肝细胞癌组织中 IL-18BPc 和 VEGF 的表达及与肿瘤血管形成的关系

目的 探讨IL-18BPc和VEGF在原发性肝细胞癌组织中的表达及其与肿瘤血管形成之间的关系。方法 应用免疫组织化学SP法检测IL-18BPc和VEGF在34例肝细胞癌组织、34例癌旁肝组织及12例正常肝组织的表达,通过CD34免疫组织化学染色评价肿瘤组织MVD值,分析IL-18BPc表达与VEGF表达及MVD的关系。结果 IL-18BPc在肝癌组织中的表达阳性率高于癌旁肝组织(P＜0.01)及正常肝组织(P＜0.01),且肝癌出现侵袭转移者较未出现侵袭转移者其IL-18BPc表达阳性率高(P＜0.01);VEGF在肝癌组织中的表达高于癌旁肝组织(P＜0.01)及正常肝组织(P＜0.01);IL-18BPc和VEGF在肝细胞癌中表达呈正相关(r=0.357, P=0.037);肝癌组织MVD值与高于癌旁肝组织(P＜0.01)及正常肝组织(P＜0.01);肝癌组织中, IL-18BPc阳性表达者MVD值高于阴性表达者(P=0.004)。结论 IL-18BPc可能通过上调VEGF的表达促进肝细胞癌血管形成。     

缺氧诱导因子-1α表达和肿瘤微血管生成与肝细胞癌生物学行为的关系探讨

目的 研究缺氧诱导因子-1α（HIF-1α）的表达和肿瘤微血管生成与肝细胞癌（HCC）生物学行为的关系及临床意义。方法 应用免疫组化SABC法检测36例肝细胞癌及15例癌旁组织中HIF-1α的表达水平和微血管密度（MVD），分析两者间及其与肝细胞癌生物学行为的相互关系。结果 肝细胞癌组HIF—1α的表达水平及MVD较癌旁组织增加（P〈0．01），且肝细胞癌组中无包膜及已转移者HIF-1α的表达水平和MVD相应较有包膜及未发生转移者高（P〈0．05）；低分化肝细胞癌MVD较高分化肝细胞癌高（P〈0．01）；肝细胞癌组织中HIF-1α表达水平和MVD呈正相关（r=0．746，P〈0．01）。结论 HIF-1α可能参与了肝细胞癌微血管形成的调控，HIF-1α表达水平和MVD可反映肝细胞癌的生物学行为，可作为预测肝细胞癌浸润转移的一项重要指标。     

高尔基体蛋白73、AFP、VEGF在原发性肝癌组织中的表达及临床意义

目的分析评价高尔基体蛋白73（GP73）、AFP、VEGF在原发性肝癌、癌旁组织以及正常肝脏组织中的表达及临床意义。方法取原发性肝癌组织、癌旁组织及正常肝组织,分别检测GP73、AFP、VEGF的含量。结果肝癌组织中GP73、VEGF和AFP表达最强,其次为癌旁组织,正常组织中表达最弱,三者比较,差异有统计学意义（P〈0.01）。肝癌组织中,GP73和VEGF的表达均显著高于AFP（P〈0.01）。经Pearson相关分析显示GP73和VEGF在肝癌组织中的表达水平具有相关性（r=0.271,P〈0.01）。结论 GP73、VEGF和AFP在肝癌组织中呈高表达,联合检测三者有助于原发性肝癌的诊断。     

乙肝相关性肝癌组织中p27、p53及增殖细胞核抗原的表达

目的探讨乙肝相关性肝细胞癌组织中p27、p53与增殖细胞核抗原（proliferating cell nuclear antigen，PCNA）的表达及其临床病理学意义。方法通过免疫组化法检测40例乙肝相关性肝细胞肝癌组织及其相应的癌旁组织中p27、p53与PCNA的表达。结果（1）p53蛋白在肝癌组织中阳性表达率明显高于癌旁肝组织（P=0.047），低分化肝癌组织中p53阳性表达率明显高于高中分化者（P=0．017）。（2）肝癌组织中p27蛋白染色指数明显低于癌旁肝组织（P=0．045），在肿瘤直径〉5cm（P=0．031）与存在肝外转移的肝癌组织中进一步降低（P=0．028）。（3）肝癌组织中PCNA染色指数明显高于癌旁肝组织（P=0.029）。在肿瘤直径〉5cm（P=0．037）与包膜侵犯的肝癌组织中进一步增高（P=0．035）。（4）Cox比例风险模型多因素分析发现临床分期（P=0．028）为独立的预后因子。结论细胞周期调控因子p53、p27与PCNA的异常表达与乙肝相关性肝细胞癌的分化、浸润及转移有着密切的联系。     

热休克转录因子1在肝细胞癌中的表达及意义

目的:用半定量逆转录聚合酶链反应(RT-PCR)方法显示肝癌组织中热休克转录因子1(HSF1)的表达情况,探讨HSF1在肝细胞癌中的表达及意义.方法:收集肝癌患者40 例手术肝癌标本及相应的癌旁组织作为对照.采用半定量逆转录聚合酶链反应(RT-PCR)方法检测肝癌标本及相应的癌旁组织HSF1的表达,分析比较它们分别在肝癌标本及相应癌旁组织的表达情况及其与肝癌临床和病理特征的关系.结果:肝细胞癌肿瘤组织HSF1 mRNA表达显著高于癌旁组织,但HSF1表达水平与患者的性别、年龄、肿瘤大小、包膜的完整与否、分级、癌栓形成及血清AFP水平未见明显相关性(P＞0.05).结论:HSF1在肝癌组织中的表达显著高于癌旁组织,HSF1可能与PHC的发生密切相关.进一步探讨HSF1在PHC中的表达机制,有望为原发性肝癌的临床诊断与治疗提供依据.     

c-met原癌基因的表达及其与人肝细胞癌转移关系的研究

以β-actin为内标,用逆转录—多聚酶链反应（RT－PCR）技术,研究c－metmRNA在32例肝癌组织、26例癌旁肝组织中的表达。结果表明,32例肝癌组织、26例癌旁肝组织中均有c-met基因表达（表达率100％）,但肝癌c－met基因的表达值显著高于癌旁肝组织（46.75％±13．03％对2531％±11,03％,P＜0．001）。32例肝癌中c－met基因过度表达者有14例,统计分析发现c-met基因过度表达与肝细胞癌的分化程度及肝内转移有关。结果提示c－met基因在人肝细胞癌中高表达,并可能与肝癌的侵袭转移有关。     

肝细胞肝癌组织中促红细胞生成素受体的表达及其与微血管密度的相关性研究

目的探讨肝细胞肝癌（HCC）微血管密度（MVD）与促红细胞生成素受体（EPOR）表达之间的关系,以及此二者与临床病理学特征之间的关系。方法应用免疫组织化学法检测46例HCC、20例肝硬化和10例正常肝组织内EPOR的表达情况,观察与HCC病理学特点及MVD之间的关系。结果（1）EPOR及MVD值在HCC中的阳性表达率和强度显著高于肝硬化和正常肝脏组织（P〈0.05）;（2）EPOR在有包膜侵犯组、低分化组及有转移HCC中的阳性表达率及强度明显高于无包膜侵犯组（χ^2=6.40,P〈0.05;）、高中分化组（χ^2=12.03,P〈0.01）;以及无转移组（χ^2=5.62,P〈0.05）;（3）肝癌〉5cm、有包膜侵犯、有转移、低分化组的MVD值明显高于肝癌≤5cm（t=2.82,P〈0.05）、无包膜侵犯（t=3.91,P〈0.05）、无转移（t=4.10,P〈0.05）及高中分化组（t=5.12,P〈0.05）;（4）EPOR阳性表达HCC中的MVD值明显高于EPOR阴性表达HCC中的MVD值（t=5.43,P〈0.05）。结论EPOR在HCC组织中的表达上调与其血管生成和浸润转移有关。     

MMP-9/TIMP-1与肝癌侵袭转移及HBsAg表达的相关性研究

目的探讨基质金属蛋白酶-9（MMP-9）及组织金属蛋白酶抑制剂-1（TIMP-1）在人肝癌及癌旁组织中的表达和肝癌生物学行为及HBsAg表达之间的关系。方法应用免疫组织化学法（SP）研究40例肝癌及癌旁组织中MMP-9、TIMP-1和HBsAg的表达。结果MMP-9在肝癌和癌旁组织表达阳性率分别为72．5％和75．0％．癌组织明显减低（P〈0．01）。TIMP-1在肝癌组织和癌旁组织中的表达阳性率分别为57．5％和62．5％，肝癌中的表达较癌旁肝组织表达减低，但差异无统计学意义。转移组癌及癌旁组织MMP-9的表达显著高于无转移组（P〈0．05）：而TIMP-1则明显低于无转移组（P〈0．05）。本组肝癌患者组织HBsAg阳性率为82．5％，HBsAg阳性组中癌及癌旁组织MMP-9表达明显高于HBsAg阴性组（P〈0．05），TIMP-1在HBsAg阳性组的表达略高于HBsAg阴性组．但差异无统计学意义。MMP-9、TIMP-1在癌旁组织中与HBsAg的表达有相关性（P〈0．05），而在癌组织中则无相关性（P〉0．05）。结论MMP-9、TIMP-1在肝癌及癌旁组织中的表达明显增高，可能对于判断肝癌的浸润、转移有重要价值：HBV感染可能与MMP-9表达增加有关。     

细胞间黏附分子-1在原发性肝癌细胞免疫逃逸过程中的作用

目的研究细胞间黏附分子-1(ICAM-1)、淋巴细胞功能相关抗原-1(LFA-1)和尿激酶型纤溶酶原激活因子(uPA)在原发性肝癌(PHC)中的表达并探讨其意义。方法采用免疫组织化学S-P法检测34例原发肝癌组织、14例癌旁正常肝组织中ICAM-1、LFA-1和uPA的表达情况。结果原发性肝癌组织中ICAM-1、LFA-1和uPA表达定位于细胞质,其表达明显高于癌旁正常肝组织(P<0.05)。三者的表达与性别、年龄、肿瘤大小等无相关性(P>0.05),与淋巴结转移、组织分化及癌栓等有关(P<0.05);三者之间阳性表达呈明显正相关(P<0.05)。结论 ICAM-1、LFA-1和uPA在PHC呈高表达,且与PHC的发生、发展和转移密切相关。     

NF-kB p65、VEGF在肝细胞癌中的表达及临床意义

目的探讨核转录因子kB（NF-kB）p65蛋白和血管内皮生长因子（VEGF）在肝癌组织中的表达及临床意义。方法用免疫组化sP法研究HCC30例、肝硬化组织10例和正常肝组织6例中NF-kBp65、VEGF的表达。结果HCC组织中,VEGF的表达与包膜完整、肝内血管癌栓及淋巴结转移相关（P〈0．05）,而与年龄、性别、肿瘤大小、结果数目、组织病理学分级及肝硬化背景无关（P〉0．05）;NF-kBP65表达与肿瘤大小、组织病理学分级、肝内血管癌栓及淋巴结转移（P〈0．05）相关,而与年龄、性别、结果数目、包膜完整、肝硬化背景无关（P〉0．05）;NF-kBP65与VEGF表达呈正相关（r=0．962,P〈0．01）。VEGF在HCC癌旁组织中表达最高,而NF-kBp65以HCC组织表达最高。结论NF-kBp65介导的VEGF异常表达可能在肝癌发生、进展和转移中独立发挥作用。     

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。     

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.