Wenting Wang

The pathogenesis of diabetic complications involves a complex interplay of metabolic disturbances, in which diverse programmed cell death (PCD) pathways play a pivotal role. This article systematically reviews the molecular mechanisms of four novel types of metabolic cell death—pyroptosis, ferroptosis, cuproptosis and disulfidptosis—with a focus on their specific pathological roles in diabetic kidney disease, retinopathy, cardiovascular complications and neuropathy. It also analyzes the crosstalk and synergistic regulatory networks among these four cell death modalities. Studies have demonstrated that in the diabetic microenvironment, these four PCD pathways do not act independently; instead, they form an interconnected regulatory network centered on oxidative stress, inflammatory signaling and metal ion homeostasis imbalance. This network collectively amplifies metabolic stress, inflammatory responses and oxidative damage, thereby accelerating the progression of multi-organ injury in diabetes. Furthermore, this article explores the therapeutic implications of this network-based perspective, highlighting the potential value of multi-target intervention strategies in the treatment of diabetic complications. In summary, this review clarifies the intricate associations between metabolic cell death pathways and diabetic complications, and underscores the importance of the crosstalk among different cell death modalities. It thus provides a novel theoretical framework for understanding the systemic pathophysiological mechanisms of diabetes, and offers insights and directions for the development of novel combination therapeutic strategies.

Pulmonary arterial hypertension (PAH) is a lethal disease characterized by inflammation‐driven vascular remodelling, with a lack of precise intervention strategies targeting pro‐inflammatory M1 macrophages' glycolytic metabolic reprogramming. This study introduced Mac@WZB117, a macrophage membrane‐camouflaged nanovesicle delivering the GLUT1 inhibitor WZB117, specifically targeting M1 macrophages for PAH treatment. In mouse models of PAH induced by MCT and SU5416 combined with hypoxia, Mac@WZB117 effectively targeted pulmonary vascular lesions, leading to a significant reversal of arterial thickening and collagen deposition. Molecular analyses indicated a downregulation of GLUT1 expression in M1 macrophages, along with a polarization shift from M1 to M2. Furthermore, intervention with Mac@WZB117 reshaped the immuno‐metabolic lineage by inhibiting glycolysis, lipid metabolism and TGF‐β signalling pathways. Spatial transcriptomics analysis confirmed the spatial reorganization of hyperactive M1 macrophages from lesion regions. Overall, Mac@WZB117 delivers WZB117 precisely to M1 macrophages, suppressing their pro‐inflammatory and metabolic functions to remodel the immune microenvironment and reverse vascular structural changes, suggesting a promising therapeutic approach for PAH and other immuno‐metabolic diseases.

The online version contains supplementary material available at 10.1186/s12933-026-03173-5.

Background: Anticoagulation has been the cornerstone for stroke prevention in patients with atrial fibrillation (AF). This study aims to describe the research trends and research hotspots in anticoagulation and AF. Methods: Publications on AF and anticoagulation were retrieved from the Web of Science Core Collection from 2004 to 2024 for bibliometric analyses. Results: A total of 12,551 articles were retrieved. The number of publications increased each year, reaching its peak in 2021. The United States has the largest number of published articles (country appearances, 18,181), followed by Italy (6525) and Japan (6,235). The most productive institutions were Harvard University (658), McMaster University (570), and the University of Birmingham (550). LIP GYH was the most prolific author, with 707 articles published. ‘Circulation’ has the highest H-index (77), followed by the ‘Thrombosis and Hemostasis’ (73), ‘Journal of the American College of Cardiology’ (72). The keyword analysis revealed that the research focused on warfarin, stroke, dabigatran, direct oral anticoagulants, rivaroxaban, antithrombotic therapy, prevention, safety, apixaban, and venous thromboembolism. Conclusions: Research in AF and anticoagulation has expanded rapidly. Coagulation contact phase (such as coagulation factor XI and XII) inhibitors have emerged as a promising future therapeutic target, and there is a critical need for global collaboration to validate these strategies across diverse populations.

The association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) is well studied. Liver fibrosis is the main histopathologic manifestations of NAFLD. However, whether concomitant NAFLD influence the association of non-invasive liver fibrosis scores with CVD remains unclear. We systematically searched PubMed, Cochrane Library, and Embase databases for cohort studies exploring the association between liver fibrosis score (LFS)and CVD events up to June 10, 2025. Random-effects model was used to pool results. CVD events were defined as cardiovascular mortality, myocardial infarction, and coronary heart disease. Nineteen cohorts involving 1,481,875 adults were included with an average age of 54.8 years old, and 50.2% males. Fibrosis 4 score (FIB-4), nonalcoholic fatty liver disease fibrosis score (NFS) and APRI (Aspartate transaminase/platelet ratio index) were associated with increased risks of CVD events (FIB-4: odds ratio [OR] 1.77, 95% confidence interval [CI] 1.58–1.99, low certainty; NFS: OR 2.40, 95% CI 1.83–3.14, low certainty; APRI: OR 1.61, 95% CI 1.17–2.21, low certainty). Each one-unit increment in FIB-4, NFS scores was associated with CVD events (FIB-4: OR 1.21, 95% CI 1.12–1.31; NFS: OR 1.38, 95% CI: 1.17–1.62). A positive linear relationship was observed between FIB-4 (P-nonlinearity = 0.000), NFS (P-nonlinearity = 0.7145) and CVD events. Risk estimates for cardiovascular events were similar in patients with NAFLD (FIB-4: OR 1.87, 95% CI 1.53–2.28; NFS: OR 2.59, 95% CI 1.55–4.33) and without NAFLD (FIB-4: OR 1.74, 95% CI 1.51-2.00; NFS: OR 2.26, 95% CI 1.64–3.11) (P for difference: FIB-4 = 0.56; NFS = 0.66). FIB-4 and NFS were associated with an increased risk of CVD events in patients with and without NAFLD. FIB-4 and NFS risk estimates for cardiovascular events were not influenced by concomitant NAFLD. URL: http://www.crd.york.ac.uk/prospero/ PROSPERO (registration number: CRD42023421092). The online version contains supplementary material available at 10.1186/s12889-025-23883-x.

Diabetes mellitus is a common chronic metabolic disease, with its prevalence escalating annually. Diabetic cardiomyopathy is a leading cause of mortality among diabetic patients, characterized by intricate metabolic disturbances and myocardial cell demise. Various forms of cellular death pathways including apoptosis, pyroptosis, autophagic cell death, necroptosis, ferroptosis, and entosis have been identified in diabetic cardiomyopathy. Inhibiting myocardial cell death pathways has shown promise in mitigating diabetic cardiomyopathy progression. However, there are still gaps in understanding the role of metal ions in diabetic cardiomyopathy pathogenesis. Recent research endeavors have found that iron, copper, zinc, calcium, manganese and other metal elements related to cell death play an intricate and critical role in the pathogenesis and progression of diabetic cardiomyopathy. Notably, many animal studies have shown that the development and progression of diabetic cardiomyopathy can be alleviated by inhibiting the cell death process induced by these metal ions. Therefore, we review the molecular mechanisms underlying the death of various metal ions and the potential pathophysiological roles they play in diabetic cardiomyopathy. In addition, the value of these metal ions in the treatment of diabetic cardiomyopathy is also described. Graphic abstract

Background: Perioperative acute kidney injury (AKI) is common in surgical patients and is associated with high morbidity and mortality. There are currently few options for AKI prevention and treatment. Due to its complex pathophysiology, there is no efficient medication therapy to stop the onset of the injury or repair the damage already done. Certain anesthetics, however, have been demonstrated to affect the risk of perioperative AKI in some studies. The impact of anesthetics on renal function is particularly important as it is closely related to the prognosis of patients. Some anesthetics can induce anti-inflammatory, anti-necrotic, and anti-apoptotic effects. Propofol, sevoflurane, and dexmedetomidine are a few examples of anesthetics that have protective association with AKI in the perioperative period. Summary: In this study, we reviewed the clinical characteristics, risk factors, and pathogenesis of AKI. Subsequently, the protective effects of various anesthetic agents against perioperative AKI and the latest research are introduced. Key Message: This work demonstrates that a thorough understanding of the reciprocal effects of anesthetic drugs and AKI is crucial for safe perioperative care and prognosis of patients. However, more complete mechanisms and pathophysiological processes still need to be further studied.

Aim: Observational studies have reported that levels of vitamin D were associated with the incidence of chronic obstructive pulmonary disease (COPD), but the relationship between them may have been confounded in previous studies. In this study, we aimed to determine the relationship between the levels of 25-hydroxyvitamin D (25OHD) and the risk of COPD by two-sample Mendelian randomization (MR) analysis.Methods: Summary statistics for 25OHD and COPD in this study were obtained from the EBI (n = 496,946) consortium and Finn (n = 187,754) consortium. MR was adopted to explore the effect of the genetically predicted levels of 25OHD on the risk of COPD. Based on three assumptions of MR analysis, inverse variance weighting was used as the main analysis. To make our results more robust and reliable, MR Egger’s intercept test, Cochran’s Q test, funnel plot, and “leave-one-out” sensitivity analysis were used to assess the potential pleiotropy and heterogeneity in this study. Then, colocalization analysis and MR Steiger approaches were used to estimate the possible directions of estimates between them. Finally, we analyzed the causal associations between the four core genes (DHCR7, GC, CYP2R1, and CYP24A1) of vitamin D and the levels of 25OHD or the risk of COPD.Results: Our results showed that each 1 standard deviation (SD) increase in the genetically predicted 25OHD level was associated with a 57.2% lower relative risk of COPD [odds ratio (OR): 0.428, 95% Cl: 0.279–0.657, p = 1.041 × 10⁻⁴], and the above association was also verified by maximum likelihood (OR: 0.427, 95% Cl: 0.277–0.657, p = 1.084 × 10⁻⁴), MR–Egger (OR: 0.271, 95% CI: 0.176–0.416, p = 2.466 × 10⁻⁴), MR-PRESSO (OR: 0.428, 95% Cl: 0.281–0.652, p = 1.421 × 10⁻⁴) and MR-RAPS (OR: 0.457, 95% Cl: 0.293–0.712, p = 5.450 × 10⁻⁴). Furthermore, colocalization analyses (rs3829251, PP.H4 = 0.99) and MR Steiger (“TRUE”) also showed a reverse association between them. Besides, the core genes of vitamin D also showed similar results except for CYP24A1.Conclusion: Our findings provide evidence for a reverse association between genetically predicted 25OHD levels and COPD risk. Taking measures to supplement 25OHD may help reduce the incidence of COPD.