P53和NM23/NDPK在非小细胞肺癌中表达的意义

目的:探讨非小细胞肺癌(NSCLC)中P53与NM23/NDPK表达的相关性及其临床意义。方法:采用S-P免疫组化染色技术,检测69例NSCLC中P53及NM23/NDPK的表达情况。结果:P53及NM23/NDPK的表达与患者的生存率有关(P<0.05),P53与NM23/NDPK的表达和肺癌淋巴结转移密切相关(P<0.01)。结论:P53和NM23/NDPK的表达在NSCLC淋巴结转移中起协同作用。联合检测NSCL中P53及NM23/NDPK的表达对于判断预后和指导治疗具有一定的临床价值。     

肺癌P53表达与临床病理特征及预后关系的研究

目的探讨大、小细胞肺癌中P53的表达及其在肺癌发生、转移以及预后中的意义。方法采用S-P免疫组化染色技术及显微分光光度术,检测86例肺癌P53的表达情况。结果肺癌P53的表达与肺癌淋巴结转移及临床分期有关,P53的表达与患者的生存率有关,但与组织学分级及分化程度无关。P53阳性率及强度,在肺癌伴淋巴结转移阳性组高于淋巴结转移阴性组(P<0.01)。随着临床分期的增高,阳性率逐渐增高(P<0.05)。P53阳性患者术后3年生存率明显低于阴性者(P<0.05)。结论对肺癌进行P53的检测,有助于预测肺癌进展程度和淋巴结转移的诊断,以及评估肺癌患者的预后。     

雄激素和雌激素受体在肺腺癌和肺鳞癌中的表达

目的 探讨雄激素受体和雌激素受体在肺腺癌、鳞癌中的表达及其与预后的关系.方法 应用免疫组化SP法检测54例肺腺癌和78例鳞癌组织标本中雄激素受体(AR)和雌激素受体(ER)的表达,并分析其与临床特性及生存率的关系.结果 AR和ER总阳性率分别为21.2%(28/132)和18.2%(24/132).非小细胞肺癌(NSCLC)组织中AR的阳性表达与TNM分期及N分期(淋巴结转移情况)相关.AR表达阳性组3年生存率显著低于阴性组(21.4%vs.45.2%)(P<0.05);ER表达阳性组3年生存率低于阴性组(29.2%vs.42.6%)(P>0.05).结论 AR的阳性表达与NSCLC淋巴结转移和肿瘤进展可能相关,并且预后较差.     

I期非小细胞肺癌病灶中nm23的表达与淋巴结微转移的关系

目的探讨I期非小细胞肺癌原发癌灶nm23基因表达与淋巴结微转移之间的关系。方法对40例根治性切除的Ⅰ期非小细胞肺癌患者的原发癌灶石蜡标本采用免疫组化方法进行nm23基因表达蛋白检测,对常规病理检查阴性的淋巴结应用免疫组化方法以Ck为标志物进行微转移检测,所得数据进行统计学分析。结果(1)本组40例非小细胞肺癌中nm23蛋白阳性表达57.5%(23/40),阴性表达42.5%(17/40)。(2)常规病理检查阴性的淋巴结192枚,有11例患者中的28枚淋巴结检出微转移灶,淋巴结微转移阳性检出率14.6%(28/192),有淋巴结微转移患者检出率27.5%(11/40)。(3)nm23蛋白阳性表达组淋巴结微转移患者发生率13.04%,nm23蛋白阴性表达组淋巴结微转移患者发生率47.06%,两组阳性率的比较有统计学意义(P<0.05)。结论Ⅰ期非小细胞肺癌患者病灶中nm23的表达和淋巴结微转移关系密切,联合检测原发癌灶中nm23的表达和淋巴结微转移灶不仅能够评估肺癌侵袭转移的程度,而且对正确评估肺癌的病理分期、预后及制定合理的治疗方案有重要意义。     

EphA2、E-cad和VEGF在非小细胞肺癌中的表达及其临床意义

目的探讨生促红素人肝细胞2(EphA2)、上皮型钙黏附蛋白(E-cad)和血管内皮生长因子(VEGF)在非小细胞肺癌(NSCLC)中的表达及其与临床病理特征的关系。方法用免疫组织化学Envision法检测62例NSCLC中EphA2、E-cad和VEGF的表达。结果 EphA2的阳性表达率与有淋巴结转移、临床分期、5年生存率有关(P<0.05),E-cad的异常表达率与有淋巴结转移、临床分期和5年生存率有关(P<0.01),VEGF的过表达与有淋巴结转移、临床分期有关(P<0.01)。EphA2与E-cad的表达呈负相关(P<0.01)。结论在NSCLC中EphA2和VEGF的过表达及E-cad的低表达与肿瘤的淋巴结转移、临床分期有关,EphA2、E-cad的异常表达与术后生存时间有关,可作为判断NSCLC预后的指标。     

微RNAlet7、高迁移率族蛋白在非小细胞肺癌中的表达及临床意义

目的探讨微RNA let7(let7)和高迁移率族蛋白(HMGA2)在非小细胞肺癌(NSCLC)中的表达及意义。方法采用原位杂交检测let7、免疫组化SP法检测HMGA2在68例NSCLC(肺癌组)及20例正常肺组织(对照组)中的表达。结果 let7在肺癌组中的阳性表达率39.7%,低于对照组的75.0%(P<0.05);HMGA2在肺癌组中的阳性表达率63.2%,高于对照组(0)(P<0.01)。HMGA2阳性率与肿瘤大小、组织类型及淋巴结转移有关。let7与HMGA2在肺癌组中的表达呈明显负相关。let7阳性表达组患者的2年生存率明显优于阴性表达组;HMGA2阴性表达组患者的2年生存率明显优于阳性表达组。结论 let7的低表达和HMGA2的高表达参与了肺癌的发生发展,let7阳性表达和HMGA2阴性表达与NSCLC预后密切相关。     

基质金属蛋白酶-9在非小细胞肺癌组织中的表达及意义

目的检测基质金属蛋白酶9(MMP-9)在非小细胞肺癌(Non small cell lung cancer,NSCLC)的表达,探讨其与NSCLC侵袭转移的关系。方法用免疫组化法检测42例NSCLC患者肺癌组织与30例癌旁正常肺组织MMP-9蛋白的表达水平。结果 MMP-9蛋白在肺癌组织的表达高于正常肺组织(P<0.05),MMP-9在有淋巴结转移肺癌组织的表达高于无淋巴结转移肺癌组织的表达(P<0.05),且其表达与NSCLC患者临床分期相关(P<0.05)。MMP-9的表达与NSCLC患者的性别、年龄、组织学类型均无明显相关性(P>0.05)。结论 MMP-9的表达与NSCLC的侵袭转移有关,可成为评价NSCLC恶性程度和预后的辅助指标。     

Ⅰ期非小细胞肺癌病灶中nm23的表达与淋巴结微转移的关系

目的 探讨Ⅰ期非小细胞肺癌原发癌灶nm23基因表达与淋巴结微转移之间的关系.方法 对40例根治性切除的Ⅰ期非小细胞肺癌患者的原发癌灶石蜡标本采用免疫组化方法 进行nm23基因表达蛋白检测,对常规病理检查阴性的淋巴结应用免疫组化方法 以Ck为标志物进行微转移检测,所得数据进行统计学分析.结果 (1)本组40例非小细胞肺癌中nm23蛋白阳性表达57.5%(23/40),阴性表达42.5%(17/40).(2)常规病理检查阴性的淋巴结192枚,有11例患者中的28枚淋巴结检出微转移灶,淋巴结微转移阳性检出率14.6%(28/192),有淋巴结微转移患者检出率27.5%(11/40).(3)nm23蛋白阳性表达组淋巴结微转移患者发生率13.04%,nm23蛋白阴性表达组淋巴结微转移患者发生率47.06%,两组阳性率的比较有统计学意义(P＜0.05).结论 Ⅰ期非小细胞肺癌患者病灶中nm23的表达和淋巴结微转移关系密切,联合检测原发癌灶中nm23的表达和淋巴结微转移灶不仅能够评估肺癌侵袭转移的程度,而且对正确评估肺癌的病理分期、预后及制定合理的治疗方案有重要意义.     

RRM1蛋白在NSCLC组织中的表达及其临床意义

目的 探讨核糖核苷酸还原酶M1蛋白(RRM1)在非小细胞肺癌(NSCLC)组织中的表达及其临床意义.方法 选取2015年10月至2016年12月我院手术后经病理学证实的NSCLC组织及其癌旁组织100例,采用免疫组化染色观察两种组织标本中RRM1蛋白的表达水平,并分析其与患者临床病理特征的关系.结果 肺癌组织中RRM1蛋白阳性表达率68.00%,其中阴性表达32例、弱阳性38例、阳性表达20例、强阳性表达10例,癌旁组织中的RRM1蛋白阳性表达率36.00%,其中阴性表达率64例、弱阳性36例,两组比较差异具有统计学意义(P<0.05);肺癌组织中RRM1蛋白阳性表达与NSCLC患者的TNM分期、组织分化程度、发生淋巴结转移具有显著的相关性(P<0.05).RRM1蛋白阴性表达与NSCLC患者的2年生存率55.88%高于阳性表达患者的34.38%(P<0.05).结论 RRM1蛋白在NSCLC组织中高表达,并且与患者的预后有关.     

非小细胞肺癌患者ERCC1蛋白表达及与预后的关系

目的探讨DNA切除修复交叉互补组1（ERCC1）蛋白在非小细胞肺癌（NSCLC）中的表达与临床预后的关系。方法采用免疫组织化学Envision法检测90例NSCLC组织中ERCC1表达。结果 NSCLC组织ERCC1总阳性率为45.55%（41/90）,与癌旁组织比较的差异有统计学意义（P〈0.003）。ERCC1表达及强度与患者年龄、性别、肿瘤大小、组织学类型、淋巴结转移和临床分期无明显关系（P〉0.05）。临床Ⅱ期以上ERCC1阳性表达者生存率低于阴性表达者（P=0.004）。临床Ⅰ期ERCC1阳性表达者生存率高于阴性表达者,但差异无统计学意义。结论 ERCC1蛋白表达可作为临床Ⅱ期以上NSCLC患者预后的评估指标。     

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.     

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.     

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.