Comparison of the effects of imputation methods for missing data in predictive modelling of cohort study datasets.

BACKGROUND: Missing data is frequently an inevitable issue in cohort studies and it can adversely affect the study's findings. We assess the effectiveness of eight frequently utilized statistical and machine learning (ML) imputation methods for dealing with missing data in predictive modelling of cohort study datasets. This evaluation is based on real data and predictive models for cardiovascular disease (CVD) risk. METHODS: The data is from a real-world cohort study in Xinjiang, China. It includes personal information, physical examination data, questionnaires, and laboratory biochemical results from 10,164 subjects with a total of 37 variables. Simple imputation (Simple), regression imputation (Regression), expectation-maximization(EM), multiple imputation (MICE) , K nearest neighbor classification (KNN), clustering imputation (Cluster), random forest (RF), and decision tree (Cart) were the chosen imputation methods. Root Mean Square Error (RMSE) and Mean Absolute Error (MAE) are utilised to assess the performance of different methods for missing data imputation at a missing rate of 20%. The datasets processed with different missing data imputation methods were employed to construct a CVD risk prediction model utilizing the support vector machine (SVM). The predictive performance was then compared using the area under the curve (AUC). RESULTS: The most effective imputation results were attained by KNN (MAE: 0.2032, RMSE: 0.7438, AUC: 0.730, CI: 0.719-0.741) and RF (MAE: 0.3944, RMSE: 1.4866, AUC: 0.777, CI: 0.769-0.785). The subsequent best performances were achieved by EM, Cart, and MICE, while Simple, Regression, and Cluster attained the worst performances. The CVD risk prediction model was constructed using the complete data (AUC:0.804, CI:0.796-0.812) in comparison with all other models with p<0.05. CONCLUSION: KNN and RF exhibit superior performance and are more adept at imputing missing data in predictive modelling of cohort study datasets.

Gallbladder disease is associated with the risk of cardiovascular disease among Uyghurs in Xinjiang: a prospective cohort study.

BACKGROUND: Gallbladder disease (GBD) can increase the risk of cardiovascular disease (CVD). However, GBD has rarely been reported in the less developed, rural areas of Xinjiang. This study aimed to determine the prevalence of GBD and incidence of CVD in a prospective cohort study in rural Xinjiang. Moreover, the study aimed to explore the association between GBD and CVD within this cohort. METHODS: The study cohort included 11,444 Uyghur adults in Xinjiang, 3rd division, from the 51st Mission. Study groups were classified according to whether GBD was present or absent at baseline. The occurrence of CVD was the end event. Demographic, anthropometric, and biochemical data were recorded, and the incidence of CVD in the GBD and non-GBD groups analysed. Cox proportional hazards regression models were used to assess the association between GBD and CVD and factors associated with their incidence. Several subgroup analyses were performed to assess CVD incidence in different subgroups. The interaction between GBD and cardiometabolic risk factors, and subsequent risk of developing CVD, was evaluated. RESULTS: Prevalence of GBD in the study cohort was 10.29%. After a median follow-up of 4.92 years, the cumulative incidence of CVD in the study cohort was 10.49%, 8.43% in males and 12.65% in females. CVD incidence was higher in the GBD group (34.04% vs. 7.78%, HR = 4.96, 95% CI: 4.40-5.59). After multivariate adjustment, the risk of CVD remained higher in the GBD group (HR = 2.89, 95% CI: 2.54-3.29). Subgroup analyses showed male sex, smoking, alcohol consumption, lack of exercise, and abnormal renal function were all associated with increased risk of CVD. Moreover, the risk of CVD was markedly higher in GBD combined with cardiometabolic risk factors (hypertension, T2DM, dyslipidaemia, overweight, and abdominal obesity), than in cardiometabolic risk factors alone and this was higher in the GBD group than in the non-GBD group regardless of whether cardiometabolic risk factors were combined. CONCLUSION: GBD is an important independent risk factor for CVD development. Awareness of these associations will raise concerns among clinicians about the risk of cardiovascular disease in patients with GBD.

Study on the prediction model of atherosclerotic cardiovascular disease in the rural Xinjiang population based on survival analysis.

PURPOSE: With the increase in aging and cardiovascular risk factors, the morbidity and mortality of atherosclerotic cardiovascular disease (ASCVD), represented by ischemic heart disease and stroke, continue to rise in China. For better prevention and intervention, relevant guidelines recommend using predictive models for early detection of ASCVD high-risk groups. Therefore, this study aims to establish a population ASCVD prediction model in rural areas of Xinjiang using survival analysis. METHODS: Baseline cohort data were collected from September to December 2016 and followed up till June 2022. A total of 7975 residents (4054 males and 3920 females) aged 30-74 years were included in the analysis. The data set was divided according to different genders, and the training and test sets ratio was 7:3 for different genders. A Cox regression, Lasso-Cox regression, and random survival forest (RSF) model were established in the training set. The model parameters were determined by cross-validation and parameter tuning and then verified in the training set. Traditional ASCVD prediction models (Framingham and China-PAR models) were constructed in the test set. Different models' discrimination and calibration degrees were compared to find the optimal prediction model for this population according to different genders and further analyze the risk factors of ASCVD. RESULTS: After 5.79 years of follow-up, 873 ASCVD events with a cumulative incidence of 10.19% were found (7.57% in men and 14.44% in women). By comparing the discrimination and calibration degrees of each model, the RSF showed the best prediction performance in males and females (male: Area Under Curve (AUC) 0.791 (95%CI 0.767,0.813), C statistic 0.780 (95%CI 0.730,0.829), Brier Score (BS):0.060, female: AUC 0.759 (95%CI 0.734,0.783) C statistic was 0.737 (95%CI 0.702,0.771), BS:0.110). Age, systolic blood pressure (SBP), apolipoprotein B (APOB), Visceral Adiposity Index (VAI), hip circumference (HC), and plasma arteriosclerosis index (AIP) are important predictors of ASCVD in the rural population of Xinjiang. CONCLUSION: The performance of the ASCVD prediction model based on the RSF algorithm is better than that based on Cox regression, Lasso-Cox, and the traditional ASCVD prediction model in the rural population of Xinjiang.

Association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and H-type hypertension: A systematic review and meta-analysis.

PURPOSE: The polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene C677T has been linked to H-type hypertension. But the conclusion remained controversial. To elucidate this issue, we performed a comprehensive meta-analysis to analyze the MTHFR C677T polymorphism and H-type hypertension. MATERIALS AND METHODS: The English and Chinese databases were systematically searched to identify relevant studies until November 2020. RevMan 5.3 and Stata 12.0 software were used for meta-analysis. The odds ratio (ORs) and 95% confidence intervals (95% CIs) were used to assess the relationship between the MTHFR C677T polymorphism and H-type hypertension. RESULTS: A total of 14 studies involving 1769 cases and 1443 controls were included. The meta-analysis results showed the association between MTHFR C677T polymorphism and H-type hypertension with the homozygous codominant model (OR = 3.30, 95% CI = 1.94-5.60), heterozygous codominant model (OR = 2.34, 95% CI = 1.53-3.58), dominant model (OR = 1.79, 95% CI = 1.33-2.41), recessive model (OR = 2.70, 95% CI = 1.73-4.21),and the allelic model (OR = 1.82, 95% CI = 1.41-2.35). All p-values were less than 0.05. Therefore, MTHFR C677T polymorphism has a positive correlation with the risk of H-type hypertension. Among them, TT mutation has the greatest impact on the activity of this enzyme, which causes Hcy to rise and leads to H-type hypertension. CONCLUSION: In summary, our results provide sufficient data to support the hypothesis that the MTHFR C677T polymorphism is related to H-type hypertension susceptibility.

Updating Framingham CVD risk score using waist circumference and estimated cardiopulmonary function: a cohort study based on a southern Xinjiang population.

PURPOSE: To explore the association between waist circumference (WC), estimated cardiopulmonary function (eCRF), and cardiovascular disease (CVD) risk in southern Xinjiang. Update the Framingham model to make it more suitable for the southern Xinjiang population. METHODS: Data were collected from 7705 subjects aged 30-74 years old in Tumushuke City, the 51st Regiment of Xinjiang Production and Construction Corps. CVD was defined as an individual's first diagnosis of non-fatal acute myocardial infarction, death from coronary heart disease, and fatal or non-fatal stroke. The Cox proportional hazards regression analysis was used to analyze the association between WC, eCRF and CVD risk. Restricted cubic spline plots were drawn to describe the association of the two indicators with CVD risk. We update the model by incorporating the new variables into the Framingham model and re-estimating the coefficients. The discrimination of the model is evaluated using AUC, NRI, and IDI metrics. Model calibration is evaluated using pseudo R2 values. RESULTS: WC was an independent risk factor for CVD (multivariate HR: 1.603 (1.323, 1.942)), eCRF was an independent protective factor for CVD (multivariate HR: 0.499 (0.369, 0.674)). There was a nonlinear relationship between WC and CVD risk (nonlinear χ2 = 12.43, P = 0.002). There was a linear association between eCRF and CVD risk (non-linear χ2 = 0.27, P = 0.6027). In the male, the best risk prediction effect was obtained when WC and eCRF were added to the model (AUC = 0.763((0.734,0.792)); pseudo R2 = 0.069). In the female, the best risk prediction effect was obtained by adding eCRF to the model (AUC = 0.757 (0.734,0.779); pseudo R2 = 0.107). CONCLUSION: In southern Xinjiang, WC is an independent risk factor for CVD. eCRF is an independent protective factor for CVD. We recommended adding WC and eCRF in the male model and only eCRF in the female model for better risk prediction.

Comparison of obesity-related indicators for identifying metabolic syndrome among normal-weight adults in rural Xinjiang, China.

BACKGROUND: This study aimed to compare the ability of certain obesity-related indicators to identify metabolic syndrome (MetS) among normal-weight adults in rural Xinjiang. METHODS: A total of 4315 subjects were recruited in rural Xinjiang. The questionnaire, biochemical and anthropometric data were collected from them. Binary logistic regression was used to analyze the association between the z-score of each index and MetS. The area under the receiver-operating characteristic (ROC) curves were used to compare the diagnostic ability of each index. According to the cut-off value of each index, nomogram models were established and their diagnostic ability were evaluated. RESULTS: After adjusting for confounding factors, each indicator in different genders was correlated with MetS. Triglyceride-glucose index (TyG index) showed the strongest association with MetS in both males (OR = 3.749, 95%CI: 3.173-4.429) and females (OR = 3.521,95%CI: 2.990-4.148). Lipid accumulation product (LAP) showed the strongest diagnostic ability in both males (AUC = 0.831, 95%CI: 0.806-0.856) and females (AUC = 0.842, 95%CI: 0.820-0.864), and its optimal cut-off values were 39.700 and 35.065, respectively. The identification ability of the TyG index in different genders (males AUC: 0.817, females AUC: 0.817) was slightly weaker than LAP. Waist-to-height ratio (WHtR) had the similar AUC (males: 0.717, females: 0.747) to conicity index (CI) (males: 0.734, females: 0.749), whereas the identification ability of a body shape index (ABSI) (males AUC: 0.700, females AUC: 0.717) was relatively weak. Compared with the diagnostic ability of a single indicator, the AUC of the male nomogram model was 0.876 (95%CI: 0.856-0.895) and the AUC of the female model was 0.877 (95%CI: 0.856-0.896). The identification ability had been significantly improved. CONCLUSION: LAP and TyG index are effective indicators for identifying MetS among normal-weight adults in rural Xinjiang. Nomogram models including age, CI, LAP, and TyG index can significantly improve diagnostic ability.

Predictive power of a body shape index and traditional anthropometric indicators for cardiovascular disease: a cohort study in rural Xinjiang, China.

BACKGROUND: A body shape index (ABSI) has been proven to be related to a population's CVD incidence. However, the application of this indicator has produced different results. AIM: This study aimed to evaluate the applicability of the ABSI in predicting the incidence of CVD in rural Xinjiang, China, and compare it with waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and body mass index (BMI). SUBJECTS AND METHODS: 5375 people aged 18 years or older were included in the study. We used the Cox proportional hazard model to evaluate the relationship between WC, WHR, WHtR, BMI, and ABSI and the incidence of CVD, the area under the curve (AUC) to evaluate the predictive power of each anthropometric index for the incidence of CVD, and restricted cubic splines are used to analyse the trend relationship between anthropometric indicators and the incidence of CVD. RESULTS: After multivariate adjustment, standardised WC, WHR, WHtR, BMI, and ABSI all positively correlated with the incidence of CVD. WC had the highest HR (95% CI) value, 1.64 (1.51-1.78), and AUC (95% CI) value, 0.7743 (0.7537-0.7949). ABSI had the lowest HR (95% CI) value, 1.21(1.10-1.32), and AUC (95% CI) value, 0.7419 (0.7208-0.7630). In the sex-specific sensitivity analysis, the predictive ability of traditional anthropometric indicators for the incidence of CVD is higher than that of ABSI. CONCLUSIONS: In the rural areas of Xinjiang, the traditional anthropometric indicators of WC had better ability to predict the incidence of CVD than ABSI.

Metabolically healthy obesity and unhealthy normal weight rural adults in Xinjiang: prevalence and the associated factors.

BACKGROUND: This study aimed to describe the prevalence of metabolically healthy obesity (MHO) and metabolically unhealthy normal weight (MUNW) rural adults in Xinjiang and to explore their influencing factors. METHODS: We selected 13,525 Uyghur, Kazakh and Han participants in Kashi, Yili and Shihezi areas in Xinjiang from 2009 to 2010. Weight status was classified according to body mass index. Metabolic phenotype was further defined based on the National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: The prevalence of normal weight, overweight, and obesity were 51.6, 30.2, and 14.4%, respectively. The mean age of the population was 45.04 years. The prevalence of MHO was 5.5% overall and was 38.5% among obese participants. The prevalence of MUNW was 15.5% overall and was 30.1% among normal weight participants. A metabolically healthy phenotype among obese individuals was positively associated with females and vegetable consumption ≥4 plates per week. However, this was inversely associated with higher age, red meat consumption ≥2 kg per week, and larger waist circumference (WC). Conversely, a metabolically unhealthy phenotype among normal-weight individuals was positively associated with higher age, red meat consumption ≥2 kg per week, and larger WC; this was however inversely associated with vegetable consumption ≥4 plates per week. CONCLUSIONS: The prevalence of MHO among obese adults in Xinjiang is higher than that of Han adults, while the prevalence of MUNW among normal weight adults is lower than that among Han adults. In obese and normal weight participants, higher age, more red meat consumption, and larger WC increase the risk of metabolic abnormality, and more vegetable consumption reduces the risk of metabolic abnormality.

The Association of Metabolic Syndrome with the development of cardiovascular disease among Kazakhs in remote rural areas of Xinjiang, China: a cohort study.

BACKGROUND: Metabolic syndrome (MS) can promote the development of cardiovascular disease (CVD). The objective of this study was to examine the association of MS and its components with CVD, to further prevent and control CVD in Kazakhs. METHODS: In the cohort study, a total of 2644 participants completed the baseline survey between April 2010 and December 2012.The follow-up survey was conducted from April 2016 to December 2016 and was completed by 2286 participants (86.46% follow-up rate). Cox regression was used to evaluate the association of each component and the number of combinations of MS components on the development of CVD. RESULTS: A total of 278 CVD patients were enrolled from rural residents of Xinjiang. The average age of the MS and non-MS groups was 46.33 and 38.71 years, respectively. Independent associations with CVD were found for elevated blood pressure (BP) (adjusted hazard ratio (HR) [aHR] = 1.50,95%confidence interval [CI]: 1.08-2.08), elevated waist circumference (WC) (aHR = 1.60, 95%CI: 1.19-2.15), and elevated triglycerides (TG) (aHR = 1.44, 95%CI: 1.04-2.01). Participants with one to 5 MS components had an increased HR for developing CVD, from 1.82to 8.59 (P for trend < 0.001), compared with those with no MS components. The risk of developing CVD increased when TG and WC coexisted (aHR = 2.16, 95%CI: 1.54-3.04)), when TG and BP coexisted ((aHR = 1.92, 95%CI: 1.32-2.79), and when WC and BP coexisted (aHR = 1.93, 95%CI: 1.33-2.82)). However, no significant interactions were found between BP, WC, and TG. CONCLUSIONS: Elevations of BP, WC, and TG were independent risk factors for CVD in Kazakhs. Control of these factors is important to prevent CVD in this population.

Roles of endoplasmic reticulum stress in 2,2',4,4'-tetrabromodiphenylether-induced thyroid cell apoptosis and autophagy.

Polybrominated diphenyl ethers are known to be toxic and impair thyroid function. However, the underlying molecular mechanisms are not well understood. We constructed a female Sprague-Dawley rat model to evaluate the role of endoplasmic reticulum stress, apoptosis and autophagy in 2,2',4,4'-tetrabromodiphenylether (PBDE-47) induced thyroid toxicity. In the brain development spurt period (postnatal day 10), rats were treated with PBDE-47 (0, 1, 5, 10 mg/kg bw, i.g). Two addition groups were administered with 4-Phenylbutyric acid, an endoplasmic reticulum stress modulator, to reverse PBDE-47-induced thyroid toxicity. Our results demonstrated that PBDE-47 significantly decreased serum thyroid stimulating hormone levels, induced histologic changes in thyroid tissues, increased the percentage of cell apoptosis and expression levels of C/EBP-homologous protein, caspase 3, glucose-regulated protein 78, inositol-requiring enzyme 1, and autophagy-related proteins Beclin1 and 1A/1B-light chain 3. Besides of decreased serum thyroid stimulating hormone levels, all these changes were reversed by 4-Phenylbutyric acid. Taken together, these data indicate that, PBDE-47 damages the thyroid tissues by triggering endoplasmic reticulum stress, apoptosis and autophagy.

Association of total bilirubin and indirect bilirubin content with metabolic syndrome among Kazakhs in Xinjiang.

BACKGROUND: Some studies have shown that a high level of bilirubin is a protective factor against metabolic syndrome (MS), while a high level of transaminase is a risk factor for MS. However, the existing results are inconsistent and few cohort studies have been published. METHODS: Using an ambispective cohort study, 565 Kazakhs from Xinjiang, China were selected as the study subjects. The baseline serum bilirubin and transaminase levels of the subjects were divided into quartiles and the relationship between these values and the incidence of MS was analyzed. The definition of MS was based on the Joint Interim Statement (JIS) diagnostic criteria. RESULTS: The average follow-up time for the subjects was 5.72 years. The cumulative incidence of MS was 36.11% (204 of the 565 subjects), and the incidence density was 63.10/1000 person-years. Multivariate Cox regression analysis showed that the levels of total bilirubin (TBIL) and indirect bilirubin (IBIL) were negatively correlated with the occurrence of MS, Compared to the lowest quartile level (Q1), the hazard ratios of MS the TBIL levels at the Q2-Q4 quartiles were: 0.47 (0.31-0.71), 0.53 (0.35-0.79), and 0.48 (0.32-0.72), respectively, while IBIL levels at the Q2-Q4 quartiles showed an MS hazard ratio of 0.48 (0.32-0.72), 0.54(0.36-0.81), and 0.52 (0.35-0.77), respectively, all at a 95% confidence level. However, no relationship was found between transaminase levels and the incidence of MS. CONCLUSION: Serum TBIL and IBIL levels were negatively correlated with the incidence of MS in a Kazakh population in China.

Microarray analysis of long non-coding RNA expression profiles in low high-density lipoprotein cholesterol disease.

BACKGROUND: Low high-density lipoprotein cholesterol (HDL-C) disease with unknown etiology has a high prevalence in the Xinjiang Kazak population. In this study, long noncoding RNAs (lncRNAs) that might play a role in low HDL-C disease were identified. METHODS: Plasma samples from 10 eligible individuals with low HDL disease and 10 individuals with normal HDL-C levels were collected. The lncRNA profiles for 20 Xinjiang Kazak individuals were measured using microarray analysis. RESULTS: Differentially expressed lncRNAs and mRNAs with fold-change values not less than 1.5 and FDR-adjusted P-values less than 0.05 were screened. Bioinformatic analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and network analyses, were used to determine relevant signaling pathways and predict potential target genes. In total, 381 lncRNAs and 370 mRNAs were differentially expressed based on microarray analysis. Compared with those in healthy individuals, several lncRNAs were upregulated or downregulated in patients with low HDL-C disease, among which TCONS_00006679 was most significantly upregulated and TCONS_00011823 was most significantly downregulated. GO and KEGG pathway analyses as well as co-expression networks of lncRNAs and mRNAs revealed that the platelet activation pathway and cardiovascular disease were associated with low HDL-C disease. CONCLUSIONS: Potential target genes integrin beta-3 (ITGB3) and thromboxane A2 receptor (TBXA2R) were regulated by the lncRNAs AP001033.3-201 and AC068234.2-202, respectively. Both genes were associated with cardiovascular disease and were involved in the platelet activation pathway. AP001033.3-201 and AC068234.2-202 were associated with low HDL-C disease and could play a role in platelet activation in cardiovascular disease. These results reveal the potential etiology of dyslipidemia in the Xinjiang Kazakh population and lay the foundation for further validation using large sample sizes.

Effect of metabolic syndrome on coronary heart disease in rural minorities of Xinjiang: a retrospective cohort study.

BACKGROUND: Metabolic syndrome is diagnosed by a cluster of risk factors that associated with an increased risk of coronary heart disease (CHD). We aimed to explore the impact of and interactions between individual metabolic syndrome components on the risk of CHD in Xinjiang. METHODS: The baseline population included 7635 participants. The degree to which the components increase the risk of CHD and the multiplicative interactions between them were assessed using hazard ratios (HRs) and 95% confidence intervals (CIs). Additive interactions were appraised by the relative excess risk due to interaction, synergy index (SI), and attributable proportion of interaction. RESULTS: A total of 304 CHD patients were enrolled from rural residents of Xinjiang. Elevated blood pressure (HR 1.81; 95% CI 1.35-2.44) and elevated fasting blood glucose (FBG) (HR 1.82; 95% CI 1.38-2.38) increased the risk of CHD after adjustment for confounding factors. We found a positive additive interaction (SI 1.14; 95% CI 0.51-2.51) between elevated blood pressure and elevated FBG, but none were significant. As the number of components increased, the risk of CHD increased. The combinations of [high triglycerides (TG) + low high-density lipoprotein cholesterol (HDL-C) + elevated FBG + large waistline] (HR 4.26; 95% CI 1.43-12.73) and [elevated blood pressure + elevated FBG + low HDL-C + large waistline] (HR 1.82; 95% CI 1.38-2.38) increased the risk of CHD. CONCLUSIONS: We provide evidence that elevated blood pressure and elevated FBG are independent risk factors for CHD and it might be necessary to maintain the normal waistline for preventing CHD.

External validation of three atherosclerotic cardiovascular disease risk equations in rural areas of Xinjiang, China.

BACKGROUND: To externally validate the Prediction for ASCVD Risk in China (PAR) risk equation for predicting the 5-year atherosclerotic cardiovascular disease (ASCVD) risk in the Uyghur and Kazakh populations from rural areas in northwestern China and compare its performance with those of the pooled cohort equations (PCE) and Framingham risk score (FRS). METHODS: The final analysis included 3347 subjects aged 40-74 years without CVD at baseline. The 5-year ASCVD risk was calculated using the PAR, PCE, and FRS. Discrimination, calibration, and clinical usefulness of the three equations in predicting the 5-year ASCVD risk were assessed before and after recalibration. RESULTS: Of 3347 included subjects, 1839 were female. We observed 286 ASCVD events in within 5-year follow-up. All three risk equations had moderate discrimination in both men and women. C-indices of PAR, PCE, and FRS were 0.727 (95% CI, 0.725-0.729), 0.727 (95% CI, 0.725-0.729), and 0.740 (95% CI, 0.738-0.742), respectively, in men; the corresponding C-indices were 0.738 (95% CI, 0.737-0.739), 0.731 (95% CI, 0.730-0.732), and 0.761 (95% CI, 0.760-0.762), respectively, in women. PCE, PAR and FRS substantially underestimated the 5-year ASCVD risk in women by 70, 23 and 51%, respectively. However, PAR and FRS fairly predicted the risk in men and PAR was well calibrated. The calibrations of the three risk equations could be changed by recalibration. The decision curve analyses demonstrated that at the threshold risk of 5%, PCE was the most clinically useful in both men and women after recalibration. CONCLUSIONS: All three risk equations underestimated the 5-year ASCVD risk in women, while PAR and FRS fairly predicted that in men. However, the results of predictive performances for three risk equations are inconsistent, more accurate risk equations are required in the primary prevention of ASCVD aiming to this Uyghur and Kazakh populations.

Synthesis of anti-1,3 Amino Alcohol Motifs via Pd(II)/SOX Catalysis with the Capacity for Stereodivergence.

We report the development of a Pd(II)/(±)-MeO-SOX/2,5-dimethylbenzoquinone system that enables unprecedented access to anti-1,3 amino alcohol motifs in good yields (33 substrates, avg. 66% isolated yield, >20:1 dr) and high selectivities (avg. 10:1 dr). Switching ligands to (±)-CF3-SOX with the use of a less bulky quinone oxidant, the kinetic syn-1,3 amino alcohol motif can be accessed in comparable yields and selectivities. Advantages of the stereodivergent nature of this reaction are seen in the synthesis of anti- and syn-1,3 amino alcohol vitamin D3 analogue intermediates in half the steps and higher overall yield relative to previous routes. Additionally, all eight possible stereoisomers of a chiral diamino alcohol core are generated from two amino acids. Mechanistic studies reveal that the anti-isomer is furnished through concurrent Pd(II)(SOX) catalyzed C-H amination and Pd(0)(SOX) catalyzed isomerization cycles.

Nomogram Based on Cytokines for Cardiovascular Diseases in Xinjiang Kazakhs.

BACKGROUND: This study involved the development of a predictive 5-year morbidity nomogram for cardiovascular diseases (CVD) in Xinjiang Kazakhs based on cytokine levels. METHODS: The nomogram was based on a baseline survey of the town of Nalati in the Kazakh Autonomous Prefecture of Xinjiang from 2009 to 2013. By 2016, we had monitored 1508 people for a median time of 5.17 years and identified CVD events in the study population by collecting case information from local hospitals. The study population was divided into the training (n = 1005) and validation cohorts (n = 503) in a 2 : 1 ratio. The area under the receiver operating characteristic curve (AUC) was used to verify the predictive accuracy of the nomogram. The result was assessed in a validation cohort. RESULTS: At the end of the study, the incidence of CVD in Xinjiang Kazakhs was found to be 11.28%. We developed a new nomogram to predict the 5-year incidence of CVD based on age, interleukin-6 (IL-6), and adiponectin (APN) levels, diastolic blood pressure, and dyslipidemia. The AUC for the predictive accuracy of the nomogram was 0.836 (95% confidence interval: 0.802-0.869), which was higher than that for IL-6 and APN. These results were supported by validation studies. CONCLUSIONS: The nomogram model can more directly assess the risk of CVD in Kazakhs and can be used for CVD risk assessment.

C-H to C-N Cross-Coupling of Sulfonamides with Olefins.

Cross-coupling of nitrogen with hydrocarbons under fragment coupling conditions stands to significantly impact chemical synthesis. Herein, we disclose a C(sp3)-N fragment coupling reaction between terminal olefins and N-triflyl protected aliphatic and aromatic amines via Pd(II)/SOX (sulfoxide-oxazoline) catalyzed intermolecular allylic C-H amination. A range of (56) allylic amines are furnished in good yields (avg. 75%) and excellent regio- and stereoselectivity (avg. >20:1 linear:branched, >20:1 E: Z). Mechanistic studies reveal that the SOX ligand framework is effective at promoting functionalization by supporting cationic π-allyl Pd.

Grape Seed Proanthocyanidin Extract Inhibits Human Esophageal Squamous Cancerous Cell Line ECA109 via the NF-κB Signaling Pathway.

Esophageal squamous cell carcinoma is the most common type of squamous cell carcinoma. Grape seed proanthocyanidin extract (GSPE) is considered to exhibit anticancer activity against several different types of cancer. We aimed to determine whether GSPE inhibited esophageal squamous cancerous cells and the possible involvement of NF-κB in this process. The human esophageal squamous cancer cell line ECA109 was treated with GSPE (0-80 µg/mL) and BAY11-7082 (10 µmol/L) for 12, 24, and 48 h. The MTT assay was used to determine cell proliferation; alterations in cell apoptosis were detected by flow cytometry; levels of inflammatory factors interleukin-6 and cyclooxygenase-2 and apoptotic proteins Bax/Bcl-2 were measured by ELISA; qRT-PCR and western blots were used to examine the activation of caspase-3 and NF-κB signaling. GSPE inhibited the proliferation of ECA109 cells and induced cellular apoptosis in a time- and dose-dependent manner. ELISA results showed that GSPE and BAY11-7082 reduced the secretion of inflammatory cytokines interleukin-6 and cyclooxygenase-2. The results of PCR and western blotting indicated that GSPE and BAY11-7082 activated caspase-3 and attenuated the activation of the NF-κB signaling pathway. GSPE induced apoptosis in ECA109 cells and inhibited ECA109 cell proliferation via a reduction in the secretion of inflammatory cytokines. This mechanism may be related to the attenuation of NF-κB activity and the sensitization of caspase-3.

Interactions of six SNPs in APOA1 gene and types of obesity on low HDL-C disease in Xinjiang pastoral area of China.

BACKGROUND: This study aims to investigate association between six single nucleotide polymorphisms(SNPs) in APOA1 gene and types of obesity with the risk of low level HDL-C in the pastoral area of northwest China. METHODS: A total of 1267 individuals including 424 patients with low HDL-C disease and 843 health subjects were analyzed based on matched for age, sex. SNPShot technique was used to detect the genotypes of rs670, rs5069, rs5072, rs7116797, rs2070665 and rs1799837 in APOA1 gene. The relationship between above six SNPs and types of obesity with low HDL-C disease was analyzed by binary logistic regression. RESULTS: Carriers with rs670 G allele were more likely to get low HDL-C disease (OR = 1.46, OR95%CI: 1.118-1.915; P = 0.005); The genotypic and allelic frequencies of rs5069, rs5072, rs7116797, rs2070665, rs1799837 revealed no significant differences between cases and controls (P < 0.05); with reference to normal weight, Waist circumference (WC), Waist-to-hip ratio (WHR) individuals, respectively, general obesity measured by BMI had 2.686 times (OR95%CI: 1.695-4.256; P < 0.01), abdominal obesity measured by WC had 1.925 times (OR95%CI: 1.273-2.910; P = 0.002) and abdominal obesity measured by WHR had 1.640 times (OR95%CI: 1.114-2.416; P = 0.012) risk to get low HDL-C disease; APOA1 rs670 interacted with obesity (no matter general obesity or abdominal obesity) on low HDL-C disease. CONCLUSIONS: APOA1 gene may be associated with low HDL-C disease in the pastoral area of northwest China; obesity was the risk factor for low HDL-C disease; the low HDL-C disease is influenced by APOA1, obesity, and their interactions.

Association of Insulin Resistance with Glucose and Lipid Metabolism: Ethnic Heterogeneity in Far Western China.

Objective. To study the relationships between IR and glucose and lipid metabolism in far western China and these relationships' ethnic heterogeneity. Methods. From the baseline survey, 419 Uygur cases, 331 Kazak cases, and 220 Han cases were randomly selected, resulting in a total of 970 cases for study. FINS concentration was measured by radioimmunoassay. Results. (1) In the Kazak population, IR was correlated with hyperglycemia; high levels of TC, TG, and LDL-C; and low levels of HDL-C and abdominal obesity (all P < 0.05). (2) In the Uygur population, the influence of IR on hyperglycemia and abdominal obesity was the greatest. In the Kazak population, IR was associated with hyperglycemia most closely. In the Han population, IR may have had an impact on the incidence of low HDL-C levels. (3) After adjusting for sex, age, smoking status, and alcohol consumption, IR was still associated with anomalies in the metabolism of the Uygur, Kazak, and Han populations. Conclusion. IR was involved in the process of glucose and lipid metabolism, and its degree of involvement differed among the ethnicities studied. We could consider reducing the occurrence of abnormal glucose and lipid metabolism by controlling IR and aiming to reduce the prevalence of metabolic syndrome and related diseases.