国产吉西他滨联合铂类进行非小细胞肺癌化疗的生存状况观察

目的:评价国产吉西他滨联合铂类治疗非小细胞肺癌患者的生存状况。方法:60例非小细胞肺癌患者根据是否进行根治性手术,将本组患者分为晚期化疗组和根治性手术治疗+化疗组。晚期化疗组22例,根治性手术治疗+化疗组38例。采用国产吉西他滨联合顺铂/卡铂方案,化疗方案采用常规剂量及用法,每3周为1周期,所有患者至少完成2周期化疗。对所有患者均进行随访,分别评估2组生存状况。结果:晚期化疗组中22例患者化疗2周期后疗效为:1例CR,8例PR,13例SD。治疗有效率(CR+PR)为40.9%。晚期化疗组患者1年生存率44.0%,中位生存期12.39个月。根治性手术治疗组1年生存率89.0%,3年生存率80.0%,中位生存期48.0个月。结论:国产吉西他滨与铂类联合方案治疗非小细胞肺癌用药安全有效,生存状况同国外文献同类药物报道相似。     

高危乳腺癌术后以吡柔比星为主密集化疗的临床分析

目的对吡柔比星为主密集化疗方案在高危乳腺癌术后应用的临床疗效进行观察。方法选取2007年10月至2008年11月在本院治疗的高危乳腺癌术后的患者45例,随机分成观察组23例和对照组22例,观察组进行以吡柔比星为主密集化疗方案进行治疗,对照组采用常规化疗方案进行治疗,比较两组的临床治疗效果。结果两组患者均经随访3年,对照组无瘤生存15例,无瘤生存率68.18%;观察组无瘤生存20例,无瘤生存率86.96%。两组在无瘤生存率上具有显著性差异,(χ2=6.85,P<0.05),有统计学意义。结论以吡柔比星为主的密集化疗方案在高危乳腺癌术后的治疗上临床效果良好,值得临床推广使用。     

EP与TP方案同步化放疗治疗Ⅲ期非小细胞肺癌疗效观察

目的观察EP与TP方案同步化放疗治疗Ⅲ期非小细胞肺癌的疗效。方法86例Ⅲ期非小细胞肺癌患者随机分为TP组42例和EP组44例,EP组采用EP方案化疗4个周期,TP组采用TP方案化疗4个周期,并于第1周期化疗第1天开始放疗。两组放射治疗均采用6MVX直线加速器常规分割治疗,放射治疗总量DT60～70Gy,6～7周完成。结果EP组CR8例,PR30例,有效率(CR+PR)86.4%;TP组CR8例,PR29例,有效率(CR+PR)88.1%,两组有效率差异无统计学意义(P>0.05)。EP组1、2、3年生存率分别为65.9%、45.5%、29.5%;TP组和EP组中位生存期分别为19.2个月和l8.5个月。2组间中位生存期及1、2、3年生存率差异无统计学意义(P>0.05)。两组的恶心、呕吐、骨髓抑制、放射性食管炎和放射性肺炎发生差异无统计学意义(P>0.05)。结论EP与TP方案同步化放疗均能对Ⅲ期NSCLC起到很好的疗效,TP组在近期有效率、中位生存期及2、3年生存期上均较EP组高;而EP组的不良反应发生率较低,患者的生活质量和治疗依从性相对较好,但二组之间的差异无统计学意义     

16例Ⅳ期神经母细胞瘤患儿多学科协作治疗分析

目的 探讨多学科协作治疗Ⅳ期神经母细胞瘤(NB)患儿的效果.方法 收集本院自2012年1月至2016年9月收治的Ⅳ期NB患儿16例,对其基本资料、病理类型、化疗情况、手术方式、自体干细胞移植情况、术后随访资料进行分析,绘制Kaplan meier生存曲线,与Ⅳ期神经母细胞瘤国内外治疗结果的Meta分析进行比较.结果 研究共纳入16例患儿,其中男9例,女7例,年龄为5～98个月(中位年龄40个月),中位随访时间24个月(12～45个月),全部患者均进行术前化疗并实施手术,术后根据危险度进行化疗,部分患者采用干细胞移植.16例患儿除1例放弃治疗于确诊后2月失访,其余15例中8例无病存活,4例患儿带病存活,3例死亡.结论 多学科协作诊疗模式不但提高Ⅳ期神经母细胞瘤患儿的远期生存率,并且可提高患儿中期部分缓解(PR)和完全缓解(CR)的概率.     

NB09 方案治疗 4 期神经母细胞瘤患儿效果分析

目的 探讨 4 期神经母细胞瘤（NB）患儿的综合治疗效果及预后。方法 回顾性分析 95 例 4 期 NB 患儿, 根据患儿接受的治疗方案, 比较 NB09 方案及非 NB09 方案的疗效差别, 并分析影响 4 期患儿预后的相关因素。全组患儿中位年龄 48 个月（4～136 个月）, 中位随访时间 21 个月（4～179 个月）, NB09 方案治疗患儿 40 例, 非 NB09 方案治疗 55 例。结果 NB09 组患儿 3 年总生存率 （OS） 及无疾病进展生存率 （PFS） 情况均明显好于非 NB09 组（χ2分别为 6.916 和 10.025, P＜0.05）。对全组患儿预后行单因素分析, 治疗方案、 病理类型、 骨髓受累>20%、 NMYC 扩增、 手术范围、 是否维甲酸诱导、 乳酸脱氢酶 （LDH） >1 000 U/L 及短期疗效达非常好的部分缓解 （VGPR） 为影响全组患儿预后的因素。多因素分析显示, 影响整组患儿预后的独立因素为骨髓受累>20% （P＜0.05）。结论 接受了 NB09 方案治疗的 4 期患儿预后较其他患儿好, 骨髓受累>20%的 4 期患儿预后差, 需加强治疗强度。     

急性早幼粒细胞白血病缓解后治疗的随访观察

目的 :观察经全反式维甲酸 (ATRA)诱导治疗取得完全缓解 (CR)的急性早幼粒细胞性白血病 (APL)的缓解后治疗的疗效。方法 :34例经ATRA治疗取得CR的APL患者 ,随机分为二组进行缓解后治疗 ,化疗组 1 6例 ,CR后予HA、DA等方案定期巩固化疗 ,持续 3a～ 4a停药 ;化疗与ATRA交替治疗组 1 8例 ,CR后采用化疗与ATRA每月交替方案进行治疗 ,持续 3a～ 4a停药。结果 :随访 1 3个月～ 85个月 ,复发 8例 ,复发率 2 3 5 %,其中化疗组复发 5例 ,复发率 31 3%,化疗与ATRA交替治疗组复发 3例 ,复发率 1 6 7%,总生存例数 2 8例 ,总生存率 (OS) 82 4 %,其中化疗组生存 1 2例 ,OS 75 %,生存 3a以上 8例 ,化疗与ATRA交替治疗组生存 1 6例 ,OS 88.9%,生存 3a以上 1 1例 ,两组复发率及OS无显著性差异 (P >0 0 5 ) ,复发后 6例接受重新诱导治疗 ,4例取得第二次CR(CR2 ) ,CR2 率 6 6 7%。结论 :APLCR后予积极治疗 ,可减少患者复发率 ,延长患者生存期。CR后采用化疗与ATRA交替治疗方案 ,与单用化疗巩固治疗比较 ,复发率低、生存率高 ,但无统计学意义。APL复发后重新诱导治疗 ,仍可取得CR2 ,但CR2 期较短。     

抗GD2抗体联合细胞因子在高危NB治疗中的研究进展

神经母细胞瘤(neuroblastoma,NB)是儿童期最常见的颅外实体瘤,具有后期易复发、远处转移、产生耐药性等特点,特别是高危NB患儿预后较差,5年生存率低于50％.抗GD2单克隆抗体(抗GD2 mAbs)作为治疗高危NB微小残留病灶的一种特异性最强免疫靶向疗法,当与IL-2或粒细胞-巨噬细胞集落刺激因子(GM-C...     

FOLFO 84方案治疗晚期结直肠癌的临床研究

目的观察FOLFOX4化疗方案治疗晚期结直肠癌的临床疗效及其毒副反应。方法 53例晚期结直肠癌患者采用FOLFOX4方案化疗,每2周为1个周期,治疗4个周期后按WHO实体瘤疗效判定标准评价疗效及毒副反应。结果总有效(CR+PR)率为56.6%,其中结肠癌总有效率为54.2%,直肠癌总有效率58.6%,两组比较差异无统计学意义(P>0.05),中位缓解时间6.7个月,中位生存期13.7个月,1年生存率为56.0%。毒副反应主要为胃肠道反应、末鞘神经毒性、骨髓抑制及静脉炎等,对症治疗均能耐受。结论 FOLFOX4方案治疗晚期结直肠癌患者有提高总生存率的趋势,耐受性较好,疗效较满意,有临床应用价值。     

肾母细胞瘤的治疗体会

目的 探讨肾母细胞瘤的综合治疗,重点是对术前化疗的研究。方法 回顾性分析我院1988～1999年收治的13例肾母细胞瘤的临床资料。结果 全部病例均行手术治疗,8例术前小剂量长春新碱诱导瘤细胞凋亡治疗2～3周,2例术前介入栓塞化疗。术后按NWTS-Ⅲ方案进行化疗、放疗。全部病例均得到随访,10例无瘤生存,1例带瘤生存,1例死于肿瘤复发,1例死于车祸。结论 提高肾母细胞瘤长期生存率的主要途径是不断发展和完善包括手术、化疗、放疗在内的综合治疗,尤其注重对术前化学疗法的研究。     

三维适形放疗联合介入治疗原发性肝癌疗效观察

目的探讨三维适形放疗(3DCRT)联合肝动脉化疗栓塞(TACE)治疗原发性肝癌的综合治疗效果及不良反应。方法经病理学证实原发性肝癌36例,采用先行TACE,再行3DCRT,观察疗效及生存期。结果全组患者在治疗后疗效判定,局控率及治疗后3个月、6个月及1年生存率,CR4例(11.1%),PR26例(72.2%),NC3例(8.3%),PD3例(8.3%),总有效率(CR PR)83.3%。主要的不良反应为消化道症状及骨髓抑制。结论三维适形放疗联合肝动脉化疗栓塞术是非手术治疗原发性肝癌的有效治疗方案。     

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.