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The ABCB1 C3435T Polymorphism is Associated with Triglyceride Reduction in Atorvastatin-treated Uygur Patients with Coronary Heart Disease and Dyslipidemia: An Observational Study.
Wang, T, Wu, J, Liu, T, Xu, L, Feng, J, Zhang, H, Shen, H, Sun, L, Li, H, Yu, L
Endocrine, metabolic & immune disorders drug targets. 2023;(9):1215-1228
Abstract
BACKGROUND The morbidity of coronary heart disease (CHD) and dyslipidemia in the Uygur population of Xinjiang is higher than the national average. Interindividual variability of the response to atorvastatin is a major clinical problem; generally, statins shed less impressive benefits for females than males. Nevertheless, it is unclear whether ABCB1 genes and sex modify the efficacy of atorvastatin in Uygur patients. OBJECTIVE To determine the impact of ABCB1 gene polymorphisms on the therapeutic response to atorvastatin in a Uygur population with dyslipidemia. METHODS Patients with dyslipidemia were treated with 20 mg/d or 40 mg/d atorvastatin for two to six months. TC, LDL-C, HDL-C, TG, APOB, APOE, LP(a), and APOA1 levels were measured before and after atorvastatin administration. We performed genotyping of ABCB1 C3435T and G2677T variants using hybridization sequencing. The association of variants between the percentage of change in TG levels was examined using multiple linear regression analysis. RESULTS We enrolled 193 Uygur patients. Atorvastatin reduced TG, LDL-C, TC, APOB, and APOE levels (P < 0.05), whereas LP(a) and APOA1 levels increased (P < 0.05). In multiple linear regression analysis, baseline TG level (beta 0.204; 95% confidence interval (CI): 1.980-10.493; P = 0.004) and TT genotype of ABCB1 C3435T (beta 0.162; 95% CI: 2.517-23.406; P = 0.023) predicted TG reduction with atorvastatin therapy in overall patients. Baseline TG level (beta 0.346; 95% CI: 4.374 -13.34; P < 0.001) with the TT genotype of ABCB1 C3435T (beta 0.401; 95% CI: 4.053-28.356; P = 0.021) was associated with a significant reduction in TG levels in men. Only baseline TG level predicted TG reduction within six months of atorvastatin therapy for females (beta 0.61; 95% CI: 3.204-20.557; P = 0.041). CONCLUSION In patients with the ABCB1 C3435T TT genotype, atorvastatin more effectively lowered TG than other polymorphisms. This investigation may provide insights into effective individualized therapies for CHD and dyslipidemia in the Uygur population.
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Long non‑coding RNA FEZF1‑AS1 facilitates non‑small cell lung cancer progression via the ITGA11/miR‑516b‑5p axis.
Song, H, Li, H, Ding, X, Li, M, Shen, H, Li, Y, Zhang, X, Xing, L
International journal of oncology. 2020;(6):1333-1347
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Abstract
Long non‑coding RNAs (lncRNAs) have emerged as key players in the development and progression of cancer. FEZ family zinc finger 1 antisense RNA 1 (FEZF1‑AS1) is a novel lncRNA that is involved in the development of cancer and acts as a potential biomarker for cancer. However, the clinical significance and molecular mechanism of FEZF1‑AS1 in non‑small cell lung cancer (NSCLC) remains uncertain. In the present study, FEZF1‑AS1 was selected using Arraystar Human lncRNA microarray and was identified to be upregulated in NSCLC tissues and negatively associated with the overall survival of patients with NSCLC. Loss‑of‑function assays revealed that FEZF1‑AS1 inhibition decreased cell proliferation and migration, and arrested cells at the G2/M cell cycle phase. Mechanistically, FEZF1‑AS1 expression was influenced by N6‑methyladenosine (m6A) modification. Since FEZF1‑AS1 was mainly located in the cytoplasmic fraction of NSCLC cells, it was hypothesized that it may be involved in competing endogenous RNA regulatory network to impact the prognosis of NSCLC. Via integrating Arraystar Human mRNA microarray data and miRNA bioinformatics analysis, it was revealed that ITGA11 expression was decreased with loss of FEZF1‑AS1 and increased with gain of FEZF1‑AS1 expression, and microRNA (miR)‑516b‑5p inhibited the expression levels of both FEZF1‑AS and ITGA11. RNA‑binding protein immunoprecipitation and RNA pulldown assays further demonstrated that FEZF1‑AS1 could bind to miR‑516b‑5p and that ITGA11 was a direct target of miR‑516b‑5p by luciferase reporter assay. Overall, the present findings demonstrated that FEZF1‑AS1 was upregulated and acted as an oncogene in NSCLC by regulating the ITGA11/miR‑516b‑5p axis, suggesting that FEZF1‑AS1 may be a potential prognostic biomarker and therapeutic target for NSCLC.
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The major causes and risk factors of total and cause-specific mortality during 5.4-year follow-up: the Shanghai Changfeng Study.
Wu, L, Lin, H, Hu, Y, Zhu, C, Ma, H, Gao, J, Wu, J, Shen, H, Jiang, W, Zhao, N, et al
European journal of epidemiology. 2019;(10):939-949
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Abstract
To investigate the major causes and predictive factors of death in a middle-aged and elderly Chinese population. A total of 6591 residents aged ≥ 45 years from Shanghai Changfeng community were followed up for an average of 5.4 years. The causes of death were coded according to the 10th Revision of International Classification of Diseases. The mortality rate was calculated by person-years of follow up and age-standardized according to the 2010 Chinese census data. Multivariable-adjusted Cox proportional hazards model was performed to investigate the predictors of all-cause and cause-specific mortality. During the total follow-up of 35,739 person-years, 370 deaths were documented (157 from malignant neoplasms, 70 from heart diseases, 68 from cerebrovascular diseases, 75 from other causes). The age-standardized all-cause mortality rate was 798.2 per 100,000 person-years (927.9 among men and 716.7 among women). Results from multivariable analyses showed that aging, diabetes, and osteoporosis at baseline were independent predictors of all-cause mortality, with hazard ratios (HR) of 1.11 (95% CI 1.10-1.13), 1.91 (1.51-2.42), and 1.71 (1.24-2.35), respectively. The population attributable risk percent of diabetes and osteoporosis was 19.7% and 11.7%, respectively. Cigarette smoking was associated with a higher risk of all-cause mortality in men (HR and 95%CI 1.44, 1.01-2.06). In women, diabetes and osteoporosis were related to a higher risk of cardiovascular mortality (3.27, 1.82-5.88 and 1.89, 1.04-3.46, respectively). While in men, osteoporosis was related to a higher risk of malignant neoplasms mortality (2.39, 1.07-5.33). Malignant neoplasms, heart diseases, and cerebrovascular diseases are the leading causes of death. Aging, smoking, underweight, diabetes, and osteoporosis are independent predictors of premature death among middle-aged and elderly Chinese community population. Moreover, there may have been some differences in the causes and predictors of premature death between men and women.
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Impact of Early Diabetic Ketoacidosis on the Developing Brain.
Aye, T, Mazaika, PK, Mauras, N, Marzelli, MJ, Shen, H, Hershey, T, Cato, A, Weinzimer, SA, White, NH, Tsalikian, E, et al
Diabetes care. 2019;(3):443-449
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Abstract
OBJECTIVE This study examined whether a history of diabetic ketoacidosis (DKA) is associated with changes in longitudinal cognitive and brain development in young children with type 1 diabetes. RESEARCH DESIGN AND METHODS Cognitive and brain imaging data were analyzed from 144 children with type 1 diabetes, ages 4 to <10 years, who participated in an observational study of the Diabetes Research in Children Network (DirecNet). Participants were grouped according to history of DKA severity (none/mild or moderate/severe). Each participant had unsedated MRI scans and cognitive testing at baseline and 18 months. RESULTS In 48 of 51 subjects, the DKA event occurred at the time of onset, at an average of 2.9 years before study entry. The moderate/severe DKA group gained more total and regional white and gray matter volume over the observed 18 months compared with the none/mild group. When matched by age at time of enrollment and average HbA1c during the 18-month interval, participants who had a history of moderate/severe DKA compared with none/mild DKA were observed to have significantly lower Full Scale Intelligence Quotient scores and cognitive performance on the Detectability and Commission subtests of the Conners' Continuous Performance Test II and the Dot Locations subtest of the Children's Memory Scale. CONCLUSIONS A single episode of moderate/severe DKA in young children at diagnosis is associated with lower cognitive scores and altered brain growth. Further studies are needed to assess whether earlier diagnosis of type 1 diabetes and prevention of DKA may reduce the long-term effect of ketoacidosis on the developing brain.