Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Tripartite motif-containing protein 37(TRIM37)is a multifunctional protein.It is an E3 ubiquitin ligase that primarily localizes to the peroxisome membrane and centrosome.It plays a crucial role in centrosome assembly,which is essential for spindle formation and the accuracy of chromosome segregation,ultimately affecting cell division.By ubiquitinating a variety of substrate proteins,TRIM37 regulates ubiquitination pathways and influences several key signaling pathways.Notably,it is involved in the activation of the mechanistic target of rapamycin complex 1(mTORC1)signaling pathway and reg-ulates autophagy by phosphorylating transcription factor EB(TFEB)via mTORC1.Furthermore,TRIM37 is integral to inflammatory and immune responses,as well as cell proliferation and apoptosis,through the activation of the nuclear factor kappa B(NF-κB)signaling pathway.It is also implicated in the regulation of other critical signaling pathways,such as Wnt/β-catenin and phosphatidylinositol-3-ki-nase/Protein Kinase B(PI3K/AKT),particularly in the context of cancer.TRIM37 enhances the prolif-eration,metastasis,and invasion of tumor cells,including those in gallbladder cancer,renal cell carci-noma,and glioma,and is linked to resistance against certain anticancer drugs.In sum,the diverse and complex functions of TRIM37 underscore its significance in various physiological and pathological proces-ses.This article reviews the biological role of TRIM37 and its association with diseases,focusing on its structure,function,involvement in cell autophagy,and the main signaling pathways.We aim to enhance the understanding of TRIM37-related disease pathogenesis and to identify potential new targets for future therapeutic research.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective This study investigated feasible cases and their significance in promoting the"generalized"development of inspection through digital-intelligent equipment.Methods A qualitative research approach was used,involving interviews conducted between February 2025 and March 2025 with experts in traditional Chinese medicine diagnostics,clinical research methodology,medical engineering integration,and related disciplines,using both online and offline methods.In accordance with the Consolidated Criteria for Reporting Qualitative Research,feasible cases involving the specific application of digital equipment in various parts of observation were collected through item enrichment.The significance of extending observation capabilities via these cases was analyzed,along with the overall implications of integrating digital technologies with traditional inspection method.Results Interviews were completed with 11 experts from domestic universities and research institutes in the fields of traditional Chinese medicine diagnosis,medical engineering integration,and related disciplines.A total of 78 feasible cases of digital-intelligent inspection were identified,along with 69 insights regarding the significance of enhancing the inspection capabilities.These insights were synthesized into two dimensions and 23 holistic meanings.The first dimension is to expand the scope of inspection,including obtaining internal environmental characteristics,observing external environmental characteristics,expanding thermodynamic characteristic data,and crossing time and space.The second dimension is to improve the quality of observation and diagnosis information collection and analysis,including 19 specific meanings,such as standardized collection environment,objective quantification,and refined observation.Conclusion Digital-intelligent equipment plays a significant role in expanding the scope of inspection content and achieving high-quality acquisition and analysis of extensive inspection information.These advancements extend and enrich the capabilities of traditional inspection method in traditional Chinese medicine.

Tripartite motif-containing protein 37(TRIM37)is a multifunctional protein.It is an E3 ubiquitin ligase that primarily localizes to the peroxisome membrane and centrosome.It plays a crucial role in centrosome assembly,which is essential for spindle formation and the accuracy of chromosome segregation,ultimately affecting cell division.By ubiquitinating a variety of substrate proteins,TRIM37 regulates ubiquitination pathways and influences several key signaling pathways.Notably,it is involved in the activation of the mechanistic target of rapamycin complex 1(mTORC1)signaling pathway and reg-ulates autophagy by phosphorylating transcription factor EB(TFEB)via mTORC1.Furthermore,TRIM37 is integral to inflammatory and immune responses,as well as cell proliferation and apoptosis,through the activation of the nuclear factor kappa B(NF-κB)signaling pathway.It is also implicated in the regulation of other critical signaling pathways,such as Wnt/β-catenin and phosphatidylinositol-3-ki-nase/Protein Kinase B(PI3K/AKT),particularly in the context of cancer.TRIM37 enhances the prolif-eration,metastasis,and invasion of tumor cells,including those in gallbladder cancer,renal cell carci-noma,and glioma,and is linked to resistance against certain anticancer drugs.In sum,the diverse and complex functions of TRIM37 underscore its significance in various physiological and pathological proces-ses.This article reviews the biological role of TRIM37 and its association with diseases,focusing on its structure,function,involvement in cell autophagy,and the main signaling pathways.We aim to enhance the understanding of TRIM37-related disease pathogenesis and to identify potential new targets for future therapeutic research.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective This study investigated feasible cases and their significance in promoting the"generalized"development of inspection through digital-intelligent equipment.Methods A qualitative research approach was used,involving interviews conducted between February 2025 and March 2025 with experts in traditional Chinese medicine diagnostics,clinical research methodology,medical engineering integration,and related disciplines,using both online and offline methods.In accordance with the Consolidated Criteria for Reporting Qualitative Research,feasible cases involving the specific application of digital equipment in various parts of observation were collected through item enrichment.The significance of extending observation capabilities via these cases was analyzed,along with the overall implications of integrating digital technologies with traditional inspection method.Results Interviews were completed with 11 experts from domestic universities and research institutes in the fields of traditional Chinese medicine diagnosis,medical engineering integration,and related disciplines.A total of 78 feasible cases of digital-intelligent inspection were identified,along with 69 insights regarding the significance of enhancing the inspection capabilities.These insights were synthesized into two dimensions and 23 holistic meanings.The first dimension is to expand the scope of inspection,including obtaining internal environmental characteristics,observing external environmental characteristics,expanding thermodynamic characteristic data,and crossing time and space.The second dimension is to improve the quality of observation and diagnosis information collection and analysis,including 19 specific meanings,such as standardized collection environment,objective quantification,and refined observation.Conclusion Digital-intelligent equipment plays a significant role in expanding the scope of inspection content and achieving high-quality acquisition and analysis of extensive inspection information.These advancements extend and enrich the capabilities of traditional inspection method in traditional Chinese medicine.

OBJECTIVE: To explore the immunological mechanisms underlying spermatogenetic malfunction in patients with non-obstructive azoospermia (NOA) based on bioinformatics and machine learning, and to screen out the key genes associated with spermatogenesis failure. METHODS: NOA-related datasets were obtained from the GEO database, and the differentially expressed genes identified by differential analysis and weighted gene co-expression network analysis (WGCNA). A model of spermatogenesis scoring was established for analysis of the immunological microenvironment and cell interaction networks related to spermatogenesis failure. The key genes were screened out by machine learning, followed by analysis of their correlation with T cells and macrophages. An NOA mouse model was constructed for validation of transcriptome sequencing. RESULTS: Seventy-five differentially expressed genes were identified for the establishment of the spermatogenesis scoring model. The low spermatogenesis score group showed a higher infiltration of the immune cells, with an increased proportion of T cells and macrophages and a correlation of cell interaction signals with immunity. SOX30, KCTD19, ASRGL1 and DRC7 were identified by machine learning as the key genes related to spermatogenesis, with down-regulated expressions in the NOA group, and their expression levels negatively correlated with the infiltration of T cells and macrophages. The accuracy of the spermatogenesis scoring and machine learning models, as well as the trend of the expression levels of the key genes, was successfully validated with the transcriptome sequencing data on the NOA mouse testis. CONCLUSION The development of NOA is closely associated with enhanced immunological microenvironment in the testis. T cells and macrophages may play important roles in spermatogenesis failure. SOX30, KCTD19, ASRGL1 and DRC7 are potential biomarkers for the diagnosis and treatment of NOA.
Male ; Azoospermia/genetics* ; Machine Learning ; Animals ; Computational Biology ; Mice ; Humans ; Spermatogenesis/genetics* ; Gene Expression Profiling ; Macrophages/immunology* ; Gene Regulatory Networks ; T-Lymphocytes/immunology* ; Transcriptome

Objective To investigate the efficacy and safety of Chinese herbal compound modified Huanglian Wendan Decoction in the treatment of hypertension complicated with sleep disorders of phlegm-heat harassing the interior type.Methods A total of 70 patients with hypertension complicated with sleep disorders of phlegm-heat harassing the interior type were randomly divided into a control group and an observation group,35 cases in each group.The patients in the control group were treated with conventional western medicine,and the patients in the observation group were treated with modified Huanglian Wendan Decoction on the basis of treatment for the control group.The course of treatment covered four weeks.The Clinical Global Impression(CGI)score,traditional Chinese medicine(TCM)syndrome score,Pittsburgh Sleep Quality Index(PSQI)score,blood pressure,and serum levels of homocysteine(Hey),interleukin 6(IL-6),interleukin 10(IL-10)and interleukin 8(IL-8)levels in the two groups were observed before and after treatment.Moreover,the safety of medication was evaluated in the two groups.Results(1)After four weeks of treatment,the CGI score of the observation group was(1.63±0.60)points,which was significantly lower than that of the control group[(2.74±0.82)points],and the difference was statistically significant(P＜0.01).(2)After treatment,the TCM syndrome score,systolic blood pressure,diastolic blood pressure and PSQI score of the two groups were significantly decreased compared with those before treatment(P＜0.01),and the decrease of TCM syndrome score,systolic blood pressure,diastolic blood pressure and PSQI score in the observation group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)After treatment,the levels of serum Hcy,IL-6 and IL-8 in the two groups were significantly decreased compared with those before treatment(P＜0.01),and the serum IL-10 level was significantly increased compared with that before treatment(P＜0.01).The decrease of serum Hcy,IL-6 and IL-8 levels and the increase of serum IL-10 level in the observation group were significantly superior to those in the control group(P＜0.01).(4)During the treatment,no treatment-related adverse reactions or complications occurred in the two groups.Conclusion Modified Huanglian Wendan Decoction has certain efficacy on patients with hypertension complicated with sleep disorders of phlegm-heat harassing the interior type.The decoction can not only reduce the blood pressure and serum Hcy level of the patients,but also regulate the level of inflammatory factors with high safety.

Objective To investigate the effect of intraoperative renal artery resistance index(RI)in predicting postoperative acute kidney injury(AKI)in patients undergoing cardiac surgery with cardiopul-monary bypass(CPB).Methods Forty-four patients undergoing elective cardiac surgery with CPB,21 males and 23 females,aged ≥18 years,BMI 18.5-30.0 kg/m2,ASA physical status Ⅰ-Ⅲ,were select-ed.Left renal artery peak systolic velocity(PSV)and end-diastolic velocity(EDV)were measured by transesophageal echocardiography(TEE)20 minutes after general anesthesia induction(T1)and 30 minutes after CPB cessation(T2).RI was calculated as(PSV-EDV)/PSV.Patients were divided into two groups:the AKI group and the non-AKI group,according to whether occurred AKI by the diagnostic criteria of the kidney disease:improving global outcomes organization(KDIGO).Logistic multivariate regression analysis was performed to identify the risk factors for AKI occurrence.Results Sixteen patients(36％)oc-curred AKI.Compared with the non-AKI group,the CPB duration and aortic cross-clamp duration were sig-nificantly prolonged(P＜0.05),the renal artery RI at T,and T2 were significantly increased in the AKI group(P＜0.05).Multivariate logstic analysis showed that RI at T2 was an independent risk factor for AKI occurrence after cardiac surgery,the AUC was 0.893(95％CI 0.794-0.991,P＜0.010),the sensitivity and specificity were 84.5％and 78.6％,respectively,and the cut-off value was 0.720.Conclusion Intra-operative renal artery RI in patients undergoing cardiac surgery is an independent risk factor for AKI after cardiac surgery,and renal artery RI＞0.720 at 30 minutes after CPB cessation can serve as a predictive in-dicator for AKI after cardiac surgery.