胃癌相关基因β-catenin、APC、siah-1、cyclin D1的研究

随着分子生物学技术的发展,人们对胃癌发病机制的研究已经深入到分子水平,发现和了解了较多的胃癌相关基因.本文就癌基因、抑癌基因、细胞周期调节因子作一综述,介绍4种基因:癌基因β-catenin、抑癌基因siah-1、结肠息肉病基因APC和细胞周期调节因子cyclin D1的定位、作用机制及与胃癌发生发展的关系.对这四种基因进行检测,对于胃癌早期诊断、预后评估都具有重要意义.     

MDM2、IGF1、STAT1、RAC1在骨巨细胞瘤的表达特点及临床意义

目的 探讨MDM2、IGF1、STAT1和RAC1在骨巨细胞瘤(GCT)中的表达及其与GCT复发的关系.方法 应用SP免疫组织化学方法检测MDM2、IGF1、STAT1和RAC1在50例骨巨细胞瘤中的表达.结果 MDM2:未复发组11/37阳性表达,复发组9/13阳性表达.IGF1:未复发组13/37阳性表达,复发组9/13阳性表达.STAT1:未复发组10/37阳性表达,复发组8/13阳性表达.RAC1:未复发组10/37阳性表达,复发组9/13阳性表达.其阳性表达与GCT复发均有高度相关性.结论 MDM2、IGF1、STAT1和RAC1在GCT中的表达与其复发有关,是影响预后、骨巨细胞瘤复发的危险因素,可作为帮助判断骨巨细胞瘤预后的指标.     

重庆地区汉族人群HLA-A、B、DRB1、DQB1等位基因多态性的研究

目的研究重庆地区人群HLA—A、B、DRB1和DQB1位点等位基因的多态性特点。方法采用序列特异性引物聚合酶链反应（PCR-SSP）技术对1664名重庆籍健康人进行HLA—A、B、DRB1、DQB1等位基因的低分辨分型,并与国内其他地区汉族人群进行比较。结果本次研究共检出HLA—A、B、DRB1、DQB1位点等住基因62种,其中A位点14种,B位点27种,DRB1位点13种,DQB1位点8种。A位点中A＊11（34．62％）、A＊02（28．81％）、A＊24（14．93％）、A＊30（5．53％）为重庆人群的优势基因。B位点中B＊46（14．92％）〉B＊40（12．96％）〉B＊13（12．39oA）〉B＊51（7．26oA）。DRB1位点中,频率最高的为DRB1＊09（15．65％）,其次为DRB1＊12（14．78％）、DRB1＊14（14．49％）、DRB1＊04（14．49％）。DQB1位点中,频率最高的为DQB1＊07（26．04％）,其次为DQB1＊05（19．94％）、DQB1＊09（15．51％）。与其他地区不同人群相比,HLA—A、B、DRB1、DQB1各位点等位基因的分布均有显著的差异。结论重庆地区人群的HLA-A、B、DRB1、DQB1位点等位基因符合南方汉族人群分布特点,具有复杂的多态性,中国各地常见的基因均有分布,白血病及其他器官移植患者在重庆不难找到合适的供者。     

丹参素对CD11b、P-selectin、ICAM-1、VCAM-1、E-selectin表达的影响

目的　考察丹参素对血小板、白细胞和血管内皮细胞表达细胞粘附分子CD11b、P selectin、ICAM 1、VCAM 1、E selectin的影响 ,以期探明其抗血栓形成作用的机制。方法　用流式细胞仪测定由TNFα、fMLP和凝血酶诱导细胞表面细胞粘附分子的表达。结果　人粒细胞受到fMLP刺激后 ,细胞表面CD11b表达明显增加。丹参素与粒细胞预孵30min后 ,则剂量依赖性地抑制CD11b的表达。血小板与凝血酶 (1× 10 3U·L-1)共孵 2 0min ,可明显增加血小板表面P selectin的表达。丹参素 (10 0～ 30 0mg·L-1)与血小板预孵 30min ,对凝血酶诱导的血小板表面P selectin的表达未见明显抑制作用。人脐静脉内皮细胞 (HUVEC)经TNFα处理后 ,明显增加细胞表面ICAM 1、VCAM 1和E selectin的表达 ,不同浓度的丹参素与HUVEC预孵 2h ,对TNFα诱导HUVEC表面ICAM 1的表达未见明显抑制作用 ,对TNFα诱导的VCAM 1、E selectin表达则可产生明显的抑制作用。结论　丹参素可抑制血管内皮细胞和粒细胞表达细胞粘附分子。这可能是丹参素发挥抗血栓形成作用的机制之一。     

发热、腹胀、腹水1例

笔者于2006年在上海瑞金医院进修期间遇到1例以发热、腹胀、腹水为主要特征的患者，现将其查房记录简述如下，目的是回顾诊断过程，提高病例分析能力。     

抗生素2488 SA_1、SA_2、SB_1、SB_2的化学研究

抗生素2488是由放线菌SIA-2488产生的一组碱性十六员环大环内酯类物质。它们抗革蓝氏阳性细菌,特别对红霉素耐药菌和青霉素耐药菌有效。经化学鉴别本组抗生素属于柱晶白霉素(Leucomycin)——麦迪霉素(Midecamycin)族,其主要组分SA_1、SA_2、SB_1、SB_2分别与柱晶白霉素A_3、A_4、A_1、A_5相同(图1)。本文报道抗生素2488的分离纯化及四个组分的理化性质和结构鉴别。     

HPLC法测定人参芦中人参皂苷Rb1、Rg1、Re的含量

目的：建立人参芦中人参皂苷Rb1、Rg1和Re的含量测定HPLC方法。方法：AgilentZorbaxODSc,。色谱柱（250姗×4．6mm,5I．Lm）,柱前加保护柱,检测波长为203nln;流动相为乙腈一水,梯度洗脱;流速：1．0ml·min-1;柱温：27℃;结果：结果表明人参皂苷fu）l在1．O～10．1μg范围内呈良好的线性关系,r=0．9998;平均回收率为99．7％,RSD=1．96％（n=5）;人参皂苷Rgl在1．0～10．1μg范围内呈良好的线性关系,r=0．9997,平均回收率为99．9％,RSD=1．54％（n=5）;人参皂苷Re在0．69～6．90μg范围内呈良好的线性关系,r=0．9994,平均回收率为99．5％,RSD=1．58％（n=5）。结论：该法简便、准确,可作为人参芦的质量控制。     

血塞通片中三七皂苷R1、人参皂苷Rg1、人参皂苷Rb1的含量测定

目的建立测定血塞通片中三七皂苷R1、人参皂苷Rg1、人参皂苷Rb1含量的反相高效液相色谱（RP-HPLC）法。方法色谱柱为DiamonsilC18柱（250mm×4.6mm,5μm）,柱温30℃,采用乙腈-水线性梯度洗脱,检测波长203nm,流速1.0mL/min。结果样品中的3种皂苷分离良好,三七皂苷R1、人参皂苷Rg1和人参皂苷Rb1进样量分别在2.555～12.775μg（r=0.9996）,8.115～40.575μg（r=0.9999）和7.665～38.325μg（r=0.9998）范围内与峰面积线性关系良好,平均回收率分别为99.33%,99.54%,99.82%。结论所用RP-HPLC法操作简便、结果准确,重现性好,可用于血塞通片的三七皂苷R1、人参皂苷Rg1、人参皂苷Rb1含量测定。     

HPLC法测定大鼠血清中三七皂苷R1、人参皂苷Rg1、Rb1的含量

目的 建立测定大鼠血清中三七皂苷R1、人参皂苷Rg1、Rb1含量的方法.方法 采用Kromasil 100-5C18色谱柱(250 mm×4.6mm,5μm),流动相为乙睛-0.2％磷酸水溶液,梯度洗脱;紫外检测波长203 nm,流速1 ml/min,柱温25℃.结果 三七皂苷R1、人参皂苷Rg1、Rb1均在0.2～5...     

支气管哮喘血清可溶性细胞间黏附分子-1和内皮细胞黏附分子-1的表达

目的　探讨可溶性细胞间黏附分子 - 1(s ICAM- 1)和血管内皮细胞黏附分子 - 1(s VCAM- 1)在支气管哮喘发病中的意义。方法　对支气管哮喘患者 2 3例和健康人 2 0名 (年龄均在 15～ 45岁之间 ) ,采用酶联免疫双抗体夹心法 (EL ISA)测定血清中的 s ICAM- 1和 s VCAM- 1;利用荧光酶联免疫法 (Uni- CAP系统 )分析血清中总 Ig E(t Ig E)和特异性 Ig E(s Ig E)。结果　血清 s ICAM- 1、s VCAM- 1、t Ig E水平测定哮喘组均高于对照组 (P<0 .0 1) ;血清中以户尘螨和蒿草花粉的特异性 Ig E含量增高为主 ;经多元逐步回归分析提示血清总 Ig E含量与s ICAM- 1存在线性关系 ,其复相关平方 (R- square)为 0 .5 0 2 ,标准偏回归系数为 0 .0 97,t=2 .841,P=0 .0 2 18。结论　支气管哮喘患者的 s ICAM- 1和 s VCAM- 1含量显著高于正常人 ;血清 s ICAM- 1与血清总 Ig E存在线性依存关系。     

1-Phenyl-1H-indazole derivatives with analgesic and anti-inflammatory activities.

The synthesis of 4-hydroxy-1-phenyl-1H-indazole-5-acetic acid 5 4-methoxy-1-phenyl-1H-indazole-5-yl-acetic acid 7 and 5-benzyl-1-phenyl-1H-indazol-4-ol 8, starting from 1,5,6,7-tetrahydro-1-phenyl-4H-indazol-4-one, is described. These compounds showed in mice an analgesic activity superior to that of acetylsalicylic acid and comparable to that of dipyrone; moreover, compound 5 exhibited an appreciable anti-inflammatory activity in rats. Grossbehavioral effects and acute toxicity in mice are also reported.     

Levels of sICAM-1, sVCAM-1 and MCP-1 in patients with hyperlipoproteinemia IIa and -IIb

OBJECTIVE: Hyperlipoproteinemia is one of the factors that are involved in the development of atherosclerosis. One of the mechanisms through which these high plasma lipid levels trigger the formation of atherosclerotic lesions is a change in the expression of adhesion molecules on endothelial and smooth muscle cells. The aim of this study was to evaluate the plasma levels of soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and monocyte chemoattractant protein-1 (MCP-1) in patients with Type IIa (HLP-IIa) and IIb (HLP-IIb) hyperlipoproteinemias. SUBJECTS: Twenty patients with HLP-IIa, 20 patients with HLP-IIb and 23 control subjects were studied. To accurately evaluate adhesion molecule levels, we excluded those hyperlipemic patients and control subjects who had an inflammatory disease. METHODS: Plasma sICAM-1, sVCAM-1 and MCP-1 levels were measured by the ELISA method. RESULTS: sVCAM-1 levels in HLP-IIa and HLP-IIb patients (535 +/- 27 ng/ml and 545 +/- 22 ng/ml, respectively) did not differ significantly from those in the control group (558 +/- 20 ng/ml). sICAM-1 levels were significantly higher in patients with HLP-IIa and HLP-IIb (279 +/- 10 ng/ml and 322 +/- 12 ng/ml, respectively) compared to the control group (226 +/- 10 ng/ml). MCP-1 levels were significantly higher in HLP-IIa and HLP-IIb patients (151 +/- 12 pg/ml vs 154 +/- 12 pg/ml, respectively) compared to healthy controls (98 +/- 4 pg/ml). sICAM-1 levels in the HLP-IIb group were significantly higher than in the HLP-IIa group. CONCLUSION: The results of the study suggest that lipid abnormalities affect the levels of adhesion molecules and chemokines in plasma.     

CYP1B1、NQO1基因多态性与肺癌易感性关系的研究

目的研究内蒙古地区蒙古族与汉族人群的CYP1B1和NQO1基因多态性及吸烟状况与肺癌易感性的关系。方法采用PCR-RFLP技术对CYP1B1基因L432V位点和NQO1基因C609T位点多态性进行检测。结果 (1)CYP1B1基因L432V位点基因型分布频率在蒙古族和汉族健康人群中差异无统计学意义(χ2=1.220,P> 0.05);NQO1基因C609T位点基因型分布频率在蒙古族和汉族健康人群中差异无统计学意义(χ2=0.221,P> 0.05)。(2)在蒙古族和汉族人群中,NQO1 C/T和T/T基因型有明显增加患肺癌风险性的作用(汉族人群OR:1.461,2.278,P <0.05;蒙古族人群OR:1.493,2.040,P <0.05),而CYP1B1 C/G和G/G基因型无明显增加患肺癌风险性的作用(汉族人群OR:1.271,1.614,P> 0.05;蒙古族人群OR:0.970,1.758,P> 0.05)。(3)在汉族人群中,携带CYP1B1 C/G+G/G基因型的吸烟者患肺癌的危险性高于携带C/C的非吸烟者(OR:2.152,P <0.05);携带NQO1 C/C、C/T+T/T基因型的吸烟者患肺癌的危险性高于携带C/C的非吸烟者(OR:2.172,2.613,P <0.05)。在蒙古族人群中,携带CYP1B1 C/C、C/G+G/G基因型的吸烟者患肺癌的危险性高于携带C/C的非吸烟者(OR:1.409,1.765,P <0.05);携带NQO1 C/C、C/T+T/T基因型的吸烟者患肺癌的危险性高于携带C/C的非吸烟者(OR:2.479,2.729,P <0.05)。结论 (1)CYP1B1基因L432V位点基因型以及NQO1基因C609T位点基因型在内蒙古地区蒙古族和汉族健康人群中的分布不具有种族差异。(2)NQO1 C/T和T/T基因型显著增加内蒙古地区蒙古族和汉族患肺癌的易感性。(3)在蒙古族和汉族人群中,CYP1B1 C/G+G/G基因型以及NQO1 C/T+T/T基因型显著增加吸烟者患肺癌的易感性。     

Poisoning with 1-propanol and 2-propanol

1-Propanol and 2-propanol are isomers of an alcohol with three carbons. They are colorless liquids with a sweet odor. 1-Propanol is metabolized by alcohol dehydrogenase to propionic acid and presents with metabolic acidosis and elevated anion gap, whereas 2-propanol is metabolized by alcohol dehydrogenase to acetone and presents with rapidly developing (within 3-4 h after exposure) ketosis and ketonuria but without metabolic acidosis. We report a patient who simultaneously ingested a lethal dose of 1-propanol and 2-propanol as a hand disinfectant in hospital. The patient lost consciousness and stopped breathing within half an hour after ingestion. He was intubated and artificially ventilated. Initial laboratory results showed mixed acidosis with elevated anion gap, but ketonuria appeared only 12 h after admission and 6 h following the regaining of consciousness. Therefore, laboratory results in simultaneous poisoning with two isomers of alcohol are not just a sum of laboratory results obtained in isolated poisoning with each isomer because they influence each other's metabolism: 1-propanol retards the metabolism of 2-propanol to acetone. In conclusion, 1-propanol and 2-propanol poisoning presents early with mixed acidosis and elevated anion gap and only later with ketonuria.     

1-phenyl-1H-pyrazole derivatives with antiinflammatory, analgesic and antipiretic activities

Reaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates 2 with phenylhydrazine gave the corresponding esters of 5-substituted 1-phenyl-1H-pyrazole-4-carboxylic acids 3 in high yields. Esters 3 were hydrolyzed to the relative carboxylic acids 4, which were converted by heating to 5-substituted 1-phenyl-1H-pyrazoles 5 in excellent yields. Reaction of methyl 5,5-dimethyl-3-dimethylaminomethylene-2,4-dioxohexanoate with phenylhydrazine afforded methyl 1-phenyl-4-pivaloyl-1H-pyrazole-5-carboxylate 8 b, which was converted as above to the corresponding carboxylic acid 10 b and this to 1-phenyl-4-pivaloyl-1H-pyrazole 11 b. Starting from 5-methoxymethyl-1-phenyl-1H-pyrazole, 1-phenyl-1H-pyrazole-5-acetic acid 18 and its alpha-methyl derivative 19 were also synthesized. Compounds 18, 19, 10 b and 11 b showed a strong antiinflammatory activity in rats; the same compounds in general as well as 8 b, showed appreciable analgesic and antipyretic activities in mice and rats, respectively.     

Interaction of Sulfonylureas with Liver Uptake Transporters OATP1B1 and OATP1B3

Sulfonylureas (SUs) such as glibenclamide, gliclazide, glimepiride, glipizide and gliquidone are one of the first oral medicines available for the treatment of type 2 diabetes and are widely used for the treatment of hyperglycaemia. The hepatic transporters, organic anion transporting polypeptide 1B1 (OATP1B1) and organic anion transporting polypeptide 1B3 (OATP1B3), play an important role in the disposition of a variety of drugs by mediating their uptake from blood into hepatocytes. Drug–drug interactions mediated by OATP1B1/1B3 may result in the hepatic transporting change for drug substrates. The inhibitory effects of glibenclamide and glimepiride on sulfobromophthalein (BSP) uptake have been previously studied, and glibenclamide has been reported as the substrate of OATP1B3, but it remains unclear whether other SUs such as gliclazide, glipizide and gliquidone are substrates of OATP1B1 and OATP1B3. Here, we investigated the relationship between the five most commonly applied SUs (glibenclamide, gliclazide, glimepiride, glipizide, gliquidone) and OATP1B1 and OATP1B3. We performed uptake and inhibition assays in HEK293T cells stably expressing OATP1B1 or OATP1B3, respectively, and established a liquid chromatography–mass spectrometry (LC‐MS) method for the simultaneous measurement of five SUs. We demonstrated that gliclazide and glimepiride are substrates of OATP1B1 and glibenclamide and glipizide are substrates of OATP1B3. We also confirmed the interaction between these SUs and rosuvastatin. No transporting was observed for gliquidone, suggesting that it is not a substrate of either transporter.     

Cornell指数和Sokolow指数诊断左室肥大价值的研究

目的探讨Cornell指数和Sokolow指数诊断左室肥大(LVH)的价值。方法随机选择2008年1月～2009年8月我院住院患者200例,依据超声心动图测定左室心肌重量指数(LVMI)分为左室肥大组(A组)104例和正常组(B组)96例,然后根据心电图测量R_(avL)+Sv_3和Rv_5+Sv_1的值,计算Cornell指数和Sokolow指数的诊断敏感度、特异度及准确度。结果 Cornell指数的诊断敏感度为61.54%,特异度为83.33%,准确度为72.00%;Sokolow指数的诊断敏感度为37.50%,特异度为89.58%,准确度为62.50%,经过统计分析,Cornell指数和Sokolow指数敏感度(P<0.01),准确度(P<0.05),均有统计学意义,而特异度(P>0.05),无统计学差异。结论 Cornell指数标准是诊断左室肥大较好的指标。     

PD-1基因多态性和肾癌患者血清PD-1、PD-L1水平及临床特点的相关性

目的 探讨程序性死亡受体-1(Programmed cell death 1,PD-1)基因多态性和肾癌患者血清PD-1、PD-L1水平,及病理分型、临床分期相关性.方法 2012年2月至2015年8月纳入本院肾癌患者84例,同时纳入健康人群50例为对照组.PCR扩增测肾癌组和对照组PD-1基因多态性,ELISA测定血清PD-1、PD-L1浓度.结果 肾癌组血清PD-1、PD-L1高于对照组(P＜0.05).肾癌患者基因突变率为16.07％,对照组为6.00％,差异有统计学意义(P＜0.05).PD-1基因T/T亚组血清PD-1、PD-L1明显高于C/C、C/T两个亚组.PD-1 rs41386349位点野生型和突变型和肾癌的病理类型、临床分期密切相关(P＜0.05);和性别、年龄无明显相关性(P＞0.05).结论 PD-1基因突变和透明细胞肾癌具有相关性,和透明细胞肾癌的发病、转移及病程密切相关.