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Objective To evaluate the value of rs61330082 and rs4730153 polymorphisms of Visfatin locus for the diagnosis of type 2 diabetes mellitus(T2DM)in a high-risk population.Methods SNPscanTM high-throughput single nucleotide polymorphism typing technique was used to genotype Visfatin gene loci rs61330082 and rs4730153 in 346 T2DM patients(T2DM group)and 1426 normal controls(NC group).Logistic regression analysis was used to analyze T2DM risk factors.ROC curves were used to analyze the optimal cut-off values of Visfatin gene rs61330082 and rs4730153 for the diagnosis of T2DM.Results The proportion of women,age,obesity,smoking,hypertension,FPG,HbA1c and TG were higher in T2DM group than those in NC group(P<0.01)and HDL-C was lower than in NC group(P<0.01).The frequency of G allele and GG genotype was higher in T2DM group compared with NC group(P<0.05).Logistic regression analysis showed that age,female,obesity,hypertension,TG,and GG genotype at rs4730153 locus were risk factors for T2DM,HDL-C was a protective factor for T2DM.The area under the ROC curve of GG genotype at Visfatin rs4730153 mutation for diagnosis of T2DM was 0.668 and the optimal cut-off point for predicting T2DM was 20.04%,with sensitivity 60.1%and specificity 66.1%,respectively.Conclusion The GG genotype of Visfatin gene rs4730153 locus is associated with the risk of T2DM and can beused as a candidate gene for predicting phenotype of T2DM.
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Objectives:To investigate the effect of inhibition of long non-coding RNA(lnc RNA)in human metastasis associated lung adenocarcinoma transcript 1(MALAT1)on glycolipitoxicity-induced human umbilical vein endothelial cell dysfunction. Methods:Human umbilical vein endothelial cells were treated with glucose and palmitic acid in vitro to establish the glycolipitoxic endothelial cell models.Following groups were examined:control group,high-glucose and high-fat group,high-glucose and high-fat + non-targeting RAN control group,high-glucose and high-lipid+MALAT1 siRNA group,and high-glucose and high-lipid+MAPK1 siRNA group.RT-qPCR was used to detect the mRNA expression of MALAT1 and MAPK1.Western blot was used to detect the expression levels of autophagy,mitochondrial fusion division,apoptosis,and pathway-related proteins.Immunofluorescence confocal localization was used to detect the fluorescence colocalization of autophagy and lysosome-related proteins.The number of autophagolysosomes in endothelial cells was observed by transmission electron microscopy.Mitochondrial probe staining was used to detect mitochondrial morphology,immunofluorescence was used to detect intracellular reactive oxygen species(ROS)production,flow cytometry was used to detect the apoptosis of cells in each group,cell proliferation and scratch assays were used to detect the proliferation and migration ability of cells in different groups at different time points.The angiogenesis was quantified by counting the number of new blood vessels in each group. Results:Compared with the control group,the expression of lncRNA MALAT1 mRNA and the expression of phosphorylated mito-activated protein kinase 1(p-MAPK1)were upregulated(both P＜0.05)and the expression of phosphorylated mammalian target protein(p-mTOR)was downregulated in the high-glucose and high-fat group and the high-sugar and high-fat control group(all P＜0.01).Compared with the high-glucose and high-fat non-targeting RNA control group,the expressions of microtubule-associated protein 1A/1B-light chain 3(LC3)and p62 were downregulated(P＜0.01,P＜0.05),LC3 and lysosome-associated membrane protein 2(LAMP2)protein co-localized positive fluorescence particles were increased(both P＜0.01),number of lysosomes were decreased,the expression of ROS was decreased(P＜0.01),the expression level of mitochondrial fusion protein optic nerve atrophin 1(OPA1)was increased(P＜0.05),the expressions of cleaved caspase-3 and BCL-2-related X protein(BAX)were decreased and BCL-2 was increased(all P＜0.05),cell proliferation,migration,and tube-forming ability were increased(all P＜0.01),and the expression of p-MAPK1 was decreased(P＜0.05)and p-mTOR expression was increased(both P＜0.05)in the high-glucose and high-lipid+si-MALAT1 group.Compared with the high-glucose and high-fat non-targeting RNA control group,the expression of p-MAPK1 in endothelial cells was decreased and the expression of p-mTOR was increased in the high-glucose and high-lipid+si-MAPK1 group(both P＜0.01). Conclusions:Inhibition of lncRNA MALAT1 expression can reduce the level of mitophagy in glycolipidotoxic environments,reduce apoptosis of endothelial cells and improve endothelial cell function,which may be related to the regulation of MAPK1/mTOR signaling pathway.
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Objective:To analyze the influencing factors of short-term prognosis, and construct a 30-day mortality risk prediction model for patients with cardiogenic shock in Xinjiang region with nomogram.Methods:The clinical data of 295 patients with cardiogenic shock from 2013 to 2019 in the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed. Univariate and multivariate Logistic regression were used to analyze the risk factors for 30-day death in patients with cardiogenic shock, the nomogram was used to construct a prediction model for the risk of death in patients with cardiogenic shock, and the consistency coefficient and receiver operating characteristic (ROC) curve were used to evaluate the model.Results:Among 295 patients, 182 died at 30 d (death group) and 113 survived (survival group). There were statistical differences in gender, age, ICU time, systolic blood pressure, white blood cell, neutrophil count, red blood cell distribution width (RDW), prothrombin time, potassium, blood glucose, serum creatinine, total bilirubin, bicarbonate, base excess, lactic acid, brain natriuretic peptide precursor (NT-proBNP), cardiac troponin I (cTnI) and the percentage of respiratory failure, liver disease, kidney disease between death group and survival group ( P<0.01 or<0.05). Multivariate Logistic regression analysis results showed that NT-proBNP, prothrombin time, cTnI, lactic acid and systolic blood pressure were independent risk factors of death in patients with cardiogenic shock ( OR = 1.00, 1.10, 1.30, 1.29 and 1.04; 95% CI 1.00 to 1.00, 1.01 to 1.18, 1.00 to 1.68, 1.01 to 1.65 and 1.02 to 1.07; P<0.01 or<0.05). The independent factors obtained from multivariate analysis were combined with clinical practice, Akaike information criterion (AIC) analysis was conducted to select modeling variables, and the variables included in the nomogram model were NT-proBNP, prothrombin time, cTnI and lactic acid. After 500 times of internal Bootstrap self-sampling verification of the nomogram model, the C index was 0.805, area under the curve was 0.846, and the optimum threshold value was 0.486, with a sensitivity of 78.6% and a specificity of 83.1%. Conclusions:NT-proBNP, prothrombin time, cTnI and lactic acid are the related influencing factors for the short-term prognosis of patients with cardiogenic shock, and the related nomogram prediction model is constructed, which has guiding significance for the early intervention of cardiogenic shock.
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Objective:To explore the association between urinary stone disease (USD) and peripheral arterial disease (PAD).Methods:The study was based on the cross-sectional chronic diseases survey performed in Pinggu district, Beijing from March to May, 2014. All subjects completed a questionnaire, physical examination, renal ultrasound examination to detect USD, ankle-brachial index (ABI) examination to detect PAD (defined as ABI<0.9 on either side of the body), and brachial-ankle pulse wave velocity (baPWV) measurement to estimate arterial stiffness. Blood and first morning urine sample were detected for serum creatinine, blood glucose and so on.Results:There were 10 281 participants included in this study. Among these participants, the prevalences of USD and PAD were 5.66% and 3.95%, respectively. Compared with non-stone participants, the persistent USD formers had a higher prevalence of PAD (8.26% vs 3.90%, P<0.001) and baPWV [(16.3±3.5) m/s vs (15.5±3.2) m/s, P<0.001]. Even after adjusting the confounding factors, the persistent USD formers also had a 2.066-fold increased risk of PAD ( OR=2.066, 95% CI 1.276-3.343, P=0.003). In the subgroup analysis, persistent USD patients in older participants who were≥60 years old, women, chronic kidney disease, and central obesity had a significantly increased risk of PAD. Conclusions:In the present population, persistent USD is positively associated with a high risk of PAD and increased arterial stiffness. Patients with persistent USD should be screened for vascular diseases.
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Objective To investigate the relationship between dyslipidemia and nephrolithiasis in a population-based study.Methods All participants were investigated by questionnaires,physical examinations and laboratory tests including liver and renal function,lipid profile,serum fasting glucose,glycosylated hemoglobin.Nephrolithiasis was diagnosed by kidney Bultrasonography.Subjects with estimated glomerular filtration rate (eGFR) ＜ 60 ml · min-1 · (1.73 m2)-1were excluded.Results 10 316 individuals were enrolled with an average age of (54.88 ± 10.27) years (range 17-88 years) and the ratio of male to female 1:1.12.The prevalence of nephrolithiasis was 5.6％,3.7％ and 7.8％ for whole population,women and men,respectively.In women,only eGFR in stone group was significantly lower than that in non-stone group (P ＜ 0.05).However,participants in stone group were significantly older (P ＜ 0.05),of higher blood pressure (P ＜ 0.01),higher serum uric acid (P ＜ 0.01),worse renal function (serum creatinine,P ＜ 0.05;eGFR,P ＜ 0.01),and higher low-density lipoprotein (LDL) (P ＜ 0.05),compared with those in non-stone group in men.Logistic regression analysis showed that only eGFR (P ＜ 0.05) was the independent influential factor for kidney stones in women;In men,LDL was an independent influential factor for nephrolithiasis with a hazard ratio of 1.149 (95％CI 1.003-1.317,P ＜ 0.05),except for mean blood pressure and eGFR.After being divided into normal group,borderline high group and high LDL group according to the LDL level,with the increase of LDL,the prevalence of nephrolithiasis was significantly increased by 7.3％,8.3％ and 10.6％ in men respectively.There was no significant relationship between total cholesterol,triglyceride,high-density lipoprotein and nephrolithiasis.Conclusions Dyslipidemia is associated with nephrolithiasis in men,and high LDL cholesterol is an independent risk factor for nephrolithiasis.Clinical lipid testing not only helps to reduce the risk of atherosclerotic disease,but also reduces the risk of kidney stones.