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 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

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.

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

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.

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.

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%.

Background Extranodal natural killer/T-cell (NK/T cell) lymphoma,nasal-type,is a rare lymphoma.Skin is the second most common site of involvement after the nasal cavity/nasalpharynx.The aim of this study was to investigate the clinicopathologic features,immunophenotype,T cell receptor (TCR) gene rearrangement,the association with Epstein-Barr virus (EBV) infection and p53 gene mutations of the lymphoma.Methods The clinicopathologic analysis,immunohistochemistry,in situ hybridization for EBER1/2,TCR gene rearrangement by polymerase chain reaction (PCR),mutations of p53 gene analyzed by PCR and sequence analysis were employed in this study.Results In the 19 cases,the tumor primarily involved the dermis and subcutaneous layer.Immunohistochemical staining showed that most of the cases expressed CD45RO,CD56,CD3ε,TIA-1 and GrB.Three cases were positive for CD3 and two cases were positive for CD30.Monoclonal TCRY gene rearrangement was found in 7 of 18 cases.The positive rate of EBER1/2 was 100％.No p53 gene mutation was detected on the exon 4-9 in the 18 cases.Fifteen cases showed Pro (proline)/Arg (arginine) single nucleotide polymorphisms (SNPs) on the exon 4 at codon 72.The expression of p53 protein was 72％ (13/18) immunohistochemically.Conclusions Cutaneous NK/T-cell lymphoma is a rare but highly aggressive lymphoma with poor prognosis.No p53 gene mutation was detected on the exon 4-9,and Pro/Arg SNPs on p53 codon 72 were detected in the cutaneous NK/T-cell lymphoma.The overexpression of p53 protein may not be the result of p53 gene mutation.