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Rationale: Autophagy dysregulation is known to be a mechanism of doxorubicin (DOX)-induced cardiotoxicity (DIC). Mitochondrial-Endoplasmic Reticulum Contacts (MERCs) are where autophagy initiates and autophagosomes form. However, the role of MERCs in autophagy dysregulation in DIC remains elusive. FUNDC1 is a tethering protein of MERCs. We aim to investigate the effect of DOX on MERCs in cardiomyocytes and explore whether it is involved in the dysregulated autophagy in DIC. Methods: We employed confocal microscopy and transmission electron microscopy to assess MERCs structure. Autophagic flux was analyzed using the mCherry-EGFP-LC3B fluorescence assay and western blotting for LC3BII. Mitophagy was studied through the mCherry-EGFP-FIS1 fluorescence assay and colocalization analysis between LC3B and mitochondria. A total dose of 18 mg/kg of doxorubicin was administrated in mice to construct a DIC model in vivo. Additionally, we used adeno-associated virus (AAV) to cardiac-specifically overexpress FUNDC1. Cardiac function and remodeling were evaluated by echocardiography and Masson's trichrome staining, respectively. Results: DOX blocked autophagic flux by inhibiting autophagosome biogenesis, which could be attributed to the downregulation of FUNDC1 and disruption of MERCs structures. FUNDC1 overexpression restored the blocked autophagosome biogenesis by maintaining MERCs structure and facilitating ATG5-ATG12/ATG16L1 complex formation without altering mitophagy. Furthermore, FUNDC1 alleviated DOX-induced oxidative stress and cardiomyocytes deaths in an autophagy-dependent manner. Notably, cardiac-specific overexpression of FUNDC1 protected DOX-treated mice against adverse cardiac remodeling and improved cardiac function. Conclusions: In summary, our study identified that FUNDC1-meditated MERCs exerted a cardioprotective effect against DIC by restoring the blocked autophagosome biogenesis. Importantly, this research reveals a novel role of FUNDC1 in enhancing macroautophagy via restoring MERCs structure and autophagosome biogenesis in the DIC model, beyond its previously known regulatory role as an mitophagy receptor.
Subject(s)
Autophagy , Cardiotoxicity , Doxorubicin , Endoplasmic Reticulum , Membrane Proteins , Mitochondrial Proteins , Myocytes, Cardiac , Animals , Doxorubicin/adverse effects , Doxorubicin/pharmacology , Mice , Autophagy/drug effects , Cardiotoxicity/metabolism , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/drug effects , Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum/drug effects , Membrane Proteins/metabolism , Membrane Proteins/genetics , Mitochondrial Proteins/metabolism , Mitochondrial Proteins/genetics , Mitochondria/metabolism , Mitochondria/drug effects , Mitophagy/drug effects , Male , Autophagosomes/metabolism , Autophagosomes/drug effects , Mice, Inbred C57BL , Disease Models, AnimalABSTRACT
This study outlines the development of a low line density, small blaze angle grating, optimized for a visible to short-wave infrared hyperspectral camera. An analysis of grating specifications was conducted to meet the precise requirements of this application, particularly focusing on the stringent tolerance limits for the blaze angle. A specialized ruling tool adjustment device was designed to adhere to these exacting blaze angle tolerances. The grating groove shape was examined using atomic force microscopy (AFM), and the theoretical diffraction efficiency of the grating was calculated based on these observations. Additionally, laser-based methods were employed to measure the actual diffraction efficiency of the grating, while interferometry was used to assess the grating's diffraction wavefront. The test results demonstrate our capability to fabricate high-quality gratings with a low line density and small blaze angles that are suitable for advanced hyperspectral imaging applications.
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Acidification can seriously affect the growth of tea trees and the yield and quality of tea leaves. In this study, we analyzed the effects of acidification on the physicochemical properties, microorganisms and metabolites of tea rhizosphere soils with different pH values, and the results showed that with the increase of soil pH, the organic matter content, cation exchange capacity, microbial biomass carbon, microbial biomass nitrogen, microbial respiration intensity, bacterial number and actinomyces number in tea rhizosphere soil all showed an increasing trend, while the fungi number decreased. The results of soil metabolite analysis showed that 2376, 2377 and 2359 metabolites were detected in tea rhizosphere soil with pH values of 3.29, 4.74 and 5.32, respectively, and the number of similar compounds reached 2331, accounting for more than 98%. The results of soil metabolite content analysis showed that with the increase of soil pH, the total contents of metabolite of tea rhizosphere soil increased significantly. The results of correlation analysis between physicochemical indexes of soil and microorganisms and soil metabolites showed that physicochemical indexes of soil and microorganisms were significantly correlated with 221 soil metabolites, among which 55 were significantly positively correlated and 166 were significantly negatively correlated. Based on correlation interaction network analysis, 59 characteristic compounds were obtained and divided into 22 categories, among which 7 categories compounds showed a significant increasing trend with the increase of soil pH, while the other 15 categories compounds showed the opposite trend. Based on the functional analysis of characteristic metabolites, this study found that with the increase of soil pH in tea rhizosphere, the diversity and number of soil microorganisms increased, and the cyclic ability of C and N of tea rhizosphere soil was enhanced, which in turn might lead to the enhancement of resistance of tea tree and promote the growth of tea tree.
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OBJECTIVE: To investigate the association between baseline hemoglobin A1c (HbA1c) levels and bleeding in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) who underwent percutaneous coronary intervention (PCI). METHODS: This observational cohort study enrolled 6283 consecutive NSTE-ACS patients undergoing PCI from January 1, 2010 to December 31, 2014. Based on baseline HbA1c levels, the patients were divided into the group with HbA1c < 7% ( n = 4740) and the group with HbA1c ≥ 7% (n = 1543). The primary outcomes are major bleeding (BARC grades 3-5) and all-cause death during follow-up. RESULTS: Of patients enrolled, 4705 (74.9%) were male, and 2143 (34.1%) had a history of diabetes mellitus, with a mean (SD) age of 64.13 (10.32) years. The median follow-up duration was 3.21 years. Compared with the patients with HbA1c < 7%, the risk of major bleeding events during follow-up was higher in patients with HbA1c ≥ 7% (adjusted hazard ratio [HR] = 1.57; 95% confidence interval [CI]: 1.01-2.44; P = 0.044), while the risk of all-cause death during follow-up was not associated with the higher HbA1c levels (adjusted HR = 0.88; 95% CI: 0.66-1.18; P = 0.398). CONCLUSIONS: Compared with the lower baseline HbA1c levels, the higher baseline HbA1c levels were associated with an increase in long-term bleeding risk in NSTE-ACS patients undergoing PCI, though higher baseline HbA1c levels were not associated with the higher risk in all-cause death.
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Frying is a common food processing method because fried food is popular with consumers for its attractive colour and crisp taste. What's concerning is that the complex physical and chemical reactions occurring during deep frying are harmful to the well-being of people. For this reason, researchers proposed various detecting methods to assess frying oil deterioration. Some studies design sensor probe, others utilize spectroscopic related methods. However, these methods all need the participating of professionals and expensive instruments. Some of the methods can only function on a fixed temperature. To fix the defects of the above models, in this study, we make use of recent advances in machine learning, specifically generative adversarial networks (GAN). We propose a GAN-based regression model to predict frying oil deterioration. First, we conduct deep frying experiments and record the values of indexes we choose under different temperature and frying time. After collecting the data, we build a GAN-based regression model and train it on the dataset. Finally, we test our model on the test set and analyze the experimental results. Our results suggest that the proposed model can predict frying oil deterioration without experiments. Our model can be applied to other regression problems in various research areas, including price forecasting, trend analysis and so on.
Subject(s)
Cooking , Hot Temperature , Cooking/methods , Food Handling/methods , Humans , Taste , TemperatureABSTRACT
Background: Infection during hospitalization is a serious complication among patients who suffered from acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI); however, there are no suitable and accurate means to assess risk. This study aimed to develop and validate a simple scoring system to predict post-AMI infection in such patients. Methods: All patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI consecutively enrolled from January 2010 to May 2016 were served as derivation cohort, and those from June 2016 to May 2018 as validation cohort, respectively. The primary endpoint was post-AMI infection during hospitalization, and all-cause death and major adverse cardiovascular events (MACE) were considered as secondary endpoints. The simplified risk model was established using logistic regression. The area under the receiver operating curve and calibration of predicted and observed infection risk were calculated. Results: A 24-point risk score was developed, with infection risk ranging from 0.7 to 99.6% for patients with the lowest and highest score. Seven variables including age, Killip classification, insulin use, white blood cell count, serum albumin, diuretic use, and transfemoral approach were included. This model achieved the same high discrimination in the development and validation cohort (C-statistic:0.851) and revealed adequate calibration in both datasets. The incidences of post-AMI infection increased steadily across risk score groups in both development (1.3, 5.1, 26.3, and 69.1%; P < 0.001) and validation (1.8, 5.9, 27.2, and 79.2%; P < 0.001) cohort. Moreover, the risk score demonstrated good performance for infection, in-hospital all-cause death, and MACE among these patients, as well as in patients with the non-ST-elevation acute coronary syndrome. Conclusion: This present risk score established a simple bedside tool to estimate the risk of developing infection and other in-hospital outcomes in patients with STEMI undergoing PCI. Clinicians can use this risk score to evaluate the infection risk and subsequently make evidence-based decisions.
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Aims: Vascular calcification is a common clinical complication of chronic kidney disease (CKD), atherosclerosis (AS), and diabetes, which is associated with increased cardiovascular morbidity and mortality in patients. The transdifferentiation of vascular smooth muscle cells (VSMCs) to an osteochondrogenic phenotype is a crucial step during vascular calcification. The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) plays an important role in regulating cell proliferation and differentiation, but whether it regulates the calcification of arteries and VSMCs remains unclear. Therefore, this study aims to understand the role of C/EBPα in the regulation of vascular calcification. Methods and Results: Both mRNA and protein expression levels of C/EBPα were significantly increased in calcified arteries from mice treated with a high dose of vitamin D3 (vD3). Upregulation of C/EBPα was also observed in the high phosphate- and calcium-induced VSMC calcification process. The siRNA-mediated knockdown of C/EBPα significantly attenuated VSMC calcification in vitro. Moreover, C/EBPα depletion in VSMCs significantly reduced the mRNA expression of the osteochondrogenic genes, e.g., sex-determining region Y-box 9 (Sox9). C/EBPα overexpression can induce SOX9 overexpression. Similar changes in the protein expression of SOX9 were also observed in VSMCs after C/EBPα depletion or overexpression. In addition, silencing of Sox9 expression significantly inhibited the phosphate- and calcium-induced VSMC calcification in vitro. Conclusion: Findings in this study indicate that C/EBPα is a key regulator of the osteochondrogenic transdifferentiation of VSMCs and vascular calcification, which may represent a novel therapeutic target for vascular calcification.
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Background: The immune infiltration and molecular mechanisms underlying septic cardiomyopathy (SC) have not been completely elucidated. This study aimed to identify key genes related to SC and elucidate the potential molecular mechanisms. Methods: The weighted correlation network analysis (WGCNA), linear models for microarray analysis (LIMMA), protein-protein interaction (PPI) network, CIBERSORT, Kyoto Encyclopedia of Genes and Genomes pathway (KEGG), and gene set enrichment analysis (GSEA) were applied to assess the key pathway and hub genes involved in SC. Results: We identified 10 hub genes, namely, LRG1, LCN2, PTX3, E LANE, TCN1, CLEC4D, FPR2, MCEMP1, CEACAM8, and CD177. Furthermore, we used GSEA for all genes and online tools to explore the function of the hub genes. Finally, we took the intersection between differential expression genes (DEGs) and hub genes to identify LCN2 and PTX3 as key genes. We found that immune-related pathways played vital roles in SC. LCN2 and PTX3 were key genes in SC progression, which mainly showed an anti-inflammatory effect. The significant immune cells in cardiomyocytes of SC were neutrophils and M2 macrophages. Conclusion: These cells may have the potential to be prognostic and therapeutic targets in the clinical management of SC. Excessive anti-inflammatory function and neutrophil infiltration are probably the primary causes of SC.
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BACKGROUND: In patients with stable coronary artery disease, low DBP is associated with an increased risk of myocardial infarction and cardiovascular death, but its association with clinical outcomes in patients with acute myocardial infarction undergoing percutaneous coronary intervention (PCI) is unknown. METHODS: Consecutive patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI from January 2010 to June 2016 were enrolled. The patients were divided into five groups according to the quintiles of DBP at admission. The primary outcome was in-hospital major adverse cardiovascular events (MACE) including all-cause death, stroke, target vessel revascularization, and recurrent myocardial infarction. RESULTS: A total of 2198 patients were enrolled, of whom 157 (7.1%) developed in-hospital MACE. Patients with DBP lower than 60âmmHg was associated with a higher rate of in-hospital MACE (14.8, 7.8, 5.6, 6.1, and 3.8%, Pâ<â0.001) and all-cause death (12.5, 6.4, 4.3, 3.9, and 1.9%, Pâ<â0.001) compared with those with DBP 60-69, 70-79, 80-89, and at least 90âmmHg. Multivariate logistic regression analysis demonstrated that DBP higher than 90âmmHg was a significant predictor of lower risk of in-hospital MACE (ORâ=â0.16, 95% CIâ=â0.04-0.61, Pâ=â0.007). Cubic spline models for the association between DBP and MACE did not demonstrate a U-type relationship after adjusting for potential risk factors. During the follow-up, lower DBP was associated with a higher risk of all-cause death (Pâ<â0.0001). CONCLUSION: Lower DBP is independently associated with an elevated risk of in-hospital MACE and follow-up all-cause death.
Subject(s)
Coronary Artery Disease , Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Myocardial Infarction/etiology , Myocardial Infarction/surgery , Percutaneous Coronary Intervention/adverse effects , Risk Factors , ST Elevation Myocardial Infarction/complications , ST Elevation Myocardial Infarction/surgery , Treatment OutcomeABSTRACT
BACKGROUND: The monocyte to high-density lipoprotein cholesterol ratio (MHR) has been demonstrated as a new marker of inflammation. However, at present, the prognostic value of MHR in type 2 diabetes mellitus (T2DM) accompanied with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI) is unclear. METHODS: T2DM patients with NSTE-ACS undergoing PCI were consecutively enrolled from January 1, 2010 to December 31, 2014 and divided according to MHR value tertiles. Baseline, procedural, and follow-up data were collected. The primary outcomes were in-hospital major adverse clinical events (MACE). The prespecified secondary outcomes included any bleeding [as indicated by Bleeding Academic Research Consortium definition (BARC) grades 1-5] and death during follow-up. RESULTS: Of the 1,405 enrolled patients, the rates of in-hospital MACE (0.2%, 0.2%, and 1.3%, P=0.043) and bleeding (12.4%, 12.2%, and 17.1%, P=0.048) increased significantly in high MHR tertiles. After 1 year of follow-up, the rates of bleeding (15.0%, 14.5%, and 22.2%, P=0.002) and all-cause death (1.5%, 1.7%, and 4.3%, P=0.010) were higher in higher MHR tertiles. Our results also suggested that MHR was an independent predictor of in-hospital MACE [adjusted odds ratio =8.36; 95% confidence interval (CI): 1.57-44.47; P=0.013] and long-term bleeding (adjusted hazard ratio =1.21; 95% CI: 1.07-1.37; P=0.002). Receiver-operating characteristic curve analysis indicated that MHR >0.022 had a sensitivity of 75.0% and specificity of 72.7% for predicting in-hospital MACE [area under the curve (AUC) =0.722; 95% CI: 0.51-0.933; P=0.040]. Furthermore, Kaplan-Meier curves showed that a higher risk of all-cause death in long-term follow-up was prevalent in patients with high MHR (P=0.033). CONCLUSIONS: The increased level of MHR was related to in-hospital MACE and long-term bleeding events in T2DM patients with NSTE-ACS undergoing PCI.
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Our previous study showed that parenteral anticoagulation therapy (PACT) in the context of aggressive antiplatelet therapy failed to improve clinical outcomes in patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome (NSTE-ACS). However, the role of PACT in patients managed medically remains unknown. This observational cohort study enrolled patients with NSTE-ACS receiving medical therapy from November 2014 to June 2017 in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. Eligible patients were included in the PACT group and non-PACT group. The primary outcomes were in-hospital all-cause mortality and major bleeding. The secondary outcome included minor bleeding. Among 23,726 patients, 8,845 eligible patients who received medical therapy were enrolled. After adjusting the potential confounders, PACT was not associated with a lower risk of in-hospital all-cause mortality (adjusted odds ratio (OR), 1.25; 95% confidence interval (CI), 0.92-1.71; P = 0.151). Additionally, PACT did not increase the incidence of major bleeding or minor bleeding (major bleeding: adjusted OR, 1.04; 95% CI, 0.80-1.35; P = 0.763; minor bleeding: adjusted OR, 1.27; 95% CI, 0.91-1.75; P = 0.156). The propensity score analysis confirmed the primary analyses. In patients with NSTE-ACS receiving antiplatelet therapy, PACT was not associated with a lower risk of in-hospital all-cause mortality or a higher bleeding risk in patients with NSTE-ACS receiving non-invasive therapies and concurrent antiplatelet strategies. Randomized clinical trials are warranted to reevaluate the safety and efficacy of PACT in all patients with NSTE-ACS who receive noninvasive therapies and current antithrombotic strategies.
Subject(s)
Acute Coronary Syndrome/drug therapy , Angina, Unstable/drug therapy , Anticoagulants/administration & dosage , Fondaparinux/administration & dosage , Hemorrhage/chemically induced , Heparin, Low-Molecular-Weight/administration & dosage , Hospital Mortality , Non-ST Elevated Myocardial Infarction/drug therapy , Aged , Aged, 80 and over , China , Dual Anti-Platelet Therapy , Female , Heparin/administration & dosage , Humans , Infusions, Parenteral , Injections , Ischemic Stroke/epidemiology , Male , Middle Aged , Myocardial Infarction/epidemiology , RecurrenceABSTRACT
We have developed an experimental system to simultaneously measure surface structure, morphology, composition, chemical state, and chemical activity for samples in gas phase environments. This is accomplished by simultaneously measuring x-ray photoelectron spectroscopy (XPS) and grazing incidence x-ray scattering in gas pressures as high as the multi-Torr regime while also recording mass spectrometry. Scattering patterns reflect near-surface sample structures from the nano-scale to the meso-scale, and the grazing incidence geometry provides tunable depth sensitivity of structural measurements. Scattered x rays are detected across a broad range of angles using a newly designed pivoting-UHV-manipulator for detector positioning. At the same time, XPS and mass spectrometry can be measured, all from the same sample spot and under ambient conditions. To demonstrate the capabilities of this system, we measured the chemical state, composition, and structure of Ag-behenate on a Si(001) wafer in vacuum and in O2 atmosphere at various temperatures. These simultaneous structural, chemical, and gas phase product probes enable detailed insights into the interplay between the structure and chemical state for samples in gas phase environments. The compact size of our pivoting-UHV-manipulator makes it possible to retrofit this technique into existing spectroscopic instruments installed at synchrotron beamlines. Because many synchrotron facilities are planning or undergoing upgrades to diffraction limited storage rings with transversely coherent beams, a newly emerging set of coherent x-ray scattering experiments can greatly benefit from the concepts we present here.
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Background: Post-acute myocardial infarction (post-AMI) infection is an infrequent but important and serious complication in patients with ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). Predicting its occurrence is essential for future prevention. However, little is known about the prediction of post-AMI infection in such patients to date. This study aims to develop and validate a new risk score based on risk factors for early prediction of infection in STEMI patients undergoing PCI. Methods: This prospective, multi-center and observational study assesses the predictive value of risk score for post-AMI infection among a cohort of patients hospitalized due to STEMI. The STEMI patients undergoing PCI enrolled between January 1st 2010 and May 31st 2016 were served as a development cohort while those enrolled from June 1st 2016 to May 31st 2018 were served as validation cohort. The primary endpoint was post-AMI infection during hospitalization, defined as infection requiring antibiotics (reflecting the clinical influence of infection compatible with the necessity for additional treatment), and all-cause death and major adverse cardiovascular events (MACE) including all-cause death, recurrent myocardial infarction, target vessel revascularization, and stroke were considered as secondary endpoints. The risk score model based on risk factors was established using stepwise logistic regression, and will be validated in other centers and external patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). Results: This study will provide evidence on prognostic property, reliability of scoring, comparative performance, and suitability of the novel model for screening purpose in order to be recommended for clinical practice. Discussion: Our study is designed to develop and validate a clinical risk score for predicting infection in participants with STEMI who have undergone PCI. This simple tool may therefore improve evaluation of post-AMI infection and enhance future researches into the best practices to prevent or reduce infection in such patients. Clinical Trial Registration: www.chictr.org.cn, identifier: ChiCTR1900028278.
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AIMS: Oral contraceptives (OCs) are widely used in women of reproductive age, but their influences on heart failure (HF) development have yet to be reported. This study was performed to assess HF risk associated with OC use. METHODS AND RESULTS: We studied women participating in the Multi-Ethnic Study of Atherosclerosis with available data on OC use. Inverse probability of treatment weighting analyses were used to reduce baseline imbalances. Cox proportional hazards models were applied to evaluate the associations of OC use and HF risk. The primary analysis comprised a total of 3594 participants [average age 62.10 (10.24) years]. During an average follow-up of 12.45 (3.75) years, 138 incident HF occurred. In unadjusted Cox model, OC use was associated with a decreased risk of HF [hazard ratio (HR) = 0.45, 95% confidence interval (CI) 0.31-0.64, P < 0.001]. However, in multivariable-adjusted and inverse probability of treatment weighting models, the results were attenuated and became non-significant (HR = 0.96, 95% CI 0.63-1.48, P = 0.86 and HR = 0.79, 95% CI 0.45-1.40, P = 0.43, respectively). Duration of OC use was not related to increased risks of HF. When stratifying HF into subtypes, similar associations were observed. In multivariable-adjusted regression models, OC use was positively associated with left ventricular end-diastolic mass [coefficient (ß) = 3.04, P = 0.006] and stroke volume (ß = 1.76, P = 0.01 for the left ventricle; ß = 2.17, P = 0.005 for the right ventricle) but had no impact on left ventricular ejection fraction (ß = 0.09, P = 0.75) and right ventricular ejection fraction (ß = 0.33, P = 0.25). CONCLUSIONS: Oral contraceptive use in women of reproductive age does not portend increased risk of HF. However, whether the formulations or dosages differently impact this association should be further investigated.
Subject(s)
Heart Failure , Ventricular Function, Left , Contraceptives, Oral , Female , Heart Failure/epidemiology , Humans , Incidence , Middle Aged , Stroke Volume , Ventricular Function, RightABSTRACT
BACKGROUND: Several studies have shown that N-terminal pro-B-type natriuretic peptide (NT-proBNP) is strongly correlated with the complexity of coronary artery disease and the prognosis of patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS), However, it remains unclear about the prognostic value of NT-proBNP in patients with NSTE-ACS and multivessel coronary artery disease (MCAD) undergoing percutaneous coronary intervention (PCI). Therefore, this study aimed to reveal the relationship between NT-proBNP levels and the prognosis for NSTE-ACS patients with MCAD undergoing successful PCI. METHODS: This study enrolled 1022 consecutive NSTE-ACS patients with MCAD from January 2010 to December 2014. The information of NT-proBNP levels was available from these patients. The primary outcome was in-hospital all-cause death. In addition, the 3-year follow-up all-cause death was also ascertained. RESULTS: A total of 12 (1.2%) deaths were reported during hospitalization. The 4th quartile group of NT-proBNP (> 1287 pg/ml) showed the highest in-hospital all-cause death rate (4.3%) (P < 0.001). Besides, logistic analyses revealed that the increasing NT-proBNP level was robustly associated with an increased risk of in-hospital all-cause death (adjusted odds ratio (OR): 2.86, 95% confidence interval (CI) = 1.16-7.03, P = 0.022). NT-proBNP was able to predict the in-hospital all-cause death (area under the curve (AUC) = 0.888, 95% CI = 0.834-0.941, P < 0.001; cutoff: 1568 pg/ml). Moreover, as revealed by cumulative event analyses, a higher NT-proBNP level was significantly related to a higher long-term all-cause death rate compared with a lower NT-proBNP level (P < 0.0001). CONCLUSIONS: The increasing NT-proBNP level is significantly associated with the increased risks of in-hospital and long-term all-cause deaths among NSTE-ACS patients with MCAD undergoing PCI. Typically, NT-proBN P > 1568 pg/ml is related to the all-cause and in-hospital deaths.
Subject(s)
Coronary Artery Disease/therapy , Natriuretic Peptide, Brain/blood , Non-ST Elevated Myocardial Infarction/therapy , Peptide Fragments/blood , Percutaneous Coronary Intervention , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Cause of Death , Coronary Artery Disease/blood , Coronary Artery Disease/diagnosis , Coronary Artery Disease/mortality , Female , Hospital Mortality , Humans , Male , Middle Aged , Non-ST Elevated Myocardial Infarction/blood , Non-ST Elevated Myocardial Infarction/diagnosis , Non-ST Elevated Myocardial Infarction/mortality , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Predictive Value of Tests , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
The aim of the present study was to investigate the potential predictive significance of pretreatment prognostic nutritional index (PNI) in intravenous immunoglobulin (IVIG) resistant Kawasaki disease (KD). The PNI, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were analyzed in 1257 eligible patients with KD. Receiver operating curve analysis was used to explore the prediction accuracy for IVIG-resistant KD. The optimal cut-off values were identified as 49.5 for PNI, 3.58 for NLR and 164.00 for PLR, respectively. Lower pretreatment PNI (< 49.5) was demonstrated to be associated with lower age, serum sodium levels and platelet counts, and with a higher incidence of IVIG resistance and higher C-reactive protein levels. There was a significantly negative association between the PNI and NLR, and PLR. Univariate and multivariate analyses revealed that PNI, NLR and PLR were independent predictive factors for IVIG resistance. The discriminatory ability of PNI was not inferior to NLR, PLR and their combination (NLR > 3.58 and PLR > 164) for predicting IVIG resistance, respectively. Pretreatment PNI may serve as a novel surrogate independent predictor for IVIG-resistant KD.
Subject(s)
Mucocutaneous Lymph Node Syndrome , Humans , Immunoglobulins, Intravenous , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/drug therapy , Neutrophils , Nutrition Assessment , Prognosis , Retrospective StudiesABSTRACT
INTRODUCTION: Renin-angiotensin system inhibitors (RASi) reduce mortality among heart failure (HF) patients, but their effect among those complicating contrast-induced acute kidney injury (CI-AKI) remains unexplored. We aimed to investigate whether the relationship between RASi prescription at discharge and mortality differs between HF patients with or without CI-AKI following coronary angiography (CAG). METHODS: About 596 HF patients from an observational cohort were divided into a CI-AKI group (n = 104) and a non-CI-AKI group (n = 492) based on whether they had CI-AKI following CAG. The endpoint was all-cause mortality. Multivariable Cox regression was performed in each group to explore the associations between RASi at discharge and mortality. RESULTS: During the median follow-up time of 2.26 (1.70; 3.24) years, higher mortality rate was observed in the CI-AKI group compared to the non-CI-AKI group (18.3% vs 8.9%, p = 0.002). Among HF patients with CI-AKI, after adjusting for confounding factors, the association was not significant between RASi prescription at discharge and mortality (HR: 0.39, 95%CI: 0.12-1.31, p = 0.128), while it was among those without CI-AKI (HR: 0.39, 95%CI: 0.18-0.84, p = 0.016). CONCLUSION: RASi prescription at discharge for HF patients complicating CI-AKI tended to be ineffective, while it benefited those without CI-AKI. Further randomized evidence is needed to confirm this trend.
Subject(s)
Acute Kidney Injury/chemically induced , Acute Kidney Injury/complications , Contrast Media/adverse effects , Heart Failure/complications , Heart Failure/mortality , Renin-Angiotensin System , Aged , Female , Hospital Mortality , Humans , Male , Middle Aged , Multivariate Analysis , Prescription Drugs/therapeutic use , Risk FactorsABSTRACT
BACKGROUND: Monoclonal non-speciï¬c suppressor factor ß (MNSFß) is a ubiquitously expressed member of the ubiquitin-like family. It functions as a regulator of cell apoptosis and a potential tumor suppressor, playing a vital role in the processes of immune cell function and apoptosis. METHODS: The present study constructed GFP-pMNSFß swine umbilical vein endothelial cell (SUVEC) lines and investigated the function of porcine MNSFß (pMNSFß) in apoptosis, as well as its interactions with pBCL-G. Results revealed that stably expressed pMNSFß protein in SUVEC lines significantly enhanced staurosporine (STS)-induced apoptosis. pMNSFß proteins interacted with pBCL-G proteins and the expression of these interacting proteins synergized to further enhance STS-induced apoptosis. RESULTS: GFP-pMNSFß stably expressed SUVEC lines through transient transfection and neomycin screening methods. Over 90% of the SUVEC cultures expressed GFP signals, and 41.5 kDa GFP-pMNSFß proteins were detected with western blotting methods. Annexin V-PE/PI staining and flow cytometry analyses showed that overexpression of pMNSFß proteins significantly elevated STS-induced apoptosis rates. Co-immunoprecipitation methods revealed an interaction between pMNSFß and pBCL-G proteins. BCL-G is a proapoptotic member of the BCL-2 family that has been shown to be misexpressed in human systemic lupus erythematosus, as well as mammary and prostate cancers. Here, we demonstrated that the co-expression and potential conjugation of pMNSFß and pBCL-G proteins synergistically enhanced STS-induced apoptosis. CONCLUSIONS: The present study was the first to characterize the function of MNSFß in porcine cells, and to clarify the function of MNSFß in apoptosis. These results reveal that pMNSFß is a potential molecular model for future investigations of diseases related to human MNSFß dysfunction.
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Congenital heart disease (CHD) has severe morbidity and mortality worldwide. Evidence suggests that circularRNAs (circRNAs) are involved in the pathogenesis of human CHD. However, the regulatory mechanism remains uncertain. This study aimed to explore that mechanism. The levels of circular RNA MGAT1 (circMGAT1) and miR-34a were measured by quantitative polymerase chain reaction (qRT-PCR). Expression of yes-associated protein isoform 1 (YAP1) was assessed by western blot. Caspase-3 activity was evaluated by Caspase 3 Activity Assay Kit. CCK-8 assay was carried out to detect cell proliferation of hypoxia-induced AC16 cells. Cell apoptosis was analyzed by flow cytometry. In addition, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to verify the relationship between miR-34a and circMGAT1 or YAP1 in vitro. The level of circMGAT1 was downregulated, while miR-34a was strikingly increased in CHD tissues and hypoxia-induced AC16 cells. CircMGAT1 was a sponge of miR-34a, and circMGAT1 targeted miR-34a to regulate cell proliferation and apoptosis in hypoxia-induced cardiomyocytes. Dual-luciferase reporter and RIP-assay verified that miR-34a directly targeted YAP1, and the expression of YAP1 was significantly suppressed by miR-34a mimics but was enhanced by miR-34a inhibitor. Interestingly, YAP1 restored the effect of miR-34a on cell proliferation and apoptosis in hypoxia-induced AC16 cells. Besides, circMGAT1 sponged miR-34a to regulate the expression of YAP1. In conclusion, circMGAT1 inhibited cell apoptosis and enhanced cell proliferation by regulating the miR-34a/YAP1 axis, providing a therapy target for the treatment of human CHD.
ABSTRACT
OBJECTIVE: To evaluate and quantify the future risk of cardiovascular events in young adults with high blood pressure. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, and Web of Science were searched from inception to 6 March 2020. Relative risks were pooled using a random effects model and expressed with 95% confidence intervals. Absolute risk difference was calculated. Dose-response relations between blood pressure and individual outcomes were assessed by a restricted cubic spline model. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were selected that investigated the adverse outcomes of adults aged 18-45 with raised blood pressure. The primary study outcome was a composite of total cardiovascular events. Coronary heart disease, stroke, and all cause mortality were examined as secondary outcomes. RESULTS: Seventeen observational cohorts consisting of approximately 4.5 million young adults were included in the analysis. The average follow-up was 14.7 years. Young adults with normal blood pressure had increased risk of cardiovascular events compared with those with optimal blood pressure (relative risk 1.19, 95% confidence interval 1.08 to 1.31; risk difference 0.37, 95% confidence interval 0.16 to 0.61 per 1000 person years). A graded, progressive association was found between blood pressure categories and increased risk of cardiovascular events (high normal blood pressure: relative risk 1.35, 95% confidence interval 1.22 to 1.49; risk difference 0.69, 95% confidence interval 0.43 to 0.97 per 1000 person years; grade 1 hypertension: 1.92, 1.68 to 2.19; 1.81, 1.34 to 2.34; grade 2 hypertension: 3.15, 2.31 to 4.29; 4.24, 2.58 to 6.48). Similar results were observed for coronary heart disease and stroke. Generally, the population attributable fraction for cardiovascular events associated with raised blood pressure was 23.8% (95% confidence interval 17.9% to 28.8%). The number needed to treat for one year to prevent one cardiovascular event was estimated at 2672 (95% confidence interval 1639 to 6250) for participants with normal blood pressure, 1450 (1031 to 2326) for those with high normal blood pressure, 552 (427 to 746) for those with grade 1 hypertension, and 236 (154 to 388) for those with grade 2 hypertension. CONCLUSIONS: Young adults with raised blood pressure might have a slightly increased risk of cardiovascular events in later life. Because the evidence for blood pressure lowering is limited, active interventions should be cautious and warrant further investigation.