OBJECTIVE To investigate the effects and mechanisms of Buyang huanwu decoction （BYHWD） and its active fractions in ameliorating non-alcoholic fatty liver disease. METHODS BYHWD and its effective fractions obtained through ethanol precipitation， as well as 30% ethanol， 50% ethanol， and 75% ethanol fractions （namely， the CC effective fraction， 30YC effective fraction， 50YC effective fraction， and 75YC effective fraction）， were prepared. These preparations were administered to rats via intragastric administration to prepare corresponding drug-containing serum （blank serum and simvastatin-containing serum were prepared using the same protocol）. Human L02 hepatocytes were divided into control group， model group， simvastatin-containing serum group， BYHWD-containing serum group， CC-containing serum group， 30YC-containing serum group， 50YC-containing serum group， and 75YC-containing serum group. Except for the control group， other groups were given 0.2 mol/L oleic acid for 24 h to induce a lipid accumulation model， and then intervened with 20% drug-containing serum/blank serum for 24 h. The lipid deposition in cells was observed， and the proportion of lipid droplet area was calculated； the levels of triglycerides （TG） and indicators of oxidative stress [malondialdehyde （MDA）， superoxide dismutase （SOD）] as well as liver function [alanine amino- transferase （ALT）， aspartate amino-transferase （AST）] in cells were detected； protein and mRNA expressions of AMP-activated protein kinase （AMPK）/sterol regulatory element-binding protein-1 （SREBP-1）/glycerol-3-phosphate acyltransferase （GPAT） signaling pathway were also measured. RESULTS Compared with the control group， cells in the model group exhibited severe cellular steatosis， with a significantly increased proportion of lipid droplet area， as well as the elevated levels of TG， ALT， AST， and MDA in cells， along with significantly up-regulated mRNA and protein expression levels of SREBP-1 and GPAT （P＜0.05）. The level of SOD， mRNA expression of AMPK， as well as the protein phosphorylation level of AMPK were decreased significantly （P＜0.05）. Compared with the model group， cellular steatosis was alleviated in all drug-containing serum groups， and the levels of most of the aforementioned quantitative indicators were significantly reversed （P＜0.05）. CONCLUSIONS BYHWD and its active fractions can exert a therapeutic effect on improving non-alcoholic fatty liver disease by regulating the AMPK/SREBP-1/GPAT signaling pathway， inhibiting oxidative stress responses， and reducing lipid deposition.

Objective To understand the status of body image disturbance and its influencing factors in patients with ankylosing spondylitis (AS), so as to provide a scientific basis for the clinical management of AS. Methods A total of 353 AS patients admitted from January 2022 to December 2024 were selected as research subjects. Chinese version of Body Image Disturbance Questionnaire (BIDQ) was used to investigate the body image disturbance in AS patients. Single factor analysis was performed by t test and analysis of variance, and multiple factors were analyzed by multivariate linear regression. Results The total score of BIDQ in 342 AS patients was (25.01±4.22). Multivariate linear regression analysis results showed that self-paid medical expense, nighttime VAS score and negative emotion PANAS score could positively predict body image disturbance in AS patients (standardized regression coefficient=0.413, 0.413, 0.460, P<0.05), and PSSS score, positive emotion PANAS score and exercise management CDSSM score could negatively predict body image disturbance (standardized regression coefficient=-0.245, -0.134, -0.247, P<0.05). Conclusion The body image disturbance in AS patients is worthy of clinical attention. Nighttime pain, negative emotion and self-paid medical treatment can increase the risk of body image disturbance. Positive emotion, social support and high self-management level of exercise behavior can reduce the formation of body image disturbance, which can provide new ideas for clinical management of AS patients.

Employing bibliometric methods and adhering to principles of textual research， this study systematically investigated prescription source， formula name， composition evolution， dose evolution， origin， processing， ancient and modern applications of Xiaofengsan. Xiaofengsan， also known as Renshen Xiaofengsan and Chantui Xiaofengsan， was first recorded in the Taiping Huimin Hejijufang（hereafter referred to as Jufang） of the Southern Song dynasty. The formula composition included Schizonepetae Spica， Glycyrrhizae Radix et Rhizoma， Chuanxiong Rhizoma， Notoptery Rhizoma et Radix， Bombyx Batryticatus， Saposhnikoviae Radix， Poria， Cicadae Periostracum， Pogostemonis Herba， Ginseng Radix et Rhizoma， Magnoliae Officinalis Cortex and Citri Reticulatae Pericarpium， a total of 12 medicinal materials. In terms of the evolution of formula composition， formulas across dynasties largely aligned with those recorded in Jufang， with only minor variations in application. The results of the formula dosage research indicated that one dose of medication in Jufang corresponded to the following modern dosages：Schizonepetae Spica of 82.6 g， Glycyrrhizae Radix et Rhizoma of 82.6 g， Chuanxiong Rhizoma of 82.6 g， Notoptery Rhizoma et Radix of 82.6 g， Bombyx Batryticatus of 82.6 g， Saposhnikoviae Radix of 82.6 g， Poria of 82.6 g， Cicadae Periostracum of 82.6 g， Pogostemonis Herba of 82.6 g， Ginseng Radix et Rhizoma of 82.6 g， Magnoliae Officinalis Cortex of 20.65 g and Citri Reticulatae Pericarpium of 20.65 g， the origins of all the constituent drugs were consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The results of the investigation into the decoction method indicated that the aforementioned drugs should be finely ground into powder（pass through the No.5 sieve）， and 8.26 g was taken for each dose， which was taken with the clear liquid obtained by steeping tea leaves in boiling water for several minutes. This mixture was administered three times daily， 30 min after meals. The ancient functional indications of this formula mainly involved dispelling wind-heat， eliminating pathogenic factors and regulating the middle Jiao. It primarily treated all wind-heat syndromes manifesting as skin diseases， predominantly affecting the upper body， especially the head and face. The diseases involved in modern applications were mostly dermatological diseases， including urticaria， eczema， atopic dermatitis and others. In this paper， by combing the relevant ancient literature， the key information of Xiaofengsan was textual researched， in order to provide reference for the modern application and development of this formula.

Esophageal cancer is a prevalent malignant tumor of the digestive tract in China, and radical surgery remains the cornerstone of its comprehensive treatment. However, multifactorial challenges such as postoperative gastrointestinal tract reconstruction, traumatic stress, and tumor-related metabolic disturbances render esophageal cancer patients highly susceptible to malnutrition. Perioperative nutritional support therapy plays a crucial role in enhancing surgical safety, improving clinical outcomes, and elevating patients' quality of life by regulating metabolic homeostasis, preserving organ function, and optimizing the immune microenvironment. This article reviews the mechanisms underlying malnutrition in esophageal cancer, methods for nutritional status assessment, and precision intervention pathways based on multi-omics evaluations. The aim is to strengthen clinicians' awareness of standardized perioperative nutritional management for esophageal cancer patients and promote its clinical implementation, thereby facilitating postoperative recovery and improving long-term quality of life.

ObjectiveThis study aims to compare the modeling effects of submaxillary gland antigen and salivary gland antigen in the establishment of Sjögren syndrome (SS) mouse models, and to characterize the phenotypic and immunological features of these models in comparison with spontaneous SS-prone non-obese diabetic (NOD)/LtJ mice. MethodsAdult C57BL/6J mice (equal numbers of males and females) were immunized with submaxillary gland antigen or salivary gland antigen, respectively, combined with Freund's adjuvant to induce SS models. Mice immunized with phosphate-buffered saline (PBS) combined with Freund's adjuvant served as the control group. Immunization was induced via multiple subcutaneous injections in the back with antigen combined with Freund's complete adjuvant (FCA) on Days 1 and 7. A booster immunization was administered via multiple subcutaneous injections in the back with antigen combined with Freund's incomplete adjuvant (FIA) on Day 14. Female NOD/LtJ mice were used as the spontaneous SS model group, with ICR mice as the corresponding control strain for comparative analysis. Body weight, water intake, and salivary flow rate of mice were dynamically monitored for 4 weeks. At the end of the experiment, tissue and serum samples were collected, the weights of submaxillary glands, thymus, and spleen were measured, and organ indices (organ-to-body weight ratios) were calculated. Pathological morphological analysis of the submaxillary gland and spleen was performed with hematoxylin and eosin (HE) staining. Serum interleukin-17 (IL-17) level was detected using enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction was used to detect the mRNA expression levels of SS type A (SSA) and SS type B (SSB) in submaxillary gland tissues. ResultsFemale mice in the submaxillary gland antigen group exhibited significantly increased water intake (P<0.05) and reduced salivary flow rate (P<0.05) compared with the female control group. No statistically significant differences were observed in the submaxillary gland index, thymus index and spleen index (P>0.05). Focal lymphocytic infiltration was observed in the submaxillary glands, and the splenic marginal zone was enlarged. Serum IL-17 levels were significantly increased (P<0.05). There was no significant difference in submaxillary gland SSA/SSB expression levels (P>0.05). Compared with the female control group, female mice in the salivary gland antigen group showed no statistically significant differences in water intake, salivary flow rate, submaxillary gland index, and spleen index (P>0.05), whereas the thymus index was significantly reduced (P<0.01). Mild inflammatory cell infiltration and glandular atrophy were observed in the submaxillary glands, and the splenic white pulp and marginal zone were slightly enlarged. Serum IL-17 levels and submaxillary gland SSB mRNA expression levels were significantly increased (P<0.01), whereas no significant change was observed in submaxillary gland SSA expression levels (P>0.05). Compared with the male control group, mild submaxillary gland atrophy was observed in male mice in the submaxillary gland antigen group, whereas no obvious changes were found in other modeling-related indicators (P>0.05). Compared with the ICR control group, NOD/LtJ model mice exhibited elevated water intake (P<0.05), significantly reduced salivary flow rate (P<0.01), no significant differences in the submaxillary gland index or spleen index (P>0.05), but a significantly increased thymus index (P<0.05). Marked focal infiltration was observed in the submaxillary glands, the splenic marginal zone was obviously enlarged, and serum IL-17 concentrations as well as submaxillary gland SSA/SSB expression levels were significantly increased (P<0.05). ConclusionSubmaxillary gland antigen and salivary gland antigen can induce SS-related features in female C57BL/6J mice. The SS-related phenotype is more pronounced in the submaxillary gland antigen group than in the salivary gland antigen group, but weaker than that in spontaneously SS-prone female NOD/LtJ mice. Immunization of male C57BL/6J mice with submaxillary or salivary gland antigens fails to induce an obvious SS phenotype.

Background Neck-related work-related musculoskeletal disorders (WMSDs) are a major type of musculoskeletal disorders with a relatively high proportion. Shanghai has a large number of occupational populations; however, the occurrence of WMSDs at neck among the occupational populations across industries in this city has not been reported, and needs to be addressed. Objective To understand the occurrence of neck-related WMSDs and their influencing factors among occupational populations in 8 industries in Shanghai, and to provide a scientific basis for the prevention and control of WMSDs in this population. Methods From February 2024 to February 2025, a cross-sectional survey employed stratified cluster sampling to select 7829 employed workers from 48 enterprises across 8 industries in Shanghai. The study investigated the occurrence of neck-related WMSDs among the participants over the preceding 12 months. Logistic regression analysis was employed to examine the relationships between WMSDs and various occupational factors. Results A total of 7770 questionnaires were collected, yielding an effective response rate of 99.2%. Overall, the positive rate of neck-related WMSDs among the participants was 11.89% (924/7770). Among different industries, the environmental sanitation industry (19.48%), pharmaceutical manufacturing industry (14.57%), and cigarette manufacturing industry (13.66%) had higher prevalence of neck-related WMSDs. Univariate analysis showed that the risk of neck-related WMSDs was higher in the following groups: those with a job tenure ≥5 years in the current position (OR=1.50–1.70), females (OR=1.77), those with higher education levels (master’s degree or above, OR=2.27), and those with worse self-rated health (very poor health, OR=4.38) (P＜0.05). Multivariate logistic regression analysis identified the following independent risk factors for neck WMSDs: environmental sanitation industry (OR=7.30, 95%CI: 4.72, 11.87), higher educational attainment (master’s degree or above: OR=2.16, 95%CI: 1.36, 3.35), worse self-rated health status (very poor: OR=1.95, 95%CI: 1.31, 2.85), work performed in a single workshop (OR=1.36, 95%CI: 1.13, 1.64), understaffing (OR=1.46, 95%CI: 1.25, 1.70), slight neck forward flexion (OR=1.64, 95%CI: 1.32, 2.06), severe neck forward flexion (OR=2.55, 95%CI: 1.97, 3.30), and maintaining a fixed neck posture for a prolonged period (OR=2.28, 95%CI: 1.93, 2.70). Conversely, work rotation (OR=0.75, 95%CI: 0.65, 0.87), adequate rest (OR=0.70, 95%CI: 0.60, 0.82), and severe back flexion (OR=0.63, 95%CI: 0.46, 0.85) were protective factors against neck-related WMSDs. For the nomogram, the area under the curve (AUC)=0.75 (95%CI: 0.74, 0.77), Hosmer-Lemeshow test P=0.764, and Brier score=0.094, indicating that the model had good discrimination and calibration. Conclusion Among the occupational populations in Shanghai, the environmental sanitation industry, pharmaceutical manufacturing industry, and cigarette manufacturing industry are identified as high-risk industries for neck-related WMSDs. Industry affiliation, educational level, work organization patterns, and awkward neck working postures are confirmed as the core influencing factors for the development of neck-related WMSDs. Targeted and comprehensive intervention measures should be formulated focusing on the aforementioned high-risk industries and key influencing factors. Multi-dimensional collaborative efforts, including ergonomic optimization, improvement of labor management systems, and strengthened health education and promotion, should be implemented to effectively control the risk of neck-related WMSDs in the occupational population, and to provide robust statistical evidence for the advancement of regional occupational health prevention and control strategies.

OBJECTIVE:Postoperative recurrence is a common complication of percutaneous endoscopic lumbar discectomy for lumbar disc herniation,which can significantly increase the risk of reoperation.A well-performing risk prediction model can help identify high-risk groups early and prevent postoperative recurrence.This study systematically evaluated the risk prediction model for postoperative recurrence after percutaneous endoscopic lumbar discectomy to provide a reference for surgical decision-making.METHODS:The PubMed,Embase,Web of Science,CNKI,WanFang Data,VIP,and CBM were electronically searched to collect studies on the recurrence risk prediction models after percutaneous endoscopic lumbar discectomy from inception to July 1,2024.Two reviewers independently screened the literature and extracted data.The models' risk of bias,applicability,and report quality were assessed using prediction model risk of bias assessment tool(PROBAST)and Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis(TRIPOD)tools,respectively.Meta-analysis of postoperative recurrence rate of percutaneous endoscopic lumbar discectomy and related predictors was performed using Revman 5.4 software.RESULTS:(1)A total of 15 studies were included,all of which were retrospective studies,including 24 models for predicting the risk of recurrence after percutaneous endoscopic lumbar discectomy.(2)The PROBAST evaluation results indicated that all 15 studies exhibited a high risk of bias.Regarding applicability,two studies demonstrated a low risk,while 13 presented a high risk.(3)Regarding the TRIPOD reporting quality,the overall quality across the 15 studies was low.The primary reasons for this low compliance included the failure to report blinding,a lack of explanation for the sample size calculation method,lack of detailed description of missing data processing methods,and lack of information such as introduction to the model used.(4)Furthermore,the area under the receiver operating characteristic curve for the model ranged from 0.684 to 0.972,with the number of potential predictor variables varying from 15 to 28.(5)The results of meta-analysis showed that the postoperative recurrence rate of lumbar disc herniation patients treated with percutaneous endoscopic lumbar discectomy was 12％(95％CI=9.0％-15.0％),Modic changes(OR=6.72,95％CI=3.90-11.59),body mass index(OR=1.28,95％CI=1.10-1.49),work intensity(OR=3.22,95％CI=1.85-5.59),age(OR=2.28,95％CI=1.50-3.48),and smoking history(OR=2.65,95％CI=1.75-4.00)were independent influencing factors for postoperative recurrence of percutaneous endoscopic lumbar discectomy(all P＜0.05).CONCLUSION:The overall predictive performance of the recurrence risk prediction models after percutaneous endoscopic lumbar discectomy is satisfactory;however,the model exhibits a high overall risk of bias and applicability,coupled with low reporting quality.Additionally,there is a lack of prospective research and external validation.Future,risk prediction models should consider factors such as Modic changes,body mass index,work intensity,age,and smoking history as potential predictors.

OBJECTIVE:Postoperative recurrence is a common complication of percutaneous endoscopic lumbar discectomy for lumbar disc herniation,which can significantly increase the risk of reoperation.A well-performing risk prediction model can help identify high-risk groups early and prevent postoperative recurrence.This study systematically evaluated the risk prediction model for postoperative recurrence after percutaneous endoscopic lumbar discectomy to provide a reference for surgical decision-making.METHODS:The PubMed,Embase,Web of Science,CNKI,WanFang Data,VIP,and CBM were electronically searched to collect studies on the recurrence risk prediction models after percutaneous endoscopic lumbar discectomy from inception to July 1,2024.Two reviewers independently screened the literature and extracted data.The models' risk of bias,applicability,and report quality were assessed using prediction model risk of bias assessment tool(PROBAST)and Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis(TRIPOD)tools,respectively.Meta-analysis of postoperative recurrence rate of percutaneous endoscopic lumbar discectomy and related predictors was performed using Revman 5.4 software.RESULTS:(1)A total of 15 studies were included,all of which were retrospective studies,including 24 models for predicting the risk of recurrence after percutaneous endoscopic lumbar discectomy.(2)The PROBAST evaluation results indicated that all 15 studies exhibited a high risk of bias.Regarding applicability,two studies demonstrated a low risk,while 13 presented a high risk.(3)Regarding the TRIPOD reporting quality,the overall quality across the 15 studies was low.The primary reasons for this low compliance included the failure to report blinding,a lack of explanation for the sample size calculation method,lack of detailed description of missing data processing methods,and lack of information such as introduction to the model used.(4)Furthermore,the area under the receiver operating characteristic curve for the model ranged from 0.684 to 0.972,with the number of potential predictor variables varying from 15 to 28.(5)The results of meta-analysis showed that the postoperative recurrence rate of lumbar disc herniation patients treated with percutaneous endoscopic lumbar discectomy was 12％(95％CI=9.0％-15.0％),Modic changes(OR=6.72,95％CI=3.90-11.59),body mass index(OR=1.28,95％CI=1.10-1.49),work intensity(OR=3.22,95％CI=1.85-5.59),age(OR=2.28,95％CI=1.50-3.48),and smoking history(OR=2.65,95％CI=1.75-4.00)were independent influencing factors for postoperative recurrence of percutaneous endoscopic lumbar discectomy(all P＜0.05).CONCLUSION:The overall predictive performance of the recurrence risk prediction models after percutaneous endoscopic lumbar discectomy is satisfactory;however,the model exhibits a high overall risk of bias and applicability,coupled with low reporting quality.Additionally,there is a lack of prospective research and external validation.Future,risk prediction models should consider factors such as Modic changes,body mass index,work intensity,age,and smoking history as potential predictors.

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.