Renal protection should be taken into account when we treat chronic gouty arthritis patients combined with chronic kidney disease.Several drugs should be individualized and adjusted dosage according to renal function parameters such as GFR.At the same time,we should closely monitor the side-effects of drugs.

Objective To study the effect of PPAR-r agonist Troglitazone on the mPGEs expression induced by high glucose in rat mesangial cells. Methods Rat mesangial cells were incubated with high glucose at presence or absence of different concentrations of Troglitanzone, and the mPGEs concentration in supernatant was measured by an enzyme-linked immunosorbent assay (ELISA). Results 5% glucose could obviously induce the mPGEs expression in the rat mesangial cells (P

ObjectiveTostudytheroleof hotshockprotein (HSP)47in tubulointerstitial fibrosis induced by transforming growth factor β1(TGF-β1),and to explore its possible mechanism.Methods Human proximal tubular epithelial cells(HK-2) were divided into threegroups:control,TGF-β1andHSP47siRNA. Theexpressionsof HSP47, collagenⅣ,fibronectin(FN),plasminogen activator inhibitor 1(PAI-1) mRNA and HSP47,collagen Ⅳ,FN protein were detected by RT-PCR and Western blotting respectively.PAl-1 protein was detected by ELISA. ResultsHK-2expressedHSP47innormalmedium. ThemRNAandprotein expressions of HSP47 up-regulated in concentration- and time-dependent manner in HK-2 cells induced with increasing concentrations of TGF-β1(0,2.5,5,10 μg/L) and with prolong times (12,24,48 h),and peaked at 10 μg/L TGF-β1 for 48 h.Similar phenomena was observed in the mRNA andproteinexpressionsof collagenⅣ, FN, PAI-1inHK-2 cellsinducedbyincreasing concentrations of TGF-β1 (0,2.5,5,10 μg/L) at different time points (12,24,48 h),and peaked at 10 μg/L TGF-β1 for 48 h.HSP47 siRNA could significantly reduce the up-regulation of mRNA and protein expressions of HSP47,collagen Ⅳ,FN,PAI-1 in HK-2 cells induced by TGF-β1.Conclusion HSP47 can promote renal tubulointerstitial fibrosis maybe through the regulation of the expressions of collagen Ⅳ,FN,PAI-1.

Objective To investigate the effects of connective tissue growth factor (CTGF) siRNA delivered by pRetro-Super (PRS) retrovirus vector on extracellular matrix and VEGF expression in human peritoneal mesothelial cells (HPMC). Methods Four pairs of oligonucleotides including 64 bp DNA were designed and synthesized in vitro according to siRNA target sequence and PRS retrovirus desire.PRS-CTGF-siRNA1-4 recombinant retrovirus vectors were constructed.The recombinant retrovirus vectors containing CTGF-siRNA were transferred into PT67 packaging cell lines with lipefectamine 2000,then infected HPMC.mRNA expression was determined by semi-quantitative RT-PCR and protein expression was determined by Western blot.Results Both mRNA and protein expressions of CTGF,FN,Col I,laminin (LN) and VEGF were significantly increased in HPMC with 5 μg/L TGF-β1 stimulation (P＜0.01,respectively).CTGF,FN,Col I,LN mRNA and protein and VEGF mRNA expression stimulated by TGF-β1 were significantly decreased in HPMC infected with PRS-CTGF-siRNA1～4 retrovirus vectors (P＜0.01,respectively).The inhibitory rates on CTGF were 69.3%,22.2%,27.4% and 38.8%,respectively (P＜0.01).At the same time,there was also a significant reduction of VEGF protein expression in HPMC infected with PRS-CTGF-siRNA1 vector (P＜0.01).There was no significant difference in HPMC infected with PRS void vector. Conclusion CTGF siRNA delivered by PRS retrovirus vector can effectively inhibit the enhancement of extracellular matrix and VEGF expression stimulated by TGF-β1 in HPMC.

Objective To investigate the role of mitochondrial respiratory chain in the hyperpermeability of human peritoneal mesothelial cells (HPMCs) induced by high glucose peritoneal glucose PDS was also added. Transmesothelial electrical resistance (TER) measurement was examined for detection of permeability damage in HPMCs. Immunostaining and Western blotting analysis were used to detect claudin-1 expression. Mitochondrial superoxide (MitoSOX) Red staining and respiratory chain complexes activities were determined for detection of mitochondrial reactive oxygen species (ROS) production and mitochondrial complexes activities. Results TER was decreased in a time- and concentration-dependent manner after culture with high glucose PDS for was also down-regulated significantly by high glucose PDS (P＜0.01). Complex Ⅲ activity was inhibited (10.8% of control, P＜0.01) accompanied with increased mitochondrial ROS generation.These changes were partially prevented by glutathione. Conclusion Mitochondrial respiratory complex Ⅲ pathway has crucial importance in maintaining TER of HPMCs, which may reveal a valuable target for novel therapies to fight hyperpermeability of peritoneum during the prolonged PD treatment.

Objective To investigate the underlying mechanism of bone marrow mesenchymal stem cells (BMSC) modulating the inflammatory response during the multiple organ dysfunction syndrome (MODS), especially the expression of inflammatory cytokines, which will provide new theoretical and experimental basis of MODS in clinic. Methods BMSC of Sprague-Dawley (SD) rat (female, 4 weeks) was extracted and cultivated, and the 4th passage were used in experimental study. According to the random number table, 60 female SD rats were divided into three groups (n = 20 per group): sham group, MODS group, BMSC group. MODS model in rats was induced by lipopolysaccaride (LPS, 1 mg/kg) via femoral vein injection. Sham group was injected with the sterile phosphate buffer saline (PBS) in the same volume. BMSC group, in which BMSC infusion was started at 2 hours after 0.5 mL LPS stimulation (1×106/cells) through the tail vein. The survival rate was observed after 72 hours in each group. Abdominal aortic blood was collected for routine blood and biochemical examination at 72 hours after operation. Protein microarray was used to detect the related 34 inflammatory cytokines. Signal ratio was defined as the differentially expressed factors when it was more than 2.0 or less than 0.5. And enzyme linked immunosorbent assay (ELISA) was be applied to validate the significant inflammation factor. Meanwhile, the heart, kidney, intestine tissue was harvested, then their pathological changes were observed by hematoxylin eosin (HE) staining.Results 20, 12, 16 rats lived in sham group, MODS group and BMSC group respectively at 72 hours after operation. Compared with the sham group, the indicators (routine blood, liver and kidney function, myocardial enzyme) were apparently unusual, and the heart, kidney, intestine tissue were injured obviously in the MODS group. After BMSC administration, the organ function was improved and tissue damaged was alleviated significantly. Protein microarray showed that interleukin-4 (IL-4) and receptor for advanced glycation end products (RAGE) were significantly different in 34 goal cytokines. The signal ratio change of IL-4 was 0.397, 1.124, 2.826 respectively, and the signal ratio of RAGE was 6.197, 1.552, 0.250, respectively in MODS/sham group, BMSC/sham group, BMSC/MODS group. ELISA validated the result that the expression level of IL-4 decreased significantly (ng/L:3.59±1.21 vs. 29.10±5.78) and the expression level of RAGE increased significantly (ng/L: 1.09±0.04 vs. 0.11±0.03) in MODS group as compared with sham group (bothP < 0.05). Compared with the MODS group, the level of IL-4 was obviously higher than that in BMSC group (ng/L: 9.59±2.21 vs. 3.59±1.21,P < 0.01), and RAGE decreased significantly (ng/L: 0.29±0.07 vs. 1.09±0.04,P < 0.05).Conclusions BMSC administration can regulate the expression of IL-4 and RAGE in the rats subjected to MODS. Moreover, BMSC can promote the restoration of tissue and organ function, thus improve the survival rate. BMSC may be the target in cell therapy for the inflammatory disease.

Objective To investigate the effect of in vitro high glucose stimulation on the expression of adiponectin receptor (adipoR) in human kidney proximal tubular cells.Methods The HK-2 cells were cultured in the low glucose DMEM culture medium containing 10% fetal bovine serum until the cells were adherent and 80% confluence. After cultured in the serum-free DMEM for 24 hours, these cells were stimulated with glucose-containing 1mg/ml, 2mg/ml, 4mg / ml, 6mg/ml, 8mg/ml serum-free DMEM for 48 hours. Then RT-PCR and western blot were used to analyze adipoR ( R1, R2) expression levels. The HK-2 cells were cultured respectively in high glucose (4mg/ml) , low glucose (1mg/ml) DMEM culture medium containing 10% fetal bovine serum to cultivate 0h, 12h, 24h, 48h, 72h, 96h, then RT - PCR was applied to analyze adipoR (R1, R2) mRNA expression levels semi-quantitatively. Results Two kinds of adiponectin receptor gene were both expressed in HK-2 cells, and the quantity of gene expression of adipoR1 (0. 63 ±0. 12) was 3. 9 times to adipoR2 (0. 16 ±0.03) , the difference was statistically significant ( P<0. 01). The different concentrations of glucose and different time of high glucose on HK-2 cells had no significant effect ( P>0. 05 ) on adipoR gene expression. Expression of adipoR 1 protein in HK-2 cells was detected by western blot, and it was not affected by glucose concentration ( P>0. 05).Conclusion adi-poR1 and adipoR2 gene were both expressed in HK-2 cells, and the adipoR1 was the major one, which suggested that adipoR1 played a more significant role in kidney disease. The expression of adipoRl/R2 of HK-2 cells was not affected by high glucose concentration.

Objective To investigate the role of oxidative stress in the epithelial-to-mesenchymal transdifferentiation (EMT) of peritoneal mesothelial cells in rat model of peritoneal fibrosis and the effect of probucol on peritoneal fibrosis. Methods The rat model of peritoneal fibrosis was induced by 4.25% high glucose peritoneal dialysis fluid (PDF). The rats were randomly divided into 4 groups:the control group, the saline group, the peritoneal fibrosis group, and the probucol group. A 4 hour peritoneal equilibration test (PET) was performed 4 weeks later. The peritoneal function and net ultrafiltration (UF) volume were determined. The level of malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in peritoneal tissue were examined. The histology of peritoneal membrane was evaluated by light microscopy. E-cadherin and α-smooth muscle actin (α-SMA) protein expression was evaluated by immunohistochemical method and Western blot.Results The mesothelial cells were detached from peritoneal membrane in peritoneal firbosis rats. Comparing with the control rats, the thickness of visceral peritoneum, the level of MDA, and the-SMA protein expression were increased while the net ultrafiltration volume, the level of GSH-Px and E-cadherin protein expression were decreased in peritoneal firbosis rats. All these changes were reversed in the rats treated with probucol.Conclusion Oxidative stress plays an important role in transdifferentiation of peritoneal mesothelial cell in the peritoneal fibrosis rats. Probucol can improve structure and function of peritoneum, and partially reverse the EMT by reducing the oxidative stress.

Objective To systematically review the efficacy and safety of repetitive transcranial magnetic stimulation (rTMS)for post-stroke dysphagia. Methods The clinical trials about rTMS for post-stroke dysphagia were searched on Pubmed,EMbase,MEDLINE,Cochrane library,China National Knowledge Infrastructure (CNKI),Chinese BioMedical Literature Database on disc (CBMdisc),and Wanfang database with computers. Two independent reviewers selected the literatures by the inclusion and exclusion criteria,data extraction and cross-checking,and then conducted the analysis. Results A total of seven trails (228 patients,136 of them in a rTMS group and 92 in a control group)were included. Four randomized controlled trials (RCTs)were used for Meta-analysis (54 patients in the rTMS group,42 in the control group). The other three non-RCTs were only reviewed systematically. (1)Meta-analysis showed that the improvement of swallowing function score after rTMS was better than that of the control group (SMD=1. 73,95%CI 0. 45 to 3. 01;P=0. 008). (2)After high-frequency rTMS (>1 Hz),there was significant difference in the improvement of swallowing function score between the two groups (SMD=1. 60,95%CI 0. 10 to 3. 11;P=0. 04). Compared to the control group,there were also significant differences in the improvement of some swallowing function scores in low-frequency rTMS (1 Hz),suggesting the potential advantages of low-frequency therapy. (3)After rTMS,there was no significant difference in the improvement of Barthel index in patients with stroke compared with the control group (MD= -21. 60,95%CI-36. 21 to-7. 00;P=0. 004). (4)In terms of adverse reactions,seven trials did not report any adverse events, such as headache,tinnitus or epilepsy,etc. Conclusion Using rTMS may significantly promote the recovery of swallowing function for patients with post-stroke dysphagia,and it is both safe and effective.

Objective To explore the relationship between serum adiponectin concentration and hyperuricemia in Han people in Hunan.Methods Cluster random sampling method was used to carry out the survey during October to December 2008 in Changsha Health Checkup Center of the Second Xiangya Hospital.All subjects completed the questionnaires,physical examination,biochemical measurements,and the data were analyzed by t test,Pearson's correlation analysis and multiple linear regression analysis.Results The Age,WC,TG,SBP,DBP,SUA,BMI were significantly higher in hyperuricemia group compared with the normal uric acid group.The concentration of adiponectin in hyperuricemia group was significantly lower than that in the normal uric acid group (5.0±2.7 vs 6.8±4.2 μg/ml,t=3.961,P＜0.05).In the normal serum uric acid group,the serum adiponectin concentration in female was significantly higher than that in male (t=4.99,P＜0.05).Pearson's correlation analysis showed that serum adiponectin concentration was negatively correlated with the serum uric acid level,but the adiponectin level was not significantly correlated with Age and blood pressure.Stepwise analysis showed that the main factors that could affect the adiponectin level were SUA,gender and BMI (P＜0.05).Conclusion The decreasing of serum adiponectin concentration might be one of the mechanisms of hyperuricemia,therefore,detecting serum adiponectin concentration may provide the basis for the prevention and treatment of hyperuricemia.