ObjectiveThis paper aims to investigate the effects of icariin on spermatogenesis in mice with exercise-induced fatigue and explore the underlying mechanisms. MethodsICR male mice were screened by swimming and randomly divided into normal group， model group， vitamin C group， icariin groups with low， medium， and high doses， and medium-dose icariin+N-nitro-L-arginine methyl ester （L-NAME） group， with 10 mice per group. Except for the normal group， all the other groups underwent weighted swimming training to establish an exercise-induced fatigue model. No gavage was administered during the first two weeks of the weighted training. From week three to four， the icariin groups with low， medium， and high doses received 0.03， 0.06， and 0.12 g·kg^-1 icariin via gavage， respectively. The vitamin C group received 0.2 g·kg^-1 vitamin C. The L-NAME group received 0.06 g·kg^-1 icariin and 0.01 g·kg^-1 L-NAME via intraperitoneal injection. The normal and model groups received equivalent physiological saline. After the experiment， body weight and the last exhaustive swimming time were recorded. Blood urea nitrogen （BUN）， lactate （LA）， lactate dehydrogenase （LDH）， malondialdehyde （MDA）， testicular testosterone （T）， testicular Ca²⁺/Mg²⁺-adenosine triphosphatase （ATPase） （micro-assay）， and the levels of testicular cyclic guanosine monophosphate （cGMP） were measured by using kits. Sperm CD46 levels were detected by flow cytometry. Testicular seminiferous tubules were observed via hematoxylin-eosin （HE） staining， and the testicular morphometric score （TMS） was used to evaluate the spermatogenic function. Protein expression of regucalcin （RGN， SMP30）， cGMP-dependent protein kinase 1 （PKG）， and cGMP-dependent protein kinase anchoring protein （GKAP1） was detected by Western blot. Testicular regucalcin expression was examined by immunofluorescence （IF）. The epididymal sperm quality of mice was observed under a microscope. Fluorescence-stained sections of stimulated by retinoic acid gene 8 （STRA8）， synaptonemal complex protein 3 （SCP3）， and transition protein 1（TNP1） in testicular seminiferous tubules were assessed by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed decreased body weight and exhaustive swimming time （P<0.01）， significantly increased fatigue markers （LA， LDH， and BUN） and lipid peroxidation product MDA （P<0.01）， reduced testicular RGN， PKG， GKAP1， testosterone， Ca²⁺/Mg²⁺-ATPase， and cGMP levels （P<0.01）， decreased sperm motility， sperm count， and TMS scores， and downregulated the expression of STRA8， SCP3， and TNP1. Compared with the model group， the icariin group with high dose exhibited increased exhaustive swimming time （P<0.01）， reduced LA， LDH， BUN， and MDA levels （P<0.01）， elevated superoxide dismutase （SOD） （P<0.01）， upregulated testicular RGN， PKG， GKAP1， testosterone， Ca²⁺/Mg²⁺-ATPase， and cGMP levels （P<0.01）， improved sperm motility， sperm count， and TMS scores， and enhanced STRA8， SCP3， and TNP1 expression. Compared with the L-NAME group， the icariin group with medium dose showed increased expression of STRA8， SCP3， and TNP1 in the testicular tissue （P<0.01） and elevated cGMP and GKAP1 levels （P<0.01）. ConclusionExercise-induced fatigue reduces the expression of RGN and cGMP/PKG/GKAP1 in mice， thereby causing abnormal spermatogenesis and impairing reproductive function in mice. Icariin ameliorates spermatogenic dysfunction in exercise-induced fatigue mice by promoting the expression of RGN and cGMP/PKG/GKAP1， thereby mitigating the damage of exercise-induced fatigue to the reproductive system.

Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β （TGF-β） regulates cell differentiation， proliferation， apoptosis， and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years， with the continuous exploration of the mechanism of liver cancer， it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine （TCM） provides a unique perspective for the classification， diagnosis， and treatment of liver cancer with its comprehensive regulatory effects of multi-components， multi-targets， and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest， apoptosis， autophagy， et al， while the pro-cancerous mechanisms included promoting cancer cell proliferation， invasion and metastasis， immunosuppression， angiogenesis， et al. The TCM compounds intervening this pathway were sorted out， including Jianpi Huayu compound， Fuyang Baoyuan compound， Yipi Yanggan compound， Fuzheng Jiedu compound， compound Astragalus and Salvia， Biejia Jianwan， Dahuang Zhechong pill， and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea， Dendrobii Caulis， Gleditsia sinensis， and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids， alkaloids， glycosides， phenolics， terpenoids， polysaccharides， and other kinds of compounds. At the same time， it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells， blocking the cell cycle， and inhibiting liver cancer cell proliferation， migration， invasion， angiogenesis， immune escape， etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal， thereby exerting positive anti-tumor effects， opening up a new direction for the precise targeted treatment of liver cancer， and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

Objective To explore the causal relationship between immune cells and heart failure (HF), and the mediating role of serum metabolites, in order to identify potential biomarkers and therapeutic targets. Methods We employed a two-sample Mendelian randomization (MR) analysis method based on genome-wide association study (GWAS) data, analyzing the direct and indirect effects of 731 types of immune cells and 1 400 metabolites on HF. We selected valid instrumental variables and conducted statistical analyses using R software. The primary analysis was performed using the inverse variance weighted method, supplemented by MR-Egger analysis and weighted median method. The stability of the results was assessed through tests such as Cochran’s Q test. Results Our research found a negative causal relationship between PD-L1 on CD14−CD16+ and HF. Sensitivity analysis supported this result. The reverse MR analysis did not find an effect of HF on PD-L1 on CD14−CD16+, indicating that PD-L1 on CD14−CD16+ might play a unidirectional role in reducing the risk of HF. Further mediation MR analysis showed that PD-L1 on CD14−CD16+ might influence the risk of HF onset by regulating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), with a mediation effect ratio of 6.7%. Conclusion PD-L1 on CD14−CD16+ may reduce the risk of HF by elevating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), which provides a new perspective for understanding the pathogenesis of HF.

Objective To compare the cost and efficacy of ambulatory versus hospitalized surgery for lung tumor patients. Methods Two researchers independently conducted a computer search on February 14, 2025, in databases including CNKI, PubMed, Web of Science, Ovid Medline, Cochrane Library, and Wanfang Database, with the search period covering from the inception of these databases to February 2025. The outcome indicators were postoperative complication rate, length of hospital stay, hospitalization costs, et al. For the included randomized controlled trials and non-randomized controlled trials, we used the Cochrane risk of bias assessment tool and the Newcastle Ottawa Scale (NOS) respectively to evaluate the quality of the literature, and extracted data from the included studies for meta-analysis using RevMan 5.4 and Stata 18.0. Results A total of 12 researches were ultimately included, consisting of 2 randomized controlled trials, 2 prospective cohort studies, and 8 retrospective cohort studies, involving a total of 76 403 patients. All researches were evaluated as high-quality. Meta-analysis showed that the ambulatory surgery group had advantages over the hospitalized surgery group in terms of operation time [MD=−21.07, 95%CI (−30.55, −11.58), P<0.001], length of hospital stay [MD=−2.17, 95%CI (−3.25, −1.09), P<0.001], hospitalization costs [SMD=−1.22, 95%CI (−2.18, −0.26), P=0.01], and overall postoperative complications [OR=0.48, 95%CI (0.32, 0.74), P<0.001]. There was no statistically significant difference between the two groups in terms of postoperative hoarseness [OR=0.62, 95%CI (0.24, 1.61), P=0.33] and postoperative chylothorax [OR=0.27, 95%CI (0.07, 1.07), P=0.06]. Conclusion Compared to conventional hospitalized lung tumor resection, ambulatory lung tumor resection can significantly reduce the patient’s surgery and hospital stay time, decrease hospitalization costs, and reduce the incidence of postoperative complications. Ambulatory surgery can improve hospital efficiency while reducing the economic burden on patients. It is worthy of further promotion and application.

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.

Objective: To analyze the current burden of autism spectrum disorder (ASD) among children and adolescents in China and globally, and to predict the disease burden from 2024 to 2035, providing a scientific basis for formulating relevant public health policies and intervention measures. Methods: Based on the Global Burden of Disease (GBD) database in 2023, the Joinpoint regression model was used to analyze the changing trends of the disease burden of ASD among children and adolescents in China and globally from 1990 to 2023, and the average annual percent change (AAPC) was calculated. An autoregressive integrated moving average (ARIMA) model was constructed to predict the disease burden trends of ASD among children and adolescents in China and globally from 2024 to 2035. Results: The prevalence and disability adjusted life years (DALYs) rate of ASD among children and adolescents in China increased from 452.69/100 000 and 86.67/100 000 in 1990 to 762.84/100 000 and 148.52/ 100 000 in 2023(AAPC=1.60%, 1.65%, both P <0.01). The prevalence and DALYs rate of ASD among children and adolescents globally increased from 648.49/100 000 and 123.47/100 000 to 862.44/100 000 and 167.16/100 000(AAPC=0.87%, 0.93%, both P <0.01). In 2023, the highest ASD prevalence and DALY rates occurred in children under 5 years old, with China reporting 848.14/100 000 and 166.69/100 000, both below the global averages of 928.80/100 000 and 181.34/100 000. Projections indicated that by 2035, the ASD prevalence and DALY rates in China would rise to 906.83/100 000 and 168.71/100 000, still below the global averages of 938.04/100 000 and 184.49/100 000. Conclusion The disease burden of ASD among children and adolescents in China and globally has generally increased from 1990 to 2023, with a higher risk of disease at younger ages.

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.

The circadian system maintains physiological homeostasis by precisely orchestrating 24-hour cycles of metabolic and cardiovascular functions. Circadian disruption has been substantiated as a contributor to cardiometabolic dysfunction, significantly elevating the risk of obesity, type 2 diabetes, hypertension, and cardiovascular diseases, thereby emerging as a crucial target for global chronic disease prevention. In 2025, the American Heart Association (AHA) issued a dedicated scientific statement that systematically reviewed the regulatory mechanisms of circadian rhythms and their intrinsic links to cardiometabolic health. It highlighted the pivotal role of modifiable behavioral factors, including light exposure, sleep-wake patterns, meal timing, and timing of physical activity, and proposed multi-faceted intervention strategies centered on chronotherapy. Considering the distinct circadian characteristics and chronic disease epidemiology in the Chinese population compared to Western counterparts, this article, grounded in the statement's core framework and incorporating evidence from localized Chinese research, provides a systematic interpretation of the biological basis of circadian rhythms, the pathophysiological mechanisms underlying disruption-related diseases, and potential intervention pathways. It particularly discusses the applicability of the statement's conclusions to clinical practice and public health strategies in China, aiming to offer an evidence-based reference for developing a cardiometabolic health support system tailored to the national context.

ObjectiveTo investigate the effect and mechanism of modified Sini San in ameliorating intestinal mucosal barrier by observing its effects on short chain fatty acids （SCFAs） and high mobility group protein B1 （HMGB1）/receptor of advanced glycation end products （RAGE） signaling pathways in chronic stress rats. MethodsThe 50 male SD rats were randomly divided into control group，model group，low-dose modified Sini San group （7.34 g·kg^-1·d^-1），high-dose modified Sini San group （14.68 g·kg^-1·d^-1），and Fructo-oligosaccharides group （3.15 g·kg^-1·d^-1），with 10 rats in each group. Except for the control group，all other groups were subjected to chronic unpredictable stress/social isolation to create a chronic stress model for 6 weeks. After 4 weeks of modeling，each treatment group was given corresponding drugs by gavage for 2 weeks while modeling. The control group and model group were given the same volume of physiological saline. The effects of Modified Sini San on behaviors，body weight，Bristol score in feces and fecal moisture content in chronic stress rats were observed. Hematoxylin and eosin （HE） staining was used to observe the pathological changes in the cecum. The content of SCFAs in the cecal contents of rats were detected by Gas chromatography-mass spectrometry （GC-MS）. Immunohistochemistry and Western blot were used to detect the expression of HMGB1/RAGE pathway related proteins in cecal tissue. The levels of ZO-1，Occludin，and Claudin-1 in the cecal tissue were detected by enzyme linked immunosorbent assay （ELISA）. ResultsCompared with the model group，the sucrose preference rate，total distance traveled and the number of grid crossings in the open field test of rats in the low-dose modified Sini San group were obviously increased （P<0.05， P<0.01），and the immobility time in the open field test and the immobility time in the forced swimming test of rats in the low-dose and high-dose modified Sini San groups were obviously reduced （P<0.05， P<0.01）. Meanwhile，the Bristol score and fecal moisture content of rats in the low and high dose groups of modified Sini San were obviously increased （P<0.05）. The low-dose group of modified Sini San had intact mucosal layer structure in the cecal tissue and reduced infiltration of inflammatory cells. The content of SCFAs in the cecal contents increased，with a obviously increase in the content of acetic acid，propionic acid，butyric acid，and isovaleric acid （P<0.05， P<0.01） and the expression levels of HMGB1，RAGE，Toll-like receptor 2（TLR2），Toll-like receptor 4（TLR4），tumor necrosis factor-α（TNF-α），and nuclear factor kappa-B p65（NF-κB p65） proteins in cecal tissue were significantly decreased （P<0.05， P<0.01） in low-dose group of modified Sini San. Meanwhile，the contents of ZO-1，Occludin，and Claudin-1 in the cecal tissue were obviously increased （P<0.01） in low-dose group of modified Sini San. ConclusionModified Sini San can improve the function of intestinal mucosal barrier in chronic stress rats by increasing the content of SCFAs in the intestine and inhibiting the HMGB1/RAGE pathway.

ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.