VEGF-C和Ki-67抗原在宫颈癌新辅助化疗前后的表达及意义

目的探讨VEGF-C和Ki-67抗原在宫颈癌新辅助化疗(adjuvant chemotherapy NACT)前后表达及意义。方法采用免疫组化SP法检测VEGF-C,Ki-67抗原在38例新辅助化疗前后宫颈癌组织中表达变化。结果 38例接受NACT后的宫颈癌患者,临床总有效率为81.58%。VEGF-C,Ki67抗原在宫颈癌患者化疗后的表达显著低于化疗前(P<0.05),VEGF-C,Ki-67抗原在临床有效病例中的表达有明显差异(P<0.05),VEGF-C,Ki-67抗原在临床无效病例中表达无显著性差异(P>0.05);VEGF-C,Ki-67抗原在不同病理参数的宫颈癌患者NACT前后阳性表达变化值无显著性差异(P>0.05)。结论 NACT对宫颈癌治疗有效,检测VEGF-C,Ki67抗原在NACT前后表达的变化可协助预测NACT的敏感性及疗效。     

EGFR、Ki-67在三阴性乳腺癌中的表达及相关性临床研究

目的：探讨三阴性乳腺癌（TNBC）表皮生长因子受体（EGFR）、Ki-67的表达及临床意义,并研究EGFR、Ki-67基因表达的相关性。方法回顾性分析67例 TNBC 和125例 NTNBC 的临床病理特征,并应用免疫组织化学方法检测 EGFR、Ki-67在二者之间的表达差异,分析 EGFR、Ki-67基因表达的相关性。结果 EGFR 在 TNBC 中的阳性表达率为89.6%,在 NTNBC 中的阳性表达率为57.6%,差异有统计学意义（ P <0.05）。EGFR 的表达与TNBC 组的年龄、肿瘤大小、淋巴结转移及病理学分级无关（ P >0.05）,与病理类型有关（ P <0.05）。Ki-67在 TNBC 中的阳性表达率为92.5%,在 NTNBC 中的阳性表达率为66.4%,差异有统计学意义（ P <0.05）。Ki-67的表达与 TNBC 组的年龄、肿瘤大小、淋巴结转移、病理类型及病理学分级无关（ P >0.05）。结论 TNBC 有其独特的临床病理特征, EGFR、Ki-67在 TNBC 组织中高表达,提示其恶性程度高,侵袭性强,预后差,EGFR、Ki-67可以做为评估 TNBC 预后的重要参考因素。     

奈达铂同步化疗对中晚期宫颈癌患者uPA、VEGF及Ki-67表达的影响

目的 探讨奈达铂同步化疗对中晚期宫颈癌患者uPA、VEGF及Ki-67表达的影响.方法 收治的80例原发性宫颈癌患者随机分为观察组和对照组,每组40例.观察组采用奈达铂同步化疗治疗,对照组采用单纯放疗治疗,比较2组患者治疗效果及治疗前后uPA、VEGF和Ki-67表达阳性率变化.结果 观察组治疗总有效率为95骀.0%显著高于对照组的80.0%(P<0.05);随访期2组患者生存率、复发率和远处转移率差异有统计学意义(P<0.05);宫颈癌患者癌变组织中uPA、VEGF和Ki-67表达阳性率显著高于正常宫颈组织,差异有统计学意义(P<0.05);2组患者治疗后uPA、VEGF和Ki-67表达阳性率显著下降(P<0.05),且观察组下降程度显著高于对照组(P<0.05);观察组患者奈达铂同步化疗Ki-67阳性组化疗有效率显著高于阴性组,差异有统计学意义(P<0.05);观察组与对照组不良反应率比较差异无统计学意义(P>0.05).结论 奈达铂同步化疗能够显著降低中晚期宫颈癌患者宫颈组织中uPA、VEGF和Ki-67表达阳性率,提高中晚期宫颈癌患者治疗疗效,且患者能够耐受相关不良反应,值得临床推广使用.     

WT1、Bcl-2、Ki-67蛋白在上皮性卵巢癌中的表达及其相关性研究

目的探讨上皮性卵巢癌组织中WT1、Bcl-2、Ki-67蛋白的表达及其相关性。方法采用免疫组化方法检测62例上皮性卵巢癌组织及10例正常卵巢组织中WT1、Bcl-2、Ki-67蛋白的表达情况。结果⑴10例正常卵巢组织中WT1、Ki-67蛋白均无阳性表达、Bcl-2蛋白1例阳性表达;62例上皮性卵巢癌中WT1、Bcl-2、Ki-67阳性蛋白表达率分别为80.64%(50/62)、53.23%(33/62)、82.26%(51/62)。⑵上皮性卵巢癌组织中WT1、Bcl-2、Ki-67蛋白的表达率高于正常组织(P<0.05);WT1、Ki-67蛋白阳性表达与组织学分级和临床病理分期相关(P<0.05),Bcl-2蛋白阳性表达与组织学分级和临床病理分期不相关(P>0.05)。⑶WT1蛋白表达与Bcl-2蛋白的表达正相关(r=0.463,P<0.05),WT1蛋白与Ki-67蛋白,Ki-67蛋白与Bcl-2蛋白表达之间无相关性(r=0.012、r=0.120、P>0.05)。结论 WT1、Bcl-2、Ki-67蛋白表达在上皮性卵巢癌的发生发展过程中起重要作用,WT1可能通过上调Bcl-2抑制细胞凋亡促使卵巢癌的发生。     

SNCG和Ki-67在胃癌组织中表达的意义

目的研究乳腺特异基因BCSG1(SNCG)和Ki-67在胃癌组织中的表达及意义。方法采用免疫组化法观察60例胃癌(A组)及20例正常胃黏膜石蜡(C组)标本中SNCG和Ki-67蛋白的表达。结果 A组SNCG和Ki-67的阳性表达率分别为65.0%和73.3%,均显著高于C组的0和20.0%(P<0.01)。SNCG和Ki-67的表达与胃癌的浸润深度、淋巴结转移及肿瘤临床分期密切相关(P<0.05或P<0.01)。且SNCG的表达和Ki-67的表达呈正相关(P<0.01)。结论 SNCG和Ki-67在胃癌组织中显著高表达,与胃癌的浸润转移相关,可能共同参与胃癌的发生、发展过程。     

甲状腺癌组织CXCR4、Ki-67表达与临床病理特征及预后的关系研究

目的:探讨甲状腺癌组织趋化因子受体4(CXCR4)、Ki-67表达与临床病理特征及预后的关系。方法:选取2017年7月~2019年10月在某院行手术治疗的90例甲状腺癌患者癌组织标本设为研究组,收集癌旁组织标本作为良性组,另外选择同期在我院行手术治疗的90例甲状腺良性病变患者病理标本为对照组。比较3组Ki-67、CXCR4阳性表达率,分析Ki-67、CXCR4阳性表达率与甲状腺癌临床病理特征关系以及Ki-67、CXCR4表达与甲状腺癌患者疾病进展时间(TTP)的相关性。结果:研究组Ki-67、CXCR4阳性表达率高于良性组、对照组,差异有统计学意义(P<0.05);良性组Ki-67、CXCR4阳性表达率与对照组相比,差异无统计学意义(P>0.05);甲状腺癌患者病理分期Ⅲ~Ⅳ期Ki-67、CXCR4阳性表达率高于病理分期Ⅰ~Ⅱ期,有淋巴结转移Ki-67、CXCR4阳性表达率高于无淋巴结转移,且有包膜侵犯Ki-67阳性表达率高于无包膜侵犯,差异有统计学意义(P<0.05);Ki-67、CXCR4阳性者TTP较阴性者高,差异有统计学意义(P<0.05)。结论:Ki-67、CXCR4在甲状腺癌中呈高表达,其表达水平与临床病理特征密切相关,并影响患者术后疾病进展,为甲状腺癌患者的治疗提供新的理论依据。     

环指蛋白180、p53及Ki-67在肾透明细胞癌中的表达及临床意义北大核心CSCD

目的研究环指蛋白180(RNF180)、p53及细胞增殖抗原标记物Ki-67在肾透明细胞癌(RCCC)组织中的表达水平及临床病理意义。方法收集225例确诊RCCC患者术后的石蜡标本及相应的远端正常组织制备组织芯片,用免疫组化法检测RNF180,p53和Ki-67在RCCC组织及癌旁组织的表达。结果在癌组织和癌旁组织中RNF180蛋白的阳性表达率分别为48.89%(110例/225例)和75.56%(170例/225例),p53蛋白的阳性表达率分别为45.71%(96例/210例)和2.38%(5例/210例),Ki-67蛋白的阳性表达率分别为32.20%(66例/205例)和2.44%(5例/205例),差异均有统计学意义(均P<0.05)。Spearman相关性分析显示,RNF180与p53及Ki-67均无相关性。Kaplan-Meier分析显示,RCCC患者的良好预后与RNF180的阳性表达呈正相关(P<0.05),而与p53及Ki-67无关。多因素Cox回归分析显示,TNM分期、肿瘤大小及RNF180是RCCC的独立预后因子。结论RNF180、p53及Ki-67可能分别参与RCCC的发生、发展过程,且RNF180可为RCCC患者预后提供参考。     

三阴型乳腺癌新辅助化疗的疗效观察

目的探讨TEC方案在三阴型乳腺癌新辅助化疗中的疗效。方法回顾性分析118例接受TEC方案新辅助化疗的乳腺癌患者,三阴型乳腺癌患者52例,非三阴型乳腺癌患者66例,观察两组患者化疗疗效和Ki67的表达情况。结果 Ki67高表达者所占比例在三阴组明显高于非三阴组(分别为78.9%,53.0%,P=0.001),三阴组Ki67高表达者比低表达者更易获得pCR(P=0.022)。三阴组pCR、CR、OPR、ORR、SD以及PD分别为28.8%、36.5%、51.9%、88.5%、9.6%以及1.9%,非三阴组分别为7.6%、17.3%、47.0%、62.1%、34.8%以及3%,其中两组pCR、CR、ORR以及SD差异均有统计学意义(P0.05)。结论 TEC方案应用于三阴型乳腺癌新辅助化疗能获得较高的pCR率,Ki67高表达在三阴型乳腺癌中更多见,且更能够获得pCR。     

Bcl-2、Ki-67和C-myc的表达与恶性淋巴瘤常规治疗后复发的关系

目的:研究Bcl-2、Ki-67和C-myc在恶性淋巴瘤(malignant lymphoma, ML)组织中的表达与常规化疗后复发的相关性.方法:采用免疫组织化学法检测65例行常规化疗的患者组织切片中Bcl-2、Ki-67和C-myc的表达.Bcl-2、Ki-67和C-myc不同表达患者的生存率统计采用Kaplan-Meier生存曲线和Log-rank检验.结果:Bcl-2表达与非霍奇金淋巴瘤(non-Hodgkin lymphoma,NHL)细胞来源有关,B细胞来源的NHL阳性率高于T细胞来源的NHL(P < 0.05),Ki-67、C-myc表达与NHL细胞来源、患者性别、年龄、临床分期和B症状等无关.C-myc的表达与常规化疗患者预后无关,Bcl-2阳性表达组和阴性表达组3年无病生存率分别为22.22%和55.56%,Ki-67阳性表达组和阴性表达组3年无病生存率分别为37.50%和61.54%,差异均有统计学意义(P < 0.05).结论:Bcl-2、Ki-67蛋白阳性表达的ML患者,常规化疗后易复发,应实施更加积极的治疗或造血干细胞移植.     

Ki-67以及p16蛋白在宫颈上皮内瘤变中的检测意义

目的探讨Ki-67蛋白以及p16蛋白在宫颈上皮内瘤变中的检测意义。方法选取2017年1月至2019年1月在我院就诊的54例宫颈上皮内瘤变患者,将其根据CIN等级分成CINⅠ组(n=24例),CINⅡ组(n=20例),CINⅢ组(n=10例)。并且选取50例慢性宫颈炎患者为对照组。对比四组研究对象的宫颈组织中Ki-67蛋白以及p16蛋白的阳性表达情况。结果 CINⅢ组、CINⅡ组以及CINⅠ组的宫颈组织中Ki-67蛋白阳性表达率均明显高于对照组(P<0.05),且CINⅢ组的Ki-67蛋白阳性表达率明显高于CINⅡ组以及CINI组(P<0.05),CINⅡ组的Ki-67蛋白阳性表达率明显高于CINⅠ组(P<0.05);CINⅢ组、CINⅡ组以及CINI组的宫颈组织中p16蛋白阳性表达率均明显高于对照组(P<0.05),且CINⅢ组的p16蛋白阳性表达率明显高于CINⅡ组以及CINⅠ组(P<0.05),CINⅡ组的p16蛋白阳性表达率明显高于CINI组(P<0.05)。结论 Ki-67蛋白以及p16蛋白可能在宫颈上皮内瘤变的发生及发展中发挥着重要的作用。     

Role of glutathione in reduction of arsenate and of gamma-glutamyltranspeptidase in disposition of arsenite in rats

Arsenate (AsV), the environmentally prevalent form of arsenic, is converted sequentially in the body to arsenite (AsIII), monomethylarsonic acid (MMAsV), monomethylarsonous acid (MMAsIII), and dimethylarsinic acid (DMAsV) and some trimethylated metabolites. Although the biliary excretion of arsenic in rats is known to be glutathione (GSH)-dependent, involving transport of arsenic-GSH conjugates, the role of GSH in the reduction of AsV to the more toxic AsIII in vivo has not been defined. Therefore, we studied how the fate of AsV is influenced by buthionine sulfoximine (BSO), which depletes GSH in tissues. Control and BSO-treated rats were given AsV (50 micromol/kg, i.v.) and arsenic metabolites in bile, urine, blood and tissues were analysed by HPLC-HG-AFS. BSO increased retention of AsV in blood and tissues and decreased appearance of AsIII in blood, bile (by 96%) and urine (by 63%). The biliary excretion of MMAsIII was also nearly abolished, the appearance of MMAsIII and MMAsV in the blood was delayed and the renal concentrations of these monomethylated arsenicals were decreased by BSO. Interestingly, appearance of DMAsV in blood and urine remained unchanged and the concentrations of this metabolite in the kidneys and muscle were even increased in response to BSO. To test the role of gamma-glutamyltranspeptidase (GGT) in arsenic disposition, the effect of the of the GGT inhibitor acivicin was investigated in rats injected with AsIII (50 micromol/kg, i.v.). Acivicin lowered the hepatic and renal GGT activities and increased the biliary as well as urinary excretion of GSH, but failed to alter the disposition (i.e. blood and tissue concentrations, biliary and urinary excretion) of AsIII and its metabolites. In conclusion, shortage of GSH decreases not only the hepatobiliary transport of arsenic, but also reduction of AsV and the formation of monomethylated arsenic, while not hindering the production of dimethylated arsenic. While GSH plays an important role in the disposition and toxicity of arsenic, GGT, which hydrolyses GSH and GSH conjugates, apparently does not influence the fate of the GSH-reactive trivalent arsenicals in rats.     

微透析取样技术在中药体内分析中的应用研究进展

本文综述了微透析取样技术在中药体内分析中的应用,介绍微透析取样技术的原理、组成、探针类型、特点,重点阐述了微透析取样技术在测定脑、血液、皮肤等组织器官中中药有效成分浓度的应用实例。表明微透析取样技术在中药药效研究中具有广阔的前景。     

应用PASS系统分析我院2010年住院医嘱

目的:了解我院2010年住院患者的合理用药情况,探讨如何利用合理用药监测系统( PASS)提高合理用药水平.方法:利用PASS对我院2010年15 966例住院患者的1 184 997条用药医嘱进行监测,以黑色警示医嘱为依据,收集不合理用药信息,并对监测结果进行统计、分析.结果:不合理用药医嘱50 261条,发生率为4.24％.绝对禁止黑色医嘱5441条,主要为药物相互作用(66.54％)、注射液体外配伍(17.86％)、用法用量(15.46％)、儿童警告(1.14％).结论:应用PASS系统能有效监测医嘱中的不合理用药情况,有利于提高临床合理用药水平,但PASS系统尚存在局限性,有待进一步完善.     

Changes in levels of dependency and predictors of mortality in elderly people in institutional care in Dunedin

The 1983 study of dependency of subjects in institutional care in Dunedin was repeated two years later. A significant increase in levels of dependency in residential homes, particularly in the Religious and Welfare sector was found. In 1983 there were 29 high dependency residents and 73 medium dependency residents in residential homes. In 1985 these numbers had increased to 55 and 86 respectively. There was no change in the number of low dependency residents. In 1983, 6 high dependency residents had been admitted to residential home care in the year prior to the study. In 1985 the number of high dependency residents recently admitted had increased to 23. There had also been a significant increase in the dependency of patients in Religious and Welfare continuing care hospitals. Of the 933 subjects in institutional care in 1983 who were able to be followed, 354 (37.9%) died in the following 2 years. Mortality rate was higher for those in hospital care (48.1%) than for those in residential home care (29.6%). Mortality rates were higher in more dependent subjects and this was evident for each measure of dependency.     

应用PASS系统对我院2008年住院医嘱的分析

目的监测分析2008年我院住院患者用药情况。方法将PASS系统嵌入医生工作站、临床药学工作站等子系统,构建合理用药计算机网络系统,对住院医嘱进行及时监测,将监测结果向医生反馈,并对其进行统计、分析。结果2008年共监测医嘱3 620 241条,不合理医嘱908条,占0.02%。不合理医嘱中,配伍禁忌(381条)占41.96%,用法用量(381条)占41.96%,药物相互作用(108条)占11.89%,儿童用药(38条)占4.19%。经与医生沟通后,更改不合理医嘱856条,占94.27%。结论PASS系统可有效监测医嘱中的不合理用药,通过与医生交流,大大减少药物不良事件的发生,值得临床推广应用,也为临床药师开展工作带来了极大的便利。但PASS系统尚存在局限性,有待进一步完善。     

Role of desacetylation in the detoxification of cephalothin in renal cells in culture

The toxicity of three cephalosporin antibiotics to rabbit kidney cells in culture was compared to their known nephrotoxic potential in vivo (cephaloridine greater than cefazolin greater than cephalothin). While cephalothin is considered to be a relatively nonnephrotoxic cephalosporin when administered to many species including humans and rabbits, in several in vitro systems involving rabbit renal tissue, cephalothin was comparatively more toxic than anticipated based on in vivo data. Cephalothin is extensively desacetylated in rabbits to a less microbiologically active metabolite, desacetylcephalothin. When a microsomal S9 fraction from rabbit kidney was added to the in vitro assay in cultured rabbit renal cells, cephalothin was desacetylated and its toxicity to kidney cells was reduced. The addition of S9 in vitro provided a toxicity ranking of the cephalosporins that correlated with their known in vivo nephrotoxic potentials (cephaloridine greater than cefazolin greater than cephalothin). The in vitro detoxification of cephalothin by S9 was blocked by the coadministration of the esterase inhibitor, aminocarb. Desacetylcephalothin was relatively nontoxic to rabbit renal tissue in vitro. These results suggest that the desacetylation of cephalothin in vivo represents a previously unrecognized mechanism of detoxification of this cephalosporin antibiotic. Furthermore, this mechanism of detoxification may be applicable to other acetylated cephalosporins.     

2009年某院住院患者抗真菌药用药调查

目的:分析讨论某院抗真菌药使用的合理性,为临床安全有效地使用抗真菌药提供参考。方法:回顾性统计分析某院2009年住院患者抗真菌药用药信息。结果:2009年某院住院患者抗真菌药DDDs排名前3名分别为:氟康唑、制霉菌素和伊曲康唑;使用金额排名前3名分别为:氟康唑、米卡芬净及卡泊芬净;更换一种抗真菌药进行治疗的患者数为176人,在全部患者中占13.4%。结论:应进一步强化用药指征的意识,提高标本送检率,同时改善某些抗真菌用药不合理更换的现象,以避免耐药性发生,从而更好更长远地体现抗真菌药的治疗价值。     

Kinetics of in vitro metabolism of methoxyphenamine in rats

1. Methoxyphenamine (MP) was metabolized in vitro by rat liver preparations to O-desmethylmethoxyphenamine (O-desmethyl-MP), N-desmethylmethoxyphenamine (N-desmethyl-MP) and 5-hydroxymethoxyphenamine (5-hydroxy-MP). These metabolic pathways were inhibited by SKF 525-A and carbon monoxide, which indicates that these reactions were mediated at least partly by an NADPH-dependent cytochrome P-450 system. 2. Strain differences in the metabolism of this drug in vitro were observed in female Lewis and Dark Agouti (DA) rats, which are proposed models for human debrisoquine phenotypes. Methoxyphenamine O-demethylase and 5-hydroxylase activity in DA rats were lower than those in Lewis rats. 3. The metabolic transformation of methoxyphenamine in vitro to O-desmethyl-MP was inhibited competitively by debrisoquine and sparteine. This indicates that the cytochrome P-450 isoenzyme mediating the metabolism of MP to O-desmethyl-MP is similar to that mediating metabolism of debrisoquine and sparteine. However, no inhibition was observed with methenytoin.     

Comparison of in vitro cell models in predicting in vivo brain entry of drugs

Although several in vitro models have been reported to predict the ability of drug candidates to cross the blood-brain barrier, their real in vivo relevance has rarely been evaluated. The present study demonstrates the in vivo relevance of simple unidirectional permeability coefficient (P(app)) determined in three in vitro cell models (BBMEC, Caco-2 and MDCKII-MDR1) for nine model drugs (alprenolol, atenolol, metoprolol, pindolol, entacapone, tolcapone, baclofen, midazolam and ondansetron) by using dual probe microdialysis in the rat brain and blood as an in vivo measure. There was a clear correlation between the P(app) and the unbound brain/blood ratios determined by in vivo microdialysis (BBMEC r=0.99, Caco-2 r=0.91 and MDCKII-MDR1 r=0.85). Despite of the substantial differences in the absolute in vitro P(app) values and regardless of the method used (side-by-side vs. filter insert system), the capability of the in vitro models to rank order drugs was similar. By this approach, thus, the additional value offered by the true endothelial cell model (BBMEC) remains obscure. The present results also highlight the need of both in vitro as well as in vivo methods in characterization of blood-brain barrier passage of new drug candidates.