Significance of TERT promoter mutation in differential diagnosis of non-invasive inverted urothelial lesions of bladder / 中华病理学杂志

Objective: To investigate the gene mutation of telomerase reverse transcriptase (TERT) promoter in inverted urothelial lesions of the bladder and its significance in differential diagnosis. Methods: From March 2016 to February 2022, a total of 32 patients with inverted urothelial lesions diagnosed in Department of Pathology at Qingdao Chengyang People's Hospital and 24 patients at the Affiliated Hospital of Qingdao University were collected, including 7 cases of florid glandular cystitis, 13 cases of inverted urothelial papilloma, 8 cases of inverted urothelial neoplasm with low malignant potential, 17 cases of low-grade non-invasive inverted urothelial carcinoma, 5 cases of high-grade non-invasive inverted urothelial carcinoma, and 6 cases of nested subtype of urothelial carcinoma were retrospectively analyzed for their clinical data and histopathological features. TERT promoter mutations were analyzed by Sanger sequencing in all the cases. Results: No mutations in the TERT promoter were found in the florid glandular cystitis and inverted urothelial papilloma. The mutation rates of the TERT promoter in inverted urothelial neoplasm with low malignant potential, low grade non-invasive inverter urothelial carcinoma, high grade non-invasive inverted urothelial carcinoma and nested subtype urothelial carcinoma were 1/8, 8/17, 2/5 and 6/6, respectively. There was no significant difference in the mutation rate of TERT promoter among inverted urothelial neoplasm with low malignant potential, low-grade non-invasive inverted urothelial carcinoma, and high-grade non-invasive inverted urothelial carcinoma (P>0.05). All 6 cases of nested subtype of urothelial carcinoma were found to harbor the mutation, which was significantly different from inverted urothelial neoplasm with low malignant potential and non-invasive inverted urothelial carcinoma (P<0.05). In terms of mutation pattern, 13/17 of TERT promoter mutations were C228T, 4/17 were C250T. Conclusions: The morphology combined with TERT promoter mutation detection is helpful for the differential diagnosis of bladder non-invasive inverted urothelial lesions.

Association between obesity and DNA methylation among the 7-16 year-old twins / 中华流行病学杂志

Objective: On whole-genome scale, we tried to explore the correlation between obesity-related traits and DNA methylation sites, based on discordant monozygotic twin pairs. Methods: A total of 90 pairs of 6-17 year-old twins were recruited in Chaoyang district, Yanqing district and Fangshan district in Beijing in 2016. Information on twins was gathered through a self-designed questionnaire and results: from physical examination, including height, weight and waist circumference of the subjects under study. DNA methylation detection was chosen on the Illumina Human Methylation EPIC BeadChip. R 3.3.1 language was used to read the DNA methylation signal under quality control on samples and probes. Ebayes function of empirical Bayes paired moderated t-test was used to identify the differential methylated CpG sites (DMCs). VarFit function of empirical Bayes paired moderated Levene test was used to identify the differentially variables CpG sits (DVCs) in obese and normal groups. Results According to the obesity discordance criteria, we collected 23 pairs of twins (age range 7 to 16 years), including 12 male pairs. A total of 817 471 qualified CpG loci were included in the genome-wide correlation analysis. According to the significance level of FDR set as <0.05, no positive sites would meet this standard. When DMC CpG site cg05684382, with the smallest P value (1.26E-06) as on chromosome 12, the DVC CpG site cg26188191 with the smallest P value (6.44E-06) appeared in CMIP gene on chromosome 16. Conclusions: In this study, we analyzed the genome-wide DNA methylation and its correlation with obesity traits. After multiple testing corrections, no positive sites were found to have associated with obesity. However, results from the correlation analysis demonstrated sites cg05684382 (chr: 12) and cg26188191 (chr: 16) might have played a role in the development of obesity. This study provides a methodologic reference for the studies on discordance twins related problems.

Association between total cholesterol and risk of lung cancer incidence in men: a prospective cohort study / 中华流行病学杂志

Objective: To assess the association and intensity of baseline TC level with the incidence of lung cancer in men in China. Methods: Since May 2006, all the male workers, including the employees and the retirees in Kailuan Group were recruited in the Kailuan male dynamic cohort study. Information about demographics, medical history, anthropometry and TC level were collected at the baseline interview, as well as the information of newly-diagnosed lung cancer cases during the follow-up period. According to guidelines for blood lipids in Chinese adults and the distribution in the population, TC level was classified into five groups as followed: <160, 160-, 180-, 200- and ≥240 mg/dl, with the second quintile group (160- mg/dl) serving as the referent category. Cox proportional hazards regression model and restricted cubic spline (RCS) model were used to evaluate the association and the nonlinear association between baseline TC level and the risk of lung cancer in the men. Results: By December 31, 2014, for the 109 884 men, a follow up of 763 819.25 person-years was made with a median follow-up period of 7.88 years. During the follow up, 808 lung cancer cases were identified. After adjustment for age, education level, income level, smoking status, alcohol consumption level, history of dust exposure, FPG level and BMI, HR (95%CI) of lung cancer for men with lower TC level (<160 mg/dl) and higher TC level (≥240 mg/dl) were 1.34 (1.04- 1.72) and 1.45 (1.09-1.92), respectively, compared with men with normal TC level (160- mg/dl). The results didn't change significantly after exclusion of newly diagnosed cancer cases within 2 years of follow up and subjects with the history of hyperlipidemia. Conclusion: Our results showed that TC might be associated with higher risk of lung cancer. Men with lower TC level or higher TC level had higher risk for lung cancer. Keep moderate TC level might be one of the effective precaution for the prevention of lung cancer.

Alcohol consumption and the risk of lung cancer in males: a prospective cohort study / 中华流行病学杂志

Objective: To investigate the association between alcohol consumption and lung cancer risk in Chinese males. Methods: Information on alcohol consumption and outcomes were collected on a biennial basis among males in Kailuan Cohort (2006-2015). In addition, electronic databases of hospitals affiliated to Kailuan Community, Insurance Systems of Kailuan Community and Tangshan were also used for supplementary information retrieval. Cox proportional hazards regression models were used to evaluate the hazard ratio (HR) and 95%CI of baseline frequency and type of alcohol consumption associated with lung cancer risk in males. Non-drinkers were used as control group. Results: A total of 101 751 males were included and 913 new lung cancer cases were identified in the Kailuan male cohort study, with a total follow-up time of 808 146.56 person-years and a median follow-up time of 8.88 years by 31 December 2015. After adjusting for potential confounding factors, the HR of former drinkers, occasional drinkers (<1/day) and drinkers (≥1/day) were 1.30 (95%CI: 0.90-1.88), 0.80 (95%CI: 0.64-1.01) and 1.04 (95%CI: 0.85-1.27), respectively, compared with non-drinkers. In addition, drinking beer/red wine (HR=0.91, 95%CI: 0.69-1.20) and white wine (HR=0.99, 95%CI: 0.83-1.19) showed no significant association with lung cancer. The results were similar when stratified analysis were conducted. Conclusion: Our study results don't support the hypothesis that alcohol consumption is significantly associated with the risk of lung cancer in males.

H nuclear magnetic resonance-based metabolomics reveals sex-specific metabolic changes of gastrodin intervention in rats

OBJECTIVES@#To explore (1)H nuclear magnetic resonance-based metabolomics on sex-specific metabolic changes of gastrodin intervention in rats.@*METHODS@#In this research, (1)H NMR-based metabolomics was used for the first time to investigate metabolic changes following chronic intervention with gastrodin in rats.@*RESULTS@#24 endogenous metabolites were identified. Body weight, daily diet and the total volume of urine in in each day of each rat were measured synchronously. Modifications in 12 metabolites were observed following gastrodin intervention, indicating gastrodin-induced alterations in carbohydrate and energy metabolism. Interestingly, these metabolic changes were not totally identical in female and male rats. Some metabolic changes arising from gastrodin intervention showed sexual dimorphism including LDL/VLDL and lactate which were on the decrease in the female but on the increase in the male, together with arginine/ornithine, creatine, and glycerol which were on the increase in the female but on the decrease in the male. While the decrease in pyruvate, succinate and glutamate was only shown in the male and the increase in valine, α-ketoglutarate, glycine and glucose was only in the female.@*CONCLUSIONS@#This research shows the sex-specific metabolic response to GAS intervention, weather GAS is a healthy dietary supplement for the male merits further investigation.