Chronic heart failure （CHF） is a major global public health problem， and myocardial infarction is one of its main causes. The mouse model of heart failure induced by coronary artery ligation is widely used in the study of CHF， while the TCM syndrome attributes of this model have not yet been clarified. According to the theory of correspondence between prescriptions and syndromes， the method of syndrome identification by prescription efficacy is an important means of current syndrome research of animal models. This method deduces the syndrome characteristics of animal models through prescription efficacy. Taking the four basic syndrome elements of Qi， blood， Yin and Yang as the classification reference， this study used coronary artery ligation to construct a mouse model of CHF and treated the model with four representative TCM injections with the effects of replenishing Qi， warming Yang， nourishing Yin， and activating blood and enalapril. Echocardiography， tongue color parameters， histopathology， serum N-terminal pro-brain natriuretic peptide （NT-proBNP） and cardiac troponin Ⅰ （cTnⅠ） levels， and systematically explored the TCM syndrome attributes of this model. The results showed that the coronary ligation model presented an obvious cardiac function decline， myocardial fibrosis， infarct size expansion， and purple dark tongue， which were consistent with the basic syndrome characteristics of blood stasis in CHF. Danhong injection had significant effects of improving the cardiac function， alleviating myocardial fibrosis， and reducing serum NT-proBNP and cTnⅠ levels. Huangqi Injection and Shenfu injection can improve the cardiac function and tongue color parameters， with limited effects. The effect of Shenmai injection group was not obvious. This study verifies that the established model conforms to blood stasis syndrome through the method of syndrome identification by prescription efficacy， which provides an experimental basis for the study of TCM syndrome mechanism of CHF.

Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.

Developing an intelligent agent for integrated traditional Chinese and western medicine diagnosis and treatment based on clinical practice guidelines is a key approach to advancing the standardization and intelligent deve-lopment of traditional Chinese medicine （TCM） and to supporting clinical decision-making. This paper argues for the necessity of building a knowledge base using guidelines as the sole data source， systematically identifies five core methodological challenges across the entire process， and proposes corresponding solutions. An ontology framework capable of distinguishing between TCM and western medicine concepts should be designed to address the difficulty of knowledge integration. A closed-loop "algorithm-based extraction-expert review" model is adopted to reduce data extraction errors. Expert consensus is incorporated to address decision gaps in specific clinical scenarios outlined in the guidelines， while a multi-stage， standardized output process for the AI system is established to eliminate model hallucinations. Furthermore， an evaluation framework reflecting clinical applicability is developed to enhance the AI system's accuracy and stability. Throughout the research process， it is essential to ensure the in-depth and continuous participation of multidisciplinary experts， strictly control the selection and quality evaluation of guidelines， and rely on the expert consensus method to address decision gaps in the knowledge base. Additionally， continuous validation and iterative optimization of intelligent agents are required to ensure the accuracy and stability of generated outputs. Limitations remain in the mechanisms for real-time knowledge synchronization in intelligent diagnostic and treatment systems， and further validation through large-scale real-world studies is warranted.

BACKGROUND:Degenerative diseases caused by bone and muscle degeneration are major reasons for the decline in physical function and mobility,increased fragility fractures,and high mortality rates in the elderly,significantly affecting their health and quality of life.OBJECTIVE:To review the research progress in the mechanisms of muscle-bone interaction and the etiology,prevention,and treatment of related diseases.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature published from 2014 to 2024.The search terms were"muscle-bone crosstalk,musculoskeletal system,inter-tissue communication,myokines,osteokines,osteosarcopenia,sarcopenia,osteoporosis,bone regeneration,fibro-adipogenic progenitors"in Chinese and English.By reading the articles,we eliminated irrelevant,outdated,and poorly focused literature,and finally 94 articles were included for review.RESULTS AND CONCLUSION:Mechanical interaction,secretion factor interaction,and stem cell interaction between muscle and bone are crucial for the metabolism and regeneration regulation of the musculoskeletal system.Systemic interventions targeting biochemical signals of muscle factors(such as myostatin and irisin)and bone factors(such as nuclear factor-κB receptor-activating factor ligand and sclerostin)can improve the quality and function of skeletal muscle and bone,and have positive effects on fracture healing.In recent years,it has been found that related stem cells in the musculoskeletal system can interact,with the activation of muscle progenitor cells(such as fibro-adipogenic progenitors)having a significant impact on bone growth,repair,and regeneration.Research on the mechanisms of muscle-bone interaction can provide insights into the etiology,prevention,and treatment of related diseases.However,there are currently no effective clinical treatments for muscle-bone comorbidities,with most research still at the cellular and animal experiment stage.Therefore,extensive research is needed in the future to gradually move from experiments to clinical applications,developing more targeted therapies and drugs to better serve clinical needs.

Angiopoietin-like proteins(ANGPTLs)are a family of proteins that are structurally similar to angio-poietin.So far,eight ANGPTLs have been discovered,namely ANGPTL1 to ANGPTL8.They are not only angiogenic fac-tors,but also play a pivotal role in various pathophysiological processes such as glucose and lipid metabolism,redox regu-lation,chronic inflammation and cancer,and having a close connection with the occurrence and development of metabolic diseases.This review focuses on the mechanism of action of ANGPTLs in metabolic associated fatty liver disease,in order to make a contribution to the prevention and treatment of MAFLD and concurrent diseases.

Objective:To evaluate the effect and causality of serum metabolites on the pathogenesis of ulcerative colitis (UC), so as to provide reference for nutritional programs for patients with UC.Methods:Two-sample Mendelian randomization (MR) analysis was performed to estimate the causal relationship between serum metabolites and UC. Genome-wide association studies (GWAS) of 1 400 metabolites were performed, with the metabolites as exposure and UC as outcome. Inverse-variance weighted (IVW) was used to calculate causal estimates. Four other MR methods with different modeling assumptions including MR-Egger, weighted median, weighted mode, and simple mode were used as additional analyses to improve the stability of the results. The results were validated through heterogeneity and pleiotropy tests. Finally, the possible causal metabolites were analyzed by metabolic pathway analysis.Results:MR analysis revealed that 85 metabolites had a possible causal relationship with UC. Among them, phosphatidylglycerol 1,2-dipalmitoyl-gpc (DPPC) ( P=2.75×10 -6) and isovaleryl carnitine (C5) ( P=1.84×10 -5) were significant risk factors for UC. Metabolic pathway analysis identified 5 metabolic pathways that might be affected by these metabolites (all P<0.05), among which the porphyrin ( P=0.004) and pyrimidine metabolic pathways ( P=0.008) had higher confidence in impacting UC. Conclusions:There are causal relationships between some serum metabolites (in particular 1,2-dipalmitoyl-GPC and isovalerylcarnitine) and the risk of UC. The porphyrin and pyrimidine metabolic pathways may impact the pathogenesis of UC.

Objective:To explore the impact of neoadjuvant immunotherapy on the occurrence of low anterior resection syndrome (LARS) in patients with locally advanced rectal cancer who underwent restorative anterior resection, and to analyze associated risk factors.Methods:This study was an observational study. Patients with adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma of the rectum located 0-10 cm from the anal verge who received neoadjuvant immunotherapy followed by curative restorative anterior resection at Peking University Cancer Hospital between November 2019 and February 2024 were retrospectively examined. Exclusion criteria were as follows: (1) metastasis detected preoperatively;(2) follow-up <1 year or stoma closure <6 months; (3) local recurrence or metastasis during follow-up; and (4) stoma without closure or stoma re-creation. The Chinese version of the LARS questionnaire was used to assess bowel function by telephone interview, and patients were classified based on score into no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30–42 points). The incidence of LARS, major LARS, and associated risk factors were analyzed.Results:A total of 52 patients (34 men) were included for analysis. Mean age was 58.0 ± 9.8 years and mean body mass index was 25.1 ± 2.6 kg/m 2. Median follow-up was 27.5 months (range, 12.0-63.7). Median LARS score was 21 (range, 1-41). Twenty-six patients (50.0%) developed LARS after surgery, and half of these (13 cases) were classified as major LARS. Stool clustering (repeated defecation within 1 hour) was observed in 80.8% (42/52) of patients. Distance between the tumor edge and the dentate line [odds ratio (OR), 3.597; 95% confidence interval (CI), 1.140-11.360; P=0.026], management of the left colic artery (OR, 0.133; 95% CI, 0.026-0.691; P=0.008), and interval of stoma closure (OR, 5.250; 95%CI, 1.381-19.960; P=0.011) were significantly associated with LARS. Interval of stoma closure was significantly associated with major LARS (OR, 4.200; 95%CI, 1.064–16.584; P=0.040). In multivariate logistic regression, ≤3.5 cm between the tumor edge and the dentate line (OR, 7.407; 95%CI, 1.377-40.000; P=0.020), non-preservation of the left colic artery (OR, 8.403; 95%CI, 1.183-58.823; P=0.033) and interval of stoma closure >6 months (OR, 10.865; 95% CI, 2.039-57.896; P=0.005) were independent risk factors for LARS. Interval of stoma closure >6 months (OR, 4.356; 95% CI, 1.105-17.167; P=0.035) were independent risk factors for major LARS. Conclusion:Patients with locally advanced rectal cancer treated with neoadjuvant immunotherapy experienced a high incidence of LARS after curative surgery, with stool clustering as the predominant symptom. Tumor edge–dentate line distance ≤3.5 cm, non-preservation of the left colic artery, and interval of stoma closure >6 months were risk factors for LARS.

Objective:To evaluate the efficacy and safety of Janus kinase (JAK) inhibitors in the treatment of acute severe ulcerative colitis (ASUC).Methods:A retrospective cohort study was conducted. Patients with ASUC treated with JAK inhibitors at the First Affiliated Hospital of Air Force Medical University between January 2021 and March 2024 were enrolled. The primary endpoints were clinical response rate at 1 week and colectomy rate at 90 days. The secondary endpoints were clinical response rate and clinical remission rate at 8 weeks, and adverse events rate at 90 days.Results:A total of 15 patients with ASUC (7 men, 8 women; mean age, 42.47±9.92 years) were included. Eight patients were treated with upadacitinib, and 7 with tofacitinib. The clinical response rate at 1 week was 53.3% (8/15), the colectomy rate at 90 days was 20.0% (3/15), the clinical response rate at 8 weeks was 60.0% (9/15), and the clinical remission rate at 8 weeks was 33.3% (5/15). During the 90-day follow-up, only 1 patient (6.7%) treated with tofacitinib experienced a mild leukopenia.Conclusion:JAK inhibitors are effective for ASUC with the high safety.

Objective:To evaluate the effect and causality of serum metabolites on the pathogenesis of ulcerative colitis (UC), so as to provide reference for nutritional programs for patients with UC.Methods:Two-sample Mendelian randomization (MR) analysis was performed to estimate the causal relationship between serum metabolites and UC. Genome-wide association studies (GWAS) of 1 400 metabolites were performed, with the metabolites as exposure and UC as outcome. Inverse-variance weighted (IVW) was used to calculate causal estimates. Four other MR methods with different modeling assumptions including MR-Egger, weighted median, weighted mode, and simple mode were used as additional analyses to improve the stability of the results. The results were validated through heterogeneity and pleiotropy tests. Finally, the possible causal metabolites were analyzed by metabolic pathway analysis.Results:MR analysis revealed that 85 metabolites had a possible causal relationship with UC. Among them, phosphatidylglycerol 1,2-dipalmitoyl-gpc (DPPC) ( P=2.75×10 -6) and isovaleryl carnitine (C5) ( P=1.84×10 -5) were significant risk factors for UC. Metabolic pathway analysis identified 5 metabolic pathways that might be affected by these metabolites (all P<0.05), among which the porphyrin ( P=0.004) and pyrimidine metabolic pathways ( P=0.008) had higher confidence in impacting UC. Conclusions:There are causal relationships between some serum metabolites (in particular 1,2-dipalmitoyl-GPC and isovalerylcarnitine) and the risk of UC. The porphyrin and pyrimidine metabolic pathways may impact the pathogenesis of UC.

Objective:To investigate the effect of natural plant compound puerarin(PUE)on expression of NLRP3 inflamma-some in macrophages and its effect in ulcerative colitis(UC)in mice.Methods:A mouse model of UC was established using dextran sulfate sodium(DSS).Mice received PUE via gavage for 7 consecutive days,body weight,disease activity index and colon length were measured.HE staining was performed to assess tissue pathological damage.Flow cytometry was used to determine the proportion of peripheral blood mononuclear cells in colonic lamina propria.Immunofluorescence was employed to assess the colocalization of NLRP3 inflammasome and macrophages.qRT-PCR was conducted to measure mRNA expression levels of pro-inflammatory cytokines and NLRP3-related genes in colonic tissues.Protein expression levels of ZO-1,Occludin,cleaved caspase-1 and IL-1β in colonic tissues were detected by Western blot.A cell model was established using lipopolysaccharide(LPS)and adenosine triphosphate(ATP).mRNA expression levels of genes related to NLRP3 inflammasome were detected by qRT-PCR.Western blot was used to detect effects of PUE on expression levels of proteins related to NLRP3 inflammasome and NF-κB signaling pathway.Results:PUE treatment signifi-cantly improved symptoms of DSS-induced UC in mice,including body weight,disease index,colon length and pathological damage.Following PUE intervention,infiltration of Ly6C+MHC Ⅱ-monocyte derived macrophages in the colonic lamina propria was reduced.Expression levels of pro-inflammatory cytokines and NLRP3 inflammasome related molecules in colonic tissues were decreased.PUE treatment increased expression levels of ZO-1 and Occludin in intestinal epithelial cells.In vitro experiments confirmed that PUE reduced expression levels of NLRP3 inflammasome-related molecules in macrophages induced by LPS combined with ATP,as well as protein expression level of p-NF-κB p65.Conclusion:PUE significantly alleviates the symptoms of UC by reducing intestinal tissue inflamma-tion and repairing the epithelial barrier.The mechanism may involve regulating NF-κB signaling pathway,thereby reducing the forma-tion and activation of NLRP3 inflammasome in macrophages.