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Following myocardial ischemic injury, the most effective clinical intervention is timely restoration of blood perfusion to ischemic but viable myocardium to reduce irreversible myocardial necrosis, limit infarct size, and prevent cardiac insufficiency. However, reperfusion itself may exacerbate cell death and myocardial injury, a process commonly referred to as ischemia/reperfusion (I/R) injury, which primarily involves cardiomyocytes and cardiac microvascular endothelial cells (CMECs) and is characterized by myocardial stunning, microvascular damage (MVD), reperfusion arrhythmia, and lethal reperfusion injury. MVD caused by I/R has been a neglected problem compared to myocardial injury. Clinically, the incidence of microvascular angina and/or no-reflow due to ineffective coronary perfusion accounts for 5-50% in patients after acute revascularization. MVD limiting drug diffusion into injured myocardium, is strongly associated with the development of heart failure. CMECs account for > 60% of the cardiac cellular components, and their role in myocardial I/R injury cannot be ignored. There are many studies on microvascular obstruction, but few studies on microvascular leakage, which may be mainly due to the lack of corresponding detection methods. In this review, we summarize the clinical manifestations, related mechanisms of MVD during myocardial I/R, laboratory and clinical examination means, as well as the research progress on potential therapies for MVD in recent years. Better understanding the characteristics and risk factors of MVD in patients after hemodynamic reconstruction is of great significance for managing MVD, preventing heart failure and improving patient prognosis.
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Insuficiência Cardíaca , Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Humanos , Células Endoteliais/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Insuficiência Cardíaca/metabolismoRESUMO
This review summarizes the ongoing researches regarding etiology, epidemiology, transmission dynamics, treatment, and prevention and control strategies of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with comparison to severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and pandemic H1N1 virus. SARS-CoV-2 may be originated from bats, and the patients and asymptomatic carriers are the source of epidemic infection. The virus can be transmitted human-to-human through droplets and close contact, and people at all ages are susceptible to this virus. The main clinical symptoms of the patients are fever and cough, accompanied with leukocytopenia and lymphocytopenia. Effective drugs have been not yet available thus far. In terms of the prevention and control strategies, vaccine development as the primary prevention should be accelerated. Regarding the secondary prevention, ongoing efforts of the infected patients and close contacts quarantine, mask wearing promotion, regular disinfection in public places should be continued. Meanwhile, rapid detection kit for serological monitoring of the virus in general population is expected so as to achieve early detection, early diagnosis, early isolation and early treatment. In addition, public health education on this disease and prevention should be enhanced so as to mitigate panic and mobilize the public to jointly combat the epidemic.
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Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Doenças Assintomáticas , Betacoronavirus/patogenicidade , COVID-19 , Teste para COVID-19 , Vacinas contra COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Tosse/etiologia , Diagnóstico Precoce , Febre/etiologia , Humanos , Vírus da Influenza A Subtipo H1N1 , Leucopenia/etiologia , Linfopenia/etiologia , Coronavírus da Síndrome Respiratória do Oriente Médio , Pandemias/prevenção & controle , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , SARS-CoV-2 , Prevenção Secundária , Vacinas ViraisRESUMO
Background: Ischemic Heart Disease (IHD) is the leading cause of death from cardiovascular disease. Currently, most studies have focused on factors influencing IDH or mortality risk, while few predictive models have been used for mortality risk in IHD patients. In this study, we constructed an effective nomogram prediction model to predict the risk of death in IHD patients by machine learning. Methods: We conducted a retrospective study of 1,663 patients with IHD. The data were divided into training and validation sets in a 3:1 ratio. The least absolute shrinkage and selection operator (LASSO) regression method was used to screen the variables to test the accuracy of the risk prediction model. Data from the training and validation sets were used to calculate receiver operating characteristic (ROC) curves, C-index, calibration plots, and dynamic component analysis (DCA), respectively. Results: Using LASSO regression, we selected six representative features, age, uric acid, serum total bilirubin, albumin, alkaline phosphatase, and left ventricular ejection fraction, from 31 variables to predict the risk of death at 1, 3, and 5 years in patients with IHD, and constructed the nomogram model. In the reliability of the validated model, the C-index at 1, 3, and 5 years was 0.705 (0.658-0.751), 0.705 (0.671-0.739), and 0.694 (0.656-0.733) for the training set, respectively; the C-index at 1, 3, and 5 years based on the validation set was 0.720 (0.654-0.786), 0.708 (0.650-0.765), and 0.683 (0.613-0.754), respectively. Both the calibration plot and the DCA curve are well-behaved. Conclusion: Age, uric acid, total serum bilirubin, serum albumin, alkaline phosphatase, and left ventricular ejection fraction were significantly associated with the risk of death in patients with IHD. We constructed a simple nomogram model to predict the risk of death at 1, 3, and 5 years for patients with IHD. Clinicians can use this simple model to assess the prognosis of patients at the time of admission to make better clinical decisions in tertiary prevention of the disease.
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BACKGROUND: Ischemic heart disease (IHD) has a high mortality in the population. Although serum creatinine (Cr) and serum total bilirubin (TBil) are rapid and readily available biomarkers in routine blood tests, there is a lack of literature on the prognostic value of combined Cr and TBil tests for IHD. This study aimed to evaluate a combined equation based on Cr and TBil to predict the long-term risk of death in IHD and to find indicators sensitive to the prognosis of IHD patients. METHOD: In this study, 2625 patients with IHD were included, and the combined value and combined equations of Cr and TBil were obtained by logistic regression analysis based on Cr and TBil collected at the time of admission. Patients were divided into four groups according to the quartiles of the combined value. COX proportional hazard regression model was used to analyze the risk factors for long-term death in IHD patients. Receiver operating characteristic (ROC) curves were used to evaluate the prognostic effect of Cr, TBil and combined value on long-term death events. RESULTS: Logistic regression analysis was performed for long-term death events with Cr and TBil as independent variables, and the logit regression model was Logit(P) = 0.0129×TBil+0.007×Cr-0.417. Multifactorial Cox regression analysis showed that high values of the equation were independent risk factors for long-term death events (all-cause death: HR 1.457, 95% CI 1.256-1.689, P<0.001; cardiovascular death: HR 1.452, 95% CI 1.244-1.695, P<0.001). Combined Cr and TBil value are more valuable in predicting long-term death (AUC: 0.609, 95% CI 0.587-0.630, P<0.001). CONCLUSION: Combined Cr and TBil assay is superior to single biomarkers for predicting long-term death in patients with IHD. High values of the equation are independent predictors of long-term death and can be used to identify patients at high risk for IHD.
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Bilirrubina , Isquemia Miocárdica , Humanos , Creatinina , Estudos de Coortes , Prognóstico , Biomarcadores , Isquemia Miocárdica/diagnóstico , Estudos RetrospectivosRESUMO
Background: The triglyceride-glucose (TyG) index is regarded as an independent predictor of cardiovascular (CV) consequences and a reliable surrogate measure of insulin resistance (IR). However, the predictive significance of the TyG index in patients with type 2 diabetes mellitus (T2DM) and ischemic cardiomyopathy (ICM) remains unknown. Methods: This study included 1514 consecutive subjects with ICM and T2DM. The tertile of the TyG index values was used to categorize these patients into three groups. Major adverse cardiac and cerebral events (MACCEs) were also noted. The TyG index was calculated using the [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2] equation. Results: After adjusting for age, BMI, and other potential confounders, the scores of multivariate Cox proportional hazards regression models for chest pain [9.056 (4.370 to 18.767), p<0.001], acute myocardial infarction [4.437 (1.420 to 13.869), p=0.010], heart failure [7.334 (3.424 to 15.708), p<0.001], cardiogenic shock [3.707 (1.207 to 11.384), p=0.022], malignant arrhythmia [5.309 (2.367 to 11.908), p<0.001], cerebral infarction [3.127 (1.596 to 6.128), p<0.001], gastrointestinal bleeding [4.326 (1.612 to 11.613), p=0.004], all-cause death [4.502 (3.478 to 5.827), p<0.001] and cumulative incidence of MACCEs [4.856 (3.842 to 6.136), p<0.001] increased significantly with an increase in TyG index levels (all p<0.05). Time-dependent ROC analysis revealed that the area under the TyG index curve (AUC) reached 0.653 in the 3rd year, 0.688 in the 5th year, and 0.764 in the 10th year. The predictive efficiency of this model on MACCEs improved [net reclassification improvement (NRI): 0.361 (0.253 to 0.454); C-index: 0.678 (0.658 to 0.698); integrated discrimination improvement (IDI): 0.138 (0.098 to 0.175), all p<0.05] following the incorporation of the TyG index into the base risk model. Conclusion: TyG index could be useful in predicting MACCEs and initiating preventive measures in subjects with ICM and T2DM.
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Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), shows a favorable anti-tumor effect while resistance is a barrier impeding patients from benefiting from it. Thus, more efforts are needed to lift this restriction. Herein, we first find that solute carrier family 27 member 5 (SLC27A5/FATP5), an enzyme involved in the metabolism of fatty acid and bile acid, is downregulated in sorafenib-resistant HCC. SLC27A5 deficiency facilitates the resistance towards sorafenib in HCC cells, which is mediated by suppressing ferroptosis. Further mechanism studies reveal that the loss of SLC27A5 enhances the glutathione reductase (GSR) expression in a nuclear factor erythroid 2-related factor 2 (NRF2)-dependent manner, which maintains glutathione (GSH) homeostasis and renders insensitive to sorafenib-induced ferroptosis. Notably, SLC27A5 negatively correlates with GSR, and genetic or pharmacological inhibition of GSR strengthens the efficacy of sorafenib through GSH depletion and the accumulation of lipid peroxide products in SLC27A5-knockout and sorafenib-resistant HCC cells. Based on our results, the combination of sorafenib and carmustine (BCNU), a selective inhibitor of GSR, remarkably hamper tumor growth by enhancing ferroptotic cell death in vivo. In conclusion, we describe that SLC27A5 serves as a suppressor in sorafenib resistance and promotes sorafenib-triggered ferroptosis via restraining the NRF2/GSR pathway in HCC, providing a potential therapeutic strategy for overcoming sorafenib resistance.
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Antineoplásicos , Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Glutationa Redutase/metabolismo , Glutationa Redutase/farmacologia , Glutationa Redutase/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteínas de Transporte de Ácido GraxoRESUMO
Backgrounds: Hypertension stands as the predominant global cause of mortality. A notable deficiency exists in terms of predictive models for mortality among individuals with hypertension. We aim to devise an effective nomogram model that possesses the capability to forecast all-cause mortality within hypertensive populations. Methods: The data for this study were drawn from nine successive cycles of the National Health and Nutrition Examination Survey (NHANES) spanning the years from 1999 to 2016. The dataset was partitioned into training and validation sets at a 7:3 ratio. We opted for clinical practice-relevant indicators, applied the least absolute shrinkage and selection operator (LASSO) regression to identify the most pertinent variables, and subsequently built a nomogram model. We also employed concordance index, receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA) to assess the model's validity. Results: A total of 17,125 hypertensive participants were included in this study with a division into a training set (11,993 individuals) and a validation set (5,132 individuals). LASSO regression was applied for the training set to obtain nine variables including age, monocytes, neutrophils, serum albumin, serum potassium, cardiovascular disease, diabetes, serum creatinine and glycated hemoglobin (HbA1C), and constructed a nomogram prediction model. To validate this model, data from the training and validation sets were used for validation separately. The concordance index of the nomogram model was 0.800 (95% CI, 0.792-0.808, p < 0.001) based on the training set and 0.793 (95% CI, 0.781-0.805, p < 0.001) based on the validation set. The ROC curves, calibration curves, and DCA curves all showed good predictive performance. Conclusion: We have developed a nomogram that effectively forecasts the risk of all-cause mortality among American adults in hypertensive populations. Clinicians may use this nomogram to assess patient's prognosis and choose a proper intervention in a timely manner.
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Leukocyte differentiation antigen 74 (CD74), also known as invariant chain, is a molecular chaperone of major histocompatibility complex class II (MHC II) molecules involved in antigen presentation. CD74 has recently been shown to be a receptor for the macrophage migration inhibitory factor family proteins (MIF/MIF2). Many studies have revealed that CD74 plays an important role in cardiovascular disease. In this review, we summarize the structure and main functions of CD74 and then focus on the recent research progress on the role of CD74 in cardiovascular diseases. In addition, we also discuss potential treatment strategies that target CD74. Our systematic review of the role of CD74 in cardiovascular disease will fill some knowledge gaps in the field.
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INTRODUCTION: Platelet activation participates in the development of both coronary artery disease (CAD) and circulating microparticles (MPs). As a commonly used medicine for coronary heart disease, whether aspirin affects the function of MPs remains unclear. AIMS: This study was designed to test MPs from healthy subjects, and stable angina (SA) patients before and after aspirin administration were obtained. MPs origins were tested by flow cytometry. Rat thoracic aortas were incubated with MPs (with or without aspirin) to determine the effects of MPs on expression of ERK1/2, JNKs, and p38 MAPK. Affect on levels of NF-κB, VCAM-1, NO, and O2-. RESULTS: Compared with healthy subjects, MPs concentrations increased in SA patients, but decreased after aspirin administration. According to flow cytometry, aspirin mainly decreased platelet-derived MP. MPs from SA patients decreased the expression of ERK1/2, increased expression of p38 MAPKs, JNKs. Increased NF-κB, VCAM-1, and (O2-) levels decreased NO content. Aspirin therapy significantly inhibited function of MPs from SA patients, and pathway inhibitors (ERK1/2 inhibitor PD98059, p38 MAPKs inhibitor SB203580, NF-kB inhibitor PDTC) show similar effects with aspirin. CONCLUSION: These results indicate that the pro-inflammatory, oxidative stress, procoagulant, and adhesion properties of MPs can be partly blocked by aspirin via the ERK-NO/O2- and p38 -NF-κB-VCAM-1 signal pathway, which clarified other functions beyond anti-atherothrombotic of aspirin.
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Angina Estável/patologia , Aspirina/uso terapêutico , Micropartículas Derivadas de Células , Endotélio Vascular/lesões , Endotélio Vascular/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Inibidores da Agregação Plaquetária/uso terapêutico , Animais , Aorta Torácica/patologia , Endotélio Vascular/efeitos dos fármacos , Voluntários Saudáveis , Humanos , Masculino , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Ratos , Superóxidos/metabolismo , Molécula 1 de Adesão de Célula Vascular/biossíntese , Molécula 1 de Adesão de Célula Vascular/genéticaRESUMO
OBJECTIVES: Percutaneous coronary interventions (PCIs) save countless acute myocardial infarction (AMI) patients. However, endothelial injury is still an inevitable complication. Circulating microparticles (MPs) play important roles in vascular dysfunction. Whether PCI affects function of MPs remains unclear. METHODS: MPs were obtained from AMI patients (nâ=â38) both preoperatively and 24âh after PCI, and healthy subjects (nâ=â20). MPs origins were tested by flow cytometry. Rat thoracic aortas were incubated with MPs to determine the effects of MPs on phosphorylation of endothelial nitric oxide synthase (eNOS), caveolin-1 expression, eNOS association with heat shock protein 90 (Hsp90), generation of nitric oxide (NO) and superoxide anion (O2), and endothelial-dependent vasodilatation. RESULTS: Compared with healthy subjects, MP concentrations increased in AMI patients. Undergoing PCI had no further effect on MPs concentration, but it results in increased endothelial-derived MPs proportion and decreased platelet-derived MP ratio. MPs from AMI patients decreased eNOS phosphorylation at Ser1177, increased eNOS phosphorylation at T495 and caveolin-1 expression, decreased eNOS association with Hsp90, decreased NO production but increased (O2) generation, damaged endothelial-dependent vasodilatation. All of these effects of MPs were strengthened by PCI. CONCLUSIONS: PCI further enhances the vascular injury effect of MPs. Circulating MPs may be a potential therapeutic target for patients undergoing PCI.
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Micropartículas Derivadas de Células , Infarto do Miocárdio , Óxido Nítrico Sintase Tipo III/biossíntese , Intervenção Coronária Percutânea , Vasodilatação , Adulto , Animais , Micropartículas Derivadas de Células/metabolismo , Micropartículas Derivadas de Células/transplante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/cirurgia , Ratos , Ratos Sprague-DawleyRESUMO
The main objective of this study was to investigate the epidemiology, drug resistance and ß-lactamase genotype distribution of enteropathogenic Escherichia coli (EPEC) isolated from pediatric patients with diarrhea in southern China. The prevalence of EPEC in children with diarrhea was 3.53%. The commonest serotypes were O55:K59 and O126:K71, and the typical EPEC were more prevalent than atypical EPEC (51 vs 7). Isolates from this region were most commonly found to be resistant to ampicillin and cotrimoxazole, followed by chloramphenicol, ceftriaxone, and ceftazidime. More than 96% of the strains were susceptible to cefoperazone/sulbactam and imipenem. The most common ß-lactamase genotypes identified in 58 strains were blaCTX-M-1 (60.3%), blaTEM (56.9%), blaCTX-M-9 (27.6%), and blaSHV (15.5%). Among 58 isolates, 22 strains were found to harbor one ß-lactamase gene, and the proportions of resistance to ampicillin, cotrimoxazole, chloramphenicol, ceftriaxone, and ceftazidime, were 81.8%, 63.6%, 40.9%, 18.2%, and 9.1%, respectively. A further 30 strains carrying multiple ß-lactamase genes had increased resistance to the above antimicrobial agents (100%, 83.3%, 70.0%, 60.0%, and 30.0%, respectively). In contrast, antibiotic resistance in the last 6 strains without a detectable ß-lactamase gene was substantially reduced. Drug resistance may be associated with the ß-lactamase gene number, with a greater the number of ß-lactamase genes resulting in higher antibiotic resistance.
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Antibacterianos/farmacologia , Diarreia/microbiologia , Escherichia coli Enteropatogênica/efeitos dos fármacos , Escherichia coli Enteropatogênica/genética , Infecções por Escherichia coli/microbiologia , beta-Lactamases/genética , Pré-Escolar , China/epidemiologia , Diarreia/epidemiologia , Farmacorresistência Bacteriana , Escherichia coli Enteropatogênica/enzimologia , Infecções por Escherichia coli/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , PrevalênciaRESUMO
The relax circle DNA (rcDNA) sequence and the covalently closed circle DNA (cccDNA) sequence in hepatitis B virus (HBV) are crucial regions for HBV infections. To analyze mutations in rcDNA and cccDNA, DNA sequencing is often used, although it is time-consuming and expensive. Herein, we report a simple, economic, albeit accurate allele-specific polymerase chain reaction (AS-PCR) to detect mutations in these regions of HBV. This method can be extensively used to screen for mutations at specific positions of HBV genome.