ObjectiveTo construct a large language model （LLM）-based intelligent pre-consultation system for traditional Chinese medicine （TCM） to improve efficacy of clinical practice. MethodsA TCM large language model was fine-tuned using DeepSpeed ZeRO-3 distributed training strategy based on YAYI 2-30B. A weighted undirected graph network was designed and an agent-based syndrome differentiation model was established based on relationship data extracted from TCM literature and clinical records. An agent collaboration framework was developed to integrate the TCM LLM with the syndrome differentiation model. Model performance was comprehensively evaluated by Loss function， BLEU-4， and ROUGE-L metrics， through which training convergence， text generation quality， and language understanding capability were assessed. Professional knowledge test sets were developed to evaluate system proficiency in TCM physician licensure content， TCM pharmacist licensure content， TCM symptom terminology recognition， and meridian identification. Clinical tests were conducted to compare the system with attending physicians in terms of diagnostic accuracy， consultation rounds， and consultation duration. ResultsAfter 100 000 iterations， the training loss value was gradually stabilized at about 0.7±0.08， indicating that the TCM-LLM has been trained and has good generalization ability. The TCM-LLM scored 0.38 in BLEU-4 and 0.62 in ROUGE-L， suggesting that its natural language processing ability meets the standard. We obtained 2715 symptom terms， 505 relationships between diseases and syndromes， 1011 relationships between diseases and main symptoms， and 1 303 600 relationships among different symptoms， and constructed the Agent of syndrome differentiation model. The accuracy rates in the simulated tests for TCM practitioners， licensed pharmacists of Chinese materia medica， recognition of TCM symptom terminology， and meridian recognition were 94.09%， 78.00%， 87.50%， and 68.80%， respectively. In clinical tests， the syndrome differentiation accuracy of the system reached 88.33%， with fewer consultation rounds and shorter consultation time compared to the attending physicians （P＜0.01）， suggesting that the system has a certain pre- consultation ability. ConclusionThe LLM-based intelligent TCM pre-diagnosis system could simulate diagnostic thinking of TCM physicians to a certain extent. After understanding the patients' natural language， it collects all the patient's symptom through guided questioning， thereby enhancing the diagnostic and treatment efficiency of physicians as well as the consultation experience of the patients.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Exercise-induced metabolic remodeling is a fundamental adaptive process whereby the body reorganizes systemic and cellular metabolism to meet the dynamic energy demands posed by physical activity. Emerging evidence reveals that such remodeling not only enhances energy homeostasis but also profoundly influences immune function through complex molecular interactions involving glucose, lipid, and protein metabolism. This review presents an in-depth synthesis of recent advances, elucidating how exercise modulates immune regulation via metabolic reprogramming, highlighting key molecular mechanisms, immune-metabolic signaling axes, and the authors’ academic perspective on the integrated “exercise-metabolism-immunity” network. In the domain of glucose metabolism, regular exercise improves insulin sensitivity and reduces hyperglycemia, thereby attenuating glucose toxicity-induced immune dysfunction. It suppresses the formation of advanced glycation end-products (AGEs) and interrupts the AGEs-RAGE-inflammation positive feedback loop in innate and adaptive immune cells. Importantly, exercise-induced lactate, traditionally viewed as a metabolic byproduct, is now recognized as an active immunomodulatory molecule. At high concentrations, lactate can suppress immune function through pH-mediated effects and GPR81 receptor activation. At physiological levels, it supports regulatory T cell survival, promotes macrophage M2 polarization, and modulates gene expression via histone lactylation. Additionally, key metabolic regulators such as AMPK and mTOR coordinate immune cell energy balance and phenotype; exercise activates the AMPK-mTOR axis to favor anti-inflammatory immune cell profiles. Simultaneously, hypoxia-inducible factor-1α (HIF-1α) is transiently activated during exercise, driving glycolytic reprogramming in T cells and macrophages, and shaping the immune landscape. In lipid metabolism, exercise alleviates adipose tissue inflammation by reducing fat mass and reshaping the immune microenvironment. It promotes the polarization of adipose tissue macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. Moreover, exercise alters the secretion profile of adipokines—raising adiponectin levels while reducing leptin and resistin—thereby influencing systemic immune balance. At the circulatory level, exercise improves lipid profiles by lowering pro-inflammatory free fatty acids (particularly saturated fatty acids) and triglycerides, while enhancing high-density lipoprotein (HDL) function, which has immunoregulatory properties such as endotoxin neutralization and macrophage cholesterol efflux. Regarding protein metabolism, exercise triggers the expression of heat shock proteins (HSPs) that act as intracellular chaperones and extracellular immune signals. Exercise also promotes the secretion of myokines (e.g., IL-6, IL-15, irisin, FGF21) from skeletal muscle, which modulate immune responses, facilitate T cell and macrophage function, and support immunological memory. Furthermore, exercise reshapes amino acid metabolism, particularly of glutamine, arginine, and branched-chain amino acids (BCAAs), thereby influencing immune cell proliferation, biosynthesis, and signaling. Leucine-mTORC1 signaling plays a key role in T cell fate, while arginine metabolism governs macrophage polarization and T cell activation. In summary, this review underscores the complex, bidirectional relationship between exercise and immune function, orchestrated through metabolic remodeling. Future research should focus on causative links among specific metabolites, signaling pathways, and immune phenotypes, as well as explore the epigenetic consequences of exercise-induced metabolic shifts. This integrated perspective advances understanding of exercise as a non-pharmacological intervention for immune regulation and offers theoretical foundations for individualized exercise prescriptions in health and disease contexts.

AIM: To investigate the clinical efficacy of pars plana vitrectomy(PPV)combined with fovea-sparing internal limiting membrane(ILM)peeling and silicone oil(SO)tamponade for treating pathological myopic foveoschisis(PMF).METHODS:This study is a retrospective observational analysis of 10 cases(10 eyes)diagnosed with PMF that underwent PPV with fovea-sparing ILM peeling and SO tamponade between January 2023 and November 2024. The best-corrected visual acuity(BCVA), central foveal thickness(CFT), foveoschisis(FS), and the detachment and reattachment of FS and macular fovea were assessed preoperatively and at 1 wk, 1 and 3 mo postoperatively.RESULTS:Among the 10 cases of PMF patients(10 eyes), the complete reattachment rate was 30%(3 eyes), while partial reattachment was observed in 70%(7 eyes). At 3 mo postoperatively, BCVA(LogMAR)was significantly improved to 0.957±0.393 compared with 1.432±0.509 before surgery(P<0.05), and both CFT(437.9±180.4 vs. 207.5±76.1 μm)and FS(686.5±172.2 vs. 290.7±86.6 μm)showed significant decreases(P<0.05). No complications such as macular hole, retinal detachment, silicone oil emulsification, or endophthalmitis were observed during the surgery or throughout the follow-up period.CONCLUSION:PPV with SO tamponade and fovea-sparing ILM peeling has been demonstrated to facilitate both visual acuity improvement and anatomical reattachment in cases of PMF.

ObjectiveTo construct an animal model of respiratory syncytial virus（RSV）-infected pneumonia suitable for preclinical studies. MethodsThe virulence of RSV to the four cell lines was observed by cytopathic effect （CPE）， and 50% tissue culture infective dose（TCID₅₀） was calculated. Twenty BALB/c mice were randomly divided into a normal group and a model group. Six BALB/c-hIGF1R mice served as the humanized IGF1R model group. Except for the normal group， the other groups received intranasal RSV infection on days 1 and 3 to establish a viral pneumonia model. The efficacy of establishing an RSV-induced pneumonia animal model based on humanized insulin-like growth factor 1 receptor （IGF1R） mice was evaluated by measuring organ indices， peripheral blood lymphocyte percentages， pulmonary pathology and imaging， and pulmonary viral load. Additionally， ten BALB/c mice served as normal group， and thirty-two BALB/c-hIGF1R mice were randomly assigned to humanized IGF1R model group， ribavirin group （82.5 mg·kg^-¹·d^-¹）， and high and low dose groups of Lianhua Qingwen （3.3 mg·kg^-¹·d^-¹ ， 1.65 mg·kg^-¹·d^-¹）， with 8 mice per group. The viral load in lung tissue was measured after ribavirin and Lianhua Qingwen intervention， and the model was applied to the evaluation of anti-RSV drugs. ResultsIn the lungs of the humanized IGF1R model group， large solid and diffuse ground-glass shadows were seen， and the lung volume was significantly increased （P<0.01）. The lung index was significantly increased （P<0.01）， and both the spleen index and thymus index were significantly decreased （P<0.01）. The percentages of CD3⁺ and CD4⁺T cells were significantly decreased （P<0.05）， and there was a large amount of inflammation and stasis in the perivascular area of the lung tissue， which was predominantly characterized by lymphocytes. The endothelium of blood vessels was partially detached， with a small number of eosinophils. After infecting BALB/c-hIGF1R mice with RSV， the expression of viral nucleic acids in the lung tissue of the mice was significantly increased， with significant differences compared with the normal group （P<0.01）. The expression of viral nucleic acids in the ribavirin group and the high and low dose groups of Lianhua Qingwen was significantly reduced， with significant differences compared with the normal group （P<0.01）. ConclusionHumanized IGF1R mice are more susceptible to respiratory SVC， and the animal model of RSV-infected pneumonia based on humanized IGF1R mice was successfully constructed， which is suitable for the evaluation of anti-RSV drugs.

ObjectiveTo construct an animal model of respiratory syncytial virus（RSV）-infected pneumonia suitable for preclinical studies. MethodsThe virulence of RSV to the four cell lines was observed by cytopathic effect （CPE）， and 50% tissue culture infective dose（TCID₅₀） was calculated. Twenty BALB/c mice were randomly divided into a normal group and a model group. Six BALB/c-hIGF1R mice served as the humanized IGF1R model group. Except for the normal group， the other groups received intranasal RSV infection on days 1 and 3 to establish a viral pneumonia model. The efficacy of establishing an RSV-induced pneumonia animal model based on humanized insulin-like growth factor 1 receptor （IGF1R） mice was evaluated by measuring organ indices， peripheral blood lymphocyte percentages， pulmonary pathology and imaging， and pulmonary viral load. Additionally， ten BALB/c mice served as normal group， and thirty-two BALB/c-hIGF1R mice were randomly assigned to humanized IGF1R model group， ribavirin group （82.5 mg·kg^-¹·d^-¹）， and high and low dose groups of Lianhua Qingwen （3.3 mg·kg^-¹·d^-¹ ， 1.65 mg·kg^-¹·d^-¹）， with 8 mice per group. The viral load in lung tissue was measured after ribavirin and Lianhua Qingwen intervention， and the model was applied to the evaluation of anti-RSV drugs. ResultsIn the lungs of the humanized IGF1R model group， large solid and diffuse ground-glass shadows were seen， and the lung volume was significantly increased （P<0.01）. The lung index was significantly increased （P<0.01）， and both the spleen index and thymus index were significantly decreased （P<0.01）. The percentages of CD3⁺ and CD4⁺T cells were significantly decreased （P<0.05）， and there was a large amount of inflammation and stasis in the perivascular area of the lung tissue， which was predominantly characterized by lymphocytes. The endothelium of blood vessels was partially detached， with a small number of eosinophils. After infecting BALB/c-hIGF1R mice with RSV， the expression of viral nucleic acids in the lung tissue of the mice was significantly increased， with significant differences compared with the normal group （P<0.01）. The expression of viral nucleic acids in the ribavirin group and the high and low dose groups of Lianhua Qingwen was significantly reduced， with significant differences compared with the normal group （P<0.01）. ConclusionHumanized IGF1R mice are more susceptible to respiratory SVC， and the animal model of RSV-infected pneumonia based on humanized IGF1R mice was successfully constructed， which is suitable for the evaluation of anti-RSV drugs.

AIM: To investigate the genetic association and potential causal relationship between diabetic nephropathy(DN)and diabetic retinopathy(DR), and to elucidate their shared molecular mechanisms through differential gene expression analysis and Mendelian randomization(MR).METHODS: Transcriptomic data of DN and DR were obtained from the Gene Expression Omnibus(GEO)database and analyzed for differentially expressed genes(DEGs). Genes meeting the significance threshold(log2FC>1, P<0.05)were identified, followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis to explore shared biological pathways. Using genome-wide association study(GWAS)summary statistics for DN and DR, two-sample MR analysis was performed, with DN as the exposure and DR as the outcome. The causal effect was primarily estimated with the inverse-variance weighted(IVW)method, and sensitivity analyses were conducted to assess robustness.RESULTS: MR analysis revealed that DN significantly increased the risk of DR. IVW estimates indicated that the odds ratio(OR)for non-proliferative DR(NPDR)was 3.23(95% CI: 2.12-4.95, P<0.001), and the OR for proliferative DR(PDR)was 1.10(95% CI: 1.06-1.15, P<0.001). DEG analysis identified several key genes, including FN1, COL1A2, and THBS2. FN1 and COL1A2 are involved in extracellular matrix remodeling and fibrosis, contributing to vascular permeability alterations and microvascular damage in diabetic complications. THBS2 is closely associated with angiogenesis and vascular homeostasis, suggesting its potential role in DR. KEGG enrichment analysis showed that these DEGs were mainly enriched in advanced glycation end products(AGEs)-RAGE signaling, extracellular matrix degradation, and oxidative stress pathways, all of which are highly relevant to the pathogenesis of DN and DR.CONCLUSION: This study demonstrates the genetic association between DN and DR using MR and DEGs analyses. The shared mechanisms, particularly involving extracellular matrix remodeling, inflammatory response, and angiogenesis, may serve as novel therapeutic targets and provide a theoretical basis for the early diagnosis and targeted treatment of diabetic complications.