ObjectiveTo explore the effects of fisetin on the learning and memory abilities impairments induced by Aβ in mice.MethodsAlzheimer's disease (AD) animal model was made by single intracerebroventricular infusion of Aβ (1-42) through guide cannula.Fisetin was orally administered 7 days before Aβ infusion once a day,and continued throughout the experimental period.Water maze test began on day 3 after Aβ infusion.All mice were sacrificed and hippocampi were dissected immediately after behavioral test.The protein expression of hippocampal nuclear Nrf2 and the mRNA level of HO-1,GCLC and GCLM were examined by western blotting and RT-RCR techniques respectively.Results ( 1 ) Aβ (1-42) significantly increased escape latency in hidden platform test ( (25.4 ± 3.33 ) s ),and decreased the number of crossings in probe test ( 1.70 ± 0.25 ) compared with control ((9.05 ± 1.37 )s) for hidden plat form ;4.50 ± 0.41 for probe test) and Aβ (42-1)-treated group ( ( 10.80 ± 1.38)s) for hidden platform test; 4.10 ±0.39 for probe test; P＜0.01 ).The prolonged treatment with fisetin dose-dependently reversed the changes (10 mg/kg:17.54 ± 3.56s for hidden platform test;2.50 ± 0.40 for probe test,P＜0.05,20 mg/kg:( 13.04 ± 2.36) s for hidden platform test;3.60 ±0.36 for probe test,P＜0.01 ).(2) Aβ (1-42) significantly decreased the nuclear Nrf2 protein level (0.07 ±0.02),and mRNA level (0.45 ±0.04) of HO-1,GCLC (0.41 ± 0.04) and GCLM (0.26 ± 0.03 ) in the hippocampus of mice compared with control (0.18 ± 0.02 for Nrf2 ;0.83 ± 0.09 for HO-1 ; 1.01 ± 0.10 for GCLC; 0.65 ± 0.07 for GCLM) and Aβ (42-1 ) -treated group (0.21 ± 0.02 for Nrf2 ; 0.90 ± 0.08 for HO-1 ; 1.11 ± 0.11 for GCLC ; 0.72 ± 0.07 for GCLM) ( P ＜ 0.05 or P ＜ 0.01 ).However,fisetin administration significantly counteracted these changes ( 10 mg/kg:0.11± 0.01 for Nrf2 ; 0.56 ± 0.06 for HO-1 ; 0.61 ± 0.04 for GCLC ; 0.35 ± 0.04 for GCLM ; 20 mg/kg:0.16 ± 0.02for Nrf2;0.79±0.10 for HO-1;0.86±0.09 for GCLC;0.51±0.04 for GCLM;P＜0.05).ConclusionFisetin attenuates learning and memory impairments induced by Aβ (1-42) through activation of Nrf2 antioxidant signaling pathway.

Objective:To investigate effect of curcumin on serum gelatinases level in patients with unstable angina pectoris (UAP). Methods:A total of 80 UAP patients admitted from January 2010 to September 2010 were enrolled and randomly divided into curcumin treatment group (n=40) and routine treatment control group (n=40). Serum levels of gelatinases [contain matrix metalloproteinase (MMP)-2 and -9] of the two groups were measured before and 30d after treatment.Results: Compared with before treatment , after treatment, serum levels of gelatinases significantly decreased [MMP-2:(52.64±6.77)ng/ml vs.(32.65±1.67)ng/ml,MMP-9:(56.75±7.34)ng/ml vs.(35±1.88)ng/ml]in curcumin treatment group (P<0.01), and they were significantly lower than those of routine treatment control group[MMP-2:(32.65±1.67)ng/ml vs.(37.78±2.76)ng/ml,MMP9:(35±1.88)ng/ml vs.(40.23±1.95)ng/ml]],P<0.05. Conclusion:Curcumin could decrease serum levels of gelatinases in patients with unstable angina pectoris, and possesses effect stabilizing coronary artery plaque.

Objective: To investigate effect of curcumin on serum gelatinases levels in patients with unstable angina pectoris（UAP）. Methods： A total of 80 UAP patients admitted from January 2010 to September 2010 were enrolled and randomly divided into curcumin treatment group (n=40) and routine treatment control group (n=40). Serum levels of gelatinases [contain matrix metalloproteinase（MMP）-2 and -9) of the two groups were measured before and 30d after treatment. Results：Compared with before treatment , after treatment, serum gelatinases levels significantly decreased [MMP-2：（52.64±6.77）ng/ml vs. （32.65±1.67）ng/ml，MMP-9：（56.75±7.34）ng/ml vs.（35±1.88）ng/ml ] (P<0.01) in curcumin treatment group (P<0.01), and they were significantly lower than those of routine treatment control group [MMP-2：（32.65±1.67）ng/ml vs.（37.78±2.76）ng/ml，MMP-9：（35±1.88）ng/ml vs.（40.23±1.95）ng/ml ] , P<0.05 all. Conclusion：Curcumin could decrease serum levels of gelatinases in patients with unstable angina pectoris, and possesses effect of stabilization coronary artery plaque.

Methods The maximum tolerated dose( MTD)of water and ethanol extracts of Radix millettiae speciosae were measured for the safety evaluation. Results Maximal tolerated dose( MTD)of water extract was higher than 1 000 g·kg-1 ,which equaled to 110 times the dose for human adults(60 kg). MTD of ethanol extract was higher than 1 700 g·kg-1 ,which equaled to 186 times the dose for human adults(60 kg). Conclusion Radix millettiae speciosae does not have obvious toxicity,thus its routine clinical dose is safe and feasible.

Objective To observe colorectal tumor's growth in hyperglycemia mice and its vascular endothelial growth factor (VEGF)'s expression, insulin-like growth factor-1 (IGF-1)'s variation of blood through the experiment, then to ascertain whether type 2 diabetes mellitus (T2DM) danger factors to promote colorectal cancer happen and progress or not. Methods The mouse model of colorectal cancer combined T2DM was established. The volume of tumor was observed. After 5 weeks, all mice were executed and IGF-1 in the blood and the expression of VEGF in the tumor tissue was examined. Results The average tumor volume of colorectal tumor-diabetes group [(1628.5±882) mm3] were larger than that of colorectal tumor group [(1950.2±726) mm3] (P <0.05), and its expression IGF-1 of blood [(105.33±32.32) ng/ml] were higher than that of the control group [(69.83±25.57) ng/ml] and colorectal tumor group [(70.17±25.27) ng/ml] (P <0.05). The expression of VEGF [(70.0±11.5)%] in colorectal tumor-diabetes group were significantly higher than that of colorectal tumor group [(42.9±7.5)%] (P <0.05), too. Conclusion The model of T2DM and transplanted colorectal tumor can be duplicated successfully in ICR mice. Diabetes mellitus may be one reason of promoting colorectal cancer progress. Besides high blood glucose, its mechanism is the high level of IGF-1 which can inhibit apoptosis, promote cell differentiation and hyperplasia, and through inducing VEGF duplicating, heighten its expression, promote the tumor vessel growth, lead to tumor happen and metastasis.

Objective:To study the correlation between serum homocysteine (Hcy) and the staging of gastric cancer,by comparing the concentrations of patients with gastric cancer at different pathological staging.Methods:90 patients with benign gastric diseases and 138 patients with gastric cancer were selected and admitted by Shandong University Qilu Hospital during the date from Mar 2014 to Jun 2015.The patients with gastric cancer were divided into 4 groups,according to the 7th AJCC Cancer Staging.To compare the difference of the concentration levels of Hcy and Tumor marks in different groups and analyze the relationship between benign disease and gastric cancer,and analyze it correlation with different pathological stagings of gastric cancer.Enzymatic cycling assay was used for detecting serum Hcy.Results:The serum Hcy concentration level in benign disease was (1 2.31 ± 3.22) μ mol/L,and significantly lower than cancer group(1 6.19 ± 4.84) μ mol/L,the difference was statistically significant (P＜0.05):The serum Hcy concentration levels increased gradually from staging I to staging Ⅳ,and the concentration level in staging Ⅰ was (13.94 ± 4.07) μ mol/L,in staging Ⅱ was (15.49 ± 4.09) μ mol/L,in staging Ⅲ was (17.10 ± 4.79) μ mol/L,in stagingⅣ was (19.81 ± 5.77) μ mol/L,the differences among the four groups were statistically significant(P＜0.05).Spearman Rank Correlation analysis confirmed that,the Hcy concentration level was positively related with pathological staging(r=0.503,P＜ 0.001).Logistic regression analysis showed that,the serum Hcy concentration level is significantly correlated with gastric cancer,after the adjustment of other risk factors (OR=1.208,P=0.003).Conclusions:The serum Hcy concentration level is closely correlated with gastric cancer staging,and increase significantly with the cancer staging (from staging Ⅰ to staging Ⅳ),so itcan be used to evaluate the severity of gastric cancer.

Objective To evaluate the immune reconstitution of HIV-1 infected individuals after long-term highly antiretroviral therapy (HAART). Methods Twenty-five HIV-1 infected individuals receiving HAART, 17 without HAART and 15 healthy controls were included in the study. CD4 +T, CD8 +T,CD8/human leukocyte antigen DR (HLADR) + T, CD8/CD38 +T cells, and the expression of CD127 on CD3 +T cells from peripheral blood samples were measured by flow cytometry. IL-7 in peripheral blood was measured by enzyme-linked immunosorbort assay (ELISA) in HAART group. t test was performed to compare the measurement data among the groups. Results Before HAART, the count of CD4 + T cells in HIV-1 infected group was lower than that of the healthy control (t =9. 12, P ＜0. 01 ), while the counts of CD8 + T,CD8/HLADR+T, and CD8/CD38 +T cells were higher than those of the healthy control (t = 4.48, 4.89 and 3.88, P＜0. 01 ). Ater 7 years' antiviral therapy, CD4 +T cells increased, CD8 +T cells decreased, but both of them didn' t reach to the normal levels ( t = 2.66 and 2.43, P ＜ 0.05 ). While the counts of CD8/HLADR+T cells and CD8/CD38 +T cells almost reached to the normal levels (t = 0. 86 and 1.39, P ＞0.05). Before HAART, the concentration of IL-7 in HIV-1 infected group was higher than that in healthy controls (t =5.31, P ＜0.01 ). It decreased with HAART, but was still higher than the normal level (t =2. 81, P ＜ 0. 05 ). The expression of CD127 on CD3 + CD8 + T cells in non-HAART group was significantly lower than that in healthy control ( t =- 6.01, P ＜ 0.01 ), while that in HAART group was higher ( t = 2.32,P ＜0.05), but still not reached to the normal level ( t = 4.49, P ＜ 0. 05 ). CD127 expression on ( CD45RA + ) CD3 + CD8 + T cells almost increased to the normal level ( t= 0. 28, P ＞ 0. 05 ), while that on ( CD45RO + ) CD3 + CD8 + T cells was still remarkably lower than the normal ( t = 4. 86, P ＜ 0. 05 ). Conclusion Long-term HAART can partially restore the count and function of lymphocyte subsets in HIV-1 infected individuals, and the abnormal immune activation can be inhibited.

In our previous work, we found that trivalent dimethylarsinous acid (DMA(III)) have high affinity binding to cysteine residue 13 of rat hemoglobin. However, it is still unknown why arsenic intermediate metabolite DMA(III) has high binding affinity for Cysl3 but not for other cysteine residues 93, 140, 111 and 125. In order to better understand the molecular mechanism of DMA(III) with rat hemoglobin, we have done current study. So, SD rats were divided into control and arsenic-treated groups randomly. Arsenic species in lysate of red blood cells were analyzed by HPLC-ICP-MS, and then determined by a hybrid quadrupole TOF MS. In addition, trivalent DMA(III) binds to different cysteine residues in rat hemoglobin alpha and beta chains were also simulated by Molecular Docking. Only Cys13 in alpha chain is able to bind to DMA(III) from the experiment results. Cys13 of alpha chain in rat hemoglobin is a specific binding site for DMA(III), and we found that amino acids compose pockets structure and surround Cys13 (but not other cysteine residues), make DMA(III) much easy to bind cysteine 13. Taken together, the DMA(III) specific binding to Cys13 is related to spatial structure of Cys13.

Objective To explore the association between the sortilin-related receptor,L (DLR class) A repeats containing (SORL1) gene single nucleotide polymorphisms (SNPs) and sporadic Alzheimer's disease (SAD) in Han Chinese populations.Methods Five candicate SNPs,including rs985421,rs12364988,rs4598682,rs3781834,and rs3781836,within the SORL1 gene were genotyped by LDR-PCR methods,and the association of these SNPs with SAD risk were also analyzed in a case-control study with 179 SAD and 106 healthy controls.Results The results indicated that the A allele frequency of the SORL1 SNP rs985421 was significant difference between SAD and healthy controls (Trend test:P =0.0044,P adj =0.022; Allelic:P=0.0023,P adj =0.012).In subjects without APOE s4 allele,higher frequency of the A allele of rs985421 was observed in SAD patients compared with control subjects by the stratified analysis (OR=2.260,95％ CI =1.269-4.024,P=0.0048).In addition,logistic regression analysis further revealed that the A allele of SORL1 SNP rs985421 was significantly associated with SAD risk (OR=1.968,95％ CI =1.273-3.042,P=0.002).However,no positive signals in other four SNPs within the SORL1 gene were observed (all P＞ 0.05).Conclusions The A allele of SORL1 SNP rs985421 may be an APOE ε4-independent factor associated with SAD risk.

Objective To observe the clinical effects on prevention of alveolar bone absorption by site preservation after tooth extraction due to periodontitis.Methods The experimental group consisted of 40 patients with 45 extracted teeth due to periodontitis.The fresh sockets were immediately grafted and filled with Bio-oss collagen and Bio-Gide after minimally invasive tooth extraction,while 40 teeth of control group were only treated with cotton balls bitten tightly over the socket for half an hour.Two groups were observed for changes in alveolar bone density by X-ray and cone beam CT (CBCT)after 6 months.Results There were the wound healing and no infection in extraction site of all patients with or without site preservation operation.The gingiva of extraction site was pink and tough in all groups.The alveolar bone loss in regular extraction patients significantly increased in horizontal and vertical aspects by X-ray and CBCT,while site preservation improved the alveolar bone defects (P<0.05).After site preservation for 6 months,CBCT analysis showed that the density of new alveolar bone markedly enhanced compared with regular extraction group.Conclusion The technique of site preservation after tooth extraction due to periodontitis is a method which can prevent and reduce disuse atrophy absorption of the alveolar ridge so that the height and width of the alveolar bone can meet aesthetic requirements.