BACKGROUND:This study aims to investigate the mediation effects of the systemic inflammation on the association between urinary polycyclic aromatic hydrocarbons (PAHs) metabolites and hypertension in general US population. METHODS:This cross-sectional study analyzed 9 urinary PAHs metabolites from the 2003-2012 National Health and Nutrition Examination Survey (NHANES). Quantile g-computation (QG-C) were applied to assess the association between PAHs mixture exposure and hypertension prevalence. The associations among PAHs (exposure), hypertension (outcome), and inflammatory markers (C-reactive protein, alkaline phosphatase, white blood cell count, neutrophil count, and monocyte count; mediators) were investigated using mediation analysis. RESULTS:Among the 6846 participants, 2473 (36.1%) were diagnosed with hypertension. The mean of systolic and diastolic BP were 138.6 (20.4) and 72.7 (16.0) mmHg in the hypertensive group, and 115.8 (10.9) mmHg and 69.0 (10.0) mmHg in the non-hypertensive group. The mixture of urinary PAHs metabolites was significantly associated with increased prevalence of hypertension, with β = 0.124 (95% CI: 0.04, 0.20) for every quantile increase. Urinary 1-PHE (36.48%), 2-FLU (27.64%) and 1-PYR (26.64%) had the greatest positive contribution to the overall effect. Mediation analysis revealed that inflammatory markers play a mediating role in the associations between PAHs metabolites (2-FLU, 3-PHE, 1-PHE, 2-PHE, 1-PYR, and 9-FLU) and hypertensive adults. CONCLUSIONS:Our study demonstrated that mixture exposure to PAHs is associated with the prevalence of hypertension in US adult population, which might be primarily driven by 1-PHE, 2-FLU and 1-PYR. Furthermore, we have observed that systemic inflammation plays a significant mediating role in this associations.

Atherosclerosis, a chronic inflammatory condition characterized by plaque formation, often leads to instability, particularly under Type 2 diabetes mellitus (T2DM) conditions, which exacerbate cardiovascular risks. However, the molecular mechanisms underlying this process remain incompletely understood. In this study, we investigated the correlation between acute coronary syndrome (ACS) and serum levels of Nε-carboxyethyl-lysin (CEL), a prominent advanced glycation end product (AGE) elevated in T2DM, in a cohort of 225 patients with coronary artery disease. Using a murine model of atherosclerosis complicated by T2DM, we examined the effects of CEL on plaque stability and macrophage autophagy. Our findings revealed that elevated serum CEL levels are independently associated with increased ACS incidence. Metabolomic profiling identified CEL as a key AGE contributing to plaque instability in diabetic conditions. Mechanistically, CEL disrupted macrophage autophagy and plaque stability by perturbing the Receptor for Advanced Glycation End products (RAGE)/Liver Kinase B1 (LKB1)/AMP-activated Protein Kinase 1 (AMPK1)/Sirtuin 1 (SIRT1) signaling cascade. This pathway further regulated autophagic activity through SIRT1-mediated acetylation of Zinc Finger with KRAB and SCAN Domains 3 (ZKSCAN3). These findings highlight CEL’s critical role in promoting plaque instability in T2DM by impairing key molecular pathways that regulate autophagy, offering potential therapeutic targets for managing atherosclerosis in diabetic patients.

Disturbances in calcium (Ca), vitamin D, and electrolyte balance have been implicated in diabetic kidney disease (DKD), yet existing evidence remains inconsistent. Moreover, the role of albumin-corrected Ca—a more accurate measure of biologically active Ca in patients with frequent hypoalbuminemia—remains poorly defined in type 2 diabetes mellitus (T2DM). We aimed to investigate the association between albumin-corrected Ca, vitamin D, electrolytes and DKD in a large T2DM cohort. In this cross-sectional study, 5550 T2DM patients were enrolled, including 1574 participants with DKD. Multivariable regression analyses were used to assess the association between albumin-corrected Ca, vitamin D and DKD. Spearman’s correlation analyses were conducted to examine the correlation between electrolyte levels, vitamin D and indicators of renal impairment. Patients with DKD in T2DM were older, predominantly male, with longer diabetes duration, higher blood pressure, poorly glycemic control and more diabetic complications compared to those without DKD. Notably, patients with DKD also showed significant electrolyte imbalances, suggesting dysregulated mineral metabolism. Multivariate logistic regression revealed albumin-corrected Ca (odds ratio [OR]: 4.032, 95

BACKGROUND Angiopoietin-like 3 (ANGPTL-3) inhibits the activity of lipoprotein lipase and endothelial lipase, increasing both serum low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels. SHR-1918 is a fully human monoclonal antibody against ANGPTL-3. OBJECTIVES The aim of this study was to assess the lipid-altering efficacy and safety of SHR-1918 in patients at moderate or higher risk of atherosclerotic cardiovascular disease (ASCVD) with suboptimally controlled hyperlipidemia. METHODS A multicenter, randomized, double-blind, placebo-controlled, dose-escalation phase 2 study was designed to evaluate the effects of SHR-1918 in hypercholesterolemic patients, who did not achieve optimal LDL-C after 4 to 8 weeks of standard lipid-lowering therapies. A total of 333 patients were enrolled sequentially into 1 of 8 dose cohorts at a 4:1 (active/placebo) ratio. Patients received subcutaneous SHR-1918 at doses of 150, 300, or 600 mg every 4 weeks (Q4W), or SHR-1918 at a dose of 600 mg every 8 weeks (Q8W), alternating with placebo for a total treatment period of 16 weeks. The extension treatment included subcutaneous SHR-1918 at a dose of 150, 300, or 600 mg Q4W over 36 weeks, or SHR-1918 a dose of 600 mg Q8W over 40 weeks and then followed for safety. Prespecified endpoints included percentage change from baseline in LDL-C and TG. Safety was assessed with laboratory test results and by the incidence and severity of adverse events. RESULTS SHR-1918 demonstrated a clear dose-response relationship with respect to percentage LDL-C lowering for both Q4W and Q8W administration: 21.7%, 27.3%, and 29.9% with 150, 300, and 600 mg Q4W compared with placebo, respectively, and 22.5% with 600 mg Q8W compared with placebo. SHR-1918 also substantially reduced TG, non-highdensity lipoprotein cholesterol, apolipoprotein B, and apolipoprotein A1, with a better achievement of LDL-C targets. SHR-1918 was generally well-tolerated. CONCLUSIONS Based on standard lipid-lowering therapy, ANGPTL-3 inhibition with SHR-1918 further reduces LDL-C by 21.7% to 29.9% in patients at moderate or higher risk of ASCVD. These additional reductions are both dose and dosing frequency dependent. (Evaluate the Efficacy and Safety of SHR-1918 in Patients With Hyperlipidemic; NCT06109831) (JACC. 2025;85:1821-1835) (c) 2025 by the American College of Cardiology Foundation.

OBJECTIVE: To investigate the protective effect of matrine on coronary microvascular dysfunction(CMD) induced by advanced glycation end products(AGEs) in a mouse model of ischemia with non-obstructive coronary artery disease(INOCA), with a focus on the underlying mechanisms, particularly the endoplasmic reticulum(ER) stress protein kinase R-like ER kinase(PERK)/nuclear factor of activated T-cells(NFAT) signaling pathway. METHODS: An INOCA model was established in mice, and CMD was induced by peritoneal injections of AGEs. Matrine was administered daily via intraperitoneal injections. Coronary microcirculation was evaluated using coronary flow velocity reserve(CFVR), and cardiac microvascular endothelial cells(CMECs) were isolated for assessment of apoptosis, inflammation, oxidative stress, and microthrombosis. Markers of ER stress and the PERK/NFAT pathway were examined through immunoblotting, immunofluorescence, and enzymatic assays. The effect of matrine were further evaluated in CMECs treated with AGEs and the PERK agonist. RESULTS: Matrine treatment significantly improved CFVR and reduced CMD in AGEs-exposed INOCA mice. In CMECs, matrine attenuated AGEs-induced apoptosis, inflammation, and microthrombosis. It also suppressed intracellular reactive oxygen species(ROS) generation, ER stress markers, and PERK/NFAT signaling. Matrine's effects were concentration-dependent and partially reversed by the PERK agonist, confirming its action through the ER stress pathway. No significant toxicities were observed with matrine administration. CONCLUSION: Matrine attenuates AGEs-induced CMD in INOCA by suppressing the ROS-mediated ER stress PERK/NFAT signaling pathway in CMECs. This study highlights matrine's potential as a therapeutic agent for CMD in diabetic cardiovascular complications.

Coronary artery disease (CAD) remains a significant global health burden, profoundly impacting both physical and mental well-being. Psychocardiology underscores the critical influence of psychological factors on the development, diagnosis, and management of cardiovascular diseases. Patients with CAD frequently experience high rates of depression and anxiety, which are closely linked to mental stress-induced myocardial ischemia, cognitive impairment, and delirium. Given that cognitive decline and delirium severely compromise patient prognosis, targeted interventions and standardized care are essential. To address these needs, the Psychocardiology Medicine Branch of Chinese Medical Association Beijing Branch and the Psychocardiology Education Professional Committee of China Medical Education Association, together with over 50 experts from 40 organizations, have developed these association standards (No. T/CAS 812-2024). This December 2025 update provides a refined framework for the clinical diagnosis and treatment of CAD complicated by depression, anxiety, and cognitive impairment. These guidelines aim to direct standardized clinical practice and improve the overall physical and psychological prognosis for this high-risk population.

Septic cardiomyopathy is a considerable complication in sepsis, which has high mortality rates and an incompletely understood pathophysiology, which hinders the development of effective treatments. α‑ketoglutarate (AKG), a component of the tricarboxylic acid cycle, serves a role in cellular metabolic regulation. The present study delved into the therapeutic potential and underlying mechanisms of AKG in ameliorating septic cardiomyopathy. A mouse model of sepsis was generated and treated with AKG via the drinking water. Cardiac function was assessed using echocardiography, while the mitochondrial ultrastructure was examined using transmission electron microscopy. Additionally, in vitro, rat neonatal ventricular myocytes were treated with lipopolysaccharide (LPS) as a model of sepsis and then treated with AKG. Mitochondrial function was evaluated via ATP production and Seahorse assays. Additionally, the levels of reactive oxygen species were determined using dihydroethidium and chloromethyl derivative CM‑H2DCFDA staining, apoptosis was assessed using a TUNEL assay, and the expression levels of mitochondria‑associated proteins were analyzed by western blotting. Mice subjected to LPS treatment exhibited compromised cardiac function, reflected by elevated levels of atrial natriuretic peptide, B‑type natriuretic peptide and β‑myosin heavy chain. These mice also exhibited pronounced mitochondrial morphological disruptions and dysfunction in myocardial tissues; treatment with AKG ameliorated these changes. AKG restored cardiac function, reduced mitochondrial damage and corrected mitochondrial dysfunction. This was achieved primarily through increasing mitophagy and mitochondrial fission. In vitro, AKG reversed LPS‑induced cardiomyocyte apoptosis and dysregulation of mitochondrial energy metabolism by increasing mitophagy and fission. These results revealed that AKG administration mitigated cardiac dysfunction in septic cardiomyopathy by promoting the clearance of damaged mitochondria by increasing mitophagy and fission, underscoring its therapeutic potential in this context.

Objective This study was to investigate the correlation between urine volatile organic compound (VOC) metabolites and obesity-related outcomes, including BMI, waist circumference, obesity, and abdominal obesity. Methods Data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2016 were utilized for this analysis. Linear regression and logistic regression models were employed to estimate β-coefficients or odds ratios (ORs) along with their corresponding 95% confidence intervals (CIs). Quantile g-computation (Qgcomp) regression, a method designed to evaluate the combined effects of multiple correlated chemical exposures, was used to assess the mixed influence of VOC metabolites on obesity-related outcomes. Results A total of 4,950 adults were included in this analysis. The median age of the participants was 47 (33, 60) years, with 49.3% being male. The median BMI was 27.7 (24.2, 32.4) kg/m2, and the median waist circumference was 98.0 (87.3, 109.0) cm. The prevalence of obesity and abdominal obesity was 36.8% and 56.5%, respectively. After adjusting for all covariates, urine VOC metabolites (including AAMA, AMCC, BMA, CYMA, DHBMA, 3HPMA, 2HPMA, MA, 2MHA, 3MHA+4MHA, MHBMA3, PGA, and HPMMA) exhibited a negative association with obesity. With the exception of BMA and DHBMA, similar results were observed regarding the association between urine VOC metabolites and the prevalence of abdominal obesity. Additionally, Qgcomp regression analysis revealed a significant negative correlation between the mixture of urine VOC metabolites and all obesity-related outcomes, with 2HPMA demonstrating the strongest influence on this negative association. Conclusion Our findings suggest a negative relationship between exposure to VOCs, as measured by urine VOC metabolite levels, and obesity in adults.

Background: Recurrence of atrial fibrillation (AF) frequently occurs in patients following catheter ablation. The identification of predictors for postprocedural AF recurrence is therefore of great importance but the discriminative value of the E/e′ ratio on echocardiography is still unclear. This study aimed to perform a comprehensive analysis of the E/e′ ratio for predicting the recurrence in patients with AF after catheter ablation.Methods: Data were retrospectively screened from seven hundred and eighty-four consecutive patients with nonvalvular AF who underwent the initial ablation. The incidence of AF recurrence was recorded during the follow-up period of 36 months after the procedure. The E and e′ velocities on echocardiography were obtained at admission. Uni- and multivariate analysis were conducted to assess the association of E/e′ ratio and AF recurrence. The nomogram model was developed to screen the score of the E/e′ ratio in relation to AF recurrence. The receiver operating characteristic and the Kaplan-Meier curves were produced to estimate diagnostic efficiency of the E/e′ ratio to predict recurrence.Findings: Of the 784 patients beyond the first three months blanking period, 209 (26.7%) cases experienced AF recurrence. The lateral E/e′ ratio was higher in patients with AF recurrence compared to those with maintenance of sinus rhythm together with body mass index, percentage of obstructive sleep apnea, CHA2DS2-Vasc score, invasive left atrial pressure, left arial diameter and septal E/e′ ratio. The nomogram model indicated the incidence of AF recurrence gradually increased with lateral E/e′ ratio. Further analysis confirmed the lateral E/e′ ratio as an independent predictor of the postprocedural recurrence of AF. It was identified that the lateral E/e′ ratio appeared a good discriminatory performance with an optimal cut-off value ≥ 9.8 to predict AF recurrence.Interpretation: The lateral E/e′ ratio could be used as a valuable predictor for AF recurrence after ablation. It would help to establish the clinical application of the lateral E/e′ ratio ≥ 9.8 as a reliable noninvasive index on echocardiography to predict recurrence after the therapeutic intervention.Funding: None.Declaration of Interest: The authors declare no competing interests.Ethical Approval: The study complied with the ethical principles for medical research involving human established by the Declaration of Helsinki and was approved by the Ethics Committee of the Second Affiliated Hospital of Xi'an Jiaotong University. Informed consent was waived since this was a retrospective study.

Atherosclerosis, characterized by chronic inflammation within the arterial wall, remains a pivotal concern in cardiovascular health. We developed a dual-targeted liposomal system encapsulating Dll4-targeting siRNA, designed to selectively bind to pro-inflammatory M1 macrophages through surface conjugation with anti-F4/80 and anti-CD68 antibodies. The Dll4-targeting siRNA is then delivered to the macrophages, where it silences Dll4 expression, inhibiting Notch signaling and reducing plaque vulnerability. Emphasizing accuracy in targeting, the system demonstrates effective suppression of Dll4, a key modulator of atherosclerotic progression, and vulnerability via VSMCs phenotypic conversion and senescence. By employing liposomes for siRNA delivery, we observed enhanced stability and specificity of the siRNA. Alongside the therapeutic efficacy, our study also evaluated the safety profile and pharmacokinetics of the dual-targeted liposomal system, revealing favorable outcomes with minimal off-target effects and optimal biodistribution. The integration of RNA interference techniques with advanced nanotechnological methodologies signifies the importance of targeted delivery in this therapeutic approach. Preliminary findings suggest a potential attenuation in plaque development and vulnerability, indicating the therapeutic promise of this approach. This research emphasizes the potential of nanocarrier-mediated precision targeting combined with a reassuring safety and pharmacokinetic profile for advancing atherosclerosis therapeutic strategies.