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BackgroundDysimmunity plays a key role in diabetes, especially type 1 diabetes mellitus. Islet-specific autoantibodies (ISAs) have been used as diagnostic markers for different phenotypic classifications of diabetes. This study was aimed to explore the relationships between ISA titers and the clinical characteristics of diabetic patients.MethodsA total of 509 diabetic patients admitted to Department of Endocrinology and Metabolism at the Affiliated Hospital of Nantong University were recruited. Anthropometric parameters, serum biochemical index, glycosylated hemoglobin, urinary microalbumin/creatinine ratio, ISAs, fat mass, and islet β-cell function were measured. Multiple linear regression analysis was performed to identify relationships between ISA titers and clinical characteristics.ResultsCompared with autoantibody negative group, blood pressure, weight, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), visceral fat mass, fasting C-peptide (FCP), 120 minutes C-peptide (120minCP) and area under C-peptide curve (AUCCP) of patients in either autoantibody positive or glutamate decarboxylase antibody (GADA) positive group were lower. Body mass index (BMI), waist circumference, triglycerides (TGs), body fat mass of patients in either autoantibody positive group were lower than autoantibody negative group. GADA titer negatively correlated with TC, LDL-C, FCP, 120minCP, and AUCCP. The islet cell antibody and insulin autoantibody titers both negatively correlated with body weight, BMI, TC, TG, and LDL-C. After adjusting confounders, multiple linear regression analysis showed that LDL-C and FCP negatively correlated with GADA titer.ConclusionDiabetic patients with a high ISA titer, especially GADA titer, have worse islet β-cell function, but less abdominal obesity and fewer features of the metabolic syndrome.
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In order to meet our country strategic needs of “The Belt and Road”, it was proposed to use the existing overseas warehouses from domestic companies as prepositioning locations. The situation and functionality were clarified. A comprehensive evaluation for the existing overseas warehouses in the Indian Ocean was conducted. The authors screened out several countries suitable for prepositioning medicinal supplies. Meanwhile, the potential problems were discussed in order to provide a theoretical basis for the future research on overseas medicinal supplies.
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Objective:To investigate the effects of Leflunomide and Azathioprine on serum chemokine cx3cl1(fractalkine), cathepsin S and vascular cell adhesion molecule-1(VCAM-1)in elderly patients with lupus nephritis.Methods:Sixty elderly patients with lupus nephritis admitted to our hospital from January 2017 to July 2019 were selected as the research objects.Patients were divided into two groups by using a random number table method: the Leflunomide group(treated with Leflunomide plus conventional treatment)and the Azathioprine group(treated with azathioprine plus conventional treatment)(n=30, each group). Serum levels of fractalkine and cathepsin S and urine VCAM-1 level before and 6, 9 and 12 months after treatment were measured in the two groups and statistically analyzed.Results:In both groups, serum fractalkine levels were decreased after versus before treatment( F=123.029 and 99.041 respectively, P=0.000). At 6 months after treatment, serum fractalkine level was lower in the leflunomide group(2.34±0.95)μg/L than in the Azathioprine group(2.97±1.01)μg/L( t=2.489, P=0.016). Serum cathepsin S levels were decreased in both groups after treatment( F=106.733 and 64.928, P=0.000). Serum cathepsin S levels were lower in the Leflunomide group that in the azathioprine group at 6 and 9 months after treatment[(24.31±3.15)μg/L vs.(26.92±4.02)μg/L, (21.72±2.67)μg/L vs.(23.89±2.75)μg/L, t=2.799 and 3.101, P=0.007 and 0.003]. After treatment, urinary VCAM-1 levels were decreased in both two treatment groups( F=907.450 and 858.114, P=0.000). At 6 months after treatment, urine VCAM-1 level was lower in the Leflunomide group than in the Azathioprine group[(74.36±9.17)μg/L Cr vs.(86.91±9.22)μg/L Cr, t=5.286, P=0.000)]. The incidences of adverse reactions were low in the two groups, and the difference was not statistically significant. Conclusions:Leflunomide and Azathioprine can effectively reduce serum levels of fractalkine and cathepsin S and urinary VCAM-1 in elderly patients with lupus nephritis, which suggests that Leflunomide and Azathioprine have similar effects in inhibiting inflammatory reaction, cell matrix degradation and remodeling and vascular cell adhesion.But at early stage of therapy, the effect of Leflunomide was better than that of Azathioprine.And two drugs can be selected according to the specific clinical situation.
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BackgroundDysimmunity plays a key role in diabetes, especially type 1 diabetes mellitus. Islet-specific autoantibodies (ISAs) have been used as diagnostic markers for different phenotypic classifications of diabetes. This study was aimed to explore the relationships between ISA titers and the clinical characteristics of diabetic patients.MethodsA total of 509 diabetic patients admitted to Department of Endocrinology and Metabolism at the Affiliated Hospital of Nantong University were recruited. Anthropometric parameters, serum biochemical index, glycosylated hemoglobin, urinary microalbumin/creatinine ratio, ISAs, fat mass, and islet β-cell function were measured. Multiple linear regression analysis was performed to identify relationships between ISA titers and clinical characteristics.ResultsCompared with autoantibody negative group, blood pressure, weight, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), visceral fat mass, fasting C-peptide (FCP), 120 minutes C-peptide (120minCP) and area under C-peptide curve (AUCCP) of patients in either autoantibody positive or glutamate decarboxylase antibody (GADA) positive group were lower. Body mass index (BMI), waist circumference, triglycerides (TGs), body fat mass of patients in either autoantibody positive group were lower than autoantibody negative group. GADA titer negatively correlated with TC, LDL-C, FCP, 120minCP, and AUCCP. The islet cell antibody and insulin autoantibody titers both negatively correlated with body weight, BMI, TC, TG, and LDL-C. After adjusting confounders, multiple linear regression analysis showed that LDL-C and FCP negatively correlated with GADA titer.ConclusionDiabetic patients with a high ISA titer, especially GADA titer, have worse islet β-cell function, but less abdominal obesity and fewer features of the metabolic syndrome.
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Background@#Dysimmunity plays a key role in diabetes, especially type 1 diabetes mellitus. Islet-specific autoantibodies (ISAs) have been used as diagnostic markers for different phenotypic classifications of diabetes. This study was aimed to explore the relationships between ISA titers and the clinical characteristics of diabetic patients. @*Methods@#A total of 509 diabetic patients admitted to Department of Endocrinology and Metabolism at the Affiliated Hospital of Nantong University were recruited. Anthropometric parameters, serum biochemical index, glycosylated hemoglobin, urinary microalbumin/creatinine ratio, ISAs, fat mass, and islet β-cell function were measured. Multiple linear regression analysis was performed to identify relationships between ISA titers and clinical characteristics. @*Results@#Compared with autoantibody negative group, blood pressure, weight, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), visceral fat mass, fasting C-peptide (FCP), 120 minutes C-peptide (120minCP) and area under C-peptide curve (AUCCP) of patients in either autoantibody positive or glutamate decarboxylase antibody (GADA) positive group were lower.Body mass index (BMI), waist circumference, triglycerides (TGs), body fat mass of patients in either autoantibody positive group were lower than autoantibody negative group. GADA titer negatively correlated with TC, LDL-C, FCP, 120minCP, and AUCCP.The islet cell antibody and insulin autoantibody titers both negatively correlated with body weight, BMI, TC, TG, and LDL-C. After adjusting confounders, multiple linear regression analysis showed that LDL-C and FCP negatively correlated with GADA titer. @*Conclusion@#Diabetic patients with a high ISA titer, especially GADA titer, have worse islet β-cell function, but less abdominal obesity and fewer features of the metabolic syndrome.
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Objective To investigate the mechanism underlying the WNK4 kinasemediated inhibitory effect on BK channel. Methods Cos-7 cells were cotransfected with BK in combination with either CD4 (control group) or wild type WNK4 (WNK4-WT).Immunostaining and confocal microscopy,chemiluminescence,Western blotting analysis were then employed to determine the BK localization in cells,BK surface expression and total protein level,respectively.To further investigate whether the reduction of BK protein expression is due to an increase in degradation through a lysosomal pathway,BK protein level was determined after treated with bafilomycin A1(Baf A1),a proton pump inhibitor affecting lysosomal degradation. Results Immunostaining and confocal microscopic study showed that BK was localized both in plasma membrane and cytosol in the control group.After cells transfected with WNK4-WT,BK expression was markedly reduced.Chemiluminescent assay found that BK surface expression level was 299.9±18.6 in the control group,whereas it was significantly reduced (148.4±13.7,P<0.01) in the WNK4-WT group.Western blotting analysis showed that total BK protein level was markedly reduced in the presence of WNK4-WT compared to the control group.WNK4-WT was shown to significantly reduce the BK total protein level (42.3%±15.2%) compared to the control group (100%) (P<0.01).When the cells was treated with Bafilomycin A1 (Baf A1,0.5 μmol/L),WNK4-mediated reduction in BK protein was reversed (82.2%±12.1%,P<0.05). Conclusions WNK4 inhibits total and surface protein expression of BK in Cos-7 cells whick is likely due to an increase in BK degradation through a lysosomal pathway.