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BACKGROUND: Serum uric acid (SUA) is an important pathogenetic and prognostic factor for heart failure (HF). Gender differences are apparent in HF. Furthermore, gender differences also exist in the association between SUA and prognosis in various cardiovascular diseases. However, the gender difference for SUA in the prediction of long-term prognosis in HF is still ambiguous. METHODS: A total of 1593 HF patients (897 men, 696 women) from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 cycle were enrolled in our final analysis. Participants were categorized according to gender-specific SUA tertile. We assessed the association between SUA and long-term prognosis of HF patients, defined as all-cause mortality and cardiovascular mortality, in different genders via Kaplan-Meier curve analysis, Cox proportional hazard model, and Fine-Gray competing risk model. The restricted cubic spline (RCS) was performed to investigate the dose-response relationship between SUA and outcomes. RESULTS: Gender differences exist in demographic characteristics, clinical parameters, laboratory tests, and medication of HF patients. After a median follow-up of 127 months (95% CI 120-134 months), there were 853 all-cause deaths (493 events in men, 360 events in women) and 361 cardiovascular deaths (206 events in men, 155 events in women). Kaplan-Meier analysis showed that SUA had gender difference in the prediction of cardiovascular mortality (Log-rank p < 0.001, for male, Log-rank p = 0.150, for female), but not in all-cause mortality. Multivariate Cox regression analysis revealed that elevated SUA levels were associated with higher all-cause mortality and cardiovascular mortality in men (HR 1.11, 95% CI 1.05-1.18, p < 0.001, for all-cause death; HR 1.18, 95% CI 1.09-1.28, p < 0.001, for cardiovascular death), but not in women (HR 1.05, 95% CI 0.98-1.12, p = 0.186, for all-cause death; HR 1.01, 95% CI 0.91-1.12, p = 0.902, for cardiovascular death). Even using non-cardiovascular death as a competitive risk, adjusted Fine-Gray model also illustrated that SUA was an independent predictor of cardiovascular death in men (SHR 1.17, 95% CI 1.08-1.27, p < 0.001), but not in women (SHR 0.98, 95% CI 0.87 - 1.10, p = 0.690). CONCLUSIONS: Gender differences in the association between SUA and long-term prognosis of HF existed. SUA was an independent prognostic predictor for long-term outcomes of HF in men, but not in women.
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Enfermedades Cardiovasculares , Insuficiencia Cardíaca , Humanos , Masculino , Femenino , Ácido Úrico , Factores Sexuales , Encuestas Nutricionales , Factores de Riesgo , Pronóstico , Insuficiencia Cardíaca/tratamiento farmacológicoRESUMEN
A cancer-targeted glutathione (GSH)-gated theranostic probe (CGT probe) for intracellular miRNA imaging and combined treatment of self-sufficient starvation therapy (ST) and chemodynamic therapy (CDT) was developed. The CGT probe is constructed using MnO2 nanosheet (MS) as carrier material to adsorb the elaborately designed functional DNAs. It can be internalized by cancer cells via specific recognition between the AS1411 aptamer and nucleolin. After CGT probe entering the cancer cells, the overexpressed GSH, as gate-control, can degrade MS to Mn2+ which can be used for CDT by Fenton-like reaction. Simultaneously, Mn2+-mediated CDT can further cascade with the enzyme-like activities (catalase-like activity and glucose oxidase-like activity) of CGT probe, achieving self-sufficient ST/CDT synergistic therapy. Meanwhile, the anchored DNAs are released, achieving in situ signal amplification via disubstituted-catalytic hairpin assembly (DCHA) and FRET (fluorescence resonance energy transfer) imaging of miR-21. The in vitro and in vivo experiments demonstrated that accurate and sensitive miRNA detection can be achieved using the CGT probe. Overall, the ingenious CGT probe opens a new avenue for the development of early clinical diagnosis and cancer therapy.
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Transferencia Resonante de Energía de Fluorescencia , Glutatión , Compuestos de Manganeso , MicroARNs , Óxidos , Humanos , Glutatión/química , Glutatión/metabolismo , Animales , Compuestos de Manganeso/química , Óxidos/química , Aptámeros de Nucleótidos/química , Ratones , Ratones Desnudos , Nanomedicina Teranóstica/métodos , Nucleolina , Neoplasias/diagnóstico por imagen , Nanoestructuras/química , Oligodesoxirribonucleótidos/química , Ratones Endogámicos BALB C , Colorantes Fluorescentes/químicaRESUMEN
The usage of adhesively bonded joints, such as single-lap and double-lap joints, is increasing rapidly in aerospace composite structures as a popular alternative to bolts and rivets. Compared to the conventional joining methods such as fastening and riveting, adhesive-bonding technology better prevents damage to composite structures due to the smooth configuration and the mitigation of stress concentration around holes. In this work, the built-in progressive-damage-modeling techniques in Abaqus, including the cohesive zone model (CZM) and the virtual crack closure technique (VCCT), are used to predict the strength and progressive failure of composite single-lap joints subjected to tensile loading. Modeling of an adhesive layer by using a zero/non-zero-thickness cohesive element, cohesive surface, and VCCT is investigated, as is the effect of brittle and ductile adhesives. Two-dimensional finite-element models with different damage-modeling strategies are performed in this study. The failure-load predictions are compared with the experimental results obtained from the literature. For the ductile adhesive, the predicted failure loads using a zero/non-zero-thickness cohesive elements and a cohesive surface are all shown to be in good agreement with the experiments. However, the VCCT technique predicts higher failure loads. For a brittle adhesive, on the other hand, the predictions by zero/non-zero-thickness cohesive elements and cohesive surfaces reveal notable deviations compared to the experimental results. In contrast to the ductile adhesive, the VCCT technique is revealed to be accurate in predicting the brittle adhesive.
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Preoperative selection of perforator is one of the key steps for successful surgery. The purpose of this study is to simulate the selection process of the perforator of the flap using the 3D models of the deep inferior epigastric artery (DIEA). A retrospective study was performed of women who underwent deep inferior epigastric perforator flap breast reconstruction from January 2011 to July 2021. Construct 3D models of the DIEA using computerized tomography angiography images, and then computational fluid dynamics simulations were performed. Correlation and regression analyses were used to analyze the geometric and hemodynamic parameters. Statistical analysis suggested that the outlet flow was positively correlated with the inlet area (r = 0.338, p = 0.000), outlet area (r = 0.840, p = 0.000), the average radius of the perforator (r = 0.592, p = 0.000), and negatively correlated with the length of perforator(r = -0.210, p = 0.024). The results of linear regression analysis showed that the outlet area (p = 0.000), the average radius (p = 0.000), and the length (p = 0.044) of the perforator were the influencing factors on outlet flow. In multiple perforators analysis, there was a significant difference in the total outlet flow among single perforator, double perforators, and triple perforators (p = 0.002). The successful implementation of this experiment provides a new approach for the selection of dominant perforators in the future.
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Etilaminas , Mamoplastia , Colgajo Perforante , Humanos , Femenino , Estudios Retrospectivos , Imagenología Tridimensional , Arterias Epigástricas/diagnóstico por imagen , Colgajos Quirúrgicos/irrigación sanguínea , Mamoplastia/métodos , Colgajo Perforante/irrigación sanguíneaRESUMEN
Background: At present, there is a paucity of research on the link between Crohn's disease (CD) and atrial fibrillation (AF). Nevertheless, both ailments are thought to entail inflammatory and autoimmune processes, and emerging evidence indicates that individuals with CD may face an elevated risk of AF. To shed light on this issue, our study seeks to explore the possibility of shared genes, pathways, and immune cells between these two conditions. Methods: We retrieved the gene expression profiles of both CD and AF from the Gene Expression Omnibus (GEO) database and subjected them to analysis. Afterward, we utilized the weighted gene co-expression network analysis (WGCNA) to identify shared genes, which were then subjected to further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Furthermore, we employed a rigorous analytical approach by screening hub genes through both least absolute shrinkage and selection operator (LASSO) regression and support vector machine (SVM), and subsequently constructing a receiver operating characteristic (ROC) curve based on the screening outcomes. Finally, we utilized single-sample gene set enrichment analysis (ssGSEA) to comprehensively evaluate the levels of infiltration of 28 immune cells within the expression profile and their potential association with the shared hub genes. Results: Using the WGCNA method, we identified 30 genes that appear to be involved in the pathological progression of both AF and CD. Through GO enrichment analysis on the key gene modules derived from WGCNA, we observed a significant enrichment of pathways related to major histocompatibility complex (MHC) and antigen processing. By leveraging the intersection of LASSO and SVM algorithms, we were able to pinpoint two overlapping genes, namely CXCL16 and HLA-DPB1. Additionally, we evaluated the infiltration of immune cells and observed the upregulation of CD4+ and CD8+ T cells, as well as dendritic cells in patients with AF and CD. Conclusions: By employing bioinformatics tools, we conducted an investigation with the objective of elucidating the genetic foundations that connect AF and CD. This study culminated in the identification of CXCL16 and HLA-DPB1 as the most substantial genes implicated in the development of both disorders. Our findings suggest that the immune responses mediated by CD4+ and CD8+ T cells, along with dendritic cells, may hold a crucial role in the intricate interplay between AF and CD.