Background:Diabetic foot ulcer (DFU) is a severe diabetic complication characterized by impaired healing, often involving fibroblast senescence and the senescence-associated secretory phenotype (SASP). The role of ribonucleic acid (RNA)-binding proteins (RBPs) in this process remains undefined. This study investigates the function and mechanism of the RBP interleukin enhancer-binding factor 2 (ILF2) in DFU pathogenesis. Methods:Differentially expressed RBPs were identified via bioinformatics analysis of public single-cell and bulk transcriptomic datasets. ILF2 downregulation was subsequently validated in clinical DFU samples and diabetic mouse models. Functional assays in high-glucose (HG)-treated fibroblasts evaluated proliferation, migration, and SASP. Mechanistically, RNA sequencing, RNA-binding protein immunoprecipitation, and RNA pull-down assays identified downstream targets, while co-IP and rescue experiments verified the NPM1/NF-κB axis. Finally, a diabetic mouse model was used to study the effects of ILF2 overexpression/knockdown and NPM1 knockdown on wound healing. Results:Bioinformatics analysis identified ILF2 as significantly downregulated in DFU. This reduction was consistently validated in DFU patient tissues, diabetic mouse wounds, and HG-treated fibroblasts. Functionally, ILF2 overexpression promoted fibroblast proliferation and migration while suppressing SASP, whereas knockdown exacerbated senescence. Mechanistically, ILF2 directly bound to nucleophosmin (NPM1) mRNA to promote its degradation. ILF2 deficiency led to aberrant NPM1 accumulation, enhancing the NPM1-phospho-p65 interaction and NF-κB pathway activation. Rescue experiments confirmed that NPM1 knockdown reversed ILF2 deficiency-induced cellular dysfunction. Crucially, these findings were validated in primary fibroblasts isolated from DFU patients. In vivo, ILF2 overexpression accelerated wound healing, while knockdown delayed the process. Furthermore, NPM1 knockdown effectively ameliorated the impaired healing phenotype and reduced SASP levels. Conclusions:This study elucidates a novel ILF2-NPM1-NF-κB regulatory axis. ILF2 acts as a critical suppressor of inflammatory senescence by destabilizing NPM1 mRNA, highlighting its potential as a therapeutic target for DFU treatment.

Polycystic ovary syndrome (PCOS) is a chronic inflammatory disease caused by a combination of genetic, environmental, and gut microbiota factors. Western medicines can improve ovulation rates, but are linked with reduced pregnancy success and side effects. Scutellaria baicalensis (BAL) is a famous anti-inflammatory Chinese herb, which has therapeutic effects for PCOS; however, the mechanism remains unclear. This study integrated network pharmacology, molecular docking, and animal experiments to investigate the mechanisms by which BAL improves gut microbiota and intestinal inflammation in a rat PCOS model. We identified 36 active components of BAL, including wogonin, baicalein, and oroxylin A, along with 145 potential targets, such as TNF, IL-6, and AKT1, and network analysis revealed that TNF, IL-6, and AKT1 occupied central positions. Enrichment analyses indicated that BAL may exert its therapeutic effects by modulating the NF-κB and Toll-like receptor signaling pathways. Molecular docking results demonstrated strong binding affinities between BAL's primary active components and the core targets TNF, AKT1, and IL-6. BAL experiments in PCOS rats showed that it restored gut microbiota balance. These results showed that BAL inhibits the LPS/TLR4/NF-κB pathway and downregulates PI3K and p-Akt/Akt protein expression in ovarian tissue. BAL also improved reproductive metabolic abnormalities, intestinal inflammation, and dysbiosis. Our study suggests that BAL inhibits the LPS/TLR4/NF-κB pathway via the gut-ovarian axis, regulating gut microbial composition and alleviating inflammatory states. This may be a mechanism for the therapeutic efficacy of BAL for PCOS and a novel therapeutic strategy for the clinical management of polycystic ovary syndrome.IMPORTANCEPCOS affects women of reproductive age. Current clinical treatment strategies still face limitations in efficacy and long-term side effects. This study employs network pharmacology, molecular docking, and experimental validation to elucidate the mechanism by which the traditional Chinese medicine BAL improves PCOS. We found that BAL modulates gut microbiota in a PCOS rat model, significantly increasing the probiotic genus Phocaeicola. This change correlates with reduced serum LPS levels and alleviated ovarian inflammation. Experiments confirm that BAL alleviates local ovarian inflammation and insulin resistance by inhibiting the LPS/TLR4/NF-κB signaling pathway, thereby improving PCOS pathological manifestations. This study reveals new mechanisms of BAL in treating PCOS and highlights the potential bridging role of probiotics like Phocaeicola. It also provides experimental evidence and theoretical support for integrated Chinese and Western medicine treatment strategies based on regulating gut microbiota.

Diabetes Mellitus (DM) increases the risk of Mild Cognitive Impairment (MCI) and dementia, severely impacting patients' quality of life and long-term future prospects. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i), a class of oral hypoglycemic drugs, have recently been shown to have neuroprotective effects. Studies show that SGLT-2i ameliorates cognitive dysfunction in diabetic animal models through various mechanisms such as insulin pathways in the brain, cerebrovascular dysfuntion, neuroinflammation and oxidative stress, inhibition of Alzheimer's disease pathology, and neurotrophic factor expression. Clinical studies also show that SGLT-2i improves cognitive performance in diabetic patients, significantly reducing the risk of dementia and MCI. Despite the promising role of SGLT-2i in preventing and treating DM-related cognitive impairment, further studies and more robust clinical evidence are needed for its clinical application.

BACKGROUND:Diabetic osteoporosis (DOP), a serious complication of type 2 diabetes mellitus (T2DM), involves ferroptosis-mediated disruption of bone metabolism. While endothelial cell-derived exosomes (EC-Exos) demonstrate inherent bone-targeting properties, their role in counteracting high glucose (HG)-induced osteoblast ferroptosis remains unexplored. AIM:To investigate whether EC-Exos protect against HG-induced osteoblast ferroptosis through microRNA (miR)-335-3p-mediated regulation of prostaglandin endoperoxide synthase 2 (PTGS2) and evaluate clinical relevance in DOP. METHODS:Mouse vascular endothelial cells (bEND.3) and osteoblasts (MC3T3E1) were used. Exosomes were isolated and subsequently characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blotting for CD63 and CD81. miR expression profiles were compared between HG-treated osteoblasts and exosome-cocultured groups using high-throughput sequencing and quantitative reverse transcription polymerase chain reaction. Targeting of PTGS2 mRNA by miR-335-3p was validated by dual-luciferase reporter assay. Ferroptosis markers, reactive oxygen species, malondialdehyde, glutathione (GSH), PTGS2, GSH peroxidase 4, solute carrier family 7 member 11, and solute carrier family 3 member 2, were quantified following miR-335-3p inhibition. Serum samples from 30 T2DM patients and 32 DOP patients were analyzed. miR-335-3p levels were measured by quantitative reverse transcription polymerase chain reaction, and PTGS2 concentrations were determined via enzyme-linked immunosorbent assay. Diagnostic performance was assessed using receiver operating characteristic curves and logistic regression. RESULTS:EC-Exos significantly reduced reactive oxygen species levels and malondialdehyde, while increasing GSH in HG-treated osteoblasts. miR-335-3p expression increased 3.7-fold in exosome-treated cells vs HG controls. miR-335-3p directly bound the PTGS2 3' untranslated region. Inhibition of miR-335-3p abolished exosomal protection against ferroptosis, as demonstrated by increased PTGS2 expression and reduced levels of GSH peroxidase 4, solute carrier family 7 member 11, and solute carrier family 3 member 2. DOP patients exhibited lower serum miR-335-3p and higher PTGS2 compared with T2DM controls, showing a strong inverse correlation. miR-335-3p demonstrated diagnostic potential for DOP. CONCLUSION:EC-Exos affect ferroptosis in osteoblasts induced by HG by activating miR-335-3p/PTGS2. Serum miR-335-3p may be a novel diagnostic biomarker.

OBJECTIVE:This study aimed to investigate the role of protein S (PROS1) in the pro-healing effects of negative pressure wound therapy (NPWT) on diabetic foot ulcers (DFU). METHODS:Serum and granulation tissue samples were collected from patients with DFU and non-diabetic skin ulcer control (SUC) subjects. PROS1 expression levels were measured before and after NPWT. For in vitro functional verification, human umbilical vein endothelial cells (HUVECs) were cultured under normal or high-glucose (HG) conditions. Experiments were performed to explore the regulatory role of PROS1 in endothelial proliferation, tube formation, and apoptosis in both PROS1 knockdown and overexpression in HG-cultured HUVECs. RESULTS:Baseline tissue PROS1 expression was lower in the DFU group compared to the SUC group. PROS1 mRNA and protein levels were significantly upregulated in the granulation tissue of both groups at Post-NPWT, accompanied by increased VEGF and CD31 expression and improved histological angiogenesis. In vitro, PROS1 knockdown restrained proliferation and tube formation but induced apoptosis of HUVECs under both normal and HG conditions. Conversely, PROS1 overexpression rescued HG-induced endothelial dysfunction by restoring cell proliferation, angiogenic capacity, and inhibiting excessive apoptosis. Importantly, the magnitude of the PROS1 increase in tissue following NPWT was positively correlated with the 4-week wound healing rate. In patients with DFU, changes in serum PROS1 were negatively correlated with C-reactive protein (CRP), an inflammatory marker. CONCLUSION:Our findings demonstrate that NPWT promotes DFU healing by upregulating PROS1 expression, which in turn enhances angiogenesis and modulates inflammation. These results establish PROS1 as a promising therapeutic target and a predictive biomarker for wound healing in DFUs.

AIMS:To investigate the role of RNA N6-methyladenosine (m6A) methyltransferase Wilms tumor 1-associated protein (WTAP) in negative pressure wound therapy (NPWT) for diabetic foot ulcers (DFU). MATERIALS AND METHODS:We enrolled 46 DFU patients and 16 non-diabetic chronic ulcer patients treated with NPWT. Total m6A levels and the expression of methyltransferases (METTL3, METTL14, and WTAP) in wound margin tissues were measured before and after NPWT. High glucose-induced HaCaT and HDF cell models, alongside an in vitro negative pressure system, were used to evaluate the effect of negative pressure on WTAP expression and the impact of WTAP alteration on cellular functions. RESULTS:Before NPWT, METTL3, METTL14, WTAP and m6A levels were significantly lower in DFU patients than in the non-diabetic chronic ulcer patients. After one week of NPWT, these parameters increased significantly in both groups, and a positive correlation was observed between WTAP and m6A levels. Notably, the increase in WTAP expression exhibited a significant positive correlation with the 4-week healing outcome in DFU patients. In vitro, negative pressure significantly reversed the high glucose-induced WTAP downregulation in both HaCaT and HDF cells, while WTAP knockdown profoundly impaired their proliferation and migration. CONCLUSIONS:NPWT is associated with improved DFU healing and the restoration of WTAP-m6A levels, and its effect may be related to negative pressure promoting WTAP expression to enhance wound cell proliferation and migration.

Background Although there is numerous studies have suggested an association between lipid metabolism and body composition, the precise relationship between the atherogenic index of plasma (AIP) and the fat-to-muscle mass ratio (F/M) remains unclear. Therefore, we aimed to elucidate the non-linear relationship between AIP and F/M. Methods This cross-sectional study was conducted among the health examination population at Hefei First People's Hospital between May and November 2023. A total of 1082 participants were included in this study. Body composition was assessed using bioelectrical impedance analysis (BIA) to calculate the F/M. Biochemical indexes including blood glucose, blood lipids, liver and kidney functions. The AIP was calculated as log10 (triglycerides / high-density lipoprotein cholesterol). The one-way ANOVA with Bonferroni correction, smoothing functions, threshold effect analyses, log-likelihood ratio tests, trend tests, interaction tests, and subgroup analyses were used to assess the association between F/M and AIP. Results A significant increasing trend in the AIP was observed across ascending F/M quartiles. After adjustment for confounding factors, a positive association was observed between F/M and AIP before the inflection point (F/M = 0.47) (β = 0.68, P < 0.0001), whereas a negative association was identified beyond this threshold (β = -0.37, P = 0.009). Trend tests revealed a statistically significant increasing trend in AIP across ascending F/M quartiles in the subgroup with F/M < 0.47 ( P < 0.0001); however, the decreasing trend was not statistically significant in the subgroup with F/M ≥ 0.47 ( P = 0.4119). Interaction tests further revealed waist-to-hip ratio (WHR) and the appendicular skeletal muscle mass-to-body mass index ratio (ASM/BMI) as significant effect modifiers in the F/M < 0.47 ( P = 0.0049) and F/M ≥ 0.47 ( P = 0.0214) subgroups, respectively. Conclusions In the health examination population, the relationship between F/M and AIP exhibited a threshold-saturation effect, characterized by a positive correlation below the inflection point (F/M = 0.47) and no correlation beyond it. For individuals with F/M < 0.47, central obesity is a primary driver of atherogenic risk, underscoring the benefit of weight loss. Conversely, in those with F/M ≥ 0.47, increasing appendicular skeletal muscle mass mitigates cardiovascular risk, calling for a focus on muscle-building training beyond weight management.

Objective To identify plasma protein differences between type 2 diabetes mellitus (T2DM) patients with and without metabolic dysfunction-associated steatotic liver disease (MASLD), and to evaluate the diagnostic potential of X-prolyl aminopeptidase 3 (XPNPEP3) for identifying MASLD in T2DM patients.Methods Twenty T2DM inpatients were categorized into groups with and without MASLD and their plasma samples were analyzed using data-independent acquisition mass spectrometry, followed by bioinformatics analysis to identify differentially expressed proteins. The cohort was then expanded to 84 patients, and plasma XPNPEP3 levels were validated by enzyme-linked immunosorbent assay. Correlation between XPNPEP3 and clinical indicators were evaluated, and diagnostic performance was determined via receiver operating characteristic (ROC) analysis. Immunohistochemistry was employed to compare hepatic XPNPEP3 expression between the two groups.Results Proteomic analysis identified 176 differentially expressed proteins, with XPNPEP3 exhibiting the most significant down-regulation by fold change. In the validation cohort, plasma XPNPEP3 was significantly lower in T2DM+MASLD versus T2DM alone. XPNPEP3 levels were negatively correlated with diabetes duration, liver function markers, and triglyceride levels, and was identified as an independent factor inversely associated with MASLD in T2DM.ROC analysis demonstrated strong diagnostic performance for XPNPEP3, further enhanced when combined with BMI and diabetes duration. Immunohistochemistry confirmed reduced hepatic XPNPEP3 expression in T2DM+MASLD patients.Conclusions Lower plasma XPNPEP3 is independently associated with MASLD in T2DM patients and demonstrates strong diagnostic potential, positioning XPNPEP3 as a promising biomarker for diagnosing MASLD in T2DM patients and a novel target for non-invasive diagnostic tool development.

Prior studies have indicated elevated plasma copper levels in patients with diabetes compared with healthy controls. However, cuproptosis remains unexplored in diabetic foot ulcers (DFUs). DFU-associated datasets (GSE165816, GSE80178, and GSE134431) were obtained from the Gene Expression Omnibus (GEO) database. Cuproptosis-associated genes (CRGs) were identified by combining single-cell and bulk RNA-sequencing data. Differentiation, enrichment, network, pseudotime, immune infiltration, cellular communication, drug sensitivity, and molecular docking analyses were performed. The CRGs were verified in a Wistar DFUs rat model. Four hub genes were obtained (DCN, IGF1, CXCL12, and CXCL8). Enrichment analysis indicated that these genes were involved primarily in cytokine storms. Moreover, network analysis revealed the relationships among competing endogenous RNAs, transcription factors, single nucleotide polymorphisms, and hub genes. In addition, pseudotime analysis revealed greater numbers of plasma cells, naive B cells, and CD4 + T cells in DFUs than controls. Furthermore, immune infiltration analysis indicated immune cells dysregulation in DFUs, characterized by lower numbers of activated mast cells, activated NK cells, and M1 macrophages than those in controls. In addition, cellular communication analysis revealed that mesenchymal stem cells frequently interacted with fibroblasts, keratinocytes, endothelial cells, and T cells. The nomogram indicated that four hub genes were included for diagnosis of DFUs and the DFU risk was approximately 0.86. Finally, drug sensitivity analysis and molecular docking demonstrated that sirolimus was an effective drug for DFU treatment. Together, our findings link IGF1 and CXCL12 to cuproptosis, thus providing novel insights for DFU diagnosis and treatment.

The association between Neutrophil-Percentage-to-Albumin Ratio (NPAR) and mortality in cardiovascular disease (CVD) patients with diabetes or pre-diabetes is not well understood. This study investigates the relationship between baseline NPAR levels and all-cause and cardiovascular mortality among American adults with CVD and diabetes or pre-diabetes. This study enrolled 6,080 patients with diabetes or prediabetes from the National Health and Nutrition Examination Survey (2001-2018). Mortality outcomes were determined by linkage to the National Death Index (NDI) records through December 31, 2019. Multivariate Cox proportional hazards models were used to explore associations between NPAR and mortality. Non-linear correlations were assessed with restricted cubic splines, and segmented Cox proportional hazards models were used to evaluate threshold effects. Receiver operating characteristic (ROC) curves were used to evaluate NPAR's predictive ability for all-cause mortality. Weighted Kaplan-Meier curves with log-rank tests assessed cumulative survival differences across NPAR levels. In this cohort study, with a total follow-up of 53,217 person-years, 1,378 deaths from all causes and 476 deaths from CVD were recorded. Restricted cubic spline analysis revealed a J-shaped association between NPAR and both all-cause and cardiovascular mortality. Threshold effect analysis identified inflection points for NPAR in relation to all-cause mortality at 15.1 and cardiovascular mortality at 14.2. When baseline NPAR exceeded these inflection points, a positive correlation was observed with all-cause mortality (HR: 1.55, 95% CI: 1.08-2.16) and cardiovascular mortality (HR: 1.25, 95% CI: 1.09-1.86). ROC curves for 3-year, 5-year, and 10-year survival rates for all-cause mortality had areas under the curve (AUC) of 0.83, 0.83, and 0.81, respectively. For cardiovascular mortality, the AUC values were 0.86, 0.87, and 0.84. Increased NPAR is significantly associated with increased all-cause and cardiovascular mortality in individuals with diabetes or prediabetes, suggesting its potential role as a prognostic marker.

Background and purpose:Insulin resistance (IR) has been linked to poor stroke prognosis even in non-diabetic patients, but the underlying mechanisms remain unclear. This study aims to explore whether the association between IR and poor prognosis in non-diabetic patients with acute ischemic stroke (AIS) treated with intravenous recombinant tissue-type plasminogen activator (IV-rtPA) is mediated by systemic inflammation. Methods:In this retrospective study, 841 consecutive patients with AIS but without a history of diabetes treated with IV-rtPA were included. IR was evaluated by means of the triglyceride-glucose index (TyG). Inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and inflammation prognostic index (IPI), were calculated based on blood parameters obtained within 24 h of admission. The primary outcome was poor prognosis at 90 days [modified Rankin Scale (mRS) score ≥3]. Multivariable logistic regression analysis was performed to explore the associations among TyG, inflammatory markers, and the poor prognosis. A mediation analysis was performed to examine the relationship between IR and the study outcome mediated by systemic inflammation. Results:In total, 107 (12.72%) had poor prognosis. After adjusting for confounders (Model 3), multivariable logistic regression analysis revealed that both TyG and NLR were significantly associated with poor prognosis [odds ratio (OR), 2.212 (95% CI, 1.564-5.617), P < 0.001; 1.059 (95% CI, 0.904-1.241), P = 0.004; respectively]. Both indicators exhibited strong predictive value for poor prognosis, with areas under the curve (AUCs) of 0.823 and 0.730, respectively. Moreover, NLR and IPI were found to partially mediate the relationship between TyG and poor prognosis, with mediation proportions of 16.5 and 13.8%, respectively. After propensity score matching (PSM), the mediating effects of inflammatory markers became more pronounced. Conclusion:Our study found that insulin resistance was associated with poor prognosis in non-diabetic patients treated with IV-rtPA, and this association was partially mediated by NLR and IPI to a modest extent. These findings offer new insights into the clinical management of non-diabetic AIS patients after IV.

BACKGROUND:Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder increasingly linked with hypertension, posing significant health risks. The need for a predictive model tailored for T2DM patients is evident, as current tools may not fully capture the unique risks in this population. This study hypothesizes that a nomogram incorporating specific risk factors will improve hypertension risk prediction in T2DM patients. AIM:To develop and validate a nomogram prediction model for hypertension in T2DM patients. METHODS:A retrospective observational study was conducted using data from 26850 T2DM patients from the Anhui Provincial Primary Medical and Health Information Management System (2022 to 2024). The study included patients aged 18 and above with available data on key variables. Exclusion criteria were type 1 diabetes, gestational diabetes, insufficient data, secondary hypertension, and abnormal liver and kidney function. The Least Absolute Shrinkage and Selection Operator regression and multivariate logistic regression were used to construct the nomogram, which was validated on separate datasets. RESULTS:The developed nomogram for T2DM patients incorporated age, low-density lipoprotein, body mass index, diabetes duration, and urine protein levels as key predictive factors. In the training dataset, the model demonstrated a high discriminative power with an area under the receiver operating characteristic curve (AUC) of 0.823, indicating strong predictive accuracy. The validation dataset confirmed these findings with an AUC of 0.812. The calibration curve analysis showed excellent agreement between predicted and observed outcomes, with absolute errors of 0.017 for the training set and 0.031 for the validation set. The Hosmer-Lemeshow test yielded non-significant results for both sets (χ 2 = 7.066, P = 0.562 for training; χ 2 = 6.122, P = 0.709 for validation), suggesting good model fit. CONCLUSION:The nomogram effectively predicts hypertension risk in T2DM patients, offering a valuable tool for personalized risk assessment and guiding targeted interventions. This model provides a significant advancement in the management of T2DM and hypertension comorbidity.

Wounds in patients with diabetes present significant physical and economic challenges due to impaired healing and prolonged inflammation, exacerbated by complex interactions between microbes. Especially, the development and healing of diabetic foot ulcers (DFUs) remain an urgent clinical problem. The human gut harbors a vast microbial ecosystem comprising intestinal flora and their metabolic products. Recent advancements in research have illuminated the concept of the "gut-skin axis," revealing intricate relationships between gut microbiota, microbiota-derived metabolites, and various skin diseases, including DFUs. This review aims to unravel the formation and healing process of DFUs in the context of the gut-skin axis. We reviewed the current research progress worldwide regarding to the gut-skin axis, compared and discussed significant changes in the microbiota colonizing the skin and gut in patients with DFUs. The roles of microbiota-derived metabolites such as lipopolysaccharides, short-chain fatty acids, and trimethylamine-N-oxide in the development of DFUs are highlighted. We also reviewed treatment strategies currently employed in clinical practice and identified potential therapeutic targets such as probiotics for treating DFUs. The need for more comprehensive experimental designs to elucidate the intricate relationship between gut microbiota and its metabolites in the context of DFUs are therefore highlighted.

AIMS:Chronic kidney disease (CKD) affects individual welfare, healthcare systems and societal progress. Of the multifaceted etiological factors, type 1 diabetes mellitus (T1DM) is a prominent contributor to CKD. MATERIALS AND METHODS:We analysed the global incidence, prevalence, deaths and disability-adjusted life-years (DALYs) with age-standardised rates of CKD due to T1DM (CKD-T1DM) in 2021, stratified by subtype. We calculated the temporal trends in the infirmity burden from 1990 to 2019 using a linear regression model. The age-period-cohort (APC) and Bayesian APC models predicted the prospective burden over the next 25 years. Sensitivity analysis was conducted using Autoregressive Integrated Moving Average and Exponential Smoothing models. RESULTS:Globally, there were 95 140 incidences, 6 295 711 prevalence cases, 94 020 deaths and 3 875 628 DALYs due to CKD-T1DM. Males and young-to-middle-aged individuals were more likely to be affected by CKD-T1DM. The middle-socio-demographic index regions were at higher risk. A considerable variation in disease burden was observed across the Global Burden of Disease super regions and countries. The number of patients with CKD-T1DM surged globally from 1990 to 2021. The projections indicated a continuous increase until 2046, driven by ageing populations and unmet therapeutic needs in low-resource settings. CONCLUSIONS:CKD-T1DM poses a growing public health threat, necessitating region-specific strategies that address healthcare inequities, promote early screening and prioritise nephroprotective therapies among T1DM populations.

Introduction:This study aims to investigate the significance of insulin resistance (IR) markers in predicting 48-hour hemorrhagic transformation and 3-month poor prognosis in acute ischemic stroke (AIS) patients of intravenous thrombolysis (IVT), with or without type 2 diabetes mellitus (T2DM). Methods:A total of 1352 patients with AIS treated with IVT between January 2019 and December 2023 were retrospectively reviewed. We analyzed the prognostic value of IR markers, including the triglyceride-glucose (TyG) index, triglyceride and body mass index (TYG-BMI), and the insulin resistance metabolic score (METS-IR), in AIS patients who received IVT with or without T2DM. The primary outcome was 48-hour hemorrhagic transformation and 3-month poor prognosis (modified Rankin Scale [mRS] ≥ 3). Results:Among 1181 enrolled patients, 328 were diagnosed with T2DM, representing 27.8% of the cohort. T2DM group showed a higher proportion of poor prognosis (23% vs.11%, p < 0.001), but no significant difference in hemorrhagic transformation between the two groups. TyG index, TyG-BMI, and METS-IR all demonstrated predictive value for 3-month poor prognosis, with the TyG index showing the highest predictive accuracy [area under the curve (AUC): 0.848]. The optimal cutoff point for predicting poor prognosis was 7.409, with sensitivity of 0.762 and specificity of 0.855 (p < 0.001). However, all three indexes were limited in their ability to predict hemorrhagic transformation. Conclusion:Elevated TyG index is an independent risk factor for 3-month poor prognosis in AIS patients of IVT with or without type T2DM, with the TyG index showing the highest predictive value. These findings provide a new understanding that IR can be used as a therapeutic target for AIS patients of IVT.

Type 2 diabetes mellitus (T2DM) mainly induced by high-fat diets (HFD) is becoming a prevalent and serious metabolic disease worldwide. Although probiotics are considered a treatment for T2DM, the underlying mechanisms and therapeutic effects of the specific strain remain unclear. Thus, elucidating the strain-dependent mechanisms and identifying effective probiotic strains for T2DM management are critically needed. In this study, Lactobacillus plantarum was administered to HFD-induced T2DM mice to evaluate its effects on fasting blood glucose (FBG), body weight (BW), gut microbiota (GM) composition, gut metabolites, and liver gene expression. We found that L. plantarum supplementation significantly reduced FBG, insulin levels, and BW, while ameliorating liver and pancreatic damage in T2DM mice. Furthermore, shifts in gut microbial composition were observed following L. plantarum intervention, characterized by the suppression of Lactobacillus johnsonii, Bacteroides acidifaciens, Alistipes sp., and bacterium D1676, along with enrichment of beneficial strains, such as L. acidophilus, Enterorhabdus sp. P55, and Bacteroides caecimuris. Besides, L. plantarum administration significantly increased the concentrations of glycocholic acid, arachidonic acid, L-tryptophan, and palmitic acid while decreasing chenodeoxycholic acid concentration. This modulation is accompanied by the upregulation of Hmgcr and Ugt1a5 mRNA expression, leading to increased levels of TGR5 (G protein-coupled bile receptor) and GLP1R (Glucagon-like peptide-1 receptor). Transcriptomic and metabolomic analyses confirmed that L. plantarum alleviates T2DM caused by HFD through upregulating the bile acid secretion pathway. The results demonstrate that L. plantarum ameliorates symptoms in T2DM mice through the gut-liver axis. IMPORTANCE:T2DM is becoming a global health problem linked to poor diet and metabolic disorders. The probiotic L. plantarum offers a promising natural approach by targeting two key factors: gut bacteria balance and bile acid function. In HFD-fed mice, this treatment helps restore healthy gut microbes and improves bile acid signaling, which together lower blood glucose, reduce inflammation, and protect against liver damage. Unlike many diabetes medications, L. plantarum works with the body's natural systems, potentially providing a safer, long-term solution. This research highlights how probiotics could complement existing therapies, offering novel therapeutic strategies for diabetes treatment through the gut-liver axis.

Our study aims to investigate the effect of negative pressure wound therapy (NPWT) on microRNA-155 (miR-155) in the granulation tissue of patients suffering from diabetic foot ulcers (DFUs) and its correlation with wound healing. A total of sixty patients diagnosed with DFUs were randomly assigned to either the NPWT group (n = 40) or the Non-NPWT group (n = 20) in a 2:1 ratio. After debridement, the NPWT group received NPWT treatment for one week, while the Non-NPWT group underwent routine dressing therapy. The expression of miR-155 in DFU granulation tissues was evaluated by qRT-PCR before and after treatment for one week. Following termination, wound healing rates were assessed in the NPWT group, and the correlation between variations in miR-155 expression (ΔmiR-155) and wound healing was analyzed pre and post NPWT treatment. In vitro experiments were conducted to investigate the effects of negative pressure on variations of miR-155 expression, as well as proliferation, migration, and apoptosis in normal human dermal fibroblasts (NHDFs). The NPWT group showed a decrease in miR-155 expression in wound granulation tissue compared with pre-treatment [4.12 (1.22, 14.85) vs. 6.83 (2.15, 15.72), P < 0.05]. Conversely, there was no statistically significant difference in miR-155 expression in wound granulation tissue between pre-treatment and post-treatment in the Non-NPWT group (P > 0.05). However, analysis revealed a positive correlation between ΔmiR-155 and wound healing rate after 4 weeks in the NPWT group (χ2 = 4.829, P = 0.028). The in vitro experiments showed a significant decrease in miR-155 expression in NHDFs under negative pressure measured at -125 mmHg (P < 0.05). This reduction in miR-155 expression, in turn, enhanced the proliferation and migration ability while decreasing the apoptosis rate of NHDFs by targeting the upregulation of fibroblast growth factor 7 (FGF7) gene expression (P < 0.05). It is concluded that NPWT promotes DFU healing by reducing the expression of miR-155 in granulation tissue and the efficacy of NPWT correlated with altered miR-155 expression in wound tissue.

BackgroundThe triglyceride-glucose (TyG) index is a novel marker of insulin resistance associated with carotid vascular disease; however, its role in type 2 diabetes mellitus (T2DM) remains unclear.MethodsThis retrospective study enrolled patients with T2DM who underwent repeated hospitalizations at our hospital between 2014 and 2024. Participants were stratified into tertiles based on TyG index values. Multivariable regression analyses were performed to assess the association between TyG index levels and carotid plaque progression.ResultsA total of 548 patients with T2DM (55.93 ± 12.26 years, 60.4% males) were included, with a median follow-up time of 4 (2–7) years. The prevalence of carotid plaque progression increased stepwise with higher TyG tertiles (45.9% vs. 62.6% vs. 57.4%; p = 0.004), and the growth rates of bilateral plaque length and width also increased (all p < 0.05). The positive association between the TyG index and the growth rates of left carotid plaque length, left width, and right width remained significant in the fully adjusted model (TyG, per 1-unit increase: 0.197 mm vs. 0.196 mm vs. 0.189 mm; tertiles of TyG: 0.156 mm vs. 0.162 mm vs. 0.164 mm; all p < 0.05). After multivariable adjustment, Cox regression analysis showed that higher TyG index levels were associated with 1.261-fold, 1.244-fold, and 1.378-fold increased risks of carotid plaque progression in patients with T2DM (all p < 0.05). ROC curve analysis indicated that the TyG index exhibited modest predictive value for carotid plaque progression in patients with T2DM, with an AUC of 0.556 (p = 0.024). Adding the TyG index to the predictive model improved the C-statistic (0.624 vs. 0.649; p < 0.001), NRI = 0.211 (p = 0.015), and IDI = 0.020 (p < 0.001).ConclusionIn patients with T2DM, a higher TyG index is an independent risk factor for carotid plaque progression.