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Observational and Genetic Associations of Body Mass Index and Hepatobiliary Diseases in a Relatively Lean Chinese Population.
Pang, Y, Kartsonaki, C, Lv, J, Millwood, IY, Yu, C, Guo, Y, Chen, Y, Bian, Z, Yang, L, Chen, J, et al
JAMA network open. 2020;(10):e2018721
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Abstract
IMPORTANCE There is some support for the existence of genetic associations between adiposity and certain hepatobiliary diseases in Western populations. However, there is little evidence of such genetic associations in China, where the causes of these diseases may differ from those in Western populations and the mean body mass index (BMI) is much lower. OBJECTIVES To compare the observational associations of BMI with hepatobiliary diseases and liver biomarkers with the genetic associations between BMI and these factors and to assess whether the genetic associations of BMI with liver diseases differed by hepatitis B virus infection status. DESIGN, SETTING, AND PARTICIPANTS This cohort study used data from the prospective China Kadoorie Biobank, including 473 938 adults aged 30 to 79 years without hepatobiliary diseases at baseline from 10 diverse areas in China from June 25, 2004, to July 15, 2008. A random sample of 75 736 participants with genotyping data was included in the Mendelian randomization analysis. Follow-up was completed January 1, 2017 (median [interquartile range] length of follow-up, 10.2 [9.2-11.1] years). Data were analyzed from January to October 2019. EXPOSURES Measured BMI obtained during the baseline survey and genetically instrumented BMI derived using 92 single-nucleotide variations. MAIN OUTCOMES AND MEASURES Incident cases of hepatobiliary diseases, liver enzymes, fatty liver index, and fibrosis score. RESULTS Among 473 938 individuals (276 041 [58.2%] women), the mean (SD) age was 52 (10.9) years and mean (SD) BMI was 23.8 (3.4). Baseline BMI was associated with higher risks of chronic liver disease (adjusted risk ratio per 1-SD increase, 1.14; 95% CI, 1.11 to 1.17) and gallbladder disease (adjusted risk ratio per 1-SD increase, 1.29; 95% CI, 1.27 to 1.31), with heterogeneity by disease subtype (P < .001). Genetically instrumented BMI was associated with higher risks of chronic liver disease (risk ratio per 1-SD increase, 1.55; 95% CI, 1.08 to 2.24) and gallbladder disease (risk ratio per 1-SD increase, 1.40; 95% CI, 1.11 to 1.76), with no heterogeneity between subtypes. A meta-analysis of the genetic associations in China Kadoorie Biobank and those calculated in UK Biobank gave a risk ratio of 1.55 (95% CI, 1.30 to 1.84) for chronic liver disease and 1.42 (95% CI, 1.22 to 1.64) for gallbladder disease. In the China Kadoorie Biobank study, there were positive genetic associations of BMI with liver enzymes, steatosis, and fibrosis scores, consistent with observational associations. The genetic associations of BMI with liver diseases and biomarkers did not differ by hepatitis B virus infection status. CONCLUSIONS AND RELEVANCE In this cohort study of a relatively lean Chinese population, there were positive genetic associations of BMI with hepatobiliary diseases. These results suggest that maintaining a healthy weight through diet and physical activity may help prevent hepatobiliary diseases.
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Serum ARCHITECT PIVKA-II reference interval in healthy Chinese adults: Sub-analysis from a prospective multicenter study.
Yan, C, Hu, J, Yang, J, Chen, Z, Li, H, Wei, L, Zhang, W, Xing, H, Sang, G, Wang, X, et al
Clinical biochemistry. 2018;:32-36
Abstract
BACKGROUND Protein induced by vitamin K absence or antagonist-II (PIVKA-II) has been widely used as a biomarker for liver cancer diagnosis in Japan for decades. However, the reference intervals for serum ARCHITECT PIVKA-II have not been established in the Chinese population. Thus, this study aimed to measure serum PIVKA-II levels in healthy Chinese subjects. METHODS This is a sub-analysis from the prospective, cross-sectional and multicenter study (ClinicalTrials.gov Identifier: NCT03047603). A total of 892 healthy participants (777 Han and 115 Uygur) with complete health checkup results were recruited from 7 regional centers in China. Serum PIVKA-II level was measured by ARCHITECT immunoassay. All 95% reference ranges were estimated by nonparametric method. RESULTS The distribution of PIVKA-II values showed significant difference with ethnicity and sex, but not age. The 95% reference range of PIVKA-II was 13.62-40.38 mAU/ml in Han Chinese subjects and 15.16-53.74 mAU/ml in Uygur subjects. PIVKA-II level was significantly higher in males than in females (P < 0.001). The 95% reference range of PIVKA-II was 15.39-42.01 mAU/ml in Han males while 11.96-39.13 mAU/ml in Han females. CONCLUSIONS The reference interval of serum PIVKA-II on the Architect platform was established in healthy Chinese adults. This will be valuable for future clinical and laboratory studies performed using the Architect analyzer. Different ethnic backgrounds and analytical methods underline the need for redefining the reference interval of analytes such as PIVKA-II, in central laboratories in different countries.
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Prediction of Chemotherapeutic Efficacy in Non-Small Cell Lung Cancer by Serum Metabolomic Profiling.
Tian, Y, Wang, Z, Liu, X, Duan, J, Feng, G, Yin, Y, Gu, J, Chen, Z, Gao, S, Bai, H, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2018;(9):2100-2109
Abstract
Purpose: No validated biomarkers that could identify the subset of patients with lung adenocarcinoma who might benefit from chemotherapy have yet been well established. This study aimed to explore potential biomarker model predictive of efficacy and survival outcomes after first-line pemetrexed plus platinum doublet based on metabolomics profiling.Experimental Design: In total, 354 consecutive eligible patients were assigned to receive first-line chemotherapy of pemetrexed in combination with either cisplatin or carboplatin. Prospectively collected serum samples before initial treatment were utilized to perform metabolomics profiling analyses under the application of LC/MS-MS. Binary logistic regression analysis was carried out to establish discrimination models.Results: There were 251 cases randomly sorted into discovery set, the rest of 103 cases into validation set. Seven metabolites including hypotaurine, uridine, dodecanoylcarnitine, choline, dimethylglycine, niacinamide, and l-palmitoylcarnitine were identified associated with chemo response. On the basis of the seven-metabolite panel, a discriminant model according to logistic regression values g(z) was established with the receiver operating characteristic curve (AUC) of 0.912 (Discovery set) and 0.909 (Validation set) in differentiating progressive disease (PD) groups from disease control (DC) groups. The median progression-free survival (PFS) after chemotherapy in patients with g(z) ≤0.155 was significantly longer than that in those with g(z) > 0.155 (10.3 vs.4.5 months, P < 0.001).Conclusions: This study developed an effective and convenient discriminant model that can accurately predict the efficacy and survival outcomes of pemetrexed plus platinum doublet chemotherapy prior to treatment delivery. Clin Cancer Res; 24(9); 2100-9. ©2018 AACR.
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Epicardial adipose tissue predicts mortality in incident hemodialysis patients: a substudy of the Renagel in New Dialysis trial.
D'Marco, LG, Bellasi, A, Kim, S, Chen, Z, Block, GA, Raggi, P
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2013;(10):2586-95
Abstract
BACKGROUND Epicardial adipose tissue (EAT) has been described in the general population as an independent risk marker for incident coronary artery disease. In hemodialysis patients, it correlates with other markers of cardiovascular disease, but it is unknown if it is associated with adverse events. METHODS post hoc analysis of the Renagel in New Dialysis (RIND) patients study, a randomized trial of sevelamer versus calcium-based phosphate binders in 109 incident hemodialysis patients, followed for all-cause mortality for a median of 49.3 months. Patients underwent baseline cardiac computed tomography imaging within 120 days of dialysis initiation. RESULTS Baseline EAT measurements were available in 95 patients; EAT was positively correlated with age, body mass index, triglycerides, C-reactive protein, coronary artery calcium and aortic calcium, and negatively correlated with systolic and diastolic blood pressure, serum high density lipoprotein (HPL) cholesterol and serum phosphate (all P < 0.05). During follow-up, a total of 27 (28.4%) patients expired [mortality per 1000 patients/year: 95% confidence interval (95% CI) = 77 (64-94)]. Five-year survival rate was 44. 6% (95% CI: 21.1-65.7) and 71.2% (95% CI: 45.95-86.25) in patients with EAT above or below the median, respectively. Each 10 cc increase in EAT volume was associated with a significant 6% increase in the risk of death during follow-up [hazard ratio (HR): 1.060; 95% CI: 1.013-1.109; P-value = 0.012]. CONCLUSIONS In this subanalysis of a randomized trial, EAT was an independent predictor of mortality in incident hemodialysis patients after ~4 years of follow-up. These hypothesis-generating findings will need confirmatory evidence.
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Safety and tolerability of Lactobacillus reuteri DSM 17938 and effects on biomarkers in healthy adults: results from a randomized masked trial.
Mangalat, N, Liu, Y, Fatheree, NY, Ferris, MJ, Van Arsdall, MR, Chen, Z, Rahbar, MH, Gleason, WA, Norori, J, Tran, DQ, et al
PloS one. 2012;(9):e43910
Abstract
BACKGROUND There are few carefully-designed studies investigating the safety of individual probiotics approved under Investigational New Drug policies. OBJECTIVES The primary aim of this prospective, double-blind placebo-controlled trial was to investigate if daily treatment of adults with Lactobacillus reuteri DSM 17938 (LR) for 2 months is safe and well-tolerated. Our secondary aim was to determine if LR treatment has immune effects as determined by regulatory T cell percentages, expression of toll-like receptors (TLR)-2 and -4 on circulating peripheral blood mononuclear cells (PMBCs), cytokine expression by stimulated PBMC, and intestinal inflammation as measured by fecal calprotectin. METHODS Forty healthy adults were randomized to a daily dose of 5 × 10(8) CFUs of LR (n = 30) or placebo (n = 10) for 2 months. Participants completed a daily diary card and had 7 clinic visits during treatment and observation. RESULTS There were no severe adverse events (SAEs) and no significant differences in adverse events (AEs). There were no differences in PBMC subclasses, TLRs, or cytokine expression after treatment. The probiotic-treated group had a significantly higher fecal calprotectin level than the placebo group after 2 months of treatment: 50 µg/g (IQR 24-127 µg/g) vs. 17 µg/g (IQR 11-26 µg/g), p = 0.03, although values remained in the normal clinical range (0-162.9 µg/g). LR vials retained >10(8) CFUs viable organisms/ml. CONCLUSIONS LR is safe and well tolerated in adults, without significant changes in immunologic markers. There was a small but significant increase in fecal calprotectin, perhaps indicating some element of immune recognition at the intestinal level. TRIAL REGISTRATION Clinical Trials.gov NCT00922727.