Both time (chronological aging) and ovarian aging contributed to substantial changes in body composition (fat and skeletal muscle mass) and waist circumference. These changes have important ramifications for establishing a metabolic environment that can be healthy or unhealthy.
Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10−7 to 4.79 × 10−44). By incorporating the PRS into EBV-serology-based NPC screening, the test’s positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.
Smoking, diet, and physical activity may impact chronic diseases in part by promoting or attenuating oxidative stress. We evaluated associations between lifestyle factors and urine F(2a)-isoprostanes, a marker of oxidative stress in 1610 participants of the Study of Women's Health Across the Nation (SWAN). Dietary intake and physical activity were assessed at baseline and the 5th year 05 (Y05). These data were related to Y05 urinary F(2a)-isoprostane concentration with regression analyses. Median urine F(2a)-isoprostane concentration was 433 ng/L overall, 917 ng/L in smokers [inter-quartile range (IQR): 467, 1832 ng/L], and 403 ng/L in nonsmokers (IQR: 228, 709 ng/L; P < 0.0001 for difference). Higher trans fat intake was associated with higher urine F(2a)-isoprostane concentration; partial Spearman correlations (rho(x|y)) between Y05 urine F(2a)-isoprostane concentration and trans fatty acids was 0.19 (P = 0.03) in smokers and 0.13 (P < 0.0001) in nonsmokers. Increased log trans fat intake from baseline to Y05 was associated with higher concentration of log urine F(2a)-isoprostanes in nonsmokers (beta = 0.131, SE = 0.04, P = 0.0003). In nonsmokers, the partial correlation (rho(x|y)) between lutein and urine F(2a)-isoprostane concentration was -0.13 (P < 0.0001). Increased intake of log lutein from baseline to Y05 was also associated with lower log urine F(2a)-isoprostane concentration (beta = -0.096, SE = 0.03, P = 0.0005) in nonsmokers. Increased zinc intake from baseline to Y05 was associated with lower log urine F(2a)-isoprostane concentration in smokers and nonsmokers (beta = -0.346, SE = 0.14, P = 0.01), and -0.117, 0.04 (P = 0.001), respectively]. In conclusion, diet (fat subtypes, zinc, and vegetable components) and smoking were associated with urine F(2a)-isoprostanes, a marker of oxidative stress.
Lysosomal-associated membrane protein 3 (LAMP3), identified as a molecular marker of mature dendritic cells, is one of the LAMP family members. Its expression was induced by hypoxia, and was associated with hypoxia mediated metastasis in breast and cervical cancers. However, epithelial expression of LAMP3 and its prognostic value in esophageal squamous cell carcinoma (ESCC) is still unknown. In the current study, mRNA expression of LAMP3 in 157 ESCC tissues and 50 adjacent normal tissues was detected by quantitative real-time PCR (qRT-PCR). LAMP3 protein expression in 46 paired cancerous and normal tissues was detected by immunohistochemistry (IHC). Then, DNA copy number was examined to observe its potential correlation with mRNA expression. The results showed that both mRNA and protein expression level of LAMP3 was significantly higher in cancerous tissues compared with normal controls (p < 0.001). LAMP3 DNA copy number was amplified in 70% of ESCC tissues and positive correlated with mRNA expression (p = 0.037). Furthermore, patients with higher LAMP3 expression had worse overall survival (HR = 1.90, 95% CI = 1.17–3.09, p = 0.010) and disease-free survival (HR = 1.80, 95% CI = 1.18–2.74, p = 0.006). In conclusion, our results suggest that epithelial LAMP3 expression is an independent prognostic biomarker for ESCC.
Background: Although there are several biomarkers for identifying in-hospital mortality in acute type A aortic dissection (AAD), timely as well as perfect prediction in-hospital mortality is still not attained. Herein, we intend to develop as well to validate an in-hospital mortality risk independent predictive nomogram for AAD patients. Methods: From January 2014 to December 2018, 703 individuals with AAD were involved in this study.They were indiscriminately categorized into training (n=520) and validation (n=183) sets. The univariate and multivariate analyses were used to screen in-hospital mortality predictors from the entire training set data. The predictors were used to establish a nomogram which was confirmed via internal as well as external authentication. This validation included discriminative capacity defined by the receiver operating characteristic (ROC) curve area under the curve (AUC) and the predictive precision via calibration curves. Results: There was 33.43% in-hospital mortality overall incidence. The uric acid, D-dimer, C-reactive protein and management were individually related to in-hospital mortality as per multivariate logistic regression. On the basis of four variables with internal of AUC 0.901 and external validation of AUC 0.903, a nomogram was established. Calibration plots showed that the predicted and actual in-hospital mortality probabilities were fitted well on both internal and external validation.Conclusions: This recommended nomogram can calculate the specific possibility of in-hospital mortality with good precision, high discrimination, and probable clinical application in AAD patients.
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