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 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 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 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.

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 investigate the clinicopathological features and immunophenotype of inflammatory myofibroblastic tumor (IMT) and their relationship with IMT diagnosis and prognosis. Methods:A total of 11 IMT cases with follow-up were analyzed morpho-logically and immunohistochemically. Results:The patients included 6 men and 5 women aged 13-66 years. The tumors were found in various anatomical sites, including lung, mediastinum, liver, intra-abdominal, and bladder. Histologically, the majority of the cases com-prised spindled fibroblastic and myofibrobalstic cells accompanied by chronic inflammatory cells in a myxoid or hyalinized stroma;the rest were individual cases of abscess formation. Prognosis mala was indicated for cases with features including atypia tumor cells with two cases demonstrating epithelioid morphology and nucleoli. Immunohistochemical study showed that vimentin, ALK, SMA, S-100, CD117, and CD34 were expressed in 91%(10/11), 55%(6/11), 100%(11/11), 27%(3/11), 18%(2/11), and 9%(1/11) of IMT, respective-ly. Ki-67 was expressed from 3%-40%respectively. CK, H-caldesmon, and DOG1 were negative in all cases. Follow-up data were avail-able for 11 patients and ranged from 4 to 22 months. Data showed that 7 patients were alive with no evidence of disease;4 patients were alive with tumor, whereas 3 showed aggressive biological behavior. Conclusion:IMTs had intermediate behavior or malignant po-tential. Most IMTs with aggressive behavior showed a minority of tumor cells with atypia, epithelioid morphology, and nucleoli. High proliferation index expression, ALK, SMA, and H-caldesmon can aid in IMT diagnosis.

Objective To investigate the scale of self-efficacy and the influencing factors among the elderly diabetic population in rural communities in Shanghai . Method The diabetic patients in the rural communities were involved in the study by questionnaire to analyze the patient′s self-efficacy and its influencing factors. Results The total score of self-efficacy was (77.48 ± 22.22), with the index score of 59.60%. By multiple stepwise regression analysis, the influencing factors were age, education level and annual income. Conclusions The self-efficacy of diabetic patients is at a low level. To improve their self-efficacy, we should strengthen the education to the diabetic patients with age of 40~49 or poor in education or lower in income.

Objective To investigate the relationship between subclinical hypothyroidism (SCH) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).Methods A total of 792 patients of T2DM were enrolled in the study.There were 448 males and 344 females,with an average age of (54.13 ± 13.06)years.The average duration of diabetes was (8.03 4±6.70) years.The patients were grouped according to the degree of DR and thyroid function.Among them,483 patients (61.0％) were no DR,240 patients (30.3％) were mild DR,69 patients (8.7％) were severe DR.725 patients (91.5％) were normal thyroid function,67 patients (8.5％) were SCH.The prevalence of SCH among no DR group,mild DR group and severe DR group was compared.And the prevalence of DR between normal thyroid function group and SCH group was compared.Logistic regression analysis was used to estimate the association between SCH and DR.Results No significant differences among the three groups (no DR group,mild DR group,severe DR group) were found in the prevalence of SCH (x2=1.823,P=0.402).There were no significant differences in the incidences of DR between normal thyroid function group and SCH group (x2=1.618,P=0.239).Logistic regression analysis demonstrated that SCH was not significant associated with DR [mild DR:odds ratio (OR)=1.361,95％ confidence interval (CI)=0.773-2.399,P=0.286;severe DR:OR=1.326,95％CI=0.520-3.384,P=0.555;DR:OR=1.353,95％ CI=0.798-2.294,P=0.261).Conclusion SCH is not significant associated with DR in patients with T2DM.