Thoracic aortic aneurysm (TAA) is a life-threatening condition characterized by pathological dilation of the aorta. While inflammatory responses have been implicated in TAA pathogenesis, the causal relationships remain elusive. This study aimed to elucidate potential causal associations between inflammatory cytokines, plasma metabolites, and TAA risk using Mendelian randomization (MR) analysis. We conducted bidirectional two-sample MR analysis utilizing genome-wide association study data from 91 inflammatory cytokines (n = 14,824), 1400 plasma metabolites (n = 8299), and TAA (n = 385,857). The inverse-variance weighted method served as the primary analytical approach, with comprehensive sensitivity analyses performed to assess pleiotropy and heterogeneity. Two-step MR analysis was employed to explore potential mediating roles of plasma metabolites. Single-cell sequencing analysis was utilized to detect cell type enrichment and elucidate cellular functions of identified cytokines. Additionally, we conducted an analysis to identify druggable proteins as potential therapeutic targets for TAA. MR analysis revealed that genetically-determined increases in C-X-C motif chemokine 10 (CXCL10) (odds ratios [OR] = 1.149, 95% confidence interval [CI]: 1.009-1.309, P = .037) and fibroblast growth factor 5 (OR = 1.101, 95% CI: 1.013-1.196, P = .024) were associated with elevated TAA risk. Conversely, C-C motif chemokine 20 (CCL20) (OR = 0.870, 95% CI: 0.759-0.996, P = .043) and CD40L receptor (CD40) (OR = 0.906, 95% CI: 0.827-0.992, P = .033) demonstrated inverse associations with TAA risk. Two-step MR analysis identified potential mediating metabolites: the phosphate to linoleoyl-arachidonoyl-glycerol ratio for CXCL10, thyroxine and X-24585 for FGF-5, and the creatine to carnitine ratio for CCL20. Single-cell sequencing analysis revealed enrichment of these cytokines in specific cell types and pathways relevant to TAA pathogenesis. Drug-gene interaction analysis identified CXCL10, CCL20, and CD40 as potential targets for treatment of TAA. This study provides robust genetic evidence supporting causal relationships between specific inflammatory cytokines and TAA risk, with plasma metabolites potentially mediating these effects. CXCL10 and FGF-5 were identified as potential risk factors, while CCL20 and CD40 may confer protective effects. These findings offer novel insights into TAA pathogenesis and suggest potential targets for intervention. Further research is warranted to elucidate the underlying mechanisms and validate these results across diverse populations.

Background : Acute Type A Aortic Dissection (ATAAD) is a severe cardiovascular emergency with complex pathogenic mechanisms. This study aims to explore the cellular heterogeneity and potential mechanisms of ATAAD, as well as evaluate the protective effects of fenofibrate on ATAAD. Methods : We established a mouse model of ATAAD and performed single-cell RNA sequencing analysis on the ascending aorta of normal control, BAPN induced ATAAD, and BAPN+fenofibrate intervention groups. Quality control, data integration, and cell clustering analyses were conducted using the Seurat package. Cell communication, pseudo-time analysis, and characteristic gene analysis were employed to investigate the pathogenesis of ATAAD and the mechanism of fenofibrate action. Results : We identified 10 major cell types, with significantly increased proportions of monocytes and macrophages in the BAPN group. Pathway analysis revealed differential expression of multiple signaling pathways in ATAAD, particularly the specific activation of the SPP1 pathway. We identified 12 macrophage subpopulations, among which the C2 subpopulation (Plekhg5+ and Timd4+) may play a role in maintaining normal aortic function, while the C5 subpopulation (Cxcl3+ and Met+) may be a potential inducer of ATAAD. Following fenofibrate intervention, inflammatory pathway activity decreased, and macrophage subpopulation distribution tended towards normal. Moreover, the expression of the Lyve1 gene in macrophages was significantly associated with favorable prognosis, suggesting its potential as a marker for assessing aortic dissection outcomes. Conclusion : This study elucidates the cellular heterogeneity and potential mechanisms of ATAAD, identifying key macrophage subpopulations and signaling pathways. Fenofibrate may ameliorate the occurrence and progression of ATAAD by modulating macrophage subpopulation distribution and function, thereby improving intimal permeability. These findings lay the foundation for developing novel therapeutic strategies for ATAAD.

ObjectiveTo systematically quantify the graded relationship between serum resistin levels and the severity of coronary heart disease (CHD) using a network meta-analysis, thereby evaluating its potential as a biological marker of disease progression.MethodsWe conducted a comprehensive search of major international and Chinese databases up to December 2025. A random-effects network meta-analysis was performed to calculate standardized mean differences (SMD) and Surface Under the Cumulative Ranking (SUCRA) values. Subgroup, sensitivity, and Trim-and-Fill analyses were conducted to investigate heterogeneity and publication bias.ResultsA total of 26 studies (n = 9,169 subjects) were included. The network meta-analysis (5,450 individuals) demonstrated a progressive, stepwise increase in serum resistin levels across the disease spectrum: from healthy controls (CHD-), to stable CHD (SMD = 0.77, 95% CI: 0.38–1.15), to acute coronary syndrome (ACS; SMD = 1.88, 95% CI: 1.22–2.54), and culminating in acute myocardial infarction (AMI; SMD = 4.68, 95% CI: 3.92–5.43), all compared to controls. SUCRA rankings confirmed this clear hierarchy (AMI > ACS > stable CHD > CHD-). However, substantial heterogeneity (I²=95.8%) and evidence of publication bias were detected.ConclusionSerum resistin levels show a clear, graded association with CHD severity, positioning resistin as a potent biological correlate of the underlying inflammatory burden. However, due to significant heterogeneity and publication bias that likely inflate the observed effect sizes, resistin is not suitable as a standalone diagnostic tool. Its potential clinical utility may lie as an adjunctive marker in multi-biomarker models for risk stratification, a role that requires validation in large-scale prospective studies using standardized assays.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO CRD420261397089.

Abstract Spinal cord ischemia–reperfusion injury (SCI/RI) triggers severe mitochondrial dysfunction and neuronal death. While mitochondrial transplantation (MT) is a promising strategy, its therapeutic potency remains limited. This study identifies the transcription factor Engrailed-1 (En-1) as a key regulator of mitochondrial homeostasis and a potential enhancer of MT. En-1 expression is significantly downregulated in SCI/RI models, whereas its restoration via hypoxic preconditioning or overexpression markedly improves neuronal survival. Mechanistically, En-1 stabilizes mitochondrial membrane potential, attenuates reactive oxygen species (ROS) production, and inhibits apoptosis by transcriptionally upregulating PDGFC. Mitochondria harvested from En-1-overexpressing cells (OE-En1-Mito) exhibit superior bioenergetic profiles and rapid neuronal uptake compared to unmodified mitochondria. In vitro, OE-En1-Mito increased ATP production and antioxidant activity; in vivo, transplantation preserved neuronal integrity and improved motor recovery in SCI/RI rats. Notably, silencing PDGFC in donor mitochondria abolished these neuroprotective benefits. Thus, En-1-modified MT provides superior neuroprotection for SCI/RI by leveraging the En-1/PDGFC axis.

Vein graft restenosis is a leading cause of long-term failure after coronary artery bypass grafting (CABG), driven by maladaptive vascular smooth muscle cell (VSMC) responses to arterialization-induced inflammation. The key molecular mediators of this pathological remodeling, however, remain incompletely defined. Here, we integrated multi-omics analyses of human and canine vein graft specimens with in vitro functional assays to identify tenascin-C (TNC)-a matricellular extracellular matrix protein-as a critical regulator of VSMC dysfunction. TNC was specifically enriched in a synthetic, pro-inflammatory VSMC subpopulation. Pro-inflammatory stimuli potently induced TNC expression, which was functionally linked to VSMC phenotypic modulation, hyperproliferation, and enhanced migration. Mechanistically, TNC acts upstream of NF-κB signaling; siRNA-mediated TNC knockdown significantly reduced nuclear p65 protein levels and attenuated inflammatory responses. Our integrated computational and experimental data suggest that TNC, NF-κB, and TNF-α function within a sequential pro-inflammatory signaling cascade that sustains vascular inflammation and promotes neointimal hyperplasia. These findings reposition TNC from a passive structural component to an active driver of vascular pathology and highlight the TNC-NF-κB axis as a candidate target for therapeutic intervention to improve vein graft patency.

Objective:The objective of this study was to investigate the neuroprotective effects of long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) on ischemic spinal cords. Materials and methods:The binding relationship between CRNDE and microRNA-181a-5p was detected using dual luciferase assays. Spinal cord ischemia was induced in rats by cross clamping the descending aorta. CRNDE expression was induced by intrathecal injection of adeno-associated virus vectors containing CRNDE. The hind-limb motor function of the rats was then assessed over a period of 3 weeks following reperfusion. Lumbar spinal cords were harvested for histologic examinations. Expressions of CRNDE, microRNA-181a-5p and related proteins were measured by quantitative reverse transcription polymerase chain reaction and Western blot. Results:Luciferase assays demonstrated that CRNDE bound to microRNA-181a-5p, and Sirt1 was a direct target of microRNA-181a-5p. The transient ischemia induced a significant decrease of CRNDE expression accompanied by a robust increase of microRNA-181a-5p expression in spinal cords. Intrathecal injection of adeno-associated virus vectors containing CRNDE resulted in a significant enhancement of CRNDE expression and a repression of microRNA-181a-5p expression in spinal cords. Consequently, CRNDE overexpression was found to inhibit neuronal apoptosis, attenuate histologic damage, increase the number of surviving neurons, and improve the hind-limb motor function after spinal cord ischemia. Conclusion:CRNDE overexpression induces spinal cord protection against ischemia-reperfusion injury, possibly via microRNA-181a-5p/Sirt1 axis.

This network meta-analysis aimed to compare different non-pharmacological interventions for insufficient perfusion after hypothermic circulatory arrest, a key technique in aortic arch surgery. The authors retrieved and analyzed 60 eligible studies from four databases up to July 2025. The results showed that moderate hypothermia combined with specific cerebral perfusion strategies achieved better overall outcomes. Moderate hypothermia generally improved multiple clinical indicators without affecting several complications, and different perfusion approaches and cannulation methods had comparable effects. This work helps surgeons select optimal interventions and improve patient prognosis after aortic arch surgery.

Delayed graft function (DGF) is a severe complication following kidney transplantation, and currently, there is a lack of accurate prediction tools tailored for the Chinese population. This study integrates data from 1,093 kidney transplant cases across four medical centers in China (2016–2024) to develop and validate a machine learning-based model for DGF prediction. By comparing nine machine learning algorithms, we found that the LightGBM model performed best in external validation (AUC = 0.80, accuracy = 0.73). SHAP analysis identified donor GFR, donor hemoglobin, and recipient plasma BNP levels as the primary predictive factors, while also highlighting novel predictors such as donor microscopic hematuria and APTT. Cox regression analysis showed that preoperative dialysis duration in recipients (HR = 1.006, 95% CI: 1.001–1.012) was an independent predictor of DGF recovery. In the follow-up study, we observed that while the DGF mortality group exhibited the most significant kidney function impairment (serum creatinine β = 200.57, eGFR β = -39.91), the prognosis of the DGF survival group was comparable to that of the non-DGF survival group. Additionally, the duration of DGF (16.66 ± 13.73 vs. 15.44 ± 14.62 days) and the number of dialysis treatments (8.13 ± 7.39 vs. 7.78 ± 7.22 sessions) were not significantly associated with prognosis. Based on these findings, we developed an online prediction platform (www.kidney-dgf-match.cn) to support clinical decision-making. This study not only establishes the first high-precision DGF prediction model for the Chinese population but also reveals the potential for favorable outcomes in DGF patients with proper management, offering new insights for optimizing post-transplant management strategies.

Resistin, a cysteine-rich adipokine, exhibits significant species-specific divergence in its cellular origins and pathophysiological functions. In humans, it is primarily secreted by monocytes, macrophages, and bone marrow-derived cells, positioning it as a pivotal mediator of inflammation and cardiometabolic disease rather than a direct regulator of glucose metabolism. This review synthesizes current evidence on the multifaceted role of resistin in cardiovascular pathophysiology, emphasizing its engagement with key receptors—toll-like receptor 4 (TLR4) and cyclase-associated protein-1 (CAP-1)—to activate downstream proinflammatory signaling cascades including nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. These mechanisms promote endothelial dysfunction, increase leukocyte adhesion and migration, and accelerate early atherogenesis. Beyond the vasculature, resistin exerts direct detrimental effects on the myocardium by impairing cardiomyocyte calcium handling and mitochondrial energetics, inducing pathological hypertrophy, and stimulating cardiac fibrosis via JAK/STAT3 and transforming growth factor-beta (TGF-β) signaling. Its ability to modulate neurohormonal pathways, including sympathetic activation and interactions with the endocannabinoid system, further integrates resistin into a complex network that exacerbates hypertension, arrhythmogenesis, and adverse cardiac remodeling. Clinically, elevated circulating resistin levels are consistently associated with acute coronary syndromes, heart failure progression, and major adverse cardiovascular events, often providing prognostic value beyond traditional risk factors, particularly in heart failure with reduced ejection fraction and cardiometabolic disease. However, significant heterogeneity exists across populations due to comorbidities such as renal dysfunction, ethnic variations influenced by genetic polymorphisms, and disease-specific contexts. The translational potential of resistin as a therapeutic target is underscored by preclinical studies demonstrating that its suppression ameliorates cardiovascular injury, though causal evidence in humans remains limited. Future research must prioritize elucidating resistin’s full receptor signaling repertoire, defining isoform-specific functions, and validating its utility in multimodal biomarker panels to enhance risk stratification and pave the way for targeted therapies in cardiovascular diseases. This review advances the field by resolving conflicting receptor data through a critical evaluation of CAP-1 and TLR4 signaling, and by integrating clinical evidence with molecular mechanisms.

To investigate the risk factors for postoperative hepatic dysfunction (HD) in patients undergoing acute Stanford type A aortic dissection (ATAAD) surgery and to develop an individualized prediction model. We retrospectively analyzed cardiac surgery patients with ATAAD treated at our hospital from January 2020 to March 2024, dividing them into 7:3 training and validation cohorts and grouping them into HD and non-HD categories based on postoperative liver function. Least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were used to identify independent predictive factors for postoperative HD, which formed the basis of a nomogram prediction model. We assessed model accuracy, calibration and clinical utility using C-statistics, calibration plots and decision curve analysis (DCA) curves. Internal validation with 1000 Bootstrap resamples was performed to reduce overfitting bias. LASSO and multivariate logistic regression identified key risk factors for HD in ATAAD patients, including chronic kidney disease, preoperative creatinine, international normalized ratio (INR), red blood cell (RBC) transfusion volume, peak intraoperative lactate, aortic cross-clamping time greater than 99 min, and reoperation. Based on these factors, a nomogram prediction model was successfully developed. The Hosmer-Leme show test yielded a p value of 0.952, indicating a good model fit. The area under the curve (AUC) values in the training and validation cohorts were 0.856 (95% CI 0.777-0.936) and 0.958 (95% CI 0.915-1) respectively, indicating good discriminatory power. The calibration curve shows that the bias corrected line is close to the ideal line. The DCA curve indicates that the use of the nomogram provides greater net clinical benefit. The AUC values before and after Bootstrap validation were 0.860 (95% CI 0.795-0.924) and 0.858 (95% CI 0.795-0.924), respectively, reflecting stable model performance and minimal risk of overfitting. The internally validated prognostic nomogram demonstrates excellent discriminative power, calibration, and clinical utility for predicting the risk of HD in patients who have undergone ATAAD surgery. This allows for an individualized evaluation and the optimization of clinical outcomes.

ObjectiveTo evaluate the effects of comprehensive perioperative nursing interventions on postoperative recovery in cardiac surgery patients with frailty, with a focus on physical activity, nutritional status, and cognitive function.DesignA prospective, randomized, single-blind, parallel-group design with a 1:1 allocation ratio.SettingCardiac surgery department in a tertiary care hospital.ParticipantsThis study included 300 patients with frailty after cardiac surgery. Using a computer-generated random number table, patients were randomly assigned to the experimental group (150 patients) and the control group (150 patients). The intervention group received preoperative psychological counseling, targeted nutritional support, skincare, and continuous hemodynamic monitoring; the control group received routine care, including postoperative vital sign monitoring, basic nutritional support, wound care, and standard cardiovascular assessments (e.g., heart rate and blood pressure).Primary outcomesPostoperative recovery was assessed through improvements in physical activity (Barthel Index), nutritional status (Mini Nutritional Assessment), cognitive function (Mini-Mental State Examination), biostatistical data and cardiopulmonary function indicators.ResultsThe intervention group showed significant improvements: Barthel Index increased by 20 points (95% CI: 15-25, p < 0.01), Mini Nutritional Assessment scores by 3 points (95% CI: 1-5, p < 0.05), and Mini-Mental State Examination scores by 4 points (95% CI: 2-6, p < 0.05). Hospital stay was reduced by 5 days (95% CI: 3-7, p < 0.01), and the 6-month survival rate was 10% higher (95% CI: 5-15%, p < 0.05) compared to the control group.ConclusionsComprehensive perioperative nursing interventions significantly improve postoperative recovery, self-care ability, nutritional status, cognitive function, and short-term survival in cardiac surgery patients with frailty.

Aortic aneurysms (AA) pose a significant risk to women of childbearing age due to the added physiological stress of pregnancy and hormonal changes. This study aims to assess the global disease burden of AA among women of childbearing age from 1990 to 2021, project future trends, and provide evidence-based insights to inform public health policies and clinical decision-making. Aortic aneurysm mortality and disability-adjusted life years (DALYs) data for women of childbearing age (15–49 years) from 1990 to 2021 were extracted from the 2021 Global Burden of Disease (GBD) dataset. Temporal trends and attributable risks were evaluated using estimated annual percentage change (EAPC) and linear regression model from 1990 to 2021. Cluster analysis identified patterns across GBD regions. The Socio-demographic Index (SDI) assessed regional and national differences in mortality and DALYs rates related to AA. In addition, all potential risk determinants associated with AA were systematically examined. An age-period-cohort model assessed trends, period, and cohort effects, while the Bayesian age-period-cohort model predicted the disease burden through 2036. In 2021, AA was associated with 2,552 (95

ObjectiveThis meta-analysis examines peak systolic velocities (PSVs) in thyroid arteries as potential biomarkers for thyroid disorders, which includes treated and untreated Graves’ disease(GD) and destructive thyrotoxicosis(DT).MethodsA search across databases including PubMed, Google Scholar, Embase, and Web of Science identified studies assessing peak systolic flow velocity in the inferior thyroid artery (ITA-PSV) and superior thyroid artery (STA-PSV) diagnostic efficacy in GD and DT.And the search was restricted to publications in the English language.The analysis compared STA-PSV and ITA-PSV across patient groups, evaluating intra-group variances and synthesizing sensitivity and specificity data.ResultsThe analysis covered 18 studies with 1276 GD, 564 DT patients, and 544 controls. The difference of STA-PSV between GD group, DT group and normal group and the difference of ITA-PSV were analyzed in subgroups, and there was no statistical significance between subgroups when comparing any two groups. Normal subjects displayed intra-group ITA-PSV and STA-PSV differences with established cut-off values of 20.33 cm/s (95% CI, 17.48-23.18) for ITA-PSV and 25.61 cm/s (95% CI, 20.37-30.85) for STA-PSV. However, no significant intra-group differences were observed in the STA-PSV and ITA-PSV cut-off values among groups with GD or DT. The combined cut-off values for these patient groups and normal subjects were 68.63 cm/s (95% CI, 59.12-78.13), 32.08 cm/s (95% CI, 25.90-38.27), and 23.18 cm/s (95% CI, 20.09-26.28), respectively. The diagnostic odds ratio(DOR) for these values was 35.86 (95% CI, 18.21-70.60), and the area under the summary receiver operating characteristic (SROC) curve was 0.91, with a sensitivity estimate of 0.842 (95% CI, 0.772-0.866).ConclusionPSVs in thyroid arteries are useful diagnostic tools in distinguishing DT from GD. A PSV above 68.63 cm/s significantly improves GD diagnosis with up to 91% efficacy. No notable differences were found between superior and inferior thyroid arteries in these conditions.

BackgroundHepatocellular carcinoma (HCC) ranks among the most prevalent and lethal malignancies worldwide. Histone modifications (HMs) play a pivotal role in the initiation and progression of HCC. However, our understanding of HMs in HCC remains limited due to the disease’s heterogeneity and the complexity of HMs.MethodsWe integrated multi-omics data from multiple cohorts, including single-cell RNA sequencing, bulk RNA sequencing, and clinical information. Weighted gene co-expression network analysis (WGCNA) and consensus clustering were employed to identify histone-related genes. We developed a histone modification-related signature (HMRS) using 117 machine learning methods. Comprehensive analyses of molecular characteristics, immune landscape, and drug sensitivity associated with the HMRS were performed.ResultsThrough integrative analysis, we defined 110 histone-related genes and identified 45 HCC-HM-related genes (HCC-HMRgenes). The HMRS demonstrated robust prognostic value across multiple cohorts. Patients with high HMRS scores exhibited distinct genomic alterations, including higher tumor heterogeneity and TP53 mutations. The high-risk group showed enrichment in cell cycle, DNA repair, and metabolic pathways. Immune landscape analysis revealed significant differences in immune cell infiltration and pathway activities between high- and low-risk groups. Drug sensitivity prediction suggested potential therapeutic strategies for different risk groups.ConclusionOur study provides a comprehensive understanding of HMs in HCC and establishes a robust prognostic signature. The HMRS not only stratifies patients into distinct risk groups but also offers insights into underlying molecular mechanisms, immune characteristics, and potential therapeutic strategies, paving the way for personalized medicine in HCC.

Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) are indispensable core techniques in cardiac surgery. Numerous studies have shown that cardiopulmonary bypass and deep hypothermic circulatory arrest are associated with the occurrence of neuroinflammation, accompanied by the activation of microglia. Microglia, as macrophages in the central nervous system, play an irreplaceable role in neuroinflammation. Current research on neuroinflammation induced by microglia activation mainly focuses on neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, neuropathic pain, acquired brain injury, and others. However, there is relatively limited research on microglia and neuroinflammation under conditions of cardiopulmonary bypass and deep hypothermic circulatory arrest. The close relationship between cardiopulmonary bypass, deep hypothermic circulatory arrest, and cardiac surgery underscores the importance of identifying targets for intervening in neuroinflammation through microglia. This could greatly benefit cardiac surgery patients during cardiopulmonary bypass and the perioperative period, significantly improving patient prognosis. This review article provides the first comprehensive discussion on the signaling pathways associated with neuroinflammation triggered by microglia activation, the impact of cardiopulmonary bypass on microglia, as well as the current status and advancements in cardiopulmonary bypass animal models. It provides new insights and methods for the treatment of neuroinflammation related to cardiopulmonary bypass and deep hypothermic circulatory arrest, holding significant importance for clinical treatment by cardiac surgeons, management strategies by cardiopulmonary bypass physicians, and the development of neurologically related medications.