Objective To investigate the efficacy of Saxagliptin on the glucose and lipids metabolism and adipokines levels in diet-induced insulin resistance rat,and to explore the regulatory mechanism of saxagliptin in insulin resistance.Methods 36 4-week-old male Wistar rats were randomly divided into two groups:control group (n=12) and high-glucose and fat diet group(HF,n =24).The HF rats were randomly divided into two subgroups:HF group and saxagliptin group,and continued the treatment for 8 weeks.Levels of blood glucose,insulin,triglyceride (TG),total cholesterol (TC),TNF-α and adiponectin were determined.Results After four months,serum levels of fasting glucose,insulin,TG,TC were significantly increased in HF group as compared with control group [(7.07±1.61) mmol/L vs.(5.10±0.44) mmol/L,(23.70±7.37) mU/L vs.(19.35 ± 6.38) mU/L],[(3.21± 1.44) mmol/L vs.(0.83 ± 0.39) mmol/L,(3.04 ± 1.62) mmol/L vs.(1.14±0.24) mmol/L,all P＜0.05],and were all decreased after the treatment of saxagliptin.The glucose infusion rate was lower in HF group than in control group and was higher in saxagliptin group than in HF group [(18.80±1.57) mg · kg-1 · min-1 vs.(24.31±2.65) mg · kg 1 · min 1,(21.45 ±1.80) mg· kg-1 · min-1 vs.(18.80±1.57) mg· kg 1 · min-1,P＜0.01 or 0.05].Compared with the control group,serum THF-α was higher and adiponectin level was lower in HF group [(1.38 ±0.18) μg/L vs.(2.33±0.21)μg/L,(2.65±0.29) mg/L vs.(1.38±0.20)mg/L,both P＜0.01].Saxagliptin can significantly increase the serum level of adiponectin and decrease the level of TNF-α in HF group (P＜0.01 or 0.05).Conclusions Saxagliptin treatment can improve high-fat dietinduced insulin resistance,decrease blood lipids levels and regulate the levels of adipokines in HF rats.

Objective To examine the correlation of imbalance of urinary exosome Th1/Th2 with diabetic nephropathy (DN).Methods A total of 120 patients with type 2 diabetes mellitus (DM) and 30 healthy volunteers as control were enrolled in the study.According to urinary albumin/creatinine ratio (UACR),type 2 diabetes mellitus patients were divided into 3 groups:diabetes mellitus without nepbropathy group (DM,n=40,UACR＜30 mg/gCr),microalbuminuria group (DN 1,n=50,UACR-30～300 mg/gCr) and clinicoalbuminuria group (DN 2,n=30,UACR＞300 mg/gCr).Urine exosome-interferon-gamma (IFN-γ) and exosome-interleukin 4 (IL-4) levels were determined by enzyme-linked immunosorbent assay (ELISA).Multiple stepwise linear regression was used to analyze the correlation of exosome-IFN-γ/IL-4 with glycated hemoglobin (HbA1c),cholesterol (CH),UACR,Scr and BUN.Results Th1/Th2 ratio in DM,DN1,DN2 groups was significantly higher than that in healthy group (0.8089±0.2458,0.8993 ±0.3515,0.8571±0.2470 vs 0.6198±0.1769,all P＜0.01).Correlation analysis showed that urinary exosomeIFN-γ/IL-4 ratio was positively correlated with UACR (r=0.213,P=0.015) and BUN (r=0.292,P=0.001).Multiple stepwise linear regression analysis showed that BUN was independent determinants for exosome-IFN-γ/IL-4 (β=0.246,P=0.006).Conclusion The imbalance of urinary exosomeTh1/Th2 is correlated with DN,which may play an important role in the pathogenesis of DN.

Objective:To explore the association between α5 subunit of gamma-aminobutyric acid receptor subtype 5(GABRA5) gene polymorphism and executive function in patients with major depressive disorder.Methods:From August 2018 to September 2020, one hundred and eighty depressed patients diagnosed by DSM-Ⅳ-TR criteria were included from Xuzhou Eastern Hospital, meanwhile 120 healthy controls with matching demographic characteristic were recruited.Gene polymorphisms were detected through the elbow vein blood of all subjects. The severity of the patients was assessed by 17 items Hamilton depression scale(HAMD-17). The executive function of subjects was tested by Wisconsin card sorting test (WCST) and event-related potential P300.The t test and χ2 test were used for statistic analysis by SPSS 17.0. Results:The cognitive function of depression patients with GABRA5 receptor gene carrying T allele was significantly lower than that of patients with C allele ( t=2.35-3.45, P<0.05). The cognitive dysfunction was associated with sleep and anxiety/somatization symptoms in depression patients ( r=-0.197-0.409, P<0.05). Anxiety/somatization symptoms in patients with depression partially mediated the association between GABRA5 receptor gene polymorphism and cognitive dysfunction(effect value=-0.611, 95% CI=-1.393--0.057). Conclusion:The GABRA5 receptor gene polymorphism is associated with cognitive dysfunction in patients with depression, and anxiety/somatization symptoms partially mediate the impairment of cognitive function caused by GABRA5 receptor gene polymorphism.