PCNA、ER和PR在子宫内膜癌中的表达

目的：探讨PCNA、ER和PR在子宫内膜癌发生、发展中的作用,对子宫内膜癌的诊断、治疗及预后提供一定的理论依据。方法：SP法检测正常子宫内膜组织、增生期子宫内膜组织、不典型增生子宫内膜组织及子宫内膜癌组织中PCNA、ER和PR蛋白的表达变化,统计分析各组间PCNA、ER和PR表达变化与临床因素及病理特征间的关系,以及各指标间的相关性。结果：①子宫内膜癌组织中PCNA表达阳性率为89．47％,显著高于正常子宫内膜组、子宫内膜单纯或复杂型增生组和子宫内膜不典型增生组（P〈0．01,P〈0．01,P〈0．01）。②子宫内膜癌组织中ER表达阳性率为54．74％,显著低于正常子宫内膜组、子宫内膜单纯或复杂型增生组（P〈0．01,P〈0．01）,与子宫内膜不典型增生组无统计学意义（P〉0．05）。⑧子宫内膜癌组织中PR表达阳性率为62．Ii％,显著低于正常子宫内膜组、子宫内膜单纯或复杂型增生组（P〈0．01,P〈0．01）,与子宫内膜不典型增生组无统计学意义（P〉0．05）。④子宫内膜癌组织中PCNA、ER和PR的表达与患者年龄无相关性;PR的表达与临床分期有相关性（P〈0．05）,与病理分级、淋巴结转移和肌层浸润深度无相关性;而PCNA、ER的表达与临床分期、病理分级、淋巴结转移以及肌层浸润深度有均无相关性。结论：子宫内膜癌中PCNA表达增加,ER和PR表达降低,PCNA、ER和PR参与了子宫内膜癌的发生与发展。PR在子宫内膜癌的侵袭和转移中起作用。联合检测PCNA、ER和PR的表达可以为临床治疗子宫内膜癌提供重要依据。     

子宫内膜癌中CD105的表达及意义

目的 通过与CD34比较,研究CD105与子宫内膜癌发生、发展及预后的关系。方法采用免疫组化法检测子宫内膜癌25例（子宫内膜癌组）、非典型增生13例（非典型增生组）、正常内膜8例（对照组）中CD州、CD34、VEGF、ki-67的表达,CD105-MVD与临床参数进行分析。结果子宫内膜癌组和非典型增生组的表达显著高于对照组（P〈0．05）,非典型增生组与子宫内膜癌组间差异无统计学意义（P〉0．05）;CD105-MVD与FIGO手术一病理分期、浸润肌层深度及局部淋巴结转移呈显著正相关（P〈0．01）。结论CD105优于CD34,可用来预测非典型增生的恶变倾向,反映子宫内膜癌增殖生长状态,并可提供更多的预后信息。     

FHIT及Ki-67在子宫内膜癌组织中的表达及临床意义

目的探讨正常子宫内膜、子宫内膜增殖症及内膜癌组织中FHIT（脆性组氨酸三联体）及增殖抗原Ki-67的表达,以及子宫内膜癌发生及临床意义。方法应用免疫组化S-P法检测30例正常子宫内膜组织、32例单纯型增生过长、31例复杂型增生过长、36例不典型增生、65例子宫内膜癌组织中FHIT及Ki67的表达。结果FHIT蛋白在正常子宫内膜、单纯性增生过长、复杂型增生、不典型增生、子宫内膜腺癌组织中的阳性表达率依次递减,而Ki-67的阳性表达率依次递增,子宫内膜样腺癌和不典型性增生中FHIT阳性表达率明显低于正常增生期子宫内膜和单纯性增生（P〈0．01）,而Ki-67的阳性表达率明显高于正常增生期子宫内膜和单纯性增生过长（P〈0．01）,FHIT阳性表达缺失与组织学分级有关（P〈0．01）、与子宫肌层浸润程度和淋巴结转移无关;而Ki-67阳性表达与组织学分级、临床分期及淋巴结转移有关（P〈0.01,P〈0.05,P〈0．01）,与子宫肌层浸润程度无关,FHIT蛋白表达与Ki67呈负相关（t=-0．450,P〈0.000）。结论FHIT蛋白与Ki-67的异常表达与子宫内膜癌的发生相关,有可能成为子宫内膜组织早期癌变的有用标记物。     

转化生长因子β1及其Ⅱ型受体表达与子宫内膜癌发生的关系

目的探讨转化生长因子β1（TGF-β1）及其Ⅱ型受体（TGFβR-Ⅱ）与子宫内膜癌发生的关系。方法采用免疫组织化学方法检测子宫内膜癌、子宫内膜复杂增生、正常于宫内膜组织中TGF-β1及TGFβR-Ⅱ的表达。利用CD34相关抗原标记血管内皮细胞,计数微血管密度（MVD）。结果子宫内膜癌及复杂增生组织中TGF-β1表达明显高于正常子宫内膜组织（P〈0．05或P〈0．01）,而前两者之间差异无统计学意义（P〉0．05）。从正常子宫内膜、复杂增生到子宫内膜癌组织中TGFβR-Ⅱ表达逐渐下降甚至缺如,且两两差异均有统计学意义（P〈0．05）。子宫内膜癌组织中MVD高于复合增生组及正常子宫内膜（P〈0．05）,与TGF-β1呈正相关（r=0．182,P〈0．01）。结论TGF-β1过度表达促进子宫内膜癌的生长与血管发生,可能是子宫内膜癌发生的早期现象,其负性调控的丧失与TGFβR-Ⅱ表达下降或缺如有关。     

KAI1蛋白在子宫内膜癌中的表达及其意义

目的研究KAI1蛋白在子宫内膜癌组织中的表达及其与临床病理参数的关系。方法采用免疫组织化学SP法检测50例子宫内膜癌、20例不典型增生子宫内膜、10例正常增生期子宫内膜组织中KAI1蛋白的表达，并分析其与子宫内膜癌的临床病理参数的关系。结果KAI1蛋白在正常子宫内膜、子宫内膜非典型增生、子宫内膜癌中的阳性表达率逐渐降低，子宫内膜癌中KAI1蛋白的阳性表达率明显低于非典型增生组及正常子宫内膜组，差异有统计学意义（P=0．016）。子宫内膜癌中KAI1蛋白的表达与临床分期、组织学分级、肌层浸润深度和淋巴结转移相关，差异有统计学意义（P〈0．05）。结论KAI1蛋白在子宫内膜癌的恶性进展过程中表达逐渐下降，其可能成为估计子宫内膜癌恶性程度的生物学指标。     

BAG-1 Bcl-2 在子宫内膜癌发生 发展中的作用研究

目的探讨BAG-1、Bcl-2在子宫内膜癌中的表达情况。方法采用免疫组织化学链霉菌抗生素蛋白-过氧化物酶连接法检测正常子宫内膜组、子宫内膜增生过长组、子宫内膜不典型增生组和子宫内膜癌组组织中BAG．1和Bcl．2蛋白的表达情况。结果BAG-1在子宫内膜癌中呈高表达,其阳性率为64．0％,明显高于正常子宫内膜组、子宫内膜增生过长组和子宫内膜不典型增生组（9．5％、26．7％和30．8％）,差异均有统计学意义（P〈0．05）。Bcl-2在子宫内膜癌中表达阳性率（46．0％）明显低于子宫内膜增生过长组（73．3％）,差异有统计学意义（P〈0．05）。结论BAG-1在子宫内膜癌的发生、发展及转移中起重要作用。BAG-1表达越高,子宫内膜癌的组织学分化程度越低,临床分期越晚,癌组织越容易浸润,提示其恶性程度越高．患者预后不良。Bcl-2的表达参与子宫内膜癌的发生、发展过程并且与肌层浸润相关,但是与组织学分化无相关性。因此缺乏预测预后的证据。     

骨桥蛋白和CD44v6在子宫内膜癌中的表达及其意义

目的检测骨桥蛋白与CD44v6在正常子宫内膜、子宫内膜癌组织中的表达及特点,探讨二者与子宫内膜癌发生发展的关系。方法对45例子宫内膜癌患者采用免疫组织化学染色S-P等方法研究正常子宫内膜组织、子宫内膜癌组织中骨桥蛋白与CD44v6的表达,比较相关临床资料之间的关系;选择30例正常子宫内膜患者（年龄45岁以下,因子宫肌瘤行手术,术前未使用激素类药,病理证实,15例增生期,15例分泌期）作为对照进行研究。结果骨桥蛋白主要定位于细胞浆中,在子宫内膜癌组织中的表达高于正常子宫内膜组织的增生期和分泌期,差异具有统计学意义（P〈0．05）;骨桥蛋白在正常子宫内膜组织的分泌期的表达高于增生期,差异具有统计学意义（P〈0．05）。CD44v6在正常子宫内膜组织的增生期无表达;CD44v6在子宫内膜癌组织中的表达明显高于正常子宫内膜组织的增生期和分泌期,差异具有统计学意义（P〈0．05）;CD44v6在正常子宫内膜组织中的分泌期中的表达高于增生期,有统计学意义（P〈0．05）。骨桥蛋白和CD44v6的表达与子宫内膜癌病理分级、肌层浸润深度及组织学类型均无关,差异无统计学意义（P〉0．05）;分类变量相关性分析显示,骨桥蛋白和CD44v6在子宫内膜癌中的表达存在正相关性（r=0．34,P〈0．05）。结论骨桥蛋白和CD44v6可能参与子宫内膜癌的发生;二者与子宫内膜癌的恶性程度及局部浸润无关,但共同参与了子宫内膜癌的发生,联合检测两者的表达将有可能作为诊断子宫内膜癌的指标。     

子宫内膜癌组织中SC3A抗原和雌激素与孕激素受全的检测及意义

为探讨子宫内膜癌组织中抗人大肠癌相关抗原MAbSC3A及雌激素受体（ER）和激素受体（PR）表达的意义,用免疫组化方法检测66例子宫内膜癌组织中SC3A抗原的表达,并与ER和PR的表达水平进行比较,结果显示,在66例中阳性表达率分别为81．8％（54／66）、56．1％（37／66）和53．0％（35／66）。29例非典型子宫内膜增生病变和31例正常子宫内膜SC3A阳性率分别为51．7％（15／29）和12．9％（4／31）。结果表明,子宫内膜癌组织中SC3A抗原的表达率明显高于ER和PR,同时也高于子宫内膜非典型增生病变和正常子宫内膜组（P＜0．05）。结论：SC3A抗原检测对子宫内膜癌的诊断和研究具有一定应用价值。     

P27^kipl蛋白在子宫内膜癌组织中的表达及意义

为探讨P27^kipl蛋白在子宫内膜癌组织中的表达及意义,用免疫组化法对66例子宫内膜癌组织中的P27^kipl蛋白表达进行检测,并与29例子宫内膜非典型增生病变和31例正常子宫内膜组织中的表达进行比较。结果显示,子宫内膜癌中P27^kipl蛋白阳性表达率为53．0％（35／66）,子宫内膜非典型增生病变和正常子宫内膜组织中的阳性表达率分别为75．8％（22／29）和87．1％（27／31）,与后比较差异有非常显意义（P＜0．01）,与前比较差异有显意义（P＜0．05）。P27^kipl蛋白在子宫内膜癌组织中的分级与组织学分级有关,其阳性表达率分别为I级59．0％,Ⅱ有47．0％,Ⅲ级为20．0％。结论：P27^kipl蛋白在子宫内膜癌组织中的表达水平也子宫内膜癌的发生发展及肿瘤组织分级有关,表明该蛋白对判别子宫内膜癌恶性程度和预测病程发展是一种有参考价值的指标。     

CD68与VEGF在子宫内膜腺癌中的表达及意义

目的探讨子宫内膜腺癌组织中CD68与VEGF的表达与子宫内膜癌临床病理参数之间的关系。方法采用免疫组化方法对40例子宫内膜腺癌（EAC）、20例正常子宫内膜（NE）及20例子宫内膜非典型增生fEAH）组织中的CD68与VEGF蛋白进行检测。结果（1）EAC组织CD68的表达明显高于NE、EAH组织（P〈0．05）;EAC组织CD68的阳性率与手术病理分期、组织学分级、淋巴转移有关（P〈0．05）,与年龄、肌层浸润无关（P〉0．05）。（2）EAC组织VEGF的表达明显高于NE、EAH组织（P〈0．05）;EAC组织VEGF的阳性率与手术病理分期、淋巴转移有关（P〉0．05）,与年龄、组织学分级、肌层浸润无关仍0．051。（3）CD68和VEGF蛋自在EAC中的表达呈现正相关（rs=0．420,P=-0．007）。结论CD68与VEGF在EAC组织中过量表达．呈明显正相关。CD68阳性细胞即肿瘤相关巨噬细胞（TAMs）、VEGF可能与EAC的发生发展有关,TAMs可能通过表达VEGF促进肿瘤的生长与转移．     

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.