MMR蛋白、p53、HER-2与Ki-67在子宫内膜癌组织中表达及与临床病理特征的关系

目的 探讨错配修复(MMR)蛋白、抑癌基因p53(p53)、表皮生长因子受体2(HER-2)与肿瘤增殖抗原(Ki-67)在子宫内膜癌组织中表达及与临床病理特征的关系。方法 选取濮阳市人民医院2019年1月至2021年1月收治的100例(均完成随访)子宫内膜癌患者为研究对象,采用免疫组化法检测子宫内膜癌组织和癌旁组织中MMR蛋白(MLH1、PMS2、MSH2、MSH6)、p53、HER-2、Ki-67表达情况,比较不同病理学参数子宫内膜癌组织中MMR、p53、HER-2、Ki-67的表达情况,分析子宫内膜癌组织中MMR、p53、HER-2、Ki-67表达与临床病理学参数的关系,分析MMR、p53、HER-2、Ki-67表达与子宫内膜癌患者预后关系。结果 子宫内膜癌组织中MMR表达缺失率、p53、HER-2、Ki-67阳性表达率高于癌旁组织(P<0.05);不同病理类型患者子宫内膜癌组织MMR表达缺失率、p53、HER-2、Ki-67阳性表达率比较：Ⅰ～Ⅱ期低于Ⅲ～Ⅳ期,高分化<中分化<低分化,无淋巴结转移低于有淋巴结转移(P<0.05);子宫内膜癌组织MMR表达缺...     

子宫内膜癌组织中c-erbB-2及ki-67表达的临床意义

目的探讨c-erbB-2、ki-67在子宫内膜癌中的表达及与子宫内膜癌发生、发展中的关系,为临床诊断和治疗提供依据。方法应用免疫组织化学SP法检测50例子宫内膜癌、45子宫内膜非典型增生及20正常子宫内膜组织中cerbB-2及ki-67的表达。结果在正常子宫内膜、子宫内膜不典型增生及子宫内膜癌中cerbB-2的阳性表达率分别为0、40.0%和68.0%,3组比较,差异有统计学意义(P<0.01)。Ki-67阳性表达率比较,子宫内膜癌中(72.0%)明显高于不典型增生子宫内膜(37.8%)、正常子宫内膜组织(35.0%)(均P<0.05)。cerbB-2、ki-67表达均与临床分期、肿瘤细胞组织学分级、浸润肌层深度密切相关(均P<0.05),但cerbB-2与淋巴结转移与否无关(P>0.05),ki-67表达与淋巴结有无转移有关(P<0.05)。结论 cerbB-2、ki-67的阳性表达对子宫内膜癌的发生、发展可能有促进作用,二者联合检测对早期诊断子宫内膜癌及判断预后有重要作用。     

自噬相关基因PTEN和Beclinl在乳头状甲状腺癌中的表达和意义

目的检测自噬相关基因PTEN和Beclinl在乳头状甲状腺癌中的蛋白表达,并探讨其与乳头状甲状腺癌发生、发展的相关性及意义。方法应用免疫组化染色法检测78例乳头状甲状腺癌和45例癌旁正常黏膜组织(距离癌组织>2cm)标本自噬相关基因PTEN和Beclinl的蛋白表达,并结合临床病理因素进行分析。结果乳头状甲状腺癌组织中PTEN和Beclinl的阳性表达率分别为41.0%和43.6%,显著低于正常组织的77.8%和73.3%(P<0.05);PTEN与乳头状甲状腺癌的包膜侵犯程度、淋巴结转移、性别、年龄无关(P>0.05);Beclinl与乳头状甲状腺癌的淋巴结转移有关(P<0.05),与包膜侵犯程度、性别、年龄无关(P>0.05)。PTEN与Beclinl在乳头状甲状腺癌中的表达呈正相关(r=0.532)。结论自噬相关基因PTEN和Beclinl在乳头状甲状腺癌组织中蛋白表达下调,并与肿瘤淋巴结转移有关。自噬活性的改变可能与乳头状甲状腺癌的发生、发展相关。     

雌激素受体、孕激素受体、p53蛋白、p16蛋白在子宫内膜癌组织中的表达及其临床意义

目的探讨雌激素受体(ER)、孕激素受体(PR)、p53蛋白(p53)、p16蛋白(p16)在子宫内膜癌组织中的表达及其临床意义。方法选取2017年1月至2021年5月于滁州市第一人民医院住院切除的子宫内膜癌组织57例作为研究组, 选取30例子宫内膜增生症患者的周围正常子宫内膜组织作为对照组。采用Envision法免疫组化染色, 观察ER、PR、p53、p16在子宫内膜组织中的表达及其与临床病理学特征间的关系。结果子宫内膜癌组ER、PR、p16的阳性表达率分别为70.2%、61.4%、38.6%, 均低于对照组的90.0%、86.7%、93.3%(χ2=4.36、5.98、24.09, 均P < 0.05);p53在子宫内膜癌组阳性表达率52.6%、明显高于对照组的13.3%(χ2=12.75, P < 0.001);有无淋巴结转移、肌层浸润程度、组织分级、病理分期等子宫内膜癌患者的ER、PR表达差异均有统计学意义(均P < 0.05);p53在病理分期、发病年龄、组织分级、肌层浸润程度、淋巴结转移中差异均无统计学意义(均P > 0.05);p16阳性表达率在子宫...     

PTEN和CerbB-2在子宫内膜腺癌中的表达及意义

目的探讨子宫内膜腺癌组织中PTEN、CerbB-2蛋白表达异常及其与子宫内膜腺癌发生发展的关系。方法应用免疫组化S-P法对24例正常增生期子宫内膜组织、37例子宫内膜增生症组织、46例子宫内膜腺癌组织中PTEN、CerbB-2蛋白的表达进行研究。结果在正常增生期子宫内膜、子宫内膜增生症、子宫内膜腺癌组织中PTEN蛋白的阳性表达率呈递减趋势熏CerbB-2蛋白的表达率呈递增趋势。子宫内膜腺癌组织中PTEN蛋白阳性表达率明显低于正常增生期子宫内膜(P<0.01)及子宫内膜单纯性增生症组织(P<0.05);正常增生期子宫内膜、复杂性增生组织中PTEN蛋白表达具有显著性差异(P<0.05);子宫内膜腺癌组织中CerbB-2蛋白表达明显高于正常增生期子宫内膜、子宫内膜增生症组织,具有显著性差异(P<0.01,P<0.01);正常增生期子宫内膜CerbB-2蛋白表达与子宫内膜单纯性增生、复杂性增生组织间具有显著性差异(P<0..05,P<0.01)。PTEN蛋白的表达与子宫内膜腺癌的组织学分级、肌层浸润、5年生存率有关(P<0.05),与有无淋巴结转移无关(P>0.05);CerbB-2蛋白的表达与子宫内膜腺癌的组织学分级、肌层浸润有关(P<0.01,P<0.05),与有无淋巴结转移无关(P>0.05)。结论PTEN、CerbB-2蛋白的异常表达与子宫内膜腺癌的发生有密切的关系,PTEN基因异常表达可促使子宫     

子宫内膜癌中淀粉样肽前体样蛋白2表达变化及对预后的影响分析

目的 探讨子宫内膜癌中淀粉样肽前体样蛋白2(APLP2)的表达变化及对预后影响,为改善患者预后提供参考依据.方法 通过免疫组织化学法对38例子宫内膜癌和42例正常子宫内膜石蜡切片的APLP2表达情况,并收集患者的临床资料和随访结果,分析APLP2的表达与患者临床资料关系,根据患者APLP2表达情况分为阳性组和阴性组,比较2组患者生存情况.结果 子宫内膜癌组织中APLP2的阳性表达率为28 T.95%,明显低于正常子宫内膜组织的85.71%(P<0.05);APLP2阳性表达与肌层浸润、雌激素受体表达、分化程度相关(P<0.05),与年龄、FI-GO分期、病理类型、淋巴结转移无关(P>0.05);随访时间6~36个月,阳性组生存率为81.48%,明显高于阴性组的55.45%(P<0.05).结论 子宫内膜癌患者中APLP2呈低表达,其低表达与肌层浸润和分化程度有关,并可作为患者预后的重要评估指标.     

错配修复基因hMLH1、hMSH2及p53在子宫内膜癌中的表达及意义

目的探讨错配修复基因hMLH1、hMSH2及p53在子宫内膜癌组织中的表达及意义。方法运用免疫组织化学S-P法对99例子宫内膜癌中hMLH1、hMSH2及p53的表达进行检测。结果99例子宫内膜癌组织中hMLH1与hMSH2的阳性表达率分别为38.3%和60.6%,与内膜癌临床分期、组织类型及组织学分化程度无关(P>0.05);99例内膜癌组织中p53阳性表达率为42.4%,组织分化程度高、临床分期早的内膜癌组织中的p53阳性率明显低于分化程度低及临床分期晚者(P<0.01);hMSH2蛋白阳性组中p53表达率明显高于阴性组(P<0.01)。结论hMLH1及hMSH2基因的缺陷及p53的表达与子宫内膜癌的发生发展过程有关。     

ER与C-erbB-2在子宫内膜癌中的表达及意义

目的分析雌激素受体(ER)、C-erbB-2在子宫内膜癌中的表达及意义。方法通过应用免疫组化技术对47例子宫内膜癌组织中ER和C-erbB-2的表达水平进行检测分析,探讨其意义。结果显示ER在正常子宫内膜组织中的表达率为100%,在子宫内膜癌组织中的阳性表达率为55.3%,差异有统计学意义(P<0.05);不同临床分期、组织学分级的子宫内膜癌患者ER阳性表达率相比,差异有统计学意义(P<0.05)。C-erbB-2在子宫内膜癌组织中的阳性表达率为51.1%,与正常子宫内膜组织中的12.0%相比,差异有统计学意义(P<0.05);不同临床分期、组织学分级的子宫内膜癌患者C-erbB-2阳性表达率相比,差异有统计学意义(P<0.05)。ER与C-erbB-2在子宫内膜癌组织中的表达有相关性(P<0.05)。结论 ER、C-erbB-2二者在子宫内膜癌的发生、发展中发挥重要作用,联合检测ER与C-erbB-2在子宫内膜癌中的表达,对子宫内膜癌的诊断、预后判断以及治疗有一定的指导意义。     

C-erB-2、ER、PR在子宫内膜癌中的表达及意义

目的 探讨雌激素受体(ER)、孕激素受体(PR)及第二人体表皮生长因子受体(C-erB-2)在子宫内膜癌中的表达及意义.方法 应用免疫组化SP法检测三者在30例正常子宫内膜、30例子宫内膜息肉及86例子宫内膜癌组织中的表达水平,分析其临床意义及相关性,并将其与子宫内膜癌手术病理分期、组织细胞学分化程度、肌层浸润深度、淋巴结转移等高危因素进行分析.结果 (1) C-erB-2、ER及PR在正常子宫内膜、子宫内膜息肉和子宫内膜癌中的阳性表达率组与组之间差异均有统计学意义(P＜0.05).(2) C-erB-2阳性表达与手术病理分期、组织细胞学分级及淋巴结转移相关(P＜0.05);ER阳性表达与手术病理分期、组织细胞学分级及肌层浸润相关(P＜0.05);PR与组织细胞学分级、肌层浸润及淋巴结转移相关(P＜0.05).(3)C-erB-2与ER的表达呈负相关(r=-0.247,P＜0.05),ER与PR的表达呈正相关(r=0.756,P＜0.05).结论 在子宫内膜癌中,C-erB-2、ER及PR 联合检测可作为早期诊断、指导内分泌治疗及判断预后的重要指标.     

子宫内膜癌中Wnt-1、β-catenin与Cyclin D1的表达及临床意义

目的:探讨Wnt-1、β-catenin与Cyclin D1在正常子宫内膜、子宫内膜癌中的表达、相关性及其与临床病理特征之间的关系。方法:采用免疫组化SP法对89例子宫内膜癌和30例正常子宫内膜组织中Wnt-1、β-catenin与Cyclin D1蛋白的表达进行检测。结果:与正常子宫内膜组比较,子宫内膜癌组中的Wnt-1阳性表达率(40.4%)、β-catenin阳性表达率(39.3%)、Cyclin D1阳性表达率(44.9%)明显较高(P0.05);子宫内膜癌患者中,Wnt-1高表达与肿瘤的手术分期和淋巴结转移相关(P0.05);同时,β-catenin与手术分期、肌层侵润和淋巴结转移的表达异常均有统计学意义(P0.05);Cyclin D1与手术分期和淋巴转移有关(P0.05),具有统计学意义。结论:Wnt-1、β-catenin与Cyclin D1蛋白表达作为判断子宫内膜癌的重要指标,与子宫内膜癌的发生、发展及转移密切相关,具有较高的临床意义。     

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.