Aconitine-induced cardiotoxicity is a serious adverse effect of Aconitum-containing medicines, with myocardial injury and malignant ventricular arrhythmias representing important clinical manifestations. However, the molecular responses underlying aconitine-induced myocardial injury remain incompletely understood. This study aimed to construct an integrated molecular network and signaling pathway landscape of aconitine-induced cardiotoxicity through multi-cohort transcriptomic analysis and to identify key hub genes associated with myocardial injury and ventricular tachyarrhythmias. Rat myocardial transcriptomic datasets related to aconitine-induced cardiotoxicity were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the thresholds of |log₂FC| > 1 and a false discovery rate (FDR) < 0.05. Weighted gene co-expression network analysis (WGCNA) was performed to identify cardiotoxicity-associated gene modules, and candidate genes were obtained by intersecting DEGs with module genes. Protein-protein interaction (PPI) network analysis was subsequently conducted to identify hub genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to characterize their biological functions and signaling pathways. The expression patterns of the hub genes showed broadly concordant trends in the independent doxorubicin-induced cardiotoxicity dataset, suggesting that these genes may represent conserved transcriptional responses to myocardial injury (GSE42177). A total of 265 DEGs were identified, and WGCNA revealed one gene module significantly associated with cardiotoxicity (r = - 0.33, P < 0.001). Integration of DEGs with the cardiotoxicity-associated module yielded 18 candidate genes, from which 12 hub genes (Abcb11, Abcc6, Fez1, Ldha, Nr3c1, Nr3c2, Pc, Pdk2, Prkcz, Slc9a1, Vcam1, and Vtn) were identified through PPI network analysis. Functional enrichment analysis indicated that these genes were primarily involved in inflammatory responses, metabolic regulation, and stress-related signaling pathways, particularly the MAPK and TGF-β signaling pathways.

Diabetic ulcers (DU) are a severe complication of diabetes mellitus and are associated with infection, recurrence, amputation, and excess mortality. Robust molecular markers that distinguish ulcer tissue from non-ulcer tissue and clarify the biological basis of impaired healing remain limited.

Public transcriptomic datasets were integrated to identify DU-associated genes initially selected from lipid metabolism-related gene sets. Differential expression analysis, random forest modeling, single-sample gene set enrichment analysis (ssGSEA), gene set enrichment analysis (GSEA), Gene Set Variation Analysis (GSVA), drug-gene interaction analysis, and single-cell RNA sequencing were used to prioritize candidate biomarkers. External transcriptomic cohorts were used for validation. A streptozotocin-induced diabetic wound model in C57BL/6 mice was evaluated by serial wound imaging, hematoxylin and eosin staining, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blotting. A ten-gene panel comprising ANGPTL4, BNIP3, EEF2K, EIF4EBP1, KLHDC1, KLK10, KLK8, NFIX, QSOX1 and S100A8 showed strong discrimination and reproducible expression patterns across validation datasets. Immune analyses linked the panel to T helper 17 (Th17) cell infiltration and interleukin receptor activity. Single-cell analysis localized these genes to distinct wound-associated cell populations. Diabetic mice exhibited delayed wound closure and greater residual wound widths than control mice. Transcript and protein assays showed concordant changes in representative genes.

These findings identify a candidate biomarker panel for DU and connect its transcriptomic pattern with immune remodeling, cell-specific expression, and impaired wound repair. Further validation in larger human cohorts is required before clinical application.

Transthyretin amyloid cardiomyopathy (ATTR-CM) causes heart failure and poor outcomes. Prognostic stratification is fundamental, yet validated staging systems rely exclusively on biomarkers, neglecting structural and functional cardiac parameters.

This study evaluates a noninvasive hemodynamic echocardiographic approach to stratify patients with ATTR-CM.

Patients were categorized into 3 groups based on stroke volume index (SVi) and systolic pulmonary artery pressure (sPAP), markers of forward flow and elevated filling pressures. We compared receiver operating characteristic curves for various potentially predictive hemodynamic parameters to identify these as the most robust candidates for risk stratification. Optimal cutoffs (30 mL/m² for SVi and 40 mm Hg for sPAP) were determined using the Liu index, supported by both univariable and multivariable survival analyses. The primary endpoint was the composite of all-cause mortality and heart failure hospitalization. Prognostic utility was evaluated using multivariable Cox regression, adjusted for age, sex, and disease-modifying therapy.

The cohort included 293 patients with ATTR-CM: group 1 (normal SVi/sPAP, n = 115 [39%]), group 2 (low SVi or high sPAP, n = 129), and group 3 (low SVi/high sPAP, n = 49). The primary outcome occurred in 108 (37%) patients. The multivariable analysis confirmed the staging system as an independent predictor of the composite outcome (group 2 HR: 1.70, 95% CI: 1.05-2.71; group 3 HR: 2.50, 95% CI: 1.44-4.30; P < 0.001).

The noninvasive hemodynamic approach provides an alternative and promising method to stratify the risk of clinical outcome in patients with ATTR-CM, potentially improving management strategies.

Mosaic loss of the Y chromosome (mLOY) is a male‑specific somatic loss of the Y chromosome that is predominantly observed in peripheral blood leukocytes, but can also be found in other tissue types. It represents one of the most common male-specific somatic mutations, particularly prevalent in aging individuals. Accumulating evidence shows that mLOY markedly increases the incidence, progression, and adverse prognosis of multiple diseases, including, but not limited to, myocardial fibrosis, lung and bladder cancers, and Alzheimer's disease. Mechanistically, for extrinsic effects of mLOY, hematopoietic mLOY affect other cell populations, thereby promoting disease initiation and progression. From an intrinsic effects, mLOY within cells reprograms autosomal gene expression and reshapes interactions with the immune microenvironment, jointly driving malignant evolution. In this review, we summarize the current understanding of both intrinsic and extrinsic mLOY effects on immune regulation and disease pathogenesis, highlighting its multifaceted roles across cancer, cardiovascular disorders, infections, and other mLOY-associated conditions.

For persons living with both type 2 diabetes and obesity, weight management may be the most effective therapy for type 2 diabetes. Glucagon-like peptide-1 (GLP-1) receptor agonists have potent weight-reducing effects, and other mechanisms may confer additional benefits. Survodutide is an investigational glucagon receptor-GLP-1 receptor dual agonist with potential weight-reducing and metabolic benefits.

In this multinational, double-blind, phase 3 trial involving adults with type 2 diabetes and a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 27 or more, we randomly assigned participants in a 1:1:1 ratio to receive once-weekly subcutaneous survodutide (3.6 mg or 6.0 mg) or placebo. The two primary end points were the percent change in body weight and a reduction in body weight of at least 5% from baseline to week 76.

Among 752 participants (250 in the 3.6-mg survodutide group, 251 in the 6.0-mg survodutide group, and 251 in the placebo group), the mean age at baseline was 55.7 years, and the mean BMI was 36.5; 49.3% were men. The mean weight change at week 76 according to the treatment-regimen estimand (which assessed effects regardless of whether the trial regimen was discontinued or interrupted or whether other antiobesity therapies were used) was -8.2% (95% confidence interval [CI], -9.2 to -7.2) in the 3.6-mg group, -9.8% (95% CI, -10.8 to -8.8) in the 6.0-mg group, and -3.9% (95% CI, -4.9 to -2.9) in the placebo group; weight reduction of at least 5% occurred in 57.6%, 64.5%, and 35.1% of the participants, respectively (P<0.001 for all comparisons with placebo). The mean change in the glycated hemoglobin level (from a baseline level of 7.4%) was -0.9 percentage points in the 3.6-mg group, -0.8 percentage points in the 6.0-mg group, and -0.2 percentage points in the placebo group. The most common adverse events were gastrointestinal (generally mild to moderate and transient), which occurred in 182 participants (72.8%) in the 3.6-mg group, 195 (77.7%) in the 6.0-mg group, and 97 (38.6%) in the placebo group.

In adults with obesity and type 2 diabetes, survodutide at a weekly dose of 3.6 mg or 6.0 mg resulted in significantly greater weight reduction than placebo. (Funded by Boehringer Ingelheim; SYNCHRONIZE-2 ClinicalTrials.gov number, NCT06066528.).

Diabetic foot ulcers (DFUs) affect approximately 18.6 million people worldwide each year. Abnormal plantar pressure during the perioperative period impairs wound healing and promotes ulcer recurrence. Although offloading interventions are fundamental to DFU management, available evidence remains fragmented, and clinical implementation lacks standardization, particularly in perioperative settings. This systematic review and evidence synthesis aimed to systematically retrieve, appraise, and synthesize the best available evidence on perioperative offloading management for DFU patients and to provide evidence-based recommendations for clinical nursing practice. A systematic search following the "6S" evidence pyramid model was conducted across PubMed, Web of Science, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and Chinese Biomedical Literature Database (CBM) databases, as well as professional society websites, from January 2015 to March 2025. Eligible publication types included clinical guidelines, expert consensus statements, clinical decisions, evidence summaries, and systematic reviews. Quality appraisal used the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument for guidelines and Joanna Briggs Institute (JBI) critical appraisal tools for systematic reviews and expert consensus. Evidence was graded using the JBI Evidence Grading System (2014 version). Fifteen publications were included: 8 guidelines, 2 expert consensus statements, and 5 systematic reviews. Thirty-one evidence items were summarized across seven domains: perioperative risk screening and assessment, multidisciplinary team composition, surgical strategy selection, offloading principles, preoperative offloading, postoperative offloading, and health education with monitoring. Evidence levels ranged from 1 to 5, with the majority at Level 5. This systematic review synthesizes comprehensive evidence on perioperative offloading management in patients with DFU. Healthcare providers should contextualize evidence selection based on clinical settings and individual patient characteristics to optimize wound outcomes and quality of life.

The acute ischemic stroke code that culminates in mechanical thrombectomy (MT) is accompanied by a significant amount of neuroimaging-CT head, CT angiogram of the head and neck, often a CT perfusion, and then the conventional angiogram performed by the neuroendovascular specialist. Immediately postprocedurally, patients who have undergone MT are at risk for reocclusion, hemorrhagic conversion of stroke, and malignant cerebral edema. While CT and MR imaging provide static images, transcranial Doppler (TCD) is becoming more commonly used to evaluate cerebral hemodynamics post-MT and screen for potential complications. Here, we outline the arguments for and against routine performance of TCD in the immediate post-MT phase of care.

Insulin-like growth factor binding protein 6 (IGFBP6) is thought to be associated with the progression of atherosclerosis (AS). However, whether IGFBP6 is involved in ferroptosis, a key biological process, in the progression of AS remains unclear. In this study, IGFBP6 expression was downregulated in oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs). Overexpression of IGFBP6 inhibited reactive oxygen species (ROS) production, reduced Fe2+ concentration and and inflammatory factor levels, and increased Glutathione (GSH) content in ox-LDL-treated HUVECs. Ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, reversed IGFBP6 silencing induced ferroptosis of HUVECs. Mechanistic studies revealed that IGFBP6 is a target of Methyltransferase-like protein 3 (METTL3) that mediates N6-methyladenosine (m6A) modification, and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) recognizes and promotes METTL3-m6A-mediated IGFBP6 mRNA degradation. Downregulated IGFBP6 reduces its protein level by interacting with GPX4, thereby promoting ferroptosis in HUVECs. In addition, APOE-/- mice fed with a high-fat diet were used as an AS animal model, and the results showed that endothelial cell specific METTL3 knockdown or IGFBP6 overexpression hindered the development of AS in mice. In conclusion, knockdown of METTL3 inhibited the degradation of IGFBP6 mRNA in a YTHDF2 dependent manner, thereby inhibiting GPX4-mediated ferroptosis and alleviating AS progression. Insight Box This study provided new molecular targets for the effective treatment of AS. In this study, we constructed an AS cell model and an AS mouse model to explore whether METTL3 affects ferroptosis of HUVECs by regulating IGFBP6 expression through m6A modification through gain of function and loss of function experiments of METTL3 and IGFBP6, thus revealing the molecular mechanism of its involvement in the occurrence and development of AS. Results showed that METTL3 induced GPX4-mediated ferroptosis in HUVECs through m6A-YTHDF2-dependent downregulation of IGFBP6, thereby promoting the progression of AS. These findings suggest that interfering with the METTL3/YTHDF2/IGFBP6/GPX4 axis with small molecules or gene therapy may be a new strategy to intervene the occurrence and development of AS.

Large language models (LLM) and generative Artificial Intelligence are increasingly providing health information. We have applied a novel method to evaluate the harm reduction information generated by popular LLMs. We focused on the filtration of oral medications for injection and the availability of local harm reduction services.

We designed a scoring rubric to evaluate the accuracy of the information provided by each LLM and applied it to four unique, commonly used LLMs.

Gemini 2.5 Flash (87%) and ChatGPT-4o (77%) scored higher than DeepSeek R1 Distill Llama 3.3 70B (22%) and Llama 4 (18%). Overall, both Gemini and ChatGPT-4o gave comprehensive and accurate instructions for the use of micron filters for drug injection, while neither DeepSeek R1 nor Llama 4 provided instructions on their use. Gemini 2.5 and ChatGPT-4o both scored highly for harm reduction general information and situational questions, while DeepSeek R1 and Llama 4 provided limited to no responses. Gemini 2.5 and ChatGPT-4o both provided accurate, location-specific information on local harm reduction services. Specific models also generated misinformation, further affirming the need for in-person, nuanced discussions with harm reduction specialists.

In this study, we presented a novel method for evaluating LLMs' potential effectiveness for harm reduction across common techniques and situations. Most of the tested LLMs provided reasonable information in a non-judgmental manner, but they also provided misinformation, and some wouldn't answer questions due to built-in safety parameters. The developed scoring rubric can be easily adapted to other harm reduction topics for ongoing evaluation.

Maternal mental health (MMH) remains a critical public health issue across Sub-Saharan Africa (SSA). Despite the high burden, access to culturally appropriate and evidence-based mental health interventions remains limited. This scoping review examines interventions targeting mental health outcomes for pregnant and postpartum women across SSA countries. Guided by PRISMA-ScR and Arksey and O'Malley's framework, a comprehensive search was conducted across 14 electronic databases for peer-reviewed intervention studies published in English between 2000 and March 2026. A total of 57 studies across 18 SSA countries were identified with interventions primarily focused on the individual or mother-infant level. The majority used strong research methods, with widely varying intervention content, including cognitive-behavioral therapy, problem-solving therapy, psychoeducation, and community-based programs, often delivered by community health workers, focusing on problem-solving skills, and involving cash transfers. While most studies reported reductions in depressive symptoms and improved psychosocial outcomes, few addressed scalability, health system integration, or cost-effectiveness. Few studies worked with health professionals or included technology interventions. A wide range of mental health interventions show promise in addressing perinatal mental health in SSA. However, gaps remain in scaling up sustainable, culturally relevant, and system-integrated interventions. Future efforts should prioritize provider education, health system strengthening, and evaluation of economic impact to enhance MMH outcomes across the region. To have a significant impact on perinatal mental health, future interventions that focus on cost-effectiveness, scalability, health professions education, and integration of technology are needed.