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 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.

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.

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.

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.

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.

[Role of oxidative stress in endoplasmic reticulum stress? induced apoptosis of alveolar macrophages triggered by quartz dust].

OBJECTIVE: To investigate the role of oxidative stress in the endoplasmic reticulum stress-induced apoptosis of alveolar macrophages triggered by quartz dust. METHODS: Seventy-two healthy adult Wistar rats were randomly divided into control group, quartz dust group, quartz dust plus N-acetyl cysteine (NAC) group, and NAC group, with 18 rats in each group. One milliliter of sterile saline (for the control and NAC groups) or 1 ml of saline with 5%ultrafine quartz dust (for dust group and dust plus NAC group) was given to each rat by non-exposed endotracheal infusion. From the second day after dust infusion, rats in dust plus NAC group and NAC group received intragastric administration of NAC (100 mg/kg). In each week, the treatment with NAC lasted for 5 consecutive days, followed by 2 days' interval. For each group, 6 rats were randomly selected on the 14th, 28th, or 56th day after dust exposure; they were sacrificed by bloodletting from the femoral artery, and the lungs were collected. Bronchoalveolar lavage fluid was collected to separate macrophages. The protein expression of caspase-12 in alveolar macrophages, the apoptosis rate and reactive oxygen species (ROS) content of alveolar macrophages, and the protein carbonyl content of alveolar macrophages were determined by Western blot, flow cytometry, and colorimetry, respectively. RESULTS: Increased protein expression of caspase-12, apoptosis rate, and content of ROS and protein carbonyl were discovered on the 14th day in the dust group, in comparison with the control group (P < 0.05), and the increase lasted till the 28th and 56th days. (P < 0.05). Compared with the dust group, the dust plus NAC group showed significant decreases in the content of ROS on the 14th, 28th, and 56th days (P < 0.05), significant decreases in the content of protein carbonyl on the 28th and 56th days (P < 0.05), and significant decreases in the protein expression of caspase-12 and apoptosis rate (P < 0.05). CONCLUSION: Oxidative stress is potentially involved in the endoplasmic reticulum stress-induced apoptosis of alveolar macrophages triggered by quartz dust. Oxidative damage of protein in the endoplasmic reticulum may play an important role in the process.

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.

Waist circumference glucose, a novel and effective predictor of type 2 diabetes: a prospective cohort study.

Introduction: Waist circumference (WC) and fasting plasma glucose (FPG) have been demonstrated as risk factors for type 2 diabetes mellitus (T2DM). Evidence is limited regarding the association of the combination of WC and FPG (WyG) with the risk of T2DM. The primary aim of the study was to investigate the relationship between WyG and T2DM. Research design and methods: The current study was a population-based cohort study using data from the NAGALA database. Participants were divided into tertiles based on WyG. Cox proportional hazard regression model was applied to identify the association of WyG with T2DM. Results: During a median follow-up of 6.19 years in the normoglycemia group and 5.58 years in the prediabetes group, respectively, 88 and 285 individuals in the two groups received a diagnosis of T2DM. After full adjustment, risk of T2DM increased in step-wise fashion with increasing tertiles of WyG. For a per-SD increase in WyG, the hazard ratios for T2DM were 3.05 (95% CI 2.64 - 3.51) in all populations, 1.94 (95% CI 1.46 - 2.58) in the normoglycemia group and 1.63 (95% CI 1.40 - 1.90) in the prediabetes group. The interaction between WyG and fatty liver on T2DM was statistically significant in the prediabetes group (P for interaction = 0.034). Conclusions: Elevated WyG was independently associated with incident T2DM in Japan. Baseline WyG help identify individuals at high risk of T2DM and implement effective preventive measures.

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.

[Role of ubiquitin ligase Ring2 in DNA damage induced by benzo[a]pyrene].

OBJECTIVE: To investigate the role of ubiquitin ligase Ring2 in the DNA damage induced by benzo[a]pyrene (B[a]P). METHODS: The expression of Ring2 in human bronchial epithelial (16HBE) cells was inhibited by small interfering RNA (siRNA) to obtain siRNA-Ring2 16HBE cells. The siRNA-Ring2 16HBE cells, as well as normal 16HBE cells, were exposed to B[a]P (0, 1, 2, 4, 8, 16, and 32 µmol/L) for 24 h; other siRNA-Ring2 16HBE cells and normal 16HBE cells were exposed to B [a]P (16 µmol/L) for 0, 1, 2, 4, 8, 12, and 24 h. The levels of DNA damage were evaluated by alkaline single cell gel electrophoresis assay. RESULTS: After being treated with siRNA for 36 h, the siRNA-Ring2 16HBE cells showed a 72% decrease in Ring2 expression compared with normal 16HBE cells. The analysis of covariance showed that whether to be treated with siRNA and concentration of B[a]P had impacts on Olive tail moment (OTM) (P = 0.032 and P < 0.001); the adjusted mean of OTM was significantly higher in siRNA-Ring2 16HBE cells than in normal 16HBE cells. Whether to be treated with siRNA and B[a]P exposure time had impacts on OTM (P = 0.031 and P < 0.001); the adjusted mean of OTM was significantly higher in siRNA-Ring2 16HBE cells than in normal 16HBE cells. CONCLUSION: The DNA of 16HBE cells with decreased Ring2 expression has increased susceptibility to B[a]P, which may be due to reduced H2A monoubiquitination following decrease in Ring2 expression.

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.

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.

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.

Role of steric effects in protein-directed enediyne cycloaromatization of neocarzinostatin.

The antibiotic neocarzinostatin comprises a carrier protein with a well-defined cavity for accommodating an active enediyne chromophore. The protein has two disulfides, one (Cys(37)-Cys(47)) lies on the cavity bottom and the other (Cys(88)-Cys(93)) in a constrained short loop. When the chromophore is not bound to the protein, a thiol-induced cycloaromatization of the enediyne into a tetrahydroindacene derivative is responsible for the potent antitumor activity. When it is protein-bound, the protein diverts the cycloaromatization pathway to form a distinct hydroxyisochromene-type product. How the protein directs the enediyne chemistry is an interesting puzzle, and various suggestions have been proposed in the past. We screened more than fifty thiols and manipulated conditions to locate reaction features and search for factors that could influence the protein directing strength. Thiol- and oxygen-concentration-dependence studies suggested that disulfides, which maintain the steric rigidity of the protein, could play a key role in diverting the cycloaromatization pathway. For direct proofs, we made mutations at each of the two disulfides by replacing sulfur atoms with oxygen. Circular dichroism and two-dimensional NMR spectroscopy studies suggested that the mutations changed neither the protein conformation nor the ligand interactions. Analyses of the thiol-induced cycloaromatization revealed that rupture of Cys(37)-Cys(47) made the protein almost completely lose its chemical directing ability, whereas rupture of Cys(88)-Cys(93) had only a minor influence. The results demonstrated that the steric rigidity of the binding cavity, but not necessary the whole protein, played an important role in the protein-directed mechanism.

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.

[Effect of necrostatin-1 on apoptosis induced by aluminum and its mechanism].

OBJECTIVE: To study the effect of necrostatin (Nec-1) on apoptosis induced by aluminum (Al), and approach the mechanism. METHODS: Neural cell death model was made by 4 mmol/L Al treated neuroblastoma cells (SH-SY5Y). Cell viabilities were detected at different concentrations of Al and/or Nec-1. Hoechst 33342/PI double staining was used to observe apoptosis and (or) necrosis that were quantified by flow cytometry using Annexin V/PI double staining. Apoptotic pathway was tested by activities of Caspase-3, Caspase-8 and Caspase-9. In addition, the expression of NF-kappa B and Cyt-c was measured by immunocytochemistry. RESULTS: Cell viabilities were significantly decreased with the increasing concentrations of Al (P < 0.05), which could be significantly upregulated by 60 micromol/L Nec-1 (P < 0.05) and were correlated with the concentrations of Nec-1 (P < 0.05, P < 0.01). Apoptosis and necrosis were observed under fluorescent microscope and quantified by flow cytometry, which suggested an increasing trend of apoptotic and necrotic rates (P < 0.05, P < 0.01). Whereas, Nec-1 could not only decrease the necrotic rate but also apoptotic rate as well (P < 0.05, P < 0.01). Data of Nec-1 on caspases activities showed that Nec-1 could not affect Caspase-9 activity (P > 0.05) and Cty-c protein expression as well (P > 0.05). However, Nec-1 could reduce Caspase-8 activity significantly (P < 0.05, P < 0.01) and increase NF-kappa B protein expression (P < 0.05, P < 0.01) and finally decrease Caspase-3 activity (P < 0.05). CONCLUSION: Nec-1 could reduce cell apoptosis induced by Al, through Caspase-8 pathway, and up-regulate the expression of NF-kappa B protein.