c-myc和p53蛋白在喉癌切缘组织的表达与局部复发的相关性研究

目的 通过检测c-myc和p53蛋白在喉癌切缘组织的表达,探讨其与术后局部复发的相关性。方法 选择2010年月1～2016年1月在湖北省襄阳市中心医院接受治疗的喉癌患者201例,将患者按复发与否分成两组,复发组A和非复发组B,校正一般资料后,采用免疫组化发对两组患者喉癌组织和切缘组织中c-myc和p53蛋白的表达进行比较。结果 ①在喉癌组织中,c-myc蛋白在复发组和未复发组表达的阳性率分别为54.5％和50．0％,差异无统计学意义（P＞0.05）;p53蛋白在复发组和未复发组表达的阳性率分别为84.8％和91.1％,差异无统计学意义（P＞0.05）;②在切缘组织中,c-myc蛋白在复发组和未复发组表达的阳性率分别为66.7％和20.8％,差异具有统计学意义（P＜0.05）;p53蛋白在复发组和未复发组表达的阳性率分别为84.8％和81.0%,差异无统计学意义（P＞0.05）;③边缘粘膜异型增生型发生率在复发组和未复发组分别是63.6%和45.8%,差异无统计学意义（P＞0.05）。结论切缘组织中c-myc蛋白的表达与喉癌术后局部复发具有明显相关性,或可作为局部复发状况的预测指标。     

Smad2蛋白在宫颈癌组织中的表达及意义

目的 探讨Smad2蛋白在宫颈癌组织中的表达情况以及意义.方法 免疫组化法检测正常子宫组(NE组,n=61)和宫颈癌组(CC组,n=53)组织中Smad2蛋白的表达情况.结果 Smad2蛋白在NE组的表达阳性率是39.3％,在CC组的表达阳性率是77.4％,两组阳性率差异有统计学意义(P＜0.01).宫颈癌高分化和中低分化者的阳性率分别为52.6％和91.2％,差异有统计学意义(P＜0.01);癌细胞浸润程度的越高≤1/2和＞1/2者阳性率分别是66.7％和91.3％,差异有统计学意义(P＜0.05).结论 Smad2蛋白在宫颈癌组织中表达减少,与宫颈癌浸润程度、癌细胞分化程度密切相关,通过检测Smad2蛋白提供临床诊断和预后的指标.     

p53与PTEN基因在喉鳞癌中的表达及意义

目的 探讨p53与PTEN的联合表达与人喉鳞状细胞癌(LSCC)的发生、发展及预后的关系.方法 应用免疫组化SP方法检测60例LSCC组织及20例癌旁组织中p53和PTEN蛋白表达.结果 (1)在LSCC组织中,p53蛋白表达阳性率为51.2%(31/60),在癌旁组织中,其阳性率为零(0/20).(2)PTEN在LSCC组织中的表达缺失率为30%(18/60),显著低于癌旁组织中的5%(1/20)(P＜0.05).(3)p53在Ⅰ～Ⅱ期喉癌组织中的表达阳性率为35.7%(10/28),显著低于Ⅲ～Ⅳ期喉癌组织的62.5%(20/32)(P＜0.05);p53在无颈淋巴转移组表达阳性率为38.7%(19/49),显著低于有颈淋巴转移组的81.8%(9/11)(P＜0.05).(4)PTEN在Ⅰ～Ⅱ期喉癌组织中的表达缺失率为17.8%(3/28),显著低于Ⅲ～Ⅳ期喉癌组织的40.6%(13/32)(P＜0.05);PTEN在无颈淋巴转移的喉癌组织中的表达缺失率为20.4%(10/49),显著低于伴颈淋巴转移的喉鳞癌组织的72.7%(8/11)(P＜0.05).LSCC组织中,PTEN表达缺失组p53阳性表达率为33.3%(6/18),显著低于PTEN蛋白表达阳性组的61.9%(26/42)(P＜0.05).结论 p53和PTEN可能在喉鳞癌的发生、发展中起重要的作用.     

WWOX蛋白与突变型P53蛋白在非小细胞肺癌中的表达及意义

目的 探讨WWOX与突变型P53蛋白在非小细胞肺癌(NSCLC)及癌旁组织中的表达与肿瘤临床病理参数的关系及两者表达的相关性.方法 用免疫组化elivision法分别检测WWOX及突变型P53蛋白在51例NSCLC及20例癌旁正常组织中表达情况.结果 WWOX蛋白在NSCLC组织中与癌旁正常组织中表达的阳性率分别为25.49％(13/51)和85.0％(17/20).突变型P53蛋白在NSCLC组织中与癌旁正常组织中表达的阳性率分别为58.82％(30/51)和10.0％(2/20).WWOX蛋白的阳性率与NSCLC的组织分化程度、病理类型、吸烟、有无淋巴结转移的表达差异有统计学意义(P＜0.05),而与患者的年龄、性别及肿瘤TNM分期无关(P＞0.05).突变型P53的阳性率与NSCLC的分化程度、肿瘤TNM分期、有无淋巴结转移有关(P＜0.05),而与患者的年龄、性别、吸烟、病理类型无关(P＞0.05).WWOX蛋白、突变型P53在NSCLC中的阳性表达呈负相关(r=-3.33,P＜0.05).结论 WWOX蛋白和突变型P53在NSCLC及癌旁组织的表达有显著差异.WWOX与突变型P53蛋白与NSCLC的发生、发展密切相关,并可能起协同作用,其综合检测对肺癌的病情判断和预后评价具有一定价值.     

细胞凋亡控基因p53、bcl-2、c-myc在大肠腺癌-癌序列中的表达

目的 研究细胞凋亡的调控基因p53、bcl-2、c-myc在大肠粘膜癌变中的作用。方法 利用免疫组织化学SP法对30例大肠腺瘤(伴轻、中、重度异型增生各10例)和30例大肠癌的活检组织标本分别进行p53、bcl-2、c-myc蛋白表达的检测,同时采用15例正常大肠粘膜作为对照。结果 (1)正常黏膜、腺瘤和腺癌的p53蛋白表达率为6.7％、40%和73.3%。三组间有显著的差异(P均<0.05)。(2)正常粘膜、腺瘤和腺癌的bcl-2蛋白表达率分别为20％、73.3％和63.3%。腺瘤和腺癌组均高于正常对照组(P均<0.01),腺癌与腺癌组间差异不显著(P>0.05)。(3)正常粘膜、腺癌和腺癌的c-myc蛋白表达率分别为26.7%、60%和76.7%。腺瘤和腺癌组均高于正常对照组(P<均0.05),腺瘤与腺癌组间差异不显著(P>0.05)。结论 (1)bcl-2基因可能通过对细胞凋亡的抑制而在大肠的早期发生作用。(2)p53基因突变在腺瘤化为腺癌的过程中起作用。(3)c-myc基因的表达与细胞增生和肿瘤发生可能关。     

RECK蛋白表达与喉鳞癌黏膜下侵袭相关性研究

目的检测抑癌基因RECK在喉癌及癌旁组织中的表达,探讨喉鳞癌黏膜下侵袭的范围,指导临床手术的安全界。方法采用PV9000免疫组织化学两步法检测24例喉鳞癌组织及对应深部切缘组织中RECK蛋白的表达情况。结果 1 RECK在喉癌组织中阳性表达率为42%,在不同距离(2,5,10,15mm)深部切缘组织中阳性表达率分别为50%、58%、88%、96%。癌组织与2,5mm处深部切缘组织之间比较差异无统计学意义(P均>0.05)。癌组织与10mm处切缘组织比较,差异有统计学意义(P<0.01),5mm与10mm处组织之间差异有统计学意义(P=0.014)。10mm与15mm处切缘组织之间阳性表达率差异无统计学意义(P=0.481)。2 RECK蛋白的表达与喉鳞癌患者的临床分期,病理分化程度有统计学关联。随着喉鳞癌分化程度的降低,RECK蛋白的阳性表达率分别为100%,63%,9%,呈明显下降趋势(P<0.01)。而随着临床分期从T1到T4的提高,RECK蛋白的阳性表达率分别为100%,80%,40%,17%,呈明显下降趋势(P<0.05)。结论1RECK在喉癌中的表达具有较高的特异性,并且与喉鳞癌的侵袭转移有密切关系。2RECK蛋白的表达与喉鳞癌的病理分化及临床分期有密切关系。310mm的距离对于喉癌的黏膜下侵袭是可靠的,可以将其作为指导临床手术的安全切缘。     

p53、p21、MDM2蛋白在卵巢子宫内膜异位症病人血清、异位及在位内膜组织中的表达及相关性

目的 探讨p53、p21、MDM2蛋白在卵巢子宫内膜异位症病人血清、异位及在位内膜组织中的表达及相关性。方法 采用随机数字表法选取2012年1月至2017年3月在郑州人民医院收治的卵巢子宫内膜异位症病人手术切除的异位内膜组织50例作为异位组、子宫内膜异位症病人自愿刮宫术取得的在位子宫内膜组织40例作为在位组,刮宫术取得非子宫内膜异位症病人的正常子宫内膜组织35例作为对照组,异位组及在位组病人(共90例,为观察组)。使用免疫组化染色法(S-P法)对p53、p21、MDM2蛋白的表达情况进行检测。结果 异位组p53、p21表达阳性率(12.00%、10.00%)明显低于对照组(37.14%、31.43%)及在位组(35.00%、30.00%),P＜0.05;异位组MDM2表达阳性率(52.00%)明显高于对照组(5.71%)及在位组(7.50%),P＜0.05;在位组与对照组比较(35.00%、30.00%、7.50% 比37.14%、31.43%、5.71%),p53、p21、MDM2表达阳性率差异无统计学意义(P＞0.05);对照组、在位组分泌期p53、p21表达(66.67%、60.00%;61.11%、61.11%)均明显高于组内增生期(15.00%、10.00%;13.64%、13.64%),P＜0.05,对照组、在位组、异位组分泌期MDM2表达阳性率(6.67%、11.11%、47.83%)与组内增生期(5.00%、4.55%、55.56%)比较,均差异无统计学意义(P＞0.05);子宫内膜异位症病人的异位子宫内膜组织中p53表达与p21表达呈正相关(r＝0.721,P＜0.01);p53表达与MDM2表达呈负相关(r＝-0.421,P＜0.01);p21表达与MDM2表达无相关性(r＝0.308,P＞0.05)。观察组血清p53、p21水平［(0.86±0.23) kU/L、(1.04±0.12) kU/L］明显低于对照组［(1.38±0.19) kU/L、(1.68±0.24) kU/L］,MDM2水平［(2.19±0.33) kU/L］明显高于对照组［(1.03±0.15) kU/L］,P＜0.05。结论 p53、p21、MDM2蛋白表达在子宫内膜异位症的发生发展中起着重要作用,且它们之间有一定的相关性。     

P53蛋白在食管癌中的表达和临床意义

目的 探讨食管癌组织中p53蛋白的表达水平和临床意义.方法 用免疫组织化学染色SP法,检测62例食管癌组织p53蛋白过度表达情况.分析其与食管癌患者性别、年龄、肿瘤分化程度、肿瘤浸润程度及淋巴结转移等之间的关系.结果 p53蛋白在62例食管癌组织中表达的阳性率为48.4%.在男性和女性患者分别为50.0%和45.0%（P〉0.05）;低于60岁年龄组和高于60岁年龄组分别为46.9%和50.0%（P〉0.05）：高、中分化组和低分化组分别为47.6%和50.0%（P〉0.05）;肿瘤浸润黏膜及肌层的患者表达阳性率为61.1%,浸润全层时为30.8%（P〈0.05）;有淋巴结转移为65.8%,无淋巴结转移组为20.8%（P〈0.05）,即p53的阳性表达率与性别、年龄及肿瘤的分化程度无显著差异,而与细胞浸润深度和淋巴瘤转移状态具有统计学意义.结论 p53蛋白表达可能是评价预后不良指标之一.     

PCNA与P53表达与非小细胞肺癌患者预后的相关性

目的 研究P53、PCNA蛋白表达与非小细胞肺癌患者预后的相关性.方法 选取本院于2008年6月～2010年7月手术切除非小细胞肺癌组织蜡块76例作观察组,同时选取正常肺组织24例作对照组,采用免疫组化SP法对两组组织中PCNA、P53表达情况进行检测;通过回顾性随访,观察其远期生存、复发转移的情况.结果 观察组PCNA、P53阳性率均显著高于对照组（P＜0.05）,分别为72.37%、8.33%和67.26%、4.9%,Ⅰ～Ⅱ期与Ⅲ期患者PCNA阳性率间差异无统计学意义（P＞0.05）,而P53表达阳性率差异有统计学意义（P＜0.05）;P53、PCNA的表达与生存期有关,生存1年以下和3年的患者的P53表达阳性率分别为50%,20%（P＜0.05）,PCNA的阳性率分别为60%,40%（P＜0.05）,从而提示P53和PCNA表达阳性率越高,患者生存期越短,预后差.PCNA阳性者1年及3年生存率均显著低于PCNA阴性患者（P＜0.05）.结论 PCNA、P53高度表达是对非小细胞肺癌患者预后造成影响的重要因素,其异常表达和肺癌发病、进展与转移间有密切关系,可作为对肺癌恶性程度与预后准确判断的重要指标.     

胃癌p53蛋白与PCNA的免疫组织化学研究

目的　探讨p53蛋白及PCNA与胃癌发生、发展的关系。方法　对39例进展期胃癌手术标本的肉眼可见的肿瘤组织、癌旁2cm处及切缘“正常”组织进行p53蛋白及PCNA免疫组化检则。结果　切缘“正常”组织、癌旁及胃癌组织均有不同程度p53蛋白和PCNA的表达,p53阳性率逐渐升高,分别为10.3%(4/39)、28.2%(11/39)及59.0%(23/39),PCNA分级也逐渐升高,与p53呈正相关(P<0.05)。p53蛋白表达与肿瘤的浸润深度、血管和淋巴管浸润及淋巴结转移有关,p53蛋白阳性的胃癌,其细胞增殖活性明显高于阴性者。结论　p53蛋白检测有助于胃粘膜癌变倾向的判断和胃癌的早期诊断,对癌前病变的研究和手术切缘的评估有一定意义。联合检测p53和PCNA对胃癌恶性程度的判断有较高的价值。     

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.