Spermatogenesis is a highly ordered and spatiotemporally regulated developmental process in the male reproductive system, during which spermatogonial stem cells (SSCs), supported by the seminiferous tubule microenvironment, sequentially undergo mitosis, meiosis, and spermiogenesis to ultimately generate structurally intact spermatozoa. This complex process is accompanied by extensive transcriptional reprogramming, chromatin remodeling, and finely tuned post-transcriptional regulation. Precise control of RNA fate is therefore essential for maintaining the continuity and fidelity of spermatogenesis, and its disruption represents a major molecular basis of male infertility. N⁶-methyladenosine (m⁶A), the most abundant internal RNA modification in eukaryotes, has emerged as a critical regulator of post-transcriptional gene expression. m⁶A methyltransferases (“writers”) catalyze the addition of a methyl group to the N⁶ position of adenosine, m⁶A demethylases (“erasers”) remove the modification, and m⁶A-binding proteins (“readers”) recognize m⁶A-modified transcripts. Through the coordinated actions of these factors, m⁶A regulates transcript fate at multiple levels, including RNA splicing, nuclear export, stability, translation, and decay. Emerging evidence indicates that m⁶A-mediated regulation is essential across multiple stages of spermatogenesis, including SSC self-renewal and differentiation, meiotic progression, maintenance of chromosomal stability, and sperm morphogenesis. Beyond its intrinsic functions in germ cells, m⁶A also contributes to the regulation of the testicular microenvironment. In sertoli cells, m⁶A is involved in maintaining blood-testis barrier integrity, RNA processing, and paracrine signaling, thereby providing structural and metabolic support for germ cell development. In Leydig cells, m⁶A regulates steroidogenesis, particularly testosterone synthesis, and participates in cellular stress responses and metabolic homeostasis. Through these mechanisms, m⁶A indirectly influences spermatogenesis by modulating the functional state of testicular somatic cells, highlighting an integrated regulatory mode that combines cell-intrinsic and microenvironment-mediated effects. Notably, distinct classes of m⁶A regulators exhibit pronounced stage-specific functions and coordinated division of labor, collectively forming a multilayered and dynamic regulatory network. Writers often display dosage- and temporal window-dependent effects; erasers contribute to stage-specific demethylation and functional compensation; while readers function through a “switch-buffer” dual-layer architecture, and RNA-binding proteins (RBPs) participate in substrate selection and post-transcriptional regulation. Importantly, emerging evidence suggests that some m⁶A-related proteins can function through noncanonical mechanisms independent of m⁶A recognition, such as intrinsic RNA-binding activity, helicase function, or ribonucleoprotein complex assembly, thereby expanding the functional landscape of the m⁶A regulatory system. Dysregulation of m⁶A machinery can lead to multiple spermatogenic defects, including impaired SSC self-renewal, meiotic arrest, abnormal chromatin remodeling, and defective sperm formation, ultimately resulting in male infertility. Despite substantial advances, several critical questions remain unresolved, including the distinction between m⁶A-dependent and -independent mechanisms, the spatiotemporal dynamics of m⁶A modifications at single-cell resolution, and the coordination and antagonism among different regulatory factors. In this review, we systematically summarize the dual regulation of spermatogenesis by germ cell-intrinsic mechanisms and the testicular microenvironment, and delineate the molecular mechanisms and stage-specific functions of the dynamic m⁶A regulatory network. We further discuss the current limitations in the field and propose feasible experimental strategies for future investigation. Collectively, this work aims to provide a comprehensive framework for understanding the epitranscriptomic regulation of spermatogenesis and to offer theoretical insights into the pathogenesis and clinical management of male infertility.

Spermatogenesis is a highly ordered and spatiotemporally regulated developmental process in the male reproductive system, during which spermatogonial stem cells (SSCs), supported by the seminiferous tubule microenvironment, sequentially undergo mitosis, meiosis, and spermiogenesis to ultimately generate structurally intact spermatozoa. This complex process is accompanied by extensive transcriptional reprogramming, chromatin remodeling, and finely tuned post-transcriptional regulation. Precise control of RNA fate is therefore essential for maintaining the continuity and fidelity of spermatogenesis, and its disruption represents a major molecular basis of male infertility. N⁶-methyladenosine (m⁶A), the most abundant internal RNA modification in eukaryotes, has emerged as a critical regulator of post-transcriptional gene expression. m⁶A methyltransferases (“writers”) catalyze the addition of a methyl group to the N⁶ position of adenosine, m⁶A demethylases (“erasers”) remove the modification, and m⁶A-binding proteins (“readers”) recognize m⁶A-modified transcripts. Through the coordinated actions of these factors, m⁶A regulates transcript fate at multiple levels, including RNA splicing, nuclear export, stability, translation, and decay. Emerging evidence indicates that m⁶A-mediated regulation is essential across multiple stages of spermatogenesis, including SSC self-renewal and differentiation, meiotic progression, maintenance of chromosomal stability, and sperm morphogenesis. Beyond its intrinsic functions in germ cells, m⁶A also contributes to the regulation of the testicular microenvironment. In sertoli cells, m⁶A is involved in maintaining blood-testis barrier integrity, RNA processing, and paracrine signaling, thereby providing structural and metabolic support for germ cell development. In Leydig cells, m⁶A regulates steroidogenesis, particularly testosterone synthesis, and participates in cellular stress responses and metabolic homeostasis. Through these mechanisms, m⁶A indirectly influences spermatogenesis by modulating the functional state of testicular somatic cells, highlighting an integrated regulatory mode that combines cell-intrinsic and microenvironment-mediated effects. Notably, distinct classes of m⁶A regulators exhibit pronounced stage-specific functions and coordinated division of labor, collectively forming a multilayered and dynamic regulatory network. Writers often display dosage- and temporal window-dependent effects; erasers contribute to stage-specific demethylation and functional compensation; while readers function through a “switch-buffer” dual-layer architecture, and RNA-binding proteins (RBPs) participate in substrate selection and post-transcriptional regulation. Importantly, emerging evidence suggests that some m⁶A-related proteins can function through noncanonical mechanisms independent of m⁶A recognition, such as intrinsic RNA-binding activity, helicase function, or ribonucleoprotein complex assembly, thereby expanding the functional landscape of the m⁶A regulatory system. Dysregulation of m⁶A machinery can lead to multiple spermatogenic defects, including impaired SSC self-renewal, meiotic arrest, abnormal chromatin remodeling, and defective sperm formation, ultimately resulting in male infertility. Despite substantial advances, several critical questions remain unresolved, including the distinction between m⁶A-dependent and -independent mechanisms, the spatiotemporal dynamics of m⁶A modifications at single-cell resolution, and the coordination and antagonism among different regulatory factors. In this review, we systematically summarize the dual regulation of spermatogenesis by germ cell-intrinsic mechanisms and the testicular microenvironment, and delineate the molecular mechanisms and stage-specific functions of the dynamic m⁶A regulatory network. We further discuss the current limitations in the field and propose feasible experimental strategies for future investigation. Collectively, this work aims to provide a comprehensive framework for understanding the epitranscriptomic regulation of spermatogenesis and to offer theoretical insights into the pathogenesis and clinical management of male infertility.

Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Thoracic anesthesia with spontaneous respiration represents a form of precision anesthesia meticulously customized to individual patients.Considering the more stringent requirements this anesthesia approach imposes on the regulation of respiratory function,the writing group of the"Consensus of Experts on the Management of Thoracic Anesthesia with Spontaneous Respiration"has formulated elaborate guidelines regarding indications and contraindications,preoperative evaluation,anesthesia implementation,common complications,and treatment strategies.This was accomplished by referencing relevant domestic and international literature and integrating it with actual clinical requirements.The objective is to standardize the rational application of this anesthesia method.

OBJECTIVE To explore the ameliorative effect of Tiaozhi Xiaoban Mixture on atherosclerosis and the potential role of long non-coding RNA(Linc RNA)in anti-atherosclerosis.METHODS A model of atherosclerosis was established in SD rats subjec-ted to a high-fat diet.At 4 weeks post-modeling,thoracic aortic tissues from atherosclerotic rats were collected for hematoxylin-eosin(HE)staining to systematically evaluate the anti-atherosclerotic effects of Tiaozhi Xiaoban Mixture at different doses.Biochemical kits were utilized to assess relevant indices related to blood lipid levels as well as liver and kidney function,thereby evaluating the impact of Tiaozhi Xiaoban Mixture on these parameters.Enzyme-linked immunosorbent assay(ELISA)was employed to measure serum inflam-mation markers influenced by Tiaozhi Xiaoban Mixture.Additionally,TUNEL staining and Western blot analysis were conducted to ex-amine the apoptotic effects of Tiaozhi Xiaoban Mixture on thoracic aorta tissue.Finally,qPCR was used to detect the expression levels of Line-HC,MALAT1,etc.,in order to evaluate how Tiaozhi Xiaoban Mixture affecting these specific RNA molecules.RESULTS Following treatment with Tiaozhi Xiaoban Mixture,the blood lipid profiles indicated that total cholesterol(TC),triglycerides(TG),and low-density lipoprotein cholesterol(LDL-C)were significantly down-regulated(P＜0.05,P＜0.01),while high-density lipopro-tein cholesterol(HDL-C)levels were up-regulated in the atherosclerotic rats.Moreover,serum levels of liver and kidney function markers such as aspartate aminotransferase(AST),alanine aminotransferase(ALT),blood urea nitrogen(BUN),and creatinine(Cr)exhibited down-regulation(P＜0.05,P＜0.01).Additionally,pro-inflammatory factors including interleukin-6(IL-6),interleukin-1 beta(IL-1β),tumor necrosis factor-alpha(TNF-α),high-sensitivity C-reactive protein(hs-CRP),and matrix metallopeptidase 9(MMP-9)were also reduced(P＜0.01),whereas the anti-inflammatory factor interleukin-10(IL-10)was found to be elevated(P＜0.01).Furthermore,after oral administration of Tiaozhi Xiaoban Mixture,expression levels of apoptosis-related factors NLRP3,ASC,Cleaved Caspase-1,Cleaved IL-1 β,Puma,Bax,Noxa,and MDM2 in thoracic aorta tissues from the atherosclerotic rats showed sig-nificant down-regulation(P＜0.05,P＜0.01).Notably,following treatment with Tiaozhi Xiaoban Mixture,mRNA levels of Linc-HC decreased while mRNA expression of MALAT1 increased(P＜0.05,P＜0.01).CONCLUSION Tiaozhi Xiaoban Mixture may inhibit the expression of Linc-HC and up-regulate the expression of MALAT1 to reduce the formation of atherosclerotic plaque,improve ab-normal blood lipids and liver and kidney function,alleviate inflammation and inhibit apoptosis.

Objective:To investigate the current situation of adverse events in hemodialysis nursing in class-A tertiary hospitals in China and analyze their nursing human resources related influencing factors, aiming at provide references for hemodialysis centers to adjust nursing human resources scientifically to reduce the occurrence of nursing adverse events.Methods:A convenient sampling method was used. From August to October 2021, a self-designed questionnaire was used to investigate nursing adverse events in hemodialysis centers of 860 class-A tertiary hospitals during 2020 in China. Multivariate Logistic regression was used to analyze the influencing factors of blood loss, hemodialysis catheter-related blood stream infection (CRBSI) and venous needle dislodgement (VND) in hemodialysis centers.Results:A total of 826 valid questionnaires were received, with an effective response rate of 96.05%(826/860). There were 826 hemodialysis centers covering 31 provinces, municipalities and autonomous regions in China. The establishment period of each center was 24(18, 30) years. There were 45(30, 62) dialysis machines, 180(110, 260) patients and 19(13, 27) registered nurses. Blood loss, hemodialysis CRBSI and VND occurred in 70.94% (586/826), 68.04%(562/826) and 46.97% (388/826) of hemodialysis centers, respectively. Multivariate Logistic regression results showed that the daily treatment shift ( OR=0.730, 95% CI 0.536-0.994), the proportion of nurses with bachelor's degree or above ( OR=1.635, 95% CI 1.142-2.342), and whether nurses worked part-time on peritoneal dialysis treatment ( OR=0.225, 95% CI 0.052-0.965) were the influencing factors for blood loss in hemodialysis centers (all P<0.05). The daily treatment shift ( OR=0.566, 95% CI 0.413-0.777), the number of patients which each nurse was responsible for per shift simultaneously ( OR=0.549, 95% CI 0.400-0.753), proportion of blood purification specialized nurses ( OR=1.661, 95% CI 1.216-2.269), whether nurses worked part-time on CRRT ( OR=0.700, 95% CI 0.511-0.957), the education level of the nursing manager was junior college and below ( OR=3.789, 95% CI 1.576-9.113) and bachelor′s degree ( OR=2.585, 95% CI 1.328-5.033) were the influencing factors for the hemodialysis catheter-associated bloodstream infection in hemodialysis centers (all P<0.05). The number of patients which each nurse ( OR=0.580, 95% CI 0.433-0.777) was responsible for per shift simultaneously was the influencing factor in the occurrence of VND in hemodialysis centers ( P<0.05). Conclusions:The nursing adverse events of blood loss, hemodialysis catheter-associated bloodstream infection and VND were relatively common in hemodialysis centers. The hospital managers should take corresponding measures aiming at the above influencing factors to prevent the occurrence of nursing adverse events and improve the quality and safety of nursing.

Objective:To study the relationship between microRNA (miRNA, miR)-675-3p, miR-675-5p, miR-29b-3p, miR-let-7b-3p and fluoride induced articular cartilage injury in rats.Methods:Using the factorial design, thirty 3-week-old specific pathogen free grade male Wistar rats (weighted 125 - 150 g) were selected and randomly divided into a control group, a 25 mg/L fluoride group, and a 50 mg/L fluoride group using a random number table method, with 10 rats in each group. The control group drank distilled water, while the fluoride exposure groups drank distilled water with fluoride ion concentrations of 25 and 50 mg/L, respectively. Five rats were euthanized in each group at 3 and 6 months of feeding, respectively. Visual observation was used to observe the occurrence of dental fluorosis in rats, and fluoride ion selective electrode method was used to detect the fluoride level in blood, urine, and cartilage. Hematoxylin-eosin staining and safranin O-fast green staining were used to observe the pathological changes of articular cartilage, and Mankin score was used to evaluate the grading of cartilage injury. Real-time fluorescence quantitative PCR was used to detect the expression levels of miR-675-3p, miR-675-5p, miR-29b-3p, and miR-let-7b-3p in cartilage.Results:After 3 and 6 months of fluoride exposure, no dental fluorosis was observed in the control group, while rats in the 25 and 50 mg/L fluoride groups showed varying degrees of dental fluorosis. There were statistically significant differences in the levels of blood fluoride (mg/L: 0.11 ± 0.04, 0.57 ± 0.32, 0.29 ± 0.06, 0.07 ± 0.01, 0.31 ± 0.05, 0.38 ± 0.06), urine fluoride (mg/L: 1.81 ± 0.58, 13.18 ± 2.29, 66.11 ± 20.74, 2.35 ± 1.08, 14.79 ± 3.87, 28.32 ± 4.79), and cartilage fluoride (mg/kg: 341.83 ± 44.07, 612.99 ± 174.72, 991.26 ± 227.32, 338.29 ± 72.53, 957.09 ± 195.86, 1 535.53 ± 89.01) among in rats the control group, 25 mg/L fluoride group, and 50 mg/L fluoride group ( F = 7.76, 42.78, 40.54, 23.10, 18.96, 80.81, P < 0.05). In the 50 mg/L fluoride group, there were statistically significant differences in the levels of urine fluoride and cartilage fluoride of rats exposed for different times ( t = 4.45, - 3.80, P < 0.05). The Mankin score grading for cartilage injury showed that at 3 months of fluoride exposure, there were 4, 0, and 0 rats with normal cartilage in the control group, 25 mg/L fluoride group, and 50 mg/L fluoride group, 1, 4, and 1 rats with mild injury, and 0, 1, and 4 rats with moderate injury, respectively. At 6 months of fluoride exposure, there were 4, 0, and 0 rats with normal cartilage in the control group, 25 mg/L fluoride group, and 50 mg/L fluoride group, 1, 3, and 0 rats with mild injury, 0, 1, and 3 rats with moderate injury, and 0, 1, and 2 rats with severe injury, respectively. Real-time fluorescence quantitative PCR results showed that fluoride exposure dose had individual effects on the expression of miR-675-3p, miR-675-5p, miR-29b-3p, and miR-let-7b-3p in cartilage ( F = 8.68, 7.97, 9.34, 10.14, P < 0.05). There was no individual effect of fluoride exposure time on the expression of miR-675-3p, miR-675-5p, miR-29b-3p, and miR-let-7b-3p in cartilage ( F = 0.00, 0.15, 0.63, 0.53, P > 0.05). However, there was no interaction effect between fluoride exposure time and dose on the above-mentioned miRNA ( F = 0.68, 0.05, 0.22, 0.24, P > 0.05). The correlation analysis results showed that miR-675-3p and miR-675-5p in cartilage were negatively correlated with blood fluoride, urine fluoride, and cartilage fluoride ( r = - 0.37, - 0.42, - 0.56, - 0.53, - 0.57, - 0.53, P < 0.05), while miR-29b-3p and miR-let-7b-3p were positively correlated with urine fluoride and cartilage fluoride ( r = 0.58, 0.40, 0.48, 0.47, P < 0.05). The results of ordered logistic regression analysis showed that miR-675-3p, miR-675-5p, miR-29b-3p, and miR-let-7b-3p were influencing factors of dental fluorosis grading ( OR = 0.13, 0.04, 1.55, 2.58, P < 0.05) and Mankin score grading ( OR = 0.04, 0.06, 1.41, 1.58, P < 0.05). Conclusion:MiR-675-3p, miR-675-5p, miR-29b-3p, and miR-let-7b-3p may be involved in the process of fluoride induced articular cartilage injury.

Objective:To investigate the effect of mindfulness-based cognitive therapy on the sense of personal control and illness perception of young and middle-aged patients after percutaneous coronary intervention (PCI), so as to provide theoretical and practical guidance for the psychological care of patients after PCI.Methods:A randomized controlled trial was conducted. From January 2022 to December 2023, young and middle-aged patients after PCI admitted to the Department of Cardiology, Qinhuai Medical District, Eastern Theater Command General Hospital of the Chinese People′s Liberation Army were selected as the research subjects by convenient sampling method, patients were divided into the experimental group and the control group by the random number table method. The control group was given routine nursing, and the experimental group was given mindfulness-based cognitive therapy on the basis of routine nursing. The Personal Mastery Scale (PMS), Cardiac Self-Efficacy Questionnaire (CSEQ), and Brief Illness Perception Questionnaire (BIPQ) were used to evaluate personal sense of control, self-efficacy, and illness perception before and after the intervention respectively.Results:A total of 80 young and middle-aged patients after PCI were included. There were 40 cases in the control group, including 25 males and 15 females, aged (49.43 ± 5.55) years old. There were 40 cases in the experimental group, including 19 males and 21 females, aged (49.03 ± 4.19) years old. Before the intervention, there was no statistically significant difference in the PMS, CSEQ and BIPQ scores between the two groups of patients (all P>0.05). After the intervention, the PMS, CSEQ scores of the patients in the experimental group were (23.03 ± 2.54), (45.85 ± 8.16) points respectively, which were higher than (21.95 ± 2.28), (39.05 ± 8.78) points in the control group, the BIPQ score of the patients in the experimental group was(39.63 ± 8.12) points, which was lower the (45.45 ± 8.64) points in the control group, the differences were statistically significant ( t=-2.00, -3.59, 3.11, all P<0.05). Conclusions:Mindfulness-based cognitive therapy can effectively improve the sense of personal control and self-efficacy of young and middle-aged patients after PCI, reduce the sense of threat to the disease.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.