Medical payment plans shape financial protection and access to care, but their associations with costs, disease progression and survival in hypertension remain poorly characterised. We analyse 8,004,039 inpatient admissions among 4,675,738 patients in Henan, China, from 2019 to 2024 using mixed-effects, multistate and survival models, and externally validate the non-mortality findings in Xinjiang. Compared with self-pay, urban employee, urban-rural resident and commercial or other insurance are associated with 24.95%, 8.71% and 16.64% higher total inpatient expenditure, respectively, while all non-self-pay plans are associated with 89.47-97.56% lower out-of-pocket spending. Urban employee insurance shows the most favourable survival (adjusted hazard ratio for all-cause mortality, 0.72; 95% confidence interval, 0.68-0.76), whereas government-supported or medical assistance arrangements show the poorest survival (1.33; 1.23-1.43) and the greatest expected time in multimorbidity. Sensitivity analyses and external validation support the direction of the main non-mortality findings. These observational associations do not isolate payment-plan effects and may reflect differences in benefit scope, care access and participants' underlying health and social vulnerability. Narrowing reimbursement gaps alone may therefore be insufficient without broader improvements in service coverage and access.

Despite the female predominance in age- and immune-associated diseases, the pathways underlying sex differences in healthy immune aging remain incompletely understood. Here, we analyze a multi-ethnic single-cell transcriptome of healthy human immune aging (35% Asian), comprising 3.8 million peripheral blood mononuclear cells (PBMCs) from 1,828 individuals aged 19-97 years. Prominent peaks of differential gene expression around 40 (mainly CD4 T cells) and after 60 (mainly CD8 T cells) years of age were accompanied by an age-dependent decline in RNA/protein homeostasis and inflammatory PBMC polarization with sex-dependent kinetics. While females displayed sustained CD8 T cell activation and late-life aging signatures in CD4 T, NK, and B cells, males exhibited early-life fluctuations in CD4 T cell immunometabolism associated with hypomethylation of SSH3 at chromosome 11q13. Deep learning-based biological age clocks stratified for sex outperformed sex-combined models, learning from transcriptional immune trajectories. We thus unravel a nonlinear PBMC aging whereby targeting sex-specific pathways might allow precision geromedicine.

Horses with endotoxemia have variable myocardial function, but little is known about the severity or persistence of myocardial dysfunction (MD).

Horses with experimentally induced endotoxemia have systolic and diastolic MD.

Twelve systemically healthy horses.

Horses were given Escherichia coli lipopolysaccharide 30 ng/kg over 60 min. Echocardiography and cardiac troponin I (cTnI) measurements were performed at baseline, 1, 3, and 5 h post-endotoxin. Fluid therapy (10 L), polymyxin B (6000 IU/kg), and flunixin meglumine (1.1 mg/kg) were administered intravenously, and then echocardiogram and cTnI measurements were performed (post-treatment). Results were compared using linear mixed models and adjusted for multiple comparisons. Significance was set at P < .05.

All horses showed signs of MD. A significant increase in heart rate from baseline was noted at all timepoints (P < .001). No significant increase in cTnI occurred at any timepoint. Ejection fraction decreased from baseline at 3 and 5 h (mean, 72%, 62%, and 65%, respectively; P < .001 at both timepoints). Using tissue Doppler imaging (TDI), the index of myocardial performance increased at 1, 3, and 5 h (mean, 0.40, 0.55, 0.66, 0.55; P < .01 at all timepoints). Using two-dimensional speckle tracking (2DST), the magnitude of global longitudinal strain was decreased from baseline at 3, 5 h, and post-treatment (mean, -21%, -16%, -17%, and -19%; P < .0001, .0001, and .04, respectively).

Systolic and diastolic MD are evident in the absence of increased cTnI. Advanced echocardiographic modalities such as TDI and 2DST improve diagnostic capability for identifying regional abnormalities.

Mastitis is a prevalent inflammatory disorder in women, this condition exhibits a particularly elevated prevalence among breastfeeding women, which significantly compromises mammary health and lactation function. This research explored the anti-inflammatory properties of YWJ-6 in lipopolysaccharide (LPS)-induced mastitis, its protective role on the blood-milk barrier (BMB), and the underlying mechanisms. An LPS-induced mastitis rat model was established. H&E staining assessed mammary tissue damage, and myeloperoxidase (MPO) activity was measured. RT-qPCR and IHC were used to demonstrate interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNFα) expression. These data indicated that inflammatory injury was alleviated. Following drug treatment, MPO expression and the mRNA/protein expression of these inflammatory factors were suppressed. Immunofluorescence staining analyzed the distribution of Zonula Occludens-1 (ZO-1), Occludin, and Claudin-3. WB quantitatively detected ZO-1 and Occludin expression, confirming that YWJ-6 promoted tight junction (TJ) protein expression restoration and distribution integrity, repairing the damaged BMB. Consistently, Evans blue extravasation assay demonstrated that YWJ-6 reduced mammary vascular permeability, providing direct functional evidence for BMB protection. mIHC detected the colocalization of CD68, MPO, and nuclear factor-kappa B (NF-κB) p65 subunit (NF-κB p65), showing that YWJ-6 modulated inflammatory cell infiltration and p65 activation. RT-qPCR, WB, and ELISA assays in HC11 and RAW264.7 cells confirmed that YWJ-6 downregulated inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and IL-1β, IL-6 and TNF-α expression in HC11 cells, and suppressed agent responsible for inflammation secretion in RAW264.7 cells. WB and immunofluorescence showed that YWJ-6 inhibited inhibitor of NF-κB alpha (IκBα) and NF-κB p65 phosphorylation in both HC11 and RAW264.7 cells. In conclusion, YWJ-6 exerts dual protective effects by targeting NF-κB signaling pathway activation, providing experimental evidence for mastitis treatment in future.

Pathological cardiac hypertrophy and heart failure remain mechanistically incompletely defined despite their clinical significance in cardiovascular disease. While ADP-ribosyltransferase cholera toxin-like (ARTC) enzymes modulate membrane protein function and downstream signaling via post-translational modifications, their role in cardiac pathology remains unexplored. Herein, we investigated the regulatory involvement of ADP-ribosyltransferase 3 (ART3) in myocardial remodeling. Cardiomyocyte-specific ART3 knockdown and overexpression murine models were established using adeno-associated virus serotype 9 (AAV9), with RNA-sequencing employed to profile ART3-dependent transcriptional responses in pathological cardiac hypertrophy. Functional validation was performed in complementary in vitro and in vivo hypertrophy models, complemented by immunoprecipitation-coupled mass spectrometry to identify ART3 substrates. ART3 was found to be cardiomyocyte-enriched and transcriptionally downregulated during progressive myocardial remodeling and heart failure. Cardiomyocyte-specific ART3 knockdown 3 accelerated the decompensatory transition of cardiac hypertrophy, whereas ART3 overexpression exerted significant anti-hypertrophic and anti-remodeling effects. Mechanistically, ART3 preserved cardiomyocyte mono-ADP-ribosyltransferase activity, catalyzing the site-specific mono-ADP-ribosylation (mADPr) of Integrin Subunit Alpha 7 (ITGA7) at residue R129. This post-translational modification was requisite for integrin signaling pathway activation, which mediated the observed cardioprotective effects. Collectively, these findings establish ART3 as a novel regulator of pathological cardiac hypertrophy by modulating ITGA7 via mADPr, highlighting its therapeutic potential as a target for heart failure intervention.

Atherosclerosis is driven by metabolic dysregulation and endothelial dysfunction; however, the precise molecular mechanisms underlying its pathogenesis remain incompletely elucidated. Fibrinogen-like protein 1 (FGL1) is a well-established hepatokine with critical roles in regulating tumorigenesis and metabolic dysfunction, while its involvement in atherogenesis remains unclear. Our clinical and preclinical studies revealed elevated plasma FGL1 levels in atherosclerotic patients and mice, correlating with arterial stenosis severity. Prolonged high-fat diet exposure specifically upregulated hepatic FGL1 expression. Hepatic FGL1 overexpression accelerated atherosclerosis, while liver-specific knockdown reduced plaque burden. Exogenous administration of FGL1 accelerated endothelial injury and atherosclerosis progression. Mechanistically, liver-derived FGL1 accumulates in vascular endothelium through fibrinogen C-terminal domain Trp225-mediated binding to integrin β1's vWFA domain. This interaction promotes the conformational change of integrin β1 and the formation of integrin β1/ILK1 complex, co-activating FAK/ERK and Smad signaling to drive transcriptional reprogramming of endothelial cells. Therapeutic interventions targeting FGL1-integrin β1 axis by integrin β1 blocking antibody, FGL1-neutralizing antibody, or RGD peptide effectively attenuated endothelial injury and atherogenic progression in murine models. These findings establish hepatic FGL1 as a novel endocrine regulator of vascular pathophysiology, highlighting the FGL1-integrin β1 axis as a promising therapeutic target for endothelial protection and atherosclerosis management.

Family with sequence similarity 19, member A5 (FAM19A5) is a secreted protein initially proposed as an adipokine with anti-inflammatory and anti-atherogenic properties. However, recent evidence has challenged this view by demonstrating minimal adipose expression and suggesting that circulating FAM19A5 may instead increase in response to vascular stress and atherogenic progression. To clarify its relevance in obesity-related dyslipidemia, this study examined the association between circulating FAM19A5 and established lipid-based atherogenic indices in a diet-induced obesity model.

This in vivo correlational study involved 14 male Sprague-Dawley rats (n=7 per group) conducted in Padang, Indonesia, in 2024. Rats were assigned to a control group (American Institute of Nutrition-93 diet) or an obesity group (high-fat and high-fructose diet) for 12 weeks. Serum FAM19A5 levels were measured by ELISA. Derived indices included the LDL/ApoB ratio, Castelli Risk Index I and II, and the HDL-based atherogenic index. Spearman's correlation analysis was used to assess the correlation (P<0.05), and all analyses were performed using SPSS version 25 (IBM Corp., USA).

FAM19A5 showed a strong positive correlation with the LDL/ApoB ratio (r=0.734, P<0.050), indicating that higher FAM19A5 levels coincide with more atherogenic ApoB-containing lipoprotein patterns. Correlations with Castelli Risk Index I (r=0.127, P>0.05), Castelli Risk Index II (r=0.369, P=0.195), and the HDL-based atherogenic index (r=0.127, P=0.666) were weak and not statistically significant.

Elevated circulating FAM19A5 may serve as a potential biomarker reflecting ApoB-related lipid alterations during obesity progression.

There are an estimated 9.5 million people living with type 1 diabetes (T1D) globally, with cardiovascular disease (CVD) remaining a major cause of morbidity and mortality despite advances in care. Atherosclerosis occurs earlier in people with T1D and those with T1D-onset in early childhood are at particularly high lifetime risk of CVD. Multiple traditional risk factors (e.g., glycaemia, lipids, blood pressure, obesity and smoking) and novel risk factors (e.g., social determinants of health, inflammation and genetics) can promote CVD in people with T1D. This highlights the need for a life-course approach to managing overall cardiovascular risk and preventing or mitigating end-stage complications such as atherosclerotic events, cardiac autonomic neuropathy and heart failure. However, most people with T1D do not meet all recommended risk factor targets. Whilst T1D-specific risk calculators for CVD are available to guide shared decision-making and risk factor management, greater awareness and further data are needed to inform their use in different T1D populations. However, there remains a relative paucity of T1D-specific clinical trial data to inform the management and therapies for CVD risk factors such as dyslipidaemia, hypertension and chronic kidney disease (CKD), and for clinically evident CVD. There is now increasing interest in the use of adjunct glucose-lowering drugs initially developed for use in type 2 diabetes, such as sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 agonists, and whilst some weight, glycaemia, blood pressure and albuminuria benefits have been shown, cardiovascular outcome trials (CVOT) in T1D are currently lacking. This review by a multidisciplinary team provides an overview of CVD pathophysiology, risk factor care, risk prediction and management in people with T1D.

Background: Research on the relationship between screen media use and mental health in youth is inconclusive. Exposure to potentially traumatic events (PTEs) is linked to both poor mental health and problematic media use (PMU).Objective: This study aimed to investigate whether PMU, including both generic PMU and problematic social media use (PSMU), mediates longitudinal changes in mental health problems (internalising and externalising) during early adolescence, and whether exposure to PTEs moderates this relationship.Method: The sample included 6,026 participants (M = 9.55, SD = 0.50 years at baseline; 52.3% girls; 46.3% white) from the Adolescent Brain Cognitive Development study who had at least one social media account. Data from baseline to 3-year follow-up (YFU) were analysed using a multi-informant approach. Moderated multiple mediation analyses were conducted using the PROCESS v4.2 macro, model 59.Results: 1YFU mental health problems (p < .001) and PTE exposure (p < .050) contributed to PMU at 2YFU. Mental health problems at 1YFU, PMU, and PSMU at 2YFU were all predictors of mental health problems at 3YFU (p < .001). The relationship between mental health problems at 1YFU and 3YFU was partially mediated by PMU and PSMU at 2YFU. However, the relationship between mental health problems and PMU/PSMU was not moderated by PTE exposure.Discussion: Mental health problems and exposure to PTEs independently contributed to PMU, which in turn exacerbated mental health problems. These findings underscore the importance of monitoring media usage, especially in vulnerable youth, and considering it in treatment, if needed.

Lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI+) patients continue to experience stigma, discrimination, and inadequate knowledge among mental health and medical professionals. These barriers can negatively impact health care outcomes, leading to delayed treatment, mistrust, and unmet medical needs within LGBTQI+ communities. Providing culturally competent care to LGBTQI+ people remains a critical challenge within health and social care. The development and use of reliable and valid assessments examining LGBTQI+ health care professional competency continue to be important in understanding and ameliorating LGBTQI+ health inequalities.

The aim of the study is to develop and psychometrically validate a new multinational instrument designed to assess health care professionals' LGBTQI+ attitudes, awareness, general skills, and knowledge, as well as to examine LGBTQI+ workplace affirmative policies, support, and climate.

An initial pool of 100 new scale items was developed by reviewing existing LGBTQI+ health care scales and consulting with LGBTQI+ health care experts in the summer of 2023. Leading experts in LGBTQI+ health care were then asked to participate in the Delphi method to provide numeric and qualitative feedback on the 100 items. This process yielded a final primary survey comprising 39 test items. A cross-sectional multicenter, multicountry scale validation study using a web-based survey was administered to health care professionals and trainees in Italy, the United States, and the United Kingdom between October 2024 and December 2025 using a convenience sampling approach complemented by snowball recruitment. Research participants were asked to complete a demographic and professional survey, the 39 new test items, the 18-item Lesbian, Gay, Bisexual, and Transgender Development of Clinical Skills Scale (LGBT-DOCSS), and the 12-item Workplace Support subscale of the LGBT Climate Inventory (LGBTCI).

Funding commenced in May 2023, and data collection was conducted from October 2024 to December 2025. A total of 1339 eligible people completed the survey. Data analysis has started, and results will be reported in theautumn of 2026. It is anticipated that the Professional Readiness in Diversity and Equity (PRIDE) scale will emerge as a reliable and valid tool for assessing health care professionals' LGBTQI+ attitudes, awareness, general skills, and knowledge, as well as examining LGBTQI+ workplace affirmative policies, support, and climate. The instrument may also serve as a useful outcome measure in research evaluating professional practice and development.

The development and validation of the new PRIDE scale represent a significant advancement toward improved cultural competence among health care professionals. Validating the scale in both English- and Italian-speaking populations will support the development of international interventions and, ultimately, treatment outcomes for LGBTQI+ people. The PRIDE scale has the potential to exert a far-reaching impact on the delivery of clinical care and public health services worldwide.