Epicardial adipose tissue density is a better predictor of cardiometabolic risk in HFpEF patients: a prospective cohort study.

BACKGROUND: Epicardial adipose tissue (EAT) accumulation is associated with multiple cardiometabolic risk factors and prognosis of heart failure with preserved ejection fraction (HFpEF). The correlation between EAT density and cardiometabolic risk and the effect of EAT density on clinical outcome in HFpEF remain unclear. We evaluated the relationship between EAT density and cardiometabolic risk factors, also the prognostic value of EAT density in patients with HFpEF. METHODS: We included 154 HFpEF patients who underwent noncontrast cardiac computed tomography (CT) and all patients received follow-up. EAT density and volume were quantified semi-automatically. The associations of EAT density and volume with cardiometabolic risk factors, metabolic syndrome and the prognostic impact of EAT density were analyzed. RESULTS: Lower EAT density was associated with adverse changes in cardiometabolic risk factors. Each 1 HU increase in fat density, BMI was 0.14 kg/m2 lower (95% CI 0.08-0.21), waist circumference was 0.34 cm lower (95% CI 0.12-0.55), non-HDL-cholesterol was 0.02 mmol/L lower (95% CI 0-0.04), triglyceride was 0.03 mmol/L lower (95% CI 0.01-0.04), fasting plasma glucose was 0.05 mmol/L lower (95% CI 0.02-0.08), TyG index was 0.03 lower (95% CI 0.02-0.04), Log2(TG/HDL-C) was 0.03 lower (95% CI 0.02-0.05), METS-IR was 0.36 lower (95% CI 0.23-0.49), MetS Z-score was 0.04 lower (95% CI 0.02-0.06), and Log2(CACS + 1) was 0.09 lower (95% CI 0.02-0.15). After adjusting for BMI and EAT volume, the associations of non-HDL-cholesterol, triglyceride, fasting plasma glucose, insulin resistance indexes, MetS Z-score, and CACS with fat density remained significant. The area under the curve (AUC) for the presence and severity of metabolic syndrome was greater in EAT density than volume (AUC: 0.731 vs 0.694, 0.735 vs 0.662, respectively). Over a median follow-up of 16 months, the cumulative incidence of heart failure readmission and composite endpoint increased with lower level of EAT density (both p < 0.05). CONCLUSIONS: EAT density was an independent impact factor of cardiometabolic risk in HFpEF. EAT density might have better predictive value than EAT volume for metabolic syndrome and it might have prognostic value in patients with HFpEF.

Relationship between adipose tissue distribution and arterial stiffness in HFpEF.

OBJECTIVES: Heart failure and preserved ejection fraction (HFpEF) in patients is often complicated by abdominal obesity and arteriosclerosis. The aim of this study was to determine the relationship between adipose tissue distribution and arterial stiffness in patients with HFpEF. METHODS: This was a cross-sectional descriptive study involving 93 patients with HFpEF. Several anthropometric measurements were measured, including height, weight, waist circumference, body fat mass, percent body fat, body fat rate, and visceral fat area (VFA). We calculated body mass index. Arterial stiffness was assessed by measurement of brachial-ankle pulse wave velocity (baPWV). The association between VFA and baPWV was investigated by linear regression analysis. RESULTS: In univariate analysis, VFA showed strong relations with bilateral baPWV in Spearman correlation analysis (P = 0.003 and P = 0.002, respectively). After adjusting for VFA, age, systolic blood pressure, diastolic blood pressure, and heart rate, VFA and age were significantly and positively associated with bilateral baPWV (P = 0.024 and P = 0.032, respectively). After adjusting for VFA, age, left ventricular posterior wall, and interventricular septal thickness, VFA and age were still significantly correlated with bilateral baPWV (P = 0.028 and P = 0.008, respectively). CONCLUSIONS: In patients with HFpEF, adipose tissue distribution was correlated with arterial stiffness. VFA was independently associated with baPWV.

The relationship between ambulatory arterial stiffness index and left ventricular diastolic dysfunction in HFpEF: a prospective observational study.

BACKGROUND: The relationship between ambulatory arterial stiffness index (AASI) and left ventricular diastolic dysfunction (LVDD) in patients with heart failure with preserved ejection fraction (HFpEF) is unknown. We aimed to investigate the association between the AASI and LVDD in HFpEF. METHODS: We prospective enrolled consecutive patients with HFpEF in Chongqing, China. Twenty-four-hour ambulatory blood pressure monitoring (24 h-ABPM) and echocardiography were performed in each patient. AASI was obtained through individual 24 h-ABPM. The relationship between AASI and LVDD was analyzed. RESULTS: A total of 107 patients with HFpEF were included. The mean age was 68.45 ± 14.02 years and 63 (59%) were women. The patients were divided into two groups according to the upper normal border of AASI (0.55). AASI > 0.55 group were more likely to be older, to have higher mean systolic blood pressure and worsen left ventricular diastolic function than AASI group ≤ 0.55. AASI was closely positive related to the diastolic function parameters, including mean E/e' (r = 0.307, P = 0.001), septal E/e' (r = 0.290, P = 0.002), lateral E/e' (r = 0.276, P = 0.004) and E (r = 0.274, P = 0.004). After adjusting for conventional risk factors, AASI was still an independent risk factors of mean E/e' > 10 in patients with HFpEF (OR: 2.929, 95%CI: 1.214-7.064, P = 0.017), and the association between AASI and mean E/e' > 14 was reduced (OR: 2.457, 95%CI: 1.030-5.860, P = 0.043). AASI had a partial predictive value for mean E/e' > 10 (AUC = 0.691, P = 0.002), while the predictive value for mean E/e' > 14 was attenuated (AUC = 0.624, P = 0.034). CONCLUSION: AASI was positive related to E/e' in HFpEF and might be an independent risk factor for the increase of mean E/e'.

Reduced graphene oxide coated nickel foam for stir bar sorptive extraction of benzotriazole ultraviolet absorbents from environmental water.

The use of porous carrier and coating sorbents in stir bar sorptive extraction (SBSE) contributes to the improvement of extraction efficiency and dynamics. Herein, porous nickel foam (NF) with large surface area and magnetic property was used as the carrier of stir bar. NF was added into the mixture of graphene oxide (GO) and reducing agent, and reduced graphene oxide (RGO) coating was obtained on the surface of NF substrate by in situ hydrothermal reduction. The characterization results of Fourier transform infrared spectroscopy, X-ray power-diffraction and scanning electron microscope showed that GO was partially reduced into RGO, and the RGO coating was uniformly loaded on the NF surface. The obtained RGO-NF composite was used as the stir bar coating for the analysis of six benzotriazole (BZTs) UV absorbents. The extraction efficiency was between 48 and 64% for six BZTs. RGO-NF stir bar exhibited faster adsorption/desorption kinetics than commercial polydimethylsiloxane coated stir bar (50 min vs 120/360 min) due to its porous structure and large specific surface area. On this basis, a method of RGO-NF coated stir bar sorptive extraction combined with high performance liquid chromatography (HPLC)-DAD was established for the determination of six BZTs. Under the optimized conditions, the limits of detection were 0.33-0.50 µg/L for six target BZTs, and the linear range was 1-100 µg/L. The proposed method merits good ability to resist matrix and was used to analyze six BZTs in environmental water samples. The recoveries of target BZTs were obtained within 83.0-112% in the spiked East Lake water and 97.0-111% in the spiked Yangtze River water, respectively.

Enhanced Osseointegration of Titanium Implants by Surface Modification with Silicon-doped Titania Nanotubes.

INTRODUCTION: Despite great progress made in developing orthopedic implants, the development of titanium (Ti) implants with ideal early osseointegration remains a big challenge. Our pilot study has demonstrated that Si-TiO2 nanotubes on the surface of Ti substrates could enhance their osteogenic activity. Hence, in this study, we aim to comprehensively evaluate the effects of silicon-doped titania (Si-TiO2) nanotubes on the osseointegration property of Ti implants. MATERIALS AND METHODS: The Ti implants were surface modified with Si-TiO2 nanotubes through in situ anodization and Si plasma immersion ion implantation (PIII) method. Three groups were divided as Ti implants (Ti), Ti modified with TiO2 nanotubes (TiO2-NTs) and Ti modified with Si-TiO2 nanotubes (Si-TiO2-NTs). The morphology of Si-TiO2 nanotubes was observed by scanning electron microscope. The growth and osteogenic differentiation of MC3T3-E1 cells on the Ti implants were evaluated. Further, the pull-out tests and in vivo osseointegration ability evaluation were performed after implanting the screws in the femur of Sprague Dawley rats. RESULTS: The Si-TiO2 nanotubes could be seen on the surface of Ti implants. The MC3T3-E1 cells could grow on the surface of Ti, TiO2-NTs and Si-TiO2-NTs, and showed fast proliferation rate on the Si-TiO2-NTs. Moreover, the production of some osteogenesis-related proteins (ALP and Runx2) at one week and calcium deposition at four week was also enhanced in Si-TiO2-NTs rather than other groups. In vivo osseointegration results showed that Si-TiO2 nanotube-modified Ti screws had higher pullout force at two and four weeks as well as enhanced new bone formation at six weeks compared to bare Ti screws and Ti screws modified with TiO2 nanotubes alone. DISCUSSION: The modification of Si-TiO2-NTs on the Ti substrate could generate a nanostructured and hydrophilic surface, which can promote cell growth. Moreover, the existence of the TiO2 nanotubes and Si element also can improve the in vitro osteogenic differentiation of MC3T3-E1 cells and early bone formation around the implanted screws. Together, findings from this study show that surface modification of Ti implants with Si-TiO2 nanotubes could enhance early osseointegration and therefore has the potential for clinical applications.

Prognostic value of NT-proBNP in patients with severe COVID-19.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury is a common condition among the hospitalized patients with COVID-19. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of severe COVID-19 patients was unknown. METHODS: The study initially enrolled 102 patients with severe COVID-19 from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. The primary outcome was in-hospital death defined as the case fatality rate. Research information and following-up data were obtained from their medical records. RESULTS: The best cut-off value of NT-proBNP for predicting in-hospital death was 88.64 pg/mL with the sensitivity for 100% and the specificity for 66.67%. Patients with high NT-proBNP values (> 88.64 pg/mL) had a significantly increased risk of death during the days of following-up compared with those with low values (≤88.64 pg/mL). After adjustment for potential risk factors, NT-proBNP was independently correlated with in-hospital death. CONCLUSION: NT-proBNP might be an independent risk factor for in-hospital death in patients with severe COVID-19. TRIAL REGISTRATION: ClinicalTrials, NCT04292964. Registered 03 March 2020.

TNAP inhibition attenuates cardiac fibrosis induced by myocardial infarction through deactivating TGF-ß1/Smads and activating P53 signaling pathways.

Tissue nonspecific alkaline phosphatase (TNAP) is expressed widely in different tissues, modulating functions of metabolism and inflammation. However, the effect of TNAP on cardiac fibrosis remains controversial and needs to be further studied. The present study aims to investigate the role of TNAP on myocardial infarction (MI)-induced fibrosis and its mechanism. TNAP was upregulated in patients with MI, both in serum and injured hearts, and predicted in-hospital mortality. TNAP was also significantly upregulated after MI in rats, mostly in the border zone of the infarcted hearts combined with collagen synthesis. Administration of TNAP inhibitor, tetramisole, markedly improved cardiac function and fibrosis after MI. In the primary cultures of neonatal rat cardiac fibroblasts (CFs), TNAP inhibition significantly attenuated migration, differentiation, and expression of collagen-related genes. The TGF-ß1/Smads signaling suppression, and p-AMPK and p53 upregulation were involved in the process. When p53 inhibitor was administered, the antifibrotic effect of TNAP inhibition can be blocked. This study provides a direct evidence that inhibition of TNAP might be a novel regulator in cardiac fibrosis and exert an antifibrotic effect mainly through AMPK-TGF-ß1/Smads and p53 signals.

Spiral stir bar sorptive extraction with polyaniline-polydimethylsiloxane sol-gel packings for the analysis of trace estrogens in environmental water and animal-derived food samples.

A spiral stir bar was proposed by using stainless steel spring as the extraction phase carrier to avoid the extraction phase friction and increase the amount of extraction phase for improving extraction efficiency. The extraction phase is filled in the cavity of the spring, resulting in a larger amount of the extraction phase than that conventionally coated on glass stir bar or stainless steel wire. Polyaniline-polydimethylsiloxane sol-gel packed spiral stir bar was prepared and evaluated for the extraction of five estrogens. The prepared spiral stir bar presented good extraction efficiency/preparation reproducibility and long lifetime (more than 150 reused times) for target estrogens. Based on it, a method of spiral stir bar sorptive extraction combined with high performance liquid chromatography coupled with ultra-violet detection was developed for the analysis of trace estrogens in environmental and food samples. The detection limit for five estrogens was 0.11-.31 µg/L, with the enrichment factors of 83.0-118-fold (maximal enrichment factor: 200-fold). The reproducibility evaluated with each estrogen of 5 µg/L (n = 5) was 5.8-8.9%. The method was successfully applied for the determination of estrogens in environmental water and animal-derived food samples.

DNA hydroxymethylation combined with carotid plaques as a novel biomarker for coronary atherosclerosis.

Little is known about the diagnostic value of DNA methylation and hydroxymethylation for coronary atherosclerosis. Carotid plaque is a common marker for coronary atherosclerosis. Our aim is to determine whether DNA methylation and hydroxymethylation combined with carotid plaques can be useful to the diagnosis of coronary atherosclerosis. The 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) levels from peripheral blood mononuclear cells (PBMCs) were measured in 113 enrolled patients. Crouse score and Gensini score were used to evaluate the severity of carotid and coronary atherosclerosis, respectively. With the increasing of severity of carotid plaque, a stepwise upward trend was observed in 5-mC and 5-hmC levels from PBMCs, which were significantly correlated with the risk factors, Crouse score and Gensini score. Crouse score and 5-hmC, not 5-mC, were the risk factors for coronary atherosclerosis after adjustment for the risk factors (the history of diabetes, FPG and HbA1c). Receiver operating characteristic (ROC) analysis indicated that 5-hmC combined with Crouse score was the diagnostic biomarker for coronary atherosclerosis, with the highest areas under the curve (AUC) for 0.980 (0.933-0.997), valuable sensitivity for 96.23% and specificity for 91.67%. These findings suggest 5-hmC level combined with Crouse score may provide the meaningful information for coronary atherosclerosis diagnosis.

DNA methylation and hydroxymethylation are associated with the degree of coronary atherosclerosis in elderly patients with coronary heart disease.

AIMS: DNA methylation and hydroxymethylation are significantly related to the occurrence and development of coronary heart disease (CHD) and atherosclerosis (AS). 5-Methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) are used to assess DNA methylation and hydroxymethylation levels, respectively. However, 5-mC and 5-hmC levels associated with CHD remain controversial. In the present study, we aimed to investigate the association of the peripheral blood levels of 5-mC and 5-hmC and the degree of coronary atherosclerosis in elderly CHD patients. MAIN METHODS: 5-mC and 5-hmC levels in peripheral blood mononuclear cells (PBMCs) were measured in 44 CHD patients and 42 matched control subjects by ELISA and dot blot analysis. Immunohistochemical staining was used to observe 5-mC, 5-hmC and TET2 expression in human aortic tissue. Gensini score was used to evaluate the degree of coronary atherosclerosis. KEY FINDINGS: 5-mC and 5-hmC levels in PBMCs from CHD patients and in human aortic atherosclerosis plaque were both higher than those in control subjects and in tissue samples. TET2 expression was significantly upregulated in CHD patients compared with control subjects, while only an increasing trend in the expression of DNMT1, DNMT3A and all the other TET genes were found. Spearman correlation analysis demonstrated that 5-mC and 5-hmC levels were positively correlated with Gensini score. 5-mC and 5-hmC were considered as the risk factors for CHD after adjustment. SIGNIFICANCE: DNA methylation and hydroxymethylation levels in PBMCs from elderly CHD patients were significantly increased, showing a positive correlation with the degree of coronary atherosclerosis.

One-pot synthesis of zeolitic imidazolate framework-8/poly (methyl methacrylate-ethyleneglycol dimethacrylate) monolith coating for stir bar sorptive extraction of phytohormones from fruit samples followed by high performance liquid chromatography-ultraviolet detection.

In this work, zeolitic imidazolate framework-8 (ZIF-8)/poly (methyl methacrylate-ethyleneglycol dimethacrylate) (MMA-EGDMA) composite monolith was in situ synthesized on stir bar by one-pot polymerization. Compared with the neat monolith, ZIF-8/poly(MMA-EGDMA) composite monolith has larger surface area and pore volume. It also exhibits higher extraction efficiency for target phytohormones than poly(MMA-EGDMA) monolith and commercial polyethylene glycol (PEG) coated stir bar. Based on it, a method of ZIF-8/poly(MMA-EGDMA) monolith coated stir bar sorptive extraction (SBSE)-high performance liquid chromatography-ultraviolet detection (HPLC-UV) was established for the analysis of five phytohormones in apple and pear samples. The developed method exhibited low limits of detection (0.11-0.51µg/L), wide linear range (0.5-500µg/L) and good recoveries (82.7-111%), which demonstrated good application potential of the ZIF-8/monolith coated stir bar in trace analysis of organic compounds.

Polydimethylsiloxane/MIL-100(Fe) coated stir bar sorptive extraction-high performance liquid chromatography for the determination of triazines in environmental water samples.

Polydimethylsiloxane (PDMS)/MIL-100(Fe) coated stir bar was prepared by sol gel technique, and good preparation reproducibility was achieved with relative standard deviations (RSDs) ranging from 2.6% to 7.5% (n=7) and 3.6% to 10.8% (n=7) for bar-to-bar and batch-to-batch, respectively. Compared with commercial PDMS coated stir bar (Gerstel) and PEG coated stir bar (Gerstel), the prepared PDMS/MIL-100(Fe) stir bar showed better extraction efficiency for target triazines compounds. It also exhibited relatively fast extraction/desorption kinetics and long lifespan. Based on it, a method of PDMS/MIL-100(Fe) coated stir bar sorptive extraction (SBSE)-high performance liquid chromatography-ultraviolet detector (HPLC-UV) was developed for the determination of six triazines (simazine, atrazine, prometon, ametryn, prometryne and prebane) in environmental water samples. Several parameters affecting SBSE of six target triazines including extraction time, stirring rate, sample pH, ionic strength, desorption solvent and desorption time were investigated. Under the optimal experimental conditions, the limits of detection (LODs, S/N=3) were found to be in the range of 0.021-0.079µgL-1. The repeatability RSDs were in the range of 2.3-6.3% (n=7, c=0.5µgL-1) and the enrichment factors (EFs) ranged from 51.1 to 102-fold (theoretical EF was 200-fold). The proposed method was applied to the analysis of target triazines in environmental water samples, with recoveries of 98.0-118% and 94.0-107% for spiked East Lake water and local pond water samples, respectively.

Water-compatible graphene oxide/molecularly imprinted polymer coated stir bar sorptive extraction of propranolol from urine samples followed by high performance liquid chromatography-ultraviolet detection.

Due to the high selectivity and stability, molecularly imprinted polymers (MIPs) have been successfully applied in stir bar sorptive extraction (SBSE) as a special coating to improve the selective extraction capability for target analytes. However, traditional MIPs usually suffer from incompatibility in aqueous media and low adsorption capacity, which limit the application of MIP coated stir bar in aqueous samples. To solve these problems, a water-compatible graphene oxides (GO)/MIP composite coated stir bar was prepared in this work by in situ polymerization. The prepared water-compatible GO/MIP coated stir bar presented good mechanical strength and chemical stability, and its recognition ability in aqueous samples was improved due to the polymerization of MIP in water environment, the adsorption capacity for target analytes was also increased by the addition of GO in MIP pre-polymer solution. Based on it, a method of water-compatible GO/MIP coated stir bar sorptive extraction combined with high performance liquid chromatography-ultraviolet detector (HPLV-UV) was proposed for the analysis of propranolol (PRO) in aqueous solution. The influencing factors of SBSE, such as sample pH, salt effect, stirring rate, extraction time, desorption solvent and desorption time, were optimized, and the analytical performance of the developed SBSE-HPLC-UV method was evaluated under the optimized conditions. The limit of detection (LOD) of the proposed method for PRO was about 0.37 µg L(-1), and the enrichment factor (EF) was 59.7-fold (theoretical EF was 100-fold). The reproducibility was also investigated at concentrations of 5 µg L(-1) and the relative standard deviation (RSD) was found to be 7.3% (n=7). The proposed method of GO/MIP coating-SBSE-HPLC-UV was successfully applied for the assay of the interested PRO drug in urine samples, and further extended to the investigation of the excretion of the drugs by monitoring the variation of the concentration of PRO in urine within 10h after drug-taking.