Novel SLC12A3 gene mutations and clinical characteristics in two pedigrees with Gitelman syndrome.

OBJECTIVE: Gitelman syndrome (GS) is an autosomal recessive tubulopathy resulting from inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). To date, more than 500 mutations have been identified in the SLC12A3 gene. In this study, we identified two new mutations in the SLC12A3 gene in two Chinese GS pedigrees. DESIGN, PATIENTS AND MEASUREMENTS: The clinical characteristics and laboratory examination of two suspected GS patients in our hospital were analyzed. In addition, two pedigrees including 11 members and 2 patients underwent SLC12A3 gene analysis. RESULTS: Both patients were middle-aged women with characteristics of hypokalemic metabolic alkalosis, hypomagnesemia, low level of urinary calcium and the elevated levels of renin-angiotensin-aldosterone system. So, they were clinically diagnosed as GS. Patient 2 also had type 2 diabetes and Graves' disease. Both patients were found to carry two mutations of SLC12A3 gene by Sanger direct sequencing, which were all compound heterozygous mutations. We identified three mutations in these two Chinese GS pedigrees, one of which was c.179C>T (Thr60Met). The novel c.2159G>T (p. Gly720Val) and c.2675T>C (p. Leu892Pro) mutations were strongly predicted to be pathogenic using four network programs-Polyphen-2, SIFT, Mutation Taster and LRT. CONCLUSIONS: We identified two novel SLC12A3 genetic variant [c.2159G>T (p.Gly720Val) and c.2675T>C (p.Leu892Pro)] in two Chinese GS pedigrees. The discovery of new mutations has enriched the spectrum of SLC12A3 genotypes.

Evaluation of the Clinical Efficacy of the Treatment of Overweight and Obesity in Type 2 Diabetes Mellitus by the Telemedicine Management System Based on the Internet of Things Technology.

Objective: To explore the application value of medical intelligent electronic system under the background of Internet of Things in the clinical study of the treatment of overweight/obesity in type 2 diabetes mellitus (T2DM) with empagliflozin combined with liraglutide; 50 overweight and obese adult T2DM patients in our hospital were randomly divided into the combined group and the control group, 25 cases in each group. The control group was treated with liraglutide alone, while the combined group was treated with empagliflozin on the basis of liraglutide. Based on the Internet of Things technology, with diabetes management as the core, the functions of information collection, transmission, and storage of T2DM patients are realized. Doctors pass the diabetes management plan to T2DM patients through the platform, supervise the implementation, and finally compare the clinical efficacy of the two groups. Results: Compared with before treatment, the body mass index (BMI), fasting blood glucose (FPG), postprandial blood glucose (2hPG), glycosylated hemoglobin (HbAlc), islet beta cell secretion function index (HOMA-ß), islet resistance index (HOMA-IR), total cholesterol (TC), and triglyceride (TG) in both groups decreased significantly after treatment. After combined treatment, systolic blood pressure (SBP), diastolic blood pressure (DBP), FPG, 2hPG, HbA1c, and HOMA-IR in the combined group were significantly lower than those in the control group (P < 0.05). Hypoglycemia occurred in both groups, with 2 cases in the control group and 4 cases in the combined group. Conclusion: The telemedicine management system based on Internet of Things technology can improve patients' self-management ability and provide a new choice for individualized treatment of overweight/obesity T2DM patients. The combination therapy of empagliflozin and liraglutide can effectively reduce blood sugar, weight, blood pressure, blood lipid, and hypoglycemia and effectively improve insulin resistance and secretion function of islet ß cells in T2DM patients.

[Comparison of endothelial differentiation capacity of adipose-derived stem cells and bone marrow mesenchymal stem cells from rats].

OBJECTIVE: To compared the differentiation capacity of rat adipose-derived stem cells (ASCs) and bone marrow mesenchymal stem cells (BMSCs) into endothelial cells. METHODS: Rat BMSCs and ASCs were isolated, cultured and identified for cell surface markers using flow cytometry. The cell growth curves were drawn by CCK-8 assay, and the cells in active growth were induced for endothelial differentiation following standard protocols. On day 21 of induction, the cells were examined for mRNA expressions of endothelial cell specific markers CD31, KDR, and vWF using qPCR. Immunostaining was performed to observe the expression of CD31 on the cells. The induced cells were also tested for Dil-labeled acetylated low-density lipoprotein (ac-LDL) uptake ability. The tube-forming ability of the induced cells was verified on Matrigel. RESULTS: We successfully isolated rat ASCs and BMSCs. Morphologically, ASCs were similar with BMSCs, both having long spindle-shaped and fibroblast-like morphology. Flow cytometry showed that both BMSCs and ASCs had high expressions of mesenchymal markers CD29 and CD90 and a low expression of hematopoietic cell surface markers CD45. CCK-8 assay showed that ASCs proliferated more quickly than BMSCs. The cells with induced endothelial differentiation exhibited increased levels of CD31, KDR, and vWF mRNA expressions and immunofluorescent staining identified CD31 antigen expression on the cell membrane. Fluorescence microscopy revealed red fluorescence in the induced cells suggesting uptake of Dil-Ac-LDL by the cells. The induced cells were capable of forming tube on Matrigel, confirming their identity of endothelial cells. CONCLUSION: Both rat BMSCs and ASCs can be induced to differentiate into endothelial cells, but ASCs differentiate more quickly into endothelial cells and possess a stronger proliferation ability, suggesting its greater potential than BMSCs in future applications.