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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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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.
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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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Neutrophil-lymphocyte ratio, gamma-glutamyl transpeptidase, lipase, high-density lipoprotein as a panel of factors to predict acute pancreatitis in pregnancy.
Zhang, L, Wang, Y, Han, J, Shen, H, Zhao, M, Cai, S
Medicine. 2018;(26):e11189
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Abstract
Acute pancreatitis in pregnancy (APIP) is a rare but dangerous complication. APIP has common symptoms with acute abdomen. Assessment of an acute abdomen is more complicated during pregnancy because the gravid uterus could mask most of symptomatic signs. It has been a challenge to diagnose APIP by physical examination or diagnostic imaging. Case studies on APIP are also limited for analysis on the risk factors associated with the disease. This retrospective study evaluated a series of risk factors from a relatively substantial number of APIP cases to determine early predictors or prognosis markers for APIP.Fifty-nine APIP patients together with 179 random normal pregnant women in Shengjing Affiliated Hospital of China Medical University were included for this retrospective study. Medical parameters of blood test in biochemistry and hematology were compared between 2 groups using t test. Multivariate logistic regression analysis was performed to investigate the relationship between various factors and APIP using Statistical Applied Software (SAS student version).Compared with normal pregnant women, APIP patients have elevated values in alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen, creatinine, C-reactive protein, direct bilirubin, fibrin degradation products, gamma-glutamyl transpeptidase (GGT), glucose, lipase, pH and decreased values in albumin, fibrinogen, high-density lipoprotein (HDL), hemoglobin, low-density lipoprotein cholesterol (LDL-D), and total proteins from their blood tests. In addition, APIP patients have decreased numbers in red cells but increased numbers in white blood cells and increased ratio of neutrophil/lymphocyte (N/L). Among these factors, N/LR, GGT, lipase, and HDL are significantly associated with APIP. This study suggests that the combination of those factors serve as a panel of indicators for early-onset prognosis of APIP.GGT, lipase, HDL, and N/LR can serve as a panel of factors to predict APIP. More case studies are important to further evaluate the predicting power of this panel factors in APIP.
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Enchondroma in the distal phalanx of the finger: An observational study of 34 cases in a single institution.
Lu, H, Chen, Q, Yang, H, Shen, H
Medicine. 2016;(38):e4966
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Abstract
UNLABELLED The goal of our study was to report the clinical presentation, treatment, and complications of enchondroma in the distal phalanx of the finger. This was a retrospective study of 34 patients (19 women and 15 men) who underwent surgery between May 2004 and September 2012 for enchondroma in the distal phalanx of the finger. The average age of the patients was 39.38 ± 10.97 years old (range 14-59). The presenting symptoms and imaging features were recorded. The surgical procedure was performed under regional or general anesthesia. The surgical technique involved removal of tumors by opening a cortical window and curetting the cavity. The defects were filled with an injectable calcium phosphate cement. All patients received follow-up in our outpatient clinic every 6 months. Expansion of bone or thinning of the cortex present in the radiological imaging, including anteroposterior and lateral plain radiographs of the fingers, was used to assess for tumor recurrence. The observational end-point was reoperation.All tumors were confirmed as enchondromas by the pathological results. None of the patients had a tumor recurrence. Three patients (9% of cases) developed an infection. After antibiotic treatment, 2 patients were cured, and 1 patient required an amputation. Enchondroma in the distal phalanx of the finger presents with a variety of clinical symptoms. Injectable calcium phosphate cement is adequate for bone grafting. Postoperative infection is more common than tumor recurrence. If patients have an infection or bilateral bone cortex defects, bone grafting is challenging. LEVEL OF EVIDENCE Therapeutic study, Level IV.
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Treatment of polycystic ovarian syndrome with insulin resistance by insulin-sensitizer.
Hu, L, Shen, H, Wu, QF, Tian, L, Hu, MH
Clinical and experimental obstetrics & gynecology. 2014;(3):288-92
Abstract
OBJECTIVE The aim of this study was to observe clinical curative effects of combination application of dimethylbiguanide and pioglitazone and single application of pioglitazone in patients with polycystic ovarian syndrome (PCOS) complicated with insulin resistance (IR). MATERIALS AND METHODS Forty cases of patients with PCOS complicated with IR were investigated, and 20 cases of infertile women without PCOS were taken as the control group. PCOS group was divided into group A and group B according to body mass index (BMI) to detect glucose and lipids metabolism indicators, C reactive protein (CRP), etc. There were 20 cases in group A (Pioglitazone) and 20 cases in group B (dimethylbiguanide and pioglitazone). After treatment for 12 weeks, changes of the above various indicators were compared. RESULTS After treatment, insulin resistance index and serum testosterone (T) of two groups patients with PCOS significantly reduced (p < 0.05). Compared to before treatment, BMI of group B significantly reduced (p < 0.05). For INS at two hours after treatment, group B reduced more significantly (p < 0.05). CONCLUSION The combination of dimethylbiguanide and pioglitazone was more effective for the treatment of PCOS complicated with IR than simple pioglitazone; chronic inflammation occurrence was possibly one of reasons for insulin sensitivity reduction of patients with PCOS.
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Risk factor analysis of calcification in aortic and mitral valves in maintenance peritoneal dialysis patients.
Wang, C, Jiang, L, Feng, S, Shi, Y, Shen, H, Shi, X, Wang, Z, Zeng, Y
Kidney & blood pressure research. 2013;(4-5):488-95
Abstract
BACKGROUND/AIMS: This study aimed to investigate potential risk factors for calcification in aortic and mitral valves in maintenance peritoneal dialysis (MPD) patients. METHODS We enrolled MPD patients who had undergone over 18 months of dialysis in our dialysis center, examined their cardiac valve calcification status by echocardiography, and recorded their biochemical data and dialysis-related indicators. These results were compared by logistic regression analyses to identify the risk factors associated with calcification in aortic and mitral valves. RESULTS Among the 117 enrolled MPD patients, 41 exhibited calcification in aortic or mitral valves, including 38 with aortic valve calcification (AVC) and 17 with mitral valve calcification (MVC); 14 of them had calcification in both aortic and mitral valves. Multivariate logistic regression analysis revealed that age (OR=1.965, p=0.01), diabetes history (OR=4.693, p=0.029), calcium-phosphorus product (OR=2.373, p=0.001) and prealbumin (OR=0.908, p=0.012) were independently related to AVC, whereas age (OR=3.179, p=0.023), calcium-phosphorus product (OR=6.512, p=0.001), prealbumin (OR=0.885, p=0.033), high-density lipoprotein (OR=19.540, p=0.011) and diabetes history (OR=6.948, p=0.038) were independently related to MVC. CONCLUSIONS The incidence of cardiac valve calcification in MPD patients is high, and the incidence of AVC is higher than MVC. Age, diabetes history, calcium-phosphorus product and hypo-prealbuminemia are independent risk factors for AVC, whereas age, calcium-phosphorus product and hypo-prealbuminemia are independent risk factors for MVC.