senior high school students in Beijing is common. Female gender, senior high school students, and unhealthy lifestyle behaviors are all risk factors for the co-occurrence of myopia and anxiety symptom. Comprehensive intervention measures can be adopted to simultaneously promote vision protection and mental health among junior and senior high school students.

ObjectiveTo explore the mechanism of Yishen Qubi Tongluo Formula （益肾祛痹通络方， YQTF） in the treatment of rheumatoid arthritis（RA）. MethodsNetwork pharmacology was employed to retrieve and screen the active components and potential targets of YQTF as well as RA-related targets using databases including TCMSP， BATMAN， ETCM and GEO. The intersection of targets related to active components and RA-related targets was identified， and a protein-protein interaction （PPI） network was constructed. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed， and a drug-active component-common target network of YQTF in the treatment of RA was established. The core components of YQTF were molecularly docked with key targets. Human rheumatoid arthritis synovial fibroblast cell line MH7A was divided into blank group， model group， methotrexate group and YQTF group. The blank group was cultured with 10% fetal bovine serum， while the other three groups were stimulated with 10 μg/L of recombinant human tumor necrosis factor-α （TNF-α） for 24 h to establish the RA cell model. On this basis， the methotrexate group was treated with methotrexate suspension at a concentration of 20 μmol/L， and the YQTF group was treated with 10% YQTF-medicated serum. After 48 h of intervention， the levels of TNF-α and interleukin-17A（IL-17A）contents in cell supernatants were detected by enzyme-linked immunosorbent assay （ELISA）， and mRNA expressions of phosphatidylinositol 3-kinase（PI3K）， protein kinase B（AKT） and mammalian target of rapamycin（mTOR） were detected by real-time quantitative polymerase chain reaction （RT-qPCR）. ResultsNetwork pharmacological analysis identified 209 active components and 583 potential target genes of YQTF， as well as 818 RA-related targets. A total of 29 common targets were obtained from the intersection of drug-related targets and RA-related targets. Quercetin，β-sitosterol， kaempferol， stigmasterol and luteolin were the core active components of YQTF for the treatment of RA， while matrix metalloproteinase-9 （MMP9）， prostaglandin-endoperoxide synthase 2 （PTGS2）， Toll-like receptor 4 （TLR4）， tumor protein p53 （TP53） and transcription factor AP-1 subunit JUN were the key targets. The GO and KEGG pathway enrichment analysis showed that the involved biological processes and pathways were mainly associated with antioxidant responses， PI3K-AKT signaling pathway and Toll-like receptor （TLR） signaling pathway. Molecular docking results showed that MMP9 and PTGS2 exhibited high binding affinities with quercetin， β-sitosterol， kaempferol， stigmasterol and luteolin； TLR4 exhibited high binding activities with β-sitosterol， stigmasterol and luteolin； and TP53 showed high binding affinity with luteolin. The results of cell experiments showed that compared with the control group， the contents of TNF-α and IL-17A as well as the mRNA expressions of AKT and mTOR in the model group significantly increased （P＜0.05 or P＜0.01）. Compared with the model group， all the above indicators significantly decreased in the YQTF group， while the contents of TNF-α and the mRNA expression of AKT significantly decreased in the methotrexate group （P＜0.05 or P＜0.01）. ConclusionThe mechanism of YQTF in the treatment of RA may be associated with reducing inflammatory cytokine secretion and inhibiting the activation of the PI3K-AKT-mTOR signaling pathway.

In recent years， repetitive transcranial magnetic stimulation （rTMS） has garnered significant attention as a therapeutic approach for sleep disorders in the elderly. However， the prevailing rTMS protocols are predominantly developed based on normative neurophysiological data derived from young adults and fail to incorporate individualized parameters tailored to the brain characteristics of the elderly. To address this gap， the consensus development group synthesized the latest evidence from 2010 to 2025 and established a standardized rTMS protocol specifically for elderly patients with sleep disorders. Adhering to the Appraisal of Guidelines for Research and Evaluation II （AGREE II） framework， systematically screened randomized controlled trials （RCTs） and systematic reviews regarding rTMS in the treatment of sleep disorders across various conditions. Meanwhile， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system was employed to rigorously grade the quality of evidence and the strength of recommendations. This consensus guideline delineates precise rTMS protocols for the management of sleep disorders in the elderly， highlights the adjustment of stimulation intensity according to scalp-cortex distance recommends either MRI‑guided neuronavigation or the Beam F3/F4 heuristic approach for accurate target localization， thereby providing precise rTMS intervention protocol for sleep disorders in the elderly， aiming to enhance clinical efficacy while ensuring treatment safety. ［Funded by National Key Research and Development Program （number， 2023YFC3603200）； General Program of Shenzhen Science and Technology Innovation Commission （number， JCYJ20240813112859008， JCYJ20240813112900002）； Youth Program of Shenzhen Kangning Hospital （number， KN2023A004）； www.guidelines-registry.cn number， PREPARE-2026CN530］

Objective To establish an in vitro enzymatic activity evaluation system for OTULIN （OTU domain DUB with linear linkage specificity）and provide an experimental basis for OTULIN inhibitor screening. Methods The linear ubiquitin substrate protein His-Ub-Ub-Flag was designed, expressed, and purified. Using OTULIN^80-352 as the target enzyme and PR619 as a positive control, the enzyme-to-substrate ratio and reaction time were optimized to establish an in vitro OTULIN activity evaluation system. Results The linear ubiquitin substrate protein His-Ub-Ub-Flag was successfully obtained. OTULIN activity was significantly inhibited by PR619, which confirmed the feasibility of the assay. The optimal enzyme-to-substrate ratio of OTULIN^80-352 to His-Ub-Ub-Flag was 1∶16, and the optimal reaction condition was incubation at 37℃ for 20 min. Conclusion An in vitro enzymatic activity evaluation system for OTULIN was successfully established, which could be used to evaluate the inhibitory effects of candidate compounds on OTULIN activity and provide technical support for subsequent screening of OTULIN small-molecule inhibitors.