黏病毒抗性蛋白A基因多态性与HBV感染转归的关系

目的 探讨干扰素诱导的黏病毒抗性蛋白A(MxA)基因单核苷酸多态性(SNP)对乙型肝炎病毒(HBV)感染自然转归的影响.方法 收集湖北地区160例HBV自限感染者和243例慢性HBV感染者的外周血标本,应用聚合酶链反应-限制性片段长度多态性分析方法,检测MxA启动子-88,-123位点基因型.结果 MxA启动子-88G/T位点基因型和等位基因在慢性HBV感染者和自限性感染者中的分布差异有高度显著性.HBV自限性感染者MxA启动子-88位点GG基因型和G等位基因频率分别为41.3%和62.8%,均较慢性感染者频率52.7%和74.9%低(P=0.025和P= 0.001),而TT基因型和T等位基因频率分别为15.6%和37.2%,均较慢性感染者频率2.9%和25.1%高(P=0.000和P= 0.001),比值比为6.24,95%可信限2.63～14.81.然而,MxA启动子-123位点不同基因型和等位基因在HBV自限性感染组和慢性感染组间的分布频率差异均无统计学意义(P＞0.05).结论 MxA启动子-88G/T位点多态性与HBV感染后的结局有关,其中TT基因型或T等位基因的存在可能有利于HBV感染后的清除.     

MxA-88G／T和IFN-γ＋874 A／T位点多态性对地方流行区HBV感染自然转归的影响

目的:探讨常见影响乙型肝炎病毒(HBV)感染自然转归的宿主遗传因素在地方性流行区的作用。方法:收集华南地区100例HBV自限感染者(抗-HBs和抗-HBc均阳性)和340例慢性HBV感染者的外周全血,采用竞争分化聚合酶链反应技术为基础的方法进行MxA-88G/T和IFN-γ 874A/T基因分型。结果:MxA-88G/T的基因型在慢性HBV感染者和自限性感染者中的分布差异有高度显著性;与慢性感染患者相比,自限性感染者有较低的GG基因型(41.0%vs52.9%,P=0.036)和较高的TT基因型(16.0%vs2.4%,P=0.000)。然而,IFN-γ 874A/T的基因型在两组患者中的分布差异并无显著性;在慢性感染者和自限性感染者中,AA基因型分布率为65.0%vs72.8%(P=0.139),TT基因型为2.0%vs1.2%(P=0.894)。结论:常见影响HBV感染自然转归的宿主基因多态性在地方性流行区的作用有所改变,值得同类研究高度注意。     

云南三民族人群eNOS G894T多态性与HBV感染的相关性研究

目的:分析云南省西双版纳基诺族、傣族和僾尼族人群eNOS G894T多态性与HBV感染的相关性。方法:采用整群随机抽样的方法运用PCR-RFLP方法对三民族人群eNOS G894T位点进行基因分型。结果:(1)僾尼族人群HBV感染率显著高于基诺族及傣族(P均为0.000)。(2)僾尼族人群eNOS G894T位点基因型与等位基因分布频率与其他两民族显著不同(P均小于0.005),GG基因型与G等位基因频率降低,而TT基因型与T等位基因频率升高。(3)HBV感染组eNOS G894T位点GG基因型与G等位基因频率显著低于正常对照组,而TT基因型与T等位基因频率显著高于HC组(P均为0.000)。(4)以非条件logistic回归校正混杂因素后,在G隐性模式下,HBV感染组与正常对照组差异有显著性意义(P为0.000;OR为0.311;95%CI为0.179～0.540)。结论:eNOS G894T基因型和等位基因频率具有民族差异,并且其多态性与HBV感染密切相关,基因型为GG纯合子的个体降低了HBV感染风险。     

海南黎族2型糖尿病患者Calpain-10基因多态性的实验研究

目的 研究中国海南黎族2型糖尿病（T2DM）Calpain-10基因多态性,旨在探讨其与T2DM发病易感性之间的关系.方法 采用病例对照研究方法及聚合酶链反应（PCR）技术,对57例T2DM组和52例正常对照组（NC） Calpain-10基因UCSNP-43、UCSNP-44多态性进行基因分型并计算其优势等位基因频率.结果 T2DM组UCSNP-43 GG基因型占88%, G等位基因频率为93%;UCSNP-44 TT基因型占80%,T等位基因频率为89%;正常对照组UCSNP-43 GG基因型占82%,G等位基因频率为90%;UCSNP-44 TT基因型占78%,T等位基因频率为88%.经卡方检验,T2DM和NC组UCSNP-43位点G等位基因和UCSNP-44位点T等位基因频率之间差异无统计学意义（P〉0.05）.结论 本研究未发现Calpain-10基因UCSNP-43和UCSNP-44位点变异与T2DM发病相关,提示Calpain-10基因UCSNP-43和UCSNP-44可能并非海南黎族人群中T2DM 常见相关发病基因.     

IFN-γ基因+874位点单核苷酸多态性与乙型肝炎病毒感染关系的研究

【目的】研究干扰素（IFN-γ）基因＋874位点单核苷酸多态性与乙型肝炎病毒（HBV）感染、转归的关系,探讨HBV感染的遗传易感因素。【方法】采用序列特异性引物-聚合酶链反应（PCR—SSP）技术检测231例慢性HBV感染者、165例自限性HBV感染者和135名正常对照者IFN-γ基因第一内含子＋874位点T／A单核苷酸多态性。【结果】慢性HBV感染组IFN-γ基因＋874位点AA基因型频率（78．8％）显著高于正常对照组（64．4％）（x^2=9．60．P=0．008）,而自限性HBV感染组（62．4％）和对照组之间差异无显著性（x^2=0．16,P=0．92）。进一步比较慢性HBV感染者IFN-γ基因＋874住点单核苷酸多态性与HBV—DNA复制的关系,发现IFN-γ基因＋874住点基因型和等住基因频率在低水平HBV-DNA组和高水平HBV-DNA组之间的分布差异无显著性。【结论】IFN-γ基因第一内含子＋874位点多态性与慢性HBV感染有关,提示该位点多态性可能在决定个体HBV感染遗传易感性方面有一定意义。     

IL-10基因启动子区-592A/C位点多态性与HBV感染转归的关系

目的探讨汉族人白细胞介素-10(IL-10)基因启动子区-592位点单核苷酸多态性与乙型肝炎病毒(HBV)感染、转归的关系。方法采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)方法,检测231例HBV感染者,165例HBV感染康复者和135例正常对照者IL-10基因启动子区-592A/C位点基因型。结果IL-10基因启动子区-592A/C位点基因型和等位基因在HBV感染组、HBV感染康复组和正常对照组之间的分布频率比较差异无显著性(P>0.05),在血清HBV-DHA<1×103copies/ml的HBV感染者组和HBV-DHA≥1×103copies/ml组之间的分布频率比较差异亦无显著性(P>0.05);但IL-10基因启动子区-592A/C位点AA基因型和A等位基因在慢性乙型肝炎组出现的频率明显高于HBV无症状携带组,两组之间分布比较差异有显著性(P<0.05)。结论汉族人IL-10基因启动子区-592A/C位点多态性可能与人群对HBV易感性及感染后的病毒血症水平无显著相关性,但该位点基因多态性与HBV感染后的肝脏炎症反应有关。     

IL-10基因启动子-592A/C多态性与HBV感染预后的关系

摘 要 目的：探讨湖北汉族人白细胞介素-10（IL-10）基因启动子区-592位点单核苷酸多态性与乙型肝炎病毒（HBV）感染、转归的关系。方法：采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）方法，检测231例慢性HBV感染者（其中慢性乙型肝炎75例，无症状携带156例），165例HBV感染自愈者和135例正常对照者IL-10基因启动子区-592A/C位点基因型。结果：IL-10基因启动子区-592A/C位点基因型和等位基因在慢性HBV感染组、HBV感染自愈组和正常对照组之间的分布频率比较差异无显著性（P>0.05），在血清HBV-DNA<1×103copies/mL的慢性HBV感染者组和HBV-DNA≥1×103 copies/mL组之间的分布频率比较差异亦无显著性（P>0.05）；但IL-10基因启动子区-592位点AA基因型和A等位基因在慢性乙型肝炎组出现的频率明显高于HBV无症状携带组，两组之间分布比较差异有显著性（P<0.05）。结论：汉族人IL-10基因启动子区-592位点多态性可能与人群对HBV易感性及感染后的病毒血症水平无显著相关性，但该位点基因多态性与HBV感染后的肝脏炎症反应有关。≥≥≥≥≥     

基质金属蛋白酶-2组织抑制剂基因多态性与慢性阻塞性肺病易感性研究

目的:研究基质金属蛋白酶-2组织抑制剂(tissue inhibitor of metalloproteinases-2,TIMP-2)基因多态性与慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)易感性.方法:采用聚合酶链反应-限制性酶切片段长度多态性(PCR-RFLP)方法检测92例COPD患者(COPD组)及80例健康对照者(对照组)TIMP-2基因启动子区域(-418位点)和外显子3区域(+853位点)单核苷酸多态性(SNPs),统计各基因型频率进行分析比较.结果:TIMP-2基因+853位点COPD组基因型频率为G/G 83.7%、G/A 15.2%、A/A 1.1%,基因型分布两组间差异有显著性(P=0.002);等位基因G在COPD组为91.3%,对照组为78.1%.等位基因频率相比两组差异有显著性(P=0.001);-418位点基因型和等位基因频率分布在两组间差异无显著性(P＞0.05).结论:(1)TIMP-2基因+853位点G/A等位基因改变在吸烟时与COPD易感性相关.(2)TIMP-2基因-418住点等位基因G/C的改变与COPD易感性无关.     

白细胞介素27启动子多态性与慢性乙型肝炎病毒感染的相关性研究

目的探讨慢性乙型肝炎病毒感染与白细胞介素27 p28基因启动子区-964A/G多态性的关系。方法采用聚合酶链式反应限制性内切酶长度多态性(PCR-RFLP)技术对168例慢性乙型肝炎感染者和152例健康对照者白细胞介素27 p28启动子区-964A/G多态性进行分析,酶联免疫吸附试验(ELISA)检测白细胞介素27血清学水平。结果慢性乙肝感染组白细胞介素27 p28启动子区-964位点的AA基因型频率明显高于健康对照组(OR=1.75;95%CI:1.12-2.72;P=0.013);白细胞介素27水平在慢性乙肝患者显著升高(P0.001)。结论白细胞介素27 p28启动子区-964A/G多态性与慢性乙肝病毒感染感染存在一定的相关性,A等位基因可能是HBV易感的遗传因素。     

CTLA-4基因启动子区多态性与系统性红斑狼疮的关系分析

目的分析细胞毒性T淋巴细胞相关抗原-4(CTLA-4)基因启动子区-1722和-318位点多态性与系统性红斑狼疮(SLE)的关联性。方法利用聚合酶链反应-限制性片段长度多态性分析方法对112例患者和110例健康者检测-1722位点胸腺嘧啶/胞嘧啶(T/C)和-318位点T/C的多态性,并进行基因扩增,依据各条带相对分子质量的大小对CTLA-4基因-1722位点T/C和-318位点T/C进行分型。结果以组一为例,CTLA-4基因-1722位点TC基因型频率明显升高,差异有统计学意义(32%vs31%,P=0.015,OR=0.618);CC基因型频率明显升高,差异也有统计学意义(30%vs21%,P=0.039,OR=1.586);TT基因型频率虽有降低趋势,但差异无统计学意义(0%vs7%,P=0.346,OR=1.008),SLE组和健康对照组CTLA-4基因-1722位点等位基因C基因型频率明显升高,差异有统计学意义(61%vs68%,P=0.053,OR=1.781);携带者C基因型频率明显降低,差异也有统计学意义(52%vs59%,P=0.040,OR=1.652)。另外列出了CTLA-4基因-1722位点TC、CC和TT基因型的电泳结果及CTLA-4基因-318位点PCR单扩结果。结论 CTLA-4基因启动子区-1722的TC、CC基因可能是SLE易感性的一个危险因子,CTLA-4基因启动子区-1722基因型和CTLA-4基因启动子区-1722和-318位点的活性水平可作为推测SLE易感性的参考指标。     

有丝分裂原激酶MEKK2调节白细胞介素2生成的研究

目的 探讨有丝分裂原激酶MEKK2对IL-2生成的影响。方法 用MEKK2和JNK激酶活性测定、荧光素酶报告基因检测、逆转录-聚合酶链反应及Western blot等方法，检测在PHA／抗CD28抗体刺激Jurkat细胞后MEKK2对IL-2转录和翻译的影响结果经PHA／抗CD28抗体刺激后，亲本Jurkat细胞AP1和IL-2启动子荧光素酶报告基因活性分别增加4倍和5倍。而MEKK2功能域灭活的Jurkat细胞AP1和IL-2启动子荧光素酶报告基因活性仅各增加1倍。经PHA／抗CD28抗体刺激后，亲本Jurkat细胞IL-2 mRNA的转录和IL-2蛋白的表达明显增加，而MEKK2功能域灭活的Jurkat细胞IL-2 mRNA的转录和IL-2蛋白的表达无明显增加。结论 MEKK2在IL-2的生成过程中起重要的调节作用，MEKK2可以作为药物作用的靶点，从而筛选有效药物抑制免疫反应，提高移植物抗宿主病和自身免疫性疾病治疗的疗效。     

History of the first synthesis of 2-deoxy-2-fluoro-D-glucose the unlabeled forerunner of 2-deoxy-2-[18F]fluoro-D-glucose.

The history of the first successful synthesis of 2-deoxy-2-fluoro-D-glucose (19FDG) is described. In many aspects, this substance imitates the behavior of naturally occurring glucose. For example, it is transported into the cells and is converted to the corresponding 6-phosphate by the enzyme hexokinase in a manner similar to glucose. Due to the presence of the fluorine atom at C-2, however, this phosphate derivative does not undergo further glycolysis but is metabolically trapped in the cell. Thanks to these properties, eight years after the synthesis of 19FDG, its 18F-labeled derivative was successfully used with positron emission tomography (PET).     

Theoretical investigation of the reaction mechanisms and kinetics of CFCl2CH2O2 and ClO in the atmosphere

The reaction between CFCl₂CH₂O₂ radicals and ClO was studied using the B3LYP and CCSD(T) methods associated with the 6-311++G(d,p) and cc-pVTZ basis sets, and subsequently RRKM-TST theory was used to predict the thermal rate constants and product distributions. On the singlet PES, the dominant reaction is the addition of the ClO oxygen atom to the terminal-O of CFCl₂CH₂O₂ to generate adduct IM1 (CFCl₂CH₂OOOCl), and then dissociation to final products P1 (CFCl₂CHO + HO₂ + Cl) occurs. RRKM theory is employed to calculate the overall and individual rate constants over a wide range of temperatures and pressures. It is predicted that the collision-stabilized IM1 (CFCl₂CH₂OOOCl) dominates the reaction at 200–500 K (accounting for about 60–100%) and the dominant products are P1 (CFCl₂CHO + HO₂ + Cl). The yields of the other products are very low and insignificant for the title reaction. The total rate constants exhibit typical “falloff” behavior. The pathways on the triplet PES are less competitive than that on the singlet PES. The calculated overall rate constants are in good agreement with the experimental data. The atmospheric lifetime of CFCl₂CH₂O₂ in ClO is around 2.04 h. TD-DFT calculations imply that IM1 (CFCl₂CH₂OOOCl), IM2 (CFCl₂CH₂OOClO) and IM3 (CFCl₂CH₂OClO₂) will photolyze under sunlight.

The reaction between CFCl₂CH₂O₂ radicals and ClO was studied using the B3LYP and CCSD(T) methods associated with the 6-311++G(d,p) and cc-pVTZ basis sets, and subsequently RRKM-TST theory was used to predict the thermal rate constants and product distributions.     

空气净化前后老年2型糖尿病患者PaO2和PaCO2的变化

目的探讨对老年 2型糖尿病患者行空气净化前后动脉血氧分压 (PaO2 )和二氧化碳分压 (PaCO2 )的变化。方法 5 5例老年 2型糖尿病患者分为观察组 ( 2 9例 )和对照组 ( 2 6例 )。观察组患者所处疗养室每日 2 4h进行空气净化。分别于净化前、净化后第 2、3、4周抽取动脉血检测PaO2 、PaCO2 、pH值和氧饱和度。 结果空气净化 4周后 ,观察组PaO2 、PaCO2 、氧饱和度有明显改善 (P <0 .0 1) ,pH值无显著性变化。结论空气净化能改善老年 2型糖尿病患者的PaO2 、PaCO2 。     

Pharmacokinetics of the antiviral agent beta-D-2'-deoxy-2'-fluoro-2'-C-methylcytidine in rhesus monkeys

beta-D-2'-Deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130) is an effective inhibitor of hepatitis C virus (HCV) replication in vitro. The purpose of this study was to evaluate the single-dose pharmacokinetics of PSIota-6130 in rhesus monkeys following intravenous (i.v.) and oral administration. Noncompartmental analysis of the serum data obtained following oral and i.v. administration was performed. Pharmacokinetic studies with rhesus monkeys indicated slow and incomplete absorption with a mean absorption time (MAT) of 4.6 h and an oral bioavailability of 24.0% +/- 14.3% (mean +/- standard deviation), with comparable mean apparent half-lives following i.v. (4.54 +/- 3.98 h) and oral (5.64 +/- 1.13 h) administrations. The average percentages of the total dose recovered unchanged and in deaminated form in the urine were 32.9% +/- 12.6% and 18.9% +/- 6.6% (i.v.) and 6.0% +/- 3.9% and 3.9% +/- 1.0% (oral), respectively. The total bioavailability, taking into account the parent drug and its deaminated metabolite 2'-deoxy-2'-fluoro-2'-C-methyluridine (PSI-6206), was 64% +/- 26%. PSI-6130 was present in the cerebrospinal fluid after oral and i.v. dosing. However, no deamination of radiolabeled PSI-6130 was detected after 8 h of incubation in monkey and human whole blood. An N(4)-modified prodrug of PSI-6130 (PSI-6419) was orally administered to monkeys, but it failed to improve the oral bioavailability of PSI-6130. Further studies are warranted to improve the oral bioavailability and reduce the deamination of PSI-6130 in order to explore the potential of this drug for the treatment of HCV-infected individuals.     

A dynamic method to estimate the time split between the A2 and P2 components of the S2 heart sound

The time interval between the aortic (A2) and the pulmonary (P2) components of the second heart sound (S2) is an indicator of pulmonary arterial pressure. However, knowledge of the A2 and P2 components of the S2 sound is difficult to obtain due to their temporal overlap and significant spectral similarity. In this work, we aim to extract the A2 and P2 components from the phonocardiogram to estimate the time interval between them. We attain our objective by first isolating the S2 sound from the phonocardiogram by utilizing the mode complexity of the heart. Then, we assume the statistical independence of the A2 and P2 components and extract them from the S2 sound by the application of blind source separation techniques. Once separated, the time interval between the A2 and P2 components is estimated with a time-centroid-based method. Experimental results using simulated data show excellent performance of the proposed algorithm to extract the A2 and the P2 components from the S2 sound and to estimate the time interval between them. Results obtained from real data are also encouraging and show promise for utilizing the proposed method in a clinical setting to non-invasively tract pulmonary hypertension.     

Evolution of AbGRI2-0, the Progenitor of the AbGRI2 Resistance Island in Global Clone 2 of Acinetobacter baumannii

A320, isolated in the Netherlands in 1982 and also known as RUH134, is the earliest available multiply antibiotic-resistant (MAR) Acinetobacter baumannii isolate belonging to global clone 2 (GC2) and is the reference strain for this clone. The draft genome sequence of A320 was used to investigate the original location and configuration of the IS26-bounded AbGRI2 resistance island found in current GC2 isolates. PCR mapping and sequencing were used to order contigs composing the resistance islands. A320 contains two IS26-bounded resistance islands, AbGRI2-0a and AbGRI2-0b, of 7.8 kb and 25.4 kb, respectively. Together they contain bla_TEM, aacC1, aadA1, sul1, catA1, and aphA1b genes, which confer resistance to antibiotics used clinically in the 1970s, as well as an incomplete mercury resistance module. Tracking the continuity of the chromosome and the target site duplications revealed that the two resistance islands were originally together as AbGRI2-0, an island of 32.4 kb, and were subsequently separated via an IS26-mediated intramolecular inversion that reversed the orientation of 1.54 Mb of the chromosome and duplicated an IS26. A320 contains an ancestral form of AbGRI2, and the original insertion site of the AbGRI2 island was identified. Many of the AbGRI2 versions present in the completed GC2 genomes can be derived from it via the variant AbGRI2-1. IS26-mediated inversions have also played a part in forming AbGRI2-0, and, upon reversal, large regions of AbGRI2-0 are identical to parts of AbaR0, the ancestral version of the AbaR islands present in GC1 isolates. This indicates a common source.     

SOCS2 regulates T helper type 2 differentiation and the generation of type 2 allergic responses

The incidence of allergy and asthma in developed countries is on the increase and this trend looks likely to continue. CD4(+) T helper 2 (Th2) cells are major drivers of these diseases and their commitment is controlled by cytokines such as interleukin 4, which are in turn regulated by the suppressor of cytokine signaling (SOCS) proteins. We report that SOCS2(-/-) CD4(+) T cells show markedly enhanced Th2 differentiation. SOCS2(-/-) mice, as well as RAG-1(-/-) mice transferred with SOCS2(-/-) CD4(+) T cells, exhibit elevated type 2 responses after helminth antigen challenge. Moreover, in in vivo models of atopic dermatitis and allergen-induced airway inflammation, SOCS2(-/-) mice show significantly elevated IgE, eosinophilia, type 2 responses, and inflammatory pathology relative to wild-type mice. Finally, after T cell activation, markedly enhanced STAT6 and STAT5 phosphorylation is observed in SOCS2(-/-) T cells, whereas STAT3 phosphorylation is blunted. Thus, we provide the first evidence that SOCS2 plays an important role in regulating Th2 cell expansion and development of the type 2 allergic responses.     

大鼠■创伤牙周组织中PGE2及TXB2水平的分析

目的:观察大鼠创伤牙周组织中的PGE2、TXB2水平的变化,探讨大鼠创伤对牙周组织的影响。方法:将48只大鼠随机分为实验组和对照组,每大组各又分为4小组,每小组6只,创伤3d、2周、4周及12周时处死大鼠,提取创伤牙龈、牙槽骨标本测定PGE2、TXB2含量。检测结果进行统计学分析。结果:对照组各组间PGE2、TXB2含量均无差异(P>0.05)。实验组各组间PGE2、TXB2含量有显著差异(P<0.001),其中3d组除牙龈TXB2高于对照组外(P<0.01),余PGE2、TXB2均明显高于对照组(P<0.001);2周组PGE2、TXB2最高,4周组PGE2、TXB2有所下降,但均高于对照组(P<0.001);12周组PGE2、TXB2明显下降,接近对照组(P>0.05)。结论:创伤牙周组织中PGE2、TXB2的变化规律是由病变到修复到适应的过程。     

金属蛋白酶-2/金属蛋白酶组织抑制因子2比值与肝细胞癌侵袭力的关系研究

目的:探讨金属蛋白酶-2/金属蛋白酶组织抑制因子2、非活化金属蛋白酶-2前酶/金属蛋白酶组织抑制因子2比值与肝细胞癌侵袭力的关系。方法:利用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳酶谱和反向酶谱分析技术对32例肝细胞癌组织中金属蛋白酶-2和金属蛋白酶组织抑制因子2含量及非活化的金属蛋白酶-2前酶/金属蛋白酶组织抑制因子-2,金属蛋白酶-2/金属蛋白酶组织抑制因子2比值进行检测并对比分析。结果:金属蛋白酶组织抑制因子2的分子量为18 000;癌旁组织中非活化金属蛋白酶-2的前酶/金属蛋白酶组织抑制因子2(0.94),金属蛋白酶-2/金属蛋白酶组织抑制因子2(0.42)均<1.0;肝细胞肝癌组织中非活化金属蛋白酶-2前酶/金属蛋白酶组织抑制因子2(1.70),金属蛋白酶-2/金属蛋白酶组织抑制因子2(1.64)均>1.0;转移组的2项比值也明显高于无转移组(P<0.01)。结论:非活化金属蛋白酶-2前酶/金属蛋白酶组织抑制因子2,金属蛋白酶-2/金属蛋白酶组织抑制因子2的异常变化可能是评价肝细胞癌生物学行为的有力指标。