In the context of the digital-intelligent era of traditional Chinese medicine （TCM）， the lack of clinical thinking is a pressing issue that limits the overall effectiveness of TCM and talent cultivation. The "disease-pulse-syndrome-treatment differentiation" thinking model， originally developed by ZHANG Zhongjing in the Treatise on Cold Damage and Miscellaneous Diseases （Shang Han Za Bing Lun）， has served as a guideline and paradigm followed by generations of medical practitioners. This study aims to construct a digitalized "disease-pulse-syndrome-treatment differentiation" thinking system， develop a digital assessment system， and implement it for practical application. The goal is to recommend a digitalized assessment model for TCM and provide a reference for the integrated innovation of talent cultivation in medicine， education， and research. First， based on the complex diagnostic and treatment framework of the Treatise on Cold Damage Diseases （Shang Han Lun）， the research team previously established a "process" + "result" thinking model that included four processes and ten steps. This study integrates knowledge unit theory and digital technology to create a digital system for "disease-pulse-syndrome-treatment differentiation" with a dual-control model of "process control" and "result control". The system consists of 46 items across three categories： knowledge body （W=20%）， knowledge element （W=30%）， and knowledge element associations （W=50%）. Second， a mixed-methods research design was employed， combining qualitative and quantitative approaches. The Delphi method was used to establish hierarchical levels and screen items， while the analytic hierarchy process （AHP） was used to assign weights. Expert surveys were conducted to reach a consensus and further validate the rationale and necessity of the system. Finally， based on the system architecture and integrating key computer technologies， a digital assessment system for "disease-pulse-syndrome-treatment differentiation" was developed. The Treatise on Cold Damage Diseases （Shang Han Lun） was used as a case study to validate the system's feasibility. Statistical results showed that the difficulty level of the assessment question bank was moderate （DL ranging from 0.65 to 0.89）， with good discrimination （D>0.4）， and reasonable reliability and validity （Cronbach's α=0.84， KMO=0.72， Bartlett's test P<0.01）. The system can perform process-oriented evaluations of candidates' thinking in "disease-pulse-syndrome-treatment differentiation" and effectively achieve the goal of clinical thinking assessment through a combination of "process control" and "result control". The examination system offers three major advantages. It standardizes， objectifies， and streamlines the assessment of thought processes， facilitates the organic transformation of TCM education from outcome-based education to thinking-based education， and from exam-oriented education to competency-oriented education， and promotes the practical transformation of TCM assessments from qualitative to quantitative evaluation， as well as from theory to practice. In summary， this system not only represents a technological upgrade to traditional examinations but also empowers the cultivation and assessment of clinical talent in the digital-intelligent era， demonstrating broad application prospects.

The oocyte， as the origin of life， provides half the chromosomes to the embryo and supplies the proteins， substrates， energy， and other support necessary for embryonic development. It is the decisive factor determining the embryo's developmental potential. Infertility caused by reproductive endocrine diseases targets the oocyte as the final target cell. Improving oocyte quality represents a key and difficult point in the field of modern reproductive medicine. The decline of oocyte quality is related to meiosis abnormalities， DNA damage， mitochondrial dysfunction， oxidative stress， and other mechanisms. For oocyte quality problems， there is no unified international guideline to recommend drugs. Because the drug intervention research on oocytes involves strict clinical ethical restrictions， the current relevant research only stays in the animal and in vitro experimental stage and has not yet been applied to the clinic. Traditional Chinese medicine compound formula has a multi-target and multi-pathway regulation mechanism and is widely used in clinics. More and more research began to pay attention to the potential mechanism of traditional Chinese medicine compound formulas in improving oocyte quality. Traditional Chinese medicine compound formula has the advantages of multi-target and multi-channel synergy as well as better safety， individualization， and conformity to clinical ethics in improving oocyte quality. This article systematically reviewed the research progress on traditional Chinese medicine compound formula interventions for oocyte quality， aiming to summarize existing findings and provide recommendations to improve oocyte quality and optimize the clinical diagnosis and treatment of female infertility within traditional Chinese medicine.

The oocyte， as the origin of life， provides half the chromosomes to the embryo and supplies the proteins， substrates， energy， and other support necessary for embryonic development. It is the decisive factor determining the embryo's developmental potential. Infertility caused by reproductive endocrine diseases targets the oocyte as the final target cell. Improving oocyte quality represents a key and difficult point in the field of modern reproductive medicine. The decline of oocyte quality is related to meiosis abnormalities， DNA damage， mitochondrial dysfunction， oxidative stress， and other mechanisms. For oocyte quality problems， there is no unified international guideline to recommend drugs. Because the drug intervention research on oocytes involves strict clinical ethical restrictions， the current relevant research only stays in the animal and in vitro experimental stage and has not yet been applied to the clinic. Traditional Chinese medicine compound formula has a multi-target and multi-pathway regulation mechanism and is widely used in clinics. More and more research began to pay attention to the potential mechanism of traditional Chinese medicine compound formulas in improving oocyte quality. Traditional Chinese medicine compound formula has the advantages of multi-target and multi-channel synergy as well as better safety， individualization， and conformity to clinical ethics in improving oocyte quality. This article systematically reviewed the research progress on traditional Chinese medicine compound formula interventions for oocyte quality， aiming to summarize existing findings and provide recommendations to improve oocyte quality and optimize the clinical diagnosis and treatment of female infertility within traditional Chinese medicine.

To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

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.

Objective: To investigate the correlation between color parameters (L^*, a^*, b^*, Eab^*) and the contents of reducing sugars, total polysaccharides, total oligosaccharides, as well as four saccharides (fructose, glucose, sucrose, and kestose) during the nine cycles of steaming and sun-drying processing of Polygonatum kingianum, and to preliminarily explore the optimal processing duration.
Methods: The color changes were objectively evaluated using a colorimeter. The anthrone-sulfuric acid method was employed to determine total polysaccharides and oligosaccharides. The 3,5-dinitrosalicylic acid (DNS) colorimetric method was used to measure total reducing sugar content. High-performance liquid chromatography coupled with charged aerosol detection (HPLC-CAD) was applied for quantitative analysis of fructose, glucose, sucrose, and kestose. Multivariate statistical analysis was conducted to assess samples from different processing stages.
Results: Significant variations in color and component contents were observed across processing stages. The herbal pieces progressively darkened with increased processing cycles: brightness (L^*) and total color difference (Eab^*) initially decreased then stabilized, while a^* (red-green) and b^* (yellow-blue) values first increased then declined. Total polysaccharides and oligosaccharides showed overall decreasing trends, whereas reducing sugars initially increased before stabilizing. Fructose and glucose levels rose continuously, while sucrose and kestose decreased progressively, becoming undetectable after five cycles.
Conclusion: The chromatic alteration and saccharide composition of P. kingianum showed significant correlation with processing duration. Both total color difference (Eab^*) and reducing sugar content stabilized after four processing cycles (12 hours), suggesting that four cycles of steaming and sun-drying may represent the optimal processing duration.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) has a relatively low incidence in the general population, but it is the most common monogenic hereditary cerebral small vessel disease in adults. White matter hyperintensities (WMH) are the earliest and most common magnetic resonance imaging (MRI) manifestations of CADASIL. However, the total WMH burden on imaging often shows a weak correlation with cognitive impairment, the degree of disability, and stroke risk, suggesting that WMH may not be single homogeneous lesions but rather have significant heterogeneity. To thoroughly elucidate the heterogeneous characteristics of WMH, this article systematically analyzes representative recent studies on postmortem human brain histopathology and in vivo advanced quantitative MRI, summarizes the histopathological features, imaging manifestations, and clinical correlations of WMH heterogeneity related to CADASIL, and explores the sources and formation mechanisms of WMH heterogeneity. Given that WMH are the earliest and most characteristic imaging manifestations of CADASIL, a comprehensive understanding of their heterogeneity at the pathological and imaging levels as well as their clinical associations will not only help deepen the understanding of the occurrence and development of WMH and the pathogenesis of CADASIL, but also enable refined risk stratification and prognostic assessment in the early stage of the disease based on their heterogeneous characteristics, thereby providing a basis for the individualized management and intervention of the disease.

Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

AIM: To discuss the expression and diagnostic value of serum trefoil factor 1(TFF1)and annexin A2(ANXA2)in diabetic retinopathy(DR).METHODS:A total of 50 DR patients(100 eyes; research group)and 50 type 2 diabetes mellitus(T2DM)patients(100 eyes; control group)without retinopathy who visited our hospital between January 2022 and December 2024 were recruited. Enzyme linked immunosorbent assay was performed to test serum TFF1 and ANXA2. Pearson method was performed to analyze the correlation between serum TFF1 and ANXA2 in DR. Logistics method was used to discuss the influencing factors of retinopathy in T2DM patients. ROC was performed to analyze the diagnostic value of serum TFF1 and ANXA2 in DR.RESULTS: The research group had clearly longer T2DM course, higher glycated hemoglobin, total cholesterol(TC), and serum ANXA2 than the control group(all P<0.001); the research group had significantly lower serum TFF1 than the control group(P<0.001); Serum TFF1 and ANXA2 in DR patients were negatively correlated(r=-0.345, P=0.014). The expression of serum TFF1 and ANXA2 was influencing factor for the occurrence of retinopathy in T2DM patients(all P<0.05). The AUC of serum TFF1 in diagnosing DR was 0.831(95%CI=0.746-0.916), and the AUC of serum ANXA2 in diagnosing DR was 0.832(95%CI=0.755-0.908). The combination of the two had an AUC of 0.932(95%CI=0.884-0.980)for diagnosing DR. The combination of serum TFF1 and ANXA2 had a higher diagnostic value for DR than individual diagnosis(Zcombination-TFF1=2.883, P=0.004; Zcombination-ANXA2=2.947, P=0.003).CONCLUSION: Serum TFF1 is reduced and serum ANXA2 is increased in DR patients. These changes are associated with the increase in risk of retinopathy in T2DM. The combination of serum TFF1 and ANXA2 has certain diagnostic value for DR.