Frailty is relevant to HIV care across middle and later life, yet Japanese data remain limited. We evaluated frailty, prefrailty and associated factors in Japanese people with HIV using the revised Japanese Cardiovascular Health Study (J-CHS) criteria.

We conducted a multicentre cross-sectional study at eight HIV care centres. Eligible participants were Japanese people with HIV aged ≥40 years on antiretroviral therapy for ≥12 months. Frailty was classified as robust, prefrail or frail. Multivariable logistic regression examined factors associated with frailty-related outcomes; sensitivity analyses excluded sex from the model and restricted analyses to men.

Among 325 participants, median age was 55 [49-64] years and 311 (95.7%) were male; 70 (21.5%) were robust, 227 (69.8%) prefrail and 28 (8.6%) frail. Common components were low physical activity (36.6%), weight loss (33.2%) and slow gait (27.1%). In the frailty versus non-frailty model, higher PHQ-9 score (adjusted odds ratio [aOR] 1.12 per point, 95% confidence interval [CI] 1.04-1.21) and polypharmacy (aOR 3.34, 95% CI 1.23-9.10) were associated with frailty. In the prefrailty/frailty versus robust model, higher PHQ-9 score and body mass index were associated with the outcome. Sensitivity analyses yielded broadly consistent findings.

Prefrailty was highly prevalent, and frailty was associated with depressive symptoms and polypharmacy. Frailty at a median age of 55 years suggests clinically relevant vulnerability in Japanese people with HIV, although longitudinal and comparative studies are needed. These findings support integrated HIV care combining mental-health screening, medication review and physical-function assessment.

BackgroundStress hyperglycemia ratio (SHR) reflects the acute glycemic response to physiological stress. This study aimed to investigate the association between SHR and clinical outcomes in hospitalized patients with intracerebral hemorrhage (ICH).MethodData were extracted from the MIMIC-IV database. SHR was calculated using the following formula: admission blood glucose (mg/dL)/(28.7 × HbA1c (%) - 46.7). Restricted cubic spline (RCS) curves were utilized to explore potential nonlinear relationships between SHR and outcomes. Cox regression models were employed to assess the association between SHR and in-hospital mortality, and Kaplan-Meier curves were used to examine survival outcomes.ResultsA total of 1663 inpatients with ICH were included, with an in-hospital mortality rate of 7.5% (125/1663). RCS analysis revealed a significant non-linear association between SHR and the risk of all-cause mortality (all P < 0.05 for non-linearity). In the multi-variable Cox regression analysis, a higher SHR was significantly associated with an increased risk of all-cause mortality [adjusted HR =2.13 (95%CI 1.20-3.70), P = 0.009]. This positive association remained consistent across specific subgroups, including individuals aged > 65 years [HR 3.23 (95% CI 1.14-9.09)], females [HR 3.33 (95% CI 1.43-7.69)], and those with diabetes [HR 2.94 (95% CI 1.54-5.88)], COPD [HR 2.86 (95% CI 1.64-4.76)], or CKD [HR 3.03 (95% CI 1.61-5.56)].ConclusionA significant non-linear relationship was observed between SHR and all-cause mortality in hospitalized patients with ICH. Elevated SHR may serve as a potential predictor of poor prognosis in patients with ICH.

Chronic inflammation is increasingly recognized as a key contributor to the development and progression of heart failure (HF), with epicardial adipose tissue (EAT) emerging as an important local immunomodulatory organ. This study examined lymphocyte populations in EAT and subcutaneous adipose tissue (SAT) across different stages of HF and compared them with individuals without HF to clarify their potential role in HF progression.

Lymphocyte subsets in EAT, SAT, and peripheral blood were analyzed by flow cytometry in subjects with HF stage D, HF stage C, and subjects without HF. Circulating hormones and inflammatory proteins were quantified using ELISA and Luminex assays.

Subjects with HF stage D exhibited a reduction in T helper (Th), cytotoxic T (Tc), natural killer T (NKT), and B cells in EAT compared with both HF stage C subjects and subjects without HF, alongside changes observed in the circulation. In contrast, HF stage C was characterized by a significantly increased presence of Th2 and Th17 lymphocytes in EAT, indicating active immune remodeling during intermediate stages of HF. This stage was also associated with elevated circulating levels of Intracellular Adhesion Molecule-1, suggesting enhanced lymphocyte trafficking into adipose tissue. Across all study groups, EAT consistently contained a higher proportion of pro-inflammatory lymphocytes compared with SAT.

Together, these findings demonstrate that HF progression is accompanied by dynamic and stage-dependent changes in lymphocyte composition within adipose tissue, supporting the concept that a progressively pro-inflammatory EAT microenvironment may contribute to myocardial inflammation dysfunction-associated HF progression.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, and cardiovascular disease remains the leading cause of death in this population. Statins are therefore a cornerstone of therapy in MASLD because of their antiatherosclerotic efficacy. Less attention has been paid to the possibility that part of the hepatic benefit observed in MASLD cohorts-including lower aminotransferase levels, slower fibrosis progression, reduced decompensation and lower hepatocellular carcinoma incidence-may reflect direct hepatic effects beyond LDL reduction. Although the evidence is predominantly observational, the direction and magnitude of the association have remained broadly consistent across independent cohorts. Recent studies have strengthened this signal, including a post hoc analysis of the PROSPER trial showing attenuation of excess mortality in individuals with elevated FIB-4, and a large Veterans Affairs cohort demonstrating a dose-dependent association between cumulative statin exposure and lower primary liver cancer risk in MASLD. This review integrates the preclinical, observational and indirect randomized evidence supporting the biological plausibility of liver-directed effects of statins. Mechanistically, the argument centres on inhibition of the mevalonate pathway as a molecular hub linking lipotoxicity, NLRP3-dependent inflammation, fibrogenesis and carcinogenesis through impaired prenylation of small GTPases. A fifth axis, intrahepatic hemodynamics mediated through KLF2/eNOS signaling, is supported by randomized evidence in compensated cirrhosis. In contrast, the LIVERHOPE-EFFICACY trial showed no benefit in decompensated cirrhosis, helping define the therapeutic window. Within the limitations of the available evidence, we propose a conceptual reframing: in MASLD, statins may act not only as cardiovascular drugs, but also as agents with potentially relevant hepatic effects mediated through a shared molecular substrate.

Ubiquitin-specific protease 25 (USP25), a pivotal deubiquitinating enzyme, has attracted increasing attention in cardiovascular and cerebrovascular research due to its regulatory function in maintaining ubiquitination homeostasis. Considerable advances have been achieved in elucidating the molecular mechanisms through which USP25 participates in the pathological progression of diverse cardiovascular and cerebrovascular disorders. From the perspective of translational medicine, notable progress has also been observed in the development of USP25-targeted therapeutics, with several inhibitors having advanced to preclinical and early-phase clinical trials, thereby offering promising targets for precision treatment. Nevertheless, a systematic synthesis of fundamental biological properties, the trajectory of research development, and the intricate upstream-downstream regulatory networks of USP25, together with its mechanistic roles and therapeutic potential in these diseases, remains absent. In response, this review provides an in-depth summary of the essential biological features of USP25, elucidates the interplay between its upstream regulators and downstream substrates, and highlights its specific molecular mechanisms in cardiovascular and cerebrovascular disease pathogenesis. Additionally, the feasibility and strategic approaches of targeting USP25 for therapeutic purposes are analyzed, while the limitations and potential breakthroughs in the development of USP25 inhibitors are discussed. Finally, priority research directions are proposed to guide future exploration, with the ultimate aim of contributing theoretical foundations and novel perspectives for clinical management of cardiovascular and cerebrovascular diseases.

Transposition of the great arteries (TGA) is one of the critical congenital heart diseases of the newborn. The transition from fetal to postnatal circulation in these infants is complex, and the presence of persistent pulmonary hypertension of the newborn (PPHN) during this period may affect surgical outcomes. This study aims to evaluate the impact of PPHN on perioperative morbidity and mortality in infants with TGA.

The study was conducted between December 1, 2024, and December 1, 2025, in two high-volume cardiac centers, involving newborns diagnosed with TGA. Patients were divided into two groups-PPHN and non-PPHN-based on clinical and echocardiographic findings. The groups were evaluated for early-term (first 30 days) mortality and morbidity. Findings were analyzed statistically.

A total of 48 newborns with TGA (60% male) were included. The median age at operation was 5 days (IQR 3-7), median weight was 3,100 g (IQR 2,900-3,400), and the median preoperative oxygen saturation was 76% (IQR 70-82). Balloon atrial septostomy was performed in eight infants prior to ASO. PPHN was identified in thirteen infants (27%). Postoperative complication rates-including duration of vasopressor use, duration of sedative medication, length of hospital stay, and duration of mechanical ventilation-were higher in the PPHN group (p < 0.05). Overall mortality was 10.4%, with no significant difference between the PPHN and non-PPHN groups (15.3% vs. 8.5%; p = 0.60).

In newborns with TGA, PPHN was associated with increased postoperative morbidity. While no statistically significant difference in early mortality was observed, larger multicenter studies are needed to better define the impact of PPHN on mortality risk.

Lipid accumulation product (LAP), derived from waist circumference and triglycerides, may reflect central lipid overaccumulation, but its relevance for a screening-defined cardiovascular disease (CVD) high-risk label is uncertain. We examined whether LAP could help flag community adults who may need more formal risk assessment rather than serve as a stand-alone prognostic tool.

This cross-sectional analysis initially considered 6,860 adults aged 35-75 years from the ChinaHEART screening program in Luohe. After excluding participants with missing LAP or screening-defined CVD high-risk outcome data, 6,803 participants were included in the base analytic sample. LAP was analyzed continuously and dichotomized using a rounded cutoff of 42 derived from the Youden index in the LAP-only receiver operating characteristic (ROC) analysis. Logistic regression, restricted cubic splines, subgroup analyses, and ROC analyses were conducted under four stepwise models. Exploratory least absolute shrinkage and selection operator (LASSO), XGBoost, and TreeSHAP analyses were added as supplementary pattern-recognition analyses.

ROC analysis identified an optimal LAP cutoff of 42.12 in the LAP-only model; the rounded value of 42 was used for categorical analyses. LAP alone showed modest discrimination for the concurrent screening-defined CVD high-risk label (AUC 0.583, 95% CI 0.566-0.600), which increased to 0.628 (95% CI 0.613-0.643) after adding age and sex and to 0.632 (95% CI 0.619-0.649) in Model 3. Using the rounded cutoff of 42, 42.3% of participants were classified as high LAP. The prevalence of screening-defined CVD high-risk status was higher in the high-LAP group than in the low-LAP group (28 vs. 17%, P < 0.001).

Higher LAP was associated with a greater likelihood of meeting a contemporaneous screening-defined CVD high-risk criterion. These findings support LAP as a pragmatic screening trigger for further formal assessment in community settings, not as evidence of causal risk stratification or prediction of hard cardiovascular events.

The mesenchymal homeobox transcription factor MEOX2 is recognized for its roles in development and homeostasis, but the full landscape of its complex and often contradictory functions in human diseases, along with its potential unifying regulatory logic, remains to be systematically elucidated. This Review synthesizes current evidence to provide a comprehensive overview of MEOX2's widespread roles in both neoplastic and non-neoplastic diseases. MEOX2 is remarkably context-dependent: it acts as an oncogene in glioblastoma and lung cancer, but as a tumour suppressor in breast cancer, hepatocellular carcinoma and other tumour types. Its dysregulation is also linked to neurovascular deficits in Alzheimer disease (AD), cardiovascular disorders, metabolic fibrosis and developmental malformations. This functional versatility stems from MEOX2's role as a key signalling integrator, subject to fine-tuned regulation by epigenetic mechanisms, non-coding RNA networks and core pathways including PI3K/AKT, ERK and Hedgehog (Hh). Given the strong association between MEOX2 expression and clinical outcomes, it has emerged as a potential diagnostic and prognostic biomarker for several diseases. Intervention strategies targeting MEOX2 and its regulatory networks show translational promise. This Review proposes a conceptual framework placing MEOX2 as a 'cross-disease core regulatory node', systematically delineates its complex disease associations and molecular mechanisms, and charts a course for the future development of precision medicine strategies targeting MEOX2.

Endovenous procedures have been shown to offer an effective treatment for Iliofemoral deep venous thrombosis with a clinically relevant reduction in postthrombotic syndrome (PTS) compared to anticoagulation alone. Catheter-based thrombolysis reduces the risk of PTS but has been shown to cause periprocedural bleeding in about 3%. This review finds that mechanical thrombectomy has emerged as an ideal technique, with thrombus extraction without bleeding and a significant reduction in PTS at 12 months. A large randomised controlled trial including this technique versus anticoagulation is ongoing.

MicroRNA‑146a (miR‑146a) has emerged as a core regulatory molecule in inflammation and metabolism in recent years, and the present review systematically elucidates its critical role and regulatory mechanisms in cardiovascular diseases as well as endocrine and metabolic disorders. Evidence indicates that miR‑146a negatively regulates the nuclear factor‑κB inflammatory signaling pathway by targeting key molecules such as tumor necrosis factor receptor‑associated factor 6 and interleukin‑1 receptor‑associated kinase 1. This regulation impacts various pathophysiological processes, including immune response, inflammatory reactions, oxidative stress, cell apoptosis and proliferation, autophagy, and anti‑fibrosis. The molecule demonstrates a bidirectional dynamic regulatory feature, exhibiting either protective or maladaptive effects in different diseases and stages of disease, particularly in the progression of cardiovascular conditions (such as myocardial ischemia‑reperfusion injury and atherosclerosis) and endocrine and metabolic disorders (such as diabetes and its complications). Additionally, miR‑146a serves as a significant biomarker and therapeutic target. Future research should focus on further elucidating its cell‑ and disease course‑specific mechanisms while promoting the clinical translation of therapeutic strategies based on targeted delivery systems.