乙酰肝素酶在食管癌中的表达及其意义

目的：探讨乙酰肝素酶在食管癌中的表达及其意义。方法应用免疫组化法检测54例食管癌组织及32例正常食管组织中的表达情况。结果乙酰肝素酶（Heparanase；HPS）在54例食管癌中的阳性率61．11％，显著高于32例正常食管组织中的阳性率13．33％（P〈0．05）。乙酰肝素酶的表达与肿瘤浸润深度、淋巴结转移和病理分期相关（P〈0．05）。乙酰肝素酶的表达与患者的性别、年龄、肿瘤的部位、大小、组织学类型、分化程度无显著相关（P〉0．05）。结论本研究结果表明乙酰肝素酶的表达对血管生成、食管癌的侵入转移起到关键性的作用，其作为食管癌治疗中的一个新靶点对治疗及预后有相当好的理论价值。     

乳腺癌组织中脆性组氨酸三联体基因的表达及意义

目的探讨乳腺癌组织中脆性组氨酸三联体（FHIT）基因的表达及其临床意义。方法应用免疫组织化学酶联免疫sP法,检测FHIT在41例乳腺癌组织及11例癌旁组织中的表达。结果乳腺癌组FHIT蛋白阳性表达率46．3％（19／41）显著低于正常乳腺组90．9％（10／11）（P〈0．05）。中／高分化组FHIT蛋白阳性表达率显著高于低分化组（53．8％vs33．3％）（P〈0．05）;淋巴结转移组FHIT蛋白阳性率低于,无淋巴结转移组（42．9％vs53．8％）（P〈0．05）;Ⅰ＋Ⅱ期组与Ⅲ＋Ⅳ期组之间FHIT蛋白阳性表达率（56．3％ vs 40．0％）差异有统计学意义（P〈0．05）。结论FHIT基因在乳腺癌的发生、发展中起重要作用,对其蛋白的检测可作为判定乳腺癌发生及转移能力的一项客观指标。     

乳腺癌组织中SPARC和Her-2的表达

目的探讨富含半胱氨酸的酸性分泌蛋白（SPARC）和人表皮生长因子受体（Her-2）在乳腺癌组织中的表达及与临床病理参数的关系。方法应用免疫组织化学方法检测70例乳腺癌和20例乳腺纤维腺瘤中SPARC和Her-2的表达。结果SPARC在乳腺癌间质细胞的高表达率为68．6％（48／70）明显高于肿瘤细胞表达率为37．1％（26／70）（P〈0．05）;间质细胞中乳腺癌的SPARC表达率为68．6％（48／70）明显高于乳腺纤维腺瘤的表达率为40．0％（8／20）（P〈0．05）;在有淋巴结转移、TNM分期为Ⅲ期的乳腺癌中SPARC的表达率升高（P〈0．05）。乳腺癌中SPARC的高表达率与腋窝淋巴结转移相关。Her-2在乳腺癌肿瘤细胞中的高表达率为45．7％（32／70）明显高于乳腺纤维腺瘤表达率的10．0％（2／20）（P〈0．05）。Her-2在淋巴结转移组的表达率较无淋巴结转移组高（P〈0．05）。结论乳腺癌中SPARC、Her-2的高表达与乳腺癌的发生、发展、转移和预后有关。     

抑癌基因P16在原发性乳腺癌组织中的表达及其意义

目的：探讨抑癌基因P16在原发性乳腺癌中的表达及其在原发性乳腺癌转移方面的意义。方法：应用SABC免疫组织化学方法检测原发性乳腺癌30例,乳腺增生症10例的石蜡包坦组织标本中P16蛋白的表达。结果：原发性乳腺癌P16蛋白阳性率20．00％,显著低于乳腺增生症阳性率60．00％（P＜0．05）。P16蛋白阳性率与患者年龄,病理分级,临床分期差异均无显著性意义（P＞0．05）。腋窝淋巴结发生癌转移者P16蛋拍摄量性率9．09％,明显低于未发生癌转移者50．00％（P＜0．05）。结论：P16蛋白的存在有可能与癌细胞是否发生转移有关。     

乳腺癌组织中VEGF-C的表达及其与临床病理指标的关系

目的：探讨血管内皮生长因子-C（vascular endothelial growth factor C，VEGF-C）在乳腺癌组织的表达情况及与临床病理指标的关系。方法：应用免疫组织化学方法检测69例乳腺癌和10例乳腺纤维腺瘤组织的VEGF-C表达情况，并分析其表达与临床病理特征的关系。结果：69例乳腺癌组织中VEGF-C阳性表达72．46％（50／69），10例乳腺纤维腺瘤表达为30％，两者差异有统计学意义（Hc=10．173，P〈0．01）。VEGF-C在乳腺癌中的表达与其组织学分级有关（χ^2=12．026，P〈0．01），组织学分化Ⅲ级的VEGF-C阳性表达率为92．86％，高于组织学分化Ⅰ级（37．5％，P〈0．01）、Ⅱ级（63．64％，P〈0．05），Ⅰ级与Ⅱ级比较差异无统计学意义（P〉0．05）；有腋淋巴结癌转移组与无转移组的VEGF-C阳性表达率分别为87．10％和60．53％，差异有统计学意义（P〈0．05）；而与月经状态、肿瘤大小、病理类型、TNM分期、ER／PR状态和预后无关（均P〉0．05）。结论：乳腺癌组织中VEGF-C的表达明显增加，其表达水平显著高于乳腺纤维腺瘤，并且与肿瘤组织学分级、区域淋巴结转移有关。     

散发性乳腺癌组织中BRCA1蛋白表达及其意义

目的探讨散发性乳腺癌患者癌组织中BRCA1蛋白表达及其临床意义。方法根据患者年龄将乳腺癌分为≤40岁及〉40岁两组,各取50例作为研究对象,病理诊断均为浸润性导管癌;术前未经任何治疗。同时选取乳腺腺病20例对照。构建组织芯片,采用免疫组化（S-P法）检测癌组织中BRCA1蛋白表达情况。结果BRCA1蛋白在腺病中表达于腺泡及导管上皮细胞核（阳性率90％）;在乳腺癌中表达于癌细胞胞质或细胞核（阳性率64％）,差异具有统计学意义（P〈0．05）。乳腺癌患者年龄≤40岁BRCAl蛋白阳性表达率（52．0％）低于年龄〉40岁组（76．0％）;同时无淋巴结转移组其BRCA1蛋白阳性表达率（80．6％）高于伴有淋巴结转移组（54．7％）,其差异具有统计学意义（P〈0．05）。而BRCA1蛋白表达与乳腺癌患者的肿瘤临床分期以及病理组织分级无关（P〉0．05）。结论散发性乳腺癌组织中BRCA1蛋白表达缺失与患者发病年龄及有无淋巴结转移显著相关,通过对BRCAl蛋白的检测,有助于筛选乳腺癌的高危人群及其患者。     

MAT1基因及其蛋白在乳腺癌中的表达研究

目的探讨MATl基因及其蛋白在乳腺癌中的表达及意义。方法选择60例乳腺癌标本和20例正常乳腺标本,采用原位杂交和免疫组化SP法分别捡测乳腺癌组织中MATlmRNA及MATl蛋白的表达水平,分析其与乳腺癌临床病理学特征之间的关系。结果38例（63.33％）MATl111RNA阳性,32例（53.33％）MATl蛋白阳性,在乳腺癌组织中阳性表达率及表达强度显著高于正常乳腺癌组织护〈0．05）。不同临床分期、组织病理学分级及有无淋巴结转移MATlmRNA阳性率和MATl蛋白阳性率比较,差异均有统计学意义（P〈0．05）,MATlmRNA和MATl蛋白表达分别与临床分期正相关（P〈0．05）。结论MATlmRNA及MATl蛋白在乳腺癌组织中高表达,表达水平与临床分期、组织病理学分级和淋巴结转移密切相关,可作为判断乳腺癌的进展,转移的参考指标及治疗的新靶点。     

乳腺癌组织中VEGF的表达与CD44v6、MMP一2的相关性研究

目的检测血管内皮生长因子（VEGF）与CD44v6、MMP-2在乳腺癌中的表达情况,探讨它们之间的关系。方法采用免疫组化SP法检测92例乳腺浸润性癌中VEGF、CD44v6、MMP-2的表达情况,并与正常乳腺组织进行比较。结果VEGF在正常乳腺组织和乳腺癌中的阳性表达率分别为6．7％（3／45）和90．2％（83／92）,且VEGF在淋巴结转移组中的阳性表达率（53／55）明显高于无淋巴结转移组（P〈0．05）。CD44v6在正常乳腺组织及乳腺癌中的阳性表达率分别为8．9％（4／45）和85．9％（79／92）,而且CD44v6在淋巴结转移组中的阳性表达率（51／55）明显高于无淋巴结转移组（P〈0．05）。MMP-2蛋白在正常乳腺组织及乳腺癌中的阳性表达率分别为4．4％（2／45）、87．0％％（80／92）,而且MMP-2在淋巴结转移组中的阳性表达率（52／55）明显高于无淋巴结转移组（P〈0．05）。VEGF与CD44v6、MMP-2的表达均存在正相关关系（P〈0．05）。结论VEGF、CD44v6、MMP-2在乳腺癌组织中高表达,且均与淋巴结转移有关,它们可能在乳腺癌的远处转移中起协同作用。     

可溶性耐药相关钙结合蛋白在乳腺癌组织中的表达及预后

目的：研究可溶性耐药相关钙结合蛋白（Soluble resistiince-related caLcittmbinding protein，Sorcin）在乳腺癌组织中的表达，评估其在乳腺癌预后中的作用。方法：采用免疫组织化学方法（IHC）检测47例手术切除的乳腺癌组织中Sorcin的表达．并分析其与临床、病理特征的关系及对预后的影响。结果：（1）Sorcin在乳腺癌组织中的阳性表达率为85．1％（40／47例），其中高表达27例（57．4％）；（2）Sorcin与月经状况、肿瘤大小、淋巴结转移、组织分级和雌激素受体状况差异均无显著性（P〉0．05），但与孕激素受体状况似有一定关系（P〈0．05）；（3）Kaplan-Meier生存分析结果表明Sorcin表达与无瘤生存期和总生存期差异均无显著性（P〉0．05）；（4）COX多因素分析显示肿瘤大小、淋巴结转移与无瘤生存期及总生存期明显相关（P〈0．05），组织分级也与无瘤生存期明显相关（P〈0．05）。结论：Sorein在乳腺癌组织中具有高表达。但与乳腺癌患者无瘤生存期和总生存期均无关。     

HER-2和TIMP-1表达与乳腺导管癌转移及预后相关性

目的：研究乳腺癌组织中表皮生长因子受体-2（HER-2）和金属蛋白酶组织抑制剂（TIMP—1）的表达情况，探讨其与乳腺癌转移及预后的相关性，寻找能够有效判断乳腺癌转移潜能的分子生物学指标。方法：采用免疫组化二步法检测60例乳腺癌组织中HER-2和TIMP—1的表达情况。结果：HER-2和TIMP—1的阳性表达率与临床分期无明显相关性，P〉0．05；HER-2的阳性表达率，在无淋巴结转移组差异无统计学意义，P〉0．05，TIMP—1的阳性表达率，在有淋巴结转移组（56．7％，17／30）高于无淋巴转移组（23．0％，7／30），差异有显著性，P〈0．01。HER-2和TIMP—1在乳腺癌组织中的表达呈显著正相关，r=0．306，P：0．018。患者的总生存率在HER-2有表达组明显低于HER-2无表达组，P〈0．05，在TIMP—1有无表达组的差异无统计学意义，P〉0．05。结论：在乳腺癌组织中TIMP—1可能有促进淋巴管转移的作用，但TIMP—1不能作为不良预后指标独立检测；HER-2可作为不良预后指标独立检测。     

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.