ObjectiveThis study aimed to explore the association between lactate dehydrogenase-to-albumin ratio and the severity of coronary artery disease in patients with acute myocardial infarction.MethodsPatients with acute myocardial infarction were categorized into three groups based on the lactate dehydrogenase-to-albumin ratio tertiles. Demographic characteristics and Gensini scores were collected. Logistic regression and the receiver operating characteristic analyses were performed to evaluate the predictive ability of the lactate dehydrogenase-to-albumin ratio for a high Gensini score (>60). The area under the curve was calculated.ResultsA total of 489 individuals were retrospectively enrolled in this study. Multivariate logistic regression analysis demonstrated that the highest lactate dehydrogenase-to-albumin ratio was an independent risk factor for a high Gensini score (odds ratio, 3.45; 95% confidence interval: 1.37-8.71; p = 0.009). The receiver operating characteristic analysis showed that the lactate dehydrogenase-to-albumin ratio had good predictive ability for identifying a high Gensini score (area under the curve, 0.743; 95% confidence interval: 0.698-0.788).ConclusionsLactate dehydrogenase-to-albumin ratio may serve as a novel indicator for predicting the severity of coronary artery disease in patients with acute myocardial infarction.

Arrhythmias such as atrial fibrillation and bradyarrhythmia impose a substantial public health burden. Although genetic predisposition contributes to arrhythmia risk, the extent to which modifiable lifestyle factors may mitigate this risk remains unclear. This study aimed to evaluate the association between a comprehensive healthy lifestyle and incident arrhythmias, and to assess whether these associations differ across levels of genetic susceptibility. A prospective cohort analysis was conducted using 341,736 UK Biobank participants after excluding individuals with baseline arrhythmias and incomplete lifestyle information. A healthy lifestyle score (HLS) incorporating smoking status, alcohol consumption, diet quality, and physical activity was constructed. Incident arrhythmias were identified through ICD-10 and procedure codes. Cox proportional hazards models were used to estimate hazard ratios (HRs) for overall arrhythmia, atrial fibrillation, and bradyarrhythmia, adjusting for demographic and clinical covariates. Genetic susceptibility was quantified using a polygenic risk score (PRS) for atrial fibrillation, and joint lifestyle–genetic risk categories were used to evaluate their combined associations with AF risk. Over a mean follow-up of 10.9 years, 37,990 participants developed an incident arrhythmia, comprising 34,491 atrial fibrillation/flutter (AF) events and 9,399 bradyarrhythmia events; the composite count is a deduplicated union, so the two subtype counts overlap by 5,900 dual-subtype cases (Supplementary Table S4). Higher HLS values were associated with lower risks of overall arrhythmia and AF, whereas the association with bradyarrhythmia appeared weaker and non-monotonic. Compared with participants in the unfavorable lifestyle category, those in the favorable category had lower risks of AF (HR, 0.89; 95

Blood urea nitrogen to serum albumin ratio (BAR) is an emerging biomarker that has been associated with sepsis, heart failure, and coronary artery disease. Nevertheless, few studies focus on its association with the prognosis of atrial fibrillation (AF). This retrospective study utilized data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Participants were categorized into three groups based on the BAR tertiles. The Kaplan–Meier analysis was performed to demonstrate the survival rates among three groups. Cox proportional hazards regression and restricted cubic spline (RCS) were conducted to explore the correlation between BAR and all-cause mortality. 1523 AF patients were enrolled in this study, with a median age of 73.8 years, of whom 933 (61.3

BACKGROUND:Retinal microvascular parameters are potential biomarkers for systemic vascular health. This study aimed to assess the interocular consistency of these parameters in patients with coronary atherosclerotic disease(CAD) using AI-based quantitative analysis. METHODS:We analysed 862 colour fundus photographs from 431 patients. Retinal vascular parameters-including fractal dimension (FD), vessel density (VD), and vessel diameters-were automatically measured using a ResNet 101-UNet deep learning model. Interocular symmetry was compared across groups stratified by Gensini score, CAD presence, and lesion location. Correlation was assessed using Pearson and intraclass correlation coefficients (ICC). RESULTS:Except for minor curvature variations in the overall population, no statistically significant interocular differences were found across any subgroups (Gensini scores, CAD vs. Non-CAD, or vessel location; all P > 0.05). All variables demonstrated good interocular consistency, with Pearson coefficients ranging from 0.387 to 0.833 and ICCs from 0.384 to 0.824. While linear regression suggested minor associations between gender and interocular differences in VD and mean branch angle, generalised linear mixed models-adjusting for age, gender, and clinical history-confirmed no significant interocular variance in fundus metrics across all subgroups (P > 0.05). CONCLUSION:Retinal vascular parameters exhibit high interocular symmetry in individuals regardless of their CAD status. These findings suggest that single-eye imaging may potentially represent retinal vascular status in cardiovascular risk assessment. This approach could help streamline screening protocols and provides a rationale for the standardised use of fundus examination as a non-invasive auxiliary tool for CAD evaluation.

Ground-level ozone pollution has emerged as a significant environmental risk factor for diabetic kidney diseases, yet the underlying mechanisms and potential interventions remain poorly defined. This study investigated the nephrotoxic effects of ozone in a diabetic model, wherein male db/db mice were exposed to ozone (0.25 or 1.0 ppm) for 8 weeks. Moreover, dapagliflozin (DAPA) and Yishen Huashi Granules (YSHS), pharmaceutical agents commonly used to treat metabolic and renal diseases, were applied to investigate their therapeutic potential against ozone-caused kidney insult. Our data demonstrated that ozone exposure could exacerbate hyperglycemia and structural renal damage, including glomerular basement membrane thickening, podocyte fusion, and fibrogenesis. Furthermore, ozone exposure disrupted the splenic Th17/Treg balance, enhanced IL-17 production, and promoted renal inflammation through upregulating RORγt/IL-17A signaling pathway. These findings suggested that ozone exposure could accelerate diabetic nephropathy progression by reshaping the systemic immune landscape. Notably, DAPA and YSHS, especially their combination, showed the potential to mitigate kidney injury by ozone through synergistically restoring glucose homeostasis, Th17/Treg balance and RORγt/IL-17 signaling to suppress systemic and local inflammation. This study provided valuable insights into the nephrotoxic effects associated with ozone exposure, and offered a reference for the development of intervention strategies targeting pollutant-driven metabolic kidney disease and the formulation of environmental regulations.

Background The triglyceride-glucose (TyG) index is a simple, cost-effective indicator of insulin resistance, strongly linked to cardiovascular/cerebrovascular risk. Advances in deep learning enable quantitative retinal microvascular analysis from non-invasive fundus photography. This study assessed correlations between retinal vascular characteristics and the TyG index to explore relationships between glucose-lipid metabolism and microvascular alterations. Methods This cross-sectional study included 712 inpatients from Beijing Tongren Hospital Cardiovascular Center. Patients were stratified by TyG index quartiles (Q1–Q4). Retinal vascular parameters were automatically quantified from color fundus photographs (CFPs) using a deep learning segmentation model. Linear regression and subgroup analyses evaluated associations with TyG. Results Significant intergroup differences existed in hypertension, diabetes, revascularization history, Gensini score, body mass index (BMI), fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), low- density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and glycated hemoglobin (HbA1c) (P < 0.01). Higher TyG levels correlated with increased BMI, TC, HbA1c, FBG, LDL-C, and decreased HDL-C. Retinal parameters fractal dimension (FD), vessel density (VD), mean blood vessel diameter (MBVD), mean venous diameter (MVD), and arteriovenous ratio (AVR) significantly differed between groups (P < 0.01), particularly Q1 vs. Q4 and Q2 vs. Q4. After full adjustment (age, sex, medical/personal history, BMI, glucose/lipids), linear regression showed FD, VD, and AVR were negatively correlated with TyG, while MVD and MBVD were positively correlated. Restricted cubic spline (RCS) confirmed linearity (P-nonlinear >0.05). Subgroup analysis further demonstrated that these linear associations (specifically for FD and VD) remained significant within the non-diabetic population. Significant interactions with age were observed (P-interaction < 0.05), where elevated TyG was associated with decreased FD and VD, and increased MBVD and MVD specifically in participants aged ≥65 years. Conclusion TyG levels negatively correlate with retinal FD, VD, and AVR, and positively correlate with MBVD and MVD. Significant interactions exist in individuals ≥ 65 years, where TyG correlates strongly with FD, VD, MBVD, and MVD.

Silica nanoparticles (SiNPs), as one of the most widely produced nanomaterials globally, have garnered widespread attention for their potential toxicity. Epidemiological and experimental evidence have illuminated that exposure to SiNPs can lead to cardiovascular toxicity, though the precise underlying mechanisms remain unclear. We previously identified PKA as a crucial regulator in SiNPs-elicited myocardial injury. Considering this, we further conducted validation in an animal model and also an in-depth investigation into the mechanisms involved. Our data manifested that the pharmacological activation of PKA via intraperitoneal administration of Forskolin greatly mitigated SiNPs-induced abnormalities in histology and function of the rat heart, along with lessening cardiac oxidative stress and mitochondrial damage. Concomitantly, copper overload was present in the rat heart and cardiomyocytes with SiNPs administration. Notably, PKA inhibition could worsen this phenomenon, whilst PKA activation alleviated it. The mechanistic investigation hinted at the PKA/DRP1/ATP7B signaling to modulate mitochondrial dysfunction and copper overload in cardiomyocytes and ultimately apoptosis caused by SiNPs.

Ground-level ozone (O3) is a potent respiratory toxicant with accumulating data demonstrating respiratory harm in humans. However, its mechanistic impact on respiratory health and potential therapeutic target has not yet been fully illuminated. Here, we investigated the toxic mode of short-term ozone insult in mice lungs, excavated underlying mediators using integrated proteomic-metabolomic analysis, and assessed the interventive efficacy of taurine supplementation against ozone-elicited lung injury. Results showed that O3 exposure dose-dependently impaired respiratory function and histology. Integrated proteomics and metabolomics analyses highlighted the crucial role of ferroptosis, cysteine and methionine metabolism, and alanine, aspartate and glutamate metabolism in O3-eclited lung injury. Especially, ferroptosis was activated in the lungs of mice by O3, as evidenced by the increased TFRC, ACSL4, and HO-1, and decreased FTH, FTL, and SLC7A11, indicating iron overload and lipid peroxidation. Ozone stimuli markedly reduced taurine and perturbed taurine and hypotaurine metabolism. More importantly, taurine supplementation could greatly improve respiratory health, including mitigating O3-induced respiratory dysfunction, pulmonary histological damage, and inflammation, while inhibiting ferroptosis as its mediating effect. Taken together, the findings identify ferroptosis as a pivotal regulator linking O3 exposure to lung injury and highlight the beneficial role of taurine in preventing O3-induced respiratory deficits.

Ambient ozone (O-3) is a major air pollutant, yet its mechanistic impact on male reproduction remains poorly understood, despite links to reduced sperm quality. We developed a short-term O-3 exposure mouse model and utilized testicular proteomics, Comparative Toxicology Database (CTD) mining, and in vitro investigations to identify mediators. Results showed that O-3 exposure dose-dependently impaired sperm quality, disrupted histology, and altered testosterone and luteinizing hormone levels. Proteomics revealed disturbances in cholesterol, steroid hormone, and retinol metabolism in mice testicular tissue in response to O-3 exposure, alongside impaired spermatogenesis. More importantly, HIF-1 alpha/mTOR signaling was suggested as a crucial mediator to O-3-elicited testicular toxicity based on proteomic and CTD analysis. Further mechanistic validation using an in vitro air-liquid interface (ALI) coculture of MLE-12 alveolar epithelial and TM3 Leydig cells demonstrated that O-3 exposure triggered reactive oxygen species (ROS)-mediated oxidative stress, subsequently inactivated HIF-1 signaling, and impaired Leydig cell steroidogenesis, thereby contributing to testicular injury and declined sperm quality. Overall, our findings identify HIF-1 signaling as a pivotal regulator linking the exposure of O-3 to steroidogenic dysfunction and spermatogenic disruption in male reproduction, offering novel mechanistic insights for male reproductive toxicology.

Objectives To investigate the association between quantitative retinal vascular parameters and coronary artery disease (CAD) and to evaluate the efficacy of a retinal phenotype-based diagnostic model as a non-invasive tool for early CAD screening.Design A retrospective cross-sectional study.Setting A single-centre study conducted at the Cardiovascular Center of Beijing Tongren Hospital, Capital Medical University, China, between January and October 2024.Participants 417 patients with suspected angina undergoing their first coronary angiography (CAG) were enrolled. Inclusion criteria were age >18 years and high-quality fundus photography within 24 hours pre-CAG. Major exclusions were prior coronary interventions, severe systemic/valvular heart diseases and ocular conditions impairing retinal vascular visualisation.Primary and secondary outcome measures The primary outcome was the association between quantitative retinal vascular parameters and the presence of CAD (defined as ≥50% stenosis). Secondary outcomes included the diagnostic performance area under the receiver operating characteristic curve (AUROC) of three predictive models: one based on quantitative retinal vascular parameters alone, one based on traditional risk factors and a combined model integrating both retinal and clinical variables.Results This study enrolled 417 patients undergoing initial CAG. Compared with non-CAD controls (n=190), patients with CAD (n=227) had higher prevalence of hypertension, dyslipidaemia and diabetes, along with elevated levels of fasting blood glucose, lipoprotein(a) (Lp(a)), triglyceride (TG) and glycated haemoglobin (HbA1c) (all p<0.05). Quantitative fundus analysis revealed that multiple retinal vascular parameters were independently associated with CAD after multivariable adjustment, including fractal dimension (FD), vessel density (VD) and specific zonal measures of vessel diameter and tortuosity (all p<0.05). Multivariable logistic regression incorporating both fundus and clinical variables identified the following independent predictors of CAD: a decrease in FD (OR=0.26, 95% CI 0.16 to 0.41, p<0.01), reduced optic disc long-to-short axis ratio (OR=0.04, 95% CI 0.004 to 0.46, p=0.01) and optic disc-to-macula distance (OR=0.91, 95% CI 0.86 to 0.97, p<0.01), male sex, dyslipidaemia and elevated levels of Lp(a), TG, low-density lipoprotein cholesterol and HbA1c (all p<0.05). The final diagnostic model achieved an AUROC of 0.802 (95% CI 0.76 to 0.845), with a sensitivity of 0.797 and a specificity of 0.679 at the optimal cut-off. Internal validation via bootstrap resampling (1000 iterations) confirmed the robustness of the identified predictors.Conclusion Our findings, derived from an artificial intelligence-based fully automated quantitative retinal vascular parameters measurement method, revealed that multiple quantitative fundus parameters—including FD, VD and other morphological parameters were significantly associated with CAD risk. The CAD diagnostic model we developed demonstrates strong performance and high interpretability, making it suitable for early CAD screening and diagnosis.

Objective Cardiovascular diseases (CVD) remain the leading cause of mortality globally, necessitating early risk identification to improve prevention and management strategies. Traditional risk prediction models, such as the Framingham Cardiovascular Risk Score and the Systematic Coronary Risk Evaluation, often fall short due to their reliance on classical statistical methods and limited variable scope.Materials and methods This study harnessed machine learning (ML) techniques to develop and validate a comprehensive CVD risk prediction model using data from the UK Biobank cohort. Our approach incorporated genetic scores, clinical parameters and lifestyle factors to create separate models for overall CVD, cerebrovascular diseases, thrombotic diseases and other cardiovascular conditions. We used a diverse set of ML algorithms, including Ridge Regression, Logistic Regression, Support Vector Machines, Random Forest, XGBoost, Multilayer Perceptron and Stacking, with rigorous cross-validation procedures to ensure robustness.Results From an initial cohort of 502 407 individuals, 240 644 participants were included in the final analysis. The integrated model, combining clinical, lifestyle and genetic data, achieved the highest predictive performance with an area under the curve (AUC) of 0.85. Models based solely on clinical data, lifestyle data and polygenic risk scores showed lower predictive power. Stratified analysis revealed variable performance across CVD subtypes, with the highest AUC of 0.83 for other cardiovascular diseases. Key predictors included age, systolic blood pressure, cystatin C levels and waist circumference.Conclusion The integration of clinical, lifestyle and genetic data substantially enhances the predictive accuracy of ML models for CVD risk. Our model demonstrates robust performance, with an improvement of 0.12 in AUC over the Framingham Cardiovascular Risk Score, highlighting its potential utility in clinical settings for early risk identification and personalised intervention strategies. Future research should focus on refining the model by incorporating additional predictors and validating its applicability across diverse populations.

To investigate whether blood pressure and blood glucose levels affect retinal microvascular parameters, reflected by density within 300 μm surrounding the avascular area of the fovea (FAZ), also called FD-300. A case series study design was used to include patients with essential hypertension and/or type 2 diabetes who were hospitalized in the Department of Geriatrics, Beijing Tongren Hospital, from January 2023 to January 2024. FD-300 was measured via optical coherence tomography angiography. Multivariate linear regression analysis was used to adjust for confounding factors and then explore the influencing factors of FD-300. Patients were divided into four subgroups according to the quartile of FD-300. The median systolic blood pressure (SBP) levels of the four subgroups were 128 mmHg, 128 mmHg, 126 mmHg, and 121 mmHg, respectively, which were significantly different (p = 0.046). The median glycated hemoglobin (HbA1C) levels of the four subgroups were 6.50

Regulatory T cells (Tregs) have been documented to accumulate in damaged myocardial tissue, where they play a pivotal role in attenuating excessive inflammatory responses during myocardial ischemia/reperfusion (I/R) injury. Concurrently, soluble receptor for advanced glycation end-products (sRAGE) has been demonstrated to alleviate myocardial I/R injury by suppressing inflammation, suggesting a potential involvement of Tregs in the inhibitory effects of sRAGE on myocardial I/R injury. I/R surgery or glucose deprivation/reoxygenation was employed to explore myocardial injury and the related mechanisms by using cardiomyocyte-specific sRAGE knock-in mice or cultured cardiomyocytes. Potential molecular mechanisms were analyzed via western blotting, immunohistochemistry, and flow cytometric analysis. The findings revealed that sRAGE overexpression significantly increased the numbers of Tregs. Depletion of Tregs abrogated the protective effects of sRAGE against I/R-induced cardiac dysfunction, myocardial fibrosis, and inflammatory response in cardiac-specific sRAGE transgenic mice. Mechanistically, sRAGE was found to enhance the expression of programmed cell death ligand 1 (PD-L1) and its upstream JAK2/STAT3 signaling axis, thereby facilitating CD4+ T cells differentiation into Tregs within myocardial tissue during I/R. The study demonstrated that sRAGE protected against myocardial I/R injury by modulating the differentiation of Tregs through upregulation of the JAK2/STAT3-PD-L1 signaling pathway.

BackgroundMyocardial infarction (MI) complicated by heart failure (HF) is a common and severe clinical condition associated with poor outcomes. Estimated plasma volume status (ePVS), a marker of congestion derived from hemoglobin and hematocrit, has shown promise in predicting outcomes in various cardiovascular diseases. This study aimed to investigate the relationship between ePVS and both short-term and long-term prognosis in patients with MI complicated by HF.MethodsA retrospective cohort study was conducted using data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, including 3,238 patients with MI complicated by HF. Patients were stratified into quartiles based on ePVS values. The primary outcomes were in-hospital mortality, 180-day mortality, and 1-year mortality. Kaplan–Meier curves, multivariate Cox regression analysis, and subgroup analyses were performed to assess the relationship between ePVS and outcomes.ResultsKaplan–Meier analysis showed significant differences in survival rates across ePVS quartiles for all outcomes (P < 0.001). Multivariate logistic regression analysis revealed that patients in the highest quartile of ePVS (Q4 vs. Q1) had an independently increased risk of in-hospital mortality (OR 1.58, 95% CI 1.16–2.13, P = 0.003). Cox regression analysis further demonstrated that higher ePVS (Q4 vs. Q1) was associated with an increased risk of 180-day mortality (HR 1.45, 95% CI 1.19–1.75, P < 0.001) and 1-year mortality (HR 1.51, 95% CI 1.27–1.80, P < 0.001). Both Kaplan–Meier survival curves and restricted cubic spline models confirmed a positive association between ePVS and long-term mortality risks.The association between ePVS and long-term outcomes was stronger than for in-hospital mortality. Subgroup analyses revealed that the relationship between ePVS and long-term mortality was more pronounced in patients with systolic blood pressure below 140 mmHg, lower LODS and OASIS scores, and those without hemorrhagic disorders or anemia (P for interaction <0.05).ConclusionePVS was an independent predictor of both short-term and long-term mortality in patients with MI complicated by HF. Its prognostic value was particularly significant for long-term outcomes, suggesting its potential utility in risk stratification and guiding treatment strategies for this high-risk population.

The massive global output and extensive application of silica nanoparticles (SiNPs) raise great human health concerns, especially in the lungs since the respiratory tract is a major portal for NPs entry. Emerging evidence has revealed that SiNPs cause pulmonary impairments, but the underlying mechanism remains elucidated. In this study, we clarify the role of ferroptosis in SiNPs-induced pulmonary toxicity and elucidate its molecular mechanism. First, the Wistar rats were administered to SiNPs (10 mg/kg·bw) with or without ferrostatin-1 (a well-known inhibitor of ferroptosis, shorted as Fer-1,1.0 mg/kg·bw). Results revealed that SiNPs induced impairments in lung function and histopathology by inducing ferroptosis, and the use of ferrostatin-1 alleviated the onset of ferroptosis and lung injury by SiNPs. In particular, the excessive activation of NCOA4 was involved in the ferroptotic process in response to SiNPs. In vitro, SiNPs generated intracellular Fe2+ accumulation, ROS generation, and GPX4 depletion in the human bronchial epithelial cells (16HBE). By contrast, the inhibition of NCOA4 using the RNAi technique protected cells against these phenomena by SiNPs, hinting that SiNPs-induced ferroptosis was dependent on NCOA4-mediated ferritinophagy. Also, the inhibition of ferroptosis or NCOA4-mediated ferritinopathy could protect lung cells/tissue from apoptosis. In conclusion, our data indicated that ferroptosis via the NCOA4-mediated ferritinopathy pathway was a novel and critical mechanism of SiNP-induced lung injury. Of note, we highlight the therapeutic potential of suppressing ferritinopathy or ferroptosis for the management of SiNPs' toxicity.

Glucose transporter 4 (GLUT4)-mediated glucose metabolism is a promising therapeutic target facilitating cardiomyocyte survival during myocardial ischemia/reperfusion (I/R) injury. Soluble receptor for advanced glycation end-products (sRAGE) has been proven to attenuate I/R injury via inhibiting AGE-RAGE mediated signaling pathways, but its role in regulating glucose metabolism remains unclear. Recently, AGEs were reported to hamper the GLUT4 translocation by interfering with the insulin signaling pathway in granulosa cells. Thus, it was speculated that sRAGE might inhibit myocardial I/R injury by enhancing the GLUT4-mediated glucose metabolism. Cardiomyocyte-specific sRAGE knock-in mice were constructed and underwent I/R surgery. H9c2 cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R). The overexpression of sRAGE in cardiomyocytes improved cardiac function, decreased infarct size, and inhibited apoptosis during myocardial I/R injury. sRAGE did not affect the expression of total GLUT4 but increased the translocation of GLUT4 to the plasma membrane, which enhanced the glucose uptake in cardiomyocytes. Meanwhile, sRAGE increased the production of lactate, NADH/NAD+, and adenosine triphosphate levels in cardiomyocytes during OGD/R. sRAGE activated the AMP-activated protein kinase (AMPK)/Akt substrate of 160 kDa (AS160) signaling pathway, and the application of AMPK inhibitor or AS160 mutant abolished the effect of sRAGE on facilitating plasma membrane GLUT4 localization and glucose metabolism. Moreover, the AMPK inhibitor or silenced GLUT4 depleted the anti-apoptotic effect of sRAGE during OGD/R in cardiomyocytes. Therefore, it was suggested that sRAGE inhibited I/R-induced apoptosis via enhancing the GLUT4 translocation to the plasma membrane and glucose metabolism through the AMPK/AS160 signaling pathway.

Although ample evidence indicated the pulmonary toxicity of silica nanoparticles (SiNPs), the persistence or reversibility of such injury, along with the intricate molecular networks involved, remains limited. This study investigated the toxicity and recovery effects of SiNPs on rats in the exposure (3-month via intratracheal instillation) and recovery (6-week) stages. Histopathological changes and collagen deposition in lung tissues were clearly observed following SiNPs exposure, accompanied by elevated hydroxyproline. After a 6-week recovery, these pathological alterations showed remarkable improvement, alongside with the restoration of pulmonary reactive oxygen species (ROS) and cytokines. Proteomic analysis indicated that the activation of immune responses in the serum was crucial for the recovery from lung damage caused by SiNPs instillation. Based on protein-protein interaction (PPI) network analysis, predictive modeling and validation, Hck in the lungs and serum complement component (i.e., C1qc) were identified as potential regulatory molecules, responsible for the reversibility of SiNPs-induced lung damage. In parallel to pulmonary inflammation upon SiNPs stimuli, Hck expression was elevated. In turn, the restored Hck in the recovery period contributed to the mitigation of lung damage. The findings firstly elucidate the reversibility of SiNPs-induced lung damage from a proteomic perspective, providing new insights to fully understand nanotoxicity and assess nanosafety.

Objective To evaluate the safety, efficacy, and long-term effects of catheter ablation with vein of Marshall ethanol infusion for bidirectional mitral isthmus block in patients with persistent atrial fibrillation. Methods Two hundred and forty patients from five centers with persistent atrial fibrillation (AF) who underwent radiofrequency ablation from October 2018 to December 2023 were retrospectively analyzed, including 120 patients who underwent traditional pulmonary vein isolation (PVI Only group) and 120 patients who underwent PVI and Marshall vein ablation (Marshall Plus group). The operation time, X-ray exposure, incidence of AF/atrial tachycardia (AT) and complications were compared between the two groups. Results Among the 240 patients (mean age: 57.2 ± 7.2 years, males: 195/240, 81.25 %), vein of Marshall ethanol infusion was successfully performed in 113 of 120 patients. At 12 and 36 months, the proportion of patients free from AF/ AT after a single procedure was 76.3 % (90/118) in the PVI plus vein of Marshall ethanol infusion group and 67.5 % (79/117) in the PVI only group (P < 0.01). Perimitral block was successfully achieved in 90.8 % (109/120) patients in the Marshall Plus group. Freedom from AF/AT at the 3-year follow-up (68.6 % vs. 59.8 %, P < 0.01) and incidence of adverse events were similar between the two groups. Conclusion PVI combined with Marshall venous infusion ablation can safely and effectively increase the long-term success rate of AF ablation. Duration of AF, left atrial volume(>42 mm,)and bidirectional mitral isthmus block were associated with recurrence of AF/AT.