AIM:To investigate the effects of silent information regulator 1 (SIRT1) on high glucose-induced acetylation of NF-κB p65 subunit and its protective role in rat mesangial cells .METHODS:Rat mesangial cells were cul-tured in DMEM supplemented with 10% FBS and were divided into control group , mannitol group , high glucose group , resveratrol group and SIRT1 RNAi group.The cell viability was determined by MTT assay .The mRNA expression of SIRT1, monocyte chemoattratant protein 1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1-1), tumor necrosis fac-torα( TNF-α) , transforming growth factor β1 ( TGF-β1 ) was analyzed by real-time quantitative PCR .The protein expres-sion of SIRT1 and the acetylation of NF-κB p65 subunit were determined by Western blotting .The protein concentrations of MCP-1, VCAM-1, TNF-α, TGF-β1 and malondialdehyde (MDA) were detected by ELISA.RESULTS:The cell viabili-ty, superoxide dismutase (SOD) activity, and the expression of SIRT1 at mRNA and protein levels were decreased by high glucose treatment as compared with control group .The acetylation of NF-κB p65 subunit was significantly increased after interfered with high glucose , resulting in the increase in the secretion of MCP-1, VCAM-1, TNF-αand TGF-β1 .Resvera-trol decreased high glucose-induced acetylation of NF-κB p65 subunit.However, silencing SIRT1 significantly enhanced the acetylation of NF-κB p65 subunit and the expression of MCP-1, VCAM-1, TNF-αand TGF-β1 .CONCLUSION:SIRT1 remarkably inhibits the inflammatory reactions by deacetylating NF-κB p65, suggesting that SIRT1 is a possible tar-get for preventing diabetic nephropathy .

OBJECTIVE:To observe clinical efficacy and safety of sitagliptin combined with metformin in the treatment of type 2 diabetes complicating with metabolic syndrome. METHODS:Totally 80 patients with type 2 diabetes complicating with meta-bolic syndrome were divided into the observation group and control group with 40 cases in each group according to simple random sampling method. Both groups were given same diet and exercise plan;control group was additionally given metformin orally,0.5 g each time,tid;observation group was additionally given sitagliptin,100 mg each time,qd,on the basis of control group. Treat-ment course of 2 groups lasted for 12 weeks. The waist circumference(WC),body mass index(BMI),blood glucose,blood lip-id,fasting insulin (FINS) and serum adiponectin were detected in 2 groups,and steady-state model insulin resistance index (HOMA-IR)and whole body insulin sensitivity index(WBISI)were calculated. The occurrence of ADR was observed. RESULTS:Before treatment,there were no statistically significant differences between 2 groups in WC,BMI,systolic blood pressure,diastol-ic blood pressure,triglycerides,cholesterol,high-density lipoprotein cholester,low-density lipoprotein cholesterol,fasting plasma glucose,2 h postprandial blood glucose,FINS,HOMA-IR,WBISI and serum adiponectin(P>0.05). After treatment,the above indexes of 2 groups were obviously improved,and the improvement of observation group was significantly better than that of con-trol group,with statistical significance(P<0.05). 2 cases and 3 cases were withdraw from the study in control group and observa-tion group because of ADR,respectively.There was no statistically significant difference in the incidence of ADR between 2 groups (P>0.05). CONCLUSIONS:Sitagliptin combined with metformin shows significant clinical efficacy in the treatment of type 2 di-abetes complicating with metabolic syndrome. Its mechanism may be related to reducing insulin resistance,enhancing insulin sensi-tivity,decreasing patients’body weight and up-regulating serum adiponectin level.

BACKGROUND:Common strategies for preventing diabetic nephropathy include effective control of blood sugar and blood pressure, inhibition of the rennin-angiotensin system and lipid-lowering therapy, but it is often difficult to get the desired results. OBJECTIVE:To investigate the effect of transplantation of bone marrow mesenchymal stem cels on levels of blood glucose and urinary total protein in diabetic nephropathy rats. METHODS: Forty-five Sprague-Dawley rats were randomly divided into three groups (n=15 per group): normal control group, diabetic nephropathy group and stem cel transplantation group. Rats in the diabetic nephropathy and stem cel transplantation groups were given single use of 60 mg/kg streptozotocin to make diabetic nephropathy models. The same dose of citric acid-sodium citrate buffer was injected in the normal control group. After modeling, 200μL of bone marrow mesenchymal stem cel solution (2×106) was injected into the left ventricle of rats in the stem cel transplantation group, and then at 7 days after the first transplantation, the cel transplantation was conducted again. The same dose of serum-free L-DMEM was injected intracardialy into the rats in the normal control and diabetic nephropathy groups. Levels of urinary total protein and blood glucose were detected. RESULTS AND CONCLUSION:At 1, 4, 8 weeks after treatment, the urinary total protein and blood glucose levels were significantly higher in the stem cel transplantation group and diabetic nephropathy group than the normal control group (P < 0.05). At 1 week after treatment, the urinary total protein and blood glucose levels were significantly lower in the stem cel transplantation group than the diabetic nephropathy group (P < 0.05). At 4 and 8 weeks after treatment, the total urinary protein and blood glucose levels were slightly higher in the diabetic nephropathy group than the stem cel transplantation group, but there was no significant difference (P > 0.05). These findings indicate that bone marrow mesenchymal stem cel transplantation in diabetic nephropathy rats can get good results in a short period, significantly improve the blood glucose and urinary total protein levels, but the long-term treatment effect is poor.

BACKGROUND:Thrombospondin-1 is an important endogenous activator of transforming growth factor beta 1 in this experimental inflammatory kidney disease model. Transforming growth factor beta 1 is considered the major cytokine that causes tissue fibrosis in many different inflammatory disease processes, in particular in renal disease.
OBJECTIVE:To investigate the expression of thrombospondin-1 on renal fibrosis in rats.
METHODS:Healthy male Sprague-Dawley rats were randomly divided into sham surgery group and model group. In themodel group, right ureters of rats were ligated to construct models of renal fibrosis. 3 weeks after surgery, blood and urine were obtained weekly. Enzyme linked immunosorbent assay and Bradford method were used to detect the contents of serum creatinine,blood urea nitrogen and urinary protein. After rats were sacrificed, kidneys were fixed. Western blot assay was utilized to identify the expression of vascular endothelial growth factor, transforming growth factor beta 1 and thrombospondin-1 protein. Hematoxylin-eosin staining was applied to detect the changes in pathological structure of the kidney after surgery.
RESULTS AND CONCLUSION:(1) One week after model induction, urinary protein, serum creatinine and urea nitrogen levels were significantly higher in the model group than in the sham surgery group (P< 0.05). Three weeks later, the difference in each index was significant (P< 0.01), which showed that the injury of the kidney was aggravated. (2) Transforming growth factor beta 1 protein and thrombospondin-1 expression was significantly higher in the model group than in the sham surgery group, but vascular endothelial growth factor protein expression was significantly lower in the model group than in the sham surgery group. (3) Hematoxylin-eosin staining results demonstrated that severe pathological changes of renal tissue in rats were detected after ligation of renal tubule. (4) These results confirmed that thrombospondin-1 expression increased in renal tissue, and its expression was strongly associated with vascular endothelial growth factor protein and transforming growth factor beta 1, which may play an important role in the renal fibrosis.

BACKGROUND:Type 1 diabetes mel itus is an autoimmune disease, which is characterized as the selective destruction of pancreatic beta cel s in the body, resulting in the lack of insulin secretion. Umbilical cord blood stem cel s have the potential to differentiate into islet cel s in vitro and in vivo, which play a certain hypoglycemic effect. OBJECTIVE:To explore the effects of umbilical cord blood stem cel s on blood glucose levels and PDX-1 and MafA levels in the pancreatic tissue of type 1 diabetic rats. METHODS:Thirty Sprague-Dawley rats were randomly divided into three groups, with 10 rats in each group. In treatment and model groups, type 1 diabetes mel itus modes were established. After modeling, the treatment group was given a single tail vein injection of umbilical cord blood stem cel s;the normal control group was given the same volume of normal saline;the model group was given the same volume of umbilical cord blood stem cel buffer solution. Oral glucose tolerance test was adopted to assess the islet function of rats;hematoxylin-eosin staining was used to observe the pancreatic morphology of rats;western blot and PCR methods were employed to detect expressions of PDX-1 and MafA in pancreatic tissues at protein and mRNA levels. RESULTS AND CONCLUSION:(1) Compared with the normal control group, the levels of blood glucose in the model and treatment groups were significantly higher at 0, 30, 60, 90 minutes (P<0.05). At 120 minutes, the blood glucose level in the model group was significantly higher than that in the normal control group (P<0.05), but there was no difference between the treatment and normal control groups (P>0.05). (2) The number of islets in the model group was decreased, and the boundary was unclear and irregular;in the treatment group, the number of islets was decreased, but the boundary was stil clear. (3) The expressions of PDX-1 and MafA in the treatment group were similar to those in the normal control group (P>0.05), but significantly higher than those in the model group (P<0.05). These findings suggest that the umbilical cord blood stem cel transplantation can significantly reduce the blood glucose levels in type 1 diabetic rats, improve the function of islet and morphology of pancreas, and up-reuglate the expressions of PDX-1 and MafA.

Objective To discuss the risk of factors influencing persistent frequency after transurethral resection of the prostate (TURP).Methods The clinical data of 119 post-TURP patients treated from January 2014 to June 2015 was retrospectively analyzed.The age was (72.1 ±2.3)years old.There were 15 cases with hypertension,23 cases with diabetes and 6 cases with heart disease.The preoperative IPSS score of 119 cases was (22.1 ± 5.9) points,with (10.2 ± 1.8) points in urinary storage period and (11.8 ± 4.7) points in urination period.Urination frequency was (10.8 ± 2.6) times per day and there were (3.8 ± 0.8) times of nocturnal urination.B-ultrasound:residual urine volume was (38.1 ± 9.1) ml and prostate volume was (34.1 ± 4.2) ml.Preoperative maximum urine flow rate was (8.8 ± 3.9) ml/s.The detrusor pressure at maximum urinary flow rate was (43.9 ± 14.1) cm H2O (1 cmH2O =0.098 kPa),maximum detrusor pressure was (99.7 ± 12.2) cmH2O and effective bladder volume was (217.5 ± 14.8) ml.Contraction of bladder weakened in 40 cases (33.6％) and 36 cases (30.2％) had detrusor overactivity.According to whether continuous urinary frequency was developed,the patients were divided into frequency-positive group and frequency-negative group.The differences between the patients in two groups were compared and univariate analysis was performed.A multivariate logistic regression was performed on statistically significant indicators.Results Among the 119 patients,21 were frequency-positive and 98 were frequency-negative.Univariate analysis showed that age,IPSS score,preoperative urinary storage score,detrusor pressure at maximum urinary flow rate,maximum detrusor pressure,effective bladder volume,contraction decrease of bladder,preoperative detrusor activity were important indicators affecting the condition of postoperative urinary frequency (all P ＜ 0.05).Multivariate analysis showed that old age (OR =3.842,P =0.021),high total IPSS score (OR =5.109,P =0.011),low maximum detrusor pressure (OR =3.477,P =0.039),low effective volume of bladder (OR =4.051,P =0.017) and detrusor overactivity (OR =3.662,P =0.025) were independent risk factors for urinary frequency after TURP.Conclusions The age,the high IPSS score before operation,low maximal detrusor pressure,low effective bladder capacity and the bladder detrusor activity could be independent predictive factors of persistent frequency after TURP.