In recent years,more and more attention has been given to aspirin resistance.Researchers have explored the mechanisms of this important phenomenon from several aspects,including patient compliance,laboratory tests,aspirin dose,genetics,and drug interactions.Many appropriate management methods of aspirin resistance have been proposed,such as improving patient compliance,avoiding drug interactions,adjusting dose,and adding other antiplatelet drugs with potential application value.This article reviews the advances in research on the mechanisms of aspirin resistance.

Objective:To get the prevalence of attention-deficit hyperactivity disorder and in Children. Methods:The subjects were 2188 children who were 4~16 year-old in Wuhan. We had their parents filled the investigation forms. Diagnosis was made according to criterion of attention-deficit hyperactivity disorder in DSM-IV. Results:of behavior problems were got through Achenbach Behavior Questionnaires. Those who were diagnosed as ADHD were classified into three subtypes: predominantly inattentive type; predominantly hyperactive-impulsive type and com-bined type. All suspicious patient and their parents were invited to have the diagnostic talk. Results: (1) The rate of ADHD was 13.58%. ADHD-C, 2.63%; ADHD-I, 8.27%; ADHD-HI, 2.68%. The male, 18.57%; female,8.78%. The ratio of male: female was 2.24:1。(2) There was significantly difference of rate of ADHD between age groups. The rate of 4~5 years-old was 15.88%, that for 6~11 years-old was 15.85%; and for 12~16 yeas-old, 9.98%. The rate of ADHD decreased by aging, especially the group of ADHD-HI. But the rate of ADHD-I was still increased, especially the male group of 6~11 years-old, 12.19%. (3) There was significantly difference of sociality ability between ADHD children and the normal. (4) No matter which age and sex, the scales of behavior problem of ADHD children were higher than the normal children. And the number of factors of behavior problem of ADHD children increased by ag-ing.Conclusion: The rate of ADHD-I was the highest in the three subtypes defined by DSM-Ⅳ, especially among boys 6~11-years-old. The rate of ADHD is significantly associated with sex and age.

Objective:To study the effect of recombinant human growth hormone(rhGH) and its combination with chemotherapy(5-FU) in tumor bearing mice.Methods:Hepatic metastases model were established in 615 mice by splenic injection of proventriculus squamous carcinoma cell(MFC).Among them,sixty mice were divided randomly into 6 groups(ten per group): control(NS),GH1,GH2,flurouracil(5-FU),flurouracil plus rhGH(GH1+5-FU) and flurouracil plus rhGH(GH2+5-FU).Body weights were measured every week.On the 28~(th) day,animals in each group were executed.The weight of body and liver was measured,and cell cycle of tumor DNA was determined by flow cytometry(FCM). Other 48 animals were divided randomly into 6 groups(eight per group) and treated with the same methods as above.They were fed till death to observe survival time. Results:Body weights in the GH1+(5-FU) and the GH2+5-FU group were increased than that of control group(P

0.05).Conclusion: rhGH can stimulate the growth of GHR2+ tumor cell lines such as SGC-7901 and weaken the inhibitory effect of 5-FU on GHR2+ tumor cells.However,such effect was not remarked for GHR+ tumor cells in vitro.

Objective:To investigate the effect of O-6-methylguananine-DNA methyltransferase (MGMT) gene promoter methylation status on the treatment and prognosis of elderly patients newly-diagnosed with glioblastoma (GBM).Methods:Clinical data of 65 newly-diagnosed GBM patients admitted to Tianjin Huanhu Hospital from January 2012 to December 2018 were retrospectively analyzed. All patients received intensity-modulated radiotherapy after surgery and 49 patients received temozolomide (TMZ) monotherapy. All patients were divided into the MGMT(+ ) group and MGMT(-) group according to the methylation status of MGMT promoter. Kaplan- Meier method and log-rank test were used for univariate survival analysis, and Cox regression model was used for multivariate prognostic analysis. Results:The median overall survival (OS) for all patients was 18.0 months. The median OS was 27.0 months and 15.3 months in the MGMT(+ ) group and MGMT(-) group, respectively. Univariate analysis revealed that tumor number, MGMT promoter methylation, postoperative concurrent chemoradiotherapy were significantly related to clinical prognosis ( P=0.029, P=0.001 and P<0.001). In multivariate analysis, tumor number and postoperative concurrent chemoradiotherapy were identified as significant prognostic factors for OS ( P=0.037, P=0.004). In the MGMT(+ ) group, the median OS was 27.0 months for patients receiving concurrent chemoradiotherapy and 12.0 months for radiotherapy alone ( P=0.040). In the MGMT(-) group, the median OS was 17.0 months for concurrent chemoradiotherapy patients and 10.0 months for radiotherapy alone ( P=0.122). Conclusions:MGMT promoter methylation status is significantly associated with longer OS in elderly GBM patients. Conventional fractional radiotherapy combined with concurrent and sequential TMZ chemotherapy probably yields better survival benefits.

Objective To investigate the effect of celastrol on space learning capability and expressions of beta-amyloid (Aβ) 40 and Aβ42 in hippocampus in APPswe/PS1dE9 double transgenic mouse after partial hepatolobectomy.Methods The 3-month-old APPswe/PS1dE9 double transgenic mice (n =96) were randomly divided into three groups according to the random number table method.Surgery group (group S, partial hepatolobectomy;n =32), celastrol group (group C, injections of dimethyl sulphoxide/DMSO and celastrol for 3 days before undergoing partial hepatectomy, on the surgery day, and for a further 4 days after surgery;n =32), and DMSO group (group D, injections of DMSO for 3 days before undergoing partial hepatectomy, on the surgery day, and for a further 4 days after surgery;n =32).Eight mice were selected randomly in each group and were Morris-water maze trained for continuous 5 days.Theirs learning and memory abilities were evaluated at 1,3, 7 and 14 d after surgery, respectively.Hippocampus was collected and the changes of β40 and Aβ42 were measured by enzyme-linked immunosorbent assay (ELISA) at the time set in advance in each group.Results The average escape latency of group C was significantly shorter than groups S and D at 3, 7 and 14 d after partial hepatectomy (P ＜ 0.05).Times of passing through the platform groups S and D were significantly less than group C (P ＜ 0.05).The expressions of Aβ40/Aβ42 in group C were lower than group S and group D at 1, 3, 7 and 14 d after partial hepatectomy (P ＜ 0.05).Conclusions Through decreasing the expressions of Aβ40 and Aβ42 in hippocampus,celastrol improves the space learning capability in APPswe/PS1dE9, the double transgenic mouse after partial hepatolobectomy.

Objective To investigate changes of coagulation function in patients with high altitude polycythemia (HAPC) .Meth‐ods Activated partial thromboplastin time (APTT) ,prothrombin time (PT) ,thrombin time (TT) and fibrinogen (Fbg) were de‐tected and compared between 69 patients with HAPC and 60 healthy subjects (controls) .Results Fbg ,APTT and TT levels in pa‐tients with HAPC were higher than controls (P<0 .05) ,while the difference of PT was not significant (P>0 .05) .Dynamic obser‐vation indicated that comprehensive therapy could these recover coagulation function .Conclusion Hemorrhage and coagulation process in patients with HAPC could be very complicated ,including physiological adaptation and the process of physiology evolving into pathology .

Objective To investigate the effect of immune modulation therapy on heart function and cytokines in elder patients with chronic heart failure (CHF). Methods The 96 patients aged 60-78 years with New York Heart Association(NYHA)functional. class Ⅱ-Ⅳ CHF were randomly divided into two groups: CHF treatment group received regular therapy and thymopetidum and CHF control group received regular therapy. Another 45 healthy individuals aged 60-80 years were involved as normal control. The ejection faction of left ventricle (LVEF), inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), anti-inflammatory cytokine interleukin-10 (IL-10), plasma high sensitive C-reactive protein (hsCRP), plasma brain natrium peptide (BNP)and Minnesota Living with Heart Failure Questionnaire (LHFQ) assessment were tested before therapy, 15 days and 75 days after treatment. Results (1) Before therapy, compared with normal control group, the levels of TNF-α, IL-1β, TNF-α/IL-10 ratio, BNP, hsCRP and LHFQ were significantly increased (P ＜ 0. 05 or P ＜ 0. 01 ), and the levels of IL-10, LVEF were markedly decreased (P＜0.01) in the patients of CHF treatment group and CHF control group. While no difference between the two CHF groups was observed. (2) After the first course of treatment,compared with CHF control group, the levels of IL-10 were increased (P＜0. 01), while the levels of TNF-α, IL-1β, BNP and hsCRP were decreased (P＜0.05 or P＜0.01) in CHF treatment group. The level of LVEF was increased, TNF-α/IL-10 ratio (4.84 ±0. 53 vs. 5.28±0. 66) and LHFQ were decreased even though there was no significant difference between the two groups. (3) After the second course of treatment, compared with CHF control group, the levels of IL-10 and LVEF were increased (P＜0. 05 or P＜0.01), while the level of TNF-α, IL-1β, TNF-α/IL-10 ratio (4.55±0. 69 vs. 5.18±0.38), BNP, hsCRP and LHFQ were decreased (P＜0.05 or P＜0.01) in CHF treatment group. Conclusions Thymopetidum, as an immunemodulating agent, might regulate the equilibrium of cytokines and improve the heart function of patients with CHF, indicating that immune modulation therapy might improve the treatment strategy for CHF patients.

Objective To observe the effects of rosuvastatin on the homocysteine (Hcy)-induced expression of matrix metalloproteinase 2 (MMP 2) and cell migration in rat vascular smooth muscle cells (VSMCs), and to explore the possible mechanism of Hcy-induced atherosclerosis and the role of statins in reversing atherosclerosis. Methods In one cell culture plate, the cultured rat VSMCs were incubated with different concentrations of Hcy (0, 50, 100, 500, 1000 μmol/L and 5000 μmol/L) in vitro for 24 h, 48 h and 72 h. And in another cell culture plate, the different concentrations of rosuvastatin (10-9, 10-8, 10-7, 10-6, 10-5 mol/L and 0 mol/L) were added to the cultured rat VSMCs (while the concentration of Hcy was 1000 μmol/L). The MMP 2 expression and enzyme activity were determined by gelatin zymography and Western blotting. The effects of Hcy and rosuvastatin on cell migration and invasiveness of VSMCs were observed. Results Hcy (50-5000 μmol/L) increased the protein expression, and Hcy (50-1000 μmol/L) increased enzyme activity of MMP 2 significantly. But Hcy (5000 μmol/L) inhibited activity of MMP 2 (F=9.31, 6.44 and 5.97, all P＜0.05). Rosuvastatin (10-9-10-5 mol/L) inhibited Hcy-induced expression and enzyme activity increasing of MMP 2. The counts of cell migration of VSMCs were 18.32±2.17, 32.68±4.34, 44.75±4.08, 61.39±5.21, 79.74±5.54 and 90.78±5.83, while the concentration of Hcy was 0, 50, 100, 500, 1000 μmol/L and 5000 μmol/L respectively (F=5.31, P＜0.05). The counts of cell migration of VSMCs were 79.74±5.54, 62.53±6.41, 48.37±5.66, 31.41±4.79, 19.27±3.62 and 11.17±2.33, while the concentration of rosuvastatin was 10-9, 10-8, 10-7, 10-6 and 10-5 mol/L respectively (F=4.99, P＜0.05). Rosuvastatin could decrease the stimulation of Hcy-induced migration of VSMCs. Conclusions Hcy can influence the MMP 2 protein expression/activity in VSMCs, and rosuvastatin can inhibit augmentation of Hcy-induced MMP 2 expression/activity and migration of VSMCs. It may be one of the multiple-effects of rosuvastatin reducing atherosclerosis.

Aim To investigate the anti-tumor effects of FS-108 an Hsp90 inhibitor, on oncogene addicted EBC-1 and A375 cells. Methods SRB assay was performed to investigate cell proliferation. Immunoblot was conducted to investigate the specific proteins. FACS was conducted to test cell cycle distribution and apoptosis. Transwell assay was conducted to investigate cell motility. Results FS-108 significantly suppressed cell proliferation of EBC-1 and A375 cancer cells with IC50 at 25. 53 nmol · L-1 and 30. 02 nmol · L-1 re-spectively. FS-108 treatment triggered the degradation of key client proteins such as c-Met and B-Raf and thereby reduced their downstream AKT and ERK signa-ling pathways. The FACS analysis results demonstrated that FS-108 treatment induced G2/M phase arrest and apoptosis significantly. Furthermore, FS-108 inhibited the migration of EBC-1 and A375 cells. Conclusion As a potent Hsp90 inhibitor, FS-108 can inhibit onco-gene addicted cancer cells proliferation through induc-tion of G2/M phase arrest and apoptosis.