Emerging insights into cuproptosis and copper metabolism: implications for age-related diseases and potential therapeutic strategies.

The expanding geriatric population, whose predisposition toward disabling morbidities and age-related diseases (ARD) is well-documented, has become a paramount social issue, exerting an onerous burden on both the healthcare industry and wider society. ARD manifest as the progressive deterioration of bodily tissues and organs, eventually resulting in the failure of these vital components. At present, no efficacious measures exist to hinder the onset of ARD. Copper, an essential trace element, is involved in a wide range of physiological processes across different cell types. In recent research, a novel variant of copper-dependent cell death, termed cuproptosis, has been identified. This mode of cellular demise stands apart from previously recognized types of cell death. Cuproptosis occurs when copper binds with acyl-CoA synthetase in the tricarboxylic acid (TCA) cycle, resulting in protein aggregation and protein toxicity stress, ultimately leading to cell death. In this paper, we provide a concise overview of the current understanding concerning the metabolism of copper, copper-related diseases, the hallmarks of copper toxicity, and the mechanisms that regulate copper toxicity. Additionally, we discuss the implications of cuproptosis mutations in the development of ARD, as well as the potential for targeting cuproptosis as a treatment for ARD.

The combination of body mass index and fasting plasma glucose is associated with type 2 diabetes mellitus in Japan: a secondary retrospective analysis.

Background: Body mass index (BMI) and fasting plasma glucose (FPG) are known risk factors for type 2 diabetes mellitus (T2DM), but data on the prospective association of the combination of BMI and FPG with T2DM are limited. This study sought to characterize the association of the combination of BMI and FPG (ByG) with T2DM. Methods: The current study used the NAGALA database. We categorized participants by tertiles of ByG. The association of ByG with T2DM was expressed with hazard ratios (HRs) with 95% confidence intervals (CIs) after adjustment for potential risk factors. Results: During a median follow-up of 6.19 years in the normoglycemia cohort and 5.58 years in the prediabetes cohort, the incidence of T2DM was 0.75% and 7.79%, respectively. Following multivariable adjustments, there were stepwise increases in T2DM with increasing tertiles of ByG. After a similar multivariable adjustment, the risk of T2DM was 2.57 (95% CI 2.26 - 2.92), 1.97 (95% CI 1.53 - 2.54) and 1.50 (95% CI 1.30 - 1.74) for a per-SD change in ByG in all populations, the normoglycemia cohort and the prediabetes cohort, respectively. Conclusion: ByG was associated with an increased risk of T2DM in Japan. The result reinforced the importance of the combination of BMI and FPG in assessing T2DM risk.

Early decrease in blood lymphocyte count is associated with poor prognosis in COVID-19 patients: a retrospective cohort study.

BACKGROUND: Previous studies have declared that baseline lymphocyte count is associated with COVID-19-related death. However, whether dynamic lymphocyte change over time affects prognosis in COVID-19 patients is unknown. This study aims to investigate the significance of lymphocyte count during the progression of the disease in COVID-19 patients. METHODS: The retrospective cohort study recruited COVID-19 patients at the First People's Hospital of Jiangxia District in Wuhan from January 7, 2020, to February 28, 2020. The demographics, medical histories, results of the blood routine test, and patients' outcomes were collected. We utilized a generalized additive mixed model to compare trends in lymphocyte count over time among survivors and non-survivors, with an adjustment for potential confounders. The statistical analysis used R software and EmpowerStats. Significance was determined at a P-value of less than 0.05 (two-sided). RESULTS: A total of 532 patients were included in the study. Overall, there were 29/532 in-hospital deaths (5.45%). Lymphocytes declined over time in the non-survivor group and increased in the survivor group in the first 10 days of hospitalization. Within 10 days after admission, lymphocyte count increased in the survivor group and decreased in the non-survivor group. The difference in lymphocyte counts between survivors and non-survivors increased by an average of 0.0732 × 109/L daily. After adjusting for several covariables, the increasing value remained at 0.0731 × 109/L per day. CONCLUSION: In the early stage, lymphocyte count can dynamically reflect the pathophysiological changes in COVID-19 patients. An early decrease in lymphocyte count is associated with mortality in COVID-19 patients.

A U-shaped association between the triglyceride to high-density lipoprotein cholesterol ratio and the risk of incident type 2 diabetes mellitus in Japanese men with normal glycemic levels: a population-based longitudinal cohort study.

Background: Several studies have verified that a high baseline TG/HDL-C ratio is a risk factor for incident type 2 diabetes mellitus (T2DM). However, for low baseline TG/HDL-C levels, the findings were inconsistent with ours. In addition, the association between baseline TG/HDL-C ratio and the risk of incident T2DM in Japanese men with normal glycemic levels is unclear. As a result, our study further investigated the relationship between baseline TG/HDL-C and the risk of incident T2DM in Japanese men with normal glycemic levels. Methods: This was a secondary longitudinal cohort study. We selected 7,684 male participants between 2004 and 2015 from the NAGALA database. A standardized Cox regression model and two piecewise Cox regression models were used to explore the relationship between the baseline high-density lipoprotein cholesterol ratio (TG/HDL-C) and incident T2DM. Results: During a median follow-up of 2,282 days, 162 men developed incident T2DM. In the adjusted model, the baseline TG/HDL-C ratio was strongly associated with the risk of incident T2DM, and no dose-dependent positive association was observed between the baseline TG/HDL-C ratio and incidence of T2DM throughout the baseline TG/HDL-C quartiles. Two-piecewise linear regression analysis showed a U-shaped association between baseline TG/HDL-C ratio and incidence of incident T2DM. A baseline TG/HDL-C ratio below 1.188 was negatively associated with incident T2DM (H.R. = 0.105, 95% CI = 0.025, 0.451; P = 0.002). In contrast, a baseline TG/HDL-C ratio >1.188 was positively associated with incident T2DM (H.R. = 1.248, 95% CI = 1.113, 1.399; P<0.001). The best TG/HDL-C threshold for predicting incident T2DM was 1.8115 (area under the curve, 0.6837). Conclusion: A U-shaped relationship between baseline TG/HDL-C ratio and incident T2DM in Japanese men with normal glycemic levels was found.

Relationship between lipid accumulation product and new-onset diabetes in the Japanese population: a retrospective cohort study.

Background: Diabetes has become a global public health problem. Obesity has been established as a risk factor for diabetes. However, it remains unclear which of the obesity indicators (BMI, WC, WhtR, ABSI, BRI, LAP, VAI) is more appropriate for monitoring diabetes. Therefore, the objective of this investigation is to compare the strength of the association of these indicators and diabetes and reveal the relationship between LAP and diabetes. Methods: 15,252 people took part in this research. LAP was quartered and COX proportional risk model was applied to explore the relationship between LAP and new-onset diabetes. Smooth curve fitting was employed to investigate the non-linear link between LAP and diabetes mellitus. Finally, the receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of the aforementioned indicators for diabetes. Results: After adjusting for confounding factors, multiple linear regression analysis showed that each unit increase in LAP was associated with a 76.8% increase in the risk of developing diabetes (HR=1.768, 95% CI: 1.139 to 2.746, P=0.011). In addition, LAP predicted new-onset diabetes better than other indicators, and the AUC was the largest [HR: 0.713, 95% CI: 0.6806-0.7454, P<0.001, in women; HR: 0.7922, 95% CI: 0.7396-0.8447; P<0.001, in men]. When LAP was used as a lone predictor, its AUC area was largest both men and women. However, after adding classical predictors (FPG, HbA1c, SBP, exercise, age) to the model, the LAP is better than the ABSI, but not better than the other indicators when compared in pairs. Conclusions: High levels of LAP correlate very strongly with diabetes and are an important risk factor for diabetes, especially in women, those with fatty liver and current smokers. LAP was superior to other indicators when screening for diabetes susceptibility using a single indicator of obesity, both in men and in women. However, when obesity indicators were added to the model together with classical predictors, LAP did not show a significant advantage over other indicators, except ABSI.

Triglyceride Glucose-Body Mass Index and Risk of Incident Type 2 Diabetes Mellitus in Japanese People With Normal Glycemic Level: A Population-Based Longitudinal Cohort Study.

Background: It has been proved that triglyceride glucose-body mass index (TyG-BMI) is a readily available and clinically significant indicator of insulin resistance (IR). Nevertheless, the association between TyG-BMI and incident Type 2 diabetes mellitus (T2DM) remains uncertain. This study aimed to study the relationship between TyG-BMI and T2DM and explore the predictive characteristics of TyG-BMI. Methods: Our study was conducted as a longitudinal cohort study. 8,430 men and 7,034 women were enrolled and analyzed. They were both non-diabetic subjects with normal glycemic levels. Follow-up lasted for 13 years, from 1994 to 2016. To make the number of TyG-BMI in each group similar, the subjects were divided into four groups with 3866 subjects in each group. Results: During the 13-year follow-up period, 373 subjects were diagnosed with incident T2DM. Our multivariate Cox regression analysis revealed that TyG-BMI was an independent predictor of incident T2DM. In addition, our research identified four specific groups, young people (18-44 years old), women, the non-hypertensive population and non-drinkers were at significantly higher risk of developing TyG-BMI-related diabetes (P-interaction< 0.05). The best threshold TyG-BMI for predicting incident T2DM was 197.2987 (area under the curve 0.7738). Conclusions: Our longitudinal cohort study demonstrated the positive correlation between baseline TyG-BMI and risk of incident T2DM in Japanese with normal glycemic levels, and this risk was significantly higher in the young people, women, the non-hypertensive population and non-drinkers.

Residual Risk of Coronary Atherosclerotic Heart Disease and Severity of Coronary Atherosclerosis Assessed by ApoB and LDL-C in Participants With Statin Treatment: A Retrospective Cohort Study.

Background: Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid-lowering therapy on the management of hypercholesterolemia in the United States and European guidelines, while apolipoprotein B (apoB) is the secondary target. The objective was to determine if elevated levels of apoB is superior to LDL-C in assessing residual risk of coronary atherosclerotic heart disease and severity of coronary atherosclerosis in participants with statin treatment. Methods: This study included 131 participants with statin treatment. The generalized linear model and relative risk regression (generalized linear Poisson model with robust error variance) were used to analyze the association of the levels of apoB and LDL-C with the severity of coronary atherosclerosis and residual risk of coronary atherosclerotic heart disease. Results: Categorizing apoB and LDL-C based on tertiles, higher levels of apoB were significantly associated with the severity of coronary atherosclerosis (Ptrend = 0.012), whereas no such associations were found for elevated levels of LDL-C (Ptrend = 0.585). After multivariate adjustment, higher levels of apoB were significantly associated with residual risk of coronary atherosclerotic heart disease. When compared with low-level apoB (≤0.66 g/L), the multivariate adjusted RR and 95% CI of intermediate-level apoB (0.67-0.89 g/L) and high-level apoB (≥0.90 g/L) were 1.16 (1.01, 1.33) and 1.31 (1.08, 1.60), respectively (Ptrend = 0.011). There was a 45% increased residual risk of coronary atherosclerotic heart disease per unit increment in natural log-transformed apoB (Ptrend <0.05). However, higher levels of LDL-C were not significantly associated with residual risk of coronary atherosclerotic heart disease. When compared with low-level LDL-C (≤1.56 mmol/L), the multivariate adjusted RR and 95% CI of intermediate-level LDL-C (1.57-2.30 mmol/L) and high-level LDL-C (≥2.31 mmol/L) were 0.99 (0.84, 1.15) and 1.10 (0.86, 1.42), respectively (Ptrend = 0.437). Similar results were observed in the stratified analyses and sensitivity analyses. No significant interactions were detected for both apoB and LDL-C (all Pinteraction>0.05). Conclusions: Elevated apoB are superior in assessing the residual risk of coronary atherosclerotic heart disease and severity of coronary atherosclerosis in participants with statin treatment.

Match of the Bimaxillary Basal Bone Arches and Its Variations among Individuals.

INTRODUCTION: This study is aimed at illustrating the bimaxillary basal bone contours, to clarify the match of the basal bone arches of the upper and lower, especially the posterior segments, including the second molar and retromolar region. METHODS: Based on 100 cone-beam computed tomography (CBCT) images (50 males and 50 females), we obtained 100 pairs of basal bone arches, which were the horizontal inner cortex contours passing the furcation of the first molar paralleled to the lower occlusal plane. The Generalized Procrustes Analysis (GPA) was applied to depict average contours and calculate the ratio and difference width of both upper and lower dental arches in different positions. Variations of the basal bone morphology among individuals were revealed using Principal Component Analysis (PCA). RESULTS: The width discrepancy occurred at 7-7 segment (male: upper 65.62 mm and lower 68.81 mm and female: upper 62.98 mm and lower 68.38 mm) and the retromolar region (male: upper 64.67 mm and lower 71.96 mm and female: upper 62.34 mm and lower 71.44 mm). The ratio (p = 0.006) and difference value (p = 0.009) of 7-7 segment and the ratio of retromolar region (p = 0.044) differed in genders. Setting 2 mm overjet, the upper basal bone arch was wider than the lower by approximate 2 mm on both sides, except the second molar and retromolar region. According to PCA, the variation of basal bone arches appeared mainly at terminal segments. CONCLUSIONS: For both male and female, the bimaxillary basal bone matched except terminal segments. Mismatch of female bimaxillary posterior basal bone was more pronounced than male. The basal bone arches of male were wider and longer than that of female.

A U-shaped association between baseline neutrophil count and COVID-19-related mortality: A retrospective cohort study.

Several descriptive studies have reported that higher neutrophil count (NC) may be correlated with poor prognosis in patients with confirmed COVID-19 infection. However, the findings from these studies are limited by methodology and data analysis. This study is a cohort study. We nonselectively and consecutively collected a total of 663 participants in a Chinese hospital from January 7 to February 28. Standardized and two-piecewise Cox regression model were employed to evaluate the association between baseline neutrophil count (bNC), neutrophil count change rate (NCR), and death. bNC had a U-shaped association with death. In the range of 0.1 to ≤1.49 × 109 /L (hazard ratio [HR] = 0.19, 95% confidence interval [CI] = 0.05-0.66) and >3.55 × 109 /L of bNC (HR = 2.82, 95% CI = 1.19-6.67), the trends on bNC with mortality were opposite. By recursive algorithm, the bNC at which the risk of the death was lower in the range of >1.49 to ≤3.55 × 109 /L (HR = 13.64, 95% CI = 0.25-74.71). In addition, we find that NCRs (NCR1 and NCR2) are not associated with COVID-19-related deaths. Compared with NCR, bNC has the potential to be used for early risk stratification in patients with COVID-19 infection. The relationship between bNC and mortality was U-shaped. The safe range of bNC was 1.64-4.0 × 109 /L. Identifying the correlation may be helpful for early risk stratification and medical decision-making.

Association between the non-HDL-cholesterol-to-HDL-cholesterol ratio and the risk of gallbladder polyp formation among men: a retrospective cohort study.

BACKGROUND: Dyslipidaemia and male sex are associated with gallbladder polyp (GBP) formation. However, the potential relation between the non-high-density lipoprotein-cholesterol-to-high-density lipoprotein-cholesterol (non-HDL-c/HDL-c) ratio and GBPs in men is unclear. METHODS: A total of 1866 eligible subjects were selected for this retrospective cohort study from Wuhan Union Hospital between April 1, 2013, and November 30, 2014. Clinical and laboratory data of subjects were collected. Patients with GBPs or cholecystectomy at baseline, with missing data for baseline lipid profiles, following abdominal ultrasonography or taking lipid-lowering drugs were excluded. The patients were divided into five groups based on their non-HDL-c/HDL-c ratios, and descriptive analyses of the baseline data were performed. A Cox proportional hazards model was applied to estimate the relationship between the non-HDL-c/HDL-c ratio and GBPs. RESULTS: After a median follow-up of 1 year, 7.34% (n = 137) of the subjects developed GBPs. Compared with subjects without GBPs, those who developed GBPs after follow-up had significantly higher triglyceride (TG) levels and non-HDL-c/HDL-c ratios. The prevalence of GBPs showed a linearity increment with age, peaked in the 30-39 years group, 40-49 years group and 50-59 years group, and then declined slightly. The results of univariate analysis showed that the non-HDL-c/HDL-c ratio (hazard ratio (HR) = 1.29, 95% confidence interval (CI), 1.05-1.60, P = 0.0159) was positively correlated with GBPs. In the fully adjusted Cox regression model, the HRs were 2.24 for quintile 2 (95% CI: 1.13-4.44, P = 0.0203), 1.50 for quintile 3 (95% CI: 0.73-3.10, P = 0.269), 2.52 for quintile 4 (95% CI: 1.26-5.01, P = 0.0087) and 2.13 for quintile 5 (95% CI: 1.04-4.37, P = 0.0397). No interaction was found among the subgroups. CONCLUSIONS: A higher non-HDL-c/HDL-c ratio is independently related to a higher risk of GBP formation in Chinese men. Further research is needed to investigate whether this association exists in different regions and races.

Clinical and Laboratory Predictors of In-hospital Mortality in Patients With Coronavirus Disease-2019: A Cohort Study in Wuhan, China.

BACKGROUND: This study aimed to develop mortality-prediction models for patients with coronavirus disease-2019 (COVID-19). METHODS: The training cohort included consecutive COVID-19 patients at the First People's Hospital of Jiangxia District in Wuhan, China, from 7 January 2020 to 11 February 2020. We selected baseline data through the stepwise Akaike information criterion and ensemble XGBoost (extreme gradient boosting) model to build mortality-prediction models. We then validated these models by randomly collected COVID-19 patients in Union Hospital, Wuhan, from 1 January 2020 to 20 February 2020. RESULTS: A total of 296 COVID-19 patients were enrolled in the training cohort; 19 died during hospitalization and 277 discharged from the hospital. The clinical model developed using age, history of hypertension, and coronary heart disease showed area under the curve (AUC), 0.88 (95% confidence interval [CI], .80-.95); threshold, -2.6551; sensitivity, 92.31%; specificity, 77.44%; and negative predictive value (NPV), 99.34%. The laboratory model developed using age, high-sensitivity C-reactive protein, peripheral capillary oxygen saturation, neutrophil and lymphocyte count, d-dimer, aspartate aminotransferase, and glomerular filtration rate had a significantly stronger discriminatory power than the clinical model (P = .0157), with AUC, 0.98 (95% CI, .92-.99); threshold, -2.998; sensitivity, 100.00%; specificity, 92.82%; and NPV, 100.00%. In the subsequent validation cohort (N = 44), the AUC (95% CI) was 0.83 (.68-.93) and 0.88 (.75-.96) for the clinical model and laboratory model, respectively. CONCLUSIONS: We developed 2 predictive models for the in-hospital mortality of patients with COVID-19 in Wuhan that were validated in patients from another center.

Early decrease in blood platelet count is associated with poor prognosis in COVID-19 patients-indications for predictive, preventive, and personalized medical approach.

BACKGROUND: Changes in platelet count are common in COVID-19 patients. The platelet count reflects the thrombocyte turnover, acting as a sensitive indicator of illness severity that is of great clinical utility to monitor a quickly changing health condition of patients affected by aggressive viral infections. This study aims to investigate the significance of platelet count during the progression of the disease in COVID-19 patients. METHODS: A total of 532 COVID-19 patients were involved in the cohort study from the First People's Hospital of Jiangxia District in Wuhan from January 7, 2020, to February 28, 2020. We collected the clinical characteristics and laboratory data of patients. Patients still hospitalized before February 29, 2020, died on admission, with malignant tumors, previous gastrointestinal surgery, missing baseline platelet count, or platelet count detected only once, were excluded. We used a generalized additive model and generalized additive mixed model to compare trends in platelet count over time among survivors and non-survivors, with an adjustment for potential confounders. RESULTS: During the follow-up, twenty-nine subjects died (mortality rate, 5.45%). The platelets among non-survivors decreased and among survivors increased gradually within 1 week after admission. In addition, the difference between the two groups showed an increasing trend during 1 week after admission. This difference increased by an average of 5.3 × 10^9/L daily. CONCLUSIONS: In the early stage, platelet count can dynamically reflect the pathophysiological changes in COVID-19 patients. Early decrease in platelet count was associated with mortality in patients with COVID-19. Causality, however, cannot be deduced from our data.

Monocyte lymphocyte ratio predicts the new-onset of chronic kidney disease: A cohort study.

BACKGROUND AND AIMS: The role of monocyte lymphocyte ratio (MLR) in predicting the risk of chronic kidney disease (CKD) is unclear, although inflammation contributes to the development of CKD. This study aimed to investigate whether elevated MLR predicts new-onset CKD. METHODS: This study enrolled 14,033 consecutively Chinese participants. The primary outcome was the new-onset CKD defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 or the presence of proteinuria after follow-up. After the descriptive analyses of baseline data, Univariate and multivariate Cox proportional models were used to evaluate the independent relationship between MLR and new-onset CKD. RESULTS: 11,280 participants were included in the final analysis, and 58.44% (n = 6592) of them were male. The mean age was 44.67 ± 12.85 years. After a median follow-up of 1.94 years, 2.55% (n = 288) of participants developed new-onset CKD. MLR was associated with the increased risk of CKD (HR = 16.12, 95% CI = 4.52-57.56, p < 0.0001). After adjustment for age, gender, body mass index, history of hypertension, systolic blood pressure, high-density lipoprotein cholesterol, triglyceride, fasting plasma glucose, uric acid and estimated glomerular filtration rate, MLR remained an independent risk factor for CKD (HR = 8.89, 95%CI = 2.18-36.27, p = 0.0023). CONCLUSION: MLR is an independent predictor of the risk of CKD, which might be expected to better guide early prevention and treatment interventions.

Maternal exposure to ambient fine particulate matter and risk of premature rupture of membranes in Wuhan, Central China: a cohort study.

BACKGROUND: The associations between maternal exposure to ambient PM2.5 during pregnancy and the risk of premature rupture of membranes (PROM) and preterm premature rupture of membranes (PPROM) are controversial. And no relevant study has been conducted in Asia. This study aimed to determine the association between maternal exposure to ambient PM2.5 during pregnancy and the risk of (P)PROM. METHODS: A cohort study including all singleton births in a hospital located in Central China from January 2015 through December 2017 was conducted. Multivariable logistic regression models, stratified analysis, generalized additive model, and two-piece-wise linear regression were conducted to evaluate how exposure to ambient PM2.5 during pregnancy is associated with the risks of PROM and PPROM. RESULTS: A total of 4364 participants were included in the final analysis, where 11.71 and 2.34% of births were complicated by PROM and PPROM, respectively. The level of PM2.5 exhibited a degree of seasonal variation, and its median concentrations were 63.7, 59.3, 55.8, and 61.8 µg/m3 for the first trimester, second trimester, third trimester, and the whole duration of pregnancy, respectively. After adjustment for potential confounders, PROM was positively associated with PM2.5 exposure (per 10 µg/m3) [Odds Ratio (OR) = 1.14, 95% Confidence Interval (CI), 1.02-1.26 for the first trimester; OR = 1.09, 95% CI, 1.00-1.18 for the second trimester; OR = 1.13, 95% CI, 1.03-1.24 for the third trimester; OR = 1.35, 95% CI, 1.12-1.63 for the whole pregnancy]. PPROM had positive relationship with PM2.5 exposure (per 10 µg/m3) (OR = 1.17, 95% CI, 0.94-1.45 for first trimester; OR = 1.11, 95% CI, 0.92-1.33 for second trimester; OR = 1.19, 95% CI, 0.99-1.44 for third trimester; OR = 1.53, 95% CI, 1.03-2.27 for the whole pregnancy) Positive trends between the acute exposure window (mean concentration of PM2.5 in the last week and day of pregnancy) and risks of PROM and PPROM were also observed. CONCLUSIONS: Exposure to ambient PM2.5 during pregnancy was associated with the risk of PROM and PPROM.

Nomogram prediction for the 3-year risk of type 2 diabetes in healthy mainland China residents.

AIMS: To develop a precise personalized type 2 diabetes mellitus (T2DM) prediction model by cost-effective and readily available parameters in a Central China population. METHODS: A 3-year cohort study was performed on 5557 nondiabetic individuals who underwent annual physical examination as the training cohort, and a subsequent validation cohort of 1870 individuals was conducted using the same procedures. Multiple logistic regression analysis was performed, and a simple nomogram was constructed via the stepwise method. Receiver operating characteristic (ROC) curve and decision curve analyses were performed by 500 bootstrap resamplings to assess the determination and clinical value of the nomogram, respectively. We also estimated the optimal cutoff values of each risk factor for T2DM prediction. RESULTS: The 3-year cumulative incidence of T2DM was 10.71%. We developed simple nomograms that predict the risk of T2DM for females and males by using the parameters of age, BMI, fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), and triglycerides (TG). In the training cohort, the area under the ROC curve (AUC) showed statistical accuracy (AUC = 0.863 for female, AUC = 0.751 for male), and similar results were shown in the subsequent validation cohort (AUC = 0.847 for female, AUC = 0.755 for male). Decision curve analysis demonstrated the clinical value of this nomogram. To optimally predict the risk of T2DM, the cutoff values of age, BMI, FBG, systolic blood pressure, diastolic blood pressure, total cholesterol, LDLc, HDLc, and TG were 47.5 and 46.5 years, 22.9 and 23.7 kg/m2, 5.1 and 5.4 mmol/L, 118 and 123 mmHg, 71 and 85 mmHg, 5.06 and 4.94 mmol/L, 2.63 and 2.54 mmol/L, 1.53 and 1.34 mmol/L, and 1.07 and 1.65 mmol/L for females and males, respectively. CONCLUSION: Our nomogram can be used as a simple, plausible, affordable, and widely implementable tool to predict a personalized risk of T2DM for Central Chinese residents. The successful identification of at-risk individuals and intervention at an early stage can provide advanced strategies from a predictive, preventive, and personalized medicine perspective.

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.

Non-HDL-cholesterol to HDL-cholesterol ratio is a better predictor of new-onset non-alcoholic fatty liver disease than non-HDL-cholesterol: a cohort study.

BACKGROUND: The nonHDLc/HDLc ratio (in which nonHDLc is defined as total cholesterol minus HDLc) is positively associated with multiple dyslipidemia-related disorders. This study aimed to determine whether the nonHDLc/HDLc ratio is an independent predictor of new-onset NAFLD (non-alcoholic fatty liver disease) in Chinese population. METHODS: A perspective cohort study consisting of 3374 Chinese adults without liver diseases or metabolic disturbances was performed. Anthropometric parameters and data of metabolic and plasma lipid profile were collected. Univariate and multivariate Cox proportional analyses were carried out to evaluate the association of the nonHDLc/HDLc ratio with incident NAFLD. ROC curve analysis was preformed to compare the predictive value between the nonHDLc/HDLc and the nonHDLc for NAFLD. RESULTS: Two thousand seven hundred seventeen participants were included in the final analysis. During a median follow-up period of 1.6 years, 264 participants (9.71%) developed NAFLD. After adjustment for potential confounders, a high nonHDLc/HDLc ratio (highest tertile) was associated with elevated risk of NAFLD (HR = 2.66; 95% CI, 1.13-6.24; P = 0.025 in female and HR = 2.11; 95% CI, 1.15-3.90; P = 0.016 in male). A nonlinear relationship was observed when the nonHDLc/HDLc ratio was ≤3.5. AUC values for nonHDLc/HDLc ratios (0.717 in female and 0.682 in male) were significantly higher than nonHDLc (0.675 in female and 0.653 in male) (P = 0.049 in female and P = 0.037 in male). In addition, the optimal cut-off value of nonHDLc/HDLc ratio for detection of NAFLD was 2.4 in female and 2.3 in male. CONCLUSIONS: The nonHDLc/HDLc ratio is an independent predictor of NAFLD and a stronger predictor than nonHDLc in Chinese population, which might be expected to better guide early identification of individuals at risk of NAFLD.

Catalytic Conversion of Biomass-Derived 1,2-Propanediol to Propylene Oxide over Supported Solid-Base Catalysts.

A series of supported alkali metal salts were investigated as catalysts to produce propylene oxide (PO) from biomass-derived 1,2-propanediol via dehydrative epoxidation in a solid-gas reaction system. The effects of supports, cations, and anions in the alkali metal salts and calcination temperature were investigated by X-ray diffraction and CO2-temperature-programmed desorption. The results indicate the catalysts with relative mild basicity having higher yields of PO. The highest yield of PO is 58.2% from reactions at 400 °C at an atmospheric pressure over KNO3/SiO2. In addition, the catalyst could be reused after calcination in air at 550 °C.

Metabolic Syndrome and Its Components Predict the Risk of Type 2 Diabetes Mellitus in the Mainland Chinese: A 3-Year Cohort Study.

INTRODUCTION: It has well established that metabolic syndrome (MetS) can predict the risk of type 2 diabetes mellitus (T2DM) in some population groups. However, limited evidence is available regarding the predictive effect of MetS for incident T2DM in mainland Chinese population. METHODS: A 3-year cohort study was performed for 9735 Chinese without diabetes at baseline. MetS and its components were assessed by multivariable analysis using Cox regression. Prediction models were developed. Discrimination was assessed with area under the receiver operating characteristic curves (AUCs), and performance was assessed by a calibration curve. RESULTS: The 3-year cumulative incidence of T2DM was 11.29%. Baseline MetS was associated with an increased risk of T2DM after adjusting for age (HR = 2.68, 95% CI, 2.27-3.17 in males; HR = 2.59, 95% CI, 1.83-3.65 in females). Baseline MetS exhibited relatively high specificity (88% in males, 94% in females) and high negative predictive value (90% in males, 94% in females) but low sensitivity (36% in males, 23% in females) and low positive predictive value (31% in males and females) for predicting the 3-year risk of T2DM. AUCs, including age and components of MetS, for the prediction model were 0.779 (95% CI: 0.759-0.799) in males and 0.860 (95% CI: 0.836-0.883) in females. Calibration curves revealed good agreement between prediction and observation results in males; however, the model could overestimate the risk when the predicted probability is >40% in females. CONCLUSIONS: MetS predicts the risk of T2DM. The quantitative MetS-based prediction model for T2DM risk may improve preventive strategies for T2DM and present considerable public health benefits for the people in mainland China.