p53和Ki67在胃癌中的表达及其临床意义

目的探讨p53蛋白、Ki67在慢性胃炎和胃癌中的表达及意义。方法采用免疫组化法分别对58例胃癌,20例胃炎,进行了p53蛋白和Ki67的检测。结果①胃癌组织中p53蛋白、Ki67的阳性表达率分别为31.03%(18/58)、70.69%(41/58),均显著高于胃炎组织,差异均有统计学意义(P=0.042,P=0.005)。②在胃癌组织中p53蛋白的阳性表达与胃癌的临床分期、浸润深度、和淋巴结转移有关(P<0.05),与组织学分化程度无关(P>0.05);胃癌中Ki67的表达阳性率与胃癌的临床分期和浸润深度有关(P<0.05),与组织学分化程度和淋巴结转移无关(P>0.05)。③p53蛋白和Ki67共同阳性者14例,共同阴性者14例,相关性分析显示,二者之间呈正相关(r=0.372,P=0.004)。结论 p53蛋白和Ki67在胃癌中的表达明显升高,可作为判断胃癌恶性程度及预后的重要参考指标。     

Ki-67、p53蛋白在胃癌组织中的表达及临床意义

目的 研究Ki-67、p53蛋白在胃癌组织中的表达情况及临床意义.方法 选择我院病理科胃癌组织标本60例,同时选择癌旁组织标本20例,应用免疫组化SP法检测 Ki-67、p53蛋白的表达情况.结果 Ki-67、p53蛋白在胃癌组织中的阳性表达率高于癌旁组织,差异有统计学意义(P<0.05);Ki-67、p53蛋白的阳性表达率在有淋巴结转移、低度分化、浸润肌层及浆膜层的组织中高于无淋巴结转移、高、中度分化、浸润黏膜层及黏膜下层的组织,差异有统计学意义(P<0.05,P<0.01);Ki-67与p53蛋白在胃癌组织中的表达呈正相关(r=0.679,P<0.01).结论 Ki-67、p53蛋白均参与胃癌的发生和发展,二者可作为判断胃癌恶性程度及评估预后的指标.     

三阴性乳腺癌中p53和Ki67的表达情况及临床意义

目的 研究三阴性乳腺癌中p53和Ki67的表达情况及临床意义.方法 选择接受治疗的经病理确诊为浸润性乳腺癌患者102例,随机分为2组,其中三阴性乳腺癌51例(观察组),非三阴性乳腺癌51例(对照组),比较2组患者p53和Ki67的阳性表达情况,分析三阴性乳腺癌p53和Ki67表达与年龄、组织学分级、脉管浸润、肿瘤直径以及淋巴结转移之间的关系,同时研究p53和Ki67表达与乳腺癌生存率之间的相关性.结果 观察组患者的p53和Ki67的阳性表达率高于对照组患者,差异有统计学意义(P<0.05).观察组的p53表达与组织学分级、脉管浸润、肿瘤直径、淋巴结转移有密切联系(P<0.05),Ki67表达与组织学分级有密切联系(P<0.05).102例浸润性乳腺癌患者中,p53表达阳性的生存率低于p53表达阴性者,且Ki67表达阳性的生存率低于Ki67表达阴性者,差异有统计学意义(P<0.05).三阴性乳腺癌中p53和Ki67为阳性患者的生存率低于阴性表达者,差异有统计学意义(P<0.05).结论 三阴性乳腺癌中p53和Ki67的阳性表达率较高,p53和Ki67的表达情况对肿瘤增殖能力、肿瘤恶性程度以及预后有着重要意义.     

P53和Ki67在食管癌中的表达及其临床意义

目的研究P53蛋白、Ki67在食管癌中的表达,探讨其临床意义。方法采用免疫组化法检测35例食管癌,13例食管炎组织中P53蛋白和Ki67的表达水平,分析其与临床及病理各参数的相关性。结果 P53蛋白、Ki67在食管癌组织中的阳性表达率显著高于食管炎,差异均有统计学意义(P=0.046,P=0.001)。在食管癌组织中P53蛋白的阳性表达率在临床分期、浸润程度、淋巴结转移及组织学分化程度方面有明显差异(P<0.05),Ki67的阳性表达率仅与食管癌的临床分期和浸润深度有关(P<0.05),与组织学分化程度和淋巴结转移无关(P>0.05)。食管癌组织中P53蛋白和Ki67的表达密切相关(P=0.006)。结论 P53蛋白和Ki67与食管癌的发生、发展有关,二者协作检测对判断食管癌恶性程度和预后具有重要的临床意义。     

p53和c-erbB-2的表达阳性率与胃癌浸润深度的关系

目的探讨p53和c-erbB-2的表达阳性率与胃癌浸润深度的关系。方法收集139例胃癌手术切除标本,包括黏膜内癌23例、浸润至黏膜下层31例、浸润至肌层47例、浸润至浆膜或浆膜外38例,切片采用免疫组化S-P法染色。结果p53和c-erbB-2的阳性表达分别从肿瘤局限于黏膜内和侵及黏膜下层时开始出现。不同浸润深度的胃癌中p53的阳性率比较,仅黏膜内癌组和浸润至浆膜或浆膜外组（P〈0.01）及浸润至黏膜下层组和浸润至浆膜或浆膜外组存在显著差异性（P〈0.05）,其余均无统计学意义。而各组c-erbB-2的表达阳性率比较均存在显著差异性（P〈0.01）。c-erbB-2表达阳性率与p53存在相关性（P〈0.05）。p53和c-erbB-2的不同表达方式中,浸润深度p53＋c-erbB-2＋组或p53-c-erbB-2＋组〉p53＋c-erbB-2-组〉p53-c-erbB-2-组（P〈0.05）,但p53＋c-erbB-2＋组与p53-c-erbB-2＋组比较无统计学意义（P〉0.05）。结论p53和c-erbB-2在胃癌中的表达不是同步的,p53突变有利于c-erbB-2的表达。在胃癌的浸润中,癌基因c-erbB-2突变或者抑癌基因p53突变是独立发挥作用的,并且二者没有明显的协同作用;表达c-erbB-2的胃癌病例比表达p53的病例更具有侵袭性。     

P53蛋白在食管癌中的表达和临床意义

目的 探讨食管癌组织中p53蛋白的表达水平和临床意义.方法 用免疫组织化学染色SP法,检测62例食管癌组织p53蛋白过度表达情况.分析其与食管癌患者性别、年龄、肿瘤分化程度、肿瘤浸润程度及淋巴结转移等之间的关系.结果 p53蛋白在62例食管癌组织中表达的阳性率为48.4%.在男性和女性患者分别为50.0%和45.0%（P〉0.05）;低于60岁年龄组和高于60岁年龄组分别为46.9%和50.0%（P〉0.05）：高、中分化组和低分化组分别为47.6%和50.0%（P〉0.05）;肿瘤浸润黏膜及肌层的患者表达阳性率为61.1%,浸润全层时为30.8%（P〈0.05）;有淋巴结转移为65.8%,无淋巴结转移组为20.8%（P〈0.05）,即p53的阳性表达率与性别、年龄及肿瘤的分化程度无显著差异,而与细胞浸润深度和淋巴瘤转移状态具有统计学意义.结论 p53蛋白表达可能是评价预后不良指标之一.     

Ki67和p63蛋白表达与舌鳞状细胞癌的相关性

目的探讨舌鳞状细胞癌(SCC)组织中Ki67和p63蛋白表达与其临床特征的相关性。方法采用免疫组化方法检测60例原发性舌SCC组织Ki67和p63蛋白的表达,分析其与舌SCC临床特征的关系。结果在舌SCC组织中,p63总阳性率明显高于Ki67总阳性率(P<0.05)。Ki67表达率随组织分化程度的降低而增高(P<0.05);Ki67在舌SCCⅠ、Ⅱ期的表达明显低于Ⅲ、Ⅳ期(P<0.05);有局部淋巴结转移者的Ki67表达明显高于无局部淋巴结转移病例(P<0.05)。p63蛋白表达与其临床病理特征无明显相关性(P>0.05)。结论 Ki67表达与舌SCC预后密切相关。     

胃癌中Ki67与pl6的表达及相关性探讨

目的分析胃炎组织、不典型增生组织和癌组织中Ki67和p16的表达情况,探讨其与胃组织癌变的关系及作为早期癌变生物学标志的可能性。方法应用免疫组织化学SP法对22例胃炎组织、80例不典型增生组织及6O例胃癌组织中的Ki67和pl6的表达情况进行检测。结果在胃炎组织、不典型增生组织及胃癌组织中Ki67则呈递增趋势,而pl6的表达阳性率呈递减趋势;结果显示Ki67和pl6表达阳性率与胃黏膜组织从胃炎至不典型增生再至癌变这一过程均相关(P0.05)。Ki67的表达与胃癌的Lauren分型、浸润深度、淋巴结转移有关,与分化程度无关。Pl6的表达与胃癌的Lauren分型、分化程度、浸润深度无关,与淋巴结转移有关。Ki67和pl6的表达在胃癌组织中呈负相关(P0.05)。结论 Ki67和pl6的表达异常与胃癌的癌变过程相关,两者有可能成为胃组织早期癌变的分子标记物。     

三阴性乳腺癌的临床病理特征及TopoⅡα、Ki67表达

目的 探讨三阴性乳腺癌的临床病理特征及TopoⅡα、Ki67表达情况.方法 分析78例三阴性乳腺癌患者发病年龄、肿瘤大小、组织学类型、淋巴结转移情况;同时采用免疫组化EnVision二步法检测TopoⅡα、Ki67蛋白表达水平,并与同期1 14例非三阴性乳腺癌患者比较.结果 三阴性乳腺癌组患者腋窝淋巴结转移率高于非三阴性乳腺癌患者,两组比较差异有统计学意义（P＜0.05）;随着肿瘤的增大,三阴性乳腺癌患者腋窝淋巴结转移率明显增高,两者呈正相关（P＜ 0.05）;Non-TNBC组Ki67阳性率低于TNBC组,差异有统计学意义（x2=4.003,P=0.045）.结论 三阴性乳腺癌侵袭性强、淋巴结转移率高,具有更高的肿瘤增殖活性,预后较其他类型患者差.     

Annexin Ⅱ、钙卫蛋白在胃癌中的表达及临床意义

目的研究AnnexinⅡ、钙卫蛋白在胃癌中的表达及意义。方法用SP法检测正常胃组织、胃溃疡组织、胃癌组织中AnnexinⅡ,钙卫蛋白表达情况,以及与性别、年龄、肿瘤浸润深度和淋巴结转移的关系。数据分析采用SPSS13.0统计软件包处理。结果 AnnexinⅡ在胃癌组织中阳性表达率明显高于胃溃疡组和正常组,差异有统计学意义(P<0.05)。钙卫蛋白在胃癌组织中的阳性表达率明显高于正常胃组织的阳性表达率(P<0.05),胃癌组织和胃溃疡组织之间的阳性表达率无统计学意义(P>0.05)。AnnexinⅡ和钙卫蛋白与胃癌的浸润深度、淋巴结转移情况有显著性差异,差异有统计学意义(P<0.05),而与患者的年龄及性别无明显差异(P>0.05)。结论AnnexinⅡ和钙卫蛋白可能参与了胃癌的形成,并且在胃癌形成后的肿瘤生长、浸润、转移过程中起促进作用。     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

Self-stimulation and amphetamine: Tolerance to d and l isomers and cross tolerance to cocaine and methylphenidate

The effects of the d and l isomers of amphetamine on self-stimulation responding were tested following acute and chronic administration. Tolerance and post-drug depression of responding occurred in tests with both isomers, indicating no role for p-hydroxynorephedrine (PHN) which is one of the metabolites of d-amphetamine. In the second experiment, d-amphetamine, methylphenidate and cocaine all produced quantitatively and qualitatively similar effects on self-stimulation responding following acute administration. Following chronic administration of d-amphetamine, animals showed tolerance to all three drugs, indicating cross-tolerance among them. These data are consistent with an hypothesis that tolerance and post-drug depression following chronic amphetamine treatment are the result of decreases in postsynaptic receptor sensitivity, which would lead to a decreased effectiveness of all three drugs, regardless of their pre-synaptic mechanisms.     

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Rationale  Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans. Objectives  The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats. Materials and methods  In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers. Results  Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats. Conclusions  The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

Alprazolam and lorazepam single and multiple-dose effects on psychomotor skills and sleep

Summary The effects of alprazolam 0.5 mg and lorazepam 2 mg on cognitive and psychomotor skills were assessed in twelve normal volunteer subjects in a randomised, double-blind, crossover design. Single and multiple dose effects were monitored using a battery of tests comprising critical flicker fusion threshold (CFFT), choice reaction time (CRT), simulated car tracking, and subjective ratings of perceived sedation (LARS) and of sleep behaviour (LSEQ). Compared with placebo baseline scores, treatment with lorazepam 2 mg (both single and multiple doses) resulted in a widespread impairment of CRT, tracking accuracy, and CFFT. Single doses of alprazolam 0.5 mg reduced CFFT with respect to the placebo baseline. Single and multiple dose treatment with both drugs resulted in subjective reports of sedation, a reduction of sleep onset latency, and improved sleep quality. Only lorazepam 2 mg significantly disrupted the integrity of behaviour on waking from sleep. These results suggest important pharmacodynamic differences between the two drugs in the doses used.