nm23-H1蛋白在宫颈上皮内瘤变及宫颈癌中的表达及临床意义

目的探讨宫颈上皮内瘤变及宫颈癌中肿瘤转移抑制基因nm23-H1蛋白（nonmetastatic protein 23 homologue 1）的表达,试图阐明nm23-H1蛋白的表达在宫颈癌发生、发展及预后的作用。方法采用免疫组化SP法检测宫颈鳞状上皮癌60例、宫颈上皮内瘤变60例（CINⅠ、CINⅡ、CINⅢ各20例）、正常宫颈上皮组织20例中nm23-H1蛋白的表达,并分析nm23-H1蛋白的表达与临床病理特征的关系。结果 nm23-H1蛋白在宫颈癌中的表达明显低于正常宫颈组织和宫颈上皮内瘤变CINⅠ及CINⅡ（P〈0.05）,CINⅢ中nm23-H1蛋白阳性表达率明显减少,但与宫颈鳞状上皮癌相比,差异无统计学意义（P〉0.05）。宫颈鳞状上皮癌中nm23-H1的表达与淋巴结转移及FIGO分期有关（P〈0.05）,与患者年龄、肿瘤的组织病理分级及肿瘤大小无关（P〉0.05）。结论 nm23-H1蛋白的低表达是宫颈癌的一个高危因素,对判断宫颈癌淋巴结转移和估计预后是一项有用的指标。     

P14、P16在宫颈癌中的表达及临床意义

目的 探讨P14、P16在宫颈癌组织中的表达及其与临床病理参数的相关性.方法 采用免疫组织化学链霉素抗生素-过氧化酶连接法(S-P法)检测P14、P16在56例宫颈鳞癌组织、20例CIN Ⅲ组织和30例正常宫颈组织中的表达情况.结果 P14和P16蛋白在正常宫颈组织中的阳性表达率明显低于CIN Ⅲ组织和宫颈癌组织,差异有显著性(P＜0.05).P14蛋白的表达与浸润深度、病理分级及淋巴转移有关(P＜0.05),与临床分期、年龄、肿瘤大小或脉管有无癌栓无关(P＞0.05);P16蛋白的表达与病理分级及淋巴转移有关(P＜ 0.05),与临床分期、年龄、肿瘤大小、浸润深度或脉管有无癌栓无关(P＞0.05).结论 P14、P16基因的高表达发生在宫颈癌和癌前病变阶段,对宫颈癌的诊断及预后判断有一定价值,故可作为肿瘤标记物用于宫颈癌的临床筛查及诊断.     

N-cadherin、E-cadherin及p63在宫颈癌中的表达及相关性

目的：研究N-cadherin、E-cadherin以及p63在宫颈癌中的表达及其与临床病理因素之间的相关性。方法采用免疫组化检测正常宫颈15例、宫颈上皮内瘤变(CIN)30例、50例宫颈癌组织中的N-cadherin、E-cadherin及p63的表达。结果 N-cadherin在正常宫颈组织、CIN以及宫颈癌中的阳性表达率逐渐升高,差异均有统计学意义(P<0.05)。而E-cadherin和p63在正常宫颈组织、CIN以及宫颈癌中的阳性表达率则逐渐降低差异均有统计学意义( P <0.05),N-cadherin的表达与肿瘤的分期、病理分级以及淋巴结转移等密切相关( P <0.05)。结论 N-cadherin的高表达及E-cadherin、p63的低表达与宫颈癌的发生、发展、侵袭、转移密切相关,对上述因子的调控有可能成为宫颈癌治疗的新的靶点。     

层粘连蛋白在宫颈癌中表达及意义

目的:研究宫颈癌组织中层粘连蛋白(LN)的表达与肿瘤侵袭和转移过程中的关系.方法:应用免疫组化法检测层粘连蛋白在宫颈基膜中的表达并分析其与不同临床分期和不同病理分级的关系.结果:1.不同宫颈组织基膜中LN表达差异无显著性(P＞0.05).2.不同临床分期的宫颈癌组织基膜中LN表达差异无显著性(P＞0.05).3. LN在不同病理分级的宫颈癌组织基膜中表达差异有显著性(P＜0.05).结论:基底膜LN表达与宫颈癌临床分期无关,与宫颈癌病理分级有关,可作为临床判断宫颈癌分化程度高低的参考指标.基底膜LN表达异常有助于判断宫颈癌预后.     

宫颈鳞癌及宫颈上皮内瘤变组织中PINCH、nm23-H1蛋白的表达及临床意义

目的探讨PINCH蛋白和nm23-H1蛋白在宫颈鳞癌及宫颈上皮内瘤变（CIN）组织中的表达及临床意义。方法应用免疫组化SP法检测60例宫颈鳞癌、30例CIN和20例正常宫颈上皮组织中PINCH和nm23-H1蛋白的表达,并结合临床病例特征进行分析。结果 PINCH蛋白在正常宫颈、CIN和宫颈鳞癌间质中的阳性表达率分别为0.0（0/20）、33.3%（10/30）、70.0%（42/60）,呈现逐渐增高的趋势（P〈0.01）;nm23-H1蛋白的阳性表达率分别为95.0%（19/20）、70.0%（21/30）、46.7%（28/60）,呈现逐渐降低的趋势（P〈0.01）。PINCH和nm23-H1的表达与患者的淋巴结转移及FIGO分期有关（P〈0.01）,与患者年龄、肿瘤的组织病理分级及肿瘤大小无关（P〉0.05）。PINCH和nm23-H1在CIN和宫颈鳞癌中表达均有相关性（C值分别为0.697和0.531,P〈0.01）。结论 PINCH蛋白和nm23-H1蛋白可能协同参与了调控宫颈鳞癌的发生、发展过程,并在宫颈鳞癌的转移和淋巴结转移中起一定作用。     

The expression and significance of PTEN and p53 in the tissues of invasive carcinoma of cervix uteri and cervical precancerous lesion

目的 探讨PTEN和p53在宫颈鳞癌组织及宫颈上皮内瘤变组织中蛋白表达及其意义.方法 采用免疫组化SP法检测30例宫颈炎组织、50例宫颈上皮内瘤变(CIN)、30例浸润宫颈癌组织中PTEN基因和p53的表达.结果 PTEN在慢性宫颈炎、CINⅠ、CINⅡ、CINⅢ、浸润性宫颈鳞癌组织中,阳性表达率分别为100%、92%、73.33%、40%、36.67%,表达率逐渐下降,差异有统计学意义(P<0.05).PTEN表达与宫颈鳞癌病理分期有关(P<0.05),宫颈癌p53阳性的中PTEN缺失为70.83%,而p53阴性PTEN的缺失为61.54%,两者比较差异无统计学意义(P＞0.05).结论 PTEN和p53可能在宫颈癌的发生、发展中起重要作用,测定宫颈CIN中PTEN可作为宫颈癌的高危人群筛选指标,PTEN 与p53检测还可作为宫颈癌的预后指标.     

人附睾蛋白4(HE4)在宫颈癌中的表达及临床意义

目的 探讨HE4在宫颈癌发生发展中的作用,并初步分析其与宫颈癌临床病理因素的关系.为寻求新的有效的宫颈癌血清标志物提供实验基础.方法 采用免疫组织化学SP法检测正常宫颈组织30例、低度宫颈上皮内瘤变30例、高度宫颈上皮内瘤变30例、宫颈癌144例患者子宫颈中HE4的表达水平及分布.结果 HE4在正常宫颈、低度宫颈上皮内瘤变、高度宫颈上皮内瘤变和宫颈癌组织的阳性表达程度不同.宫颈组织癌中HE4表达显著高于正常宫颈组织,差异具有统计学意义;而在正常宫颈、低级别、高级别CIN中的阳性表达程度存在有差异,但无统计学意义(26.3％、59.0％、67.3％,P=0.181、P=0.086).HE4的阳性表达率与宫颈癌的肌层浸润深度、腹膜后淋巴结转移情况、高危型HPV感染等有相关性,HE4表达与宫颈癌患者年龄、分娩次数、临床分期、病理分级无相关性(P＞0.05).结论 宫颈癌组织中的HE4表达显著高于正常宫颈组织.子宫颈癌是HE4高表达的肿瘤.HE4与子宫颈癌肌层浸润深度、腹膜后淋巴结转移情况、高危型HPV感染等有相关性,HE4可作为宫颈癌高危因素指标.     

Survivin、Ki67和P63在宫颈上皮内瘤变及宫颈癌中的表达及临床意义

目的探讨Survivin、Ki67和P63在宫颈上皮内瘤变（CIN）及宫颈癌中的表达及临床意义。方法采用免疫组化PV-9000二步法检测Survivin、Ki67和P63在20例正常宫颈组织、30例CIN、50例宫颈鳞癌中的表达情况及三者间的相关性。结果正常宫颈组织、ClN及宫颈鳞癌组织中Survivin、Ki67与P63三者阳性表达率均随病变程度加重而逐渐升高（P均〈0.05）。在宫颈癌中,Survivin阳性表达与临床分期及淋巴结转移呈正相关;Ki67阳性表达仅与临床分期呈正相关;P63阳性表达仅与组织学分级相关;宫颈鳞癌组织中Ki67与P63、Survivin的表达均密切相关（P均〈0.01）。结论 Survivin、Ki67及P63联合检测可作为早期诊断CIN及宫颈癌的标记物,可提高宫颈癌的早期诊断率,对预后起到重要作用。     

HER3表达与宫颈鳞状细胞癌局部血管生成和浸润转移及预后的关系

目的 探讨HER3在宫颈鳞状细胞癌组织的表达及其临床意义.方法 采用免疫组化SP法检测HER3在28例宫颈正常上皮(NCE)、36例宫颈上皮内瘤变(CIN)和68例宫颈鳞状细胞癌(SCC)组织的表达,并检测其中Ki-67标记的增殖指数(PI)和CD34标记的微血管密度(MVD).结果 HER3在NCE、CIN及SCC组的阳性表达率分别为10.7%(3/28)、22.2%(8/36)及54.4%(37/68).HER3在SCC组的阳性表达率均高于CIN和NCE组(P＜0.05).HER3在SCC组表达分别与PI及MVD显著正相关(PI:r=0.375,P=0.002;MVD:r=0.273,P=0.024).HER3在SCC组表达分别与FIGO分期及组织学分级有关(P＜0.05),而与患者年龄、有否盆腔淋巴结转移、脉管浸润、间质浸润深度及生存率无关(P＞0.05).FIGO分期为Ⅱ期及组织学分级为Ⅲ级者,其HER3的阳性表达率分别显著高于FIGO分期为Ⅰ期及组织学分级在Ⅱ级以内者(P＜0.05).结论 HER3过度表达可能上调宫颈鳞癌细胞增殖及间质血管新生,可能促进宫颈鳞癌病程进展.     

转移相关基因蛋白CD44v6和nm23-H1在宫颈病变中的表达及意义

目的探讨CD44v6和nm23-H1与宫颈癌的早期发生、发展及淋巴结转移的关系。方法应用间接免疫荧光染色法和流式细胞技术检测102例宫颈组织中CD44v6和nm23-H1蛋白的表达。结果CD44v6在宫颈癌组、宫颈上皮内瘤样病变（CIN）组及正常宫颈组的表达依次增高（P〈0．05）。nm23-H1在宫颈癌组与CIN组的表达接近（P〉0．05）,但高于正常组（P〈0．05）。CD44v6在CINⅡ、Ⅲ级表达接近（P〉0．05）,但高于CINI级（P〈0．01）。nm23-HI在CIN各级表达接近（P〉0．05）。CD44v6随宫颈癌期别表迭增高（P〈0．01）,盆腔淋巴结转移的宫颈癌组CD44v6表达高于无转移者（P〈0．01）。nm23-H1表达与CD44v6结果相反。结论CD44v6、nm23-HI与宫颈癌的早期发生、发展及淋巴结转移均有相关性。     

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.     

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.     

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.     

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.     

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。     

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.     

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.     

Synthesis and anti-inflammatory and analgesic activities of pyridyloxy- and phenoxyalkanoic acid derivatives

Synthesis of pyridyloxy-, pyridyloxyphenoxy- and phenoxylphenoxyalkanate derivatives and their anti-inflammatory and analgesic activities were investigated. Analysis of structure-activity relationships showed that in pyridyloxyalkanoic acid derivatives anti-edematous potency was associated with the presence of chlorophenoxypropionic acid moiety and 2-nitrated methyl propionates contributed to the analgesic activity.