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.

AIM To optimize the cellulase-assisted ultrasound extraction process for total flavonoids from Plumbago zeylanica L.,and to evaluate their anti-oxidant activity.METHODS With extraction time,liquid-solid ratio,cellulase addition amount,extraction temperature and ultrasonic power as influencing factors,extraction rate of total flavonoids as an evaluation index,the extraction process was optimized by response surface method on the basis of single factor test.Subsequently,The scavenging rates of extract on DPPH,ABTS and OH free radicals were determined.RESULTS The optimal conditions were determined to be 34∶1 for liquid-solid ratio,3％for cellulase addition amount,51 ℃ for extraction temperature,38 min for extraction time,and 400 W for ultrasonic power,the extraction rate of total flavonoids was(33.411±0.97)％.The IC50 values of three free radicals were 0.13,0.042,3.29 mg/mL,respectively.CONCLUSION This reasonable and reliable method can be used for the cellulase-assisted ultrasound extraction of total flavonoids from P.zeylanica with strong anti-oxidant activity.

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

AIM To compare the chemical constituents in traditional decoction and formula granule decoction of classical famous prescription Wendan Decoction.METHODS The HPLC fingerprints were established,after which the contents of adenosine,synephrine,liquiritin,naringin,hesperidin,6-gingerol and adenosine cyclophosphate were determined,cluster analysis,principal component analysis and multidimensional scaling analysis were adopted in the investigation of component differences,and the equivalent of formula granules was adjusted.RESULTS The similarities of HPLC fingerprints for 10 batches of traditional decoctions were higher than those of HPLC fingerprints for 9 batches of formula granule decoctions(P＜0.01).Adenosine,synephrine,liquiritin,hesperidin and cyclic adenosine monophosphate demonstrated higher contents in traditional decoctions than those in formula granule decoctions(P＜0.05),6-gingerol displayed lower content than that in the latter produced by manufacturers A,C(P＜0.05),which was higher than that in the latter produced by manufacturer B(P＜0.01).Various batches of traditional decoctions and formula granule decoctions could be obviously distinguished,adenosine,synephrine and hesperidin exhibited great influences on the classification of principal component analysis,and the quality of formula granule decoctions produced by manufacturer C was closer to that of traditional decoctions.After equivalent correction,the contents of various constituents in formula granule decoctions produced by manufacturers A,C showed no significant differences as compared with those in traditional decoction(P＞0.05).CONCLUSION The formula granules of Wendan Decoction from different manufacturers exist quality differences,so the preparation process and extraction process of this preparation should be optimized to improve quality,and equivalent ratio should be adjusted according to actual requirements to ensure its scientific and rational clinical application.

Objective:To investigate the risk factors for patients with hypertriglyceridemia-related acute pancreatitis (HTG-AP) developing into severe acute pancreatitis or experiencing organ failure.Methods:This retrospective cohort study collected clinical data from 2 429 patients diagnosed with acute pancreatitis from five hospitals in China between January 2019 and December 2023 using a pre-designed data collection form. The cohort included 1 516 males and 913 females,with an age of (50.2±16.5)years(range: 11 to 99 years). Among them,353 patients (16.1%) had HTG-AP,while 1 846 (83.9%) had non-HTG-AP. HTG-AP was defined as serum triglyceride levels>500 mg/dl with other etiologies excluded. Intergroup comparisons were performed using t-tests,Mann-Whitney U test or χ2 tests,respectively. Univariate and multivariate logistic regression analyses were conducted to assess risk factors for severe acute pancreatitis after adjusting for potential confounders,and a predictive model was developed and validated. Results:Compared with other etiologies,HTG-AP patients had a higher risk of progressing to SAP ( OR=1.415,95% CI: 0.866 to 2.312, P=0.017) and organ failure ( OR=1.256,95% CI: 1.015 to 1.554, P=0.036). Among HTG-AP patients,risk factors for SAP included body mass index ( OR=1.856,95% CI: 1.742 to 1.987, P=0.033),fasting blood glucose ( OR=1.128,95% CI: 1.036 to 1.229, P=0.006),white blood cell count( OR=1.162,95% CI: 1.055 to 1.281, P=0.002),and the presence of pleural effusion ( OR=13.151,95% CI: 4.330 to 19.946, P<0.01). A nomogram prediction model for SAP in HTG-AP was constructed based on these risk factors,demonstrating good discriminative ability with area under the curve values of 0.877 in the training set and 0.894 in the validation set,along with satisfactory calibration. Conclusions:HTG-AP patients are at higher risk of developing SAP and organ failure. The risk prediction model incorporating body mass index,fasting blood glucose,white blood cell count,and pleural effusion shows good predictive value for SAP.

Objective:To investigate the prevalence and influencing factors of frailty among older adults diagnosed with non-ST-segment elevation acute coronary syndrome(NSTE-ACS).Methods:We conducted a cross-sectional study involving patients aged 65 years and older with NSTE-ACS, who were admitted to the Cardiology Center and the Department of Geriatrics at Beijing Friendship Hospital, Capital Medical University, between January 2020 and November 2021.Patients were categorized into non-frail, pre-frail, and frail groups based on the FRAIL scale.We collected clinical data, including general health conditions, comorbidities, laboratory results, treatments, and comprehensive geriatric assessments.Logistic regression analysis was employed to identify the influencing factors associated with frailty and pre-frailty in older adults with NSTE-ACS.Results:A total of 528 patients with NSTE-ACS were included in the study, comprising 308 males(58.3%)and 220 females(41.7%). The age range of participants was from 65 to 90 years, with a median age of 72(68, 76)years.The prevalence of frailty among older adults with NSTE-ACS was 11.4%(60/528), while pre-frailty was observed in 51.9%(274/528), and non-frailty in 36.7%(194/528). Compared to the non-frail and pre-frail groups, patients in the frail group were older, had a higher proportion of females, exhibited a greater prevalence of chronic diseases, and presented with elevated inflammatory markers.Additionally, frail patients demonstrated poorer nutritional status and reduced functional ability(all P<0.005). Risk factors for frailty in older adults with NSTE-ACS included older age( OR=1.110, 95% CI: 1.032-1.194, P=0.005), diabetes( OR=2.489, 95% CI: 1.091-5.679, P=0.030), cerebrovascular disease ( OR=4.151, 95% CI: 1.660-10.384, P=0.002), chronic kidney disease ( OR=42.874, 95% CI: 3.957-464.513, P=0.002), and elevated white blood cell levels( OR=1.424, 95% CI: 1.125-1.802, P=0.003). Conversely, being male( OR=0.252, 95% CI: 0.105-0.604, P=0.002)was identified as a protective factor against frailty in this patient population.For pre-frail older adults with NSTE-ACS, identified risk factors included diabetes( OR=1.882, 95% CI: 1.199-2.955, P=0.006), cerebrovascular disease( OR=1.938, 95% CI: 1.176-3.195, P=0.009), and chronic kidney disease ( OR=12.137, 95% CI: 1.536-95.934, P=0.018). Similarly, being male( OR=0.601, 95% CI: 0.376-0.961, P=0.033)was also a protective factor for pre-frailty in older adults with NSTE-ACS. Conclusions:The prevalence of frailty and pre-frailty among older adults with NSTE-ACS is notably high.Common risk factors for frailty and pre-frailty in this population include female gender, diabetes, cerebrovascular disease, and chronic kidney disease.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To observe the value of AcoStream thrombus aspiration catheter for treating intermediate-high risk acute pulmonary embolism(APE).Methods Twenty-six patients with intermediate-high risk APE who underwent treatment with AcoStream thrombus aspiration catheter were retrospectively collected.The immediate technical success rate,procedure success rate and thrombus clearance rate of target vessels were recorded,as well as clinical success rate and complications in perioperative period and the recurrence of pulmonary embolism(PE)during follow-up.Results Among 26 patients with intermediate-high risk APE,the immediate technical success rate was 100%(26/26),the procedure success rate was 92.31%(24/26),and the immediate thrombus clearance rate of target vessels was 63.37%as median,including 16 cases(16/26,61.54%)achieved thrombus clearance rate grade Ⅱ or above.The perioperative period clinical success rate of treating intermediate-high risk APE was 96.15%(25/26).Two patients experienced transient arrhythmia and other 2 patients experienced worsening transient chest tightness during the procedure,and 1 case developed hematoma at the puncture site after treatment.During follow-up,no recurrence of symptomatic PE was observed.Conclusion AcoStream thrombus aspiration catheter was safe and effective for treating intermediate-high risk APE,worthy clinical promotion and application.