The aim of this study was to investigate serum miR-101 and miR-146a expression levels in adult sepsis, compare them with healthy controls, and assess their relationships with inflammatory markers and disease severity.

In total, 15 adults meeting Sepsis-3 criteria and 15 healthy controls were prospectively enrolled. Serum miR-101 and miR-146a levels were quantified by quantitative polymerase chain reaction within 24 h using the 2-∆Ct method and reassessed on day 3. Associations with clinical, laboratory, and disease severity parameters were analyzed.

On day 1, miR-101 expression was significantly higher in the sepsis group than in controls (1.17 vs. 0.14; p=0.011). miR-146a levels were lower in sepsis but did not differ significantly (p=0.152). Neither miRNA showed a significant change from day 1 to day 3 (miR-101: p=0.776; miR-146a: p=0.191). miR-101 demonstrated positive correlations with procalcitonin, white blood cell count, C-reactive protein, creatinine, and a negative correlation with albumin. Levels were markedly higher in patients with cardiovascular comorbidities (ρ=0.622; p=0.013). miR-101 correlated positively with Acute Physiology and Chronic Health Evaluation II (ρ=0.412; p=0.024), while no association was observed with Sequential Organ Failure Assessment. miR-146a showed no meaningful correlations with clinical or laboratory parameters.

miR-101 is significantly elevated in adult sepsis and reflects systemic inflammatory burden and disease severity; however, given its limited specificity, it should be considered a complementary biomarker rather than a standalone diagnostic or prognostic tool. Its stable expression between days 1 and 3 suggests a sustained early phase molecular response. miR-146a shows no significant change and has limited diagnostic relevance in adult sepsis. Larger multicenter studies are needed to validate these findings.

Myocardial ischemia-reperfusion injury (MIRI) remains a major clinical problem, and its regulatory mechanisms are not fully defined. This study aimed to identify key MIRI-related targets and clarify their roles in cellular and animal models.

Differentially expressed genes in MIRI were screened using the GEO dataset GSE6381, and core genes were identified through protein-protein interaction analysis and weighted gene co-expression network analysis. External datasets GSE249812 and GSE123342 were used to validate core gene expression. Transcription factors regulating cystic fibrosis transmembrane conductance regulator (CFTR) were predicted using the KnockTF database. In AC16 cells, an oxygen-glucose deprivation/reoxygenation (OGD/OGR) model was established. Microphthalmia-associated transcription factor (MITF) was knocked down or overexpressed, CFTR was silenced or overexpressed, and cell viability, proliferation, apoptosis, and NO/L-arginine/citrulline levels were assessed. The MITF-CFTR interaction was examined by dual-luciferase assay and chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR). A rat ischemia-reperfusion (I/R) model was used to evaluate the effects of MITF silencing and CFTR rescue on cardiac injury.

A total of 42 core genes related to MIRI were identified. CFTR showed consistent upregulation across datasets and was linked to pathways including arginine biosynthesis. CFTR-related transcription factors included MITF, TP53, and STAT3, but ChIP-qPCR showed detectable enrichment only for MITF at the CFTR promoter. In AC16 cells, CFTR protein increased during early reoxygenation. OGD/OGR elevated CFTR and MITF, while MITF knockdown or CFTR silencing further reduced cell viability and proliferation, increased apoptosis, and was accompanied by lower NO and citrulline levels and higher L-arginine levels. MITF overexpression showed the opposite trend, and CFTR overexpression partially reversed the effects of MITF deficiency. In vivo, MITF knockdown aggravated cardiac dysfunction, increased CK and CK-MB levels, worsened tissue injury, and elevated cleaved caspase-3 after I/R, whereas CFTR overexpression partly improved these changes.

MITF regulates CFTR expression in MIRI, and disruption of the MITF-CFTR axis is associated with aggravated injury in cellular and animal models. Restoring CFTR partially mitigates MITF deficiency-related damage. These findings support the involvement of MITF-CFTR regulation in MIRI and provide a basis for further mechanistic investigation.

Positive airway pressure (PAP) has shown inconsistent effects on cardiovascular (CV) outcomes in obstructive sleep apnoea (OSA). Physiological biomarkers derived from sleep studies such as sleep apnoea-specific hypoxic burden (SASHB) and event-related heart rate response (ΔHR) may help identify OSA patients with modifiable CV risk.

3370 PAP-treated moderate-to-severe OSA patients, from the Pays de la Loire sleep-clinic cohort linked to the French health database (SNDS), were stratified by a high-risk status defined by SASHB >40.6%·min·h⁻¹ or ΔHR >21.7 bpm, using percentile-based approach for threshold estimation. The primary composite outcome was defined using the first occurrence in SNDS of major adverse CV event (MACE). Cox models assessed the association between PAP adherence (mean PAP use ≥4 h/night) and MACE occurrence.

Over a median follow-up of 9 years, 740 patients experienced a MACE. PAP adherence versus non-adherence was associated with a reduced risk of MACE (adjusted hazard ratio [HR] 0.53, 95% CI [0.46-0.62], p<0.001), but the association was greater in patients with (71.7%) versus without (28.3%) high risk status (interaction HR 0.61 [0.43-0.87]; interaction p value =0.006). Similar findings were obtained using a simplified version of SASHB and ΔHR automatically derived from the single oximetry signal. The interaction of high-risk status between PAP adherence and MACE appeared stronger in non-sleepy patients.

In sleep-clinic, the association of PAP adherence with reduced MACE risk was stronger in high risk OSA. These findings support the integration of hypoxic and autonomic biomarkers into clinical decision pathways for CV risk reduction in OSA.

We present the case of an otherwise previously healthy female in middle childhood with severe renovascular hypertension secondary to midaortic syndrome with ascending aortic dilation. She presented with hypertensive emergency (>200/100 mm Hg) and a marked blood pressure gradient between upper and lower extremities. She underwent successful surgical revascularisation by way of aorto-aortic bypass with a polytetrafluoroethylene graft and revascularisation of the superior mesenteric artery and both renal arteries by way of reimplantation for refractory hypertension despite four antihypertensives (ie, amlodipine, metoprolol, losartan and transdermal clonidine). At 18 months postoperatively, she is normotensive with a single agent, losartan, and has resolution of both left ventricular hypertrophy and symptoms. She follows with her multidisciplinary team with surveillance renal duplex and echocardiogram two times per year.

Cardiovascular diseases remain a global health priority, with oral health linked to cardiovascular risk. However, existing studies have mainly focused on limited periodontal measures and lack analyses of multidimensional oral health.

Using data from 4670 participants in the China Multi-Ethnic Cohort, this cross-sectional study employed an exposure-wide analysis to systematically examine associations between multidimensional oral health indicators and cardiovascular disease-related outcomes, and to exploratorily assess the role of blood and urine-based biomarkers as potential intermediary indicators.

We found that indicators regarding caries, periodontal status, occlusal function, and oral prosthesis were significantly associated with carotid plaque prevalence in total and sex-stratified population. For age-stratified analysis, the associations between oral health indicators and hypertension were predominantly confined to participants aged under 65 years, whereas those with carotid plaque were observed among participants aged 65 years and above. The association with Framingham risk score was observed in both populations.

These findings indicate that multidimensional oral health correlates with cardiovascular outcomes, with obvious sex and age differences, and that blood biomarkers may partially explain these associations. Our findings provide new insights by highlighting the relevance of multidimensional oral health to cardiovascular risk, supporting its consideration in cardiovascular risk assessment.

Multidimensional oral health indicators, including caries, periodontal status, occlusal function, and oral prosthesis are associated with cardiovascular risk, exhibiting sex and age heterogeneity. Blood biomarkers may partially indicate these associations. These findings indicate the potential value of considering oral health in cardiovascular risk assessment.

Basal metabolic rate (BMR) may play a key role in the prevalence of aortic aneurysm and dissection. This study aimed to explore the association between BMR and the risk of abdominal aortic aneurysm (AAA), thoracic aortic aneurysm (TAA), and aortic dissection.

Mendelian randomization (MR) analyses were conducted to examine the causal relationship between BMR and aortic aneurysm and dissection. The data from 360,292 participants in the UK Biobank were analyzed using Cox regression models and restricted cubic spline. The results were further validated in a Chinese cohort of 10,169 participants for AAA.

The two-sample MR showed that BMR was associated with increased risk of AAA (odds ratio [OR] = 1.49, 95% confidence interval [CI] 1.20-1.84, P < 0.00), TAA (OR = 2.13, 95% CI 1.71-2.64, P < 0.00), and aortic dissection (OR = 1.94, 95% CI 1.32-2.86, P < 0.00). Multivariable MR confirmed these associations after adjusting for confounders. In the UK Biobank cohort, multivariable analysis showed that the highest BMR quartile was associated with increased risk of AAA and TAA (hazard ratio= 1.70, 95% CI 1.27-2.27, P < 0.01; hazard ratio= 2.01, 95% CI 1.29-3.13, P < 0.01). The restricted cubic spline model demonstrated a J-shaped relationship between BMR and AAA as well as TAA (nonlinear P < 0.001). In the Chinese cohort, Model 4 showed that higher BMR quartiles were associated with increased AAA risk (OR = 1.78, 95% CI 1.33-2.23, P = 0.01).

MR analyses suggest a causal relationship between BMR and the risk of AAA and TAA, which is further validated by positive associations in two large cohorts, highlighting BMR's potential utility in clinical risk stratification and management.

Physical conditions are increasingly recognized as contributors to suicide risk, independent of psychiatric comorbidity. The aim of this study was to descriptively examine the association between a range of lifetime physical conditions and suicide attempts in a large, population-based US sample. Data were analyzed from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III; N = 36,171). Lifetime suicide attempts (n = 1995) were assessed via self-report. Physical conditions were self-reported based on physician diagnosis and included a range of metabolic, infectious, cardiovascular, gastrointestinal, neurological, respiratory, and autoimmune diseases. Over 20% of those with arteriosclerosis and hypertension, arthritis, and dyslipidemia, sleep problems, and cardiovascular disease (20.1-27.9%) endorsed a lifetime suicide attempt. With the exception of cancer, all physical conditions were associated with suicide attempts. After adjustment for sociodemographic factors and psychiatric conditions, most associations were attenuated but remained significant (adjusted odds ratio [AOR] range across the significant conditions: 1.16-2.75), with the strongest associations observed for epilepsy and HIV/STIs. Only cancer, osteoporosis, and traumatic brain injury were not significantly associated with suicide attempts in the fully adjusted models. Increasing number of health conditions was also significantly associated with suicide attempts across all models. Findings may inform suicide prevention efforts by highlighting the need for integrated physical and mental health care, particularly for patients living with multimorbidity. Results were correlational and future research should examine relationships longitudinally.

Doxorubicin (DOX) is a widely utilized anthracycline chemotherapeutic agent in clinical settings; however, its application is significantly constrained by the cardiotoxic effects it induces, the underlying mechanisms of which remain inadequately understood. Ferroptosis, a recently identified form of iron-dependent programmed cell death, has been implicated in cardiovascular diseases, yet its involvement in doxorubicin-induced cardiotoxicity (DIC) requires further elucidation. Yes-associated protein (YAP), a pivotal component of the Hippo signaling pathway, plays a crucial role in myocardial cell survival and the preservation of cardiac function. Elucidating the alterations and mechanisms of YAP in the regulation of ferroptosis within the context of DIC may facilitate the identification of novel therapeutic targets for its prevention and treatment.

A DIC model was established both in vivo and in vitro using doxorubicin (DOX). Myocardial tissue damage and morphological changes in mice were assessed using echocardiography, lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) assays, hematoxylin and eosin (HE) staining, and transmission electron microscopy. Additionally, dihydroethidium (DHE) and C11-BODIPY fluorescence staining was employed to evaluate alterations in reactive oxygen species (ROS) and lipid peroxidation levels in mice and HL-1 cardiomyocytes. Utilizing the DIC model, YAP was overexpressed in HL-1 cardiomyocytes. Cell viability, along with levels of LDH, GSH, and Fe²⁺ in HL-1 cardiomyocytes, were quantified using specific commercial assay kits. The expression levels of GPX4, ferritin, FSP1, DHODH, xCT, YAP, phosphorylated YAP, and nuclear YAP were evaluated in mouse models and HL-1 cardiomyocytes using RT-qPCR analysis, Western blot analysis, and immunofluorescence techniques.

Results indicated that within the DIC model, there was an increase in ferroptosis in both murine myocardial tissue and HL-1 cardiomyocytes, accompanied by a decrease in YAP protein expression and the translocation of nuclear YAP. Notably, YAP overexpression in HL-1 cardiomyocytes was found to inhibit ferroptosis and mitigate doxorubicin-induced cardiotoxicity. However, this protective effect was partially reversed by inhibition of YAP, GPX4, FSP1, and DHODH.

Our findings suggested that YAP overexpression attenuate DIC by inhibiting ferroptosis. These observations point to YAP as a potential therapeutic target for reducing DOX-induced myocardial injury.

Incident dysnatremia has been reported amongst varied intensive care unit disease populations and is associated with worse clinical outcomes, but less is known about the impacts of dynamic changes in serum sodium during intensive care unit admission. The primary objective of this study was to conduct a scoping review of the published literature on patient outcomes associated with dynamic changes in serum sodium in critically ill adults, to inform future research priorities. A scoping review was conducted according to the Joanna Briggs Institute method. PubMed®, Embase, CINAHL, Scopus, and Web of Science databases were searched for relevant articles on sodium "change", "trajectory", "fluctuation", or "variability" in adult patients managed in the intensive care unit. Seventeen articles were extracted; seven involved patients with subarachnoid hemorrhage in the intensive care unit, and ten involved mixed or other specific primary diagnoses requiring intensive care unit admission. In subarachnoid hemorrhage, higher magnitudes of serum sodium change, independent of incident dysnatremia, are associated with greater mortality and delayed cerebral ischemia. A similar association between the magnitude of serum sodium change and mortality is observed in other intensive care unit disease populations. There is limited literature on dynamic changes in serum sodium in intensive care unit populations, but current evidence suggests that greater magnitude is associated with higher mortality and morbidity across multiple intensive care unit disease populations. Current observational literature is insufficient to establish causal links between dysnatremia and worse patient outcomes.