维吾尔族妇女子宫颈病变中抑癌基因和人乳头瘤状病毒表达相关性研究

目的 探讨抑癌基因人第10号染色体缺失的磷酸酶及张力蛋白同源的基因(PTEN)、人乳头瘤病毒(HPV)与新疆维吾尔族妇女子宫颈病变的相关关系.方法 选取维吾尔族妇女正常或炎症的子宫颈组织标本30例为对照组,宫颈病理标本按病变程度及病理学诊断分为宫颈上皮内瘤样病变(CIN)Ⅰ组、CINⅡ～Ⅲ组各30例、宫颈鳞癌组织30例子宫颈鳞癌组采用免疫组化SP法检测PTEN蛋白表达,采用聚合酶链反应(PCR)检测HPV阳性率.结果 PTEN的蛋白表达率在正常或炎症的子宫颈组织、CIN Ⅰ、CINⅡ～Ⅲ、宫颈鳞癌组织中分别为83.3％ 、73.3％、56.7％、23.3％,子宫颈鳞癌组阳性表达率明显减少,与前3组比较差异有统计学意义(P＜0.05).4组HPV阳性率分别为43.3％、56.7％、76.7％、93.3％,HPV阳性率和子宫颈病变程度呈正相关(P＜0.05).结论 新疆维吾尔族妇女子宫颈病变组织中PTEN蛋白水平表达减少,与其宫颈病变呈负相关关系;是子宫颈组织恶变的信号.HPV感染与子宫颈病变的严重程度呈正相关,HPV感染在子宫颈病变的发展过程中起到了极大的促进作用,是子宫颈癌致病因素之一.     

宫颈鳞癌中癌基因C-myc与相关蛋白E_2F-1P15~(INK4b)的表达及临床意义的研究

目的探讨宫颈鳞状细胞癌癌变过程中C-myc基因与其相关蛋白E2F-1、P15INK4b的表达以及与宫颈鳞癌临床病理特征的相关性。方法选取60份宫颈鳞癌、61份宫颈上皮内瘤变(CIN)组织(其中CINⅠ～Ⅱ级31份,CINⅢ级30份)和21份正常宫颈组织。所有病例制成组织芯片,采用原位杂交技术检测各组宫颈病变中C-mycmRNA的表达情况;免疫组织化学法(Elivison二步法)检测各组中E2F-1、P15INK4b蛋白的表达。统计学方法采用χ2检验和Spearman等级相关分析。结果随着宫颈从正常组织到发生CINⅠ～Ⅱ、CINⅢ直至发展为鳞状细胞癌,C-mycmRNA、E2F-1和P15INK4b蛋白的阳性表达率显著增高,差异有统计学意义(P<0.05)。C-mycmRNA在2组间的表达差异均有统计学意义。E2F-1蛋白的阳性表达在CINⅢ与宫颈鳞癌组之间差异有统计学意义。P15INK4b蛋白的阳性表达在CINⅠ～Ⅱ与CINⅢ、CINⅢ与鳞癌组间比较差异有统计学意义(P<0.05)。C-mycmRNA与E2F-1、P15INK4b的阳性表达均呈正相关(P<0.01)。E2F-1与P15INK4b的阳性表达呈正相关(P<0.01)。结论 C-myc癌基因在子宫颈鳞状细胞癌的发生、发展过程中起重要作用,其高表达预示子宫颈鳞状细胞的不良转化。C-myc癌基因与E2F-1、P15INK4b蛋白共同作用于CINⅢ向浸润性鳞癌的发展过程。     

p16INK4A蛋白在子宫颈癌及癌前病变中表达的意义

目的 探讨p16INK4A蛋白在子宫颈癌及癌前病变中表达的意义.方法 采用免疫组织化学技术S-P法检测45例子宫颈鳞癌组织、25例子宫颈上皮内瘤变(CIN)组织、20例宫颈正常组织或反应性增生组织中的p16INK4A表达情况.结果 p16INK4A在宫颈鳞癌组织中阳性表达率为100%,宫颈上皮内瘤病变组织中阳性表达率为88%(22/25),正常子宫颈鳞状上皮及反应性增生的鳞状上皮组织中阳性表达率为0(0/20).结论 p16INK4A蛋白的过度表达可以作为宫颈癌及其CIN的病理诊断指标之一.     

宫颈上皮内瘤样病变及宫颈癌中细胞周期素D1、Ki67的表达

目的探讨细胞周期素D1和Ki67在宫颈上皮内瘤样病变中表达及其意义。方法采用免疫组化法检测慢性宫颈炎组织11例、宫颈上皮内瘤样病变不同分级组织53例和宫颈鳞癌15例组织中细胞周期素D1和Ki67表达。结果宫颈鳞癌和CIN组织中细胞周期素D1表达明显高于子宫颈慢性炎症组织;细胞周期素D1表达与CIN分级程度成正相关。Ki67阳性表达与CIN分级程度成正相关,在宫颈鳞癌中有显著性(P<0.01);Ki67在细胞周期D1阳性表达组的标记指数高于阴性组(P<0.05)。结论细胞周期素D1蛋白过度表达可能在宫颈CIN及宫颈鳞癌发生、发展中发挥作用,Ki67与CIN及宫颈鳞癌发生有关,细胞周期素D1及Ki67与CIN分级有关。     

Wnt-1蛋白在宫颈鳞癌及癌前病变中的表达及意义

目的探讨Wnt-1蛋白在子宫肌瘤组织,宫颈病变组织（上皮内瘤变和宫颈鳞癌）中的表达及意义。方法取同期因子宫肌瘤行子宫全切的患者30例,宫颈上皮内瘤变患者（CIN）63例,宫颈鳞癌患者51例,术前均未接受放化疗,或其他治疗。用免疫组化SABC法对Wnt-1蛋白在正常宫颈组织、宫颈上皮内瘤变（CIN）组织和宫颈鳞癌组织中的表达水平进行检测。结果宫颈病变组Wnt-1表达明显高于子宫肌瘤组,差异有统计学意义（P〈0．001）：Wnt-1表达高度病变组高于低度病变组,差异有统计学意义（P=0．048）,宫颈鳞癌组高于低度病变组,差异有统计学意义（P〈0．001）;宫颈鳞癌组高于高度病变组（P=0．039）。结论Wnt信号通路的主要成员Wnt-1蛋白的过高表达与宫颈病变的发生、发展有关。     

基质金属蛋白酶组织抑制因子-1、2在宫颈鳞癌中的表达及意义

目的:探讨基质金属蛋白酶组织抑制因子(TIMP)-1和TIMP-2在宫颈鳞癌组织中的表达及其与宫颈癌临床病理特征的关系。方法:采用免疫组织化学MaxvisionTM法,检测46例宫颈鳞癌,34例宫颈原位癌(CINⅢ)和20例正常宫颈上皮(NCE)组织中TIMP-1、TIMP-2的表达,分析其表达与宫颈鳞癌的临床分期、病理类型及有无淋巴结转移的关系。结果:宫颈鳞癌、原位癌和正常宫颈上皮中TIMP-1的阳性表达率分别为54.3%(25/46)、73.5%(25/34)和20.0%(4/20)。TIMP-2为60.9%(28/46)、50.0%(17/34)和20.0%(4/20)。TIMP-1和TIMP-2蛋白阳性表达率在鳞癌组及原位癌组明显高于对照组,差异有统计学意义(P<0.01);在不同的临床分期和病理类型宫颈鳞癌患者中,TIMP-1和TIMP-2的阳性表达率差异无统计学意义(P>0.05);TIMP-2在宫颈鳞癌无淋巴结转移患者的阳性表达率较有转移患者高(P<0.05),而TIMP-1未发现此现象。结论:TIMP-1和TIMP-2在子宫颈鳞癌浸润和转移中起重要的作用。     

应用组织芯片探讨宫颈癌前病变及宫颈癌中DNA拓扑异构酶Ⅱα的表达及其临床意义

目的探讨DNA拓扑异构酶Ⅱα(TopoⅡα)蛋白在宫颈癌前病变及宫颈癌中的表达及其在宫颈癌发生发展中的作用。方法选取2007—2008年在山西省肿瘤医院行宫颈病变诊治的患者,其中包括慢性宫颈炎,低级别和高级别宫颈上皮内瘤变(CIN)和宫颈浸润性鳞癌(SCC)的患者分别21、33、30、73例,制作组织芯片,应用免疫组织化学法(SP)检测宫颈组织中TopoⅡα蛋白的表达情况。结果结果 TopoⅡα蛋白在慢性宫颈炎上皮组织、CINⅠ、CINⅡ^Ⅲ、SCC中的表达率分别是5%,12%,90%,97%,表达率逐渐增加,高级别CIN和浸润性鳞癌的表达显著高于低级别CIN和正常宫颈组织,差异有统计学意义;而高级别CIN与浸润性癌之间、低级别CIN与正常宫颈上皮之间的表达差异均无统计学意义。结论 TopoⅡα蛋白表达随着宫颈癌前病变的严重程度的加重而增加,因此TopoⅡα蛋白可能参与了宫颈上皮的异常增生和恶性转变。     

PTEN和p53在宫颈浸润癌和癌前病变组织中的表达及意义

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、CIN Ⅰ、CIN Ⅱ、CIN Ⅲ、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。     

HPV16-E6蛋白在宫颈病变组织中的表达及临床应用

目的：探讨16型人乳头瘤病毒（HPV16）E6蛋白在宫颈病变组织中的表达及其意义。方法：选择2009年12月～2010年12月于本院妇科门诊检查后临床诊断为宫颈炎、宫颈上皮内瘤变（CIN）、宫颈癌、宫颈正常的患者,分别为12例、20例、27例、10例,采用免疫组化SP法检测病变组织标本HPV16-E6蛋白表达情况。结果：HPV16-E6蛋白在正常宫颈上皮、宫颈炎、CIN、浸润性宫颈鳞癌中的阳性表达率分别为0（0/10）、33.3%（4/12）、45.0%（9/20）、66.6%（18/27）,组间比较,差异有统计学意义（P〈0.05）。病变组织的HPV16-E6蛋白阳性表达率显著高于正常宫颈组织（P〈0.05）,其中宫颈癌的阳性表达率最高,显著高于宫颈炎和CIN。结论：HPV16-E6蛋白表达与宫颈病变有重要联系,HPV16-E6蛋白的检测可以作为宫颈癌前病变转归的指标。     

免疫组织化学检测P16、Ki67在宫颈鳞状上皮内病变中的应用

目的 分析免疫组化P16、Ki67在宫颈鳞状上皮内病变中的应用及意义.方法 收集经活检或手术切除宫颈组织标本,其中宫颈鳞状上皮内病变80例将其作为病例组,此外将30例非宫颈病变手术切除正常宫颈组织标本作为对照组.采用S-P免疫组化方法对所有标本进行P16、Ki67表达的检测,并分析其表达及意义.结果 P16阳性率依次由对照组、CINⅠ、CINⅡ、CINⅢ组呈上升趋势,对照组与病例组两两比较差异有统计学意义(P<0.05);对照组Ki67阳性率明显低于病例组CINⅠ、CINⅡ、CINⅢ,差异有统计学意义(P<0.05),病例组内比较差异无统计学意义(P>0.05);P16、Ki67的关联性比较差异无统计学意义(P>0.05).结论 Ki67和P16的表达情况可有效甄别子宫颈良性反应病变情况,但二指标的关联性不强,提示其对病变的指示方向并非相同,因此,对于Ki67和P16的表达情况进行联合检测,可以更为公允的帮助相关人员鉴定子宫颈病变情况,值得在临床中进一步推广.     

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.