Objective To investigate the effect of olmesartan medoxomil on renal oxidative stress in mice with chronic heart failure. Methods C57 mice were divided into sham operation group(SHAM group),chronic heart failure group(CHF group)and olmesartan medoxomil treatment group(OLM group).Experimental CHF model was established by coronary artery ligation,in which OLM group fed with a daily dose of 10 mg/kg.The heart rate,blood pressure,cardiac function,Scr,BUN,and plasma and kidney angiotensin(Ang)Ⅱ were measured.Real-time PCR was used to examine renal gp91phox,p22phox and NOX4 expression.AZAN and DHE staining was used to detect renal pathological change after 12 weeks. Results Compared with SHAM group,left ventricular-end diastolic dimension (LVDd)and left ventricular end-systolic dimension(LVDs)were significantly increased(P<0.05),while fractional shortening(FS)and ejection fraction(EF)were significantly decreased in CHF and OLM groups (P<0.05).Compared with SHAM group,systolic blood pressure,Scr,BUN,and AZAN and DHE staining positive area were significantly increased in CHF group(P<0.05),while above indexes were significantly lower in OLM group as compared to CHF group(P<0.05).Compared with SHAM group,plasma and kidney Ang Ⅱ levels,gp91phox,p22phox and NOX4 expression were increased in CHF group(P<0.05),while above indexes were significantly lower in OLM group as compared to CHF group (P<0.05).Conclusions Chronic heart failure can activate intrarenal NADPH oxidase resulting in renal injury.Olmesartan medoxomil can protect kidney by inhibiting the effect of Ang Ⅱ-induced oxidative stress.

Objective To explore related influencing factors for postoperative delirium in elderly patients, to provide a reference for the prevention and treatment. Methods Fifty-four patients with delirium after surgery were used as observa?tion group, and a total of 150 subjects with no delirium after surgery during the same period were selected as the control group. Data of age, gender, malnutrition, disorders of water and electrolyte metabolism, postoperative mechanical ventilation, postoperative hypoxemia, severe infection and postoperative pain degree, and the combination of basic diseases were com?pared and analysed between two groups. The binary logistic regression analysis was used to analyse the influencing factors of postoperative delirium. The outcome and prognosis were observed and analyzed in observation group. Results The average age was significantly higher in observation group than that of control group (P<0.05). The percentages of postoperative hy?poxemia and severe infection were significantly higher in observation group than those of control group ( P<0.05). Patients with higher age, postoperative hypoxemia and severe infection were risk factors for postoperative delirium. In observation group,1 case died of lung infection, 1 case died of multiple organ failure, the remaining 52 patients were improved and dis?charged from hospital after three months. Conclusion For patients with higher age, postoperative hypoxemia and severe in?fection are the risk factors for occurrence of postoperative delirium. More attention should be paid to clinical preoperative and postoperative periods.

Objective To investigate the role of the clock gene promoter methylation in aging. Methods C57BL mice of 4- (young, n=9) and 20- (old, n=10) month-old were determined the promoter methylation level of clock genes (Per1/2, Bmal1/2, Cry1/2, Clock, Npas2) in the stomach, spleen, vascular, kidney and striatum with methylation-specific polymerase chain reaction (MSP). Results The incidence of promoter methylation of Cry1, Bmal2 and Npas2 in spleen increased in old mice (P<0.05), while the promoter methylation of Per1 in stomach decreased (P<0.05), and the promoter methylation of Bmal1 in vascular increased (P<0.05). Conclusion Promoter methylation of some clock genes is involved in process of aging in a tissue-specific way.

Objective To investigate the effects of type 2 diabetes on learning and memory of APP/PS1/Tau triple transgenic (3 × Tg) mice of Alzheimer’s disease, and the protective mechanism of liraglutide (LIR) thereof. Methods One month old C57BL/6 mice were set to be control group (WT). One month old 3×Tg mice were divided into control group (Tg), liraglutide group (Tg+LIR), type 2 diabetes group (Tg+T2DM) and liraglutide treatment group (Tg+T2DM+LIR). The model of T2DM was established by feeding the high fat and sugar fodder, and then injecting streptozotocin (STZ) in mice, making sure the fasting blood glucose was more than 7 mmol/L. Then the subcutaneous injection of LIR was administered for 2 months. The values of body weight and fasting blood glucose were detected at age of 5-month. Morris water maze was applied to evaluate the spatial learning and memory ability. Western blotting assay was used to measure the levels of phosphorylated Tau, neurofilament (NFs) and insulin receptor substrates. ELISA was used to detect the human Aβ42 to evaluate the effect of LIR on-amyloid. Results LIR can reduce body weight and blood glucose, can alleviate spatial learning and memory damaging caused by T2DM, and also can improve phosphorylated Tau levels, NFs and insulin receptor substrates caused by T2DM, and finally can reduce the deposition ofβ-amyloid of 3 × Tg mice. Conclusion T2DM can aggravate symptoms of AD in 3×Tg mice, and LIR has a protective effect on it.

Objective To investigate the effects of penehyclidine hydrochloride (PHCD) pretreatment on NF-κB mRNA expression and SOD activity in lung tissues in rats with acute lung injury (ALI) induced by LPS.Methods Thirty-two male SD rats, 2 months old, weighing 230-280 g, were randomly divided into 4 groups (n=8 each): control group (group C), ALI group, low dose PHCD group (group LP) and high dose PHCD group (group HP). ALI was induced by intravenous LPS 5 mg/kg via tail vein. Group LP and HP received intraperitoneal PHCD 0. 3 and 1 mg/kg respectively 30 min before LPS administration. The rats were killed at 6 h after LPS administration. The lungs were removed immediately for determination of W/D lung weight ratio, lung water content, NF-κB mRNA expression, TNF-α and MDA content, and SOD activity and microscopic examination. Results NF-κB mRNA expression, TNF-α and MDA content, W/D lung weight ratio and lung water content were significantly higher, while SOD activity was significantly lower in group ALI, LP and HP than in group C (P ＜ 0.05). NF-κB mRNA expression, TNF-α and MDA content, W/D lung weight ratio and lung water content were significantly lower, while SOD activity was significantly higher in group LP and HP than in group ALI and HP than in group LP (P ＜ 0.05). The LPS-induced changes were mitigated by pretreatment with low and high doses of PHCD in group LP and HP.Conclusion Pretreatment with PHCD attenuates LPS-induced ALI by downregulating NF-κB mRNA expression, decreasing local inflammatory response and enhancing anti-oxidant activity.

Objective To verify and valuate the performance of small dense low-density lipoprotein cholesterol (sdLDL-C) detection by the direct clearance method and evaluate its preliminary clinical application in acute coronary syndrome (ACS).Methods Case control study:The performance (accuracy,precision,linearity) of sdLDL-C was assessed by direct clearance method.In 143 cases of ACS patients selected from Cardiology Department and Emergency Department of Shangdong Provincial Hospital from April to October in 2016,with 100 cases male,female 43 cases,including acute myocardial infarction (AMI)group of 59 cases,unstable angina pectoris (UAP) group of 84 cases;83 cases of healthy volunteers as a control group selected from health physical examination center of Shandong Provincial Hospital,with 59cases male,female 24 cases.Levels of sdLDL-C,total cholesterol (TCH),triglyceride (TG),low-density lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol (HDL-C),apolipoprotein A (ApoA I),apolipoprotein B (ApoB),lipoprotein (a) (Lpa) and high sensitive C-reactive protein (Hs-CRP) were detected separately by automatic biochemical analyzer.Non high density lipoprotein cholesterol (non-HDL-C) equals TCH minus HDL-C.x2 test,t test,one-way ANOVA,Pearson correlation and multiple linear regression analysis were used as statistical methods.Results The within-lot or between-lot variation was 2.85％ and 3.36％.Methodological comparison:regression equation Y =0.984X + 0.018,r2 =0.966,t =-0.191,P =0.850.There was a good linear correlation (Y =1.026X + 0.007,r2 =0.999) between theoretical values and actual detection results in range of 0.15-2.65 mmol/L.SdLDL-C concentrations were positive correlated with TCH,non-HDL,LDL-C,TG,ApoB (r =0.758,0.848,0.839,0.514,0.885,respectively,P ＜0.01),and negative correlated with HDL-C (r =-0.224,P =0.001),but no correlation with APOA I,Lpa and Hs-CRP(r =-0.021,0.050,0.003,respectively,P ＞ 0.05).Multiple linear regression analysis showed that the factors influencing sdLDL-C level were HDL-C,ApoB,LDL-C and TG.The levels of sdLDL-C,TG in the ACS group were significantly higher than those in the control group (t =3.415,4.660,respectively,P ＜ 0.01),but no difference between the two groups in the levels of TCH,non-HDL-C and LDL-C (t=-1.831,-0.452,-1.398,respectively,P ＞0.05).Comparing AMI group with control group,sdLDL-C,TG and Hs-CRP were significantly higher than the control group (P =0.000,0.000,0.000,respectively),but TCH,LDL-C and non-HDL were similar between the two groups (P =0.800,0.320,0.120,respectively);Comparing UAP group with control group,TG and Hs-CRP were higher than control group (P =0.001,0.047,respectively),TCH and LDL-C were significantly lower than the control group (P =0.003,0.008,respectively),but sdLDL-C had no difference (P =0.305);Comparing AMI group with UAP group,sdLDL-C,TCH,LDL-C and Hs-CRP were significantly higher than UAP group (P =0.000,0.003,0.001,0.000,respectively),and TG were no statistical significance (P =0.473).Conclusions Direct clearance method can meet the requirement of sdLDL-C detection.sdLDL-C level can assess the metabolism of blood lipids and be used as an independent risk factor and predictive index of ACS,superior to LDL-C.

Objective:To observe the effect of tannic acid on renal morphology and function of diabetes mellitus model rats ,and to explore the mechanism of improving effect of tannic acid from oxidative stress , nitrosative stress angle.Methods: 8 rats were randomly selected from 68 6-week-old male Wistar rats as normal control group and the remaining 60 rats accepted high-sugar and high-fat diet for 4 weeks, then were injected streptozotocin ( STZ, 52 mg/kg ) intraperitoneally in order to manufacture a diabetic rat model.Further the diabetic rats were randomly divided into model group ,aminoguanidine group ,low-dose of tannic acid group and high dose of tannic acid group.The rats in aminoguanidine group were injected aminoguanidine [AG,40 mg/(kg· d)] intraperitoneally, those in low-dose of tannic acid group were injected tannic acid [TA,20 mg/(kg· d)] and those in high-dose of tannic acid group were injected tannic acid [TA,30 mg/(kg· d)].The rats in normal control group and model group were injected normal saline [NS, 30 mg/(kg· d)] and all rats were sacrificed and tissues were derived at the end of the week 10.Morphologic changes of kidney in diabetic rats were observed by HE staining and correlative biochemical indices of renal function were detected by biochemical analyzer.8-hydroxy deoxyguanosine (8-OHdG) and 3-nitrotyrosine (3-NT) content of renal tissue in rats in different groups were detected by ELISA method.Mesangial cells cultured in vitro were treated with high concentration of glucose (30 mmol/L) and AGEs (250 mg/L) and at the same time with different concentration of tannic acid (10,20,40 and 80μmol/L) on the basis of setting corre-sponding control group.The contents of 8-OHdG and 3-NT in the culture supernatant were measured by ELISA method after 48 hours.Results:Tannic acid can effectively improve the renal pathological changes and improve renal function of diabetic rats .The contents of 8-OHdG and 3-NT in kidney tissue homogenate of diabetic rats and in the supernatant of GMC cultured with high glucose or AGEs were all significantly increased and can be reduced by tannic acid.Conclusion:Tannic acid improving the structure and function damage of kidney in diabetic rats might be achieved by oxidative stress and nitrosative stress mechanism .

Objective To evaluate the effect of chlamydiaphage virus protein 2(Vp2) on the recombinant virus and virus screening research, and it clinical value thereof. Methods To compare the Vp2 protein sequences to get the conserva-tive region with COBALT. A phylogenetic tree was built with ProteinBlast of Distance tree. The amino acid sequence in the high conservative region was predicted by the methods of Gamier-Robson and Chou-Fasman, and its flexibe regions were predicted by Karplus method. The hydrophilicity plot was predicted by Kyte-Doolittle and Hopp-Woods method. The sur-face probability was analysed by Emini, and the antigenic index was analysed by Jameson-Wolf method. Results The six Chlamydiaphage Vp2 proteins were the highly conserved sequences. There were obvious differences between Chp1Vp2 and other 5 Vp2 proteins. There were the main structure-alpha helix and some cell epitopes in the high conserved region. Con-clusion Vp2 protein is the important component of chlamydia phage capsid with the conservative nature. Vp2 protein has complicated structures and high conservative region with strong immunogenicity, playing a practical value of research in vi-rus recombinantment and screening the wild strains of chlaymdia trachomatis phage.

Objective To explore the potential mechanisms of non-small cell lung carcinoma cells to rsTRAIL protein-induced apoptosis by phosphatidylinositol 3′-kinase (PI3K/Akt)inhibitor LY294002,and to provide new ways to increase killing activities of rsTRAIL protein for non-small cell lung cancer.Methods The A549 cells at logarithmic growth phase were selected and randomly divided into rsTRAIL group and LY294002+rsTRAIL group. The inhibitory rate of growth of the A549 cells was tested by MTT assay.The cell cycle and apoptotic rate were detected by flow cytometry analysis. The expression levels of Ser473 phosphorylated form of Akt (p-Akt),c-FLIPL protein and Bcl-2 protein in the A549 cells in two groups were analyzed by Western blotting method. Results The inhibitory rate of growth of the A549 cells in LY294002+rsTRAIL group (74.6 %± 2.63%)was higher than that in rsTRAIL group (5.61% ± 0.32%) (P< 0.05 ). Compared with rsTRAIL group, the percentage of the cells at G0/G1 phase in LY294002+rsTRAIL group was increased(P<0.05)and the percentage of the cells at S phase was decreased(P<0.05).The apoptotic rate of the A549 cells in LY294002+rsTRAIL group (61.5%±3.02%)was higher than that in rsTRAIL group (3.21%±0.96%)(P<0.05). The Western blotting results showed that the expression levels of p-Akt, c-FLIPL and Bcl-2 proteins in the A549 cells in LY294002+rsTRAIL group were decreased (P<0.05 )and the ratio of Bax/Bcl-2 was increased (P<0.05 ) compared with rsTRAIL group.Conclusion LY294002 can increase the killing activity of rsTRAIL protein in A549 cells by inhibiting the activity of PI3K.

Objective:To explore the proportions of Th17 cells in the peripheral blood and levels of IL-17,IL-23 in the serum of patients with Graves′disease ( GD ) and their clinical significance.Methods: We studied 29 patients with GD ( GD group ) , and reevaluated the GD group after therapy ( euthyroid GD group ).29 gender-and age-matched volunteers were selected as the normal control ( NC group).The proportions of Th17 cells were investigated by flow cytometry.The levels of IL-23,IL-17 in the serums were measured by ELISA.The levels of FT3,FT4,TSH were determined by ECLIA and the levels of TrAb were tested by RRA.Results:There were no significant difference among 3 study groups in sex and age match ( F=0.0075 , P>0.05;χ2=0.4213 , P>0.05 ).The proportions of Th17 cells and the levels of IL-17 , IL-23 were increased in the GD and euthyroid GD patients compared with the control group (respectively,P<0.05).The proportions of Th17 cells and the concentrations of IL-23 in euthyroid GD group were significantly lower than those of GD group ( respectively , P<0.05 ) , but there were no significance in the concentrations of IL-17 between euthyroid GD group and GD group(P>0.05).Correlation analysis revealed that the proportions of Th17 cells ,and the levels of IL-17,IL-23 were positively correlated with the levels of FT3,FT4,TrAb(r=0.588 2,0.337 2,0.371 0;0.549 6,0.287 5,0.342 7;0.361 0,0.420 8, 0.330 8;P<0.05 ,for all parameters ) ,and were negatively correlated with the levels of TSH ( r=-0.319 7 ,-0.472 8 ,-0.428 2;P<0.05,for all parameters).Conclusion:Th17 cells and their related cytokines IL-17,IL-23 are highly expressed in the serum of patients with GD.Th17 cells and their relative cytokines have certain relevance with 4 thyroid function parameters of the patients with GD , which can be used as biological markers for GD.