Objective To evaluate the clinical effects of sitagliptin and sitagliptin combined with glimepiride in the treatment of type 2 diabetes (T2DM).Methods Ninety-two patients with T2DM were randomly divided into sitagliptin group (group J),glimepiride group (group G) and sitagliptin combined with glimepiride group (group U),group J took sitagliptin,group G took glimepiride,group U took sitagliptin and glimepiride.Before and after treatments,blood glucose and insulin were determined in the fasting and 2-hour blood samples after taking glucose (fasting blood-glucose (FPG),2-hour postprandial blood glucose (2hPG),insulin (FIns),2-hour postprandial insulin (2hIns),and glycosylation hemoglobin (HBA1 c) were also determined and homeostasis model assessment was applied to estimate the functions index of islet β cell(HOMA-β).Results The levels of blood glucose and HBA1C in three groups decreased after treatments(FPG,(before treatment:(9.2±3.0),(9.2±2.8),(9.3±3.2) mmol/L),(after treatment:(7.7 ± 3.0),(6.9 ± 2.6),(6.0 ± 2.5) mmol/L),and t values are 2.205,3.203,3.691,P ＜ 0.01,P ＜ 0.05 ;2 hPG (before treatment:(14.1 ± 5.7),(14.8 ±6.3),(15.0±6.8) mmol/L),(after treatment:(7.9 ±2.9),(9.0 ±3.1),(7.1 ±3.1) mmol/L),and t values are 3.881,3.159,4.189,P ＜ 0.01 ; HBA1c (before treatment:(8.52 ± 2.01)％,(8.48 ± 1.94)％,(8.56 ±2.27)％,(after treatment:(7.64 ± 1.92)％,(6.81 ± 1.55)％,(6.19 ± 1.84)％),t values are 2.292,2.184,3.269,P ＜ 0.01,P ＜ 0.05) ; HOMA-β in the three groups increased after treatment ((before treatment:1.42 ± 0.07,1.44 ± 0.06,1.41 ± 0.11),(after treatment:1.76 ± 0.14,1.68 ± 0.20,1.85 ±0.17),t values are 2.180,2.073,2.882,P ＜ 0.01,P ＜ 0.05);levels of HBA1c and blood glucose in group U were lower than those in group J and G(HBA1 c:t values are 2.785,2.138,P ＜ 0.05,P ＜ 0.01 ;FPG:t values are 2.252,2.346,P ＜0.05;2hPG:t values are 2.147,2.829,P ＜0.01,P ＜0.05),HOMA-β in which was higher than that of group G(t =2.153,P ＜ 0.05),but with no significant difference compared with group J (t =1.796,P ＞ 0.05),levels of HBA1C,FPG and HOMA-β in group J were higher than those of group G (t values are 2.108,2.202,2.121,P ＜ 0.05),level of 2hPG of group J was lower than that of group G(t =2.307,P ＜ 0.05).Conclusion Sitagliptin provides significant glycaemic control,together with glimepiride,clinical effect of treatment of type 2 diabetes will be enhanced.

Background and purpose: Multidrug resistance (MDR) is the dominating obstacle to the chemotherapy. There is strong evidence that the phosphoinositide 3-kinases (PI3Ks) signaling pathway is involved in MDR phenotype, however, the mechanism of MDR occurrence is still unknown. This study tended to investigate the regulating effect of PI3K/Akt signaling pathway and its downstream target genes in P-glycoprotein (P-gp) (ABCB1 gene encoding)-mediated MDR in human colon carcinoma HCT-116/L-OHP cells. Methods:Pretreatment with PI3K selective inhibitor LY294002 (20μmol/L) for 2 h, the sensitivity of L-OHP was evaluated by the CCK-8 (cell counting kit-8) assay in HCT-116/L-OHP cells, and the expressions of P-gp, LRP, MRP-2, Akt, p-Akt, IκB and p-IκB were evaluated by Western blot. The activity of ABCB1 promoter was evaluated by chromatin immunoprecipitation analysis (CHIP). Results: After inhibiting the activity of PI3K/Akt signaling pathway, the IC50 value of L-OHP decreased from(157.48±16.73)μg/mL to (53.68±3.18)μg/mL in HCT-116/L-OHP cells, and the reversal index was 2.93 (P<0.01). The expressions of P-gp, p-Akt and p-IκB were down-regulation compared with the concrol group (P<0.01), but the expressions of LRP, MRP-2, Akt and IκB didn't change signiifcantly. CHIP result has conifrmed that NF-κB protein could bind to the region of ABCB1 gene promoter in HCT116/L-OHP cells. Conclusion:Blocking of PI3K/Akt/NF-kB signal pathway could increase the drug sensitivity to MDR cells, inhibit the phosphorylation of p-Akt and p-IκB, and reversing ABCB1/P-glycoprotein-mediated multidrug resistance in colon carcinoma cells.

BACKGROUND:The establishment of a safe, reliable and easily repeatable mouse model of nonalcoholic fatty liver disease is the prerequisite for the study of the diagnosis and treatment of the disease.
OBJECTIVE:To establish a C57BL/6 mouse model of nonalcoholic fatty liver disease and observe changes of biochemical indicators, which can provide a theoretical basis for its pathogenesis and drug treatment.
METHODS:Sixty healthy male C57BL/6 mice were randomly divided into a control group of 30 cases (normal diet), and a model group of 30 cases (high fat diet). Models of nonalcoholic fatty liver were established. At 8 weeks, body mass, liver index, and homogenate superoxide dismutase activity in the liver were detected. Changes in serum alanine aminotransferase, aspartate aminotransferase, triglyceride glycerol, cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were observed. Pathological examination was performed.
RESULTS AND CONCLUSION:(1) Pathological sections showed that large droplets and smal lipid droplets in the mouse liver and spread the whole liver. Swel ing of the liver cel s, visible cytoplasmic vacuoles and obviously inflammatory changes in liver cel s were observed in the model group. (2) Body weight and liver index were significantly higher in the model group than in the control group (P<0.05). Superoxide dismutase activity was significantly reduced in the liver (P<0.05). (3) Triglycerides, cholesterol, and low-density lipoprotein cholesterol levels were significantly higher, but high-density lipoprotein cholesterol levels were significantly lower in the model group than in the control group (P<0.05). (4) Nonalcoholic fatty liver mouse model is ideal for high-fat diet-induced animal model. The method is simple, repetitive, and can provide a stable animal model for the study on the mechanism of nonalcoholic fatty liver disease and drug treatment.