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.

ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

Palmitoylation, an essential covalent attachment of a fatty acid (usually C16 palmitate) to cysteine residues within proteins, is crucial for regulating protein functionality and enzymatic activities. This lipid modification facilitates the anchoring of proteins to cellular membranes, dictating their subcellular distribution and influencing protein transport dynamics and intracellular positioning. Additionally, it plays a role in regulating protein degradation through the ubiquitin-proteasome system. Palmitoylation is implicated in the pathogenesis and progression of cardiovascular diseases by modulating substrates and prompting additional post-translational modifications, as well as by interacting with other molecular alterations. Moreover, an intervention strategy focusing on palmitoylation processes is anticipated to offer novel therapeutic avenues for cardiovascular pathologies and address extant challenges in clinical settings. This review consolidates current research on the role and importance of palmitoylation in cardiovascular diseases by exploring its regulatory functions, the catalyzing enzymes, and the involved substrates. It highlights recent discoveries connecting palmitoylation-targeted therapies to cardiovascular health and examines potential approaches and future challenges in cardiovascular treatment.

Objective To investigate the effects of perampanel on the C-C chemokine receptor 5(CCR5)/cAMP-dependent protein kinase A(PKA)/cyclic-AMP response binding protein(CREB)pathway and hippocampal neuronal damage in epileptic rats.Methods Seventy-two male SPF-grade SD rats were randomly divided into epilepsy group,perampanel group,CCR5 inhibitor(maraviroc)group,recombinant CCL5 protein(rCCL5,CCR5 activator)group,perampanel+rCCL5 group,and a control group,with 12 rats in each group.The duration and frequency of epi-leptic seizures were detected in above groups.HE staining was used to observe the morphology of the hippocampal CA1 region.ELISA was employed to measure the contents of cyclooxygenase-2(COX-2),TNF-α,and IL-18 in the hippocampal CA1 region.Western blotting was conducted to measure the expression levels of CCR5,PKA,and p-CREB in the hippocampal CA1 region.Results Compared with the control group,the epilepsy group demonstrated badly-arranged and swollen neurons in the hippocampal CA1 region,longer duration of epilepsy,higher seizure frequency,increased COX-2,TNF-α and IL-18 contents in the CA1 region,elevated apoptotic rate and CCR5 protein level,and prolonged escape latency,while less number of crossing platforms and reduced protein levels of PKA and p-CREB(P＜0.05).While,both perampanel and maraviroc treatment could reverse above indicators when compared with the levels of the epilepsy group(P＜0.05).In the rCCL5 group,the neural injury was significantly aggravated,the duration of epilepsy and the frequency of epileptic seizures were increased,the contents of COX-2,TNF-α and IL-18 in the hip-pocampal CA1 region were enhanced,the rate of neuronal apoptosis and the expression of CCR5 protein were significantly enhanced,the escape latency was prolonged,and the number of crossed platforms,PKA,and the expression of p-CREb protein were declined(P＜0.05).When compared with the perampanel group,addition of rCCL5 resulted prolonged duration of epilepsy and escape latency,increased frequency of epileptic seizures and protein levels of COX-2,TNF-α,IL-18 and CCR5,more severe neuronal injury in the CA1 region,less platforms crossed,and decreased pro-tein expression of PKA and p-Creb(P＜0.05).The neural apoptotic rate in the hippocampal CA1 region was significantly higher in the perampanel+rCCL5 group than the perampanel group[(10.58±0.43)％vs(6.36±0.31)％,P＜0.05].Conclusion Perampanel may inhibit neuroin-flammation and neuronal apoptosis in epileptic rats by down-regulating CCR5 and then activating the PKA/CREB pathway,and thus attenuate hippocampal neuronal damage.

Objective To investigate the metabolic characteristics of patients with early-onset type 2 diabetes mellitus(T2DM)and to develop a risk prediction model for microvascular complications.Methods A retrospective study was conducted on 980 T2DM patients admitted for treatment between April 2020 and April 2024.Based on age at diagnosis,the patients were divided into two groups,an early-onset T2DM group(age at diagnosis<40 years,n=265)and a late-onset T2DM group(age at diagnosis≥40 years,n=715).Differences in metabolic indicators between the two groups were compared.Patients in the early-onset group were further divided into a complication subgroup(n=142)and a non-complication subgroup(n=123)based on the presence or absence of microvascular complications.Data on baseline characteristics,metabolic parameters,and laboratory indicators were collected and compared between the two groups.Multivariate logistic regression analysis was used to identify independent risk factors for microvascular complications,and a nomogram prediction model was constructed.The model's discriminative performance was assessed using receiver operating characteristic(ROC)curves,and its calibration was evaluated using calibration curves and the Hosmer-Lemeshow test.Decision curve analysis(DCA)was also performed to assess the model's clinical utility.Results Compared with the late-onset group,patients in the early-onset group exhibited more pronounced metabolic abnormalities,including higher body mass index(BMI),proportion of family history of diabetes mellitus,glycated hemoglobin(HbA1c)levels,total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),triglyceride-glucose index(TyG),and lactate dehydrogenase(LDH)levels(all P<0.05),along with a shorter disease duration and lower levels of high-density lipoprotein cholesterol(HDL-C)(P<0.05).According to a multivariate analysis,systolic blood pressure(SBP),total bilirubin(TBIL),HDL-C,LDL-C,TyG,and LDH were identified as independent risk factors for microvascular complications in patients with early-onset T2DM.A predictive model based on these factors was established as the follows,Log(P)=-19.915+0.017×SBP-0.136×TBIL-1.241×HDL-C+0.684×LDL-C+0.769×TyG+0.050×LDH.The area under the ROC curve(AUC)was 0.864(95%CI,0.820-0.907),and the Hosmer-Lemeshow test indicated good model fit(χ2=10.286,P=0.246).The slope of the DCA curve was also close to 1.Conclusion The nomogram prediction model based on SBP,TBIL,HDL-C,LDL-C,TyG,and LDH demonstrates good predictive performance for microvascular complications and can provide a reference for clinical risk stratification and individualized intervention.

Objective To explore the risk factors for postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass grafting (OPCAB) alone. Methods A retrospective analysis was conducted on the clinical data of patients who underwent OPCAB in the Department of Cardiac Surgery Ward No.1 of Zhengzhou Seventh People’s Hospital from January 2020 to January 2024. Patients were categorized into a POAF group and a non-POAF group based on the occurrence of POAF. The clinical data of both groups were analyzed. Parameters underwent univariate analysis, and variables with P≤0.05 in univariate analysis were further analyzed through binary multivariate logistic regression to identify independent risk factors. Results A total of 496 patients were included. There were 312 males and 184 females, with age ranging from 50 to 78 years. There were 148 patients in the POAF group and 348 patients in the non-POAF group. The incidence of POAF after isolated OPCAB surgery was 29.8%. Results of univariate analysis showed that there were statistical differences in the incidence of diabetes (P=0.012), >75% stenosis of the left circumflex artery (LCX) (P=0.036), shock (P<0.001), graded left ventricular diastolic function (P<0.001), left ventricular ejection fraction (P<0.001), age (P<0.001), preoperative resting heart rate (P<0.001), left atrial diameter (P<0.001), E/A ratio (P<0.001), postoperative K+ concentration (P<0.001), and postoperative Mg2+ concentration (P<0.001). Binary multivariate logistic regression analysis revealed that age (OR=1.436, 95%CI 1.094 to 1.884, P=0.009), diabetes (OR=2.032, 95%CI 1.006 to 4.145, P=0.043), preoperative resting heart rate (OR=1.008, 95%CI 1.001 to 1.015, P=0.018), left atrial diameter (OR=4.409, 95%CI 1.711 to 11.359, P=0.002), and E/A ratio (OR=1.713, 95%CI 1.115 to 2.633, P=0.014) were independent risk factors for POAF after isolated OPCAB. The occurrence of POAF significantly prolonged mechanical ventilation time and ICU stay (both P＜0.001). Conclusion Age, diabetes, left atrial diameter, E/A ratio, and preoperative resting heart rate are potential independent risk factors for POAF following OPCAB surgery. Additionally, the occurrence of POAF can lead to prolonged mechanical ventilation and extended stay in the intensive care unit.

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.