Individuals with cardiovascular-kidney-metabolic (CKM) syndrome face an elevated risk of stroke, yet effective risk stratification indicators remain limited. This prospective study aims to investigate the associations of biological age acceleration (BioAge-gap) and heart age acceleration (HeartAge-gap) with new-onset stroke in individuals with CKM syndrome Stages 0-3, utilizing data from the China Health and Retirement Longitudinal Study (CHARLS) collected between 2015 and 2020. Baseline BioAge-gap and HeartAge-gap were calculated via the Klemera-Doubal method (KDM) and Framingham risk score (FRS), respectively. The primary outcome was self-reported physician-diagnosed stroke identified during the 2018 and 2020 follow-ups. Analysis of 7283 eligible participants aged 45-75 years revealed a positive association between BioAge-gap and new-onset stroke (odds ratio [OR] = 1.05, p < 0.01). Furthermore, compared to participants with a non-positive HeartAge-gap, those with HeartAge-gaps of 0-5 years and ≥5 years exhibited significantly increased risks of stroke by 74% and 141%, respectively. Subgroup analyses and interaction tests identified a significant gender interaction in the association between HeartAge-gap and stroke, indicating that men with accelerated heart age represent a vulnerable subgroup. Restricted cubic splines (RCSs) confirmed a linear association, and sensitivity analyses validated the robustness of these findings. Integrating these intuitive indicators into clinical practice could facilitate primary stroke prevention and mitigate CKM syndrome progression.

Fully automated diagnostic echocardiography allows for broader screening, earlier diagnosis for patients with mitral regurgitation (MR). This feasibility study developed a deep learning (DL) framework to automatically detect MR in echocardiography videos and classify regurgitation samples into central or eccentric regurgitation.

We designed a Transformer-based deep learning model for fully automatic Doppler video detection of MR. This framework can automatically detect MR and classify central or eccentric regurgitation. The algorithm was trained, validated, and tested using retrospectively selected studies. A prospective dataset of 217 patients was used as an independent test database.

(a) The model demonstrated exceptional diagnostic accuracy for MR, achieving accuracy rates of 0.94(95%CI: 0.90-0.97) and 0.92(95%CI: 0.89-0.96) in retrospective and prospective test sets, respectively, with area under the curve (AUC) values of 0.98 (95%CI: 0.96-1.0) and 0.97 (95%CI: 0.95-0.99). Its performance aligned with that of middle seniority physicians. (b) The model achieved an accuracy of 0.93 in identifying central and eccentric MR across both retrospective and prospective test sets, AUC values of 0.96 (95%CI: 0.89-0.99) and 0.95 (95%CI: 0.89-0.98), respectively. (c) On the tasks of MR, the diagnostic performance of the model in multiple views was better than that of the parasternal long-axis view (PLAX) alone or the apical four-chamber view (A4C) in both retrospective and prospective datasets.

The Transformer-based algorithm proposed in this study can automate and improve the efficiency of clinical workflows, screen multi-view for the presence of MR, and assist in classifying regurgitation characteristics.

Heart Failure (HF) is a major global health concern affecting approximately 64 million individuals. Because early asymptomatic stages are frequently overlooked, many patients are diagnosed late, after preventable morbidity and hospitalization. Screening that identifies high-risk individuals earlier may enable timely intervention and disease modification.

This narrative review searched PubMed and Embase for English-language literature published between 2018 and 2025 on HF screening. Search themes included heart failure, early detection, screening strategies, natriuretic peptides, biomarkers, echocardiography, cardiac imaging, digital health, wearable technologies, and Artificial Intelligence (AI). Relevant guidelines, clinical studies, meta-analyses, and review articles were evaluated and synthesized with emphasis on diagnostic performance, feasibility, and implementation across different healthcare settings.

Targeted screening of high-risk groups (e.g., hypertensives, diabetics, those with established cardiovascular diseases) was consistently more effective than symptom-based evaluation. Natriuretic peptides (BNP/NT-proBNP) showed high sensitivity for ruling out HF in non-acute settings and for biomarker triage of individuals at increased risk, while echocardiography remained the cornerstone for confirmatory structural and functional assessment. Digital health tools, including wearables and AI-driven algorithms, showed promise for widely applicable risk stratification and remote monitoring, although performance and feasibility varied by setting.

Key gaps include limited prospective outcome-driven trials, heterogeneity of screening thresholds and pathways, disparities in access to biomarkers and imaging, and unresolved issues in data quality, privacy, bias, and workflow integration for digital/AI approaches in practice.

Integrated, stepwise HF screening frameworks that combine risk stratification, biomarker triage, confirmatory imaging, and context-appropriate digital support may facilitate earlier detection and link positive screens to practical preventive and therapeutic care. Future research should prioritize context-adapted pathways and randomized evaluations of patientcentred outcomes and cost-effectiveness.

The transient receptor potential vanilloid 1 (TRPV1) is a cation channel implicated in neurological disorders. Although TRPV1 activation contributes to intracerebral hemorrhage (ICH) pathology, its microglia-specific role and underlying mechanisms remain poorly defined. This study investigates how microglial TRPV1 influences ICH injury.

We utilized a mouse ICH model alongside microglia-specific TRPV1 knockout mice, BV2 cells, and primary microglial cultures. Interventions included TRPV1 antagonist capsazepine (CPZ), agonist capsaicin (CAP), microglial depletion agent PLX5622, and TRPV1 knockdown. Outcomes were assessed using immunofluorescence, behavioral tests, Western blot, magnetic resonance imaging (MRI), and transmission electron microscopy (TEM).

TRPV1 expression was significantly upregulated post-ICH, primarily in microglia. TRPV1 blockade with CPZ treatment reduced hematoma volume, brain edema, neuronal apoptosis, and improved neurological function, whereas CAP exacerbated injury. These benefits were replicated in microglia-specific TRPV1 knockout mice. Mechanistically, CPZ shifted microglia from a pro-inflammatory (iNOS+) to a regulatory (Arg1+) phenotype and suppressed excessive mitophagy via the Ca²⁺-AMPK-PINK1 pathway.

TRPV1 activation in microglia exacerbates ICH injury by promoting inflammation and disruptive mitophagy. Targeted inhibition of microglial TRPV1 represents a promising therapeutic strategy for ICH.

Intermediate monocytes (IM) exhibit proinflammatory properties and contribute to atherosclerosis. Elevated lipoprotein(a) [Lp(a)] levels modulate monocyte behavior, while proprotein convertase subtilisin/kexin type 9 (PCSK9) has been implicated in inflammatory pathways beyond lipid metabolism. The effects of PCSK9 inhibition on monocyte subset distribution in high-risk coronary artery disease patients remain unclear.

To assess the effects of lipoprotein fractions and PCSK9 inhibitor (PCSK9i) therapy on monocyte subset distribution in patients with stable coronary artery disease and highly elevated Lp(a) levels.

We followed 100 statin-treated patients in the stable phase after myocardial infarction with highly elevated Lp(a), randomized to PCSK9i or placebo for six months. Biochemical, genetic, and cellular analyses were performed at baseline and follow-up.

At baseline, IM levels correlated with total cholesterol (ρ = -0.202, p = 0.044), triglycerides (ρ = -0.324, p < 0.001), apolipoprotein A1 (ρ = 0.241, p = 0.016), and PCSK9 concentrations (ρ = -0.282, p = 0.006). PCSK9 levels were positively associated with CC-motif chemokine ligand 2 (CCL2) (ρ = 0.298, p = 0.005), a marker of monocyte recruitment. PCSK9i therapy did not alter monocyte subset distribution. After treatment, only the association between IM and Lp(a) remained significant (ρ = -0.258, p = 0.041). KIV-2 repeat number inversely correlated with CCL2 levels (ρ = -0.319, p = 0.011).

In high-risk patients, PCSK9 inhibition modulates monocyte-lipoprotein interactions without affecting the monocyte subset distribution. PCSK9 may promote vascular inflammation through CCL2 regulation, which appears more closely related to Lp(a) composition than its circulating concentration.

NCT04613167; https://www.clinicaltrials.gov/study/NCT04613167, date of registration: 6th of October 2020.

Cognitive impairment (CI) affects self-management in chronic diseases, leading to poor decision-making, delayed care, and increased mortality. The specific impact of CI on adverse outcomes in chronic kidney disease (CKD) remains poorly explored.

The French CKD - Renal Epidemiology and Information Network (CKD-REIN) cohort included 3033 patients with CKD stage 2 to 5 and 5 years of follow-up. CI was assessed using the Mini-Mental State Examination (MMSE), and estimated glomerular filtration rate (eGFR) was estimated using the CKD Epidemiology Collaboration creatinine equation. Cox models evaluated the risks of all-cause mortality, kidney replacement therapy (KRT) initiation, and major adverse cardiovascular (CV) events (MACEs).

A total of 3004 patients were included in the analysis (mean age: 67 years, mean eGFR: 34 ml/min per 1.73 m²), and 64%, 23%, and 13%, respectively had MMSE scores > 26, from 24 to 26, and < 24 at baseline. During the follow-up period (mean: 3.87 years), 21.5% of patients initiated KRT, 13.4% died, and 15.3% experienced a MACE before KRT or non-CV death. In adjusted Cox models, patients with a MMSE < 24 had a higher risk of clinical adverse outcome, relative to those with a MMSE > 26: hazard ratio (HR) [95% confidence interval] was 1.42 [1.12-1.81], 1.57 [1.19-2.07], and 1.32 [1.02-1.70] for KRT initiation, all-cause mortality, and MACE, respectively. In addition, CI was associated with all-cause mortality in the MMSE of 24 to 26 group (HR: 1.45, 95% confidence interval: 1.15-1.83).

In CKD, a baseline MMSE score < 24 predicts higher overall-death, KRT initiation, and MACEs, relative to a baseline score > 26. These results highlight CI's prognostic value, and suggest that earlier detection could better personalize management, particularly for kidney and CV complications.

There is increasing evidence that even a small variation in thyroid function, even within the reference range, is associated with adverse clinical outcomes. Furthermore, there exists a substantial interindividual variation of thyroid function even within euthyroid individuals suggesting an individual hypothalamus-pituitary-thyroid (HPT) axis setpoint. Here we assess potential contributions of the HPT axis organ volumes to the variation of thyroid hormones in the general population. Using linear regression models, we analyzed the association of circulating free T3, free T4, and log-transformed TSH levels with hypothalamus, pituitary gland, and log-transformed thyroid volume in a subsample of up to n = 3438 participants from the population-based Study of Health in Pomerania with a mean age 50.6 years, 44.6% female, and a mean TSH 1.38mU/L. Performing cross-sectional analyses at baseline, we observed inverse associations of pituitary volume with free T4 levels ( β = - 0.74 , P = 0.017 , n = 1 , 372 ) and of thyroid volume with TSH levels ( β = - 0.72 , P = 3.1 × 10 - 147 , n = 3 , 430 ), as well as positive associations of thyroid volume with free T3 ( β = 0.11 , P = 1.3 × 10 - 4 , n = 3 , 310 ) and free T4 levels ( β = 0.81 , P = 1.2 × 10 - 18 , n = 3 , 311 ) but observed no association regarding hypothalamus volume (n ≤ 1636). The findings for free T3 and free T4 were supported by longitudinal analyses in a subsample of up to n = 2040 participants with available longitudinal data and a mean follow-up time of 7.3 years. In summary, using data from a population-based sample, we identified associations between pituitary volume and circulating free T4 as well as thyroid gland volume with circulating levels of TSH, free T3, and free T4 contributing to the variation of thyroid hormone levels.

Myocardial fibrosis is a common pathological substrate across a broad spectrum of cardiovascular diseases and represents a key determinant of adverse clinical outcomes, including heart failure progression, arrhythmias, and sudden cardiac death. It may present as focal replacement fibrosis, typically following myocardial infarction, or as diffuse interstitial fibrosis, more frequently observed in non-ischemic cardiomyopathies and pressure-overload conditions. At the cellular level, fibrosis is driven by fibroblast activation and differentiation into myofibroblasts, mediated by profibrotic signaling pathways and sustained extracellular matrix deposition. Inflammation and myocardial edema also play a critical role in initiating and amplifying fibrotic remodeling, linking acute injury to chronic structural changes. Cardiac magnetic resonance imaging has emerged as a reference non-invasive modality for myocardial tissue characterization. Parametric mapping techniques, including T1, T2, and extracellular volume fraction mapping, provide a quantitative and highly reproducible assessment of myocardial composition. Native T1 mapping and extracellular volume fraction allow sensitive detection and quantification of diffuse myocardial fibrosis and have demonstrated significant prognostic value across several cardiovascular conditions, while T2 mapping is particularly sensitive to myocardial edema and active inflammation, enabling differentiation between acute and chronic myocardial injury. When integrated, these techniques enable a comprehensive evaluation of the inflammation-fibrosis continuum. Clinically, T1 and T2 mapping have demonstrated substantial value across ischemic and non-ischemic heart diseases, valvular disorders, and infiltrative cardiomyopathies. These techniques contribute to improved risk stratification, prediction of adverse ventricular remodeling, guidance of therapeutic decision-making, and monitoring of treatment response. Compared with late gadolinium enhancement imaging, echocardiographic strain analysis, and circulating biomarkers, parametric mapping offers greater tissue specificity and quantitative characterization of myocardial remodeling, although its implementation requires specialized equipment and technical expertise.

Cerebral ischemia-reperfusion injury (CIRI) remains a major cause of neurological disability and lacks effective neuroprotective interventions. Soy isoflavones (SI), phytoestrogens with antioxidant and anti-inflammatory properties, have shown neuroprotective potential. Given that ferroptosis contributes to CIRI pathogenesis and AMP-activated protein kinase (AMPK) regulates redox homeostasis, iron metabolism, and lipid peroxidation, we investigated whether SI protect against CIRI by activating AMPK and inhibiting ferroptosis.

Male Sprague-Dawley rats subjected to middle cerebral artery occlusion (MCAO) were pretreated with SI (120 mg/kg, gavage) for 21 days. Neurological outcomes were assessed by infarct volume (TTC), brain water content, and behavioral scoring (Longa, mNSS). Ferroptosis was evaluated via cerebral Fe²⁺/total iron levels, oxidative stress indices (MDA, GSH, SOD, ROS), and protein expression of GPX4, ACSL4/3, xCT, and ferritin (FTH/FTMT). AMPK activation (p-AMPK/AMPK) was determined by Western blotting. Mechanistic validation employed RSL3 (ferroptosis inducer) and compound C (AMPK inhibitor).

SI pretreatment significantly reduced infarct size, alleviated edema, and improved neurological function. SI attenuated cerebral iron accumulation, suppressed ROS and MDA production, and enhanced GSH and SOD activities. Western blot analysis revealed downregulation of ACSL4 and upregulation of GPX4, ACSL3, xCT, and ferritin, consistent with ferroptosis suppression. The protective effects of SI were abolished by RSL3, confirming ferroptosis dependence. Furthermore, MCAO suppressed AMPK activation, which was restored by SI; inhibition of AMPK with compound C intensified ferroptotic injury and negated SI's benefits, whereas co-treatment with SI reversed these detrimental effects.

SI confer neuroprotection against CIRI by activating AMPK signaling and inhibiting ferroptosis. These findings highlight the AMPK-ferroptosis axis as a promising therapeutic target for ischemic stroke.