OBJECTIVE:Renal tubular pyroptosis is a key driver of inflammation and fibrosis in diabetic kidney disease (DKD), yet the contribution of the NAIP-NLRC4 inflammasome arm and its upstream transcriptional control have remained undefined. This study investigated whether NAIP causally promotes tubular pyroptosis in DKD and identified the transcription factor responsible for its induction. METHODS:NAIP and IRF8 expression were examined across Nephroseq DKD cohorts and correlated with renal function. Naip1-6Δ/Δ and Irf8-knockout mice, together with high glucose-treated HK-2 cells, were used to assess pyroptosis and fibrosis. IRF8 binding to the NAIP promoter was tested by JASPAR prediction, chromatin immunoprecipitation and dual-luciferase reporter assays, and causality was confirmed by NAIP knockdown/overexpression and by AAV9-mediated NAIP restoration in Irf8-knockout mice. RESULTS:NAIP was upregulated in diabetic renal tissue and correlated with declining renal function. Naip deletion attenuated proteinuria, fibrosis and NLRP3/NLRC4-dependent pyroptosis in STZ-diabetic mice, and NAIP knockdown reproduced this protection in high glucose-treated HK-2 cells. IRF8 was concurrently induced under hyperglycemia and correlated with NAIP expression; IRF8 bound directly to the NAIP promoter and transcriptionally activated it. NAIP overexpression abolished the protective effects of IRF8 silencing in vitro, and AAV9-mediated NAIP restoration similarly reversed the renoprotection conferred by Irf8 knockout in vivo. CONCLUSION:IRF8 transcriptionally drives NAIP expression to promote tubular inflammasome activation, pyroptosis and fibrosis in DKD, establishing the IRF8-NAIP axis as a novel mechanistic link and candidate therapeutic target in diabetic kidney disease.

Background The Hemoglobin Glycation Index (HGI) addresses several limitations of glycated hemoglobin and provides an accurate assessment of blood glucose control. It is associated with poor prognosis in diabetes and various cardiovascular diseases. However, the relationship between HGI and outcomes in heart failure (HF) populations requires further investigation. This study aims to explore the correlation between HGI and all-cause mortality in various phenotypes of HF populations using the MIMIC-IV database. Methods A linear regression model based on fasting blood glucose and glycated hemoglobin of HF patients was used to derive the HGI, which was then categorized into quartiles. The primary outcomes assessed were all-cause mortality at 30 days and 360 days. Kaplan-Meier (KM) curves were employed to analyze the relationship between each group and the occurrence of outcome events, with log-rank P-values used to evaluate differences between groups. Restricted cubic spline (RCS) analysis and Cox proportional hazard models, along with subgroup analyses, were utilized to determine the relationship between HGI and outcome events. Results This study included 3,470 HF patients, of whom 837 patients (24.1%) died within 365 days post-discharge. The KM curves indicated that HF patients in the lowest and highest quartiles of HGI had lower survival rates than those in the middle quartiles, with significant intergroup differences (log-rank P < 0.05). RCS analysis revealed a nonlinear U-shaped relationship between HGI, treated as a continuous variable, and all-cause mortality at both 365 days and 30 days in HF patients. The multivariate Cox model showed a close association between HGI and all-cause mortality at both 365 days and 30 days, demonstrating a trend in hazard ratios (HR) that initially decreased and then increased as HGI moved from low to high. Subgroup analyses and interaction tests confirmed the robustness of these results. Conclusions HGI is closely associated with both short-term and long-term all-cause mortality across all HF populations. This index may serve as an effective indicator for risk stratification and management of HF patients upon admission.

Background Heart failure (HF) is closely associated with abnormalities in glucose metabolism, which substantially influence clinical outcomes. The hemoglobin glycation index (HGI), reflecting the discrepancy between observed and predicted glycated hemoglobin, has emerged as a marker of interindividual variation in glycation beyond conventional HbA1c. However, the prognostic significance of HGI in hospitalized patients with HF remains unclear. Methods In this retrospective cohort study, we analyzed data from the MIMIC-IV database and included 3,470 adult patients hospitalized with HF. HGI was calculated as the difference between measured HbA1c and predicted HbA1c derived from fasting plasma glucose, and participants were categorized into quartiles. The primary outcome was 365-day all-cause mortality, and the secondary outcome was 30-day all-cause mortality. Kaplan–Meier survival analysis, restricted cubic spline modeling, multivariable Cox regression, and subgroup analyses were performed to evaluate the association between HGI and mortality. Results Among the 3,470 included patients, 837 (24.1%) died within 365 days after discharge. Restricted cubic spline analysis demonstrated a predominantly L-shaped association between HGI and both 30-day and 365-day all-cause mortality, with excess mortality risk mainly concentrated at low HGI values. In multivariable Cox models, compared with the lowest quartile, higher HGI quartiles were associated with significantly lower risks of both short-term and long-term mortality, supporting the particular vulnerability of patients with extremely low HGI. Subgroup analyses generally supported the robustness of these findings, although a significant interaction with diabetes status was observed for 365-day mortality. Conclusions HGI was independently associated with short-term and long-term all-cause mortality in hospitalized patients with HF, with a predominantly L-shaped pattern observed. Excess mortality risk was mainly concentrated at low HGI values. HGI may serve as a simple and accessible marker for risk stratification in this population.

Referral to, participation in, and execution of cardiac rehabilitation programs are comparatively lower in females than in males. The current study aimed to explore potential sex disparities in cardiorespiratory capacity and clinical outcomes after cardiac rehabilitation for coronary artery disease. Systematic searches were conducted across the PubMed, Embase, Cochrane Library, and Web of Science databases to identify studies assessing primary outcomes of cardiorespiratory capacity (peak oxygen uptake, peak metabolic equivalents, and its changes), secondary outcomes of cardiovascular endpoints (all-cause mortality, myocardial infarction, rehospitalization) and quality of life following cardiac rehabilitation in both female and male patients with coronary artery disease. A total of 22 predominantly observational studies involving 27 624 patients were analyzed, with 7441 (26.9%) being female and 20 183 (73.1%) being male. After cardiac rehabilitation, females showed lower peak oxygen uptake (mean difference −4.82, 95% confidence intervals −6.30 to −3.34 mL/kg/min, P < 0.00001), peak metabolic equivalents (−1.74, −2.34 to −1.14 units, P < 0.001) and its absolute changes from baseline (−0.40, −0.44 to −0.36 units, P < 0.001), as well as the worse quality of life when compared to males. However, there were no significant sex variations in all-cause mortality, myocardial infarction, and rehospitalization. In conclusion, females exhibited lower cardiorespiratory capacity and quality of life than males following cardiac rehabilitation. Despite these disparities, no sex-based differences existed in cardiovascular outcomes during the follow-up period after cardiac rehabilitation in patients with coronary artery disease. (Registration No. CRD42021269222)

Obstructive sleep apnea (OSA) is a widespread disorder impacting more than one billion individuals globally. Hypertension, a frequent cardiovascular comorbidity associated with OSA, can exacerbate and advance the condition. Recent research has identified a synergistic effect between anemia and OSA concerning the development of hypertension. This study explores the relationship between hemoglobin (Hb) and follow-up and 365-day all-cause mortality in individuals suffering from OSA and hypertension. Data were obtained from the MIMIC-IV database. Kaplan-Meier (KM) analyses and Cox proportional hazards models were utilized to assess associations with outcomes. Restricted cubic spline (RCS) models were selected to assess nonlinear relationships. A total of 6155 patients with first-time hospitalization for OSA and hypertension were included in this study. The KM survival curves demonstrated that the survival rate for the lowest Hb quartile (Q1) was significantly lower than that of the other quartiles. Findings from the multivariable Cox regression analysis revealed that elevated Hb correlates with a significant decrease in mortality risk. The RCS analysis demonstrated an L-shaped nonlinear relationship between Hb and outcome events (P-Nonlinear < 0.05). The relationship between Hb and outcome events remained consistent across all subgroups, further supporting the robustness of the conclusions drawn in this study. Hemoglobin is closely associated with all-cause mortality in patients with OSA and hypertension and can serve as an effective biomarker for risk management and prognostic assessment upon admission. Monitoring Hb in patients with OSA and hypertension and actively correcting anemia when present may improve prognostic survival.

The triglyceride-glucose body mass index (TyG-BMI) is acknowledged as a dependable surrogate biomarker for the evaluation of insulin resistance (IR). Current research indicates a significant correlation between TyG-BMI and the risk of subsequent cardiovascular events in individuals diagnosed with cardiovascular-kidney-metabolic syndrome (CKM) at stages 0-3. Nevertheless, the prognostic significance of TyG-BMI in patients with CKM stage 4 has not been extensively investigated, and there is a paucity of evidence available on this topic. The study utilized patient data from the Medical Information Mart for Intensive Care (MIMIC-IV) database, categorizing the data into quartiles based on the TyG-BMI index. The primary outcomes of interest were all-cause mortality at 180 days and at one year. To assess the relationship between the TyG-BMI index and these outcomes in patients diagnosed with stage 4 CKM, a Cox proportional hazards model was employed. Additionally, a restricted cubic splines(RCS) model was applied to further investigate the associations between the TyG-BMI index and the specified outcomes. A total of 1,885 patients participated in the study, with 62.49% of the cohort being male. The all-cause mortality rates were recorded at 30.50% at 180 days and 35.12% at one year. Analysis using a multivariate Cox proportional hazards model revealed that an increase in the TyG-BMI index was significantly correlated with a reduction in the risk of all-cause mortality at both the 180-day and one-year marks. Specifically, for each standard deviation increase in the TyG-BMI index, the risk of all-cause mortality decreased by 17% within 180 days (HR = 0.83, 95% CI: 0.76-0.91) and by 21% within one year (HR = 0.79, 95% CI: 0.71-0.87). Furthermore, regression analysis utilizing RCS indicated a linear decrease in all-cause mortality rates associated with increasing TyG-BMI index values over both the 180-day and one-year periods (P for nonlinearity = 0.171 and P for nonlinearity = 0.141, respectively). In patients diagnosed with stage 4 CKM syndrome, a reduced TyG-BMI index was found to be significantly correlated with a heightened risk of all-cause mortality within both 180 days and one year. Consequently, the TyG-BMI index may be utilized as an effective instrument for risk stratification and prognostic assessment in this patient population.

IntroductionObesity, especially abdominal obesity, is more common in patients with heart failure (HF), but body mass index (BMI) cannot accurately describe fat distribution. Several surrogate adiposity markers are available to reflect fat distribution and quantity. The objective of this study was to explore which adiposity marker is most highly correlated with HF prevalence, all-cause mortality and patients’ long-term survival.MethodsThe National Health and Nutrition Examination Survey (NHANES) database provided all the data for this study. Logistic regression analyses were adopted to compare the association of each surrogate adiposity marker with the prevalence of HF. Cox proportional hazards models and restricted cubic spline (RCS) analysis were employed to assess the association between surrogate adiposity markers and all-cause mortality in HF patients. The ability of surrogate adiposity markers to predict long-term survival in HF patients was assessed using time-dependent receiver operating characteristic (ROC) curves.Results46,257 participants (1,366 HF patients) were encompassed in this retrospective study. An area under the receiver operating characteristic curve (AUC) for the prevalence of HF assessed by weight-adjusted-waist index (WWI) was 0.70 (95% CI: 0.69-0.72). During a median follow-up of 70 months, 700 of 1366 HF patients’ death were recorded. The hazard ratio (HR) for HF patients’ all-cause mortality was 1.33 (95% CI: 1.06-1.66) in the a body shape index (ABSI) quartile 4 group and 1.43 (95% CI: 1.13-1.82) in the WWI quartile 4 group, compared with the lowest quartile group. The AUC for predicting 5-year survival of HF patients using the ABSI was 0.647 (95% CI: 0.61-0.68).ConclusionsWWI is strongly correlated with the prevalence of HF. In HF patients, those with higher WWI and ABSI tend to higher all-cause mortality. ABSI can predict patients’ long-term survival. We recommend the use of WWI and ABSI for assessing obesity in HF patients.

The ST segment elevation myocardial infarction (STEMI) patients tend to experience cardiovascular events following percutaneous coronary intervention (PCI), and the prognosis remains suboptimal. The objective of this investigation was to examine the correlation between the ratio of glycosylated hemoglobin A1c/Apolipoprotein A1 (HbA1c/ApoA-1) and the short-term prognosis in STEMI patients following PCI. This study conducted a retrospective analysis of the clinical data of 182 patients diagnosed with STEMI following PCI and admitted to our hospital between January 2022 and June 2023. The patients were categorized into two groups based on the occurrence of major adverse cardiovascular events (MACEs), and a comparative analysis of baseline characteristics was performed. The significant correlation between HbA1c/ApoA-1 with short-term MACEs in STEMI patients post-PCI were determined through univariate and multivariate logistic regression analysis. Different models and Subgroup analysis demonstrated that HbA1c/ApoA-1 was independent risk factor for MACEs in STEMI patients post-PCI and exhibited high stability. Receiver operating characteristic (ROC) curve and area under curve (AUC) value were utilized to validate the predictive value of HbA1c/ApoA-1 in forecasting outcomes among STEMI patients post-PCI, with an AUC of 0.752 (95% CI: 0.68-0.86), sensitivity of 85.7%, and specificity of 56.8%. Restricted cubic spline (RCS) was employed to evaluate the potential non-linear relationship between HbA1c/ApoA-1 levels and MACEs in STEMI patients post-PCI. Our results demonstrated high and significant correlation between HbA1c/ApoA-1 and short-term prognosis, and indicated that HbA1c/ApoA-1 was independent risk factor for MACEs in STEMI patients following PCI and possessed significant predictive value, facilitating the early identification of high-risk cohorts and the anticipation of MACEs.

AIMS:This study evaluates 16 commonly used glucose and lipid metabolism indicators closely associated with type 2 diabetes (T2D) risk, utilizing data from a prospective cohort study with a maximum follow-up of 12 years, to identify the optimal indicator for early recognition of future T2D risk. METHOD:Through conducting receiver operating characteristic (ROC) analysis to assess the predictive value of all indicators and multivariable Cox analysis to assess their importance in diabetes incidence, the optimal indicator was identified. Subgroup ROC and Time-dependent ROC (TimeROC) analyses were employed to verify the robustness of the optimal indicator's predictive performance. RESULTS:A total of 15,453 participants were included. ROC indicated that triglyceride glucose-waist height ratio index (TyG-WHtR) had the highest area under the curve value of 0.786. The fully adjusted multivariable model showed that TyG-WHtR had a high hazard ratio of 2.99 (95 % CI 2.45, 3.65). Subgroup ROC and TimeROC indicated that TyG-WHtR maintained excellent and sustained predictive capability across different populations and times over 1 to 12 years. CONCLUSION:TyG-WHtR is a promising and robust indicator for predicting the long-term risk of T2D in the general population, enables the detection of T2D high-risk individuals, and offers personalized and accurate risk stratification.

Tafamidis is approved in many countries for the treatment of patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Approval is largely based on findings from an international phase 3 trial. This post-approval commitment study aimed to evaluate the safety and efficacy of tafamidis in patients with ATTR-CM in China. A multicenter, single-arm study in Chinese patients with symptomatic ATTR-CM in China. All patients received once-daily, open-label tafamidis free acid 61 mg for 12 months. Safety reporting was ongoing with efficacy assessments at months 6 and 12, including 6-min walk test distance, New York Heart Association (NYHA) functional classification, National Amyloidosis Centre staging, N-terminal pro-B-type natriuretic peptide and troponin I concentrations, Kansas City Cardiomyopathy Questionnaire Overall Summary score, 5-level EQ-5D index score, EQ visual analog scale, and 12-item Short Form Survey. Patients (n = 53) were aged 60 (standard deviation [SD]: 12) years, 89

Background: The atherogenic index of plasma (AIP) is closely associated with various metabolic disorders, cardiovascular diseases, and chronic kidney disease, and it has also been shown to correlate with cardiovascular risk in patients with Cardiovascular-kindey-metabolic syndrome (CKM) stages 0-3; however, the role of AIP in the prognosis of patients with CKM stage 4 remains to be investigated. Methods: This study used data from the MIMIC database, with outcome events defined as long-term mortality and 365-day mortality. We examined the relationship between the AIP and the occurrence of outcome events in patients with CKM stage 4 using Kaplan-Meier curves, restricted cubic splines (RCS), and Cox proportional hazards models, while ensuring the robustness of our conclusions through subgroup analyses and interaction terms. Results: A total of 7,672 patients were included, of whom 4,466 (58.2%) were male. Multivariable Cox analysis revealed that compared to the lowest quartile, the hazard ratio (HR) for follow-up mortality in the highest quartile was 1.27 (95% CI: 1.11-1.46, P<0.001), and the HR for 365-day mortality was 1.39 (95% CI: 1.17-1.66, P<0.001). The risk of death increased linearly with increasing AIP (P for trend < 0.05). The results from the RCS, subgroup analyses, and interaction terms confirmed the robustness of these conclusions. Conclusions: AIP is an independent risk factor for the long-term prognosis of patients with CKM stage 4, and this index can serve as an effective indicator for risk stratification upon admission and long-term prognosis assessment. Monitoring AIP and implementing early interventions for dyslipidemia may help improve survival rates in patients with CKM stage 4. Keywords: Atherogenic index of plasma, Cardiovascular-kindey-metabolic syndrome, Long-term prognosis, Retrospective cohort study

BACKGROUND:Sex-related differences in outcomes of sodium-glucose co-transporter 2 (SGLT2) inhibitors therapy in acute myocardial infarction remain inconclusive. METHODS:This real-world retrospective study compared sex disparities in primary outcomes (pro-brain natriuretic peptide levels and left ventricular ejection fraction), secondary outcomes (major adverse cardiovascular and cerebrovascular events), and additional laboratory outcomes (serum lipids, fasting glucose, glycosylated hemoglobin, serum creatinine, urea nitrogen, and estimated glomerular filtration rate) among women and men with acute myocardial infarction who were treated with SGLT2 inhibitors. RESULTS:A total of 310 patients participated in the study, of whom 244 (78.7%) were men and 66 (21.3%) were women. The baseline characteristics revealed distinct clinical and demographic profiles between the sexes regarding age, type of myocardial infarction, presence of multivessel disease, incidence of new-onset heart failure, and renal function within the study population. After two years of follow-up, no significant sex differences were observed in cardiac function (assessed by pro-brain natriuretic peptide and left ventricular ejection fraction), major adverse cardiovascular and cerebrovascular events, metabolic parameters, or renal outcomes among acute myocardial infarction patients treated with SGLT2 inhibitors. Exploratory analysis revealed a higher risk of recurrent myocardial infarction and heart failure hospitalization in female versus male patients in this cohort. CONCLUSION:Among patients with acute myocardial infarction treated with early SGLT2 inhibitor initiation, cardiorenal-metabolic and primary clinical outcomes are sex-independent, indicating no significant sex disparities in outcomes of SGLT2 inhibitor therapy.

The Cardiovascular-kidney-metabolic (CKM) syndrome is a health disorder caused by interactions between cardiovascular disease, kidney disease, and metabolism-related risk factors. The stress hyperglycemia ratio (SHR) has been shown to correlate with the prognosis of participants with diabetes mellitus, heart failure, and myocardial infarction. However, the predictive value of SHR in the CKM syndrome population is unclear and requires further exploration. This study analyzed 19,345 participants from the National Health and Nutrition Examination Survey (1999–2018). CKM syndrome was staged according to the American Heart Association (AHA) guidelines. SHR was calculated using fasting blood glucose (FBG) and glycated hemoglobin type A1c (HbA1c). Participants were grouped into four quartiles based on SHR. The primary and secondary outcomes were all-cause mortality and cardiovascular mortality, respectively. Kaplan-Meier survival curves and Cox proportional hazard regression models were used to evaluate the association between SHR and outcomes. Then, the potential nonlinear relationship was explored using restricted cubic spline (RCS) analysis. We also performed subgroup analyses to assess the effects of different variables. A total of 2,736 all-cause deaths and 699 cardiovascular deaths were recorded during a median follow-up period of 115 months. Kaplan-Meier analysis revealed that participants in quartile 2 had the lowest risk for both all-cause and cardiovascular mortality (Log Rank P < 0.05). Multivariate Cox regression demonstrated the lowest all-cause mortality in the 2nd quartile (HR = 0.84, 95

OBJECTIVE:Qiliqiangxin (QLQX) capsule- a traditional Chinese medicine used for treating heart failure (HF), can modulate inflammatory cytokines in rats with myocardial infarction. However, its immune-regulating effect on dilated cardiomyopathy (DCM) remains unknown. The aim of this study was to investigate whether QLQX has a unique regulatory role in the imbalance of pro- and anti-inflammatory cytokines in patients with DCM. METHODS:The QLQX-DCM is a randomized- double-blind trial conducted at 24 tertiary hospitals in China. A total of 345 patients with newly diagnosed virus-induced DCM were randomly assigned to receive QLQX capsules or placebo while receiving optimal medical therapy for HF. The primary endpoints were changes in plasma inflammatory cytokines and improvements in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDd) over the 12-month treatment. RESULTS:At the 12-month follow-up, the levels of IFN-γ, IL-17, TNF-α, and IL-4 decreased significantly, while the level of IL-10 increased in both groups compared with baselines (all P<0.0001). Furthermore-these changes, coupled with improvements in LVEF, NT-proBNP and New York Heart Association (NYHA) functional classification, excluding the LVEDd in the QLQX group, were greater than those in the placebo group (all P<0.001). Additionally, compared with placebo, QLQX treatment also reduced all-cause mortality and rehospitalization rates by 2.17% and 2.28%, respectively, but the difference was not statistically significant. CONCLUSION:QLQX has the potential to alleviate the imbalance of inflammatory cytokines in patients with DCM, potentially leading to further improvements in cardiac function when combined with anti-HF standard medications.

BACKGROUND: There is mounting evidence that exercise hypertension (EH) in hypertensive patients is linked to cardiovascular disease events, end-organ damage, and mortality. This study aimed to investigate the effect of diverse antihypertensive medications on exercise hypertension (EH) and cardiopulmonary exercise performance in patients with essential hypertension. METHODS: Clinical data from 205 patients with essential hypertension achieving standard resting blood pressure after medication were retrospectively collected. Patients were categorized into EH group and general group based on their CPET results. Logistic regression analysis was used to assess the correlation between treatment options and EH. Additionally, multiple sample rank sum tests were conducted to evaluate the effects of treatment options on cardiopulmonary exercise performance. RESULTS: In monotherapy options, β-blockers significantly reduced the risk of EH; For combination therapy options, β-blockers combined with non-ARNI also showed a significant reduction in EH risk. Additionally, β-blockers were more effective than other drugs in reducing HPr , BPr , VO2peak, HRR at 1min?12 times/minute proportion, and more effective than ARNI in reducing BPr and VO2peak. Moreover, β-blockers + ARNI are found to be more effective than other drugs in reducing HRr and VO2peak, and more effective than ARNI in reducing VO2peak. CONCLUSIONS: Among essential hypertensive patients achieving standard resting blood pressure levels through therapy, the therapy involving β-blockers can reduce the risk of EH. However, ACEI/ARBs, ARNI or CCBs alone did not reduce EH risk. Compared to ARNI, therapy involving β-blockers reduces cardiorespiratory tolerance, heart rate and blood pressure responseand,and increases vagal tone in hypertensive patients. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Key Research and Development Program of Shaanxi Province grant 2020ZDLSF02-09 ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study received approval from the Medical Ethics Committee of the Second Affiliated Hospital of Xi'an Jiaotong University (approval number: 2020055). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes I hereby declare that all authors have read and approved the submission of the manuscript; the manuscript has not been published and is not being considered for publication elsewhere, in whole or in part, in any language, except as an abstract.

Autoimmune myocarditis (AM) is characterized by an intricate inflammatory response within the myocardium. Dynamin-related protein 1 (Drp1), a pivotal modulator of mitochondrial fission, plays a role in the pathogenesis of various diseases. A myosin-induced experimental autoimmune myocarditis (EAM) mouse model was successfully established. Flow cytometry was employed to detect M1/M2-like macrophages. Mitochondrial fragmentation was assessed using Mito-Tracker Red CMXRos. Drp1 was upregulated and activated in EAM mice. Depletion of Drp1 was observed to mitigate inflammation, macrophage infiltration and M1 polarization within the cardiac tissue of EAM mice. In M1-like macrophages derived from the hearts of EAM mice, Drp1 was found to promote mitochondrial fission and diminish mitochondrial fusion. Furthermore, the depletion of Drp1 reduced the NF-κB-related pro-inflammatory response in EAM-associated M1-like macrophages. Drp1 drives mitochondrial fission in macrophages, driving their M1 polarization and the subsequent inflammatory response. Drp1 may represent an effective target for the prevention and treatment of AM.

Background Although previous research has substantiated lifestyle and cardiovascular-related measures have some impact on cognitive function, studies focusing on the correlation between Life's Essential 8 (LE8), an indicator for quantifying cardiovascular health (CVH), and cognitive function are limited. Consequently, this study sought to explore the potential link between CVH and cognitive function as well as to determine if depressive states mediated the relationship.Methods A total of 2,263 individuals were selected from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). Post-averaged LE8 scores was classified as low CVH (0-49), moderate CVH (50-79), and high CVH (80-100) according to the American Heart Association (AHA). Cognitive function was evaluated using the Animal Fluency Test (AFT), the Digit Symbol Substitution Test (DSST), the instant recall test (IRT), and the delayed recall test (DRT). The Z-score is figured by subtracting the average of the scores of four test sections and dividing by the standard deviation. Models of multi-variable linear regression were employed to appraise the relationships between CVH and the Z-score for cognitive function. Depression was assessed through the utilization of the Patient Health Questionnaire (PHQ-9). Points of 10 or above indicated a positive diagnosis. Weighted linear regression and restricted cubic spline (RCS) were employed to evaluate the correlation between CVH and cognitive function. Pearson's test was utilized to explore the interrelation among primary variables and mediated effects analyses of depressive states.Results A significant positive linear relationship was observed between LE8 score and cognitive function Z-score. In all models, there was a positive correlation between higher Z-score for cognitive function and every ten points added to the LE8 score, which evaluates CVH. The findings of the mediating effect study indicated that the effects of cardiovascular health on cognitive function were partially mediated by depression.Conclusion Results showed a meaningful positive linear correlation between the level of CVH and cognitive function, with a mediating role for depression. These results accentuate the significance of sustaining high CVH and avoiding depression to improve cognitive functioning.

Viral myocarditis (VMC) is a common myocardial inflammatory disease characterized by inflammatory cell infiltration and cardiomyocyte necrosis. Sema3A was reported to reduce cardiac inflammation and improve cardiac function after myocardial infarction, but its role in VMC remains to be explored. Here, a VMC mouse model was established by infection with CVB3, and Sema3A was overexpressed in vivo by intraventricular injection of an adenovirus-mediated Sema3A expression vector (Ad-Sema3A). We found that Sema3A overexpression attenuated CVB3-induced cardiac dysfunction and tissue inflammation. And Sema3A also reduced macrophage accumulation and NLRP3 inflammasome activation in the myocardium of VMC mice. In vitro, LPS was used to stimulate primary splenic macrophages to mimic the macrophage activation state in vivo. Activated macrophages were co-cultured with primary mouse cardiomyocytes to evaluate macrophage infiltration-induced cardiomyocyte damage. Ectopic expression of Sema3A in cardiomyocytes effectively protected cardiomyocytes from activated macrophage-induced inflammation, apoptosis, and ROS accumulation. Mechanistically, cardiomyocyte-expressed Sema3A mitigated macrophage infiltration-caused cardiomyocyte dysfunction by promoting cardiomyocyte mitophagy and hindering NLRP3 inflammasome activation. Furthermore, NAM (a SIRT1 inhibitor) reversed the protective effect of Sema3A against activated macrophage-induced cardiomyocyte dysfunction by suppressing cardiomyocyte mitophagy. In conclusion, Sema3A promoted cardiomyocyte mitophagy and suppressed inflammasome activation by regulating SIRT1, thereby attenuating macrophage infiltration-induced cardiomyocyte injury in VMC.

Background The triglyceride glucose-body mass (TyG-BMI) index is acknowledged as both a reliable indicator of the risk of cardiovascular disease and an accurate surrogate biomarker for evaluating insulin resistance (IR). The importance of the TyG-BMI index among people with heart failure (HF), however, requires more investigation. The objective of this study was to inquire about the relationship between HF patients’ TyG-BMI index and their risk of 360-day mortality. Methods The Medical Information Mart for Intensive Care (MIMIC-IV) database provided the study’s patient data, which were divided into quartiles according to their TyG-BMI index. The endpoint was mortality from all causes within 360 days. Kaplan-Meier analysis was used to compare this primary endpoint amongst the four groups indicated above. The association between the TyG-BMI index and the endpoint was investigated using restricted cubic splines and Cox proportional hazards analysis. Results The study enrolled a total of 423 patients with HF (59.2% male), of whom 70 patients (16.9%) died within 360 days. Patients with higher TyG-BMI indexes had significantly lower mortality risks, according to the Kaplan-Meier analysis (log-rank P = 0.003). Furthermore, the restricted cubic spline analysis illustrated a decrease in the risk of all-cause mortality with an increasing TyG-BMI index. Additionally, multivariable Cox proportional hazards analyses showed that the risk of 360-day death from all causes was considerably higher in the lowest quartile of TyG-BMI. In comparison to the lowest TyG-BMI group, the fully adjusted Cox model yielded a hazard ratio (HR) of 0.24 (95% CI: 0.10, 0.59; p = 0.002) for 360-day mortality. Conclusions In patients diagnosed with HF, a lower TyG-BMI index is strongly related to a higher risk of 360-day mortality. This index can be employed to categorize the risk levels of patients with HF and predict their one-year all-cause mortality .

OBJECTIVE:To explore whether metformin reduces cardiotoxicity of doxorubicin through the AMPK pathway. METHODS:We analyzed the data of 123 patients with myeloid leukemia, non-Hodgkin's lymphoma, or breast cancer receiving doxorubicin for phased chemotherapy, including 43 patients receiving combined treatment with metformin (test group) and 80 without metformin treatment (control group). The changes in plasma levels of CK-MB, LDH, and BNP, left ventricular ejection fraction (EF) and left ventricular fractional shortening (FS) of the patients were observed. The effect of treatments with metformin and doxorubicin, alone or in combination, on myocardial damage, cardiac function and myocardial cell apoptosis were also observed in C57BL/6 mice with AMPKα2 gene knockout (AKO). RESULTS:CK-MB, LDH and BNP levels increased and EF and FS decreased significantly in the control group after chemotherapy (P<0.05). In the test group, CK-MB, LDH and BNP levels were significantly lowered after the combined treatment (P<0.05), while EF and FS did not undergo obvious changes (P>0.05). CK-MB, LDH and BNP levels were lower and EF and FS were higher significantly in the test group than in the control group after the treatment (P<0.05). Doxorubicin treatment reduced FS in both wild-type and AKO mice, but the reduction was less obvious in AKO group (P<0.05). The combined treatment restored FS in wild-type mice (P<0.05) but not in AKO mice. Doxorubicin significantly increased LDH and cTnI levels in both wild-type and AKO mice, but with smaller increments in the latter (P<0.05); The combined treatment with metformin reduced doxorubicin-induced elevation of LDH and cTnI levels in the wild-type mice (P<0.05) but not in AKO group (P>0.05). Doxorubicin increased myocardial cell apoptosis in both mice (P<0.01) but less strongly in AKO mice (P<0.05). CONCLUSION:Chemotherapy with doxorubicin causes cardiotoxicity, which can be mitigated by combined treatment with metformin possibly through a mechanism involving the AMPK pathway.