miR-10b、miR145及miR155在乳腺癌患中的表达及临床意义

目的 探讨microRNA-10b(miR-10b)、microRNA-145(miR-145)及microRNA-155(miR-155)在乳腺癌患者病理组织及血清中的表达水平,进而评价其在乳腺癌诊断中的价值.方法 收集100例正常健康志愿者,150例乳腺癌患者血液和39例乳腺癌患者的癌组织和癌旁组织,提取血液和组织中的microRNA,采用实时荧光定量PCR检测miR-10b、miR-145及miR-155表达水平,分析其与乳腺癌患者临床病理参数之间的相关性,并绘制ROC曲线分析其在乳腺癌诊断中的价值.结果 治疗前乳腺癌患者血清中的miR-10b,miR-145和miR-155表达水平高于对照组(P＜0.05),三者表达水平均与肿瘤转移显著相关,与年龄、组织学特征、ER表达无相关性(P＞0.05)miR-10 b与临床分期显著相关(P＜0.05),miR-10b的ROC曲线下面积为0.936,miR-145的ROC曲线下面积为0.904,miR-155的ROC曲线下面积为0.91.miR-10b,miR-145,miR155在Ⅲ级乳腺癌患者肿瘤组织的表达水平明显高于Ⅰ～Ⅱ级乳腺癌患者癌组织的表达水平(P＜0.05).结论 血清中miR-10 b、miR-145及miR-155有可能作为乳腺癌早期诊断的肿瘤标志物.     

长链非编码RNA MALAT1 在肝细胞癌行肝切除患者中的表达及临床意义

摘要： 目的 探讨长链非编码 RNA 肺腺癌转移相关转录子 1 （MALAT1） 与肝细胞癌患者预后的关系, 为患者的围手术期治疗提供参考。方法 收集 2008 年 6 月—2014 年 6 月在天津市人民医院治疗的 125 例原发性肝细胞癌患者癌组织及其对应的癌旁组织标本, 采用实时定量聚合酶链式反应 （RT-PCR） 检测组织中 MALAT1 的表达水平,分析 MALAT1 表达水平与肝细胞癌行肝切除患者预后的关系, 并筛选影响患者预后的危险因素。结果 MALAT1 在肝细胞癌组织内的表达上调 （P＜0.05）, MALAT1 的表达与患者年龄、 有否乙肝、 有否肝硬化、 肿瘤最大径、 肿瘤数目、 肿瘤 TNM 分期、 肿瘤有否血管侵犯、 病理分化程度以及术前甲胎蛋白 （AFP） 含量无关 （P＞0.05）。Kaplan-Meier 生存分析显示, MALAT1 低表达组患者 1、 3 和 5 年术后累积生存率分别为 85.9%、 55.2%和 33.8%, MALAT1 高表达组分别为 66.0%、 34.6%和 3.9%; 2 组患者生存率差异有统计学意义 （P＜0.01）。多因素 COX 回归模型分析显示, 肿瘤有血管侵犯 （RR=3.055, 95%CI： 1.986～4.053, P＜0.01）、 MALAT1 高表达 （RR=2.918, 95%CI： 1.736～3.672, P＜ 0.01） 是影响肝细胞癌患者术后生存率的独立危险因素。结论 长链非编码 RNA MALAT1 是肝癌手术后判断患者预后的新型肿瘤标志物, 可以用于肝癌的术前及术后评估。     

呼吸系统肿瘤标志物检测的临床应用价值

目的 探讨CEA、CYFRA21-1、NSE作为肺癌肿瘤标志物的临床意义.方法 采用回顾性研究的方法 研究200例肺良性疾病患者、131例确诊肺癌患者血清CEA、CYFRA21-1、NSE水平.结果 与肺良性疾病比较,肺癌患者血清CEA、CYFRA21-1、NSE水平显著升高(P＜0.001).CYFRA21-1水平在非小细胞患者血清中显著高于小细胞患者(P＜0.05).CEA水平在肺腺癌患者中显著高于其它病理类型肺癌患者(P＜0.01).NSE水平在小细胞肺癌患者中显著高于非小细胞患者(P＜0.05).CEA和CYFRA21-1水平在肺癌患者中具有较高的灵敏度(54%和53.7%),CYFRA21-1在检测肺癌中具有较高的特异性(84%),联合检测多种肿瘤标志物比单一检测某种肿瘤标志物具有更高的敏感度.结论 血清CEA、CYFRA21-1、NSE是有助于诊断肺癌的标志物,联合检测标志物可提高诊断的灵敏度和准确度.     

Ku70蛋白在肝细胞癌患者体内的表达规律及其意义

目的研究Ku70蛋白在肝细胞癌(HCC)患者体内的表达规律及其临床意义。方法采用免疫组织化学染色方法检测106例肝癌、癌旁和92例正常肝组织中Ku70蛋白的表达,探讨Ku70蛋白表达与临床病理参数的关系及与生存情况的关系。结果肝癌组织中Ku70蛋白阳性表达率高于癌旁组织和正常肝组织(P<0.01)。ChildPugh分级、肿瘤大小、肿瘤分化程度、TNM分期是HCC患者肝癌组织中Ku70蛋白表达水平升高的危险因素。生存分析表明低表达组的生存率显著高于高表达组(P<0.05)。结论 Ku70蛋白可作为HCC早期筛查和预后判断的新型肿瘤标志物。     

上皮间质转化相关标志物在舌鳞癌组织中的表达及其临床意义研究

目的 探讨上皮间质转化标志物锌指E-盒结合同源异形盒-1(ZEBl)、E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)在舌鳞癌组织中的表达及其临床意义.方法 采用免疫组织化学St reptavidin-Peroxidase (SP) 法检测68例舌鳞癌组织、63例舌癌癌旁组织和68例正常舌上皮组织中ZEBl、E-cadherin、和N-cadherin的表达情况,并分析其表达与患者临床病理特征及转移的关系.结果 ZEB1、E-cadherin蛋白在舌鳞癌组织中的阳性表达率低于癌旁组织、正常上皮组织(P＜0.05);而N-cadherin蛋白在舌鳞癌组织中的阳性表达率高于癌旁组织、正常上皮组织(P＜0.05).舌鳞癌组织中ZEB1、E-cadherin和N-cadherin蛋白的阳性表达率在不同肿瘤TNM分期、肿瘤分化程度及有无淋巴结转移间比较差异有统计学意义(P＜0.05).舌癌组织中ZEB1蛋白的阳性表达与E-cad-herin蛋白阳性表达呈正相关;ZEB1蛋白的阳性表达与N-cadherin阳性蛋白表达呈负相关.结论 ZEB1、E-cadherin和N-cadherin在舌鳞癌演变过程起重要的作用,可能参与了舌鳞癌侵袭和转移的过程.     

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.     

CEANSECYFRA21-1三项血清标志物在肺癌诊断中的应用

目的:探讨联合检测血清肿瘤标志物癌胚抗原(carcinoembryonic antigen,CEA)、神经元特异性烯醇化酶(neurons specific enolase,NSE)、细胞角蛋白19片段(CYFRA21-1)在肺癌诊断中的应用价值.方法:对74例肺癌组,46例健康对照组,33例肺部良性疾病组,采用电化学发光法进行CEA、NSE、CYFRA21-1检测并对比分析.结果:肺癌组的三项肿瘤标志物水平均高于肺良性疾病和健康对照组.CEA、NSE、CYFRA21-1分别在腺癌、小细胞癌、鳞癌中表达水平最高,其阳性率分别为82.6％、81.3％、68.6％,与其他单项肿瘤标志物比较差异有统计学意义(P＜0.05),且三项联合检测对肺癌诊断敏感性明显高于单项标志物.结论:血清CEA、NSE和CYFRA21-1的联合检测有助于临床对肺癌的诊断,并对组织分型有较高的参考价值.     

P14、P16在宫颈癌中的表达及临床意义

目的 探讨P14、P16在宫颈癌组织中的表达及其与临床病理参数的相关性.方法 采用免疫组织化学链霉素抗生素-过氧化酶连接法(S-P法)检测P14、P16在56例宫颈鳞癌组织、20例CIN Ⅲ组织和30例正常宫颈组织中的表达情况.结果 P14和P16蛋白在正常宫颈组织中的阳性表达率明显低于CIN Ⅲ组织和宫颈癌组织,差异有显著性(P＜0.05).P14蛋白的表达与浸润深度、病理分级及淋巴转移有关(P＜0.05),与临床分期、年龄、肿瘤大小或脉管有无癌栓无关(P＞0.05);P16蛋白的表达与病理分级及淋巴转移有关(P＜ 0.05),与临床分期、年龄、肿瘤大小、浸润深度或脉管有无癌栓无关(P＞0.05).结论 P14、P16基因的高表达发生在宫颈癌和癌前病变阶段,对宫颈癌的诊断及预后判断有一定价值,故可作为肿瘤标记物用于宫颈癌的临床筛查及诊断.     

乳腺浸润性导管癌患者血清胸苷激酶1表达及其与临床病理特征的关系

目的 探讨细胞质胸苷激酶1(TK1)在乳腺浸润性导管癌(乳腺导管癌)患者血清中的表达,及其在乳腺导管癌侵袭转移过程中的作用.方法 回顾性分析行手术治疗的60例乳腺导管癌患者的临床资料,选择健康体检者为对照组,采用化学发光结合斑点杂交技术检测其血清TK1水平.结果 乳腺癌组TK1阳性表达率为75.0％,显著高于对照组的6.7％(x2=23.155,P＜0.05).患者肿瘤直径≥5 cm 、TNM分期Ⅲ～Ⅳ期、淋巴结转移组患者血清TK1阳性表达率显著高于肿瘤直径＜5 cm、TNM分期Ⅰ～Ⅱ期、无淋巴结转移组(P＜0.05).而TK1阳性表达率与性别、分化程度无明显相关性(P＞0.05).结论 血清TK1在乳腺导管癌中呈高表达,血清TK1水平与肿瘤大小、TNM分期、淋巴结转移有关,高水平的TK1表明乳腺导管癌的侵袭和进展.     

结肠癌患者组织中VEGF和血清IGF-1表达的临床意义

目的:检测结肠癌组织中血管内皮生长因子(VEGF)的表达情况和血清中胰岛素样生长因子-1 (IGF-1)的含量.阐述血管内皮生长因子(VEGF)和胰岛素样生长因子-1 (IGF-1)在结肠癌中相关性.探讨血管内皮生长因子(VEGF)和胰岛素样生长因子-1 (IGF-1)在结肠癌中的临床意义.方法:血管内皮生长因子(VEGF)检测采用免疫组化方法,对32例结肠癌组织血管内皮生长因子(VEGF)的表达进行检测,对照正常12例非肿瘤外伤患者.胰岛素样生长因子-1 (IGF-1)检测采用双位点免疫放射测定方法(IRMA),结肠癌Dukes分期(A期8例,B期7例,C期9例,D期8例)32例做术前术后两组血清IGF-1检测,与正常12例非肿瘤外伤患者对照.结果:VEGF在结肠癌患者的组织中的表达率高于对照组,有统计学意义(P＜0.01).结肠癌患者术前、术后及对照组合量显示,术前血清中IGF-1含量明显高于术后及对照组(P＜0.05).依据结肠癌Dukes分期VEGF癌组织的阳性表达与IGF-1在结肠癌血清水平,有统计学意义(P＜0.05).结论:VEGF的表达与结肠癌Dukes分期有相关性.结肠癌患者血清IGF-1水平与结肠癌Dukes分期具有正相关性,组织VEGF的阳性表达增高,结肠癌患者IGF-1含量增加.说明IGF-1和VEGF共同参与了结肠癌的发生发展过程,而且这两种因子的联合检测对发现结肠癌较单一检测更有意义.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.