We present a longitudinal electronic health record (EHR) dataset from Wuhan Union Hospital, compiled from two distinct hospital information systems. The first dataset, derived from a legacy system, includes 35,243 patients and covers the period from 2010 to 2020. The second dataset, collected via the research-oriented YIDUYUN system, includes 37,975 patients and spans from 2011 to 2024. Both datasets provide structured and de-identified clinical information, including medical record number, demographics, diagnoses, admissions, discharges, timestamps record, laboratory test results (including COVID-19 test records) and patients' residential region. Using the patients' residential regions, we combined the data with information from the China Statistical Yearbook to collect regional socioeconomic indices. While not specifically designed for pandemic research, the dataset captures both pre-pandemic and post-pandemic periods with de-identified exact timestamps, making it suitable for analyzing long-term healthcare utilization, population behavior, and policy impacts. With comprehensive metadata and rigorous validation, this resource supports a wide range of applications in longitudinal health system research and data-driven modeling.

Cardiovascular diseases (CVDs) are a leading cause of morbidity, disability, and mortality worldwide, posing a significant threat to global health. These diseases include myocardial infarction (MI), heart failure (HF), hypertension, atherosclerosis (AS), and other pathological cardiac disorders. Despite notable advances in CVD management, such as cardiac-targeted pharmacotherapies, interventional procedures, and heart transplantation, major challenges persist, including adverse drug effects, postoperative complications, and the persistent shortage of heart donors. Extracellular vesicles (EVs) have recently emerged as a promising therapeutic modality owing to their high delivery efficiency, precise targeting potential, and capacity to promote cardiac repair and regeneration. EVs carry a diverse repertoire of bioactive cargos, including proteins, nucleic acids, lipids, and metabolites, facilitating intercellular regulation of immune response, tissue repair, and regenerative processes. Advances in bioengineered EVs also develop the therapeutic potential by enabling the design of vesicles with enhanced targeting specificity and controlled cargo delivery. This review summarizes the complex interactions between EVs and the cardiovascular system, with particular emphasis on their roles in cellular communication, microenvironment modulation, and immune regulation. We further highlight the regenerative capacity of EVs in cardiovascular repair, and discuss emerging clinical applications of native and bioengineered EVs in cardiovascular homeostasis, remodeling, metabolism, and regeneration. These insights pave the way for further exploration of bioengineered EVs as a novel therapeutic platform in cardiovascular medicine.

Vascular dementia (VaD) is a major therapeutic challenge. Tar DNA-binding protein 43 (TDP-43), known for its role in neurodegeneration, may contribute to VaD pathogenesis under chronic cerebral hypoperfusion (CCH). This study investigates TDP-43 dysregulation in VaD.

TDP-43 and phosphorylated TDP-43 (pTDP-43) expression and localization were assessed in a VaD animal model, neuronal cells exposed to oxygen-glucose deprivation (OGD), and post mortem human brain tissues.

Bilateral Common Carotid Artery Stenosis (BCAS)-induced CCH led to increased pTDP-43 and aberrant redistribution of both TDP-43 and pTDP-43. In vitro OGD triggered similar mislocalization. Post mortem VaD brains showed no TDP-43 abnormalities, while Alzheimer's and mixed dementia cases exhibited marked pathology.

TDP-43 dysregulation appears early in VaD under hypoperfusive stress, distinguishing it from other dementia subtypes. These findings indicate that TDP‑43 may warrant further investigation as a potential early molecular feature of VaD.

Tar DNA-binding protein 43 (TDP-43) is dysregulated early in vascular dementia models. Hypoperfusion triggers TDP-43 mislocalization and phosphorylation. TDP-43 pathology is absent in late-stage human vascular dementia. TDP-43 is a transient, novel target for vascular cognitive impairment.

Elevated homocysteine (Hcy) levels are well established as an independent risk factor for atherosclerosis and its associated cardiovascular diseases. Macrophage pyroptosis- mediated inflammation plays a crucial role in the progression of atherosclerosis. Notably, glycoprotein non-metastatic melanoma protein B (GPNMB) expression is increased in macrophages within atherosclerotic plaques; however, whether GPNMB participates in Hcy-induced macrophage pyroptosis remains elusive. In the present study, we found that GPNMB expression was upregulated in Hcy- treated THP-1- derived macrophages. Consistently, serum GPNMB levels were significantly higher in patients with hyperhomocysteinemia (HHcy) compared with healthy controls. Functional experiments showed that silencing GPNMB reduced Hcy-triggered pyroptosis in THP-1-derived macrophages, whereas GPNMB overexpression exerted the opposite effect. Mechanistically, GPNMB upregulated the NOX2/NF-κB signaling pathway in THP-1-derived macrophages. Importantly, the pro-pyroptotic effect of GPNMB overexpression in Hcy-treated THP-1-derived macrophages was counteracted by either inhibition of NADPH oxidase 2 (NOX2) using the specific inhibitor gp91ds-tat or blockade of NF-κB activation with the inhibitor BAY11-7082. Moreover, serum GPNMB levels were correlated with serum Hcy levels and lipid profiles in both healthy individuals and HHcy patients. Collectively, these findings demonstrate that GPNMB facilitates Hcy-induced macrophage pyroptosis associated with the upregulation of the NOX2/NF-κB signaling pathway, highlighting the potential relevance of GPNMB as a candidate target for the clinical management of HHcy-related atherosclerotic cardiovascular disease.

Atherosclerosis (AS) severely threatens global health, while current therapies exhibit limitations. Recognized as a 'superior-grade' herb in the Shennong Ben Cao Jing, Salvia miltiorrhiza Bunge (Danshen) has been shown in modern studies to protect against cardiovascular diseases.

The aim of this study was to investigate the therapeutic potential and protective mechanism of pharmacological components of Salvia miltiorrhiza against AS.

Relevant animal studies were collected from 8 databases, namely, PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang Data, VIP, and SinoMed. Risk of bias of the included studies was evaluated using the SYRCLE's tool. Statistical analysis was performed using R 4.2.0 and Python 3.14.2 software. Machine learning model was trained to predict optimal intervention parameters and was subsequently validated.

A total of 64 studies were included. The pharmacological components of Salvia miltiorrhiza ameliorated atherosclerotic plaque formation and stability, and modulated various biomarkers, including lipid profiles, inflammatory cytokines, oxidative stress indicators, endothelial function markers, as well as matrix metalloproteinases. Machine learning identified an optimal Tanshinone IIA regimen against AS, which was defined as a single dose of 33.18 mg/kg dose over 84 days and demonstrated predictive robustness in validation.

The pharmacological components of Salvia miltiorrhiza attenuate AS by regulating lipid metabolism, anti-inflammatory and antioxidant actions, improving endothelial function, modulating of vascular smooth muscle cells, remodeling extracellular matrix, and regulating programmed cell death. These findings provide translational insights that pave the way for subsequent preclinical and early-clinical studies, pending systematic validation through more rigorous research.

As innovative therapies for renal anemia, roxadustat and daprodustat are specifically indicated for populations with chronic kidney disease (CKD) who exhibit a significantly higher susceptibility to cardiovascular complications. Platelets are important participants in cardiovascular and cerebrovascular thrombotic diseases, and the effects of roxadustat and daprodustat on platelets have not been clarified. The study explored their modulatory effects on platelet functions (using human platelets) and antithrombotic activity in vivo (via mouse pulmonary embolism and mesenteric thrombus models). Mechanistically, thromboxane A2/cyclic adenosine monophosphate (TXA₂/cAMP) levels were measured by ELISA, and protein expression by immunoblotting. Results revealed that roxadustat and daprodustat treatment could effectively inhibit platelet functions. Roxadustat and daprodustat inhibited collagen-induced platelet aggregation ex vivo and FeCl₃-induced mesenteric arteriolar thrombosis in mice and were protective in pulmonary embolism models. Additionally, roxadustat and daprodustat caused a decrease in TXA₂ production and an increase in cAMP signaling. Western blot assay results displayed that roxadustat and daprodustat downregulated collagen-induced platelet PI3K/AKT/HIF-1α pathway. Our study revealed the pharmacological effects of roxadustat and daprodustat in inhibiting platelet activation and thrombosis. The effects may provide some insights into the physiological activity of HIF and clinical medication safety.

Treating drug-resistant tuberculosis (DR-TB) is clinically complex and economically burdensome compared to drug-susceptible tuberculosis (DS-TB). China's diagnosis-intervention packet payment system initially omitted risk adjustment for drug resistance. In 2022, a diagnosis-intervention packet (DIP)-pilot city implemented such adjustment, establishing distinct reimbursement standards for DR-TB and DS-TB. This study aimed to assess the impact of this DR-type risk adjustment on medical expenditures, treatment efficiency, and care quality for TB patients.

A quasi-experimental difference-in-differences design was employed, involving 8465 TB patients from June 2021 to December 2023. Linear regression was performed with time and treat fixed effects and the interaction term between time and treat. Subgroup analyses for DR-TB and DS-TB patients were conducted.

Under the DIP system, risk adjustment led to marginally significant reductions in inpatient expenditure per hospitalization [β = - 151.14, P = 0.065; 95% confidence interval (CI) for difference in proportions: - 311.66, 9.38] and in annual total inpatient expenditure per patient (β = - 200.58, P = 0.078, 95% CI - 423.26, 22.10) for all TB patients. It also resulted in significant reductions in inpatient out-of-pocket per hospitalization (β = - 257.51, P < 0.001, 95% CI - 316.20, - 198.81), annual total inpatient out-of-pocket per patient (β = - 266.78, P < 0.001, 95% CI - 342.02, - 191.53), inpatient length of stay per hospitalization (β = - 3.58, P < 0.001, 95% CI - 4.53, - 2.62), and annual total length of stay per patient (β = - 3.21, P < 0.001, 95% CI - 4.50, - 1.92). For DR-TB patients, all outcome measures in expenditures, efficiency, or care quality showed P > 0.1, indicating no significant changes. For DS-TB patients, measures of expenditures and efficiency showed P < 0.1, supporting significant or marginally significant reductions.

The DR-type risk adjustment policy under China's diagnosis-intervention packet system proved effective in optimizing resource use and enhancing efficiency, particularly for DS-TB patients, while preserving care quality for DR-TB patients. These findings demonstrate the value of tailored risk adjustment within payment frameworks for heterogeneous diseases like tuberculosis, providing crucial evidence for optimizing TB care and implementing effective payment reforms in China and similar settings.

This study evaluates the impact of the Housing First (HF) intervention on healthcare utilization among homeless adults with mental illness, comparing ethno-racial (ER) and non-ER groups with moderate mental health support needs. We linked data from the At Home/Chez-Soi (AH/CS) randomized controlled trial with health administrative data from Ontario, including the Ontario Health Insurance Plan and several healthcare databases (e.g., Discharge Abstract Database, Ontario Mental Health Reporting System). We analyzed outcomes such as primary care visits, hospitalizations, emergency department (ED) visits, and Ambulance arrival Incidents. Applying the intention-to-treat principle, we used generalized estimating equation models using the Poisson distribution which included the intervention (HF vs. TAU), the time period (0-7 years post-randomization vs 1-year pre-randomization) and their interaction. Incidence rate ratios (IRRs) were estimated to assess the differences in outcome rate changes between HF vs TAU comparing the 0 to 7 year follow-up period with the pre-randomization year for each stratified ethno-racial group. The results revealed a mitigated HF effect among non-ER participants, with increased utilization rates for both primary care and acute care services. [Primary care visits [IRR 2.17 95% (1.03-4.57)], acute care visits (Mental health hospitalization [IRR 2.68 95% CI (1.17-6.20)], Ambulance arrivals to ED [IRR 1.94 95% (1.05-3.56)] and number of Ambulance arrivals to ED [IRR 3.67 95% (1.05-13.02)]). However, no statistically significant effect was found among the ER participants in any of the healthcare services examined. The differential impact of HF on healthcare utilization suggests persistent systemic barriers to care, such as stigma and discrimination among ER participants.Trial Registration: The study is registered with the ISRCTN (#42520374).

Emerging evidence suggests regional neuroanatomical variability may be predictive of early alcohol use (before age 15). However, the relationship between whole-brain network organization and early alcohol initiation remains unknown. Using data from the Adolescent Brain Cognitive Development (ABCD) study, we conducted a structural covariance network (SCN) analysis to examine brain network features preceding early alcohol initiation. Structural MRI data collected at baseline (ages 9-10) were used to generate SCNs based on regional cortical thickness measurements. Early alcohol initiation was defined as consuming a full drink between baseline and 4-year follow-up ( ≤ age 15). Participants who reported a full drink of alcohol at baseline, did not participate in the 4-year follow-up, or did not meet imaging quality control criteria were excluded. The remaining participants were compared to a subsample matched at a 1:1 ratio (n = 160 per group). SCN properties, including network segregation (modularity, clustering coefficient), integration (characteristic path length, global efficiency), and resilience (degree assortativity), were compared between groups. While no differences in regional cortical thickness between groups were identified, early initiators demonstrated lower segregation and higher integration compared to non-initiators. These findings suggest that cortical thickness network topology at ages 9-10 may serve as a neuroanatomical risk marker for early adolescent alcohol initiation, independent of prior alcohol exposure, sociodemographic differences, and regional neuroanatomical variability.