Age differences in the association of body mass index-defined obesity with abdominal aortic calcification.

Objectives: In cardiovascular disease, previous studies have suggested young age as one of the reasons to explain the obesity paradox. This study attempts to provide a different opinion on this claim through unexpected findings. Methods: We used a cross-sectional analysis of the US nationally representative data, total of 10,175 participants were recruited in 2013-2014 from NHANES. A total of 947 participants were selected to be included in this study through inclusion criteria and exclusion criteria for statistical analysis of the relationship between obesity and abdominal aortic calcification(AAC). Smooth curve fitting and multivariate regression analyses were conducted to examine the associations of obesity with AAC after adjusting for age, gender and associated variates. Results: Depending on the age of the population, the relationship between obesity and AAC showed the different outcome. Obesity was associated with the lower risk of AAC among individuals older than 52 years of age. According to the difference of adjusted covariates, the AAC scores in the obesity group decreased by 0.92, 0.87, and 1.11 for 52 years old or older individuals. In particular, the risk of AAC was lower for patients with obesity with the following characteristics: male, low LDL, low triglyceride, DM, non-cancer patient, smoking, drinking, vigorous work activity, low annual household income, education of 9 - 11th grades and non-Hispanic white. Conclusions: In US, adults aged 52 years or older, obesity was associated with decreased AAC risk. Older age may be one potential reason for the obesity paradox.

Clinical features predicting mortality risk in older patients with COVID-19.

BACKGROUND: Since December 2019, the cumulative number of coronavirus disease 2019 (COVID-19) deaths worldwide has reached 1,013,100 and continues to increase as of writing. Of these deaths, more than 90% are people aged 60 and older. Therefore, there is a need for an easy-to-use clinically predictive tool for predicting mortality risk in older individuals with COVID-19. OBJECTIVE: To explore an easy-to-use clinically predictive tool that may be utilized in predicting mortality risk in older patients with COVID-19. METHODS: A retrospective analysis of 118 older patients with COVID-19 admitted to the Union Dongxihu Hospital, Huazhong University of Science and Technology, Wuhan, China from 12 January to 26 February 2020. The main results of epidemiological, demographic, clinical and laboratory tests on admission were collected and compared between dying and discharged patients. RESULTS: No difference in major symptoms was observed between dying and discharged patients. Among the results of laboratory tests, neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase, albumin, urea nitrogen and D-dimer (NLAUD) show greater differences and have better regression coefficients (ß) when using hierarchical comparisons in a multivariate logistic regression model. Predictors of mortality based on better regression coefficients (ß) included NLR (OR = 31.2, 95% CI 6.7-144.5, p < .0001), lactate dehydrogenase (OR = 73.4, 95% CI 11.8-456.8, p < .0001), albumin (OR < 0.1, 95% CI <0.1-0.2, p < .0001), urea nitrogen (OR = 12.0, 95% CI 3.0-48.4, p = .0005), and D-dimer (OR = 13.6, 95% CI 3.4-54.9, p = .0003). According to the above indicators, a predictive NLAUD score was calculated on the basis of a multivariate logistic regression model to predict mortality. This model showed a sensitivity of 0.889, specificity of 0.984 and a better predictive ability than CURB-65 (AUROC = 0.955 vs. 0.703, p < .001). Bootstrap validation generated the similar sensitivity and specificity. CONCLUSIONS: We designed an easy-to-use clinically predictive tool for early identification and stratified treatment of older patients with severe COVID-19.

Studies on the Inhibitory Effects of Nano-Hydroxyapatite-Loaded As2O3 on Hepatoma Cells.

A stable monodisperse hydroxyapatite (HAP) nanoparticle suspension was prepared by chemical method-assisted ultrasound irradiation. HAP nanoparticles were characterized by atomic force microscopy (AFM) and particle size potentiometry. The effects of HAP nanoparticles on BEL-7402 human hepatocarcinoma cells were studied by MTT colorimetric assay and morphological observation. The mechanism of HAP nanoparticles was studied by analyzing single cell fluorescence element microregion, the change of ultrastructure and cell cycle. The experimental results show that HAP nanoparticles have an obvious inhibitory effect on BEL-7402 human hepatocarcinoma cells in vitro. By entering the cancer cells and blocking the progress of cell cycle, HAP nanoparticles induce the accumulation of cells in G1 phase, which leads to cancer cell swelling and apoptosis.

Liver Enzymes and the Risk of Atrial Fibrillation: A Meta-Analysis of Prospective Cohort Studies.

Background: The association between liver enzymes and the future development of atrial fibrillation (AF) from observational studies is unclear. We, therefore, performed a meta-analysis to systematically evaluate the relationship between liver enzymes and AF risk. Methods: We searched the PubMed and Embase databases for observational cohort studies assessing the association between liver enzymes and AF risk. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random effects model. Results: Five prospective studies with 282,615 participants and 7062 AF events were included. The pooled fully adjusted RRs (95% CIs) for AF were 1.10 (1.06-1.14) per 1-standard deviation change in log baseline level of gamma glutamyltransferase (GGT). No positive association was found between alanine aminotransferase (ALT, RR 1.04, 95% CI 0.90-1.20, p = 0.607) or aspartate aminotransferase (AST, RR 1.05, 95% CI 0.96-1.15, p = 0.268) and the risk of AF. Conclusions: The baseline GGT level is positively associated with the AF risk in a log-linear manner. We found no significant association between ALT or AST and the risk of AF. However, further well-designed prospective studies are needed to confirm these findings and elucidate the pathophysiological mechanisms.

Recurrent fever of unknown fungal infection in a low-risk patient: A case report.

RATIONALE: Fungal infectious disease does not usually occur in low-risk patients. Clinicians tend to ignore the role of fungi in the fevers of low-risk patients. If there is not timely control of fungal infections and associated fever, the disease will continue to worsen, resulting in physical dysfunction or death. PATIENT CONCERNS: Recurrent fever continued for 1 month in a young adult. DIAGNOSES AND INTERVENTIONS: Non-albicans Candida (NAC) species probably was the main pathogen in this case based on the resolution of fever after capsofungin administration. OUTCOMES: The fever and the associated indicators, including white blood cell count, C-reaction protein, erythrocyte sedimentation rate, and BDG levels, showed improvement quickly. The patient left the hospital successfully after 18 days of caspofungin treatment. There was no recurrent fever at a follow-up of 1 year. LESSONS: Clinicians should be aware that the incidence of fungal infection is increasing in low-risk patients. The BDG assay is still an effective tool used to diagnose invasive fungal diseases. Caspofungin is an effective drug for the treatment of some unknown fungal infections.

Growth arrest-specific gene 6 transfer promotes mesenchymal stem cell survival and cardiac repair under hypoxia and ischemia via enhanced autocrine signaling and paracrine action.

Poor cell viability after transplantation has restricted the therapeutic capacity of mesenchymal stem cells (MSCs) for cardiac dysfunction after myocardial infarction (MI). Growth arrest-specific gene 6 (Gas6) encodes a secreted γ-carboxyglutamic acid (Gla)-containing protein that functions in cell growth, adhesion, chemotaxis, mitogenesis and cell survival. In this study, we genetically modified MSCs with Gas6 and evaluated cell survival, cardiac function, and infarct size in a rat model of MI via intramyocardial delivery. Functional studies demonstrated that Gas6 transfer significantly reduced MSC apoptosis, increased survival of MSCs in vitro and in vivo, and that Gas6-engineered MSCs (MSCGas6)-treated animals had smaller infarct size and showed remarkably functional recovery as compared with control MSCs (MSCNull)-treated animals. Mechanistically, Gas6 could enhance phosphatidylinositol 3-kinase (PI3K)/Akt signaling and improve hypoxia-inducible factor-1 alpha (HIF-1α)-driven secretion of four major growth factors (VEGF, bFGF, SDF and IGF-1) in MSCs under hypoxia in an Axl-dependent autocrine manner. The paracrine action of MSCGas6 was further validated by coculture neonatal rat cardiomyocytes with conditioned medium from hypoxia-treated MSCGas6, as well as by pretreatment cardiomyocytes with the specific receptor inhibitors of VEGF, bFGF, SDF and IGF-1. Collectively, our data suggest that Gas6 may advance the efficacy of MSC therapy for post-infarcted heart failure via enhanced Gas6/Axl autocrine prosurvival signaling and paracrine cytoprotective action.

Prognostic Value of Neutrophil to Lymphocyte Ratio for In-hospital Mortality in Elderly Patients with Acute Myocardial Infarction.

Coronary artery disease (CAD) is a multifactorial disease in which inflammation plays a central role. This study aimed to investigate the association of inflammatory markers such as the neutrophil to lymphocyte ratio (NLR), the Global Registry of Acute Coronary Events (GRACE) score with in-hospital mortality of elderly patients with acute myocardial infarction (AMI) in an attempt to explore the prognostic value of these indices for elderly AMI patients. One thousand consecutive CAD patients were divided into two groups based on age 60. The laboratory and clinical characteristics were assessed retrospectively by reviewing the medical records. The NLR and GRACE score were calculated. In the elderly (≥60 years), patients with non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI) had significantly higher NLR than did those with unstable angina (UA) and stable angina pectoris (SAP) (P<0.01). The NLR was considerably elevated in older AMI patients compared with their younger counterparts (<60 years) (P<0.05). In elderly AMI patients, the NLR was considerably higher in the high-risk group than in both the low-risk and medium-risk groups based on the GRACE score (P<0.05 and P<0.01, respectively), and the NLR was positively correlated with the GRACE score (r=0.322, P<0.001). Either the NLR level or the GRACE score was significantly higher in the death group than in the surviving group (P<0.05). By curve receiver operator characteristic curve (ROC) analysis, the optimal cut-off levels of 9.41 for NLR and 174 for GRACE score predicted in-hospital death [ROC area under the curve (AUC) 0.771 and 0.787, respectively, P<0.001]. It was concluded that an elevated NLR is a potential predictor of in-hospital mortality in elderly patients with AMI.

The clinical value of inflammatory biomarkers in coronary artery disease: PTX3 as a new inflammatory marker.

OBJECTIVE: Previous experiments have demonstrated that several inflammatory biomarkers, including pentraxin 3 (PTX3), matrix metalloprotein 9 (MMP9), interleukin-6 (IL-6), and the neutrophil to lymphocyte ratio (NLR), are differentially elevated in coronary artery disease (CAD). This study aims to compare the associations between plasma levels of these biomarkers and CAD, identifying the best biomarker that has the most powerful association with CAD. METHODS: Blood samples were collected from 64 patients admitted to the Department of Cardiology, 31 of whom had CAD and 33 of whom were CAD-free. Plasma levels of PTX3, MMP9, and IL-6 were measured via ELISA. The coronary Gensini score was used to evaluate the severity of coronary artery lesions. RESULTS: PTX3 levels and NLR levels between the CAD group and the CAD-free group were statistically significant (P<0.05). Stepwise multiple linear regression analysis showed that PTX3 levels and NLR levels were independently associated with CAD (r=1.3, P<0.05; r=1.8, P<0.05). Only PTX3 was associated with the severity of coronary artery stenosis. A PTX3 threshold of 4.38ng/mL maximized true-positive and false-negative results. PTX3 displayed a greater area under the receiver operating characteristic curve (AUC) than NLR, MMP9, and IL-6 (0.733 versus 0.612 versus 0.725 versus 0.518). CONCLUSIONS: Compared to NLR, MMP9, and IL-6, PTX3 displayed greater AUC and association with CAD. PTX3 may become a potentially powerful inflammatory biomarker for CAD.

Pentraxin 3 (PTX3) promoter methylation associated with PTX3 plasma levels and neutrophil to lymphocyte ratio in coronary artery disease.

BACKGROUND: Pentraxin 3 (PTX3) is expressed in the heart under inflammatory conditions and plays an important role in atherogenesis. Patients with increased PTX3 levels may suffer from higher rates of cardiac events. Regulation of specific genes by promoter methylation is important in atherogenesis. The factors influencing PTX3 levels and the association between epigenetics and PTX3 levels have not been investigated. METHODS: Blood samples were collected from 64 patients admitted to the Department of Cardiology, 35 who had coronary artery disease (CAD), and 29 who were CAD-free. Plasma levels of PTX3 were measured by ELISA. PTX3 promoter methylation was evaluated via methyl-specific PCR. The severity of coronary artery lesion was evaluated by angiography. RESULTS: The level of PTX3 promoter methylation in the CAD group was 62.69% ± 20.57%, significantly lower than that of the CAD-free group, which was 72.45% ± 11.84% (P = 0.03). Lower PTX3 promoter methylation levels in the CAD group were associated with higher plasma PTX3 concentrations (r = -0.29, P = 0.02). Furthermore, lower PTX3 promoter methylation levels were associated with higher neutrophil to lymphocyte ratio (NLR) in men (r = -0.58, P = 0.002). CONCLUSIONS: The present study provides new evidence that methylation of the PTX3 promoter is associated with PTX3 plasma levels and NLR in coronary artery disease. This study also shows that modification of epigenetics by chronic inflammation might be a significant molecular mechanism in the atherosclerotic processes that influence plasma PTX3 concentrations.

PTX3 is located at the membrane of late apoptotic macrophages and mediates the phagocytosis of macrophages.

Apoptotic macrophages are removed by neighboring phagocytes (efferocytosis), which is an important event in advanced atherosclerosis. Recent reports have elucidated some key molecular regulators in efferocytosis including complement C1q, MFGE8, and MERTK. However, it remains unknown whether the long pentraxin 3 (PTX3), which is an important molecule that is involved in apoptotic cell clearance in the immune response, plays a part in efferocytosis during advanced atherosclerosis. In this study, we modeled macrophage apoptosis in advanced plaques by incubating macrophages (peritoneal macrophages isolated from C57 mice) with free cholesterol (free cholesterol-induced apoptotic macrophages, FC-AMs). FC-AMs were added to a monolayer of fresh phagocytes to study the engulfment response. We observed that PTX3 was mainly located at the membrane of late apoptotic macrophages. The anti-PTX3 monoclonal Ab 16B5 inhibited the engulfment of late apoptotic macrophages by phagocytes in a dose-dependent manner (from 14.63% inhibition at 5 µg/ml to 26.19% inhibition at 50 µg/ml). These results suggest that PTX3 located at the membrane of late apoptotic macrophages mediates their phagocytosis by phagocytes in a cell model of advanced atherosclerosis.