AIM:We investigated the effects of Danshen Dripping Pill(DSP) on the glucose metabolism in rats during the insulin resistant(IR) statue. METHODS:HOMA-IR was used to show the degree of insulin resistant and Sprague-Dawley rats were randomly divided into 5 groups,normal control,IR control,Pioglitazone(PIO),Danse Injection(DSZ) and DSP groups,and the model rats were given dexamethasone to induce the insulin resistant statue.After being treated for 8 weeks,the serum adiponectin concentration and the relative expression amount of Glut-4 mRNA in skeletal muscles were detected by ELISA and real time PCR,respectively. RESULTS:The insulin resistant model rats induced by dexamethasone had a series of characters with the high level of HOMA-IR,and the serum adiponectin concentration was decreased,the Glut-4 mRNA relative expression amount in skeletal muscle cell and its translocation on the plasma membrane were inhibited.The effects of dexamethasone were significantly reversed by PIO,DSZ and DSP,respectively(P

Purpose:To investigate the status of p16 gene and its influence in p16 mRNA expression in primary hepatocellular carcinoma (HCC). Methods:The methylation status of p16 gene and expression of p16 mRNA were examined by methylation-specific PCR (MSP) and RT-PCR in twenty-five primary HCC and corresponding paracancerous tissue specimens.Results:Methylation was detected in 12 of 25 (52.0%) tumor tissue specinmens, while 6 of 25 (24.0%) in corresponding paracancerous tissue specimens. Loss of p16 mRNA expression was found in 19 specimens with methylated p16 gene,while expression of p16 mRNA was detected in 27 of 31 specimens with unmethylated p16 gene. There was significant difference in mRNA expression between specimens with methylated p16 and unmethylated p16.Conclusions:p16 gene methylation is a frequent event in HCC. The methylation of p16 gene might lead to loss of p16 mRNA expression. Detection of p16 gene methylation may be a useful marker in the molecular diagnosis of hepatocellular carcinomas.

Objective To investigate the effects and the mechanism of Danshen dripping pill(DSP,复方丹参滴丸) on the lipid metabolism in rats under insulin resistant(IR) status.Methods Twenty-four Sprague-Dawley(SD) rats were randomly divided into normal control(n=8),IR control(n=8) and DSP groups(n=8).The rats were given dexamethasone(1 mg/kg) intramuscular injection once every other day to induce the IR status in the latter two groups,and the rats in DSP group were administered intra-gastrically with DSP 0.5 g/kg dissolved in normal saline once a day in the morning at 9 o′clock,and in the mean time,the rats in the normal and IR control groups were given intra-gastrically with equal amount of 0.9% NaCl. After 8 weeks of treatment,fasting blood glucose(FBG),fasting insulin(FINS),total cholesterol(TC),triglyceride(TG),nitric oxide synthase(NOS),nitrogen monoxidum(NO),smooth muscle depth/wall thickness of thoracic aorta were detected,and serum adiponectin concentration was measured by enzyme linked immunosorbent assay(ELISA),respectively.Results After IR model was successfully established,the insulin resistance index(HOMA-IR),TC and TG were increased,the serum NOS production and NO were decreased, smooth muscle depth/wall thickness of thoracic aorta was increased significantly,and the secretion of adiponectin concentration was decreased(P

Objective To evaluate the efficacy and safety of human glucagon-like peptide-1 analogue liraglutide in newly diagnosed type 2 diabetes mellitus (T2DM) with glycosylated hemoglobin A1c (HbA1c) ＞ 9％.Methods This was an open-labelled,randomized,parallel-group,treat-to-target trial.Newly diagnosed T2DM patients with HbA1c ＞ 9％ were enrolled.These patients were treated with metformin with repaglinide and randomized to receive once-daily liraglutide (LIRA,n =25) or the insulin glargine (IGla,n =24) at bedtime.Efficacy and safety were assessed and compared after 18-month treatment.Results (1) Compared with the baseline,patients with LIRA had significantly reduced mean body weight,BMI and waist circumference (P ＜ 0.01),whereas,the above indexes were increased (P ＜ 0.01) in patients treated with IGla.(2) After 18 months of treatment,fasting plasma glucose (FPG),2-hour plasma glucose after a 75g oral glucose load(2hPG) and HbA1c were significantly improved in all patients (P ＜ 0.01),with 2hPG,mean blood glucose (MBG),the largest amplitude of glycemic excursions (LAGE),mean amplitude of glycemic excursions (MAGE) were significantly lower in LIRA group than in IGla group (all P ＜ 0.05).(3) HOMA-IR decreased in both groups (P ＜ 0.05).However,△I30/△G30,AUCCP180 and Matsuda index were only significantly increased in patients treated with LIRA (respectively,4.88 ± 1.55 vs 7.60 ± 1.91,9.23 ± 2.66 vs 13.18 ± 2.72,39.28 ± 20.35 vs 54.64 ± 23.34,all P ＜ 0.01),while HOMA-IR reduced(4.41 ± 1.58 vs 3.52 ± 1.44,P ＜0.05).But in IGla group only HOMAIR was reduced (4.92 ± 1.84 vs 4.57 ± 1.80,P ＜0.05).The index of △I30/△G30,AUCCP180 and Matsuda index in LIRA group are higher than those of indexes in IGla group(respectively,7.60 ± 1.91 vs 4.18 ± 1.00,13.18 ± 2.72 vs 10.53 ± 2.68,54.64 ± 23.34 vs 41.65 ± 17.84,all P ＜ 0.05),while HOMA-IR is lower (3.52 ± 1.44 vs 4.57 ± 1.80,P ＜ 0.05).(4) The rate of HbA1 c ≤ 6.5 ％ and the dosages of oral anti-diabetic drugs in LIRA group were significantly better than that in IGla group.(5) No significant differences were observed in hypoglycemic episodes and adverse events between two groups.Conclusion It seems that liraglutide is superior to insulin glargine in newly diagnosed T2DM patients with HbA1c ＞ 9％ in improving beta-cell function,insulin sensitivity and glucose homeostasis.

The effects of pioglitazone on the expressions of hypoxia-inducible factor-1 α (HIF-1 α) and vascular endothelial growth factor (VEGF) in renal tissues of diabetic rats were observed. Diabetic rat model was established by feeding high-carbonhydrate-fat diet and injecting streptozotocin. After the treatment with pioglitazone, the kidney index, 24 h urinary albumin, blood urea nitrogen, serum creatinine, fasting blood glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), total cholesterol,triglycerides, and low-density lipoprotein-cholesterol of diabetic rats were significantly lower than those of untreated ones, high-density lipoprotein-cholesterol was increased, the expressions of HIF-1α and VEGF in renal tissue were decreased ( all P＜0. 01 ). It suggested that pioglitazone may improve renal function and the balance of glucose-lipid metabolism in diabetic rats via down-regulating HIF-1/VEGF pathway.

Objective To observe the effect and safety of the human glucagon-like peptide-1 analogue,liraglutide,versus insulin glargine in patients with type 2 diabetes mellitus inadequately controlled with metformin alone.Method Ninty patients with type 2 diabetes mellitus(aged 18-79 years,HbA1C 7.5％-10.0％,body mass index＜40 kg/m2) who had inadequate glycaemic control on metformin were allocated for the research with an open,randomized,parallel controlled clinical research method.The patients kept the original dose of metformin unchanged and were randomly assigned to the liraglutide group or the insulin glargine group according to a proportion of 1 ∶ 1.Liraglutide group started with a dose of 0.6 mg subcutaneous injection qd,changed to 1.2 mg subcutaneous injection qd after one week and kept unchanged until the end of the research.Insulin glargine group started with a dose of 0.1-0.2 U/kg according to the fingertips peripheral blood glucose level before breakfast on the continuous 3 d before every follow-up.At the baseline,after 4 weeks,12 weeks,20 weeks,and 26 weeks of treatment,HbA1C,blood glucose,lipids weight,blood pressure were arranged to measured.86 patients finally completed the study.Results Mean HbA1C and the success rate of HbA1C ＜7％ were similar between liraglutide group and insulin glargine group [(7.06 ± 0.87) ％ vs (7.25 ± 1.20) ％,47.73 ％ vs 45.23 ％,P＞0.05],while the percentage of subjects reaching the composite endpoint of HbA1C＜7％ with no hypoglycemia and no weight gain was significantly higher in liraglutide group than insulin group(P＜0.05) ; Fasting plasma glucose decreased more markedly in insulin glargine group,2 h postprandial plasma glucose was decreased more markedly in liraglutide group(P＜0.05 or P＜0.01).Liraglutide significantly reduced mean body weight by (3.21 ± 1.18) kg,waist circumference by (3.82 ± 1.21) cm,and body mass index by (1.95 ± 0.61) kg/m2 (P＜0.01 or P＜0.05),while in the insulin glargine group there sere rise of respective figure of(2.86 ± 0.43) kg,(1.52 ± 0.56) cm,and (0.61 ± 0.25) kg/m2 (P＜0.05),systolic blood pressure and serum triglyceride declined.There was no serious adverse affect in both groups,the incidence of mild hypoglycemia was significantly less in liraglutide group and has a statistically significant difference (4.55％ vs 21.43％,P＜0.05).Conclusions Liraglutide showed a good effect on reducing weight,systolic blood pressure,blood lipid and in addition to blood glucose control which is comparable to insulin glargine.What is more,liraglutide had good safety and tolerability,which can be regarded as a good choice for patients with type 2 diabetes mellitus inadequately controlled with metformin alone.

ObjectiveTo investigate the effects of liraglutide on the differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) into insulin-producing cells (IPCs).MethodsIn vitro,hBM-MSCs were induced into IPCs by three-stage induction procedure containing high glucose,nicotinamide,and liraglutide.The morphological change of cells was observed by inverted microscope during induction and the induced cells were confirmed by dithizone(DTZ) staining.The protein expressions of pancreatic and duodenal homeobox-1 (PDX-1),glucose transporter 2 (GLUT2),glucokinase(GK),and insulin in each stage of the induced cells were detected by Western blot.Insulin secretion was measured by ELISA.ResultsThe induced effect was pronounced after adding 10 nmol/L liraglutide for 7 days.Cells began to aggregate and get round gradually during induction,and the morphology of most cells appeared as grape-like aggregation and clustered islet-like cells by the end of induction.The number of DTZ positive cells and the protein expressions of PDX-1,GLUT2,GK,and insulin were increased gradually( P＜0.05 ).The basal and glucose-stimulated insulin secretion from induced cells was also increased gradually(P＜0.05).Conclusion BM-MSCs could be induced into IPCs by high glucose,nicotinamide,and liraglutide in vitro.

ObjectiveTo investigate the diagnostic value of ultrasound on patients with papillary thyroid carcinoma(PTC) coexisted with Hashimoto thyroiditis(HT).Methods The preoperative ultrasonography data of 2144 cases with PTC from January 2006 to December 2011 who treated with operation and diagnosed by pathology were analyzed retrospectively.Among them,265 cases coexisted with HT (PTC coexisted with HT group),1879 cases were not coexisted with HT (non-PTC coexisted with HT group).ResultsMost of the cancerous nodes in two groups exhibited in the ultrasonographic performance just like irregular shape,unclear boundary and so on (P ＞ 0.05).Most of the cancerous nodes in non-PTC coexisted with HT group exhibited hypoechoic nodules with microcalcifications,those in PTC coexisted with HT group exhibited various internal echoes with mainly microcalcifications,and the coarse calcification occupied a certain proportion(P＜ 0.01 ).The cancerous nodes in PTC coexisted with HT group were not rich in blood flow compared with non-PTC coexisted with HT group,but mostly exhibited blood disorders.When compared with non-PTC coexisted with HT group,the rate of ultrasound diagnosis in PTC coexisted with HT group was lower [ 52.8 ％( 140/265 ) vs.75.0 ％ (1409/1879),P ＜ 0.01 ],and the false positive rate in lymph node was higher [84.0％(487/580) vs.74.8％ (77/103)] (P ＜0.05).ConclusionsThe nodules are malignant when they appear as hypoechoic solid nodules,have unclear boundary and have microcalcifications should be highly suspected.The hyperechoic solid nodules or coarse calcification nodules should also be awared and taken further observation of the characteristics around the echoes and the internal blood flow,making comprehensive analysis to determine whether it could be malignant transformation and try best to reduce the misdiagnosis and missed diagnosis rates of this disease.

Objective To observe the clinical effect of percutaneous transluminal angioplasty (PTA)combined with autologous peripheral blood stem cells(PBSC)transplantation in the treatment of lower extremity ischemic disorders.Methods Fourty-two cases of lower extremity ischemic disorders in the treatment group were treated with PTA and autologous peripheral blood stem cells injection and 40 cases in control group were treated with PTA exclusively.Results All the procedures were successful.In treatment group,ABI improved from 0.32 ±0.11 to(at the 3rd month)and 0.49 ±0.13(at the 6th month)(t=-6.765,-6.040,P＜0.05)while TcPO_2 improved from(26.1 ± 2.3)mm Hg to(32.7 ±4.2)mm Hg(at the 3rd month)and(34.5 ±2.7)mm Hg(at the 6th month)(t=-8.901,-14.250,P＜0.05).In control group,ABI improved from 0.30 ±0.12 to 0.47 ±0.15 and 0.47 ±0.130=-5.631,-5.873,P＜0.05)while TcPO_2 increased from(25.9 ±2.4)mm Hg to(28.9 ±2.9)mm Hg(at the 3rd month)and(28.9 ± 2.1)mm Hg(at the 6th month)(t=-5.090,-5.389,P＜0.05).There was significant difference in TcPO_2 on follow-up between the two groups after the treatment(P＜0.05).Conclusion Autologous PBSC transplantation in combination of PTA was effective for the treatment of lower extremity ischemic disorders.PBSC injection helps to increase TcPO_2.

Objective To investigate the protective effect of quercetin on diabetic nephropathy and to explore its possible mechanism.Methods Type 2 diabetes mellitus rat model was established by feeding high-carbonhydrate-fat diet and injecting with streptozotocin.At 72 hour after injection,blood samples were collected from the tail veins of all rats.Those rats with blood glucose level ≥ 16.7 mmol/L were considered as the diabetes model been successfully established.The model rats were randomly divided into type 2 diabetic group ( group DM,n =9 ) and quercetin group ( group QUE,n =9 ).Other rats were used as normal controls (group NC,n =8).All rats were performed by intragastric administration for 8 weeks.At the end of experiment,the rats were sacrificed and fasting plasma glucose( FPG),fasting insulin( Flns),serum creatinine (SCr),blood urea nitrogen(BUN),TG,TC,LDL-C,24 h urine protein (24 h UP),and kidney index ( KI ) were evaluated.Pathological changes of kidney were observed by periodic acid-silver metheramine( PASM ).The expressions of ubiquitin and NF-κB p65 on glomeruli w ere examined by immunohistochemical method,and its association with the incidence of proteinuria was analyzed.Results In groups DM and QUE,the level of FPG [ ( 25.45 ± 1.23 ) mmol/L and ( 19.99 ± 1.20 ) mmoL/L],FIns [ ( 25.67 ± 2.58 ) mU/L and ( 19.29 ± 1.80 ) mU/L ],SCr[ ( 44.00 ± 2.53 ) μmol/L and ( 34.43 ± 2.23 )μmol/L],BUN[ ( 11.60 ± 0.39 )mmol/L and (8.20 ± 0.37) mmoL/L],TG [ (3.32 ± 0.22 ) mmol/L and (2.43±0.25)mmol/L],TC[(2.95 ±0.21) mmol/L and (2.24 ±0.17)mmol/L],LDL-C[(2.03 ±0.22 ) mmol/L and ( 1.49 ± 0.13 ) mmol/L ],24 h UP [ ( 46.67 ± 2.50 ) mg/24 h and ( 25.57 ± 2.82 )mg/24 h]and KI[ (9.76 ±0.30) × 103 and (8.44 ±0.26) × 103 ] were significantly increased than the indexes of group NC [ (6.56 ± 0.41 ) mmol/L,( 12.63 ± 1.41 ) mU/L,( 22.88 ± 2.36 ) μmol/L,( 5.45 ±0.51 ) mmoL/L,( 1.64 ± 0.1 1 ) mmol/L,( 1.33 ± 0.17 ) mmol/L,(0.46 ± 0.05 ) mmol/L,( 12.38 ±1.19)/24 h and (6.78 ±0.12) × 103].Moreover,the above indexes in group QUE were obviously lower than group DM.There was evidence of pathological changes associated with diabetes,such as focal and segmental sclerosis and thickened basement and mesangial expansion.The expressions of ubiquitin and NF-κB p65 in renal tissues of group DM increased significantly ( P ＜ 0.01 ).The expression of ubiquitin and NF-κB p65 were positively related with the level of 24 h UP ( r =0.893,0.879,P ＜ 0.01 ).Compared with group DM,all above indexes in group QUE were markedly alleviated ( P ＜ 0.01 ).The expression of ubiquitin and NF-κB p65 was reduced but didn't reach level in group NC ( P ＜ 0.01 ).Conclusion The increased expression of NF-κB induced by ubiquitin-proteasome system may participate in the pathogenesis of proteinuria in diabetic nephropathy.Quercetin has renal protective effects partly through reducing NF-κB p65 expression.