吉非替尼治疗晚期非小细胞肺癌临床观察

目的评价吉非替尼单药治疗晚期化疗后：进展的非小细胞肺癌的疗效和不良反应。方法108例经病理确诊既往化疗失败的晚期非小细胞肺癌患者,吉非替尼250mg口服,每目1次,连续用药至肿瘤进展或发生不可耐受的不良反应。结果106例可评价,总有效率22．6％。女性的有效率高于男性（P=0．018）,腺癌的有效率高于非腺癌（P=0．040）,不吸烟者的有效率高于吸烟者（P=0．019）。疾病控制率73．6％,中位无进展生存期为5个月,中位生存期为9个月。不良反应主要是Ⅰ、Ⅱ度皮疹和腹泻。。结论吉非替尼治疗既往化疗失败的晚期非小细胞肺癌,具有较好的疗效和安全性。     

吉非替尼治疗晚期非小细胞肺癌58例的效果

目的观察吉非替尼治疗晚期非小细胞肺癌（NSCLC）的临床疗效及毒副作用。方法回顾性分析2011年1月至2012年12月在我院接受化疗失败的58例口服吉非替尼治疗晚期非小细胞肺癌患者的临床资料,每日口服1次,250mg／次,服药1个月后进行疗效观察。结果58例患者中,总有效率34．5％,总疾病控制率62．5％。其中,女性治疗的有效率高于男性,对于腺癌的效果好于鳞癌。结论吉非替尼治疗晚期非小细胞肺癌有效,并且可能在女性和腺癌患者中的治疗效果更佳,值得进一步研究。     

厄洛替尼治疗晚期非小细胞肺癌的疗效及安全性研究

目的厄洛替尼是治疗非小细胞肺癌的靶向药物,多项国内外研究已证明该药可延长非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的生存。本研究回顾性总结了厄洛替尼在非选择NSCLC人群中的应用,旨在探讨厄洛替尼治疗晚期非小细胞肺癌的远期疗效及安全性。方法回顾分析本院2006年3月至2009年7月之间接受化疗后应用厄洛替尼治疗化疗失败的晚期NSCLC患者,口服150 mg/d厄洛替尼直至疾病进展,观察疗效、生存时间和副反应。结果共有36例患者入组。36例患者中PR 22.2%(8/36),SD 50.0%(18/36),PD 27.8%(10/36),CR=O,DCR(CR+PR+SD)72.2%;PFS为5.8个月。其中腺癌与非腺癌、无吸烟者与吸烟者的疗效差异无统计学意义,但是生存曲线提示腺癌比非腺癌患者(7.6个月vs 1.0个月,P=0.037)、无吸烟比吸烟患者(11.1个月vs 4.6个月,P=0.025)具有更长的PFS,差异有统计学意义;性别因素未能影响疗效或PFS。毒副作用主要为为轻度皮疹、腹泻、转氨酶升高。结论厄洛替尼治疗晚期非小细胞肺癌有效,对腺癌和非吸烟人群有一定优势,且耐受性良好,是治疗晚期非小细胞肺癌患者的一个新的选择。     

清金化痰汤联合吉非替尼治疗化疗失败晚期肺腺癌的临床疗效观察

目的 探讨清金化痰汤联合吉非替尼治疗化疗失败晚期肺腺癌的临床疗效及安全性,为临床治疗化疗失败晚期肺腺癌提供经验.方法 选取26例化疗失败晚期肺腺癌的患者,按照随机数字表法将其分为对照组和观察组,每组均为13例,对照组连续服用吉非替尼,观察组在对照组的基础上加用清金化痰汤进行治疗,比较两组临床治疗效果、毒副作用等.结果 经治疗后,两组临床有效率均为53.85％,观察组疾病控制率为84.62％,对照组为69.23％,观察组疾病控制率显著高于对照组（x2 =4.92,P＜0.05）;对照组1年生存率为23.1％,观察组为38.5％.观察组显著高于对照组（x2 =3.86,P＜0.05）;两组均未出现严重的毒副作用.结论 采用清金化痰汤联合吉非替尼用于治疗化疗失败晚期肺腺癌的临床效果较好,毒副作用小,患者容易接受.     

吉非替尼治疗晚期非小细胞肺癌的疗效观察

目的观察吉非替尼治疗晚期非小细胞肺癌的临床疗效及安全性。方法 对70例化疗失败、不宜化疗及不愿意化疗的非小细胞肺癌患者用吉非替尼治疗,对其临床疗效、不良反应及患者生存状况进行评价。结果 治疗结束后随访3～20个月,客观有效率为38.6%,临床获益率为61.4%,且不良反应较小。结论 吉非替尼是一种良好的靶向治疗非小细胞肺癌的药物,疗效好,可明显地提高患者的生活质量,具有良好的临床应用前景。     

吉非替尼治疗化疗失败后晚期肺腺癌的临床研究

目的探讨吉非替尼治疗失败后的晚期非小细胞肺癌患者的临床疗效和不良反应。方法 17例病理确诊并化疗失败的晚期非小细胞肺癌患者服吉非替尼250mg,每日1次,直至疾病进展或患者不能耐受不良反应时停药,对临床疗效、毒副反应进行分析。结果全组17例患者中,CR1例,PR5例,SD4例,PD7例,疾病控制率(CR1+PR5+SD4)为58.8%(10/17),常见毒副反应为皮疹和腹泻,中位无进展时间为3.3月,中位生存时间为11.2月。结论吉非替尼治疗化疗失败后的晚期非小细胞肺癌有一定疗效,不良反应较轻。     

吉非替尼治疗一线化疗失败的非小细胞肺癌

目的了解一线化疗失败的非小细胞肺癌的临床症状与治疗方法,探讨吉非替尼或多西他赛对一线化疗失败的非小细胞肺癌的临床疗效,评价吉非替尼或多西他赛对一线化疗失败的非小细胞肺癌的安全性。方法将60例一线化疗失败的非小细胞肺癌患者随机分为两组,A组30例,使用吉非替尼进行治疗,B组30例,使用多西他赛进行治疗,然后观察评价两组患者治疗后的生存质量,并进行比较分析。结果两组中位无疾病进展生存率及客观有效率相比具有显著统计差异,P<0.05,但两组中位生存时间和中位无疾病进展生存时间相比没有显著统计差异,P>0.05;而且两组3～4级不良反应发生率和因不良反应而调整药物用量的发生率相比也具有显著统计差异,P<0.05。结论对于一线化疗失败的非小细胞肺癌,吉非替尼和多西他赛对它的总体疗效是差不多的,但吉非替尼的耐受性更好,对患者生活质量改善方面明显优于多西他赛,应予以临床推广应用。     

吉非替尼与多西他赛二线治疗晚期非小细胞肺腺癌的临床效果分析

目的:观察分析吉非替尼与多西他赛二线治疗晚期非小细胞肺腺癌的临床效果.方法:选取我院收治的60例一线化疗失败的晚期非小细胞肺腺癌患者作为研究对象,根据随机数字表法分为吉非替尼组和多西他赛组,每组30例.吉非替尼组给予吉非替尼口服,1次/d,250mg/次;多西他赛组给予多西他赛75mg/m2,静滴1h,d1,每21d重复.比较两组临床疗效、控制率、治疗费用和毒副反应.结果:吉非替尼组治疗总有效率和疾病控制率显著高于多西他赛组(P<0.05);且毒副反应较轻,用于治疗毒副反应的费用低.结论:吉非替尼较多西他赛二线治疗晚期非小细胞肺腺癌的临床总有效率和疾病控制率较高,毒副反应较轻,患者耐受性好.     

吉非替尼联合化疗治疗晚期肺腺癌疗效观察

目的:观察吉非替尼联合化疗治疗晚期肺腺癌的疗效。方法:从2013年9月到2014年4月这8个月来本院就诊的50例晚期肺腺癌患者随机分为试验组和对照组。实验组接受吉非替尼联合化疗治疗,对照组仅接受吉非替尼治疗,对两组的治疗效果进行统计比较。结果:试验组的有效率为48%,对照组的有效率为64%,差异有统计学意义(P<0.05),仅服用吉非替尼的效果优于吉非替尼联合化疗的治疗方法。结论:吉非替尼联合化疗治疗晚期肺腺癌效果不明显,而且存在毒副反应。因此,吉非替尼不能与放化疗同时进行。     

吉非替尼治疗化疗失败的晚期非小细胞肺癌58例疗效观察

目的观察吉非替尼治疗化疗失败的晚期非小细胞肺癌（NSCLC）的疗效和不良反应。方法 58例患者给予吉非替尼250mg,每天1次,至出现不能耐受的不良反应后停药。观察疗效、影响疗效的因素和不良反应。结果 58例有效率为41.4%,疾病控制率为72.4%;中位生存期为7.1个月,1年生存率为36.0%;女性患者有效率为51.9%,疾病控制率为85.2%,均高于男性的32.3%和67.7%;腺癌、细支气管肺泡癌的有效率分别为50.0%和60.0%,疾病控制率为79.4%和100.0%,均高于其他类型;无吸烟史有效率为55.2%,疾病控制率为82.8%,高于有吸烟史的27.6%和62.1%。差异均有统计学意义（P〈0.05）。化疗次数和ECOG评分对疗效无影响（P〉0.05）。所有患者均未发生严重不良反应。结论吉非替尼对于化疗失败的晚期NSCLC疗效满意,不良反应轻,是最佳的治疗方法 。     

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.