The association between Chinese Visceral Adipose Index and coronary heart disease: A cohort study in China.

BACKGROUND AND AIMS: The purpose of this study is to explore the relationship between Chinese visceral adipose index (CVAI) and the risk of coronary heart disease (CHD) in Chinese through a large cohort study. METHODS AND RESULTS: This study included 42,165 adults who were without CHD at baseline and who completed at least one annual follow-up between 2009 and 2016. We used the Cox proportional hazards model to estimate Hazard Ratios (HRs) and 95% Confidence Intervals (CIs) for the association between CVAI and risk of CHD. During the median follow-up of 3.36 years (154,808 person years), 520 participants developed CHD, including 374 males and 146 females. Compared with the first quartile of CVAI, the risk of CHD was significantly increased in the fourth quartile of CVAI in multivariate model (HR [95% CI]: 9.92 [5.45, 18.04], P < 0.001). Sensitivity analysis by excluding incident CHD developed in the first two years of follow-up reinforced our results. Gender stratification analyses showed that the relationship between CVAI and CHD risk was higher in males than that in females. The restricted cubic spline showed a non-linear dose-response relationship between CVAI and CHD risk. In addition, CVAI was associated with CHD risk in the subgroups of participants without T2DM, without hypertension, and without fatty liver. CONCLUSION: CVAI was significantly associated with the risk of CHD. Individuals should keep CVAI at normal level to prevent CHD.

The association between low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio cholesterol ratio and thickened carotid intima-media thickness: A case-control study.

BACKGROUND: It is indicated that Low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C ratio) has greater predictive value for thickened carotid intima-media thickness (CIMT) comparing with classic lipid parameters. However, there have been few reports about their association in general Chinese population. METHOD: We included a total of 1220 CIMT participants and 2440 matched controls, who had ultrasonography of carotid artery during 2009 and 2016. Univariate and multivariate logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for thickened CIMT risk associated with LDL-C/HDL-C ratio. RESULT: In the univariate logistic regression model, there was significant association between LDL-C/HDL-C ratio and thickened CIMT (Q4 vs. Q1, OR = 1.94, 95% CI: 1.60-2.36; ptrend < 0.05). After adjusting for potential covariates, LDL-C/HDL-C ratio remained significantly associated with thickened CIMT (Q4 vs. Q1, OR = 1.81, 95% CI: 1.41-2.34, ptrend < 0.001; ≥3.05 v.s. <3.05, OR = 1.66, 95% CI: 1.37-2.02). In subgroup analyses, the association between LDL-C/HDL-C ratio and thickened CIMT remained significant in the subgroups stratified by sex, impaired fasting glucose (IFG), hypertension, and fatty liver disease but only remained significant in the subgroups of ≥45 years (OR = 2.01, 95% CI: 1.46-2.76; Ptrend<0.05), BMI ≥24 (kg/m2) (OR = 2.22; 95% CI = 1.63-3.03; Ptrend < 0.05) and BMI ≥25 (kg/m2) (OR = 2.50, 95% CI: 1.76-3.54; Ptrend < 0.05), dyslipidemia (OR = 3.28, 95% CI: 1.83-5,85; Ptrend < 0.001), and without periodontitis (OR = 2.08, 95% CI: 1.54-2.81 ; Ptrend < 0.05) comparing Q4 to Q1. Similar results were observed in the subgroup analyses for LDL-C/HDL-C ratio ≥3.05 v.s. <3.05 except for the age stratification. CONCLUSION: High LDL-C/HDL-C ratio could significantly increase the risk of thickened CIMT independent of gender, IFG, hypertension, and fatty liver disease in general Chinese population.

Platelet-Lymphocyte Ratio, Neutrophil-Lymphocyte Ratio and Their Dynamic Changes with Type 2 Diabetes Mellitus: A Cohort Study in China.

BACKGROUND: This study aimed at investigating the relationships between Platelet-Lymphocyte ratio (PLR) and Neutrophil-Lymphocyte ratio (NLR) and their dynamic changes (∆PLR, ∆NLR) with type 2 diabetes mellitus (T2DM) in a Chinese cohort study. METHODS: This study recruited 41,439 individuals who were diagnosed without T2DM at first health examination and completed at least one follow-up. The relationships between NLR, PLR, ∆PLR, ∆NLR and T2DM risk were analyzed using the Cox regression model with corresponding Hazard Ratios (HRs) and 95% Confidence Intervals (CIs). RESULTS: PLR exhibited significant correlation with T2DM risk in a linear reverse dose-response pattern, the corresponding HRs and 95% CIs were 0.81 (0.72, 0.90), 0.71 (0.63, 0.80) and 0.56 (0.49, 0.64) respectively (Ptrend < 0.001) for Q2, Q3 and Q4 vs Q1 after adjusting for age, gender, BMI, TG, TC, HDL-C, FPG, ALT, AST, heart rate, smoking, family history of diabetes, and alcohol consumption at baseline in Model 3. The significance remained in subgroups of women, <45 years, ≥45 years, BMI ≥ 24, with fatty liver disease, without fatty liver disease and normotension. Comparing with the largest decrease group of NLR (∆NLR < -0.32), the risk of T2DM increased for -0.003 ≤ ∆NLR < 0.31 (HR 1.17, 95% CI 1.01-1.36) and ∆NLR ≥ 0.31 (HR 1.23, 95% CI 1.06-1.43). CONCLUSIONS: Higher PLR could reduce the risk of T2DM. Larger increase of NLR could increase T2DM risk.

Dose-response association of the ZJU index and fatty liver disease risk: A large cohort in China.

AIM: The aim of this study is to investigate the sex-specific association between the ZJU index and risk of fatty liver disease in a large Chinese cohort. METHODS: A total of 28 729 adults without fatty liver disease at baseline and who completed at least one follow-up of annual examinations between 2009 and 2016 were included in this study. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for fatty liver disease risk associated with the ZJU index. RESULTS: During a median follow-up of 3.01 years, 7373 developed fatty liver disease. There were significant associations between the ZJU index and fatty liver disease for women and men with increasing HRs as the quartiles increase across Q2-Q4, corresponding HRs (95% CIs) in M3 were 2.28 (1.98-2.64), 3.52 (3.07-4.04), and 4.87 (4.24-5.59) for women and 2.44 (2.17-2.75), 4.18 (3.73-4.68), and 6.23 (5.56-6.98) for men. The association between the ZJU index and fatty liver disease risk remained significant in all the subgroups except that of T2DM and abdominal obesity subgroups for men. However, the association became nonsignificant when comparing Q3 and Q2 of the ZJU index with reference in the subgroups of T2DM for men, and nonsignificant when comparing Q3 of the ZJU index with reference in the subgroups of participants with T2DM and abdominal obesity for women. CONCLUSION: The ZJU index was significantly associated with the risk of fatty liver disease in Chinese population. It will be better to keep body mass index, alanine aminotransferase, aspartate aminotransferase, triglyceride, and fasting plasma glucose at a normal level for preventing fatty liver disease.

Association between blood urea nitrogen and incidence of type 2 diabetes mellitus in a Chinese population: a cohort study.

To examine the association between blood urea nitrogen (BUN) and risk of type 2 diabetes (T2DM) among Chinese adults, we performed an ongoing cohort study of 38578 Chinese adults (56.3% males; average age, 41.6 y) who underwent repeated health check-up examinations between 2009 and 2016 and without T2DM at baseline. During follow-up, incident T2DM cases were identified based on self-report, medication use, measurements of fasting plasma glucose, 2 h post oral glucose, or haemoglobinA1c. 2009 (5.2%) cases confirmed with incident T2DM were identified during median follow-up of 3.1 years. With increasing quartiles of BUN levels, the incidences of T2DM gradually increased with 0.69%, 1.11%, 1.53%, and 1.87% for quartile 1 to quartile 4 (p trend <0.001). Compared with quartile 1, the multivariate-adjusted hazard ratios (HRs) and its 95% confidence intervals (95% CIs) for T2DM risk were 1.16 (0.97-1.38) for quartile 2, 1.28 (1.07-1.51) for quartile 3, and 1.28 (1.08-1.52) for quartile 4 (p trend = 0.005). HR for per each standard deviation increase in BUN level was 1.10 (1.04-1.16) (p trend <0.001). This association tended to be more pronounced in those with a lower body mass index at baseline (p-interaction <0.001). Our results suggested that BUN levels were positively associated with incident T2DM risk among Chinese adults. Future prospective investigations in other populations are necessary to confirm our findings.

A comprehensive association analysis between homocysteine metabolic pathway gene methylation and ischemic stroke in a Chinese hypertensive population.

BACKGROUND: Ischemic stroke (IS) is a serious global health burden. In order to improve our understanding of the risk factors associated with IS, we investigated the combined effect of the methylation of five genes related to the metabolism of homocysteine on developing IS. METHODS: Quantitative methylation-specific PCR was used to measure the levels of promoter methylation in hypertensive and stroke patients. The cutoff value calculated by the maximum Youden index was used to classify the levels of gene methylation as hypomethylation and hypermethylation. Logistic regression was used to explore the relationship between gene methylation and IS. RESULTS: The methylation levels of the genes encoding methylenetetrahydrofolate dehydrogenase 1 [MTHFD1], cystathionine ß-synthase [CBS], and dihydrofolate reductase [DHFR] in hypertensive patients were higher than those in stroke patients (all p < 0.01). MTHFD1 hypermethylation, CBS hypermethylation, and DHFR hypermethylation were protective factors for stroke after adjustment for confounding factors. Compared with individuals carrying none of the biomarkers, the ORs [95% CIs] for stroke of those with 1 and 2 elevated biomarkers were 4.068 [1.670-9.913] and 15.345 [6.198-37.994] after adjustment for confounding factors. The participants with a larger number of biomarkers had an increased risk of stroke (p for trend <0.001). For the combination biomarkers, the area under the curve of the receiver operating characteristic was 0.716. CONCLUSION: A significant linear relationship between the number of elevated biomarkers and the risk of stroke has been observed, suggesting that elevations of these biomarkers could be used for potentially predicting the disease.

Baseline serum albumin and its dynamic change is associated with type 2 diabetes risk: A large cohort study in China.

BACKGROUND: The study aimed to investigate the associations of baseline serum albumin level and its dynamic change with type 2 diabetes mellitus (T2DM) risk in a large Chinese cohort study. METHODS: This cohort study included 30 442 adults without T2DM at first entry, who completed at least one follow-up of annual examinations between 2009 and 2016. Serum albumin level was measured at baseline and at every annual check-up. The dynamic change in serum albumin level (∆ALB) was calculated by subtracting serum albumin level at baseline from that at the last follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox regression models. RESULTS: During 7 years of follow-up, we identified 1634 T2DM events. From the lowest to the highest quartile of serum albumin level, adjusted HRs (95% CI) were 1.00 (reference), 0.96 (0.94, 1.01), 0.98 (0.95, 1.02) and 0.88 (0.85, 0.98), respectively. As compared with stable change in serum albumin (-0.2 ≤ ∆ALB <1.0 g/L), the risk of T2DM increased for ∆ALB < -2.0 g/L (HR 1.44, 95% CI 1.24-1.68) and decreased for ∆ALB ≥3.0 g/L (0.81, 0.68-0.97) after adjusting for potential confounding factors. Restricted cubic splines showed a linear dose-response association between baseline serum albumin level and T2DM risk (Pnonlinearity 0.715) and a nonlinear dose-response association between ∆ALB and T2DM risk (Pnonlinearity 0.011). CONCLUSIONS: Baseline serum albumin level appears to be inversely associated with T2DM risk. Adults with reduced serum albumin level could be early identified for diabetes risk in clinical practice.

LDL-cholesterol to HDL-cholesterol ratio discordance with lipid parameters and carotid intima-media thickness: a cohort study in China.

BACKGROUND: The discordance of the low-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio with alterative lipid parameters may explain the inconsistent association of CIMT with the LDL-C/HDL-C ratio. Therefore, this study aimed to explore the associations between LDL-C/HDL-C ratio discordance with alternative lipid parameters and elevated carotid intima-media thickness (CIMT) risk in a large cohort in Beijing, China. METHODS: In total, 13,612 adults who didn't have elevated CIMT at baseline and who participated in at least one follow-up of annual examination between 2009 and 2016 were included in this cohort study. A multivariable Cox regression model was utilized to evaluate the associations of discordance of the LDL-C/HDL-C ratio with TC, TGs, LDL-C and HDL-C with elevated CIMT risk. RESULTS: During 37,999 person-years of follow-up, 2004 individuals (1274 men and 730 women) developed elevated CIMT. Among individuals with normal TC and TGs, 16.6 and 15.2% individuals had a discordantly high LDL-C/HDL-C ratio, respectively, and the risk of elevated CIMT increased by 1.54 (95% CI 1.33, 1.77) and 1.53 (95% CI 1.33, 1.76), respectively, comparing to individuals with a concordantly low LDL-C/HDL-C ratio. A high LDL-C/HDL-C ratio could significantly increase elevated CIMT risk regardless of discordance/concordance with LDL-C and HDL-C (P < 0.001). A low LDL-C/HDL-C ratio with discordantly normal HDL-C and high LDL-C (13.2% of individuals) had a 32% (HR = 1.32, 95% CI 1.11, 1.57) higher risk of elevated CIMT than concordantly low LDL-C and normal HDL-C. Sensitivity analysis by excluding CIMT developed in the first 2 years follow-up further confirmed the above results. CONCLUSIONS: A high LDL-C/HDL-C ratio could significantly increase elevated CIMT risk regardless of discordance/concordance with TC, TGs, LDL-C and HDL-C Even a low LDL-C/HDL-C ratio with discordantly high LDL-C and normal HDL-C could also significantly increase CIMT risk. Individuals should maintain both the LDL-C/HDL-C ratio and LDL-C at normal levels to prevent elevated CIMT.

Association of Plasma 7-Ketocholesterol With Cardiovascular Outcomes and Total Mortality in Patients With Coronary Artery Disease.

RATIONALE: 7-Ketocholesterol (7-KC), a form of cholesterol oxidation product, plays an essential role in the atherogenesis in animal models. OBJECTIVE: We sought to determine the association of circulating 7-KC with clinical cardiovascular outcomes and total mortality in patients with stable coronary artery disease. METHODS AND RESULTS: We measured the plasma 7-KC levels by high-performance liquid chromatography in a prospective cohort study of 1016 patients (mean age, 63.2 years; male 61.1%) with stable coronary artery disease who were recruited from December 2008 to December 2011 and followed up for a median of 4.6 years. We adjudicated myocardial infarction, hospitalization of heart failure, cardiovascular death, all-cause death, and composite end points of myocardial infarction/heart failure/death by review of medical records and death certificates. We used multivariable Cox proportional hazards analysis to compare the incidence rate of cardiovascular events and all-cause death according to the quartile of the plasma 7-KC. During the median 4.6 years follow-up, totally 221 participants (21.8%) experienced a cardiovascular event or death. The adjusted risk of the composite end points was higher in the highest 7-KC quartile than in the lowest quartile (hazard ratio, 1.76; 95% confidence interval, 1.42-2.21; P<0.001). After adjustment for demographic and clinical variables and other biomarkers, including high-sensitivity C-reactive protein and NT-proBNP (N-terminal pro-B-type natriuretic peptide), 1 SD increase in the 7-KC level remained associated with a 36% higher rate of composite outcomes (hazard ratio, 1.36; 95% confidence interval, 1.22-1.48; P=0.007). Plasma 7-KC clearly improved various model performance measures, including C statistics, integrated discrimination, and category-free net reclassification. CONCLUSIONS: High 7-KC levels are associated with increased risk of cardiovascular events, total death, and composite outcomes in patients with stable coronary artery disease.

Evaluating Surgical Resident Needle Insertion Skill Gains in Central Venous Catheterization Training.

BACKGROUND: Training for ultrasound-guided central venous catheterization (CVC) is typically conducted on static manikin simulators with real-time feedback from a skilled observer. Dynamic haptic robotic trainers (DHRTs) are an alternative method that simulates various patient anatomies and provides consistent feedback for each insertion. This study evaluates CVC needle insertion efficiency and skill gains of both methods. MATERIALS AND METHODS: Fifty-two first-year surgical residents were trained by placing internal jugular (IJ) CVC needles in manikins (n = 26) or robots (n = 26). Manikin-trained participants received verbal feedback from an experienced observer, whereas robotically trained participants received quantitative feedback from the personalized DHRT learning interface. All participants were pretested on a Blue Phantom manikin; participants completed posttesting on a Blue Phantom manikin (n = 26) or a novel manikin (n = 26) with different vessel depth and position. During pretests and posttests residents were timed, motion-tracked, and scored on an IJ CVC checklist. RESULTS: (1) All skills on the IJ CVC checklist showed significant (P < 0.014) improvements from pretests to posttest; (2) Average angle of insertion, path length, and jerk improved significantly (P < 0.005); (3) Average procedural completion time, with standard error (SE) reported, decreased significantly from pretest (M = 3.516 min, SE = 0.277) to posttest (M = 1.997, SE = 0.409). CONCLUSIONS: No significant group differences were observed in overall skill gains, but residents' average procedural completion time decreased significantly from pretests to posttest. Overall results support DHRT as an effective method for training IJ CVC skills.

Retinol-Binding Protein-Dependent Cholesterol Uptake Regulates Macrophage Foam Cell Formation and Promotes Atherosclerosis.

BACKGROUND: Retinol-binding protein 4 (RBP4) is an adipokine that plays decisive roles in glucose metabolism and insulin sensitivity. Elevated circulating RBP4 levels were reported to be associated with increased risk for cardiovascular disease, but the precise role of RBP4 in atherosclerotic diseases and its mechanisms of action remain elusive. METHODS: Serum RBP4 levels of 1683 participants from South China were evaluated and the occurrence of major adverse cardiovascular events was followed up for 5 years. Apolipoprotein E-deficient mice infected with RBP4-overexpressing/silencing adenovirus, J774A.1 macrophages, and primary peritoneal macrophages from RBP4 transgenic mice were used for investigating the function of RBP4 in foam cell formation. RESULTS: Prospective cohort studies revealed that baseline serum RBP4 level was an independent predictor for incidence of adverse cardiovascular events after adjustment for traditional risk factors. Increased RBP4 expression was observed in atherosclerotic lesions of aortic specimens from both humans and apolipoprotein E-deficient mice, and RBP4 was localized to areas rich in macrophage foam cells. RBP4 inhibition attenuated whereas overexpression accelerated atherosclerosis progression in apolipoprotein E-deficient mice. Both treatment with exogenous recombinant RBP4 and overexpression of RBP4 gene promoted macrophage-derived foam cell formation through the activation of scavenger-receptor CD36-mediated cholesterol uptake, and RBP4 transcriptionally upregulated CD36 expression in a manner dependent on jun N-terminal kinase and signal transducer and activator of transcription 1. The tyrosine kinase c-Src was identified as the upstream regulator of jun N-terminal kinase-signal transducer and activator of transcription 1-mediated CD36-dependent cholesterol uptake, and RBP4 challenge was found to alter the membrane distribution of c-Src and cause c-Src to partition into lipid-raft membrane subdomains, where the kinase was activated. Lastly, Toll-like receptor 4, but not retinol or stimulated by retinoic acid 6, mediated the inductive effects of RBP4 in macrophages. CONCLUSIONS: Inclusion of RBP4 levels in traditional models enhances the predictive ability for the incidence of atherosclerotic events. RBP4 promotes atherogenesis by inducing macrophage-derived foam cell formation.

Association of Serum Retinoic Acid With Risk of Mortality in Patients With Coronary Artery Disease.

RATIONALE: Retinoic acid (RA) and its mediated nuclear receptor signaling have broad protective effects on vascular systems. Whether circulating levels of RA are associated with mortality in patients with coronary artery disease is still unknown. OBJECTIVE: To evaluate the association of circulating RA with the risk of mortality. METHODS AND RESULTS: We measured serum RA concentrations in 1499 patients with angiographically confirmed coronary artery disease (mean age, 61 years; male, 67%) recruited from October 2008 and December 2011 in the Guangdong Coronary Artery Disease Cohort. During a median (interquartile range) period of 4.4 (3.6 to 6.1) years of follow-up, there were 295 all-cause mortality, among which 208 had cardiovascular mortality. Serum RA level was significantly lower in participants with mortality (median 21 [11-47] nmol/L) than in those without mortality (median 39 [19-86] nmol/L). In multivariate analyses, the hazard ratios for total mortality among those in the lowest (referent) to highest quartiles of serum RA measured at study entry were 1.0, 0.83, 0.74, and 0.56, respectively (P-trend<0.001). For cardiovascular mortality, the comparable hazard ratios were 1.0, 0.76, 0.69, and 0.60 (P-trend<0.001). Furthermore, high RA levels (defined as >median) were associated with lower risk of total mortality (adjusted hazard ratios, 0.68; 95% confidence interval, 0.50-0.85; P=0.001) and cardiovascular mortality (adjusted hazard ratios, 0.62; 95% confidence interval, 0.45-0.78; P<0.001) compared with low RA (defined as ≤median). CONCLUSIONS: Serum RA level was associated with lower risk of mortality in a population-based coronary artery disease cohort.

PGC-1ß suppresses saturated fatty acid-induced macrophage inflammation by inhibiting TAK1 activation.

Inflammation of infiltrated macrophages in adipose tissue is a key contributor to the initiation of adipose insulin resistance. These macrophages are exposed to high local concentrations of free fatty acids (FFAs) and can be proinflammatory activated by saturated fatty acids (SFAs). However, the regulatory mechanisms on SFA-induced macrophage inflammation are still elusive. Peroxisome proliferator-activated receptor γ coactivator-1ß (PGC-1ß) is a member of the PGC-1 family of transcriptional coactivators and has been reported to play a key role in SFAs metabolism and in the regulation of inflammatory signaling. However, it remains unclear whether PGC-1ß is involved in SFA-induced macrophage inflammation. In this study, we found that PGC-1ß expression was significantly decreased in response to palmitic acid (PA) in macrophages in a dose dependent manner. PGC-1ß inhibited PA induced TNFα, MCP-1, and IL-1ß mRNA and protein expressions. Furthermore, PGC-1ß significantly antagonized PA induced macrophage nuclear factor-κB (NF-κB) p65 and JUN N-terminal kinase activation. Mechanistically, we revealed that TGF-ß-activated kinase 1 (TAK1) and its adaptor protein TAK1 binding protein 1 (TAB1) played a dominant role in the regulatory effects of PGC-1ß. We confirmed that PGC-1ß inhibited downstream inflammatory signals via binding with TAB1 and thus preventing TAB1/TAK1 binding and TAK1 activation. Finally, we showed that PGC-1ß overexpression in PA treated macrophages improved adipocytes PI3K-Akt insulin signaling in a paracrine fashion. Collectively, our results uncovered a novel mechanism on how macrophage inflammation induced by SFAs was regulated and suggest a potential target in the treatment of obesity induced insulin resistance.

Retinoic acid induces macrophage cholesterol efflux and inhibits atherosclerotic plaque formation in apoE-deficient mice.

It has been suggested that retinoic acid (RA) has a potential role in the prevention of atherosclerotic CVD. In the present study, we used J774A.1 cell lines and primary peritoneal macrophages to investigate the protective effects of RA on foam cell formation and atherogenesis in apoE-deficient (apoE- / -) mice. A total of twenty male apoE- / - mice (n 10 animals per group), aged 8 weeks, were fed on a high-fat diet (HFD) and treated with vehicle or 9-cis-RA for 8 weeks. The atherosclerotic plaque area in the aortic sinus of mice in the 9-cis-RA group was 40·7 % less than that of mice in the control group (P< 0·01). Mouse peritoneal macrophages from the 9-cis-RA group had higher protein expression levels of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) than those from the control group. Serum total and LDL-cholesterol concentrations were lower in the 9-cis-RA group than in the control group (P< 0·05). In vitro studies showed that incubation of cholesterol-loaded J774A.1 macrophages with 9-cis-RA (0·1, 1 and 10 µmol/l) induced cholesterol efflux in a dose-dependent manner. The 9-cis-RA treatment markedly attenuated lipid accumulation in macrophages exposed to oxidised LDL. Moreover, treatment with 9-cis-RA significantly increased the protein expression levels of ABCA1 and ABCG1 in J774A.1 macrophages in a dose-dependent manner. Furthermore, 9-cis-RA dose-dependently enhanced the protein expression level of liver X receptor-α (LXRα), the upstream regulator of ABCA1 and ABCG1. Taken together, the present results show that 9-cis-RA suppresses foam cell formation and prevents HFD-induced atherogenesis via the LXRα-dependent up-regulation of ABCA1 and ABCG1.

Ionization of high-density deep donor defect states explains the low photovoltage of iron pyrite single crystals.

Iron pyrite (FeS2) is considered a promising earth-abundant semiconductor for solar energy conversion with the potential to achieve terawatt-scale deployment. However, despite extensive efforts and progress, the solar conversion efficiency of iron pyrite remains below 3%, primarily due to a low open circuit voltage (VOC). Here we report a comprehensive investigation on {100}-faceted n-type iron pyrite single crystals to understand its puzzling low VOC. We utilized electrical transport, optical spectroscopy, surface photovoltage, photoelectrochemical measurements in aqueous and acetonitrile electrolytes, UV and X-ray photoelectron spectroscopy, and Kelvin force microscopy to characterize the bulk and surface defect states and their influence on the semiconducting properties and solar conversion efficiency of iron pyrite single crystals. These insights were used to develop a circuit model analysis for the electrochemical impedance spectroscopy that allowed a complete characterization of the bulk and surface defect states and the construction of a detailed energy band diagram for iron pyrite crystals. A holistic evaluation revealed that the high-density of intrinsic surface states cannot satisfactorily explain the low photovoltage; instead, the ionization of high-density bulk deep donor states, likely resulting from bulk sulfur vacancies, creates a nonconstant charge distribution and a very narrow surface space charge region that limits the total barrier height, thus satisfactorily explaining the limited photovoltage and poor photoconversion efficiency of iron pyrite single crystals. These findings lead to suggestions to improve single crystal pyrite and nanocrystalline or polycrystalline pyrite films for successful solar applications.

Facile Multiple Graded Wrinkle Construction Strategy for Vastly Boosting the Sensing Performance of Ionic Skins.

The construction of surface microstructures (e.g., micropyramids and wrinkles) has been proven as the most effective means to boost the sensitivity of ionic skins (I-skins). However, the single-scale micronano patterns constructed by the common fabrication strategy generally lead to a limited pressure-response range. Here, a convenient repeated stretching/coordinating/releasing strategy is developed to controllably construct multiple graded wrinkles on the polyelectrolyte hydrogel-based I-skins for increasing their sensitivity over a broad pressure range. We find that the small wrinkles allow for high sensitivity yet small pressure detection range, while the large wrinkles can reduce structural stiffening to generate large pressure-response range but incur limited sensitivity. The multiple graded wrinkles can combine the merits of both the small and large wrinkles to simultaneously improve the sensitivity and broaden the pressure-response range. In particular, the sensing performance of multiple-wrinkle-based I-skins substantially outperforms the superposition of the sensing performance of different single-wrinkle-based I-skins. As a proof of concept, the triple-wrinkle-based I-skins can provide an extremely high sensitivity of 17,309 kPa-1 and an ultrawide pressure detection range of 0.38 Pa to 372 kPa. The approach and insight contribute to the future development of I-skins with a broader pressure-response range and higher sensitivity.

Association between serum albumin concentration change trajectory and risk of hypertension: a cohort study in China.

Background: We sought to assess the risk of hypertension based on the trajectory of changes in serum albumin concentrations. Methods: A total of 11,946 nonhypertension adults aged 30-60 years who underwent at least 3 medical examinations between 2009 and 2016 were included in this study. Group-based trajectory models were obtained for 4 category groups, and logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each category group of serum albumin concentration and the risk of hypertension. Results: During a mean follow-up period of 4.30 years, 1,537 hypertension events occurred in 11,946 subjects without hypertension. A high stable trajectory of serum albumin concentrations (OR, 0.70, 95% CI, 0.51-0.96) was associated with a significantly lower risk of developing hypertension. The results of the sensitivity analysis of the high stable trajectory (OR, 0.64, 95% CI, 0.43-0.96) remained statistically significant. Subjects with normal weight and those ≥45 years of age had a significantly lower risk of hypertension at moderate increase (P = 0.053 or 0.026) and high stable trajectories (P = 0.011 or 0.016). In males and overweight subjects, the risk of hypertension was significantly lower in the high stable trajectory (P = 0.038 or 0.044). Conclusion: In this study, we found that moderate increase in serum albumin concentrations and a high stable trajectory were significantly associated with a reduced risk of hypertension in subjects aged ≥45 years and those with normal weight and that high stable serum albumin concentrations were significantly associated with a reduced risk of hypertension in males and overweight subjects.

Association between hyperuricemia and hypertension and the mediatory role of obesity: a large cohort study in China.

OBJECTIVE: This study aimed to investigate the sex-specific association between hyperuricemia and the risk of hypertension and whether obesity mediates this association. METHODS: This study included 31,395 (47.0% women) adults without hypertension, cardiovascular disease, or cancer at baseline who completed at least one follow-up annual examination between 2009 and 2016. Cox regression models were performed to calculate hazard ratios and 95% confidence intervals. Mediation analysis was conducted to estimate the effect of body mass index on the association between hyperuricemia and hypertension. RESULTS: During a median 2.9-year follow-up, hyperuricemia was significantly associated with a higher risk of hypertension (HR 1.15, 95%CI 1.07-1.24 for all participants; HR 1.12, 95%CI 1.03-1.22 for men; and HR 1.23, 95%CI 1.02-1.48 for women) after adjustment for potential confounders. Additional adjustment for body mass index attenuated this association (HR 1.09, 95%CI 1.08-1.10 for all participants; HR 1.07; 95%CI 0.98-1.16 for men; HR 1.18; 95%CI 0.96-1.44 for women). Mediation analysis showed that BMI partially mediated the relationship between hyperuricemia and incident hypertension (indirect effect HR 1.09, 95%CI 1.08-1.10; direct effect: HR 1.08, 95%CI 1.02-1.15). The percentage of the mediation effect was 53.2% (95%CI 37.9-84.5). CONCLUSION: Hyperuricemia is associated with a risk of hypertension in both sexes, and BMI partially mediates hyperuricemia-related incident hypertension.

Predicting the Risk of Type 2 Diabetes Mellitus with the New Chinese Diabetes Risk Score in a Cohort Study.

Objectives: The New Chinese Diabetes Risk Score (NCDRS) is a noninvasive tool to assess the risk of type 2 diabetes mellitus (T2DM) in the Chinese population. Our study aimed to evaluate the performance of the NCDRS in predicting T2DM risk with a large cohort. Methods: The NCDRS was calculated, and participants were categorized into groups by optimal cutoff or quartiles. Hazard ratios (HRs) and 95% confidential intervals (CIs) in Cox proportional hazards models were used to estimate the association between the baseline NCDRS and the risk of T2DM. The performance of the NCDRS was assessed by the area under the curve (AUC). Results: The T2DM risk was significantly increased in participants with NCDRS ≥25 (HR = 2.12, 95% CI 1.88-2.39) compared with NCDRS <25 after adjusting for potential confounders. T2DM risk also showed a significant increasing trend from the lowest to the highest quartile of NCDRS. The AUC was 0.777 (95% CI 0.640-0.786) with a cutoff of 25.50. Conclusion: The NCDRS had a significant positive association with T2DM risk, and the NCDRS is valid for T2DM screening in China.

Association between Periodontitis and Aortic Calcification: A Cohort Study.

The present study investigated the association between the presence of periodontitis and aortic calcification (AC) risk among Chinese adults. A total of 6059 individuals who underwent regular health check-ups and received a diagnosis of periodontitis between 2009 and 2016 were included. The outcome was AC, assessed by a chest low-dose spiral CT scan. Cox proportional hazards regression analysis was used to assess the association between periodontitis and AC risk after adjusting for several confounders. After a median follow-up period of 2.3 years (interquartile range: 1.03-4.97 years), 843 cases of AC were identified, with 532 (12.13%) and 311 (18.59%) patients in the non-periodontitis group and periodontitis group, respectively. Multivariate analyses demonstrated that, compared with those without periodontitis, the hazard ratio and 95% confidence interval for AC risk in participants with periodontitis was 1.18 (1.02-1.36) (P = .025) in the fully adjusted model. Stratified analyses showed that the positive relationship between periodontitis and AC was more evident in males and participants <65 years of age (pinteraction = .005 and .004, respectively). Our results show that the presence of periodontitis was positively associated with AC among Chinese adults, especially among males and younger participants.