纤溶酶原激活剂抑制物-1基因启动子区4G/5G、-844G/A单核甘酸多态性及其单倍型与缺血性脑卒中的关联分析

目的：研究广东粤西地区汉族人PAI-1基因启动子区4G/5G、-844G/A单核甘酸多态性及其单倍型与缺血性脑卒中的关系。方法用ELASA方法测定130例广东粤西地籍缺血性脑卒中患者和130名广东粤西地区籍正常对照个体的血浆PAI-1水平,用等位基因特异性PCR或PCR-限制性片段长度多态法测定基因型,用EH＋程序分析单核甘酸多态性的单倍型,用卡方检验分析病例组和对照组的基因型、等位基因频率及单倍型频率的差异。结果4G/5G、-844G/A的基因型、等位基因频率在病例组和对照组之间的差异有统计学意义（P〈0.05）,4G/5G 的4G、A-844等位基因的携带者比非携带者患缺血性脑卒中的相对危险度（OR）分别大1.789倍、1.681倍。单倍型分析发现对照组中单倍型5G-G-844的频率高于病例组,而病例组中4G-A-844的频率高于对照组。结论多位点和单倍型分析结果提示PAI-1基因启动子区4G/5G、-844G/A单核甘酸多态性可能是粤西地区汉族人群与缺血性脑卒中关联的危险因素。     

急性冠状动脉综合征患者白细胞介素-6基因多态性的研究

目的探讨白细胞介素-6（IL-6）基因-597G／A及-572C／C多态性在中国汉族人群中的分布频率及与急性冠状动脉综合征（ACS）的关系方法应用聚合酶链反应-限制性片段长度多态性分析方法检测了157例ACS患者和168例对照者的白细胞介素-6基因-597G／A及-572C／G基因型。结果ACS组和对照组两组研究对象中-597位点均仅发现C,G基因型；-572位点均存在CC、CG、C,G三种基因型，三种基因型频率依次分别为51．59％、42．68％、5．73％；63．10％、35．71％、1．19％：-572C／G基因型和等位基因频率在两组间分布存在显著差异（P均〈0．02），以CC基因型为参照，暴露于C6＋GC．基因型的OR值是1．60（95％可信区间CI：1．03～2．50，P〈0．02），校正了传统危险因素的影响后，该OR值仍然具有统计学意义195％可信区间（CI）：1．01～2．91，P〈0．051。-572C／G多态性与冠状动脉病变程度无关（P〉0．05）。结论中国汉族人群中可能不存在IL-6基因-597G／A多态性，存在-572C／G多态性，后者可能是中国汉族人群ACS发病的易感基因之一。     

卵巢恶性肿瘤患者血浆纤溶酶原激活物抑制剂含量及其基因启动子区多态性研究

目的探讨纤溶酶原激活物抑制剂(PAI-1)含量和启动子区基因多态性在卵巢恶性肿瘤分期过程中的作用。方法收集52例卵巢癌,30例健康人作对照。所有标本均用微量法抽提DNA,采用等位基因特异性引物PCR分析PAH-1基因启动子4G/5G多态性,用ELISA法分别检测PAI-1浓度。结果卵巢癌病例组按照国际妇产科联盟(International Federation of Gynecology andObstetrics,FlGO)标准进行分期,FIGOI：PAI-1=37.8±9.1ng/ml;FIGOⅡ：PAI-1=41.8士9.6ng/m1;FIGOⅢ：PAI-1=45.2±12.2ng/ml;FIGOⅣ：PAI-1=20.7±14.0 ng/ml。PAI-1在卵巢癌FIG0 I～Ⅲ期浓度持续升高,但在FIG0Ⅳ期显著下降,与前三期比较差异有极显著性(P＜0.01)。PAI-1与对照组之间差异均有极显著性(P＜0.01)。PAI-1基因分布及4G和5G基因频率和健康对照纽比较差异无显著性(P＞0.05),4G/4G的PAI-1含量最高(39.3±9.6 ng/m1),4G/5G的含量次之(32.2±14.6 ng/m1),5G/5G含量最低(24.6±10.3 ng/m1),且差异有显著性(P＜0.05)。结论PAI-1与卵巢癌的分期之间有一定的相关性。PAI-1基因4G/5G多态性可能不是卵巢癌的发病危险因素。     

亚甲基四氢叶酸还原酶基因C677T多态性及同型半胱氨酸与静脉血栓栓塞症的关联性

目的：探讨亚甲基四氢叶酸还原酶基因C677T（MTHFR C677T）基因多态性及同型半胱氨酸与静脉血栓栓塞症的关联及静脉血栓栓塞症的影响因素。方法：收集200例VTE患者和同期入院体检的200例健康志愿者进行病例对照研究。分析两组受试对象MTHFR基因C677T基因型和血浆同型半胱氨酸浓度,行统计学分析和影响因素分析。结果：VTE组TT基因型70例,NC组TT基因型32例,VTE组突变率显著高于NC组（58.5%vs.40.5%,P<0.05）。同型半胱氨酸测定结果显示,VTE组的同型半胱氨酸水平显著高于NC组（15.58±6.86 vs.13.14±4.53,P<0.05）,亚组分析显示TT型人群的同型半胱氨酸水平显著高于其他型（P<0.05）。Logsitic回归分析显示,同型半胱氨酸（OR=1.074,95%CI=1.021~1.130）和MTHFR C677T位点突变（OR=2.660,95%CI=1.536~4.609）是VTE发生的独立危险因素。结论：MTHFR C677T位点突变和同型半胱氨酸水平升高是VTE发生的独立危险因素。MTHFR TT基因型个体同型半胱氨酸水平升高,患VTE风险显著升高。此外,吸烟、静脉曲张、血型、叶酸也与VTE疾病显著相关。     

新疆汉族健康人群维生素K环氧化物还原酶亚单位1启动子区1639A/G基因多态性研究

目的了解VKORC1-1639A/G基因多态性在新疆汉族健康人群中的分布及其与其他不同民族之间的差异。方法采用PCR-RFLP技术对205名乌鲁木齐地区汉族体检健康人群VKORC1-1639A/G基因多态性进行检测,计算其基因型和等位基因频率,并与国外多个民族VKORC1-1639A/G基因多态性分布进行比较。结果新疆汉族健康人群中共检测到2种等位基因:A和G。等位基因频率分别为87%和13%。新疆汉族健康人群VKORC1-1639A/G基因多态性共检测到3种基因型,以AA基因型常见,基因型频率74%。其次是AG基因型,基因型频率分别为26%。GG基因型的个体仅检测到1例,基因型频率小于1。结论新疆汉族VKORC1-1639A/G基因多态性以A等位基因和AA基因型常见,新疆汉族VKORC1-1639A/G基因多态性与欧美人群相比存在较大差异。     

MIF-173G＞C基因多态性与卵巢癌易感性的关系

目的 研究巨噬细胞移动抑制因子(MIF)基因-173G＞C多态性与江苏人群卵巢癌遗传易感性的关系.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测MIF-173G＞C多态性在130例卵巢癌患者和145例年龄相匹配正常对照者的频率和分布,比较不同基因型携带者患卵巢癌的危险性;通过分层分析探讨年龄、初潮年龄、产次、流产数及绝经状态对罹患卵巢癌的影响.结果 与携带MIF-173GG基因型相比,携带MIF-173GC/CC基因型者罹患卵巢癌的风险降低了43.2％(OR=0.568,95％CI=0.323～0.997).分层分析结果显示,产次0～1次、流产≥2次及已绝经的女性携带-173GC/CC基因型较携带GG基因型者罹患卵巢癌的风险降低尤为显著(产次0～1:OR=0.392,95％CI=0.179～0.860;流产≥2次:OR=0.394,95％CI=0.166～0.934;已绝经:OR=0.436,95％CI=0.221～0.861).结论 MIF-173G＞C多态性可能与江苏人群卵巢癌的发生有关.     

MTHFR和PAI-1基因在不良妊娠人群中的多态性分布及风险评估

本研究对146例妊娠不良事件人群（研究组）和98例正常生育人群（对照组）进行MTHFR 677C>T和PAI-1 4G/5G基因分型，探讨基因多态性分布，并对研究组人群进行风险评估。研究显示，MTHFR 677C>T等位突变率为43.03%，PAI-1 4G/5G等位基因突变率为54.31%，且研究组MTHFR 677T等位基因突变率明显高于对照组（44.52% vs 40.80%，P<0.05），4G等位基因突变频率亦高于对照组（56.51% vs 51.02%，P<0.05）。研究组人群中，11例（7.53%）和52例（35.62%）为极高度和高度风险人群。MTHFR基因和PAI-1基因多态性对不良妊娠的发生有重要影响，携带突变等位基因可影响叶酸疗效，从而增加发生不良妊娠的风险。     

IL-10 基因多态性及血清水平与颅内动脉瘤发病的关系

目的 分析白细胞介素（IL）-10 基因启动子区－ 1082G/A、－ 819C/T 单核苷酸多态性（SNP）及血清 IL-10 水平与颅内动脉瘤（IAs）发病的关系。 方法 运用 PCR 及 DNA 直接测序的方法, 检测 206 例 IAs 患者（IAs 组）和 187 例非 IAs 患者（对照组）的 IL-10 基因启动子区 SNP 位点, － 1082G/A、－ 819C/T 的基因型频率和等位基因频率, χ2检验分析 IAs 组和对照组之间的差异; 采用 ELISA 法检测血清中 IL-10 水平, t 检验分析 2 组之间的差异。 结果 IL-10 基因启动子区－ 1082G/A 位点的 GG 基因型和 GA＋ AA 基因型, 以及 G 等位基因和 A 等位基因频率比较, IAs 组较对照组 GA＋ AA 基因型以及 A 等位基因频率更高, 差异均有统计学意义（P < 0.01）, GA＋ AA 基因型（OR 值为 4.137, 95%CI 2.476~6.914）和 A 等位基因（OR 值为 3.368, 95%CI 2.476~4.583）携带者有更高的 IAs 发病风险; IL-10 基因启动子区－ 819C/T 位点的 CC 基因型和 CT＋ TT 基因型以及 C 等位基因和 T 等位基因频率比较, IAs 组较对照组 CT＋ TT 基因型以及 T 等位基因频率更高, 差异均有统计学意义（P < 0.01）, CT＋ TT 基因型（OR 值为 3.393, 95% CI 1.952~5.900）和 T 等位基因（OR 值为 3.764, 95%CI 2.730~5.192）携带者有更高的 IAs 发病风险。 IAs 组血清 IL- 10 水平低于对照组（P < 0.01）。 结论 IL-10 基因启动子区 SNP 影响 IL-10 表达,IL-10 基因启动子区－ 1082G/A、－ 819C/T 多态性与 IAs 的发病有关。     

海洛因依赖和μ阿片受体A118G多态性的关联：Meta分析

目的：探讨汉族人群中海洛因依赖和μ阿片受体基因（OPRM1）A118G多态性的关联。方法：检索PubMed，CNKI，维普等数据库，搜集有关汉族人群海洛因依赖和A118G多态性关联研究的相关文献，然后进行Meta分析。结果：A118G基因型G／G在海洛因依赖组和对照组之间的比较中，异质性检验无显著性差异（P=O．49），遂选用固定效应模型，合并OR=0．90（95％CI，0．64—1．25），效应检验结果提示没有显著性差异（P=0．51）；A118G等位基因G在海洛因依赖组和对照组之间的比较中，异质性检验存在显著性差异（P=0．03），则选用随机效应模型，合并OR=0．94（95％CI，0．71—1．23），效应检验结果提示不存在显著性差异（P=0．63）。结论：汉族人群海洛因依赖与A118G多态性的基因型和等位基因不存在关联性。     

白细胞介素-18基因多态性与脑梗死相关性研究

目的探讨白细胞介素-18（IL-18）基因启动子区-137G／C与脑梗死关系及其对血脂、脂蛋白水平的影响。方法运用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法检测190例脑梗死患者及对照组210例的IL-18基因型,同时测定血浆脂质、脂蛋白水平。结果IL—18基因-137G／C多态性在两组人群中的分布差异具有统计学意义（P〈0．05）,等位基因频率的相对风险分析发现,C等位基因携带者患脑梗死的风险是G等位基因的1．624倍（OR=1．624,95％CI：1．134—2．324）;携带C等位基因的脑梗死个体血清TC水平显著高于不携带者（P〈0．05）。结论IL-18基因．137G／C多态性与脑梗死发病具有相关性,其中C等位基因可能是脑梗死的遗传易感基因。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.