Genetic associations with sporadic neuroendocrine tumor risk

Genetic risk factors for sporadic neuroendocrine tumors (NET) are poorly understood. We tested risk associations in patients with sporadic NET and non-cancer controls, using a custom array containing 1536 single-nucleotide polymorphisms (SNPs) in 355 candidate genes. We identified 18 SNPs associated with NET risk at a P-value <0.01 in a discovery set of 261 cases and 319 controls. Two of these SNPs were found to be significantly associated with NET risk in an independent replication set of 235 cases and 113 controls, at a P value ≤0.05. An SNP in interleukin 12A (IL12A rs2243123), a gene implicated in inflammatory response, replicated with an adjusted odds ratio (95% confidence interval) (aOR) = 1.47 (1.03, 2.11) P-trend = 0.04. A second SNP in defender against cell death, (DAD1 rs8005354), a gene that modulates apoptosis, replicated at aOR = 1.43 (1.02, 2.02) P-trend = 0.04. Consistent with our observations, a pathway analysis, performed in the discovery set, suggested that genetic variation in inflammatory pathways or apoptosis pathways is associated with NET risk. Our findings support further investigation of the potential role of IL12A and DAD1 in the etiology of NET.     

纳米Ag-SiO2导尿管的细胞毒性评价

背景:具有抗菌活性的纳米Ag-SiO2导尿管可有效降低普通医用导尿管相关性尿路感染的发生率,其物理、化学性质发生很大变化,所以对其安全性需重新评价。目的:比较纳米Ag-SiO2导尿管和普通医用导尿管浸提液对兔尿道上皮细胞的体外细胞活性影响,初步评价纳米Ag-SiO2导尿管的生物安全性。方法:应用机械分离与酶消化法分离培养兔尿道上皮细胞,在体外行扩增后制成细胞悬液,将培养液更换为浸泡纳米Ag-SiO2导尿管及普通导尿管的培养液,采取四甲基偶氮唑盐比色法量化两组浸提液对兔尿道上皮细胞的体外细胞毒性。用酶联免疫检测仪分别测定两组体外细胞的吸光度值,并计算其相对增殖率(RGR),进行毒性评价及比较。结果与结论:纳米Ag-SiO2导尿管和普通医用导尿管均毒性轻微。纳米Ag-SiO2导尿管与普通医用导尿管相对增殖率均数间背景:具有抗菌活性的纳米Ag-SiO2导尿管可有效降低普通医用导尿管相关性尿路感染的发生率,其物理、化学性质发生很大变化,所以对其安全性需重新评价。目的:比较纳米Ag-SiO2导尿管和普通医用导尿管浸提液对兔尿道上皮细胞的体外细胞活性影响,初步评价纳米Ag-SiO2导尿管的生物安全性。方法:应用机械分离与酶消化法分离培养兔尿道上皮细胞,在体外行扩增后制成细胞悬液,将培养液更换为浸泡纳米Ag-SiO2导尿管及普通导尿管的培养液,采取四甲基偶氮唑盐比色法量化两组浸提液对兔尿道上皮细胞的体外细胞毒性。用酶联免疫检测仪分别测定两组体外细胞的吸光度值,并计算其相对增殖率(RGR),进行毒性评价及比较。结果与结论:纳米Ag-SiO2导尿管和普通医用导尿管均毒性轻微。纳米Ag-SiO2导尿管与普通医用导尿管相对增殖率均数间差别无显著性意义(P>0.05)。结果表明,纳米Ag-SiO2导尿管对细胞的生长繁殖同普通医用导尿管一样影响轻微,无(或)低细胞毒性,符合医疗器械生物学评价标准要求。     

5,10-亚甲基四氢叶酸还原酶基因多态性及补充叶酸与非综合征性唇腭裂的相关性

背景：对于5, 10-亚甲基四氢叶酸还原酶(5, 10-methylene tetrahydrofolate reductase, MTHFR)基因C677T位点多态性与唇腭裂相关性的研究国内外结果不一,未见结合干预因素叶酸影响的相关报道。 目的：探讨河南地区汉族人群MTHFR基因C677T位点多态性及补充叶酸与非综合征性唇腭裂的发病关系。 方法：选取2008-09/2010-03在郑州大学第一附属医院及郑州市第一人民医院整形外科就诊的非综合征性唇腭裂患者110例,采用PCR-RFLP法检测外周血中MTHFR基因C677T位点基因型并与40例健康对照比较频数差异。同时结合母孕期是否补充叶酸进行统计学分析。 结果与结论：病例组和对照组C677T基因型及等位基因频率比较差异均具有显著性意义(P < 0.01),且有家族史的患者TT基因型及T等位基因频率高于无家族史患者(P < 0.05)。对母孕期是否补充叶酸进行比较,发现非综合征性唇腭裂与叶酸摄入呈负相关(χ2=4.304,r=-0.169,P < 0.05)。结果提示MTHFR基因C677T位点突变与河南汉族人群非综合征性唇腭裂的发生相关,母孕期补充叶酸能降低非综合征性唇腭裂的发病风险。     

Entry of hepatitis B virus: Mechanism and new therapeutic target

Entry of hepatitis B virus (HBV) into human hepatocytes constitutes the initial step in viral infection. The study of HBV entry had long been hampered by the lack of efficient cell culture systems and small animal models. The situation was greatly improved in the last decade with the development of HBV-infectible HepaRG cell line and primary Tupaia hepatocyte culture. Armed with these new tools, marked progresses have been achieved in the elucidation of the mechanism of HBV entry. Plenty of evidences indicate that the viral large surface protein (LHBs) is essential for HBV entry. Several regions in the PreS1 domain of LHBs have been verified to contribute directly to the viral attachment. In addition, a myristate moiety linked to the N-terminal glycine of PreS1 appears critical for HBV infectivity. Recently, the cysteine-rich antigenic loop of the S domain was identified as another crucial determinant for HBV infectivity. On the other hand, several cellular proteins were implicated in HBV attachment to hepatic cells, though definitive proofs are required in support to their functional involvement in HBV infection. Aiming to blocking viral entry, a couple of approaches based on acylated PreS1-derived peptides and short PreS1-binding peptides are currently under investigation, which have the potential to become novel antiviral therapeutics.