Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases across the world, but there is still no specific treatment for NAFLD. Glucogon-like peptide 1 receptor agonist (GLP-1Ra) is a novel drug for the treatment of type 2 diabetes, based on incretin hormone target. Animal and clinical studies have demonstrated that GLP-1Ra can effec?tively reduce fat deposit in liver and attenuate hepatic steatosis. Therefore, GLP-1Ra is a promising therapeutic approachagainst NAFLD. In this review, we provided an overview of the clinical and basic research evidences and mechanisms in re?lieving NAFLD.

Objective To investigate the possible mechanisms of glucagon-like peptide 1 receptor agonists (GLP-1Ra) induced weight loss. Methods High fat diet induced obese c57BL/6 mice were divided into normal control group (N, n=8), high fat feeding group (HF, n=32) and GLP-1Ra group treated with GLP-1Ra (liraglutide 200μg/(kg·d) or 400μg/(kg·d) for 8 weeks). Changes of body weight, blood glucose and three acyl glycosides (TG) levels were observed in three groups. HE staining was used to observe the morphological changes. Immunofluorescence staining and real-time PCR were used to mea?sure the expression of UCP-1. Furthermore, the expression of PGC-1αin protein level was observed to explore the possible mechanism of GLP-1Ra induced browning in white fat (WAT). Results After 8-week liraglutide (Lira) administration, the body weights were significantly reduced in obese mice (P<0.05). The levels of blood glucose and TG were significantly high?er in HF group than those in N group, which reduced significantly in Lira (200μg·kg-1) and Lira (400μg·kg-1) administra?tion groups (P<0.05). HE staining showed adipocytes in perirenal and inguinal subcutaneous adipose tissue partly acquired brown-like morphological characteristics. The expression levels of UCP-1 protein and mRNA and PGC-1αprotein were ele?vated in adipse tissues, which increased more in Lira (400) than those in Lira (200, P<0.05). Conclusion GLP-1Ra can induce weight loss through white fat browning by activation of UCP-1.

Objective To investigate the mechanism of a dipeptidyl-peptidase-4 (DPP-4) inhibitor, saxagliptin, pro?moting the regeneration of islet beta cells in diabetic rats. Methods The male SD rats were randomly divided into three groups including control group (NC, n=10), diabetes group (DM, n=10) and diabetes treated with saxagliptin group (DM-S, n=10). DM-S group was treated with saxagliptin 1 mg/(kg·d) for twelve weeks. The pancreaticβcell function was analysed by hyperglycemic clamps. Immunohistochemistry with anti-PCNA was performed to observe the proliferation rate of pancreaticβcells. Immunofluorescence double staining with anti-insulin, anti-glucagon, anti-DPP-4 and anti-SDF-1 were performed to observe the expression of insulin, glucagon, DPP-4 and SDF-1 in pancreatic tissue. Western blot assay was performed to test the expression of Akt, p-Akt,β-catenin and free-β-catenin protein, and RT-PCR was performed to test the expressionlevels of c-myc and cyclinD1 mRNA in pancreatic tissue. Results Compared with NC group, there were significantly in?creased blood glucose, decreased islet function andβcell mass in DM group. Compared with DM rats, saxagliptin treatment significantly inhibited the expression of DPP-4, decreased the degradation of SDF-1, stimulated the proliferation ofβcells, and ultimately improved the islet function and histopathological changes of pancreas. Conclusion DPP-4 inhibitor saxa?gliptin can significantly improve islet function, which involved in the inhibition of the expression of DPP-4, the decreased degradation of SDF-1 and the stimulation of the proliferation ofβcells.

Objective:To explore the effects of compound Danshen dripping pills (CDDP) and CDDP combined with transplantation of human umbilical cord blood cells (HUMNCs) on the inlfammatory response, oxidative stress, myocardial cell apoptosis and cardiac function, and also to investigate the possible mechanisms of the combined therapy in the acute myocardial infarction (AMI).
Methods:Rabbit model of AMI successfully established by ligation of the letf anterior coronary artery (LAD). Forty rabbits were randomly divided into 4 groups (n=10 per group):a control group, injected with 0.5 mL of saline in 24 h atfer AMI and then gavaged with 5 mL of saline daily;a CDDP group, injected with saline 0.5 mL atfer AMI and then gavaged with CDDP (270 mg/d) daily;a transplantation group, injected with 0.5 mL of saline contained 3 × 107 HUCBMCs [labeled with green fluorescent protein (GFP)] and then gavaged with 5 mL of saline daily;a combined group, injected with 0.5 mL of saline contained 3 × 107 HUCBMCs (labeled with GFP) and then gavaged with CDDP (270 mg/d) daily. Cardiac function index such as left ventricular fractional shorting (LVFS) and ejection fraction(LVEF) were measured by echocardiography;the pathological changes were observed by HE staining and the white blood cells in the myocardium were determined by light microscopy. hTe superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in myocardium were detected by nitrotetrazolium blue chloride (NBT) and thiobarbituric acid colorimetric measurement respectively. hTe number of transplanted cells in the myocardium was examined by GFP positive cells counted with lfuorescence microscopy.
Results:1) Compared with the control group (at 1 or 4 week), LVEF and LVFS were signiifcant improved in the CDDP group, the transplantation group and the combined groups (all P<0.05), the improvement degree of cardiac function in the combined group was the most significance. There was no significant difference between the CDDP group and the transplantation group. 2) Compared with the control group (at 1 or 4 week), the number of white blood cell, myocardial cell apoptosis ratio were decreased signiifcantly in the CDDP group, the transplantation group and the combined groups (all P<0.05), this decrease in the combined group was the most signiifcance, and there was no significant difference between the CDDP group and the transplantation group. 3) Compared with control (at 4 week), the SOD activity was increased signiifcantly, and MDA content in myocardium was decreased in the CDDP group, this change in the combined group was the most signiifcance. 4) GFP-positive cells were found to be present in the peri-myocardial infarction area in the transplantation group and the combined group at 1, 4 weeks post-transplantation. hTe number of the GFP positive cells in the combined group was more than that in the transplantation group (P<0.05).
Conclusion:The intravenous transplantation of HUMNCs combined with the CDDP in the treatment of rabbits with AMI could increase the survival rate of transplanted cells and inhibit the myocardial cell apoptosis, therefore improve the heart function. hTe possible mechanism of the combined treatment may be involved in the inhibition of the inlfammatory response and oxidative stress in the myocardium following AMI.

Objective To discuss the application of digital simulation positioning machine in radiation oncology. Methods We used digital simulation positioning machine to shoot isocenter reset digital simulator images of 0 degrees direction and 90 degrees direction, 10 × 10 cm2 rectangular field and actual time radiation field with any field number. Compared the images taken with the TPS corresponding DRR image through bone marker matching to measure the error of isocenter and actual time radiation field , the linear accelerator Iview-GT system with the same method was shot in rectangular field simulator the same field number EPID image , and the TPS corresponding DRR image. Finally, we compared the measured error of the digital simulator positioning machine with the error of Iview-GT system image. Results The result of measured isocenter error of the digital simulator positioning machine was better than EPID image error (P=0.000). Conclusion The application of digital simulation positioning machine in radiation oncology can be more accurate to measure the error and correct the position deviation, however, it can also make the radiotherapy and the treatment more accurate.

Objective To explore the operation procudure and notice of establishing a rat model of abdominal heterotopic heart transplantation by single operator,and summarize the detailed skill and experience for beginners.Methods 68 pairs male SD(recipients)/Wistar(donors) rats,preoperative anesthesia for recipients and donors at the same time,8/0 line was preparing for blocking recipients vena cava and abdominal aortic,blocking the branch vessel.Left and right superior vena ligature respectively with hilar,cutting the ascending aorta,perfusion cardioplegia,free pulmonary artery,across transverse sinus of pericardium for pulmonary artery cutting,atrial wash,free donor heart.Choosed appropriate incision of receptor abdominal blood vessels,mattress suture at 6 and 12 points,a single suture for vent gases,continuous suture in artery,single needle in vein,reperfusion after exhaust gas.Recording operation time,HE staining,IL-1β/CD3 immunohistochemistry slice,flow cytometry analysis of CD4+T/CD8+T lymphocytes subsets in the peripheral blood.Results Sixty-eight cases were treated by single operater,the operation time was(58.8±4.5)minutes,artery suture time was(7.6±2.2)minutes,vein suture time was(13.5±4.2)minutes,the total donor heart ischemic time was(31.8±4.5)minutes,the success rate was 88.2％.The rejection reaction was stronger on the third and fifth day after surgery,with high expression of IL-1β/CD3 in cardiac allografts.The CD4+T/CD8+T lymphocytes subsets increased in the peripheral blood at first day after heart transplantation.Conclusion By fully preparation and skillfully operation,establishing a rat model of abdominal heterotopic heart transplantation by single operator has a stable success rate.

Objective To investigate the effect of pentoxifyccine (FIX) on the pathway of high glucosd-induced expression of CTGF in mesangial cells. Methods Cultured rat mesangial celld were used to study the influence of different concentration of high glucose on the expression of TGF-β, CTGF, p-Smad2/3, Smad7 and FN in different exposure time. Furthermore the effect of high glucose plus TGF-β neutral antibody and different concentration of FIX on the obove expression was evaluated as well. Results High glucose could increase TGF-β, CTGF mRNA and protein expression in mesangial cells (P<0.05) in time-and dose-dependent manner, and at the same time p-Smad2/3 expression increased and Smad7 expression decreased (P<0.05).The blockage of TGF-β could decrease high glucose-induced CTGF mRNA and protein expression by 86.4% and 91.8%. PTX could suppress high glucose-induced CTGF expression in mesangial cells. When the PTX dosage increased, the suppressive effect became more remarkable, but PTX had no influence on the TGF-β expression. Conclusions High glucose up-regulates CTGF mRNA and protein expression mainly through TGF-β-Smads pathway. PTX can suppress CTGF expression effectively, but has no direct inhibition of TGF-β expression.

Objective To investigate the possible mechanisms of glucagon-like peptide 1 receptor agonists (GLP-1Ra) protection against hyperglycemic induced beta cell apoptosis through depression of NOX2-dependent ROS production. Methods The rat model of type 2 diabetes (T2DM) was established by injecting small doses of streptozotocin (STZ) fol?lowed by 8-week high fat diet. The experimental animals were divided into three groups:normal control (N) group, diabetes (T2DM) group and GLP-1Ra group [treated with liraglutide 200 μg/(kg · d)for 12 weeks]. The blood glucose levels were compared before and after modeling, before treatment and 12-week after treatment with GLP-1Ra. The level of glycosylated hemoglobin (HbA1c) was detected by high-pressure liquid chromatography. Automatic biochemical analyzer was used to de?tect levels of aspertate aminotransferase (AST), creatinine (CR) and urea nitrogen (BUN). The apoptotic rates of islets were determined by TUNEL method and cleaved caspase 3 was detected by immunohistochemistry. DCFH-DA fluorescent probe was used to detect reactive oxygen species (ROS) levels of islets. Levels of NADPH oxidase (NOX) catalytic subunit (NOX 2) in islets were measured by immunohistochemistry. Results At the end of the study, glycemic control (average blood glucose/week and HbA1c) and lipid situation were improved significantly in the GLP-1Ra group than those of N group (P<0.05). TUNEL staining and displayed thatβcell apoptotic and cleaved caspase 3 level were significantly decreased in GLP-1Ra group compared to those of T2DM group (P<0.05). ROS levels were significantly decreased in GLP-1Ra group than those of T2DM group before treatment with Apocynin, but no significant difference between GLP1-Ra group and N group (P>0.05). After application Apocynin for inhibition, there were no significant differences between three groups (P>0.05). The level of NOX2 was significantly lower in GLP-1Ra group compared to that of T2DM group (P<0.05). Conclusion GLP-1Ra can inhibit apoptosis ofβcells in diabetes rat, and the depression of NOX2-dependent ROS may be one of the important underly?ing mechanisms.

Objective To observe the effect of adding on glimepiride in treating type 2 diabetic patients who had suffered the disease for more than 10 years and were poorly controlled with insulin combined with nonsulfonylureas drugs. Methods Seventy-five type 2 diabetic patients poorly controlled with insulin combined with non-sulfonylureas drugs were randomly divided into glimepiride-added group (INS+GM, n = 39 )and continuation of insulin group ( INS, n = 35 ). HbA1c, plasma glucose, daily insulin dose, number of hypoglycemic events, body weight, plasma lipid concentration,and high-sensitive C-reactive protein (hs-CRP)were recorded at weeks 0, 12,and 24. The levels of plasma free fatty acid ( FFA), adiponectin, and tumor necrosis factor-α ( TNF-α ) were measured before and 24 weeks after the therapy. Results At 12 and 24 weeks, fasting blood glucose, 2 h postprandial blood glucose,and HbA1c were improved in INS+GM group more markedly than in INS group, and daily insulin dose and body weight were decreased in INS+GM compared with INS ( P＜0. 05 ). The number of hypoglycemic events and plasma lipid concentration did not differ between two groups ( P＜0.05 ). The levels of plasma FFA,TNF-α,hs-CRP, and HOMA-IR were lower in INS+GM than INS ( P＜0.05 ), the adiponectin was higher in INS + GM than INS ( P ＜ 0.05 ). Conclusion Adding glimepiride to insulin therapy resulted in a sustained better glycemic control with less insulin daily dose, decresed body weight, and no increase in hypoglycemic events as compared with the continuing insulin therapy group. Increased adiponectin, as well as decreased plasma FFA and TNF-α may underlie the improvement of insulin resistance with glimepiride treatment.

OBJECTIVE:To observe the efficacy and safety of Shenqi jiangtang granule in the adjuvant treatment of type 2 dia-betes knee arthritis. METHODS:62 patients with type 2 diabetes knee arthritis were randomly divided into control group(31 cas-es) and observation group (31 cases). Control group received hypoglycemic and basic treatment for arthritis,including diet con-trol,exercise therapy and health education,as well as 0.25 g Metformin hydrochloride tablet with a meal,3 times a day + 50 mg Acarbose tablet with a meal,3 times a day,chewing;patients with arthritis pain 100 mg Aspirin enteric-coated tablet after a meal, once a day (chewing or breaking apart was prohibited). Observation group additionally received 3 g Shenqi jiangtang granule half an hour before a meal with 50 ml warm water,3 times a day. The treatment course for both groups was 6 months. Clinical effica-cy,and fasting plasma glucose(FPG),2 h postprandial blood glucose(2 h PG),glycated hemoglobin(HbA1c),interleukin-1β(IL-1β),IL-6 before and after treatment,and the incidence of adverse reactions in 2 groups were observed. RESULTS:The total effective rate in observation group was significantly higher than control group,the difference was statistically significant(P<0.05). Before treatment,there were no significant differences in the FPG,2 h PG,HbA1c,IL-1β and IL-6 between 2 groups(P>0.05). After treatment,FPG,2 h PG,HbA1c,IL-1β and IL-6 in 2 groups were significantly lower than before,and observation group was lower than control group,the differences were statistically significant(P<0.05). And there was no significant in the incidence of adverse reactions between 2 groups (P>0.05). CONCLUSIONS:Based on conventional treatment,Shenqi jiangtang granule shows obvious efficacy in the adjuvant treatment of type 2 diabetes knee arthritis.,it can reduce blood glucose and inflammation cy-tokine levels,mild symptoms of adverse reactions.