Expression and Clinical Significance of LKB1 and VEGFR2 in Non-Small Cell Lung Cancer

目的:探讨LKB1和血管内皮生长因子受体-2(VEGFR2)在非小细胞肺癌中的表达情况及临床意义.方法:选取不同临床分型及进展程度的非小细胞肺癌78例,分别取材自癌组织及癌周围正常组织,应用免疫组化方法检测并分析组织中LKB1和VEGFR2的表达情况.结果:LKB1蛋白和VEGFR2在肺癌组织及癌旁正常肺组织中均有表达.在正常肺组织LKB1高于肺癌组织,VEGFR2低于肺癌组织;在肺癌组织LKB1在高分化组织和无淋巴转移组高于中、低分化和有淋巴转移组,而VEGFR2高分化组和无淋巴转移组低于中、低分化组,亦低于有淋巴转移组,差异均有统计学意义(P＜0.05或P＜0.01).结论:LKB1蛋白和VEGFR2在非小细胞肺癌中的表达呈相反趋势,LKB1的低表达、VEGFR2的高表达可能与非小细胞肺癌的肿瘤细胞分化及淋巴结转移有关.     

BCL11A、LKB1在非小细胞肺癌组织中的表达及意义

目的:本研究旨在探讨非小细胞肺癌中BCL11A、LKB1的表达情况,探索BCL11A与LKB1在肺癌发生及演变过程中的作用机制及两者之间的关系,为非小细胞肺癌的发生机制提供理论基础,并为非小细胞肺癌的早期诊断提供新思路。方法:(1)试验分组:60例非小细胞肺癌标本及40例正常对照肺组织。(2)采用免疫组织化学方法检测BCL11A及LKB1表达情况。结果:(1)非小细胞肺癌组织中,BCL11A阳性表达率显著高于对照组(P<0.05)。LKB1阳性表达率显著低于对照组(P<0.05)。两者的表达与性别、年龄及组织学类型无关,而与癌组织的分化程度、临床分期及淋巴结转移密切相关。(2)非小细胞肺癌组织中,BCL11A和LKB1两者表达强度之间呈负相关(P<0.05)。结论:(1)在非小细胞肺癌组织中BCL11A的高表达与LKB1的低表达密切相关,可能参与了非小细胞肺癌的演进。(2)LKB1基因蛋白表达缺失在不同类型和不同分化程度的非小细胞肺癌发生、发展中存在重要意义,可作为判断肺癌生物学行为和患者预后的参考指标。     

HMGN5和Twist在非小细胞肺癌组织中的表达及意义

目的:探讨HMGN5和Twist在非小细胞肺癌(NSCLC)组织中及癌旁组织中的表达及临床意义,观察两者在肺癌发生、发展及演变过程中的作用机制和两者之间的关系,为非小细胞肺癌的发生机制提供理论基础及为NSCLC的早期诊断提供新思路、新方法。方法:①试验分组:60例非小细胞肺癌标本及30例癌旁正常对照肺组织。②采用免疫组织化学方法检测HMGN5及Twist表达情况及其与临床病理学之间的联系。结果:60例NSCLC组织中,HMGN5、Twist蛋白阳性表达率分别为65.0%、71.7%,HMGN5显著高于癌旁肺组织阳性率16.7%,表明两者比较有统计学意义(P<0.05);HMGN5在NSCLC组织中阳性高表达率与吸烟史、年龄及组织学类型无关,而是与癌组织的临床分期、分化程度、淋巴结转移密切相关(P<0.05)。Twist在非小细胞肺癌组织中的阳性率为71.7%,显著高于非肺癌组织的阳性率16.7%,两者比较有统计学意义(P<0.01);Twist的表达与肺癌患者的TNM分期、细胞分化程度、肿瘤直径相关(P<0.05)。结论:HMGN5和Twist两者高表达强度之间呈显著正相关。在非小细胞肺癌组织中HMGN5的高表达与Twist的的高表达密切相关,可能参与了NSCLC的发生和发展。HMGN5、Twist基因蛋白高表达在不同类型和不同分化程度的非小细胞肺癌发生、发展中存在重要意义,可作为判断肺癌生物学行为和患者预后的重要参考指标。     

RECK及MMP-9在非小细胞肺癌中的表达及意义

目的:观察RECK和基质金属蛋白酶-9(MMP-9)在非小细胞肺癌组织中的表达,探讨RECK、MMP-9与非小细胞肺癌发生、发展及转移的关系。方法:采用免疫组织化学方法检测45例非小细胞肺癌组织标本、30例正常肺组织中RECK、MMP-9蛋白因子的表达情况。结果:RECK在非小细胞肺癌组织中的阳性表达率为53.3%,低于在正常肺组织的阳性表达;MMP-9在非小细胞肺癌的阳性表达率为80%,明显高于在正常肺组织中的阳性表达。RECK的表达与肺癌分化程度及淋巴结转移相关(P<0.05),MMP-9的表达与肺癌淋巴结转移及临床分期相关(P<0.05),RECK、MMP-9的表达之间存在显著负相关(r=-0.356,P<0.05)。结论:RECK与MMP-9在NSCLC的发展、转移过程中起重要的作用,RECK和MMP-9的联合检测有待成为非小细胞肺癌早期诊断和预后判断的分子指标之一。     

抑癌基因PTEN和P16在非小细胞肺癌中的表达及其临床意义

目的 研究抑癌基因PTEN及P16蛋白在非小细胞肺癌中的表达及其临床意义。方法 应用免疫组织化学法检测50例非小细胞肺癌石蜡切片及20例癌旁正常组织中PTEN及P16蛋白的表达情况。结果 PTEN及P16在肺癌中的阳性表达与正常肺组织相比差异有显著意义,PTEN表达在鳞癌,腺癌,鳞腺癌中差异有显著意义,腺癌高于鳞癌和鳞腺癌,而P16表达在鳞癌,腺癌,鳞腺癌中差异无显著意义;在非小细胞肺癌中,PTEN及P16蛋白表达随组织分化越差呈递减趋势;PTEN在肺癌中高中分化与低分化,有无淋巴结转移,Ⅰ/Ⅱ,Ⅲ期的阳性表达差异均有显著意义,在生存5年以上的病人中PTEN蛋白的表达显著高于生存5年以下的病人;而P16在高中分化与低分化,有无淋巴结转移中的蛋白表达差异有显著意义,但在Ⅰ/Ⅱ,Ⅲ期及5年生存情况中的蛋白表达差异无显著意义;非小细胞肺癌中PTEN及P16蛋白表达有相关性。结论 PTEN及P16在非小细胞肺癌的发生发展中起重要作用,其蛋白表达与肺癌的分化、分期、分级、转移及生存率密切相关;检测PTEN及P16蛋白的表达有助于非小细胞肺癌的早期诊断及预后判断。     

非小细胞肺癌中MMP-10和TIMP-3的表达

目的探讨非小细胞肺癌(NSCLC)组织中基质金属蛋白酶10(MMP-10)和组织金属蛋白酶抑制剂3(TIMP-3)的表达及其意义。方法采用免疫组化S-P法检测65例非小细胞肺癌组织和33例正常肺组织中MMP-10和TIMP-3的表达。结果非小细胞肺癌组织中MMP-10的表达显著高于正常肺组织(P<0.05)。非小细胞肺癌中MMP-10的表达有淋巴结转移者高于无淋巴结转移者(P<0.05),Ⅲ期高于Ⅰ、Ⅱ期(P<0.05)。非小细胞肺癌组织中TIMP-3的表达显著高于正常肺组织(P<0.05),非小细胞肺癌中TIMP-3的表达有淋巴结转移低于无淋巴结转移(P<0.05)。结论MMP-10和TIMP-3表达与非小细胞肺癌的侵袭、转移密切相关。     

非小细胞肺癌中乙酰肝素酶蛋白的表达及临床意义

目的研究非小细胞肺癌中乙酰肝素酶（HPSE）蛋白的表达状况及临床意义。方法采用免疫组化SABC三步法检测HPSE蛋白在非小细胞肺癌中和正常肺组织中的表达,结合非小细胞肺癌的临床病理特征进行分析。结果 HPSE蛋白在非小细胞肺癌组织的表达高于对照组（正常肺组织）,差异有显著性（P〈0.05）,有淋巴结转移的癌组织HPSE高于无淋巴结转移组（P〈0.01）,TNM分期Ⅲ～IV的癌组织表达高于Ⅰ～Ⅱ组（P〈0.01）,均有高度统计学意义。结论 HPSE的高表达可能在非小细胞肺癌的发生发展中起重要作用,HPSE可作判断非小细胞肺癌生物学行为和预后的参考指标。     

线粒体融合蛋白2、PCNA在非小细胞肺癌组织中的表达及意义

目的:探讨非小细胞肺癌(NSCLC)中线粒体融合蛋白2(Mfn2)、增殖细胞核抗原(PCNA)的表达与临床病理特征之间的关系及二者的相关性。方法:采用免疫组化SP法检测92例非小细胞肺癌组织中Mfn2、PCNA的表达。结果:肺鳞癌组织中Mfn2的表达(IOD值)高于腺癌(P<0.01),高分化、中分化的肺癌组织中Mfn2的表达高于低分化的肺癌组织(P<0.01);PCNA在肺癌组织中的表达(IOD值)随分化程度的降低而升高,高、中分化与低分化组相比较,差异均有统计学意义(P<0.05或P<0.01);有淋巴结转移组PCNA的表达高于无淋巴结转移组(P<0.01)。结论:Mfn2在非小细胞肺癌中的表达与组织学分型、分化程度有关;PCNA在非小细胞肺癌组织中的表达与分化程度、淋巴结转移有关,且二者的表达呈负相关。     

异质性细胞核核糖蛋白A2/B1在非小细胞肺癌的表达研究

目的观察异质性细胞核核糖蛋白A2/B1(HeterogeneousnuclearribonucleoproteinA2/B1,hnRNPA2/B1)在非小细胞肺癌的表达,探讨hnRNPA2/B1对非小细胞肺癌的诊断价值及与非小细胞肺癌临床分期、淋巴结转移的关系。方法采用免疫组织化学方法检测83例原发性非小细胞肺癌(肺癌组)、32例肺良性肿瘤(肺良性肿瘤组)及20例正常肺(正常肺组)组织中hnRNPA2/B1的表达。结果肺癌组hnRNPA2/B1表达阳性率79.50%(66/83),肺良性肿瘤组阳性率43.80%(14/32),正常肺组阳性率40.05%(8/20)。肺癌组阳性率显著高于肺良性肿瘤组及正常肺组(均P<0.05);肺良性肿瘤组阳性率与正常肺组无显著性差异(P>0.05)。Ⅰ～Ⅱ期肺癌的hnRNPA2/B1表达阳性率为67.60%(25/37),Ⅲ～Ⅳ期肺癌的阳性率为89.10%(41/46)。Ⅲ～Ⅳ期肺癌的阳性率显著高于Ⅰ～Ⅱ期肺癌(P<0.05)。有淋巴结转移患者的hnRNPA2/B1表达阳性率为88.00%(44/55),无淋巴结转移者的阳性率为66.70%(22/33)。有淋巴结转移患者的阳性率显著高于无淋巴结转移者(P<0.05)。结论hnRNPA2/B1过量表达与非小细胞肺癌的发生、发展和转移密切相关。检测hnRNPA2/B1对非小细胞肺癌的早期诊断、病情预测有重要的临床意义。     

PTEN在非小细胞肺癌组织中的表达及临床意义

目的：探讨抑癌基因PTEN在非小细胞肺癌组织中的表达缺失及与其发生发展的关系。方法：采用免疫组织化学（S-P）法评价非小细胞肺癌组织及癌旁组织中PTEN蛋白表达情况。结果：非小细胞肺癌中PTEN蛋白的阳性率为30.00%（12/40）,癌旁肺组织中PTEN蛋白的阳性率为100.00%（40/40）。肺癌组织的表达明显低于癌旁肺组织（χ2=37.48,P〈0.05）,其中在中-高分化的癌中PTEN的阳性率为83.33%（15/18）,在低分化癌中其阳性率为27.27%（6/22）,差异具有统计学意义（χ2=12.76,P=0.00）;临床分期,I＋II期PTEN的阳性率为70.83%（17/24）,在III＋IV期阳性率为31.25%（5/16）,差异具有统计学意义（χ2=6.77,P=0.01）;在无淋巴结转移的患者中,PTEN的阳性率为80.00%（16/20）,在有淋巴结转移的患者中其阳性率为35.00%（7/20）,差异具有统计学意义（χ2=9.05,P=0.00）。非小细胞肺癌组织中PTEN蛋白阳性率与分化程度、临床分期及有无淋巴结转移有相关性（P〈0.05）。而与组织学类型、性别、年龄、肿瘤大小无关（P〉0.05）。结论：非小细胞肺癌中PTEN蛋白的不表达或表达下降可能与非小细胞肺癌的发生有很大的相关性。     

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.     

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。     

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.     

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.     

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.