Sichong Qian

Objective: Aortic aneurysm (AA) is a life-threatening vascular disease characterized by immune disturbance and metabolic dysregulation. Multi-omics-driven precision toxicity prediction, integrating human genetic causal inference with functional in-vitro toxicology, remains under-explored for uncovering metabolite mediators underlying AA disease risk.This study aimed to dissect metabolite-dependent causal pathways linking immune cells to AA, and evaluate dose-response cytotoxicity of key mediating metabolites toward vascular cells. Methods: Two-sample Mendelian randomization (MR) and two-step mediation analysis were performed using European-ancestry GWAS summary datasets covering 731 immune-cell traits, 1,091 plasma metabolites, 3,230 AA cases and 475,964 controls. Complementary in-vitro CCK-8 cytotoxicity experiments on human aortic smooth muscle cells (HASMCs) were further conducted for candidate metabolites Adrenate (22:4n6) and BAFF-R. Results: BAFF-R on CD20 ⁻ (OR = 0.859, 95%CI: 0.797–0.926, P = 7.17 × 10 ⁻⁵ ) and, to a lesser extent, Granulocyte AC (OR = 0.900, 95%CI: 0.843–0.961, P = 1.57 × 10 ⁻³ ) emerged as candidate protective immune-cell markers for AA. Adrenate (22:4n6) and Nisinate (24:6n3) mediated 4.47% and 9.84% of these protective effects, respectively. Adrenate triggered significant dose-dependent cytotoxicity in HASMCs. Conclusion: This multi-omics genetic-toxicology study provides causal genetic evidence for immune-metabolite regulatory axes in AA pathogenesis. Notably, Adrenate presents dual biological effects: it transmits immune-protective signals but exerts direct vascular cellular toxicity. Our findings highlight the utility of MR-assisted precision toxicity prediction for disease risk evaluation and therapeutic target mining for AA.

Background: Ischemic heart disease (IHD) remains a leading cause of mortality in the United States, yet it remains unclear whether postpandemic recovery patterns differ across population subgroups. Methods: Using CDC WONDER data (1999–2023), we analyzed IHD deaths among US adults aged ≥25 years. Age-adjusted mortality rates (AAMRs) were stratified by sex, race/ethnicity, urbanization, and region; crude mortality rates (CMRs) by age. Urban–rural analyses were restricted to 1999–2020. Joinpoint regression estimated temporal trends, and tests of parallelism assessed between-group differences. Results: Among 10,200,362 IHD deaths, overall AAMRs declined from 300.8 to 127.07 per 100,000 (average annual percent change, AAPC = −3.51; p < 0.001), with the fastest decline during 2021–2023 (APC = −5.59). Males had higher AAMRs than females (245.58 vs. 138.69; p < 0.001). Non-Hispanic (NH) Black individuals had the highest AAMR (217.58). The steepest age-specific CMR decline occurred at 75–84 years (AAPC = −4.04). Metropolitan areas had lower AAMRs than non-metropolitan areas (189.07 vs. 212.60; p < 0.001). Pairwise tests confirmed significant trend differences across most subgroups (all p < 0.05), except NH Other vs. NH White ( p = 0.396). Conclusions: Despite sustained IHD mortality declines, significant disparities persist across demographic and geographic subgroups, supporting targeted prevention for high-risk populations.

Portable physiological monitoring is essential for early detection and management of cardiovascular disease, but current methods often require specialized equipment that limits accessibility or imposes impractical postures that patients cannot maintain. Video-based photoplethysmography on smartphones offers a convenient non-invasive alternative, yet it still faces reliability challenges caused by motion artifacts, lighting variations, and single-view constraints. Few studies have demonstrated that this technology can be reliably applied to physiological monitoring of cardiovascular patients, and no widely used open datasets exist for researchers to examine its cross-device accuracy. To address these limitations, we introduce the M ³ PD dataset—the first publicly available dual-view mobile photoplethysmography dataset—comprising synchronized facial and fingertip videos captured simultaneously via front and rear smartphone cameras from 60 participants (including 47 cardiovascular patients). Building on this dual-view setting, we further propose the F ³ Mamba, which fuses the facial and fingertip views through Mamba-based temporal modeling. The model reduces heart-rate error by 21.9-30.2% over existing single-view baselines while showing enhanced robustness across challenging real-world scenarios, and further achieves a 4.4-16.4% MAE reduction over the best standard dual-view fusion baselines. Data and code are released at https://github.com/Health-HCI-Group/F3Mamba.

Histone deacetylase (HDAC) inhibitors are approved for cancer treatment and are being investigated for a wide range of other diseases. Despite their therapeutic promise, clinical studies have reported cardiac side effects, particularly electrocardiogram (EKG) abnormalities, with QT interval prolongation being one of the most consistently reported findings. The mechanisms underlying these cardiac effects remain unclear. In this study, we investigated the role of HDAC3 in cardiac electrophysiology. We found that postnatal depletion of cardiac HDAC3 in mice caused QT interval prolongation, recapitulating the EKG abnormalities reported with HDAC inhibitor use. Adult-onset inducible depletion of cardiac HDAC3 induced additional EKG abnormalities, including T-wave flattening, inversion, and biphasic T waves, which are also observed clinically. Loss of HDAC3 deacetylase activity, without affecting HDAC3 protein levels, was sufficient to induce QT prolongation. Disruption of HDAC3 function altered the expression of ion channel genes, including the downregulation of potassium channel genes such as Kcnh2, Kcne1, and Kcnip2. Moreover, a single dose of HDAC inhibitors, romidepsin or mocetinostat, caused reversible QT prolongation in mice. Consistent with these findings, HDAC inhibitor treatment altered the expression of potassium channel genes, with a predominant downregulation of multiple Kcn family members, including Kcnq1, Kcnh2, and Kcnip2. These findings establish HDAC3 enzymatic activity as a key regulator of cardiac repolarization and provide mechanistic insight into HDAC inhibitor-associated cardiotoxicity.

Aortic aneurysm (AA) and aortic dissection (AD) are life-threatening cardiovascular diseases. AA includes thoracic (TAA) and abdominal (AAA) subtypes, whil

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive disease characterized by adipose and fibrous replacement of the myocardium. While e

Objectives: This study aims to investigate whether surgery performed during night compared with daytime were associated with an increased risk of operative mortality of type A aortic dissection (TAAD) patients. Methods: A total of 2015 TAAD patients who underwent surgical repair were collected from two cardiovascular centers from Jan 2015 to Jan 2021. According to the start time of surgery, patients were divided into daytime group (06:01 a.m. to 06:00 p.m.) and night-time group (06:01 p.m. to 06:00 a.m.), and retrospective analyses were performed between them. Results: The operative mortality of night-time group (12.2%, 43/352) was dramatically higher than daytime group (6.9%, 115/1663; p = 0.001). There was significant difference between night-time and daytime groups in terms of 30-days mortality (5.8% vs 10.8%; p = 0.001) and in-hospital mortality (3.5% vs 6.0%; p = 0.03). The night-time group had a longer duration of intensive care unit stay (4 vs two; days; p < 0.001) and ventilation support (34 vs 19; hours; p < 0.001), compared with daytime group. The risk factors for operative mortality were night-time surgery (odds ratio [OR], 1.545; p = 0.027), age (odds ratio, 1.152; p < 0.001), total arch replacement (OR, 2.265; p < 0.001) and previous aortic surgery (OR, 2.376; p = 0.003). Conclusion: Night-time surgical repair may be associated with higher operative mortality of patients with TAAD. Nevertheless, it is reasonable to offer emergency surgery at night-time for such patients who were more likely to present disastrous complications with delayed surgical intervention, as outcomes indicate acceptable operative mortality.