The disease-syndrome combination animal model in traditional Chinese medicine （TCM） andrology serves as an important bridge linking TCM theory with modern medical research， providing a key experimental platform for elucidating the 'syndrome-disease' correlation mechanism in male-specific diseases and for screening effective prescriptions. This article reviews recent progress in animal model research on common TCM andrological diseases， including prostatic diseases， sexual dysfunction， and male infertility， with a focus on analyzing the application， advantages， and disadvantages of various modeling strategies， such as immune induction， hormonal intervention， and multi-factor combination across different syndrome types. However， despite breakthroughs in model construction techniques， current research still faces several challenges， including insufficient standardization of syndrome differentiation and difficulties in quantifying TCM-specific indicators. Future studies need to optimize model evaluation systems by integrating modern technologies， in order to promote the standardization and internationalization of TCM andrology research.

Retinal degenerative diseases are a group of blinding ocular disorders characterized by progressive and irreversible loss of retinal neural cells. They mainly include age-related macular degeneration and retinitis pigmentosa. At present, there are no curative clinical therapies capable of reversing the disease course. Patients have poor long-term visual prognosis, imposing a heavy public-health burden on families and society. Mesenchymal stem cell(MSC)-derived exosomes, as a novel cell-free therapeutic vector, have emerged as a research hotspot due to their low immunogenicity, no tumorigenic risk, and excellent tissue barrier penetration ability. This review systematically summarizes the core mechanisms of MSC-derived exosomes in regulating immune inflammation, inhibiting apoptosis, and promoting retinal neuroprotection and structural/functional recovery via miRNA and tsRNA, compares the efficacy differences and existing controversies among exosomes from different sources, and outlines the advances in intraocular delivery technologies and engineering modification strategies. Combined with preclinical and clinical data, the current bottlenecks and safety evidence for clinical translation were objectively described. Meanwhile, in view of the heterogeneity among existing studies, this review proposes future directions including standardized preparation and the establishment of efficacy evaluation systems, so as to provide theoretical references for the development of novel therapeutic strategies for retinal degenerative diseases.

Objective To explore the effect and mechanism of Gegen Qinlian decoction (GQD) on myocardial injury induced by high-fat diet combined with streptozotocin in type 2 diabetic mice through network pharmacology and animal experiments. MethodsNetwork pharmacology was applied to screen the potential signaling pathways of GQD in the intervention of diabetic heart disease (DHD). A total of 36 specific pathogen-free (SPF) male C57BL/6J mice aged 8 weeks were acclimatized for 1 week and randomly divided into a normal control group (n=6) and a model group (n=30). Mice in the model group were fed a 60% high-fat diet and 5% glucose water for 4 weeks, and were intraperitoneally injected with 100 mg/kg streptozotocin after 12 h of fasting to establish the type 2 diabetes model. Mice in the normal control group were given a conventional diet and drinking water, and were intraperitoneally injected with an equal volume of citrate buffer after 12 h of fasting at the same time point. After successful establishment of the diabetic mouse model, the model mice were randomly divided into five groups according to body weight: model control group, GQD low-dose group, GQD medium-dose group, GQD high-dose group, and metformin positive control group, with 6 mice in each group. After 6 weeks of intragastric administration of corresponding doses of GQD, metformin, and ddH₂O respectively, all mice in the six groups (one normal control group and five model groups) were anesthetized with inhaled 2% isoflurane, blood samples were collected via eyeball enucleation, and heart tissues were harvested after euthanasia by cardiac exsanguination. Hematoxylin-eosin (HE) staining and wheat germ agglutinin (WGA) staining were performed to observe the pathological damage of myocardial tissues and measure the cross-sectional area of cardiomyocytes. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of pro-inflammatory cytokines in serum. Immunohistochemical staining was adopted to determine the protein expression levels of receptor for advanced glycation end products (RAGE), nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), and phosphorylated nuclear factor-κB p65 (p-p65) in myocardial tissues. ResultsNetwork pharmacology analysis revealed that the targets of GQD against DHD were significantly enriched in inflammatory pathways, including the advanced glycation end products (AGEs)-RAGE axis, tumor necrosis factor (TNF) and interleukin-17 (IL-17) signaling pathways. HE and WGA staining results showed that, compared with the normal control group, the model control group exhibited myocardial fiber rupture, cardiomyocyte swelling, and significantly increased cardiomyocyte cross-sectional area (P<0.05). Compared with the model control group, GQD intervention significantly ameliorated the pathological changes, including myocardial fiber rupture, cell swelling, and cardiomyocyte hypertrophy. The results of immunohistochemical staining and ELISA indicated that compared with the model control group, GQD intervention markedly downregulated the protein expression of RAGE, NLRP3, and p-p65 in myocardial tissues, as well as the levels of serum pro-inflammatory cytokines (P<0.05). ConclusionGQD can effectively alleviate myocardial pathological injury in diet-induced type 2 diabetic mice, and its mechanism may be related to inhibiting the activation of the RAGE/p-p65/NLRP3 signaling pathway and reducing myocardial inflammatory response.

Objective To investigate the predictive value of the triglyceride glucose (TyG) index in major adverse cardiovascular events (MACE) in patients after coronary artery bypass grafting (CABG) surgery. Methods A retrospective collection of patients with coronary heart disease who underwent CABG treatment in the Department of Cardiac Surgery Ward 1, the 7th People’s Hospital of Zhengzhou, from 2015 to 2024 was conducted. The X-tile software was used to calculate the optimal cutoff value of the TyG index, and patients were divided into two groups based on this optimal cutoff value. The association between the TyG index and MACE was explored through univariate analysis, Kaplan-Meier survival curve analysis, and Cox regression analysis. The predictive ability of the TyG index was evaluated by important factor ranking and the area under the receiver operating characteristic curve (AUC). Results A total of 998 patients were included, with 630 patients having a TyG index ≤8.80, including 438 males and 192 females, with a median age of 60 (55, 65) years; and 368 patients with a TyG index >8.80, including 236 males and 132 females, with a median age of 63 (57, 69) years. Cumulative survival curves showed that the incidence of MACE in the TyG index≤8.80 group was significantly lower than that in the TyG index>8.80 group (log-rank test, P<0.001). Cox regression analysis indicated that TyG>8.80 was an independent risk factor for MACE [HR=2.581, 95%CI (1.201, 5.549), P<0.001]. In the important factor ranking, the TyG index had the greatest impact on MACE. The TyG index could enhance the predictive ability of the MACE prediction model, with the AUC increasing from 0.712 to 0.872. Conclusion The TyG index is independently associated with MACE after CABG, and may improve the discriminative performance of the predictive model in internal samples; however, prospective, multicenter studies and external validation are still required for confirmation.

Objective To screen the mutations of ABCC8 gene in probands of maturity-onset diabetes of the young pedigrees,and investigate it sgenetic and clinical characteristics.Methods Whole exome sequencing were performed to screen ABCC8 mutations in 56 MODY probands who were admitted to Department of Endocrinology and Metabolism,Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2021 to December 2023.The mutations were verified by Sanger sequencing,and all participants were genotyped.Clinical phenotypes of the mutation carriers were compared with non-DM controls within the families.The identified mutations were evaluated by bioinformatic softwires.Then the pharmacogenomic characteristics of the mutation carriers were analyzed.Results Two heterozygous mutations D655V and R825Q were identified in two MODY probands and their families respectively,and the D655V was a novel mutation.Bioinformatics studies showed that both mutations were deleterious and pathogenic.In comparison with non-DM controls in the two families,mutation carriers with diabetes exhibited significantly lower fasting insulin/fasting plasma glucose,two-hour postprandial insulin/two-hour postprandial insulin plasma glucose,homeostatic model assessment-β(P<0.05).Treatment with oral hypoglycemic agents such as metformin or insulin in these mutation carriers resulted in a moderate reduction in plasma glucose levels.However,switching to targeted Sulfonylurea's(SUs)proved to be more effective.Conclusions In this study,the prevalence of MODY12 is 3.6%in these MODY pedigrees.The remarkable hypoglycemic efficacy of SUs suggests that both D655V and R825Q were activating mutations of ABCC8,and maybe the cause of MODY12 characterized by impaired insulin secretion.

Objective:To investigate the role and mechanism of TrxR1 in reprogramming tumor-associated macrophage in breast cancer,providing novel insights and theoretical foundations for clinical breast cancer treatment.Methods:TISIDB database was used to analyze the relationship between TXNRD1(encoding TrxR1)and tumor immunity.Mouse breast cancer 4T1 cells conditioned medium was collected and co-cultured with bone marrow-derived macrophage(BMDM)cells for 48 h to detect the expression of macrophage immunosuppression-related factors.TrxR1 secretion by tumor cells was measured using ELISA kits.TXNRD1 knockdown efficiency was verified via Western blot.Fluorescence quantitative PCR(qPCR)and flow cytometry were used to detect the expression levels of macrophage immunosuppressive factors after TXNRD1 knockdown in tumor cells.JASPAR database was used to analyze the potential regulatory factors,and Western blot was used to verify the expression of pathway-related proteins.Results:Database analysis found that TXNRD1 expression positively correlated with survival risk indices across multiple cancers,with the strongest association observed in breast cancer.Further analysis found that elevated TXNRD1 expression correlated with reduced infiltration of M1 macrophages and natural killer(NK)cells,but increased M2 macrophage infiltration.qPCR and flow cytometry demonstrated that tumor-conditioned medium enhanced macrophage immunosuppression,whereas medium from TXNRD1-knockdown tumor cells suppressed this effect.And TrxR1-neutralizing antibodies could also reversed this effect.JASPAR database analysis identified STAT3 and STAT6 as potential transcriptional regulators,and Western blot confirmed that TXNRD1-knockdown tumor cells conditioned medium inhibited STAT6 pathway activation in macrophages.Conclusion:In the tumor microenvironment,breast tumor-derived TrxR1 promotes macrophage immunosuppression,potentially through activation of the STAT6 signaling pathway.

Objective:To investigate the value of serum IgG4 detection in diagnosis,treatment,evaluation and outcome of IgG4-associated diseases(IgG4-RD).Methods:By integrating the clinical data of patients,retrospectively and systematically analyze the results of common laboratory examinations,imaging examinations,pathological examinations,etc.26 patients who were diagnosed with IgG4-RD in Huaian First Hospital Affiliated to Nanjing Medical University from March 2013 to October 2023.Results:The median age of onset was 65(31～90)years old,and the male to female ratio was 3.33∶1.The first three symptoms were abdominal discomfort,skin scleral yellow stain and fever.Patients mainly involved multiple organs,the most commonly involved organs were lung,pancreas,liver,kidney,bile duct.Compared with the control group,NLR,PLR,ESR,CRP,TBIL,DBIL,ALT,AST,GGT,IgG,IgA and IgM were all abnormally elevated in the first hematological,biochemical and immune tests of the patients,the difference was statisti-cally significant,while C3 and C4 were all decreased,but there was no statistical difference.The first IgG4 level of IgG4-RD patients was correlated with the length of hospitalization,the length of return visit,and the dynamic changes of IgG4 level after return visit.Conclusion:Serum IgG4 detection plays an important role in the diagnosis and treatment of IgG4-RD.In patients with abnormally high level of IgG4,those who are sensitive to high-dose glucocorticoid therapy have a faster decline in IgG4 levels and a longer duration of symptom remission.

Objective:To investigate the role and mechanism of TrxR1 in reprogramming tumor-associated macrophage in breast cancer,providing novel insights and theoretical foundations for clinical breast cancer treatment.Methods:TISIDB database was used to analyze the relationship between TXNRD1(encoding TrxR1)and tumor immunity.Mouse breast cancer 4T1 cells conditioned medium was collected and co-cultured with bone marrow-derived macrophage(BMDM)cells for 48 h to detect the expression of macrophage immunosuppression-related factors.TrxR1 secretion by tumor cells was measured using ELISA kits.TXNRD1 knockdown efficiency was verified via Western blot.Fluorescence quantitative PCR(qPCR)and flow cytometry were used to detect the expression levels of macrophage immunosuppressive factors after TXNRD1 knockdown in tumor cells.JASPAR database was used to analyze the potential regulatory factors,and Western blot was used to verify the expression of pathway-related proteins.Results:Database analysis found that TXNRD1 expression positively correlated with survival risk indices across multiple cancers,with the strongest association observed in breast cancer.Further analysis found that elevated TXNRD1 expression correlated with reduced infiltration of M1 macrophages and natural killer(NK)cells,but increased M2 macrophage infiltration.qPCR and flow cytometry demonstrated that tumor-conditioned medium enhanced macrophage immunosuppression,whereas medium from TXNRD1-knockdown tumor cells suppressed this effect.And TrxR1-neutralizing antibodies could also reversed this effect.JASPAR database analysis identified STAT3 and STAT6 as potential transcriptional regulators,and Western blot confirmed that TXNRD1-knockdown tumor cells conditioned medium inhibited STAT6 pathway activation in macrophages.Conclusion:In the tumor microenvironment,breast tumor-derived TrxR1 promotes macrophage immunosuppression,potentially through activation of the STAT6 signaling pathway.

Diffuse large B-cell lymphoma(DLBCL)is a highly heterogeneous disease.Although standard first-line regimens can cure＞50%of patients,approximately one-third of them develop relapsed/refractory DLBCL(r/r DLBCL).Consequently,immunotherapy targeting molecular abnormalities has become pivotal for managing r/r DLBCL.The results of this review show that with advances in understanding DLBCL pathogenesis and the tumor immune microenvironment,antibody-based therapies have evolved rapidly,progressing from monoclonal antibodies(e.g.,rituximab,tafasitamab)to bispecific antibodies(e.g.,odronextamab,glofitamab,epcoritamab)and antibody-drug conjugate(e.g.,polatuzumab vedotin,loncastuximab tesirine).These engineered agents enhance immune cytotoxicity and tumor-specific targeting,providing novel therapeutic options for r/r DLBCL patients.

Pancreatic β-cell dysfunction is a critical factor in the pathogenesis of type 2 diabetes mellitus(T2DM).Recent studies have identified iron overload as a significant risk factor for T2DM, wherein excess iron contributes to β-cell dysfunction through multiple pathways, including oxidative stress, mitochondrial dysfunction, and a reduction in the number of pancreatic β-cells.These mechanisms adversely affect insulin synthesis, secretion, and release.This review aims to summarize the recent advancements in understanding the relationship between iron overload and pancreatic β-cell dysfunction.