Objective To investigate the effects and the mechanism of telmisartan and pyridoxamine on oxidative stress in spontaneously hypertensive rats(SHR).Methods SHRs(male,20 weeks of age) were randomly divided into four groups (n＝ 12 for each):hypertension control (HC) group (2 ml of distilled water),telmisartan group[T,6 mg/(kg · d)],pyridoxamine group[P,200 mg/(kg · d)]and combined group(TP,6 mg/kg telmisartan and 200 mg/kg pyridoxamine per day).Treatments were continued for 16 weeks.The normal control group included 13 WKY rats and received gastric lavage with distilled water.SBP of tail artery was measured during the intervention ervey 2 weeks.The levels of AGEs,SOD and MDA were measured by ELISA,xanthine oxidase and thiobarbituric acid methods after the intervention.Expressiones of NF-κBp65,ERK1 and ERK2 in renal tissue were detected by immunohistochemistry.Expression of RAGE in the renal cortex was investigated by Western blot.Results SOD activity was decreased in the HC group.The levels of AGEs,MDA,RAGE and the activations of NF-κBp65 and ERK1/2 were increased in the HC group (t＝4.53,5.52,2.93,al1 P＜0.05).After the 16 weeks' intervention,SOD activity was elevated in T,P and TP groups compared to that in HC group (P＜0.05).The positive expressiones of NF-κBp65,ERK1 and ERK2 were significantly reduced in T,P and TP groups compared to those in HC group (F＝20.13、148.82、18.70,all P＜0.05).All the positive expressiones of NF-κBp65,ERK 1and ERK2 were lowest in the TP group versus T and P groups (t ＝ 3.58、2.84,P ＜ 0.05).Conclusions Telmisartan and pyridoxamine can alleviate the oxidative stress in spontaneously hypertensive rats,which may result from the blocking effect of Ang Ⅱ,the reduction of AGEs-RAGE and inhibiting the signal pathways of ROS,NF-κBp65 and ROS-ERK1/2.

Objective To strengthen the quality control management and enhance the detection capacity of the experimental animal quality control laboratoriesin our country through the detection of serum esterase-1 (Es-1) in the experimental mice.Methods The samples were prepared according to the standard procedure, and then were randomly numbered and distributed to participating units by cold-chain transport.Before the deadline, the participants submitted the results and the copies of original records.When the results were completely consistent with the standard results,the results were regarded as satisfactory, otherwise were unsatisfactory.Results A total of 11 laboratories participated in this program, of which 10 laboratories were regarded as satisfactory (90.9%) and one laboratory obtained unsatisfactory result (9.1%).Conclusions The results of this proficiency testing project demonstrate that the overall detection level of Es-1 in laboratory mice is highof the participating laboratories.However, more attention still should be paid to standard specifications and some test details.

Objective To systematically evaluate the effectiveness and safety of glucoside tripterygium total (GTT) combined with antihistamine medicine for chronic idiopathic urticaria (CIU). Methods All randomized or semi-randomized controlled trials (RCTs or semi-RCTs) of GTT in treating CIU were collected from CNKI, VIP, WanFang Data, CBM, Embase, PubMed and Cochrane Library clinical controlled trials database. After two researchers conducted screening and data extraction independently, the quality of the included literature research was evaluated according to the risk of bias tool described in the Cochrane Handbook version 5.1.0, and then RevMan 5.3 was used to undertake Meta analysis. Results A total of 21 articles about RCTs and semi-RCTs were obtained, including 2194 patients. Meta analysis indicated that GTT combined with antihistamine medicine treatment showed higher effective rates compared with the control group [RR=1.33, 95%CI (1.26, 1.40), P<0.000 01], with obviously lower recurrence rate [RR=0.45, 95%CI (0.33, 0.62), P<0.000 01]. There was no statistical significance in adverse reactions. Conclusion GTT combined with antihistamine medicine for CIU has definite efficacy, and is relatively safe. Whether apply GTT combined with antihistamine medicine for CIU should be verified through randomized controlled trial with large-scale samples, multiple centers and high quality.

Objective:To explore influence of monotherapy or combined use of telmisartan and pyridoxamine on aor-tic remodeling in spontaneously hypertensive rats (SHR)and its possible mechanism.Methods:A total of 48 male SHE were randomly and equally divided into hypertension control group,telmisartan group,group,and telmisartan+ group (combined treatment group). Kyoto Wistar rats of the same age and gender were regarded as normal blood pressure control group (normal control group). Thoracic aortic section were examined by related staining af-ter 16 weeks intervention to calculate the ratio of aortic wall thickness to radius of lumen (Tw/Rl),the ratio of wall area to lumen area (W/L),and the area ratio of media elastic fiber/collagen fiber. Concentrations of related en-zymes and receptor etc. of abdominal aortic were measured.Results:Compared with hypertension control group, there was significant rise in ratio of media elastic fiber/collagen fiber area and significant reduction in media collagen fiber/media area ratio in telmisartan group,pyridoxamine monotherapy group and combined treatment group,and there were significant decrease in Tw/Rl [(0.17±0.02)vs. (0.12±0.01)]and W/L [(0.29±0.03)vs. (0.22± 0.02)]ratios in combined treatment group,P <0.05 or <0.01;immunohistochemistry indicated that there were significant reductions in thoracic aortic receptor of advanced glycation end products (RAGE) [(0.24±0.03)vs.(0.17±0.03)]and extracellular signal-regulated kinase 1/2 (p-ERK1/2 )expression [(0.63 ± 0.06)vs. (0.37± 0.04)]in combined treatment group,P <0.05,<0.01. Fluorescence quantitative PCR indicated that medication can significantly reduce nicotinamide adenine dinucleotide phosphate (NADPH)oxidase subunit p47phox mRNA ex-pression (P <0.01 all),especially in combined treatment group (P =0.001).Conclusion:Combined use of telmis-artan and pyridoxamine is superior to the single use of either drug on improving thoracic aortic remodeling in SHR, the mechanism may be related to it reduces local expression of RAGE and p-ERK1/2 ,and inhibits oxidase subunit p47 of NADPH.

Objective To investigate the detection capacity of malic enzyme 1 and isocitrate dehydrogenase 1 ( Mod1&Idh1) in the laboratory animal monitoring laboratories in China in order to understand the detection capacity of la-boratories and to improve the detection level of laboratory animals’ quality.Methods Based on the program approved by CNAS, samples preparing, homogeneity test and stability test of malic enzyme 1 and isocitrate dehydrogenase 1 in the mouse kidneys were carried out.Standard operation procedure and samples with random numbers were distributed to the la-boratories.The laboratories should submit the result reports before the time limit expires.If the laboratory reports were the same with the standard results, the laboratories will receive satisfactory remark.If laboratory reports were not the same with the standard results, the laboratories will receive unsatisfactory remark.If a laboratory did not submit report, the laboratory will also receive unsatisfactory result.Results Eight laboratories out of 10 (80%) enrolled laboratories reported satisfac-tory experiment results, and two laboratories (20%) presented unsatisfactory results.Conclusions The whole detection level of laboratories in Mod1 &Idh1 is relatively high in the laboratory animals monitoring laboratories in China.It can re-flect the detection level of laboratories to conduct the laboratory capacity evaluation.

Objective To screen the markers of chromosome 12, which is vacant in the Beijing local standard DB11/T828.3-2011 for genetic quality control of miniature pigs in Beijing, and to study the applicability of the local standard by comparison of two different methods for evaluation of the genetic quality of the same population.Methods According to the literature, we selected four pairs of microsatellite markers of chromosome 12 and studied the polymorphism through monitoring the genetic quality of two populations of China Agricultural University miniature pigs.We screened the highly polymorphic markers of chromosome 12, combined them with the microsatellite primers of the standard 18 pairs of chromosomes to establish the whole chromosome method.We compared and analyzed the applicability of the local standard DB11/T828.3-2011 through monitoring the genetic quality of the same population of miniature pigs with different method.The data were processed and analyzed using software Popgen32.Results All the screened four pairs of microsatellite markers of chromosome 12 were highly polymorphic (PIC>0.5).The local standard showed a chromosome coverage of 94.7%, stability of amplification of 96.0%, and certified that the China Agricultural University miniature pig III was qualified, while the China Agricultural University miniature pig I was not qualified.When the markers of chromosome 12 were added, the whole chromosome method showed result of 100% chromosome coverage and 96.6% amplification stability, both of the two populations of pigs were certified as qualified.Conclusions The four screened markers of chromosome 12 are all highly polymorphic, and provide a support for supplement of the local standard DB11/T828.3-2011.

Objective To evaluate the value of virtual touch tissue imaging quantification (VTIQ),which was combined with ultrasound Breast Imaging Reporting and Data System (BI-RADS),for differentiating benign from malignant breast lesions.Methods Totally 190 patients with 214 breast lesions were enrolled in this study.All lesions were classified according to the BI-RADS for sonography.The maximum,minimum and mean shear wave velocity (SWV) values on VTIQ in the lesions were obtained.The SWV between benign and malignant lesions were analyzed.Receiver operating characteristic(ROC) curves were plotted to determine the cut off value of VTIQ for differential diagnosis of breast lesions. Results Pathology confirmed 166 benign lesions and 48 malignant lesions.The SWVmax,SWVmin,SWVmean of malignant lesions were significantly higher than those of benign lesions (all P<0.001).The SWVmean 3.67 m/s as the best value in the diagnosis of benign and malignant lesions.The sensitivity,specificity,positive predictive value and negative predictive value of the combination of the SWVmean and BI-RADS classification standard in the diagnosis of benign and malignant breast lesions were 77.6%,97.5%,92.7%,91.3%,respectively.Conclusions The combination of VTIQ and ultrasonic BI-RADS can improve the ability of differential diagnosis of benign and malignant breast lesions.

Objective To investigate the relationship between regular exercise habit and coronary collaterals of patients with acute coronary syndrome (ACS).Methods TWo hundred and thirty-night patients diagnosed ACS and operated coronary angiography (CAG) showing severe coronary stenosis were enrolled hospitalized from May 2012 to October 2012.They were divided into regular exercise group (n =102) and irregular exercise group(n =137) according to the exercise frequency.The information of the general data,the information of CAG and other relevant index were collected.The coronary artery score was recorded according to the Censini and the coronary collateral class was made according to the Rentrop.Other characters in clinical and laboratory were recorded.Multi-factor regression analysis was used to analysis the influence factors of coronary collateral.Results The proportion of coronary collaterals (41.2％ (42/102)) in the regular exercise group was higher than that in the irregular exercise group (24.1％ (33/137)),and the difference was statistically significant(x2 =7.929,P =0.005).Lg(Gensini score) was (1.89 ± 0.18) the and (1.94 ± 0.19) in the regular exercise group,The left ventricular ejection fraction was 57.0％ (52.0％,60.0％) in the regular exercise group and 50.0％ (45.0％,57.0％) in the irregular exercise group,and the difference was statistically significant (Z =-5.152,P =0.000).Multi-factor regression analysis showed that regular exercise (OR =3.423,95％ CI:1.790-4.578),diabetes mellitus (OR =0.451,95％ CI:0.212-0.962),B-type natriuretic peptide (OR =2.412,95 ％ CI:1.271-4.578),non-ST-segment elevation ACS (OR =2.383,95％ CI:1.185-4.791),chest pain history (OR =2.207,95％ CI:1.175-4.145),Gensini score (OR =1.538,95％ CI:1.141-2.073) were independent influence factors of coronary collateral(P ＜ 0.05).After adjusting other factors,the patients with regular exercise had better coronary collaterals than that with irregular exercise (OR=3.423,95％CI:1.790-6.548,P ＜0.001).Conclusion The regular exercise can promote coronary collateral emergence for the patients with ACS.

AIM: To investigate the effects of adenovirus-mediated human tissue kallikerin (Ad-hKLK1) gene delivery on the proliferation, migration of VSMC_(SHR) induced by platelet derived growth factor-BB (PDGF-BB). METHODS: The VSMC_(SHR) proliferation induced by PDGF-BB was accessed by cell counting and methyl thiazolyl tetrazoliuin (MTT). The migration was assessed by modified Boyden chamber assay. Western blotting was used to determine the expressions of the cycle-independent kinase inhibitors p27~(Kip1) and p21~(Cip1).RESULTS: Proliferation of VSMC_(SHR) induced by PDGF-BB was inhibited after transfection of Ad-hKLK1 (20-100 MOI) in a MOI-dependent manner. The peak inhibition titer of Ad-hKLK1 fell on 100 MOI, with the peak inhibition rate of 39.3% (cell counting, n=3, P<0.01), 30.2% (MTT, n=3, P<0.01), peak stunning rate of cell-cycle in phase G0/G1 at 36.4%. The inhibitory effects of proliferation and cell-cycle caused by hKLK1 gene delivery were significantly abolished by Hoe140, a bradykinin B2 receptor antagonist. Migration of VSMC_(SHR) induced by PDGF-BB was inhibited after hKLK1 gene delivery, with the peak inhibitory rate of 34.6% (n=6, P<0.01). However the inhibitory effects of migration were not blocked by Hoe140. The protein expression of p27~(Kip1) and p21~(Cip1) increased significantly after the hKLK1 gene delivery, whereas Hoe140 nearly completely blocked these effects (n=3, P<0.01, respectively).CONCLUSION: The hKLK1 gene delivery may inhibit the proliferation and migration of VSMC_(SHR) induced by PDGF-BB. Bradykinin B2 receptor probably mediates the up-regulating expression of p27~(Kip1) and p21~(Cip1) that contributes to the inhibitory effects of proliferation of hKLK1. However, the inhibitory effects of migration by hKLK1 gene delivery may not be mediated by bradykinin B2 receptor.

Objective To explore the effect of resveratrol on the expression of matrix metalloproteinases-9 (MMP-9) in soluble CD40 ligand (sCD40L)-activated macrophages. Methods Human monocytic cell line THP-1 cells under an inducing of phorbol ester differentiated into macrophages. Then the macrophages were sitimulated by sCD40L independently and after a preincubation with resveratrol. The mRNA expression of MMP-9 and tissue-inhibitor of metalloproteinase-1 (TIMP-1) in macrophages were investigated by semiquantitative RT-PCR. The secretions of MMP-9 and TIMP-1 protein were measured by Western blot. The MMP-9 activity was analyzed by gelatin zymography technique. Results The expressions of MMP-9 gene(1.53±0.04 vs. 0.75±0.01,P＜0.05) and protein(244 930.8±31 268.6 vs. 192 976.8±20 223.1,P＜0.05)were higher in macrophages when stimulated by sCD40L. Resveratrol (10 μmol/L and 50 μmol/L)can inhibit the CD40L-induced gene expression and the protein secretion of MMP-9 (P＜0.01). The activity of MMP-9 was degraded by resveratrol (P＜0.05). Meanwhile resveratrol could increase the gene expression and protein secretion of TIMP-1 (P＜0.05). Conclusions Resveratrol can inhibit the CD40L-activated macrophage expression of MMP-9. It may be one of its mechanisms on antiatherosclerosis and stabilization of atheromatous plaques.