Objective: To address the dual challenges of long-tail distribution and feature sparsity in traditional Chinese medicine (TCM) syndrome differentiation within real clinical settings, we propose a data-efficient learning framework enhanced by knowledge graphs. Methods: We developed Agent-GNN, a three-stage decoupled learning framework, and validated it on the Traditional Chinese Medicine Syndrome Diagnosis (TCM-SD) dataset containing 54 152 clinical records across 148 syndrome categories. First, we constructed a comprehensive medical knowledge graph encoding the complete TCM reasoning system. Second, we proposed a Functional Patient Profiling (FPP) method that utilizes large language models (LLMs) combined with Graph Retrieval-Augmented Generation (RAG) to extract structured symptom-etiology-pathogenesis subgraphs from medical records. Third, we employed heterogeneous graph neural networks to learn structured combination patterns explicitly. We compared our method against multiple baselines including BERT, ZY-BERT, ZY-BERT + Know, GAT, and GPT-4 Few-shot, using macro-F1 score as the primary evaluation metric. Additionally, ablation experiments were conducted to validate the contribution of each key component to model performance. Results: Agent-GNN achieved an overall macro-F1 score of 72.4%, representing an 8.7 percentage points improvement over ZY-BERT + Know (63.7%), the strongest baseline among traditional methods. For long-tail syndromes with fewer than 10 samples, Agent-GNN reached a macro-F1 score of 58.6%, compared with 39.3% for ZY-BERT + Know and 41.2% for GPT-4 Few-shot, representing relative improvements of 49.2% and 42.2%, respectively. Ablation experiments confirmed that the explicit modeling of etiology-pathogenesis nodes contributed 12.4 percentage points to this enhanced long-tail syndrome performance. Conclusion This study proposes Agent-GNN, a knowledge graph-enhanced framework that effectively addresses the long-tail distribution challenge in TCM syndrome differentiation. By explicitly modeling manifestation-mechanism-essence patterns through structured knowledge graphs, our approach achieves superior performance in data-scarce scenarios while providing interpretable reasoning paths for TCM intelligent diagnosis.

Functional constipation （FC） is a common functional disorder of the intestines， mainly characterized by reduced bowel movement frequency， difficulty in defecation， a sensation of incomplete evacuation， and hard stools， which severely affect patients’ quality of life. Research indicates that the pathogenesis of FC is closely related to gut microbiota dysbiosis and abnormal bile acid secretion. Bile acids， as endogenous natural laxatives， promote bowel movements by enhancing colonic secretion and regulating intestinal motility； meanwhile， gut microbiota influence colonic transit function by regulating the enteric nervous system， immune system， and their metabolic products. Based on an overview of the relationship between gut microbiota and bile acid metabolism， this article systematically reviews the current research status on the mechanisms of traditional Chinese medicine （TCM） in treating FC by regulating the balance of the gut microbiota-bile acid axis. It is found that single Chinese medicinal herbs （such as Atractylodes macrocephala）， isolated compounds （such as Platycodon grandiflorum polysaccharides）， herbal formulas （such as Shanger huang pill）， acupuncture， and moxibustion can up-regulate the abundance of beneficial bacteria， reshape the microbial structure， correct bile acid metabolism， and activate the Takeda G-protein receptor 5/farnesoid X receptor pathway to treat FC.

low transit constipation （STC） is a common functional intestinal disorder caused by impaired colonic transit function， characterized by reduced bowel movement frequency， hard stools， and difficulty in defecation. The mitogen-activated protein kinase （MAPK） signaling pathway， which mainly includes extracellular signal-regulated kinase （ERK）， c-Jun N-terminal kinase （JNK）， and p38 subtypes， plays a critical regulatory role in the occurrence and development of STC. This paper systematically reviews the multiple pathogenic mechanisms of the MAPK signaling pathway in STC and the research progress of traditional Chinese medicine （TCM） intervention.At the mechanistic level， the MAPK signaling pathway promotes the progression of STC through the following links：（1） Activation of p38 upregulates the expression of aquaporin 3 （AQP3）/AQP4 in the colon， leading to excessive reabsorption of water in the intestinal lumen； （2） It forms a positive feedback loop with nuclear factor-κB （NF-κB） to maintain low-grade intestinal inflammation， releases inflammatory factors such as tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， and inhibits smooth muscle contraction； （3） Overactivation of p38 downregulates the expression of occludin and mucin 2 while upregulates the expression of claudin-2， thereby disrupting the mucosal barrier； （4） The JNK/p38 signaling pathway activates the caspase cascade to induce apoptosis of intestinal epithelial cells， neurons， and interstitial cells of Cajal； （5） Abnormal ERK signaling and excessive activation of p38/JNK inhibit intestinal smooth muscle contraction and reduce 5-hydroxytryptamine secretion， ultimately resulting in impaired colonic transit function.At the intervention level， TCM compound formulas and single herbs have been proven to improve STC by regulating the MAPK signaling pathway. Their effects are syndrome type-dependent：yin-nourishing formulas （Zengye Chengqi Tang， Tongbian Tang） mainly regulate the ERK/AQP axis； yang-warming formulas （Jichuan Jian） target both ERK/JNK and anti-apoptosis； heat-clearing formulas （Sanren Tang） focus on p38/NF-κB anti-inflammation. A single drug can simultaneously cover multiple aspects including water metabolism， inflammation， barrier function， apoptosis， and intestinal motility.Current relevant studies still have limitations such as mechanisms mostly remaining at the correlational level and a lack of disease-syndrome integrated research models. Future studies should combine specific inhibitors or gene knockout to identify core targets， establish disease-syndrome integrated STC models， and use network pharmacology and molecular docking techniques to deeply analyze the fine mechanism of “component-target-phenotype”， so as to provide high-quality evidence for the precise regulation of the MAPK signaling pathway by TCM in the intervention of STC.

Objective: To examine the association of physical activity with cognitive function and mental health among primary school students based on latent subgroup identification and dose response modeling, and to clarify cognitive-psychological profiles and the protective role of physical exercise, so as to provide evidence based support for physical exercise promoting mental health among primary school students. Methods: A study was conducted among 546 primary school students aged 8-12 years old from a primary school in Shanghai from March to June 2025. Physical fitness indicators, including vital capacity, 50 m sprint, sit and reach, and 1 min rope skipping were measured. Physical exercise was assessed by using the Physical Activity Rating Scale-3 (PARS-3), and mental health was assessed by using the Revised Child Anxiety and Depression Scale, 47-item version (RCADS-47). Cognitive function was assessed by using Stroop, N-back, and task-switching tasks. Latent profile analysis (LPA) was performed for cognitive-psychological health of primary school students based on seven cognitive indicators and six psychological indicators. Multivariable Logistic regression, trend test, and restricted cubic spline (RCS) analysis were used to examine associations between physical exercise and psychological highrisk status. Results: Five cognitive psychological health subgroups were identified:high symptom and impaired cognition group ( n =40, 7.3%), low cognition and low symptom group ( n =108, 19.8% ), and high cognition and high symptom group ( n =110, 20.2%), cognitive advantage and psychologically healthy group ( n = 272, 49.8%), and extremely high symptom and cognitively vulnerable group ( n =16, 2.9%). Among them, the high symptom and impaired-cognition group and extremely high symptom and cognitively vulnerable group were classified as psychologically high risk types. Significant differences were observed across subgroups in psychological symptoms, cognitive function, some physical fitness indicators and physical exercise level, except for body weight, body mass index, and sit and reach ( F =2.64-297.53, all P < 0.05). The results of the multivariate Logistic regression analysis indicated that high level sports, including high total volume of physical exercise, single session duration >30 min, high intensity, and frequency ≥3 times/week, was associated with lower psychological high risk status ( OR =0.20, 0.36, 0.33, 0.40, all P <0.05). Trend analysis showed that total volume of physical exercise and single session exercise duration were negatively associated with psychological high risk status among primary school students ( OR =0.98, 0.79, both P trend <0.05). RCS analysis showed no statistically significant overall or nonlinear association between total volume of physical exercise and psychological high risk status ( χ 2=2.92, 0.01, both P >0.05). Conclusions Cognitive-psychological health among primary school students is heterogeneous. Physical exercise is associated with psychological health improvement and may show a threshold effect, with total volume of physical exercise and single session exercise duration being the key dimensions.

In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.

In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.

Advanced atherosclerosis is the major global cause of death, as featured by the aggregation of apoptotic cells (ACs) in necrotic cores. The defective efferocytosis and dysfunctional cholesterol efflux of macrophages are the main reasons for forming necrotic cores in advanced atherosclerosis. In this study, we constructed self-assembled procyanidins (PC) NPs for loading pitavastatin (Pita). The designed HA@PC@Pita NPs with hyaluronic acid (HA) modification combined the advantages of efferocytosis restoration of Pita and cholesterol efflux enhancement of PC. In vitro assay indicated that HA@PC@Pita NPs could induce M1/M2 repolarization and upregulate ERK5/Mertk expression to restore efferocytosis of macrophages. Simultaneously, HA@PC@Pita NPs notably promoted cholesterol efflux by promoting macrophage lipophagy, a selective autophagy of lipid droplets. In vivo study showed that HA@PC@Pita NPs cleared necrotic core and enhanced plaque stability in the ApoE ^-/- mice model with advanced atherosclerosis. Taken together, this study demonstrated the potential of HA@PC@Pita NPs for the treatment of advanced atherosclerosis.

OBJECTIVE: This cross-sectional study assessed the methodological quality of systematic reviews (SRs) of Chinese herbal medicine (CHM) published in Chinese between Jan 2021 and Sep 2022. METHODS: Chinese language CHM SRs were identified through literature searches across 3 international and 4 Chinese databases. Methodological quality was appraised using A MeaSurement Tool to Assess systematic Reviews 2. Logistic regressions were used to explore associations between bibliographical characteristics and quality. RESULTS: Analyses of methodological quality found that among the 213 sampled SRs, 69.5% were of critically low quality, 30.5% were of low quality, and none achieved high or moderate quality. Common shortcomings included the failure to identify the studies excluded from the analysis, failure to disclose funding sources, and limited evaluation of the potential impact of bias on conclusions. Logistic regressions revealed that SRs led by corresponding authors affiliated with universities or academic institutions tended to be of lower quality than SRs led by authors affiliated with hospitals or clinical facilities. CONCLUSION Recent Chinese language CHM SRs exhibited limited methodological quality, making them unlikely to support the development of clinical practice guidelines. Urgent initiatives are needed to enhance training for researchers, peer-reviewers and editors involved in the preparation and publication of SRs. Adoption of Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines in Chinese language journals is crucial to improve the relevance of SRs for Chinese medicine development. Addressing deficiencies in methodology and reporting is essential for promoting evidence-based practices and informed clinical decisions in Chinese medicine. Please cite this article as: Jiang Y, Zhong CC, Wang BH, Xu SS, Ho FF, Kwong MH, Ho L, Zhou JHS, Lam KC, Liu JP, Zhang BT, Chung VCH. Methodological quality of systematic reviews on orally administered Chinese herbal medicine published in Chinese between 2021 and 2022: A cross-sectional study. J Integr Med. 2025; 23(5):492-501.
Cross-Sectional Studies ; Drugs, Chinese Herbal/administration & dosage* ; Systematic Reviews as Topic/standards* ; Humans ; China ; Administration, Oral ; Medicine, Chinese Traditional