经肛门内镜显微手术切除直肠肿瘤

目的评价经肛门内镜显微手术(TEM)切除直肠绒毛状腺瘤和早期直肠癌的应用效果。方法分析我院总结1995年11月至2001年12月27例TEM手术的临床资料。结果本组患者肿瘤直径中位值2.5cm,肿瘤下缘与齿状线距离(8.9±3.4)cm,肿瘤侵犯直肠周径范围(35.7±17.5)%。平均手术时间(109±46)min。平均住院日4.5d。无围手术期死亡。手术并发症有尿潴留、暂时性大便失禁和慢性阻塞性肺病(COPD)复发。术中2例切穿至腹腔,即刻内镜下修补成功。切缘100%瘤细胞阴性。病理示直肠绒毛状腺瘤14例、直肠腺癌13例,后者包括pTis2例,pT16例和pT25例。直肠癌腔内超声肿瘤T分期符合率为84.6%。5例pT2中2例中转前切除术,1例接受术后放疗,2例无附加任何治疗。平均随访18个月,所有病例无局部复发。死亡2例,但无复发迹象。结论TEM易行且安全,是直肠绒毛状腺瘤和部分T1直肠癌的治愈性手术,也可作为T2直肠癌的姑息性治疗手段。     

Isolation of a Natural Antioxidant, Dehydrozingerone from Zingiber officinale and Synthesis of Its Analogues for Recognition of Effective Antioxidant and Antityrosinase Agents

In the present study, the antioxidative and inhibitory activity of Zingiber officinale Rosc. rhizomes-derived materials (on mushroom tyrosinase) were evaluated. The bioactive components of Z. officinale rhizomes were characterized by spectroscopic analysis as zingerone and dehydrozingerone, which exhibited potent antioxidant and tyrosinase inhibition activities. A series of substituted dehydrozingerones [(E)-4-phenyl-3-buten-2-ones] were prepared in admirable yields by the reaction of appropriate benzaldehydes with acetone and the products were evaluated in terms of variation in the dehydrozingerone structure. The synthetic analogues were examined for their antioxidant and antityrosinase activities to probe the most potent analogue. Compound 26 inhibited Fe2+-induced lipid peroxidation in rat brain homogenate with an IC50 = 6.3+/-0.4 microM. In the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical quencher assay, compounds 2, 7, 17, 26, 28, and 29 showed radical scavenging activity equal to or higher than those of the standard antioxidants, like alpha-tocopherol and ascorbic acid. Compound 27 displayed superior inhibition of tyrosinase activity relative to other examined analogues. Compounds 2, 17, and 26 exhibited non-competitive inhibition against oxidation of 3,4-dihydroxyphenylalanine (L-DOPA). From the present study, it was observed that both number and position of hydroxyl groups on aromatic ring and a double bond between C-3 and C-4 played a critical role in exerting the antioxidant and antityrosinase activity.     

内皮素1对家兔动脉粥样硬化斑块环氧合酶2表达的影响

目的:观察由内皮素1激活的内皮素A受体对家兔动脉粥样硬化斑块环氧合酶2表达的影响。方法:实验于2006-03/09在上海交通大学医学院附属新华医院科研中心完成。①实验分组:32只雄性新西兰大白兔完全随机设计分成基础组、模型组、BQ-123组以及辛伐他汀组,每组8只。②实验方法:基础组饲喂普通饲料10周,其余3组均饲喂高脂饲料(1%胆固醇、10%蛋黄粉、5%猪油、84%普通饲料)10周。模型组于第6周开始静脉注射生理盐水(4mL/d)连续注射5周,作为阴性对照;BQ-123组于第6周开始用微量输液泵静脉点滴选择性内皮素A受体拮抗剂BQ-123(4mL/d,30min滴完),连续点滴5周;辛伐他汀组于第6周开始添加药物饲料(含辛伐他汀10mg/d)连用5周。③实验评估:饲喂10周后,采耳动脉血检测血清总胆固醇、三酰甘油、高密度脂蛋白胆固醇以及低密度脂蛋白胆固醇水平;采用免疫组织化学SP法检测主动脉标本中组织内皮素1、巨噬细胞及环氧合酶2蛋白表达。结果:纳入动物32只,均进入结果分析。①4组血清总胆固醇水平比较:模型组、BQ-123组及辛伐他汀组高于基础组(P均<0.01)。BQ-123组及辛伐他汀组低于模型组(P均<0.05)。②4组血清三酰甘油水平比较:模型组、BQ-123组及辛伐他汀组高于基础组(P均<0.01)。BQ-123组及辛伐他汀组低于模型组(P均<0.01)。辛伐他汀组高于BQ-123组(P<0.01)。③4组血清低密度脂蛋白胆固醇水平比较:模型组、BQ-123组及辛伐他汀组高于基础组(P均<0.01)。辛伐他汀组低于模型组(P<0.05)。④4组血清高密度脂蛋白胆固醇水平比较:模型组、BQ-123组及辛伐他汀组低于基础组(P均<0.01)。BQ-123组高于模型组(P<0.01)。⑤BQ-123组及辛伐他汀组家兔动脉粥样硬化斑块内皮素1、巨噬细胞源泡沫细胞、环氧合酶2蛋白阳性表达均较模型组明显降低,BQ-123组家兔动脉粥样硬化斑块内皮素1、巨噬细胞源泡沫细胞、环氧合酶2蛋白阳性表达又较辛伐他汀组进一步降低。结论:内皮素1激活的内皮素A受体可以导致家兔动脉粥样硬化斑块环氧合酶2表达的上调;选择性内皮素A受体拮抗剂可以预防家兔动脉粥样硬化进程的发展。     

白藜芦醇对一次性力竭游泳大鼠肝脏组织保护作用的量效关系

目的:观察白藜芦醇对一次性力竭游泳大鼠肝脏组织的作用及发挥作用的最佳口服剂量。方法:实验于2006-05/07在成都体育学院运动医学系动物实验室完成。①实验分组:选取雄性SD大鼠70只,随机分为7组,每组10只,分别为安静对照组,运动对照组,运动 15mg/kg白藜芦醇组,运动 50mg/kg白藜芦醇组,运动 100mg/kg白藜芦醇组,运动 200mg/kg白藜芦醇组,运动 300mg/kg白藜芦醇组。②实验干预:不同剂量白藜芦醇组每天灌胃15,50,100,200,300mg/kg白藜芦醇,安静对照组和运动对照组分别灌胃相同体积的溶媒(二甲亚砜 生理盐水),连续5周。末次给予实验用样品1h后,各运动组每只鼠尾跟部负荷3%体质量铅皮,置于水深50cm、水温(31±1)℃游泳槽中游泳。游泳力竭后即刻,股动脉取血并迅速取出肝组织。③指标检测:赖氏比色法测定血清中谷丙转氨酶活性;邻苯三酚自氧化法测定肝组织超氧化物歧化酶活性;硫代巴比妥酸法测定肝组织丙二醛含量。结果:纳入动物70只,均进入结果分析。①血清谷丙转氨酶活性和肝组织中丙二醛含量:运动对照组显著高于安静对照组,不同剂量白藜芦醇组低于运动对照组(P<0.05或P<0.01)。运动 100,200,300mg/kg白藜芦醇组低于运动 15,50mg/kg白藜芦醇组[谷丙转氨酶活性:(972.36±121.86),(944.36±105.35),(888.34±88.68),(1773.52±89.35),(1377.78±27.01)nkat/L,P<0.01;丙二醛含量:(7.90±2.56),(7.69±3.69),(7.13±2.62),(19.90±2.21),(12.16±1.78)μmol/g,P<0.05]。100,200,300mg/kg白藜芦醇组间差异无显著性。②肝脏组织中超氧化物歧化酶活性:运动对照组显著低于安静对照组,不同剂量白藜芦醇组高于运动对照组(P<0.05或P<0.01)。运动 100,200,300mg/kg白藜芦醇组高于15,50mg/kg白藜芦醇组[(2325.80±163.37),(2379.14±121.86),(2447.16±89.18),(1096.05±120.19),(1514.64±28.17)μkat/g,P<0.01]。结论:①白藜芦醇对力竭性运动大鼠肝脏组织具有保护作用。②100,200,300mg/kg白藜芦醇对肝脏组织发挥保护作用效果优于15,50mg/kg,建议使用100mg/kg白藜芦醇就能达到理想效果。     

Effects of hepatitis C and B viruses infection on the development of hepatocellular carcinoma

A case control study consisting of 102 patients with HCC, 102 sex-matched and age-matched patients with nonhepatic disease, and 204 matched healthy controls was carried out to investigate the effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the development of hepatocellular carcinoma (HCC). The prevalence of antibody to HCV (anti-HCV) in HCC (34.3%) was higher than in nonhepatic disease (10.7%, P< 0.001) or in healthy controls (2.4%, P< 0.001). The prevalence of hepatitis B surface antigen (HBsAg) in HCC (77.4%) was higher than in nonhepatic disease (16.6%, P< 0.001) or in healthy controls (19.6%, P< 0.001). Anti-HCV positivity in nonhepatic disease was higher than in healthy controls (P<0.01). Using patients with nonhepatic disease as controls, stepwise logistic regression analysis indicated that both anti-HCV (odds ratio, 3.4; 95% confidence interval, 2.1-5.6) and HBsAg (odds ratio, 5.6; 95% confidence interval, 3.6–8.5) are independent risk factors for HCC. Using healthy controls, the development of HCC was also strongly associated with anti-HCV (odds ratio, 8.0; 95% confidence interval, 4.3–14.6) and HBsAg (odds ratio, 5.5; 95% confidence interval, 3.7–8.2). Calculation of incremental odds ratio indicated that there is no interaction between HBV and HCV. In conclusion, HBV and HCV are risk factors of HCC. They act independently and without interaction. © 1994 Wiley-Liss, Inc.     

Mechanism of action and inhibition of dehydrosqualene synthase

"Head-to-head" terpene synthases catalyze the first committed steps in sterol and carotenoid biosynthesis: the condensation of two isoprenoid diphosphates to form cyclopropylcarbinyl diphosphates, followed by ring opening. Here, we report the structures of Staphylococcus aureus dehydrosqualene synthase (CrtM) complexed with its reaction intermediate, presqualene diphosphate (PSPP), the dehydrosqualene (DHS) product, as well as a series of inhibitors. The results indicate that, on initial diphosphate loss, the primary carbocation so formed bends down into the interior of the protein to react with C2,3 double bond in the prenyl acceptor to form PSPP, with the lower two-thirds of both PSPP chains occupying essentially the same positions as found in the two farnesyl chains in the substrates. The second-half reaction is then initiated by the PSPP diphosphate returning back to the Mg(2+) cluster for ionization, with the resultant DHS so formed being trapped in a surface pocket. This mechanism is supported by the observation that cationic inhibitors (of interest as antiinfectives) bind with their positive charge located in the same region as the cyclopropyl carbinyl group; that S-thiolo-diphosphates only inhibit when in the allylic site; activity results on 11 mutants show that both DXXXD conserved domains are essential for PSPP ionization; and the observation that head-to-tail isoprenoid synthases as well as terpene cyclases have ionization and alkene-donor sites which spatially overlap those found in CrtM.