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PubMed2026

Efficacy and safety of rib-guided percutaneous thoracic sympathetic radiofrequency thermocoagulation at two different targets for primary palmar hyperhidrosis: a randomized controlled trial.

OBJECTIVES: To compare the efficacy and safety of computed tomography-guided percutaneous thoracic sympathetic radiofrequency thermocoagulation (RFT) targeting the upper versus lateral margin of the fourth rib head for severe primary palmar hyperhidrosis (PPH). METHODS: Patients with severe PPH were randomly divided into Group U (upper margin target) and Group L (lateral margin target). Outcome measures included 1-year recurrence rate, Hyperhidrosis Disease Severity Scale (HDSS), Dermatology Life Quality Index (DLQI), palm skin temperature, finger perfusion index (PI), compensatory hyperhidrosis and patient satisfaction. RESULTS: Both groups (n = 55 each, 110 sides) successfully underwent RFT. No preprocedural PI differences were found (p > 0.05). Immediately post-RFT, PI in Group L was significantly higher than in Group U (left p = 0.025, right p = 0.013). No significant differences in HDSS grades were observed between groups before and at 1 day, 2 weeks, 1 month and 3 months post-procedure. However, at 6 and 12 months, Group L showed significantly lower HDSS grades (left p = 0.033 and 0.016; right p = 0.039 and 0.025) and lower DLQI scores (p = 0.037 and 0.024) than Group U. Patient satisfaction did not differ within 6 months, but Group L had significantly higher satisfaction at 12 months (p = 0.036). CONCLUSIONS: Targeting the lateral margin of the fourth rib head for RFT achieved greater efficacy, better quality of life and higher patient satisfaction compared to the upper margin target.

Humans↗

PubMed2026

A study on the differences in recovery effects of different types of nutritional supplements on competitive performance of esports athletes under mental fatigue.

BACKGROUND: To compare the effects of different nutritional supplements on the recovery of core competitive performance abilities in esports athletes following mental fatigue and to observe changes in the autonomic nervous system during recovery after nutritional supplementation by monitoring heart rate variability (HRV). METHODS: A randomized crossover within-subject controlled experimental design was adopted, including nutritional supplement type (caffeine, nitrate, Ginkgo biloba extract, catechins, placebo) × mental fatigue state (initial, fatigued, post-supplementation). Twenty high-level first-person shooter (FPS) esports athletes were recruited. Mental fatigue was induced using a Stroop task. After ingesting the different supplements and resting for 60 minutes, the participants completed assessments of shooting accuracy, shooting stability, spatial localization, and multitasking ability using the KovaaK's simulation trainer. HRV indices were also recorded to evaluate changes in autonomic regulation. RESULTS: For shooting accuracy, compared with the placebo condition, all four supplements significantly improved shooting accuracy scores following mental fatigue (all p < 0.05); however, no significant differences were observed among the effects of the different supplements. For shooting stability, caffeine, nitrate, and catechins produced significant recovery effects on shooting stability (all p  < 0.05); however, no significant differences were observed among the effects of these three supplements. For spatial localization and multitasking ability, the improvements in these two abilities in the post-supplementation state may have resulted from natural recovery, and none of the four nutritional supplements demonstrated a significant recovery effect. The HRV results showed that indices including RMSSD and SDNN changed under some supplement conditions. CONCLUSIONS: Mental fatigue significantly reduced the competitive performance of esports athletes. Four types of nutritional supplements all promoted the recovery of shooting accuracy, while caffeine, nitrate, and catechins promoted the recovery of shooting stability. However, no additional recovery advantages of the nutritional supplements over placebo were identified for spatial localization or multitasking ability. Changes in HRV may reflect changes in autonomic regulation during recovery, but further research is still warranted.

Humans↗

PubMed2026

Toward real-time quantification of driving risks: a systematic review and research agenda of risk field theory.

In complex traffic systems, driving risk often evolves in a continuous and progressive manner prior to crash occurrence. How to effectively represent and analyze such latent risk states remains a central challenge in traffic safety research. In recent years, risk field-based approaches have introduced spatial and spatiotemporal continuous modeling paradigms, providing new perspectives for characterizing the distribution of traffic risk and its dynamic evolution. Motivated by the rapid growth of this research area and the lack of a systematic synthesis, this paper presents a comprehensive review of studies applying risk field theory to driving safety and traffic risk analysis. Following the PRISMA guidelines, relevant literature was collected through multi-database searches and analyzed using a combination of bibliometric analysis and qualitative review. The review systematically summarizes the theoretical foundations, modeling elements, data sources, analytical methods, and application domains of risk field-related research. Particular attention is given to studies that conceptualize traffic risk as a continuous field, complemented by a broader review of traffic risk factor literature to identify key elements and analytical dimensions involved in risk field modeling. On this basis, the paper synthesizes research progress in major application areas, including traffic safety state representation, driving behavior analysis, traffic conflict assessment, and autonomous driving and human-machine cooperative systems. Differences and commonalities among existing studies are compared in terms of modeling strategies, data support, and application scenarios. Through this systematic review, the paper clarifies the main research themes and methodological trends of risk field-based studies, providing a structured framework for understanding the evolution and application of this approach and offering methodological insights for risk perception modeling and safety-oriented decision support in intelligent transportation systems (ITS).

Humans↗

PubMed2026

Associations between prescribed amphetamines and spontaneous cervical artery dissection: a matched case-control study.

AIMS: To assess whether prescribed amphetamines are associated with spontaneous cervical artery dissection (sCeAD), an important cause of stroke in young adults. METHODS: We conducted a retrospective matched case-control study within a large academic health system in Chicago, Illinois. Adults aged 18-85 years with incident sCeAD were matched 1:4 to controls without dissection on age, sex, and race/ethnicity. The primary exposure was documented amphetamine prescription. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) controlling for relevant vascular and clinical covariates. Sensitivity analyses included strict matched-strata and inverse probability-weighted models. RESULTS: Among 11,463 individuals, including 2,293 cases and 9,170 controls, amphetamine exposure was associated with higher odds of sCeAD (adjusted OR 1.70, 95% CI 1.18-2.46). Results were unchanged in strictly matched strata (OR 1.70, 95% CI 1.18-2.46) and remained directionally consistent after inverse probability weighting (OR 1.40, 95% CI 1.09-1.79). High-dose amphetamine exposure (≥30 mg/day) had the strongest association (OR 1.96, 95% CI 1.18-3.26), whereas low-dose exposure was not statistically significant. CONCLUSION: Prescribed amphetamines were associated with modestly increased odds of sCeAD. While these findings are observational and hypothesis-generating, they may support a possible association in susceptible patients.

Humans↗

PubMed2026

Effect of atenolol versus ivabradine on heart rate variability in patients of schizophrenia with clozapine-induced tachycardia: a randomized controlled trial.

BACKGROUND: A third of schizophrenia cases are resistant to antipsychotics, where clozapine is the only FDA-approved medication. Clozapine use is often limited by intolerable adverse effects. Persistent tachycardia occurs in approximately 25-54% patients receiving clozapine. Heart rate variability (HRV) is a non-invasive, clinically relevant marker of autonomic nervous system functioning. Atenolol and Ivabradine are usually prescribed for clozapine-induced tachycardia (CIT), although evidence guiding their optimal use remains limited. AIM: This study aimed to compare the effects of atenolol versus ivabradine on HRV in patients with treatment-resistant schizophrenia (TRS) receiving clozapine. METHODS: This open-label randomised clinical trial, conducted at a tertiary-care center over 20 months, involved TRS patients on clozapine for more than three months and having persistent tachycardia. Twenty patients received atenolol 25mg once-daily, while twenty received ivabradine 5mg twice-daily for two months. The primary outcome was the change in the frequency domain of HRV, while the secondary outcomes were time-domains, central and peripheral blood pressure, pulse rate and treatment-emergent adverse events (TEAE). RESULTS: While both drugs significantly reduced pulse-rates (atenolol: -20.56±13.00, p<0.001; ivabradine: -21.855±12.873, p<0.001). Within-group analysis showed that, the atenolol group had significant improvements in high-frequency [HF] power (p=0.048) and LF/HF ratio (p=0.044), along with a non-significant trend towards increased total power (p=0.053); no significant within-group changes were observed in the ivabradine group. CONCLUSION: No significant between-group differences in HRV parameters were established between atenolol and ivabradine. Ivabradine could be a viable option in patients where atenolol is either contraindicated or not tolerated. Future larger multicentric studies are needed for greater generalisability. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06505668.

Humans↗

PubMed2026

Diagnostic communication in functional neurological disorder: A systematic review and meta-analysis of patient acceptance and clinical outcomes.

OBJECTIVES: Diagnostic disclosure is a key therapeutic moment in Functional Neurological Disorder (FND). This systematic review aimed to evaluate quantitative evidence on diagnostic acceptance, understanding, satisfaction, symptom outcomes, and healthcare utilisation following diagnostic disclosure in FND, and to conduct a meta-analysis of diagnostic acceptance. METHODS: Systematic searches of PubMed, Scopus, PsycINFO, and Web of Science identified quantitative studies in adults with FND. Screening followed predefined inclusion criteria. Data were extracted using a structured template and risk of bias was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis of proportions was conducted using the Freeman-Tukey transformation. RESULTS: Fifteen studies were included, four of which contributed to the meta-analysis (n = 481). Reported diagnostic acceptance rates ranged from 38.7% to 90%, although the timing and method of assessment varied across studies. Pooled acceptance was 0.68 (95% CI 0.44-0.88), with substantial heterogeneity. Structured or reinforced communication was frequently associated with improved understanding and satisfaction, although its superiority for diagnostic acceptance was not established. In some studies, diagnostic acceptance was associated with more favourable clinical outcomes, although findings were inconsistent. Some studies reported reductions in healthcare utilisation or costs following satisfactory diagnostic explanation, whereas others found no sustained overall reduction. CONCLUSIONS: Diagnostic communication in FND is associated with differences in acceptance, understanding, and downstream clinical and healthcare outcomes. Approximately two-thirds of patients were reported as accepting the diagnosis following disclosure, although the timing and method of assessment varied substantially across studies. Empathic and evidence-informed communication may enhance understanding and engagement, although its effects on healthcare use and recovery remain uncertain. PRACTICE IMPLICATIONS: Diagnostic disclosure should be delivered clearly, empathically, and with reinforcement over time. Written information, reputable educational resources, and opportunities for follow-up clarification may support patient understanding and engagement, although stronger comparative evidence is needed.

Humans↗

PubMed2026

Short-term psychodynamic psychotherapy for functional neurological disorder: A pilot randomized controlled trial.

BACKGROUND: Evidence-based psychotherapeutic treatments for Functional Neurological Disorder (FND) remain limited. This pilot trial evaluated the preliminary efficacy of Short-term Psychodynamic Psychotherapy (STPP) plus Standard Medical Care (SMC) compared with SMC alone in reducing FND symptom frequency. METHODS: Adults with FND were randomized (1:1) to receive either SMC alone or 12 weekly sessions of STPP plus SMC. The primary outcome was symptom frequency (days with symptoms in the last 4 weeks) assessed at the end of treatment (3 months) and at 6-month follow-up. Secondary outcomes included treatment response (≥50% reduction in symptom frequency) and scores on the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). RESULTS: Of 91 randomized patients (mean age 38.2 years, 75.8% female), 81.3% completed follow-up. Intention-to-treat analysis using Linear Mixed Models showed that STPP plus SMC significantly reduced symptom frequency compared with SMC alone (estimated mean difference -5.72 [95% CI -8.68 to -2.77]; Cohen's d = 0.77; p < 0.001).Treatment response was achieved by 65.8% in the intervention group versus 16.7% in controls (OR 8.21 [95% CI 2.79-24.19]; p < 0.001; NNT 2.0).Significant improvements were also observed for depression (HAM-D: estimated mean difference -10.80; d = 1.45), anxiety (HAM-A: -7.94; d = 1.06), and disability (WHODAS 2.0: -5.77; d = 0.74), all p < 0.001. CONCLUSIONS: STPP was associated with clinically meaningful improvements in FND symptom frequency and all secondary outcomes, with large effect sizes and high treatment response rates. These findings support the preliminary efficacy of STPP for FND and justify larger, multicenter confirmatory trials.

Humans↗

PubMed2026

Chronic neurological diseases with acute respiratory failure in a real-life cohort: insights into ICU and long-term survival-A retrospective study.

BACKGROUND: Patients with chronic neurological diseases (CND) are at increased risk of pulmonary complications that often require ICU admission. This study aimed to identify clinical factors associated with ICU mortality and long-term survival in patients with CND who developed acute respiratory failure (ARF). METHODS: This retrospective cohort study was conducted in a level III respiratory ICU. Patients with pre-existing CND admitted to the ICU with ARF were included. ICU mortality was analyzed using multivariable logistic regression. Long-term survival after ICU discharge was evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. Mortality timing was further characterized using hazard function analysis. RESULTS: A total of 220 patients were included; the most common neurological diagnoses were dementia (37.3%), stroke (22.7%), and amyotrophic lateral sclerosis (14.1%). ICU mortality was 33.6%. Higher APACHE II scores were independently associated with increased ICU mortality (OR 1.076 per point increase; 95% CI 1.029-1.126; p < 0.001). Long-term survival differed significantly by post-discharge respiratory support strategy, with Kaplan-Meier analysis demonstrating more favorable survival patterns among patients receiving home non-invasive mechanical ventilation (NIMV) (p = 0.003). In Cox regression analysis, age, home NIMV, and feeding modality at discharge were independently associated with long-term outcomes. Survival analyses revealed an early clustering of deaths within the first months after ICU discharge, particularly among patients with dementia. CONCLUSIONS: In patients with CND, acute physiological severity was the main determinant of ICU mortality, whereas long-term survival after ICU discharge was poor, with deaths clustering within the first months thereafter. Post-discharge respiratory support and nutritional management should be individualized according to the expected clinical trajectory and patient values.

Humans↗

PubMed2026

Cross-tissue multi-omics integration highlights BPHL and mitochondrial targets in Alzheimer's disease.

BACKGROUND: Mitochondrial dysfunction is a hallmark of Alzheimer's disease (AD), yet specific molecular targets remain to be fully characterized. METHODS: A summary-data-based Mendelian randomization (SMR) framework integrated AD genome-wide association study (GWAS) statistics (39,918 cases) with blood DNA methylation quantitative trait loci (mQTL), gene expression (eQTL), and protein (pQTL) data for 1136 mitochondria-related genes. Associations were assessed using Bayesian colocalization and HEIDI testing. Tissue relevance was evaluated in four brain regions (hippocampus, amygdala, cortex, frontal cortex) using GTEx and external transcriptomic datasets. RESULTS: Screening identified eight candidates supported across blood mQTL and eQTL layers. Stepwise central nervous system (CNS) evaluation singled out biphenyl hydrolase-like (BPHL) as the consistent candidate. Higher genetically predicted BPHL expression was associated with reduced AD risk across the hippocampus (OR=0.920, 95% CI 0.873-0.970), amygdala (OR=0.925, 95%CI 0.880-0.973), cortex (OR=0.943, 95% CI 0.908-0.978), and frontal cortex (OR=0.938, 95%CI 0.901-0.976). These findings aligned with protein-protein interactions connecting BPHL to respiratory complexes and lower BPHL expression in independent AD brains. Functional enrichment converged on oxidative phosphorylation pathways. CONCLUSIONS: By integrating multi-omics data with tissue-specific validation, this study nominates BPHL as a consistent protective candidate in the brain. These findings provide genetic support for mitochondrial molecular perturbations in AD, offering insights for future validation.

Alzheimer Disease↗

PubMed2025

Systematic meta-analysis of the toxicities and side effects of the targeted drug lenvatinib.

BACKGROUND: Lenvatinib, an effective targeted drug for various cancers, has clinical medication safety concerns due to its toxicities and side effects. OBJECTIVE: This study evaluated lenvatinib-induced any adverse events (any AEs) and nine aspects: vascular toxicities related to the circulatory system (vascular toxicities, blood system, and heart), toxicities of the skin and its appendages (skin/subcutaneous tissue and taste system), toxicities of the respiratory system (respiratory, thoracic, and mediastinal and respiratory tract), toxicities of the nervous system (nervous system and general), toxicities of the digestive system (gastrointestinal and liver), toxicities of the urinary system, toxicities of the endocrine and metabolic system (endocrine and metabolism/nutrition), toxicities of the musculoskeletal system, and other severe toxicities. Toxicities and side effects were stratified by severity into any and ≥3 grades for analysis. PATIENTS/MATERIALS AND METHODS: Multiple databases were searched for lenvatinib cancer clinical studies (cohort studies and randomized controlled trials) from inception to December 31, 2024; toxicity and side effect data were extracted and analyzed. RESULTS: Nine high-quality studies were included, showing that lenvatinib is effective in cancers but has notable toxicities. Taking hypertension as an example, for any grade, the risk ratio (RR) was 2.34 with a 95% confidence interval (CI) of [2.09, 2.62], a Z-value of 14.74, and a P-value <0.00001; for grade ≥3, the RR was 2.60 with a 95% CI of [2.21, 3.06], a Z-value of 11.44, and a P-value <0.00001. CONCLUSION: Lenvatinib is effective for cancer but toxic, and this study supports its rational clinical use.

Humans↗

PubMed2026

Characteristics of post-exercise responders versus non-responders following aerobic or isometric exercise in physically inactive adults of African and South Asian descent with high-normal blood pressure or grade I hypertension.

OBJECTIVE: To investigate interindividual variability in post-exercise hypotension (PEH) and to characterise cardiovascular and autonomic differences between responders and non-responders following aerobic and isometric exercise in adults of African and South Asian descent with elevated blood pressure (BP). METHODS: Physically inactive adults of African and South Asian descent living in Suriname (18-65 years) with high-normal BP or grade I hypertension participated in a randomised controlled crossover trial. In this randomised cross-over trial, 47 adults (50.1 ± 10.8 years; 38% male) with high-normal blood pressure or grade I hypertension completed three conditions: aerobic exercise (30 min at 40-60% heart rate reserve), isometric handgrip exercise, and a non-exercise control. Ambulatory BP was assessed over 24 h. PEH was defined as the net effect: (post-exercise - pre-exercise) - (post-control - pre-control). Participants were classified as responders if daytime BP decreased ≥5 mmHg. Arterial stiffness, cardiac, and autonomic parameters were assessed. RESULTS: Following aerobic exercise, 46% of participants were classified as systolic responders compared with 28% after isometric exercise. No baseline differences were observed in demographic or clinical characteristics between responders and non-responders, suggesting that PEH variability may reflect underlying physiological rather than clinical differences. Aerobic responders demonstrated greater reductions in aortic augmentation index (-19.4% vs. -10.9%, p = 0.05), larger increases in stroke volume (+8.1 vs. -5.3 mL, p = 0.05) and cardiac output (+1.54 ± 1.89 vs. +0.58 ± 1.60 L/min, p = 0.009), and more favourable autonomic recovery. Among all variables, only the change in cardiac output was associated with PEH magnitude (r = -0.46, p = 0.006). No consistent physiological differences were observed following isometric exercise. CONCLUSION: PEH following aerobic exercise is characterised by a distinct responder phenotype associated with greater reductions in aortic augmentation index and favourable cardiac adaptations. These findings highlight substantial interindividual variability in BP responses and support the need for individualised exercise strategies in hypertension management.

Adolescent↗

PubMed2026

An individualized nomogram for predicting progression-free survival in systemic anaplastic large cell lymphoma: a multicenter, retrospective, and internally validated study.

OBJECTIVES: To develop an individualized nomogram for predicting disease progression risk in systemic anaplastic large cell lymphoma (sALCL). METHODS: Independent predictors of progression-free survival (PFS) were identified using Cox regression in a multicenter retrospective cohort of 109 sALCL patients (2010-2022). These were incorporated into a three-factor nomogram, evaluated via bootstrapped internal validation (1000 resamples), ROC analysis, C-index, decision curve analysis (DCA), and clinical impact curve (CIC). RESULTS: A total of 29 PFS events occurred during a median follow-up of 31 months. Multivariable modelling selected serum β2-microglobulin elevation, extranodal disease, and front-line chemotherapy choice (CHOP versus CHOPE or BV+CHP) as autonomous progression drivers. Upon internal bootstrap validation, the nomogram yielded strong prognostic accuracy, achieving AUCs of 0.81, 0.85 and 0.87 for 1-, 3- and 5-year progression-free survival, alongside a corrected C-index of 0.779 (95% CI: 0.699 - 0.861). Calibration plots showed close agreement between predicted and observed outcomes, while DCA confirmed superior net clinical benefit versus conventional IPI or Ann Arbor stratification across multiple decision thresholds. CONCLUSION: This first sALCL-specific nomogram integrates clinical and treatment variables to provide personalized PFS risk estimation. While internally validated, this exploratory, observation-based tool requires external validation and recalibration in prospective cohorts before clinical implementation.

Humans↗

PubMed2026

Electroencephalographic evidence of cortical network disruption preceding overt cardioinhibition during tilt-induced reflex syncope.

OBJECTIVE: Reflex syncope is a common cause of transient loss of consciousness. However, the early cerebral mechanisms underlying cardiovascular changes remain poorly understood. Our objective was to investigate early cerebral changes by quantitatively analyzing EEG activity preceding overt cardioinhibition during tilt-induced reflex syncope. METHODS: EEG recordings from patients undergoing tilt testing were retrospectively analyzed. Patients who experienced reflex syncope were compared to those who did not. Spectral and functional connectivity analyses were performed across baseline, pre-cardioinhibition, and syncopal phases. RESULTS: Prior to the onset of cardioinhibitory pathological reflex, a significant increase in theta-band spectral power was observed in the right temporal region, accompanied by a widespread increase in functional connectivity within the same frequency band. These findings suggest the involvement of brain networks before cardioinhibition. CONCLUSIONS: EEG changes in the theta band (power and functional connectivity) were observed before overt cardioinhibition during tilt-induced reflex syncope. SIGNIFICANCE: Our findings support the hypothesis of cortical processing preceding cardioinhibition in reflex syncope. EEG may represent a valuable complementary tool for improving the understanding and diagnosis of these events.

Humans↗

PubMed2026

GPR3 in neuro-metabolic-immune-reproductive nexus - a potential therapeutic target for Multi-System diseases.

BACKGROUND: GPR3(G-protein-coupled receptor 3), an orphan G-protein-coupled receptor (GPCR) with constitutive Gs activity, is expressed in the brain, liver, ovary, and other tissues, regulating cell proliferation, differentiation, and apoptosis across the nervous, reproductive, immune, and metabolic systems. This review synthesizes evidence on its integrated signaling and physiological functions to address the lack of a comprehensive multisystem pathophysiology overview. METHODS: A systematic literature search was conducted on PubMed and Web of Science, using keywords such as "GPR3", "GPCR", "neurodegeneration", "metabolism", "immune", "reproduction", "agonist", "inhibitor", and "therapeutic target". This search identified GPR3's roles in neurodegenerative diseases, immune inflammation, reproduction, and energy metabolism. The analysis focused on signaling pathways, ligand regulation, and therapeutic potential. RESULTS: The research indicates that GPR3 is involved in neuronal survival, synaptic plasticity, and microglial activity via the cAMP/PKA, PI3K/Akt, and β - arrestin pathways. It promotes amyloid - β formation in Alzheimer's disease (AD), yet provides neuroprotection in Parkinson's disease (PD) models. It may contribute to anxiety/depression - like states, maintain oocyte meiotic arrest in the ovary, and activate thermogenic genes in adipose tissue. GPR3 modulates immune responses. Using oleic acid (OA) and diphenyleneiodonium (DPI) as activators, and AF64394 and cannabidiol (CBD) as antagonists, it shows potential in disease models. CONCLUSION: GPR3 acts as a central molecular hub integrating neural, metabolic, immune, and reproductive signaling, highlighting its potential as a therapeutic target for chronic multisystem disorders. However, its dual roles in certain pathologies and translation challenges necessitate further research.

Humans↗

PubMed2026

Integrated multi-omics analyses identify an RAS-SLC11A2-associated molecular framework linking iron metabolism with PCOS-related cardiometabolic risk.

INTRODUCTION: PCOS is a common endocrine disorder with elevated cardiometabolic risk, yet the role of the renin-angiotensin system (RAS)-iron metabolism axis in this comorbidity remains unclear. We explored its underlying mechanisms and evaluated the therapeutic potential of gentiopicroside. METHODS: Integrated multi-omics analyses combining transcriptomics, single-cell RNA sequencing, Mendelian randomization, machine learning, molecular docking, and in vitro functional assays were performed to identify shared molecular pathways and therapeutic targets across PCOS, hypertension, NAFLD, and T2DM. RESULTS: SLC11A2 was consistently dysregulated in PCOS transcriptomic datasets, and associated with iron metabolism, inflammatory response and oxidative stress pathways. Genetic analyses validated RAS-related regulation in hypertension susceptibility and revealed shared genetic architecture between PCOS and cardiometabolic traits. Network and single-cell analyses characterized SLC11A2-associated molecular patterns in disease-relevant cell types; machine learning identified disease-classifying molecular signatures. Gentiopicroside alleviated inflammatory and oxidative stress phenotypes, including reduced IL-6 expression and reactive oxygen species accumulation. CONCLUSION: This study defines an RAS-SLC11A2 molecular framework linking iron metabolism dysregulation to PCOS-related cardiometabolic risk, elucidating the mechanisms connecting ovarian dysfunction, inflammation, oxidative stress and hypertension, and supports gentiopicroside as a promising therapeutic candidate.

Humans↗

PubMed2025

Uncovering parental exposure risks of TCPP: Impaired development and metabolic homeostasis in zebrafish offspring.

As brominated flame retardants are phased out, tris (1‑chloro-2-propyl) phosphate (TCPP), a phosphorus-based flame retardant, has emerged as a prominent detectable flame retardant in the environment. However, TCPP has been found to exhibit endocrine-disrupting effects on organisms, raising significant safety concerns. In our study, we utilized the zebrafish model to explore the toxic effects of parental TCPP exposure on offspring and uncover its regulatory mechanisms through metabolomics analysis. Moreover, the impact on the nervous system and lipid metabolism was examined through behavioral analysis and specific staining. Our findings demonstrated that both embryonic and parental TCPP exposure induced developmental disorders in larvae, along with decreased locomotor activity and disordered lipid metabolism homeostasis. Parental exposure to TCPP, exhibiting stronger developmental toxicity than direct embryonic exposure, notably led to reductions in crucial energy substrates such as amino acids and carbohydrates. Meanwhile, embryonic TCPP exposure primarily affected the endogenous lipid-related metabolites including phospholipids, lipid-soluble vitamins, steroids and fatty acids, promoting lipid accumulation in larval liver and subcutaneous tissue. What's more, continuously parental and embryonic exposure showed the most pronounced effects on zebrafish development and metabolic regulation. Our study highlights the risk posed by parental exposure to TCPP on offspring zebrafish, underscoring the need for comprehensive consideration of the impact from parental exposure in pollutants regulation.

Animals↗

PubMed2026

From pathobiology to prescribing in obesity-driven HFpEF: A systematic review and practical therapeutic framework.

Heart failure with preserved ejection fraction (HFpEF) is increasingly driven by obesity and cardiometabolic dysfunction. In this phenotype, the dominant biology extends beyond congestion alone and includes visceral and epicardial adiposity, systemic inflammation, impaired myocardial energetics, endothelial dysfunction, and exertional elevation in filling pressures. We performed a PRISMA-compliant systematic review with structured narrative evidence synthesis to evaluate pharmacological therapy in obesity-driven HFpEF, searching PubMed/MEDLINE, Scopus, Web of Science Core Collection, ClinicalTrials.gov, and WHO ICTRP through December 2025. Eighteen reports were included in the final qualitative synthesis. The available evidence supports sodium-glucose cotransporter 2 inhibitors as the pharmacological foundation because they provide the most mature outcome data across the preserved ejection fraction spectrum. Semaglutide improves symptoms, physical limitations, exercise capacity, and body weight in dedicated obesity-related HFpEF trials, whereas tirzepatide extends this signal by improving clinical status and reducing worsening heart failure events. Finerenone broadens the therapeutic platform in HF with mildly reduced or preserved ejection fraction, although obesity-specific data remain indirect. Conventional neurohormonal therapies retain a selective role, but they are not the principal biological match for this phenotype. Obesity-driven HFpEF should therefore be managed as a cardiometabolic syndrome with heart failure expression, using a phenotype-based sequence that links diagnosis, decongestion, SGLT2 inhibition, obesity-directed therapy, and selective adjunctive intensification.

Humans↗

PubMed2026

Cine-derived mitral annular relaxation velocity for detection of preclinical left ventricular diastolic dysfunction.

OBJECTIVES: Imaging diastolic dysfunction in pre-clinical heart failure (HF) is challenging. We evaluated a novel cardiac MRI (CMR) biomarker, CMR e-prime (CMR-MARV), in patients at risk of HF. METHODS: In this substudy of the PARABLE trial (NCT04687111), 236 patients (71.6 ± 7.7 years, 61.6% male) fulfilling trial-defined ALVDD citeria underwent CMR with measurement of mitral annular relaxation velocity (CMR-MARV) at four mitral annular anchor points. Diastolic strain rates from FT were also assessed. Twenty-five age- and sex-matched controls were included (73.8 ± 3.1 years, 52% male). Group differences were tested with t-tests, diagnostic accuracy with ROC analysis, and predictors of diastolic dysfunction with adjusted logistic regression. RESULTS: Compared with controls, patients had significantly higher indexed maximal left atrial volume (LAVimax), LV end-diastolic and end-systolic volumes, and LV mass (all p < 0.001). Of FT variables, only peak diastolic longitudinal velocity differed between groups (p < 0.001). In multivariate models, CMR-MARV correlated with radial, circumferential, and longitudinal diastolic strain rates, radial and longitudinal diastolic velocities (all p < 0.001), echocardiographic e' (r = 0.20, p = 0.007), LV mass (r = -0.18, p = 0.008), LAVimax (r = -0.18, p = 0.008), and NT-proBNP (r = -0.30, p < 0.0001). LAVimax and CMR-MARV were strongly independently associated with ALVDD (AUC 0.89 and 0.76, respectively; p < 0.0001). A combined model (LAVimax + CMR-MARV) achieved excellent discrimination (AUC 0.91, 95% CI 0.86-0.97, p < 0.0001). Independent predictors included LAVimax, CMR-MARV, and peak diastolic longitudinal velocity (all p < 0.001). CONCLUSION: CMR-MARV provides a simple cine-derived measure of longitudinal relaxation that correlates with established structural and biochemical markers of diastolic burden. Within an at-risk population, it offers incremental functional information beyond conventional parameters and may support multiparametric CMR phenotyping of preclinical diastolic dysfunction.

Aged↗