Primary Sjögren's disease (pSjD) confers a markedly elevated risk for developing CVD, an important contributor to mortality in this population. This study was designed to identify factors associated with CVD in pSjD and to develop a classification model.

In this cross-sectional analysis of pSjD individuals (2013-2023), multivariable logistic regression was used to identify CVD-related factors. A classification model was constructed with variable selection via LASSO regression and the Boruta algorithm.

Among 734 patients with pSjD, 192 (26.2%) had CVD. Age (odds ratio [OR]: 1.06, P < 0.001), body mass index (BMI; OR: 1.14, P < 0.001), triglyceride-glucose (TyG) index (OR: 3.49, P < 0.001), and positive anti-Ro52 status (OR: 1.58, P = 0.022) were independent correlates of CVD in pSjD. Moreover, age, BMI, and TyG index showed a trend of gradually increasing CVD risk in patients with pSjD (P < 0.05). A five-variable classification model incorporating age, BMI, TyG index, anti-Ro52 antibody, and corrected QT interval was developed to identify CVD status. Good discrimination (area under the curve: 0.768), proper calibration, and clinical applicability were observed for this model. Its performance remained robust upon internal validation and testing in the test set (area under the curve: 0.753 and 0.821).

The TyG index and anti-Ro52 antibody serve as significant factors associated with prevalent CVD in patients with pSjD. A novel classification model that integrates these biomarkers with age, BMI, and corrected QT interval showed good performance and generalizability, and may provide a practical tool for identifying cardiovascular status in this population.

Chronic somatic diseases (CSDs), particularly cardiometabolic diseases (CMDs) are recognized contributors to functional disability, yet limited evidence examines these associations by employing longitudinal approaches.

This study aimed to investigate the association between early adulthood patterns of CMDs and other CSDs with the incidence and trajectories of later-life functional disability.

Data were drawn from the China Health and Retirement Longitudinal Study implemented during 2011-2020. Functional disability was measured by activities of daily living (ADL) and instrumental activities of daily living (IADL). Latent class trajectory modeling was used to identify 10-year trajectories of functional disability. Sequence analysis was used to cluster CSD patterns from ages 18 to 44 and time-dependent Cox proportional hazard models and logistical regressions were employed to detect the associations between early adulthood CSD patterns and the incident risk and longitudinal trajectory of functional disability in later life.

Among 7,077 participants, four distinct early adulthood disease patterns were identified: (I) "Long-term health," (II) "Long-term with a non-CMD CSD", (III) "Later fast transition to CMDs or non-CMD CSDs", and (IV) "Early transition to CMDs or multimorbidity". After adjusting for covariates, participants with a history of CSDs showed higher risks of functional disability.

This study confirms that early adulthood patterns of CSDs are differentially associated with later-life functional disability, through the establishment of a lifespan-based disease-disability research framework and multi-disease trajectory modeling. Early diagnosis and interventions for CSDs are important to sustain functional function in aging.

Not applicable.

The cardiovascular-kidney-metabolic (CKM) syndrome is a major public health challenge driven by intertwined cardiometabolic and renal dysfunction. Diet-related inflammation and oxidative stress may accelerate biological aging, as reflected by DNA methylation age acceleration, thereby contributing to CKM progression and mortality. However, these pathways have not been comprehensively examined.

We analysed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002, including non-pregnant adults aged ≥ 20 years with complete dietary, epigenetic, and cardiometabolic data. Dietary inflammatory potential and antioxidant capacity were assessed using the Dietary Inflammatory Index (DII) and Dietary Oxidative Balance Score (DOBS), derived from 24-hour dietary recall data. DNA methylation age acceleration (DNAmAA) was quantified using multiple established epigenetic clocks. Cardiovascular-kidney-metabolic (CKM) syndrome was defined and staged according to contemporary criteria. Associations of dietary indices with DNAmAA, CKM stages, and all-cause and cause-specific mortality were examined using weighted regression and Cox proportional hazards models. Mediation analyses were performed to evaluate the role of DNAmAA in linking dietary patterns with CKM progression and mortality. All analyses accounted for the complex NHANES survey design and relevant confounders.

Participants with higher dietary inflammatory potential (higher DII) and lower antioxidant capacity (lower DOBS) exhibited less favourable sociodemographic and cardiometabolic profiles and more advanced CKM stages at baseline. Higher DII was consistently associated with accelerated epigenetic aging across multiple DNAmAA measures, whereas higher DOBS showed protective associations. Pro-inflammatory and pro-oxidative dietary patterns were associated with increased odds of advanced CKM stages and higher risks of all-cause and cardiovascular mortality, while anti-inflammatory and antioxidant dietary patterns were associated with lower risks. Mediation analyses demonstrated that GrimAge acceleration and DunedinPoAm partially mediated the associations of dietary indices with CKM progression and mortality, supporting a role for biological aging in linking diet-related inflammation and oxidative stress to adverse CKM outcomes.

Dietary inflammatory and oxidative potential is associated with epigenetic aging, CKM progression, and mortality, partly mediated by GrimAge and DunedinPoAm. Improving dietary quality may represent a modifiable strategy to reduce CKM burden.

The association between coffee or caffeine intake and cardiovascular diseases (CVDs) and their risk factors has been extensively researched. However, there has been conflicting evidence. Therefore, the current updated meta-analysis assessed the relationship between coffee or caffeine with CVDs, such as coronary heart diseases (CHDs), myocardial infarction (MI), heart failure (HF), stroke, cardiac arrhythmias, and CVD mortality.

Five electronic databases, namely PubMed, Web of Science, Cochrane Library, Embase, and Scopus, were extensively searched for all records published between January 2000 and December 2025. Studies were included if they examined the effects of coffee on any CVD and reported the associations in terms of the hazard ratio (HR), relative risk (RR), or odds ratio (OR). Moreover, quality appraisal was conducted using the Newcastle Ottawa Scale for cohort studies and the Joanna Briggs Institute tool for case-control studies.

After exclusions, 38 studies involving 2,856,002 participants were reviewed and analyzed. The pooled analysis showed no significant associations between coffee consumption and total CHDs or HF, when comparing the highest and lowest coffee consumption categories (HR: 0.98; p = 0.80 and HR: 1.03; p = 0.62, respectively). In contrast, the pooled results showed a significant positive association between higher coffee consumption and the risk of developing MI (OR: 1.48; p < 0.0001). The pooled analysis also showed an inverse relationship between coffee consumption and stroke or cardiac arrhythmias (HR: 0.89; p = 0.01 and HR: 0.94; p = 0.04, respectively). Furthermore, we observed a non-linear relationship between caffeine intake and CVD mortality among hypertensive patients (HR: 0.68; p = 0.001).

Higher coffee intake might increase the risk of MI, but can also offer protective effects against stroke and cardiac arrhythmias. Moreover, higher caffeine intake can reduce the risk of CVD mortality in hypertensive patients.

PROSPERO: CRD420251073620.

Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery, and perioperative amiodarone is recommended for POAF prophylaxis, while the optimal timing, route, and dosage remain unclear. The purpose of this study is to evaluate the efficacy of perioperative amiodarone for the prevention of POAF in patients undergoing cardiac surgery and to reevaluate the impact of its timing, route, and dosage.

Data were collected through searching PubMed, Embase, and the Cochrane Library from inception until September 30, 2025, for randomized controlled trials (RCTs). Data were pooled using a random-effects model.

Forty RCTs involving 6,166 patients were included. Amiodarone was associated with a substantial reduction in the incidence of POAF (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.31 to 0.49, P < 0.00001, I² = 57%). The preventive efficacy may be primarily influenced by the combination of administration timing and route, rather than by the cumulative dose alone. Notably, a significant dose-response relationship was observed within the preoperative through postoperative oral strategy. Statistically significant differences were found in length of hospital stay (mean difference -1.33 days, P < 0.0001) and cerebrovascular accident (OR = 0.59, P = 0.04), and an increased risk of bradycardia (OR = 2.33, P < 0.00001). No statistically significant differences were found in mortality, heart block, or hypotension.

Prophylactic perioperative amiodarone may be associated with a reduced incidence of POAF, consistent with current guideline recommendations, and the timing and route of administration appear to play a more important role than the dose alone. While an increased risk of bradycardia was observed, no clear association with major adverse outcomes was identified. These results should be interpreted cautiously and may help optimize prophylactic strategies in appropriate clinical contexts.

Spinal cord infarction (SCI) is a rare but severe cause of acute myelopathy, and evidence supporting reperfusion therapies remains limited.

We report a 73-year-old man with spontaneous cervical SCI treated with intravenous alteplase and perform a systematic review (database search from inception to 13 November 2025) of case reports/series describing intravenous (IV) or intra-arterial (IA) thrombolysis for SCI, extracting data about clinical presentation, diagnostic and therapeutic work-up and functional outcomes.

Our patient improved after thrombolysis and achieved functional independence at 3 months (modified Rankin Scale [mRS] 2). The review identified 21 studies (19 case reports, 2 case series) totaling 25 patients; including our case, 26 patients were analyzed. Mean age was 57.4 years (range 14-83), and anterior spinal artery (ASA) syndrome was the most common presentation. Most patients received IV thrombolysis; 4 underwent IA therapy (alone or combined). Considering the last available assessment, 14/25 patients (56.0%) had a favorable outcome (mRS 0-2), 8/25 (32.0%) had mRS 3, and 3/25 (12.0%) had mRS 4-5. No symptomatic treatment-related hemorrhagic complications were reported. DISCUSSION AND CONCLUSION: Published experience suggests that thrombolysis in carefully selected patients with suspected SCI may represent a reasonably safe therapeutic option, but evidence is limited and subject to major bias. Prospective registries and multicenter studies are needed to clarify safety, efficacy, and selection criteria.

A critical question in Duchenne muscular dystrophy (DMD) research is whether regulatory mechanisms beyond dystrophin loss contribute to impaired muscle regeneration. Through integrative analysis of proteomics and single-nucleus RNA sequencing database, we identify the upregulation of ANXA11, a gene encoding a Ca²⁺-dependent phospholipid-binding protein, in MYH3⁺ regenerative myofibers from both mdx mice and DMD patients. This upregulation disrupts the maturation of regenerative myofibers, preventing adequate compensation for muscle loss in mdx mice due to dysregulation of the mTOR pathway. Suppression of Anxa11 via genetic knockout or AAV9-mediated knockdown significantly enhanced MYH3⁺ myofiber maturation, accompanied by restored S6 phosphorylation and robust functional muscle recovery in mdx mice. These results establish ANXA11 as a key regulator of muscle regeneration and a potential therapeutic target for DMD.

Mitochondrial cristae ultrastructure enables ATP synthase organization for adaptive energy production. This process is critical for regulating microglia mediated neuroinflammation in ischemic stroke pathology. However, therapeutic strategies targeting cristae remodeling remain unexplored. We identified a chemical probe, icariin II (ICS), which restores mitochondrial cristae by targeting triose phosphate isomerase 1 (TPI1). ICS-induced TPI1 conformational switching recruits ATP5MF to drive F₁F_o-ATP synthase dimerization, thereby resulting in cardiolipin-mediated membrane curvature generation for cristae morphogenesis. Functionally, TPI1-targeted intervention reprograms microglial immunometabolism by rescuing oxidative phosphorylation, suppressing mtDNA-STING neuroinflammation, and promoting M2 polarization. In vivo, pharmacologically targeting TPI1 inhibits microglial activation to reverse the pathological processes in a middle cerebral artery occlusion rat model (male only). Further, evidence from stroke patients suggests an association between TPI1 and microglial activation. Collectively, our findings reveal that cristae plasticity is a promising therapeutic target for mitochondrial disorders, with TPI1 as a central regulator for ischemic stroke.

Natural killer (NK) cell-based therapies are under assessment for the treatment of various cancers due to their intrinsic ability to distinguish between malignant and healthy cells in an allogeneic context, enabling off-the-shelf manufacturing possibilities. However, cryopreservation reduces both the recovery and function of NK cells, thereby limiting their therapeutic feasibility. In this study, we evaluated three cryoprotectants (CryoStor 10; ZKCELL FM-01; FBS + DMSO) for the cryopreservation of NK cells. Post-thaw viability, ATP levels, and cytotoxicity were assessed and found to have persistent differences between cryopreserved and fresh cells. Transmission electron microscopy, flow cytometry, and Western blot analysis revealed a complex mode of cell death in cryopreserved cells, which could be partially mitigated by adding some death inhibitors. We further investigated the effects of centrifugation on thawed cells, identifying lysosomal stability as a key determinant of cell death. Pretreatment with low-dose LLOMe prior to cryopreservation induced stress granule formation, stabilizing lysosomes and improving cell recovery rates without compromising effector functional capacity. These findings offer new insights for optimizing NK cell cryopreservation and facilitating their clinical application.

Acute limb ischemia (ALI) is a limb- and life-threatening vascular emergency that necessitates prompt revascularization. While both surgical and endovascular interventions are established treatment modalities, contemporary comparative data remain limited. The study aims to evaluate and compare outcomes between these revascularization strategies.

A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review and meta-analysis were performed. Three databases were searched through January 2026. All studies comparing endovascular versus surgical treatment for ALI were identified. Outcomes of interest included periprocedural and mid-term mortality, major amputation, and reintervention rates. Mid-term outcomes were defined as events occurring at any point during the reported follow-up period. Risk ratios (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted and analyzed using a random-effects model.

Twenty-four studies (5 randomized controlled trials, 2 prospective, and 17 retrospective observational studies) comprising 382 465 patients (endovascular: 172 308; surgical: 210 157) were analyzed. In these studies, there was no difference in periprocedural mortality between endovascular and surgical treatment (RR 0.84, 95% CI 0.62-1.14). Endovascular treatment was associated with lower mid-term mortality compared with surgical revascularization (HR 0.84, 95% CI 0.76-0.94). Major amputation showed a similar trend, with comparable periprocedural risk (RR 0.93, 95% CI 0.51-1.71) and reduced mid-term risk with endovascular therapy (HR 0.84, 95% CI 0.77-0.91). Periprocedural reintervention rates were significantly higher in the endovascular group (RR 1.94, 95% CI 1.80-2.08), while mid-term reintervention rates were comparable (HR 1.79, 95% CI 0.79-4.06).

In this contemporary meta-analysis of patients treated for ALI, endovascular revascularization was associated with lower mid-term mortality and major amputation rates, whereas surgical intervention was linked to a lower risk of periprocedural reintervention. These findings underscore the importance of a multidisciplinary approach involving a dedicated vascular team to ensure optimal, patient-tailored management.

Prospective Register of Systematic Reviews, ID=1042195.Clinical ImpactAcute limb ischemia (ALI) carries high morbidity and mortality, yet comparative data on endovascular versus surgical revascularization are limited. In this meta-analysis of 24 studies including 382 465 patients, periprocedural mortality was similar between approaches, but endovascular therapy reduced mid-term mortality and major amputation risk, despite higher periprocedural reintervention rates. These findings suggest that endovascular-first strategies may be a safe and effective alternative to surgical revascularization. Optimal care requires a multidisciplinary vascular team to tailor interventions, balancing immediate procedural risks with long-term outcomes for each patient.