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Pulmonary hypertension (PH) is a life-threatening condition characterized by pulmonary vascular remodeling and endothelial dysfunction. Current therapies primarily target vasoactive imbalances but often fail to address adverse vascular remodeling. Long non-coding RNA (lncRNA), which are key regulators of various cellular processes, remain underexplored in the context of PH. To investigate the role of lncRNA in PH, we performed a comprehensive analysis using Weighted Gene Co-expression Network Analysis (WGCNA) on the GSE113439 dataset, comprising human lung tissue samples from different PH subtypes. Our analysis identified the lncRNA SNHG11 as consistently downregulated in PH. Functional assays in human pulmonary artery endothelial cells (HPAECs) demonstrated that SNHG11 plays a critical role in modulating inflammation, cell proliferation, apoptosis, and the JAK/STAT and MAPK signaling pathways. Mechanistically, SNHG11 influences the stability of PRPF8, a crucial mRNA spliceosome component, thereby affecting multiple cellular functions beyond splicing. In vivo experiments using a hypoxic rat model showed that knockdown of SNHG11 alleviates PH development and improves right ventricular function. These findings highlight SNHG11 as a key regulator in PH pathogenesis and suggest it as a potential therapeutic target.
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OBJECTIVE: Patients on extracorporeal membrane oxygenation (ECMO) are often complex and have a high mortality rate. Currently, risk assessment and treatment decisions for patients receiving ECMO are controversial. Therefore, we sought to identify risk factors for mortality in patients receiving ECMO and provide a reference for patient management. METHODS: We retrospectively analyzed the clinical data of 199 patients who received ECMO support from December 2013 to April 2023. Univariate and multivariable logistic regression analyses were used to identify risk factors. The cutoff value was determined by receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 199 patients were selected for this study, and the mortality rate was 76.38%. More than half of the patients underwent surgery during hospitalization. Multivariable logistic regression analysis revealed that continuous renal replacement therapy (CRRT) implantation (OR = 2.994; 95% CI, 1.405-6.167; p = 0.004) and age (OR = 1.021; 95% CI, 1.002-1.040; p = 0.032) were the independent risk factors for mortality. In the ROC curve analysis, age had the best predictive effect (AUC 0.646, 95% CI 0.559-0.732, p = 0.003) for death when the cutoff value was 48.5 years. Furthermore, in patients receiving combined CRRT and ECMO, lack of congenital heart disease and previous surgical history were the independent risk factors for mortality. CONCLUSIONS: CRRT implantation and age were independent risk factors for patients with ECMO implantation in a predominantly surgical cohort. In patients receiving a combination of CRRT and ECMO, lack of congenital heart disease and previous surgical history were independent risk factors for mortality.
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Oxigenação por Membrana Extracorpórea , Curva ROC , Humanos , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Fatores de Risco , Adulto , Modelos Logísticos , Terapia de Substituição Renal Contínua , Medição de Risco , Fatores Etários , Idoso , Mortalidade HospitalarRESUMO
OBJECTIVES: Bleeding complications are one of the most serious postoperative complications after cardiac surgery and are associated with high mortality, especially in patients with infective endocarditis (IE). Our objectives were to identify the risk factors and develop a prediction model for postoperative bleeding complications in IE patients. METHODS: The clinical data of IE patients treated from October 2013 to January 2022 were reviewed. Multivariate logistic regression analysis was used to evaluate independent risk factors for postoperative bleeding complications and develop a prediction model accordingly. The prediction model was verified in a temporal validation cohort. The performance of the model was evaluated in terms of its discrimination power, calibration, precision, and clinical utility. RESULTS: A total of 423 consecutive patients with IE who underwent surgery were included in the final analysis, including 315 and 108 patients in the training cohort and validation cohort, respectively. Four variables were selected for developing a prediction model, including platelet counts, systolic blood pressure, heart failure and vegetations on the mitral and aortic valves. In the training cohort, the model exhibited excellent discrimination power (AUC = 0.883), calibration (Hosmer-Lemeshow test, P = 0.803), and precision (Brier score = 0.037). In addition, the model also demonstrated good discrimination power (AUC = 0.805), calibration (Hosmer-Lemeshow test, P = 0.413), and precision (Brier score = 0.067) in the validation cohort. CONCLUSIONS: We developed and validated a promising risk model with good discrimination power, calibration, and precision for predicting postoperative bleeding complications in IE patients.
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Endocardite Bacteriana , Endocardite , Humanos , Medição de Risco , Endocardite/complicações , Endocardite/diagnóstico , Endocardite/cirurgia , Fatores de Risco , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Hemorragia Pós-Operatória/diagnóstico , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Heart failure (HF) and platelet count are often considered risk factors for mortality in patients with infective endocarditis (IE); however, their effects on various complications have not been elucidated. HYPOTHESIS: We speculated that HF and platelet count have significant impact on the short-term outcomes of IE. METHODS: This single-center retrospective study analyzed data from 320 IE patients who underwent surgery. A multivariate Cox proportional hazards model was used to identify the risk factors for adverse outcomes. The effect of the platelet count on the prognosis of patients with HF was determined by subgroup analysis and Kaplan-Meier analysis. RESULTS: The study population was divided into the HF group (n = 102) and the non-HF group (n = 218). The median age of the total population was 44.5 years (31-56 years), of which 227 (70.94%) patients were male. The incidence rates of 1-year all-cause mortality, cardiac outcomes, and composite outcomes were respectively almost sixfold, fourfold, and threefold higher in the HF group than in the non-HF group (all p < 0.001). In multivariate Cox regression analysis, HF was an independent risk factor for 1-year all-cause mortality, cardiac outcomes, cerebral outcomes, and composite outcomes. The Kaplan-Meier survival curves revealed that the patients with both HF and thrombocytopenia demonstrated the worst composite outcomes than the patients of the other groups (log-rank p < 0.001). In the HF group, the platelet count was significantly associated with mortality and composite outcomes. CONCLUSIONS: HF and preoperative platelet count are significantly associated with 1-year all-cause mortality and adverse outcomes postoperatively in IE patients. Patients with HF and thrombocytopenia have the worst short-term prognosis.
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Anemia , Endocardite Bacteriana , Endocardite , Insuficiência Cardíaca , Trombocitopenia , Humanos , Masculino , Adulto , Feminino , Contagem de Plaquetas , Estudos Retrospectivos , Mortalidade Hospitalar , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/complicações , Endocardite/diagnóstico , Endocardite/cirurgia , Prognóstico , Fatores de Risco , Trombocitopenia/complicações , Trombocitopenia/epidemiologiaRESUMO
BACKGROUND: Intro-aortic balloon pump (IABP) is widely used in cardiac surgery patients nowadays. This study aimed to analyze the predictor of short-term survival in cardiac valvular surgery patients with intra-aortic balloon pump implantation. METHODS: This was a retrospective study and a total of 102 cardiac valvular surgery patients who received intra-aortic balloon pump implantation were consecutively included. We retrospectively collected the baseline characteristics and short-term outcomes. Baseline characteristics were compared between survivors with non-survivors, and logistic regression was performed to identify predictors for short-term mortality. RESULTS: Among all the patients, there were 71 (69.6%) patients successfully weaned from IABP and survived to discharge, the other 31 (30.4%) patients failed to wean from IABP and died within the first 30 days after surgery. When compared with non-survivors, survivors had a higher proportion of males (62% vs 32.3%, p = 0.006), a lower rate of Atrial fibrillation (38% vs 62%, p < 0.03). After IABP implantation, vasoactive drug use was significantly lower in survivors compared with non-survivors, and survivors showed significant improvements in cardiac function and urine volume. Univariate and multivariate logistic regression analysis indicated that atrial fibrillation and combined use of continuous renal replacement therapy (CRRT) were significant independent predictors for short-term mortality. CONCLUSION: Timely implantation of IABP can improve patients' cardiac and renal function and reduce the dosage of vasoactive drugs. Atrial fibrillation and combined use of CRRT are independent predictors for short-term mortality in patients who underwent cardiac valvular surgery with IABP implantation.
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OBJECTIVE: In patients receiving extracorporeal membrane oxygenation (ECMO), continuous renal replacement therapy (CRRT) is increasingly being used for renal replacement and fluid management. However, critically ill surgical patients receiving combined ECMO and CRRT tend to have a high mortality rate, and there are limited studies on this population. Therefore, we aimed to investigate the risk factors for mortality in surgical patients receiving combined ECMO and CRRT. METHODS: Data of surgical patients who underwent ECMO between December 2013 and April 2023 were retrospectively reviewed. Univariate and multivariate logistic regression analysis were used to identify the risk variables. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff value of albumin and age to predict death. RESULTS: A total of 199 patients on ECMO support were screened, of which 105 patients were included in the final analysis. Of 105 patients, 77 (73.33%) were treated with CRRT. Veno-arterial ECMO was performed in 97 cases (92.38%), and the rest were veno-venous ECMO (n = 8, 7.62%). Cardiovascular-related surgery was performed in the main patients (n = 86, 81.90%) and other types of surgery in 19 patients. In surgical patients on ECMO support, the logistic regression analysis showed that CRRT implantation, male sex, and age were the independent risks factors for mortality. Furthermore, the ROC curve analysis showed that age 48.5 years had the highest Youden index. In surgical patients on combined CRRT and ECMO, age, valvular heart disease, and albumin were the independent risk factors for prognosis. Albumin had the highest Youden index at a cutoff value of 39.95 g/L for predicting mortality, though the overall predictive value was modest (area under ROC 0.704). Age had the highest Youden index at a cutoff value of 48.5 years for predicting mortality. CONCLUSIONS: In our cohort of surgical patients requiring ECMO, which consisted mostly of patients undergoing cardiovascular surgery requiring VA-ECMO, the need for CRRT was an independent risk factor for mortality. In the subset of patients on combined CRRT and ECMO, independent risk factors for mortality included higher age, lack of valvular heart disease, and lower serum albumin.
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Terapia de Substituição Renal Contínua , Oxigenação por Membrana Extracorpórea , Doenças das Valvas Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Albumina SéricaRESUMO
Asthma is a frequently chronic respiratory disease with inflammation and remodeling in the airway. OTUB1 has been reported to be associated with pulmonary diseases. However, the role and potential mechanism of OTUB1 in asthma remain unclear. The expressions of OTUB1 in the bronchial mucosal tissues of asthmatic children and TGF-ß1-induced BEAS-2B cells were determined. The biological behaviors were assessed in an asthma in vitro model using a loss-function approach. The contents of inflammatory cytokines were detected by ELISA kits. The related protein expressions were performed using western blot assay. Besides, the interaction between OTUB1 and TRAF3 was detected by Co-IP and ubiquitination assays. Our results showed that OTUB1 level was increased in asthmatic bronchial mucosal tissues and TGF-ß1-induced BEAS-2B cells. OTUB1 knockdown promoted proliferation, inhibited apoptosis and EMT of TGF-ß1-treated cells. The inhibition of OTUB1 attenuated the TGF-ß1-induced inflammation and remodeling. Furthermore, OTUB1 knockdown inhibited the deubiquitination of TRAF3 and further suppressed the activation of NLRP3 inflammasome. The overexpression of TRAF3 or NLRP3 reversed the positive role of OTUB1 knockdown in TGF-ß1-induced cells injury. Collectively, OTUB1 deubiquitinates TRAF3 to activate NLRP3 inflammasome, thereby leading to inflammation and remodeling of TGF-ß1-induced cells, and further promoting the pathogenesis of asthma.
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Asma , Fator de Crescimento Transformador beta1 , Criança , Humanos , Fator de Crescimento Transformador beta1/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Fator 3 Associado a Receptor de TNF/genética , Fator 3 Associado a Receptor de TNF/metabolismo , Inflamassomos/efeitos adversos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Linhagem Celular , Asma/induzido quimicamente , Asma/metabolismo , InflamaçãoRESUMO
ABSTRACT Introduction: There are few circulating biomarkers for valvular heart disease. Angiopoietin (Ang) 1, Ang2, and vascular endothelial growth factor are important inflammation-associated cytokines. The aim of this study was to investigate the clinical significance and association of Ang1, Ang2, and vascular endothelial growth factor in valvular heart disease. Methods: This is a retrospective study; a total of 62 individuals (valvular heart disease patients [n=42] and healthy controls [n=20]) were included. Plasma levels of Ang1, Ang2, and vascular endothelial growth factor were detected by enzyme-linked immunosorbent assays. We retrospectively collected the baseline characteristics and short-term outcomes; logistic regression was performed to identify predictor for short-term mortality. Results: Ang2 was significantly decreased in the valvular heart disease group compared with the healthy control group (P=0.023), while no significant difference was observed in the Ang1 and vascular endothelial growth factor levels. The Ang2 level of New York Heart Association (NYHA) I/II patients — but not NYHA III/IV patients — was significantly decreased compared with that of healthy control individuals (NYHA I/II: P=0.017; NYHA III/IV: P=0.485). Univariable logistic regression analysis indicated that Ang2 was a significant independent predictor for short-term mortality (odds ratio 18.75, P=0.033, 95% confidence interval 8.08-102.33). Ang1 was negatively correlated with Ang2 (P=0.032, Pearson's correlation coefficient =-0.317) and was positively correlated with vascular endothelial growth factor (P=0.019, Pearson's correlation coefficient = 0.359). Conclusion: Ang2 might serve as a therapeutic and prognostic target for valvular heart disease.
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INTRODUCTION: There are few circulating biomarkers for valvular heart disease. Angiopoietin (Ang) 1, Ang2, and vascular endothelial growth factor are important inflammation-associated cytokines. The aim of this study was to investigate the clinical significance and association of Ang1, Ang2, and vascular endothelial growth factor in valvular heart disease. METHODS: This is a retrospective study; a total of 62 individuals (valvular heart disease patients [n=42] and healthy controls [n=20]) were included. Plasma levels of Ang1, Ang2, and vascular endothelial growth factor were detected by enzyme-linked immunosorbent assays. We retrospectively collected the baseline characteristics and short-term outcomes; logistic regression was performed to identify predictor for short-term mortality. RESULTS: Ang2 was significantly decreased in the valvular heart disease group compared with the healthy control group (P=0.023), while no significant difference was observed in the Ang1 and vascular endothelial growth factor levels. The Ang2 level of New York Heart Association (NYHA) I/II patients - but not NYHA III/IV patients - was significantly decreased compared with that of healthy control individuals (NYHA I/II: P=0.017; NYHA III/IV: P=0.485). Univariable logistic regression analysis indicated that Ang2 was a significant independent predictor for short-term mortality (odds ratio 18.75, P=0.033, 95% confidence interval 8.08-102.33). Ang1 was negatively correlated with Ang2 (P=0.032, Pearson's correlation coefficient =-0.317) and was positively correlated with vascular endothelial growth factor (P=0.019, Pearson's correlation coefficient = 0.359). CONCLUSION: Ang2 might serve as a therapeutic and prognostic target for valvular heart disease.
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Doenças das Valvas Cardíacas , Fator A de Crescimento do Endotélio Vascular , Humanos , Angiopoietinas , Prognóstico , Estudos Retrospectivos , Fatores de Crescimento do Endotélio VascularRESUMO
Lung cancer is the leading cause of cancer-related mortality worldwide and cigarette smoking is reported to contribute to the lung cancer-related mortality. The present study aimed to investigate the molecular mechanism underlying nicotine-induced chemoresistance in lung cancer. The expression of microRNA (miR)-21-3p and its predicted target FOXO3a in lung cancer cells was detected via reverse transcription-quantitative PCR, in the presence or absence of nicotine. The regulatory effect of miR-21-3p and FOXO3a on lung cancer cell proliferation and apoptosis induced by docetaxel or cisplatin treatment was evaluated by performing Cell Counting Kit-8 and Annexin V/PI staining assays, respectively. The interaction between miR-21-3p and FOXO3a was analyzed by performing luciferase reporter assays and western blotting. FOXO3a overexpression rescue experiments were conducted in vitro and in vivo using a xenograft mouse model to assess the function of miR-21-3p/FOXO3a in lung cancer. Nicotine induced miR-21-3p expression in lung cancer cells in a dose-dependent manner. miR-21-3p downregulated FOXO3a expression by directly binding to the 3'-untranslated region of FOXO3a. Moreover, miR-21-3p knockdown sensitized lung cancer cells to docetaxel or cisplatin treatment. Mechanistically, FOXO3a was predicted as a direct target of miR-21-3p. FOXO3a overexpression promoted the chemosensitivity of lung cancer cells to docetaxel or cisplatin treatment. Furthermore, FOXO3a overexpression antagonized the regulatory function of miR-21-3p on docetaxel- or cisplatin-treated lung cancer cells. In the docetaxel- or cisplatin-treated lung cancer xenograft mouse model, miR-21-3p promoted chemoresistance via negatively regulating FOXO3a. Therefore, the present study demonstrated that nicotine-induced miR-21-3p promoted chemoresistance to docetaxel or cisplatin treatment via negatively regulating FOXO3a, which may serve as a novel therapeutic strategy for the treatment of patients with chemoresistant lung cancer.
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Previously, we demonstrated that the disheveled binding antagonist of ß-catenin 1 (DACT1) was involved in atrial fibrillation by regulating the reorganization of connexin 43 and ß-catenin in cardiomyocytes. Little is known, however, about DACT1 in human normal myocardial cells. Therefore, we used cardiomyocytes (CMs) derived from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) to investigate the role of DACT1 and its connection with ß-catenin and connexin 43. While the ESC-CMs and iPSC-CMs were differentiated using commercial differentiation kits, the cardiac-specific markers were detected by immunofluorescence. The expression level of DACT1 was detected using western blotting, whereas the interaction of DACT1 and connexin 43 or ß-catenin was detected by immunofluorescence and co-immunoprecipitation (co-IP) assays. Both H1-CMs and SF-CMs were immunostained for cardiac-specific markers, including Troponin I, Troponin T, α-actinin, NKX2.5, and GATA6. While DACT1 was not expressed in both H1 ESCs and SF-iPSCs, it was, however, highly expressed in differentiated CMs, being also localized in the cytoplasm and the nucleus of differentiated CMs. Interestingly, the DACT1 expression in different nuclei was different in the same multinucleated cell. Moreover, DACT1 colocalized with ß-catenin in both the cytoplasm and nucleus of differentiated CMs, and it also colocalized with connexin 43 in the perinuclear region and the gap junctions of differentiated CMs. Co-IP results showed that DACT1 could directly bind to ß-catenin and connexin 43. Taken together, DACT1 interacted with ß-catenin and connexin 43 in human-induced pluripotent stem cells-derived cardiomyocytes.
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Células-Tronco Pluripotentes Induzidas , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Diferenciação Celular , Conexina 43/genética , Conexina 43/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Miócitos Cardíacos/metabolismo , Proteínas Nucleares/metabolismo , beta Catenina/metabolismoRESUMO
BACKGROUND: Serum creatinine, an important diagnostic indicator for acute kidney injury (AKI), was considered to be a risk factor for cardiovascular disease. This study aimed to investigate the significance of postoperative serum creatinine in predicting the prognosis of cardiac surgery patients. METHODS: The Medical Information Mart for Intensive Care III (MIMIC-III) database was used to extract the clinical data. Adult (≥18 years) cardiac surgery patients in the database were enrolled. The correlation of postoperative serum creatinine with lengths of intensive care unit (ICU) stay was analyzed with Spearman correlation, and the association of postoperative serum creatinine with hospital mortality was analyzed with chi-square tests. Multivariable logistic regression was used to identify postoperative serum creatinine as an independent prognostic factor for hospital mortality. RESULTS: A total of 6,001 patients were enrolled in our study, among whom, 108 patients (1.8%) died in the hospital. Non-survivors had much higher postoperative serum creatinine levels (initial: 0.8 vs. 1.2 mg/dl, P < 0.001; maximum: 1.1 vs. 2.8 mg/dl, P < 0.001; minimum: 0.8 vs.1.1 mg/dl, P < 0.001). Positive correlations were observed between postoperative serum creatinine (P < 0.001) and lengths of ICU stay. For all models, postoperative initial creatinine, postoperative maximum creatinine, and postoperative minimum creatinine were all positively associated with hospital mortality (all P < 0.001). The predictive performance of postoperative serum creatinine was moderately good (area under the curve (AUC) for initial creatinine = 0.7583; AUC for maximum creatinine = 0.8413; AUC for minimum creatinine = 0.7063). CONCLUSIONS: This study demonstrated the potential to use postcardiac surgery serum creatinine as an outcome indicator.
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Aims: To explore the value of preoperative liver function tests (LFTs) for the prognosis of cardiac surgery patients without liver disease. Methods: The Medical Information Mart for Intensive Care III (MIMIC-III) database was used to extract the clinical data. Adult cardiac patients (≥18 years) without liver disease in the database were enrolled. The association of LFTs with the time of hospital stay and ICU stay was analyzed with the Spearman correlation. Survival curves were estimated using the Kaplan-Meier method and compared by the log-rank test. Multivariable logistic regression was used to identify LFTs that were independent prognostic factors of mortality. Results: A total of 2,565 patients were enrolled in this study. Albumin (ALB) was negatively associated with the time of hospital stay and ICU stay, while alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin were positively associated with the time of hospital stay and ICU stay (all p < 0.001). Abnormal ALB, ALT, AST, and total bilirubin were associated with lower 90-day and 4-year survival (all p < 0.001) and could be used as independent risk factors for hospital mortality and 90-day mortality. However, only ALB and total bilirubin were independent risk factors for 4-year mortality. Conclusion: Preoperative LFT abnormalities were associated with short-term and long-term prognosis of cardiac surgery patients without liver disease.
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OBJECTIVE: To explore the diagnostic value of FTO combined with CEA or CYFRA21-1 for nonsmall cell lung cancer (NSCLC) and to provide a theoretical basis for molecular diagnosis of NSCLC. METHODS: Totally, 60 patients with nonsmall cell lung cancer (NSCLC) treated in our hospital between Feb. 2018 and Feb. 2019 were enrolled into the patient group (Pat group) and 50 healthy individuals with normal physical examination results in our hospital over the same time span into the control group (Con group). Serum of each participant was collected, and then qRT-PCR was adopted for quantification of serum FTO and the chemiluminescence method for quantification of serum CEA and CYFRA21-1. Additionally, corresponding ROC curves were drawn for diagnostic value analyses of FTO, CEA, and CYFRA21-1 in NSCLC and Cox regression analysis was performed for analysis of independent factors impacting the patients' 3-year prognosis. RESULTS: The Pat group presented notably higher FTO, CEA, and CYFRA21-1 levels than the Con group (all P < 0.05), and patients with a high FTO level faced notably higher probabilities of stage III + IV and lymph node metastasis (LNM) (both P < 0.05). Additionally, according to ROC curve-based analysis, with a high level in patients with NSCLC, FTO had high specificity and sensitivity in diagnosing NSCLC; joint detection of it with CEA or CYFRA21-1 demonstrated a higher sensitivity in NSCLC diagnosis and presented a higher specificity in diagnosing early NSCLC compared with detection of CEA or CYFRA21-1 alone. According to Cox regression analysis, clinical stage, LNM, and FTO were independent risk factors impacting the prognosis of patients with LC (all P < 0.05). CONCLUSION: FTO presents a high level in NSCLC cases, and joint detection of it with CEA or CYFRA21-1 delivered a higher specificity in diagnosing NSCLC in contrast to detection of CEA or CYFRA21-1 alone, so the joint detection is worth popularizing in clinical scenarios.
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Background: Blood pressure variability (BPV) has long been considered a risk factor for cardiovascular events. We aimed to investigate whether post-operative systolic BPV was associated with early and late all-cause mortality in patients undergoing coronary artery bypass grafting (CABG). Methods: Clinical variables and blood pressure records within the first 24 h in the post-operative intensive care unit stay from 4,509 patients operated on between 2001 and 2012 were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. BPV was measured as the coefficient of the variability of systolic blood pressure, and we compared patients in the highest quartile with patients in the other three quartiles. Results: After full adjustment, patients in the highest quartile of BPV were at a higher risk of intensive care unit mortality (OR = 2.02, 95% CI: 1.11-3.69), 30-day mortality (OR = 1.92, 95% CI: 1.22-3.02), and 90-day mortality (HR = 1.64, 95% CI: 1.19-2.27). For 2,892 patients with a 4-year follow-up, the association between a higher post-operative BPV and the risk of 4-year mortality was not significant (HR = 1.17, 95% CI: 0.96-1.42). The results were supported by the comparison of survival curves and remained generally consistent in the subgroup analyses and sensitivity analyses. Conclusions: Our findings demonstrated that in patients undergoing CABG, a higher post-operative BPV was associated with a higher risk of early mortality while the association was not significant for late mortality. Post-operative BPV can support doctors in identifying patients with potential hemodynamic instability and making timely clinical decisions.
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AIM: The purpose of the present study was to explore the function and mechanism of tensin 1 (TNS1) in non-small cell lung cancer (NSCLC) progression. METHODS: The expression of TNS1 in NSCLC cells and tissues was assessed by RT-PCR and Western blot. Besides, Kaplan-Meier survival analysis was recruited to explore the association between TNS1 and NSCLC. Cell growth was analyzed by MTT and flow cytometry assay, while cell metastasis was determined by wound healing and transwell assays. The targeting relationship between TNS1 and miR-152 was assessed by luciferase activity assays. And Western blot was employed to determine the expression of related proteins of Akt/mTOR/RhoA pathway. RESULTS: TNS1 level was boosted in NSCLC cells and tissues, related to the prognosis of NSCLC patients. Furthermore, it was proved that TNS1 promoted the growth and metastasis of NSCLC cells via Akt/mTOR/RhoA pathway. And miR-152 targeted TNS1 to affect the progression of NSCLC. CONCLUSION: miR-152/TNS1 axis inhibits the progression of NSCLC by Akt/mTOR/RhoA pathway.
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Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Tensinas/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/metabolismoRESUMO
AIMS: Influenza A virus (IAV) infection accelerates the inflammatory injury of lung epithelial cells that contributes to pulmonary lesion. Recently, stromal interaction molecule 1 (STIM1) was found to mediate cellular immune response and participated in lung tumorigenesis. Our study aimed to illustrate the function and mechanism of STIM1 in IAV-induced inflammation injury and oxidative stress of lung epithelial cells. MAIN METHODS: We evaluated the levels of STIM1 in IAV-infected patients' serum and BEAS-2B cells using RT-qPCR, Elisa and western blotting methods. MTT and Elisa were performed to measure cell viability and cytokine contents. Besides, ROS intensity, SOD contents and cell apoptosis were detected based on DCFH-DA probe, colorimetry and cell death kits. A luciferase assay and Pearson's correlation analysis evaluated the associations between target genes. KEY FINDINGS: STIM1 was dramatically up-regulated in IAV-infected patients' serum and BEAS-2B cells. Silencing STIM1 in vitro inhibited oxidative stress and inflammatory responses induced by IAV, and reversed cell viability and suppressed apoptosis. Moreover, miR-223 and NLRP3 were negatively and positively correlated with STIM1. STIM1 was found to regulate NLRP3 expression by binding the AACUGAC motif in miR-223. STIM1/miR-223/NLRP3 axis modulated IAV-induced inflammation injury of lung epithelial cells. SIGNIFICANCE: Our evidence indicated that silencing STIM1 alleviated IAV-induced inflammation injury of lung epithelial cells by inactivating NLRP3 and inflammasome via promoting miR-223 expression. These findings may contribute to understand the mechanism of IAV-induced lung injury and help for therapy of IAV infection.
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Inflamassomos/metabolismo , Inflamação/patologia , Influenza Humana/complicações , Pulmão/imunologia , MicroRNAs/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas de Neoplasias/metabolismo , Molécula 1 de Interação Estromal/metabolismo , Adulto , Apoptose , Estudos de Casos e Controles , Sobrevivência Celular , Citocinas/metabolismo , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Células Epiteliais/virologia , Feminino , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Vírus da Influenza A/isolamento & purificação , Influenza Humana/virologia , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas de Neoplasias/genética , Prognóstico , Molécula 1 de Interação Estromal/genéticaRESUMO
AIMS: The present study explored the function and regulatory mechanism of High mobility group box 1 (HMGB1) in asthma. MAIN METHODS: OVA (ovalbumin)-induced asthmatic mice model and LPS-treated cellular model were established in this study. Airway inflammation was measured through detecting the expression of IL-4, IL-5, IL-13 and Interferon-γ (IFN-γ) in serum and BALF (bronchoalveolar lavage fluid) by ELISA kits. Bioinformatics predictive analysis, ChIP assays, Luciferase reporter assay and Western blotting were used to explore the relation between HMGB1 and HSF1 (Heat shock factor 1). KEY FINDINGS: HMGB1 expression was increased in OVA-induced asthmatic mice. Silencing HMGB1 attenuated the increasing of IgE, inflammatory factors (IL-4, IL-5 and IL-13), and airway hyperresponsiveness that induced by OVA. In addition, our study found that HSF1 directly bind with the HMGB1 promoter and negatively regulation of HMGB1. HSF-1 were upregulated in OVA-induced asthmatic mice, and knockdown of HSF1 aggravated the OVA-induced airway inflammation and airway hyperreactivity in mice may through promoting the expression of HMGB1 and the activation of the Toll-like receptor 4 (TLR4)/Myeloid differentiation primary response 88 (MyD88)/Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signal pathway. SIGNIFICANCE: The expression of HMGB1 could be negatively regulated by HSF1, and the TLR4/MyD88/NF-κB signal pathway was involved in HSF1/HMGB1-mediated regulation of asthma.
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Asma/patologia , Proteína HMGB1/metabolismo , Fatores de Transcrição de Choque Térmico/fisiologia , Inflamação/patologia , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Apoptose , Asma/induzido quimicamente , Asma/genética , Asma/metabolismo , Sequência de Bases , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/metabolismo , Hiper-Reatividade Brônquica/patologia , Citocinas/metabolismo , Células HEK293 , Proteína HMGB1/genética , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/genética , NF-kappa B/genética , Ovalbumina/toxicidade , Regiões Promotoras Genéticas , Transdução de Sinais , Receptor 4 Toll-Like/genéticaRESUMO
An atypically large, free-floating thrombus extending from primary pulmonary malignancy into the left atrium (LA) is a rare phenomenon. Here, we report a 61-year-old man presenting with a large mass in the lower lobe of the left lung, extending to LA via the left inferior pulmonary vein.The thrombus remained clinically silent and was detected by computed tomography (CT) and transthoracic echocardiography. To prevent life-threatening complications including systemic embolism and sudden death, the patient underwent surgical excision of the mass under cardiopulmonary bypass. Pathology of the tumor and the embolus was confirmed as moderately differentiated squamous cell carcinoma. Furthermore, immunohistochemical studies demonstrated consistency of the tumor cells in this pathological category.The patient tolerated the surgery well and his condition began to improve gradually after the operation.
Assuntos
Carcinoma de Células Escamosas/complicações , Átrios do Coração , Neoplasias Pulmonares/complicações , Veias Pulmonares , Trombose/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Trombose/etiologiaRESUMO
A class of adhesion protein that occurs in the membrane with both extracellular and intracellular domain and play vital role in maintaining multicellularity is TRASK, also called CUB-domain containing protein1, CD318 (CDCP1). Specifically, in the current study, documented aggressive grades of lung cancers and distant metastatic tissues were examined for protein interactions of Trask and compared with lung cancer variants in situ. The intracellular domain of Trask has the ability to undergo tyrosine phosphorylation and thereafter undergo increased genomic expression, as well as interact with cytoskeletal proteins in the cell periphery and other local signal transduction machinery to induce invadopodia formation and distant metastasis. We incorporated proximity ligation assay to examine protein interactions of Trask in metastatic lung cancer tissues and compare with advanced and low-grade lung cancers restricted to the primary site of origins. Here, we provide direct evidence that activated Trask, which is a phosphorylated form, binds with cytoskeletal proteins actin and spectrin. These interactions were not seen in locally growing lung cancer and cancer in situ. These interactions may be responsible for invadopodia formation and breaking free from a multicellular environment. Functional studies demonstrated interaction between Trask and the STOCs Orai1 and Stim1. Calcium release from internal stores was highest in metastatic lung cancers, suggesting this mechanism as an initial stimulus for the cells to respond chaotically to external growth factor stimulation, especially in aggressive metastatic variants of lung cancers. Recently, inhibitors of STOCs have been identified, and preclinical evidence may be obtained whether these drugs may be of benefit in preventing the deadly consequences of lung cancer.