The aim of this study was to investigate and evaluate the antitumor effects of a novel poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor, YHP-836, in combination with temozolomide (TMZ) for the treatment of glioblastoma (GBM). The cytotoxicity of YHP-836 was tested alone or in combination with TMZ using MTT assay. Immunoblotting and flow cytometry were also employed to assess the combination activity of YHP-836 and TMZ in multiply GBM cell lines. Further, the antitumor activity of YHP-836 and TMZ was evaluated using subcutaneous and orthotopic mice xenograft tumor models. All procedures were approved by the Ethics Committee for Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and conducted under the Guidelines for Animal Experiments of Peking Union Medical College. The approval number is 00009138. It was demonstrated that the combination of YHP-836 and TMZ increased the cytotoxicity against GBM cells and upregulated histone H2AX phosphorylation (γH2AX) expression levels compared to TMZ treatment alone. The combination also led to the S-phase cell cycle arrest. Moreover, YHP-836 significantly enhanced TMZ antitumor effects without significantly increasing chemotherapy drug toxicity in vivo, whereas YHP-836 alone showed limited therapeutic efficacy against GBM. In conclusion, the novel PARP1/2 inhibitor, YHP-836, sensitizes TMZ and provides a basis for further investigation into its mechanism of action. These findings suggest that YHP-836 may be a potential candidate for combination therapy with TMZ in patients with TMZ resistance.

Objective To evaluate retrospectively the role of 18 F-fluorodeoxyglucose (FDG) PET/CT associated with MRI in the localization of epileptogenic foci. Methods Sixty-seven patients with medically resistant epilepsy were included from 2003 to 2008. All underwent 18F-FDG PET/CT and MRI for presurgical evaluation as well as post-surgical evaluation 12 to 65 months after operation. Based on postoperative seizure occurrence, patients were divided into two groups. One group was free of seizures ( Engel classification Ⅰ, Group 1) and the other was with postoperative seizure occurrence of any type ( Engel classification Ⅱ-Ⅳ, Group 2). X2-test or Fisher's exact test was used for the statistical analysis. Results About 71.6% (48/67) patients were defined as group 1, and 19 patients were group 2 ( 11 were Engel Ⅱ , 5 were Engel Ⅲ, and 3 were Engel Ⅳ ). In Group 1, no statistically significant difference was found between concordant (45/63) and discordant findings (3/4) with regard to 18F-FDG PET/CT and MRI images (Fisher's exact test, P ＞0.05). For 41 patients that showed focal abnormality both on MRI and 18F-FDG PET/CT, 80.5% (33/41) were found in group 1. For 20 patients that showed focal lesions on MRI while with multi-focal or generalized abnormal metabolism on 18F-FDG PET/CT, 11 (55.0%) were in group 1 and9 (45.0%) were group 2. There was no significant difference (33/41 vs 11/20, X2 =4.34, P ＜0.05 ). Conclusion 18F-FDG PET/CT associated with MRI may offer more helpful information for pre-surgical evaluation and prediction of prognosis of epileptic patients.

Objective To assess the efficacy and safety of topiramate monotherapy in the treatment of alcohol de?pendence. Methods The Cochrane library, PunMed, EMBase, CNKI, VIP and CBM database were searched to collect the randomized contolled trials (RCTs) of topiramate monotherapy to compare with placebo or positive control drug in al?cohol dependence. Data were extracted from the included literatures after the literatures’qualities were assessed. The meta-analyses were conducted with RevMan 5.2 software. Results Thirteen trials were included. Compared with place?bo, topiramate reduced score of obsessive compulsive drinking scale(MD=-5.90,95%CI:-10.99~-0.82,P=0.02), de?creased drinks per drinking day(MD=-6.94,95%CI:-12.20~-1.68,P=0.01), and increased percentage of days absti?nent(MD=15.36,95%CI:4.15~6.56,P<0.01). The incidence of paraesthesia, taste perversion, weight loss, memory or concentration impairment, dizziness, psychomotor retardation in topiramate group was higher. But the incidence of other adverse events was similar between groups. Compared with naltrexone, topiramate significantly postponed the days to first relapse(MD=2.10,95%CI:0.23~3.97,P=0.03). The adverse events were similar between groups. Conclusions Topira?mate in treatment of alcohol dependence is effective and safety.

Objective To study the relationship between expression of CD44v6 in gastric carcinoma and neoplasm metastasis and prognosis. Methods Expression of CD44v6 in 52 cases of gastric carcinoma was assayed by flow immunocytometry, and its relation with clinical pathology and prognosis was analyzed. Results In 52 cases of gastric carcinoma tissue, the positive rate of CD44v6 expression was 67.31%(35/52); but the positive rate of CD44v6 expression in normal gastric tissue was 25.00% (13/52). The positive rate of expression was significantly different (P

Aged ; Coal Mining ; Electrocardiography ; Heart Rate ; Humans ; Male ; Middle Aged ; Pneumoconiosis ; complications ; physiopathology ; Tachycardia ; etiology

AIM To compare the contents of benzoyl mesaconitine,benzoyl hypaconitine,benzoyl aconitine,aconitine,hypaconitine and mesaconitine in Zingiberis Rhizoma Recens boiled juice-processed,Zingiberis Rhizoma boiled juice-processed,Zingiberis Rhizoma Recens juicing-processed,Zingiberis Rhizoma Recens slice malaxation steaming,and Zingiberis Rhizoma slice malaxation steaming Aconiti lateralis Radix Praeparata.METHODS Acid-base titration method was adopted in the content determination of total alkaloids.HPLC was applied to determining the contents of six alkaloids,the analysis was performed on a 35 ℃ thermostatic Waters Symmetry(C)C1scolumn (4.6 mm × 250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.04 mol/L ammonium acetate flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 235 nm.RESULTS The contents of total alkaloids and diester-type alkaloids (mesaconitine,aconitine and hypaconitine)in various processed products,especially for Zingiberis Rhizoma Recens slice,Zingiberis Rhizoma slice malaxation steaming products,were obviously lower than those in the raw product.The contents of benzoyl hypaconitine and benzoyl aconitine in Zingiberis Rhizoma slice malaxation steaming product were the lowest,while that of benzoyl mesaconitine in the raw product was the lowest.CONCLUSION Compared with other Zingiber-processing methods,both Zingiberis Rhizoma Recens slice and Zingiberis Rhizoma slice malaxation steaming can reduce the toxicity of Aconiti lateralis Radix Praeparata more effectively.

Objective To investigate the clinical value of cardiac troponin Ⅰ(cTnⅠ) and creatinine kinase MB(CK-MB) in early diagnosis of myocardial injury(MCI) in neonatal asphyxia.Methods The serum cTnⅠ and CK-MB in neonates [34 with asphyxia and MCI,38 with asphyxia but no MCI(NMCI)],and 30 cases of normal control(NC) were measured with direct immunoassay chemiluminometric technology and immunoinhibition enzymes-activated assay.Results The cTnⅠ level in NC group had no changes within 10 days after birth,MCI group were significantly higher than those in NMCI and NC groups(all P0.05).The diagnostic sensitivity,specificity and accuracy of cTnⅠ for neonates with MCI were 91%,88% and 89%,respectively;and of CK-MB were 85%,68% and 74%,respectively.Conclusions cTnⅠ and CK-MB can be taken as early diagnostic markers of MCI in neonates with asphyxia,(cTnⅠ) is better than CK-MB.

Objective To study the results of functional hemispherectomy for pediatric intractable epilepsy with hemisphere lesions , and to explore the indications of functional hemispherectomy , as well as the prognosis. Methods Twenty-four children with intractable epilepsy caused by hemisphere lesions were included , who underwent functional hemispherectomy. All patients were followed up for 3 ~ 48 months. Results All 24 cases obtained improvement of abnormal behavior , and no significant exacerbation of neurological deficits was observed. During the follow-up, 18 cases were in EngelⅠ(75%), 5 in Engel Ⅱ(21%), and 1 in Engel Ⅰ(4%) respectively. No long-term complication was observed. Conclusion Comprehensive presurgical evaluation is a prerequisite for the surgical treatment of pediatric intractable epilepsy caused by hemisphere lesions. Functional hemispherectomy can effectively control seizures and obviously improve the prognosis.

Introduction:The 2010 targets of the China Hepatitis B Prevention Programme were a prevalence of hepatitis B surface antigen (HBsAg) less than 1.0% for children less than five years old and less than 6.0% for the total population. This survey assessed the prevalence of Hepatitis B infection in Lianyungang, Jiangsu province, China in 2009–2010.Methods:Multistage sampling was used with 2372 subjects among 17 selected villages. Blood specimen collection and testing by enzyme-linked immunosorbnet assay (ELISA) were completed using the following markers for hepatitis infection: HBsAg and antibody to HBsAg (anti-HBs); hepatitis B e antigen (HBeAg) and antibody to HBeAg (anti-HBe); and hepatitis B core antibody (total anti-HBc). The data were analysed with Epi Info, version 3.3.2.Results:The prevalence of HBsAg was 2.4% (95% Confidence Interval [CI]: 1.8–3.0; Adjusted Prevalence [AP] 2.9%); anti-HBs prevalence was 51.1% (95% CI: 49.1–53.1; AP 49.2%) and total anti-HBc prevalence was 41.7% (95% CI: 39.8–43.7; AP 45.5%). The prevalence of HBsAg and total anti-HBc positivity increased from young to older age groups, yet the prevalence of anti-HBs positivity decreased from young to older age groups (P< 0.001 for all). There was no difference in the prevalences of HBsAg and anti-HBs among females and males (P= 0.108 and 0.089), but females had a higher prevalence than males for total anti-HBc positivity (P< 0.001). Discussion: This survey showed that in 2010 the prevalence of HBsAg among children aged less than five years was lower than the national target of 1.0% and that the prevalence of HBsAg for the total population was lower than the national target of 6.0%.

Objective To observe the protein expression of Notch 1 in the cultured calcified human heart valve interstitial cells (hVICs) in vitro and related mechanisms.Methods hVICs were divided into two groups:control hVICs were cultured in conventional media for 14 days and calcified hVICs were cultured with calcification inducers:[3-glycerophosphate (500 μl),ascorbic acid (200 μl),dexamethasone (100 μl) for 7 days.The calcified hVICs were further divided into calcified hVICs group and inhibited calcified hVICs by adding specific Notch1 inhibitor DAPT (50 μmol/L(4 μl/hole))groups and cultured for another 7 days.Inflammatory response of all groups were induced by lipopolysaccharide (LPS) for 8 to 12 hours.Western blot was used to detect the protein expression of Notch1,phosphorylation nuclear transcription factor κB (p-NF-κB),bone morphogenetic protein-2/4(BMP-2/4).ELISA was applied to detect the content of BMP-2 secretion of the groups.Von Kossa staining was used to observe of cellular calcification.Results (1)Von Kossa staining is positive in the induced calcification group,the expression of Notch1,p-NF-κB,BMP-2 and BMP-4 is significantly higher in the induced calcification group than in the control group (all P ＜ 0.05).The expression of BMP-2 is significantly higher in the induced calcification group than in control group ((88.23 ± 3.28) pg/ml vs.(25.41 ± 3.68) pg/ml,P =0.02).(2) After treatment with DAPT,the calcification and the expression of Notch1,p-NF-κB,BMP-2 and BMP-4 were significantly decreased compared to calcification group (all P ＜ 0.05).The expression of BMP-2 is (26.74 ± 4.62) pg/ml in the calcification inhibition group and (80.41 ± 2.96) pg/ml in calcified control group (P =0.02).Conclusions Upregulated Notch 1 expression promotes BMP-2/4 secretion in LPS stimulated hVICs,and contributes to osteogenic changes in hVICs.Inhibiting Notch1 can decrease the BMP-2/4 secretion and calcification in hVICs,which may serve as a novel therapeutic option for treating calcific valve disease.