不同年龄段食管癌患者临床病理特点和生存状况研究

目的探讨不同年龄段食管癌患者临床病理特点以及生存状况的差异。方法 426例食管癌患者根据患者的年龄进行分组,>45岁的患者作为中老年组(356例),≤45岁的患者作为分为青年组(70例)。收集患者的临床资料,分析其临床病理特点以及预后。结果所有患者的5年和10年生存率分别为35.2%(150/426)和26.3%(112/426),青年组和中老年组的5年生存率(37.1%vs.34.8%,P>0.05)、10年生存率(30.0%vs.25.6%,P>0.05)差异无显著差异。但青年组患者TNM分期的III期人数比例(51.4%,36/70)高于中老年组(36.5%,130/356),χ2=5.469,P<0.05。Kaplan-Meier法单因素分析,患者淋巴结无转移、淋巴结转移区域数少、分化程度高的食管癌患者预后较好(P<0.05)。Cox回归分析,淋巴结转移(χ2=8.110,P<0.05)、淋巴结转移区域数(χ2=9.992,P=0.002)、分化程度(χ2=4.468,P<0.05)是食管癌患者预后的影响因素。结论虽然青年患者食管癌的病理分期较晚,但其预后与中老年患者无明显差异,淋巴结转移、淋巴结转移区域越多、分化程度低不利于食管癌患者的预后。     

食管鳞状细胞癌组织上皮间质转化因子和E-钙黏蛋白的表达及临床病理意义

目的探讨上皮间质转化因子(Twist)和E-钙黏蛋白(E-cd)在食管鳞状细胞癌组织及正常食管鳞状上皮黏膜中的表达及其与食管鳞状细胞癌各临床病理因素的相关性。方法采用免疫组织化学方法(SP法)检测10例正常食管鳞状上皮及58例食管鳞状细胞癌石蜡切片中Twist和E-cd的表达情况;分析正常食管鳞状上皮组织及食管鳞状细胞癌组织中二者的表达与食管鳞状细胞癌患者年龄、临床分期、肿瘤分化程度和淋巴结转移的关系及二者表达的关系。以磷酸盐缓冲液(PBS)代替一抗作为阴性对照。结果食管正常鳞状上皮组织中Twist的阳性表达率为10%,食管鳞状细胞癌组织中Twist的表达则明显增强(53%,31/58),二者差异有统计学意义(P<0.01)。Ⅰ、Ⅱ和Ⅲ～Ⅳ期中,食管鳞状细胞癌Twist的阳性表达率为73%(11/15)、53%(10/19)和42%(10/24),差异有统计学意义(P=0.011)。Ⅲ、Ⅳ期食管鳞状细胞癌中Twist的阳性表达率显著低于Ⅰ期、Ⅱ期食管鳞状细胞癌。有淋巴结转移和无淋巴结转移的食管鳞状细胞癌Twist的阳性表达率分别为69%(18/26)和41%(13/32),差异有统计学意义(P=0.015)。E-cd在正常食管鳞状上皮组织中的正常表达率为90%,食管鳞状细胞癌组织的正常表达率仅为28%(16/58),二者差异有统计学意义(P<0.01)。72%(42/58)的食管鳞状细胞癌组织中检测出的E-cd细胞质和(或)核表达,视为细胞膜表达降低。Ⅰ、Ⅱ、Ⅲ级中食管鳞状细胞癌,E-cd的膜表达降低率分别为55%(11/20)、72%(13/18)和90%(18/20),差异有统计学意义(P=0.005)。Ⅲ级食管鳞状细胞癌中E-cd的膜表达降低率显著高于Ⅰ、Ⅱ级。有淋巴结转移和无淋巴结转移的食管鳞状细胞癌中E-cd的膜表达降低率分别为77%(20/26)和69%(22/32),差异有统计学意义(P=0.019)。结论 Twist的表达与食管鳞状细胞癌的临床分期和淋巴结转移相关,E-cd的膜表达降低与食管鳞状细胞癌的低分化和淋巴结转移相关。食管鳞状细胞癌中Twist和E-cd的表达呈负相关。     

食管鳞癌组织中MMP-9与E-Cad蛋白表达及其意义

目的检测MMP-9和E-Cad在食管鳞状细胞癌(ESCC)中的表达,探讨两者的相关性及其临床病理学意义。方法应用免疫组化SP法检测71例ESCC、33例癌旁不典型增生及29例正常食管黏膜组织中MMP-9和E-Cad蛋白的表达。结果MMP-9蛋白表达在正常食管黏膜、癌旁非典型增生及ESCC中的表达率依次增高,分别为13.8%,52.2%,81.7%,组间比较差异有统计学意义(P<0.05);而E-Cad蛋白表达在正常食管粘膜、癌旁非典型增生及ESCC中的表达率依次降低,分别为89.7%,84.5%,40.8%,组间比较差异有统计学意义(P<0.05)。MMP-9和E-Cad蛋白表达与ESCC的浸润深度、淋巴结转移及组织学分级密切相关;两者的表达呈负相关关系(rs=-0.347,P=0.003)。结论MMP-9和E-Cad蛋白与ESCC的浸润、转移和组织学分级有关,并在食管黏膜上皮癌变过程中起重要作用。     

埃兹蛋白和上皮型钙黏蛋白在肾透明细胞癌的表达及意义

目的:探讨埃兹蛋白(Ezrin)和上皮型钙黏蛋白(E-cadherin)在肾透明细胞癌及癌旁正常肾组织中的表达及与肿瘤侵袭、转移的关系.方法:采用免疫组织化学Elivision方法检测45例肾透明细胞癌组织及相应癌旁正常肾组织中Ezrin和E-cadherin的表达情况.结果:45例癌组织Ezrin异常表达率84.4%(38/45),癌旁正常肾组织Ezrin异常表达率40%(18/45),Ezrin在癌组织中的异常表达明显高于癌旁正常肾组织(χ2=18.9,P<0.005);45例癌组织E-cadherin异常表达率73.3%(33/45),癌旁正常肾组织E-cadherin异常表达率35.6%(16/45),E-cadherin在肾透明细胞癌中的异常表达明显高于癌旁正常肾组织(χ3=12.9,P<0.05);两者呈负相关;Ezrin和E-cadherin的表达与淋巴结转移、静脉瘤栓形成有关(P<0.05),与患者年龄、性别、肿瘤大小、病理分期无相关性(P>0.05).结论:Ezrin和E-cadherin与肾透明细胞癌的浸润转移有关,可能作为预测肾癌转移和判断预后的肿瘤标志物.     

食管鳞状细胞癌中P16、nm23表达研究

目的:研究食管鳞状细胞癌中P16、nm23表达状况与临床病理及预后的关系。方法:采用SP免疫组织化学方法检测70例经术后病理证实的食管鳞状细胞癌患者P16和nm23在不同病理分级及有无淋巴结转移组中的表达,使用SPSS10.0软件进行统计分析。结果:1P16蛋白阳性表达率在无淋巴结转移组(75%)明显高于有淋巴结转移组(44.7%),P<0.05;2P16蛋白阳性表达率随病理分级的升高而降低(级81.8%;级56.5%;级40%),P<0.01;3nm23在无淋巴结转移组(84.4%)明显高于有淋巴结转移组(50%),P<0.05。结论:测定P16、nm23可作为判定食管鳞状细胞癌患者预后的重要指标。     

食管鳞状细胞癌中β-catenin和MMP-7的表达及意义

目的探讨β-catenin和MMP-7蛋白在食管癌组织中的表达变化及与病理学分级、浸润深度和淋巴结转移的关系。方法应用免疫组化方法检测β-catenin和MMP-7蛋白在55例食管鳞癌组织及15例食管正常组织中的表达。结果 (1)β-catenin在食管鳞状细胞癌组织和食管正常组织中异常表达率分别为61.82%和6.67%;MMP-7在食管鳞状细胞癌组织和食管正常组织中异常表达率分别为69.09%和13.33%,两者比较差异有统计学意义(P<0.05);(2)β-catenin在食管癌组织中异常表达与细胞分化程度及淋巴结转移有关(P<0.05),但与患者的性别、年龄和浸润深度无关(P>0.05);MMP-7蛋白在食管癌组织中异常表达与细胞分化程度及淋巴结转移和浸润深度有关(P<0.05),但与患者的性别、年龄无关(P>0.05);(2)β-catenin的异常表达与MMP-7的表达有一定的相关性(r=0.487,P<0.05)。结论β-catenin和MMP-7在食管鳞状细胞癌组织中阳性表达可能在食管癌的发生发展及转移中起重要作用。     

血管内皮生长因子mRNA及其蛋白、上皮细胞钙黏蛋白在喉鳞状细胞癌中表达的研究

目的 观察血管内皮生长因子(VEGF)mRNA及其蛋白、上皮细胞钙黏蛋白(E-cadherin)在喉鳞状细胞癌组织中的表达及其与临床病理特征的关系,并探讨它在喉鳞状细胞癌发生、发展中的作用及其临床应用价值.方法 应用原位分子杂交和免疫组织化学SP法,检测VEGF mRNA及其蛋白、E-cadherin在60例喉鳞状细胞癌、30例喉不典型增生和20例慢性喉炎组织中的表达.结果 ①60例喉鳞状细胞癌组织中,VEGF mRNA及蛋白阳性率为80.0%(48/60)、73.3%(44/60),E-cadherin阳性率为18.3%(11/60).②VEGF mRNA及蛋白的表达与淋巴结转移、甲状腺软骨累及、T分期、TNM分期有关(P＜0.05);VEGF蛋白表达与病理分级有关(P＜0.05),而VEGF mRNA表达与病理分级无关(P＞0.05),两者与性别、年龄、临床分型、肿瘤大小及部位无关(P＞0.05).E-cadherin的表达与淋巴结转移、病理分级、T分期、TNM分期有关(P＜0.05),而与性别、年龄、肿瘤大小、部位及甲状软骨累及无关(P＞0.05).③VEGF mRNA及蛋白在喉鳞状细胞癌组织中的表达呈显著正相关(r=0.358,P＜0.05),而VEGF蛋白和E-cadherin在喉鳞状细胞癌组织中的表达呈显著负相关(r=-0.396,P＜0.05).结论 ①VEGF在喉鳞状细胞癌中过度表达及E-cadherin的下调对喉鳞状细胞癌的发生、发展可能起协同作用.②联合检测VEGF和E-cadherin对预测喉鳞状细胞癌浸润转移有重要意义,并可作为判断喉鳞状细胞癌生物学行为的指标.     

鼻咽癌组织中钙黏蛋白和MMP-2的表达

目的探讨上皮型钙黏蛋白(E-Cad)和基质金属蛋白酶2(MMP-2)在鼻咽癌组织中的表达及其与淋巴结转移的关系。方法应用免疫组化检测E-Cad与MMP-2蛋白在鼻咽癌组织标本52例(A组)和正常鼻咽部黏膜标本20例(B组)的表达;A组再分为有淋巴结转移组(A1组,41例)和无淋巴结转移组(A2组,11例)。结果 A组E-Cad表达率明显低于B组(55.8%vs.85.0%)(P<0.01);A1组E-Cad表达率明显低于A2组(53.7%vs 63.6%)(P<0.05)。A组MMP-2表达率为73.08%,而B组仅少数上皮细胞表达MMP-2(P<0.01);A1组MMP-2表达率明显高于A2组(85.4%vs 27.3%)(P<0.01)。MMP-2与E-Cad表达呈负相关(r=-0.412,P<0.01)。结论鼻咽癌组织低表达E-Cad,高表达MMP-2;其表达差异也明显存在于有、无淋巴结转移的鼻咽癌组织中。     

FOXQ1在卵巢高 低级别浆液性癌中的阳性表达与淋巴结转移及其远期生存率的关系

目的分析FOXQ1在卵巢高、低级别浆液性癌中的阳性表达与淋巴结转移及其远期生存率的关系。方法选取我院80份卵巢浆液性癌标本,选取同期收治的卵巢肿瘤患者40例;另选取子宫肌瘤切除术中切除正常卵巢组织标本20例进行对照。采用免疫组织化学法染色,统计FOXQ1在卵巢不同组织中的阳性表达,分析其与淋巴结转移及其患者预后生存率的关系。结果 FOXQ1在恶性卵巢肿瘤、交界性肿瘤、卵巢良性肿瘤、正常卵巢组织中均有表达,FOXQ1在高级别浆液性卵巢癌、低级别浆液性卵巢癌、交界性囊腺瘤、浆液性囊腺瘤、正常卵巢组织中的阳性表达呈逐渐降低趋势(P<0.05);FOXQ1在高级别浆液性癌阳性表达患者的淋巴结转移情况大于低级别浆液性癌,差异有统计学意义(P<0.05);高级别卵巢浆液性癌中FOXQ1阳性表达患者3年生存率与阴性表达患者比较,差异有统计学意义(P<0.05)。结论高级别浆液性卵巢癌FOXQ1阳性表达最强,且与卵巢高级别浆液性癌生存率存在紧密联系,而与低级别浆液性癌生存率无明显相关性,可作为患者不良预后的独立指标。     

HMGB1/RAGE蛋白在食管鳞癌中的表达及临床意义

目的探讨HMGB1/RAGE蛋白在食管鳞癌中的表达及其对食管鳞癌预后判定的作用。方法以食管鳞癌旁正常组织40例为对照,免疫组化检测80例食管鳞癌组织HMGB1、RAGE蛋白的表达,分析HMGB1、RAGE表达与临床病理因素的关系及其对食管鳞癌预后的影响。结果HMGB1、RAGE蛋白在食管鳞癌组织和正常鳞状上皮的阳性表达率分别为47.5%vs17.5%和72.5%vs42.5%,差异均具有统计学意义;HMGB1、RAGE蛋白的阳性表达与食管鳞癌浸润深度、淋巴结转移及TNM分期正相关（P〈0.05）,与癌细胞分化程度负相关（r分别为-0.51、-0.242,P〈0.05）;HMGB1和RAGE之间的表达呈正相关（r=0.35,P=0.001）;HMGB1、RAGE蛋白阳性表达食管鳞癌患者预后较差,COX分析显示HMGB1蛋白为影响食管鳞癌预后的独立因素（HR=4.853,P=0.000）。结论HMGB1和RAGE蛋白的表达与食管鳞癌的临床病理学特征密切相关,HMGB1与其受体RAGE的结合可能参与了食管鳞癌的侵袭和转移,HMGB1可作为预测食管鳞癌预后的重要指标。     

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.