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Renal dysfunction (RD) often characterizes the worse course of patients with advanced heart failure (AHF). Many prognosis assessments are hindered by researcher biases, redundant predictors, and lack of clinical applicability. In this study, we enroll 1736 AHF/RD patients, including data from Henan Province Clinical Research Center for Cardiovascular Diseases (which encompasses 11 hospital subcenters), and Beth Israel Deaconess Medical Center. We developed an AI hybrid modeling framework, assembling 12 learners with different feature selection paradigms to expand modeling schemes. The optimized strategy is identified from 132 potential schemes to establish an explainable survival assessment system: AIHFLevel. The conditional inference survival tree determines a probability threshold for prognostic stratification. The evaluation confirmed the system's robustness in discrimination, calibration, generalization, and clinical implications. AIHFLevel outperforms existing models, clinical features, and biomarkers. We also launch an open and user-friendly website www.hf-ai-survival.com , empowering healthcare professionals with enhanced tools for continuous risk monitoring and precise risk profiling.
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Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Masculino , Feminino , Idoso , Prognóstico , Pessoa de Meia-Idade , Inteligência Artificial , Medição de Risco/métodos , Análise de Sobrevida , Insuficiência Renal/mortalidade , Insuficiência Renal/fisiopatologia , Insuficiência Renal/diagnóstico , BiomarcadoresRESUMO
Homocysteine (Hcy) and C-reactive protein (CRP) are critical biomarkers for numerous chronic diseases, with cardiovascular disease (CVD) being the most prevalent. The ability to simultaneously detect both biomarkers in point-of-care settings is in high demand for CVD early diagnosis and prevention. Herein, we prepared the eutectic gallium indium (EGaIn) nanoparticles decorated with p-phenylenediamine (PPD) on the surface to facilitate the subsequent attachment of gold nanoparticles (AuNPs) to achieve EGaIn-PPD@Au, which was modified on the screen-printed electrochemical paper-based analytical devices (ePADs). Aptamers that are specific to Hcy and CRP were then immobilized on the EGaIn-PPD@Au surface to achieve the sensing interface on ePADs. The presence of EGaIn-PPD@Au significantly enhanced the electrical conductivity, leading to amplified electrochemical signals. This aptasensor demonstrated high specificity, capable of detecting Hcy in a range of 1-50 µM with a detection limit of 0.22 µM, and the detection range for CRP was 1-100 ng/mL with a detection limit of 0.039 ng/mL. The aptasensor also effectively detected Hcy and CRP in clinical saliva samples, yielding an area under the curve (AUC) of about 0.80 when the individual biomarker was considered and 0.93 when both biomarkers were taken into account. The positive correlation observed between salivary and blood concentrations of Hcy and CRP, coupled with their association with cardiovascular disease (CVD), suggested the potential of this methodology as a noninvasive point-of-care strategy for the early diagnosis of CVD.
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Syntaxin 17 (STX17) has been identified as a crucial factor in mediating the fusion of autophagosomes and lysosomes. However, its specific involvement in the context of atherosclerosis (AS) remains unclear. This study sought to elucidate the role and mechanistic contributions of STX17 in the initiation and progression of AS. Utilizing both in vivo and in vitro AS model systems, we employed ApoE knockout (KO) mice subjected to a high-fat diet and human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL) to assess STX17 expression. To investigate underlying mechanisms, we employed shRNA-STX17 lentivirus to knock down STX17 expression, followed by evaluating autophagy and inflammation in HUVECs. In both in vivo and in vitro AS models, STX17 expression was significantly upregulated. Knockdown of STX17 exacerbated HUVEC damage, both with and without ox-LDL treatment. Additionally, we observed that STX17 knockdown impaired autophagosome degradation, impeded autophagy flux and also resulted in the accumulation of dysfunctional lysosomes in HUVECs. Moreover, STX17 knockdown intensified the inflammatory response following ox-LDL treatment in HUVECs. Further mechanistic exploration revealed an association between STX17 and STING; reducing STX17 expression increased STING levels. Further knockdown of STING enhanced autophagy flux. In summary, our findings suggest that STX17 knockdown worsens AS by impeding autophagy flux and amplifying the inflammatory response. Additionally, the interaction between STX17 and STING may play a crucial role in STX17-mediated autophagy.
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Aterosclerose , Autofagia , Células Endoteliais da Veia Umbilical Humana , Inflamação , Lipoproteínas LDL , Proteínas Qa-SNARE , Autofagia/genética , Animais , Humanos , Aterosclerose/metabolismo , Aterosclerose/genética , Aterosclerose/patologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Inflamação/genética , Proteínas Qa-SNARE/metabolismo , Proteínas Qa-SNARE/genética , Camundongos , Lipoproteínas LDL/metabolismo , Técnicas de Silenciamento de Genes , Lisossomos/metabolismo , Camundongos Knockout , Masculino , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Dieta Hiperlipídica/efeitos adversos , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Apolipoproteínas E/deficiênciaRESUMO
BACKGROUND: Ischemic cardiomyopathy (IC) is primarily due to long-term ischemia/hypoxia of the coronary arteries, leading to impaired cardiac contractile or diastolic function. A new form of cell death induced by copper, called "cuproptosis" is related to the development and progression of multiple diseases. The cuproptosis-related gene (CuGs) plays an important role in acute myocardial infarction, while the specific mechanisms of CuGs in ischemic cardiomyopathy remain unclear. METHODS: The expressions of CuGs and their immune characteristics were analyzed with the IC datasets obtained from the Gene Expression Omnibus, namely GSE5406 and GSE57338, identifying core genes associated with IC development. By comparing RF, SVM, GLM and XGB models, the optimal machine learning model was selected. The expression of marker genes was validated based on the GSE57345, GSE48166 and GSE42955 datasets. Construct a CeRNA network based on core genes. Therapeutic chemiacals targeting core genes were acquired using the CTD database, and molecular docking was performed using Autodock vina software. By ligating the left anterior descending (LAD) coronary artery, an IC mouse model is established, and core genes were experimentally validated using Western blot (WB) and immunohistochemistry (IHC) methods. RESULTS: We identified 14 CuGs closely associated with the onset of IC. The SVM model exhibited superior discriminative power (AUC = 0.914), with core genes being DLST, ATP7B, FDX1, SLC31A1 and DLAT. Core genes were validated on the GSE42955, GSE48166 and GSE57345 datasets, showing excellent performance (AUC = 0.943, AUC = 0.800, and AUC = 0.932). The CeRNA network consists of 218 nodes and 264 lines, including 5 core diagnostic genes, 52 miRNAs, and 161 lncRNAs. Chemicals predictions indicated 8 chemicals have therapeutic effects on the core diagnostic genes, with benzo(a)pyrene molecular docking showing the highest affinity (-11.3 kcal/mol). Compared to the normal group, the IC group,which was established by LAD ligation, showed a significant decrease in LVEF as indicated by cardiac ultrasound, and increased fibrosis as shown by MASSON staining, WB results suggest increased expression of DLST and ATP7B, and decreased expression of FDX1, SLC31A1 and DLAT in the myocardial ischemic area (p < 0.05), which was also confirmed by IHC in tissue sections. CONCLUSION: In summary, this study comprehensively revealed that DLST, ATP7B, FDX1, SLC31A1 and DLAT could be identified as potential immunological biomarkers in IC, and validated through an IC mouse model, providing valuable insights for future research into the mechanisms of CuGs and its diagnostic value to IC.
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Apoptose , Biologia Computacional , Isquemia Miocárdica , Animais , Humanos , Masculino , Camundongos , Cardiomiopatias/genética , Cardiomiopatias/imunologia , Bases de Dados Genéticas , Modelos Animais de Doenças , Redes Reguladoras de Genes , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Isquemia Miocárdica/genética , Isquemia Miocárdica/imunologia , CobreRESUMO
BACKGROUND: There is evidence indicating that both lipoprotein(a) [Lp(a)] and fibrinogen (FIB) are associated with mortality, However, the impact of their combination on mortality has not been determined. Thus, the aim of this study was to examine the association between the combination of Lp(a) and FIB with all-cause and cause-specific mortality. METHODS: This prospective cohort study enrolled 4,730 participants from the third National Health and Nutrition Examination Survey. The exposure variables included Lp(a), FIB and their combination, while the outcome variables consisted of all-cause, cardiovascular disease (CVD) and cancer-related mortality. Multivariate COX regression, subgroup analysis, sensitivity analysis and restricted cubic spline (RCS) were used to investigate the association between Lp(a), FIB and their combination with all-cause, CVD and cancer-related mortality. RESULTS: Over a median follow-up period of 235 months, 2,668 individuals died, including 1,051 deaths attributed to CVD and 549 deaths due to cancer. Multivariate Cox regression analyses revealed independent associations between both Lp(a) and FIB with all-cause, CVD, and cancer-related mortality. Compared to participants in the 1st to 50th percentiles of both Lp(a) and FIB, those in the 90th to 100th percentiles exhibited multivariable adjusted HRs of 1.813 (95% CI: 1.419-2.317, P < 0.001), 2.147 (95% CI: 1.483-3.109, P < 0.001) and 2.355 (95% CI: 1.396, 3.973, P = 0.001) for all-cause, CVD and cancer-related mortality, respectively. Subgroup and sensitivity analyses did not substantially attenuate the association between the combination of high Lp(a) and high FIB with the risk of all-cause and CVD-related mortality. Additionally, the RCS analysis showed that the relationship between Lp(a) and the risk of all-cause and cancer-related mortality, as well as the relationship between FIB and the risk of cancer-related mortality, were linear (P for nonlinearity > 0.05). Conversely, the relationship between Lp(a) and the risk of CVD-related mortality, as well as the relationship between FIB and the risk of all-cause and CVD-related mortality, were nonlinear (P for nonlinearity < 0.05). CONCLUSIONS: High levels of Lp(a) and FIB together conferred a greater risk of mortality from all-cause, CVD and cancer.
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Doenças Cardiovasculares , Causas de Morte , Fibrinogênio , Lipoproteína(a) , Neoplasias , Inquéritos Nutricionais , Humanos , Neoplasias/mortalidade , Lipoproteína(a)/sangue , Doenças Cardiovasculares/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Fibrinogênio/análise , Adulto , Estados Unidos/epidemiologia , Idoso , Fatores de RiscoRESUMO
Many clustered regularly interspaced short palindromic repeat and CRISPR-associated protein 12b (CRISPR-Cas12b) nucleases have been computationally identified, yet their potential for genome editing remains largely unexplored. In this study, we conducted a GFP-activation assay screening 13 Cas12b nucleases for mammalian genome editing, identifying five active candidates. Candidatus hydrogenedentes Cas12b (ChCas12b) was found to recognize a straightforward WTN (W = T or A) proto-spacer adjacent motif (PAM), thereby dramatically expanding the targeting scope. Upon optimization of the single guide RNA (sgRNA) scaffold, ChCas12b exhibited activity comparable to SpCas9 across a panel of nine endogenous loci. Additionally, we identified nine mutations enhancing ChCas12b specificity. More importantly, we demonstrated that both ChCas12b and its high-fidelity variant, ChCas12b-D496A, enabled allele-specific disruption of genes harboring single nucleotide polymorphisms (SNPs). These data position ChCas12b and its high-fidelity counterparts as promising tools for both fundamental research and therapeutic applications.
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CRISPR-Cas12a, often regarded as a precise genome editor, still requires improvements in specificity. In this study, we used a GFP-activation assay to screen 14 new Cas12a nucleases for mammalian genome editing, successfully identifying 9 active ones. Notably, these Cas12a nucleases prefer pyrimidine-rich PAMs. Among these nucleases, we extensively characterized Mb4Cas12a obtained from Moraxella bovis CCUG 2133, which recognizes a YYN PAM (Y = C or T). Our biochemical analysis demonstrates that Mb4Cas12a can cleave double-strand DNA across a wide temperature range. To improve specificity, we constructed a SWISS-MODEL of Mb4Cas12a based on the FnCas12a crystal structure and identified 8 amino acids potentially forming hydrogen bonds at the target DNA-crRNA interface. By replacing these amino acids with alanine to disrupt the hydrogen bond, we tested the influence of each mutation on Mb4Cas12a specificity. Interestingly, the F370A mutation improved specificity with minimal influence on activity. Further study showed that Mb4Cas12a-F370A is capable of discriminating single-nucleotide polymorphisms. These new Cas12a orthologs and high-fidelity variants hold substantial promise for therapeutic applications.
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Alelos , Proteínas Associadas a CRISPR , Sistemas CRISPR-Cas , Edição de Genes , Edição de Genes/métodos , Proteínas Associadas a CRISPR/metabolismo , Proteínas Associadas a CRISPR/genética , Humanos , Endodesoxirribonucleases/metabolismo , Endodesoxirribonucleases/genética , Endodesoxirribonucleases/química , Animais , Engenharia de Proteínas/métodos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Polimorfismo de Nucleotídeo Único , Mutação , DNA/metabolismo , DNA/genética , Células HEK293RESUMO
Background: The triglyceride-glucose (TYG) index is a novel and reliable marker reflecting insulin resistance. Its predictive ability for cardiovascular disease onset and prognosis has been confirmed. However, for advanced chronic heart failure (acHF) patients, the prognostic value of TYG is challenged due to the often accompanying renal dysfunction (RD). Therefore, this study focuses on patients with aHF accompanied by RD to investigate the predictive value of the TYG index for their prognosis. Methods and Results: 717 acHF with RD patients were included. The acHF diagnosis was based on the 2021 ESC criteria for acHF. RD was defined as the eGFR < 90 mL/(min/1.73 m2). Patients were divided into two groups based on their TYG index values. The primary endpoint was major adverse cardiovascular events (MACEs), and the secondary endpoints is all-cause mortality (ACM). The follow-up duration was 21.58 (17.98-25.39) months. The optimal cutoff values for predicting MACEs and ACM were determined using ROC curves. Hazard factors for MACEs and ACM were revealed through univariate and multivariate COX regression analyses. According to the univariate COX regression analysis, high TyG index was identified as a risk factor for MACEs (hazard ratio = 5.198; 95% confidence interval [CI], 3.702-7.298; P < 0.001) and ACM (hazard ratio = 4.461; 95% CI, 2.962-6.718; P < 0.001). The multivariate COX regression analysis showed that patients in the high TyG group experienced 440.2% MACEs risk increase (95% CI, 3.771-7.739; P < 0.001) and 406.2% ACM risk increase (95% CI, 3.268-7.839; P < 0.001). Kaplan-Meier survival analysis revealed that patients with high TyG index levels had an elevated risk of experiencing MACEs and ACM within 30 months. Conclusion: This study found that patients with high TYG index had an increased risk of MACEs and ACM, and the TYG index can serve as an independent predictor for prognosis.
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Glicemia , Insuficiência Cardíaca , Nefropatias , Triglicerídeos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Doença Crônica , Nefropatias/sangue , Nefropatias/diagnóstico , Nefropatias/etiologia , Triglicerídeos/sangue , Prognóstico , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-IdadeRESUMO
Objective: Although lipoprotein(a) [Lp(a)] and high-sensitivity C-reactive protein (Hs-CRP) are closely associated with the mortality of acute myocardial infarction (AMI), their synergistic effect on the risk of death remains unknown. Therefore, this study aimed to explore the combined effect of Lp(a) and Hs-CRP on the incidence of all-cause and cardiovascular death in AMI patients. Methods: A comprehensive cohort study enrolled 912 AMI patients, categorizing them into four groups based on Lp(a) and Hs-CRP levels: Group 1 [Lp(a) < 30 mg/dL & Hs-CRP < 2 mg/L], Group 2 [Lp(a) < 30 mg/dL & Hs-CRP ≥ 2 mg/L], Group 3 [Lp(a) ≥ 30 mg/dL & Hs-CRP < 2 mg/L], and Group 4 [Lp(a) ≥ 30 mg/dL & Hs-CRP ≥ 2 mg/L]. Cox regression analysis, Kaplan-Meier survival analysis and sensitivity analysis were employed to determine the combined effects of Lp(a) and Hs-CRP on the risk of all-cause and cardiovascular death. Results: Over a median observation period of 38.98 months, 217 patients passed away, with 137 deaths attributed to cardiovascular causes. The multivariate Cox regression analysis revealed that in the comprehensively adjusted Model 3, only Lp(a) and the combination of Lp(a) and Hs-CRP exhibited a strong association with cardiovascular death risk. Specifically, for Lp(a) levels ≥ 30 mg/dL compared to < 30 mg/dL, the hazard ratio (HR) was 2.434 with a 95% confidence interval (CI) of 1.653-3.583 (P < 0.001); for log10(Lp(a)), the HR was 2.630 with a 95% CI of 1.530-4.523 (P < 0.001); for Group 4 versus Group 1, the HR was 2.346 with a 95% CI of 1.054-5.220 (P = 0.037); and for Group 4 versus Groups 1 + 2 + 3, the HR was 1.878 with a 95% CI of 1.284-2.748 (P = 0.001). Sensitivity analysis indicated that the synergy between Lp(a) and Hs-CRP continued to be independently associated with the risk of cardiovascular death. For Group 3 versus Group 1, the HR was 3.353 with a 95% CI of 1.133-9.917 (P = 0.029); for Group 4 versus Group 1, the HR was 3.710 with a 95% CI of 1.466-9.392 (P = 0.006); and for Group 4 versus Groups 1 + 2 + 3, the HR was 2.433 with a 95% CI of 1.620-3.656 (P < 0.001). Conclusions: Compared to elevated levels of either Lp(a) or Hs-CRP alone, the concurrent high levels of both significantly increased the risk of cardiovascular death in patients with AMI, underscoring the importance of considering their combined effects in the prognostic management of AMI patients.
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Proteína C-Reativa , Lipoproteína(a) , Infarto do Miocárdio , Humanos , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Masculino , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/sangue , Feminino , Pessoa de Meia-Idade , Lipoproteína(a)/sangue , Estudos Prospectivos , Idoso , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Fatores de Risco , Biomarcadores/sangue , Prognóstico , Causas de Morte , Estudos de CoortesRESUMO
Since the discovery of ferromagnetic nanoparticles Fe3O4 that exhibit enzyme-like activity in 2007, the research on nanoenzymes has made significant progress. With the in-depth study of various nanoenzymes and the rapid development of related nanotechnology, nanoenzymes have emerged as a promising alternative to natural enzymes. Within nanozymes, there is a category of metal-based single-atom nanozymes that has been rapidly developed due to low cast, convenient preparation, long storage, less immunogenicity, and especially higher efficiency. More importantly, single-atom nanozymes possess the capacity to scavenge reactive oxygen species through various mechanisms, which is beneficial in the tissue repair process. Herein, this paper systemically highlights the types of metal single-atom nanozymes, their catalytic mechanisms, and their recent applications in tissue repair. The existing challenges are identified and the prospects of future research on nanozymes composed of metallic nanomaterials are proposed. We hope this review will illuminate the potential of single-atom nanozymes in tissue repair, encouraging their sequential clinical translation.
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Enzimas , Humanos , Enzimas/química , Enzimas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Catálise , Nanoestruturas/química , NanotecnologiaRESUMO
Background: Diabetic kidney disease (DKD) had been proposed as a contributor in the pathogenesis of coronary artery disease (CAD). However, the relationship of DKD and the long-term adverse outcomes in patients with CAD after percutaneous coronary intervention (PCI) was still undiscovered. Methods: Approximately 892 patients with CAD enrolled from January 2012 to December 2016. The patients were divided into two groups, the DKD group (n = 341) and the None DKD group (n = 551). The primary outcome was major adverse cardiac events (MACE) after PCI. The average follow-up time was 1,897 ± 1,276 days. Results: Baseline data showed that some factors were significantly different between the two groups, including age, body mass index, gender (female), hypertension, smoking, stroke history, heart failure, duration of diabetic mellitus (DM), low-density lipoprotein cholesterol, urinary protein/creatinine ratio, serum creatinine, hemoglobin, platelet, antiplatelet, beta blocker, statin, antihypertensive drugs, and insulin (all p < 0.005). There were significant differences between the two groups in MACE, 40.3% vs. 52.2% (p = 0.001), and in cardiovascular death events and all-cause death events (5.6% vs. 20.5%, p < 0.001 and 4.4% vs. 13.5%, p < 0.001, respectively). In the DKD group, the risk of MACE was elevated to 141.9% [hazard ratio (HR) = 1.419, 95% confidence interval (CI): 1.164-1.730, p = 0.001] in the Cox univariable regression analyses; after adjusting co-variables, the Cox multivariable regression analyses demonstrated that DKD was an independent predictor for MACE (HR = 1.291, 95% CI: 1.027-1.624, p = 0.029) in patients with CAD after PCI, as well as in cardiovascular death events (HR = 2.148, 95% CI: 1.292-3.572, p = 0.003) and all-cause death events (HR = 2.229, 95% CI: 1.325-3.749, p = 0.003). Conclusion: This study suggests that DKD is an independent and novel predictor of long-term adverse outcomes in patients with CAD and DM who underwent PCI.
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Compact Cas9 nucleases hold great promise for therapeutic applications. Although several compact Cas9 nucleases have been developed, many genomic loci still could not be edited due to a lack of protospacer adjacent motifs (PAMs). We previously developed a compact SlugCas9 recognizing an NNGG PAM. Here we demonstrate that SlugCas9 displays comparable activity to SpCas9. We developed a simple phage-assisted evolution to engineer SlugCas9 for unique PAM requirements. Interestingly, we generated a SlugCas9 variant (SlugCas9-NNG) that could recognize an NNG PAM, expanding the targeting scope. We further developed a SlugCas9-NNG-based adenine base editor and demonstrated that it could be delivered by a single adeno-associated virus to disrupt PCSK9 splice donor and splice acceptor. These genome editors greatly enhance our ability for in vivo genome editing.
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Bacteriófagos , Sistemas CRISPR-Cas , Sistemas CRISPR-Cas/genética , Pró-Proteína Convertase 9 , Adenina , Endonucleases/genéticaRESUMO
Background: The association between waist-to-height ratio (WHtR) with hypertension has not been adequately explained, so in this study we sought to clarify the predictive role of WHtR on the incidence of hypertension as well as the potential nonlinear associations in the general population. Methods: In this large prospective cohort study, a total of 4,458 individuals from the China Health and Nutrition Survey (CHNS) were included in the analysis. Multivariate Cox regression analyses, subgroup analyses, receiver operator characteristic (ROC) and restricted cubic spline (RCS) analyses were used to examine the association of WHtR with the risk of new-onset hypertension. Results: Hypertension occurred in 32.8% of participants during the maximum six-year follow-up period. Compared with the group with lower WHtR, the group with higher WHtR had a higher incidence of hypertension (p < 0.001). Multivariate Cox regression analysis showed that the risk of hypertension was 1.45 times higher in the high WHtR group than in the low WHtR group, and that the risk of hypertension increased by 30.4% for every 0.1 unit increase in WHtR (p < 0.001). Subgroup analyses also validated the stratified associations between WHtR and the risk of new-onset hypertension in most subgroups (p < 0.05). ROC analyses also revealed that WHtR was superior to body mass index in predicting new-onset hypertension (AUC: 0.626 vs. 0.607, p = 0.009). Further RCS analysis detected a nonlinear association between WHtR and risk of new-onset hypertension (P for nonlinearity <0.001). Conclusion: WHtR was nonlinearly associated with the risk of new-onset hypertension in the general population.
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Osteoarthritis (OA), the commonest arthritis, is characterized by the progressive destruction of cartilage, leading to disability. The Current early clinical treatment strategy for OA often centers on anti-inflammatory or analgesia medication, weight loss, improved muscular function and articular cartilage repair. Although these treatments can relieve symptoms, OA tends to be progressive, and most patients require arthroplasty at the terminal stages of OA. Recent studies have shown a close correlation between joint pain, inflammation, cartilage destruction and synovial cells. Consequently, understanding the potential mechanisms associated with the action of synovial cells in OA could be beneficial for the clinical management of OA. Therefore, this review comprehensively describes the biological functions of synovial cells, the synovium, together with the pathological changes of synovial cells in OA, and the interaction between the cartilage and synovium, which is lacking in the present literature. Additionally, therapeutic approaches based on synovial cells for OA treatment are further discussed from a clinical perspective, highlighting a new direction in the treatment of OA.
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Acute myocardial infarction dominates coronary artery disease mortality. Identifying bio-signatures for plaque destabilization and rupture is important for preventing the transition from coronary stability to instability and the occurrence of thrombosis events. This computational systems biology study enrolled 2,235 samples from 22 independent bulks cohorts and 14 samples from two single-cell cohorts. A machine-learning integrative program containing nine learners was developed to generate a warning classifier linked to atherosclerotic plaque vulnerability signature (APVS). The classifier displays the reliable performance and robustness for distinguishing ST-elevation myocardial infarction from chronic coronary syndrome at presentation, and revealed higher accuracy to 33 pathogenic biomarkers. We also developed an APVS-based quantification system (APVSLevel) for comprehensively quantifying atherosclerotic plaque vulnerability, empowering early-warning capabilities, and accurate assessment of atherosclerosis severity. It unraveled the multidimensional dysregulated mechanisms at high resolution. This study provides a potential tool for macro-level differential diagnosis and evaluation of subtle genetic pathological changes in atherosclerosis.
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AIMS: To analyze the association between hemoglobin glycation index (HGI) and the long-term prognosis of patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). METHODS: Predicted glycated hemoglobin (HbA1c) level was calculated using an established formula and HGI represented the difference between laboratory measured HbA1c and predicted HbA1c. A total of 1780 patients were stratified into three subgroups (HGI < -0.4, -0.4 ⦠HGI < 0.12 and HGI ⧠0.12). The primary endpoints included all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). RESULTS: ACM occurred in 54 patients: 22 (3.7) in the low-HGI subgroup, 8 (1.3) in the moderate-HGI subgroup and 24 (4.1) in the high-HGI subgroup (p = .012). After adjusting for the traditional clinical prognostic factors, multivariate Cox regression analysis showed that patients in both the low and high HGI subgroups had significantly increased risk of ACM as compared with patients in the moderate HGI subgroup (hazard ratio [HR] = 4.979, 95% confidence interval [CI]: 1.865-13.297, p = .001 and HR = 2.918, 95% CI: 1.075-7.922, p = .036). However, we did not find significant differences in the incidence of CM, MACEs and MACCEs. CONCLUSION: HGI can predicts risk for long-term mortality in patients undergoing PCI. This index could be helpful for the effective clinical management of the CAD population.
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Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Hemoglobinas Glicadas , Estudos Retrospectivos , Reação de Maillard , Intervenção Coronária Percutânea/efeitos adversos , PrognósticoRESUMO
The coronary artery bypass grafting is a main treatment for restoring the blood supply to the ischemic site by bypassing the narrow part, thereby improving the heart function of the patients. Autologous blood vessels are preferred in coronary artery bypass grafting, but their availability is often limited by due to the underlying disease. Thus, tissue-engineered vascular grafts that are devoid of thrombosis and have mechanical properties comparable to those of natural vessels are urgently required for clinical applications. Most of the commercially available artificial implants are made from polymers, which are prone to thrombosis and restenosis. The biomimetic artificial blood vessel containing vascular tissue cells is the most ideal implant material. Due to its precision control ability, three-dimensional (3D) bioprinting is a promising method to prepare biomimetic system. In the 3D bioprinting process, the bioink is at the core state for building the topological structure and keeping the cell viable. Therefore, in this review, the basic properties and viable materials of the bioink are discussed, and the research of natural polymers in bioink, including decellularized extracellular matrix, hyaluronic acid, and collagen, is emphasized. Besides, the advantages of alginate and Pluronic F127, which are the mainstream sacrificial material during the preparation of artificial vascular graft, are also reviewed. Finally, an overview of the applications in the field of artificial blood vessel is also presented.
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As one of the most prevalent heritable cardiovascular diseases, dilated cardiomyopathy (DCM) induces cardiac insufficiency and dysfunction. Although genetic mutation has been identified one of the causes of DCM, the usage of genetic biomarkers such as RNAs for DCM early diagnosis is still being overlooked. In addition, the alternation of RNAs could reflect the progression of the diseases, as an indicator for the prognosis of patients. Therefore, it is beneficial to develop genetic based diagnostic tool for DCM. RNAs are often unstable within circulatory system, leading to the infeasibility for clinical application. Recently discovered exosomal miRNAs have the stability that is then need for diagnostic purpose. Hence, fully understanding of the exosomal miRNA within DCM patients is vital for clinical translation. In this study, we employed the next generation sequencing based on the plasma exosomal miRNAs to comprehensively characterize the miRNAs expression in plasma exosomes from DCM patients exhibiting chronic heart failure (CHF) compared to healthy individuals. A complex landscape of differential miRNAs and target genes in DCM with CHF patients were identified. More importantly, we discovered that 92 differentially expressed miRNAs in DCM patients undergoing CHF were correlated with several enriched pathways, including oxytocin signalling pathway, circadian entrainment, hippo signalling pathway-multiple species, ras signalling pathway and morphine addiction. This study reveals the miRNA expression profiles in plasma exosomes in DCM patients with CHF, and further reveal their potential roles in the pathogenesis of it, presenting a new direction for clinical diagnosis and management of DCM patients with CHF.