奥拉帕利维持治疗乳腺癌易感基因突变铂敏感卵巢癌疗效的meta分析

目的 系统评价奥拉帕利维持治疗乳腺癌易感基因（BRCA）突变铂敏感卵巢癌的临床疗效及安全性。方法 计算机检索PubMed、Cochrane、Web of Science、中国知网、万方数据库、维普数据库等,收集奥拉帕利（观察组）与安慰剂（对照组）治疗BRCA突变铂敏感卵巢癌的随机对照试验。应用RevMan5.3软件进行meta分析。结果 最终纳入5篇文献。meta分析结果显示,观察组患者的中位无进展生存期（HR=0.35,95%CI:0.22～0.56,P<0.001）、总生存期（HR=0.77,95%CI:0.62～0.95,P<0.05）均明显长于对照组,差异有统计学意义。观察组的关节痛、腹痛、便秘、鼻咽炎等不良反应发生率与对照组差异无统计学意义（P>0.05）;而头痛、消化不良、发热等发生率高于对照组,差异有统计学意义（P<0.05）,但是这些不良反应的程度较轻,多为1～2级反应,大多数患者通过对症治疗和（或）奥拉帕利剂量调整后是可控的,只有极少数患者需要停用奥拉帕利。结论 奥拉帕利维持治疗BRCA突变铂敏感卵巢癌患者中疗效显著,安全可控,值得向临床推荐。     

奥拉帕利维持治疗铂敏感复发性卵巢癌的不良事件

目的 分析奥拉帕利在铂敏感复发性卵巢癌患者维持治疗中的不良事件。方法 回顾性分析2018年7~12月安徽省肿瘤医院使用奥拉帕利维持治疗的18例铂敏感复发性卵巢癌门诊患者的临床资料,通过门诊访视,统计分析患者在服药期间的不良事件。结果 奥拉帕利治疗过程中有15例（83.33%）患者出现恶心、乏力、贫血、白细胞降低及血小板减少等不良事件,其中以白细胞数降低占比最高（13例,占72.22%）。15例患者中,9例（50.00%）出现3~4级不良事件,贫血（8例,占44.44%）是最常见的3级以上不良事件。3例（16.67%）患者奥拉帕利减量,2例（11.11%）患者奥拉帕利永久停药。结论 奥拉帕利在铂敏感复发性卵巢癌维持治疗中,不良事件以白细胞数降低最常见,贫血是最常见的3级以上不良事件。     

奥拉帕利在卵巢癌真实世界治疗中的不良反应

目的 分析奥拉帕利在真实世界中治疗卵巢癌的不良反应及最常见血液学不良反应——贫血的影响因素。方法 回顾性分析2018年7月至2022年10月在我院妇科收治的146例卵巢癌患者使用奥拉帕利治疗期间的不良反应数据，尤其是贫血的发生情况，并对≥3级贫血的相关因素进行单因素及多因素分析。结果 146例患者治疗期间不良反应总发生率为76.7%，≥3级不良反应发生率为37.0%，其中最常见的为贫血（31.5%）。开始治疗的前3个月、4~6个月及6个月后，≥3级贫血的发生率分别为60.5%、16.3%、23.2%，因贫血暂停用药的发生率在1年后仍为11.6%。多因素Logistic回归分析显示，年龄（χ²=7.914， P=0.005， OR=1.066）、末次含铂化疗期间发生过≥3级贫血（χ²=5.269， P=0.022， OR=3.563）是奥拉帕利维持治疗期间发生≥3级贫血的独立危险因素。结论 贫血是奥拉帕利在卵巢癌真实世界治疗中最常见的血液学不良反应及最主要的≥3级不良反应，同时也是导致患者暂停用药的主要原因。奥拉帕利维持治疗期间，贫血的发生风险不限于3个月内，临床需持续关注。年龄及既往含铂化疗期间发生过≥3级贫血是奥拉帕利维持治疗期间重度贫血的高危因素，临床对高危人群应加强监测，避免重度不良事件的发生。     

奥拉帕利用于铂敏感复发性卵巢癌维持治疗的成本-效用分析

目的 评价奥拉帕利用于铂敏感复发性卵巢癌维持治疗的经济性。方法 从中国卫生体系角度出发,基于SOLO2/ENGOT-Ov21Ⅲ期临床试验数据建立分区生存模型,模拟得到奥拉帕利维持治疗及安慰剂治疗卵巢癌的成本和质量调整生命年（QALY）,以增量成本-效用比（ICUR）为指标,评价用于铂敏感复发性卵巢癌维持治疗的经济性。采用单因素敏感性分析和概率敏感性分析评价参数不确定性对模型结果稳定性的影响。结果 基础分析结果显示,奥拉帕利相较于安慰剂治疗的ICUR为874 865.84元/QALY,高于意愿支付（WTP）阈值的242 928元/QALY。单因素敏感性分析结果显示,对ICUR结果影响最大的参数为奥拉帕利的价格。概率敏感性分析结果显示,在现有WTP阈值下,奥拉帕利维持治疗方案不具有成本-效用优势的概率为100.00%。结论 奥拉帕利目前用于铂敏感复发性卵巢癌的维持治疗不具有成本-效用优势。     

复发性上皮性卵巢癌的药物治疗及进展

卵巢癌是妇科恶性肿瘤中预后最差的肿瘤,80%的上皮性卵巢癌患者会复发。根据卵巢癌对铂类的敏感性不同将复发性卵巢癌分为:铂类敏感、铂类部分敏感、铂类耐药及难治性,对铂类敏感性的不同是影响复发性卵巢癌(ROC)治疗选择的重要特征。以贝伐单抗(Bevacizumab)为代表药物的抗血管生成药物是在复发性卵巢癌治疗中研究最多的靶向药物,而对于存在生殖系或体系BRCA突变的卵巢癌患者,可通过使用PARP抑制剂作为维持治疗直到进展来优化化疗效果并延长无进展生存期(PFS)。复发性卵巢癌患者可通过二次减瘤术、常用化疗药物联合抗血管生成剂或PARP抑制剂的"个性化"方法整合,延长复发性卵巢癌患者的PFS。     

奥拉帕利致免疫性血小板减少症

1例69岁女性患者行卵巢癌细胞减灭术后接受白蛋白紫杉醇+卡铂方案化疗6个周期, 此后予奥拉帕利300 mg口服、2次/d。服用奥拉帕利前血小板计数(PLT)151×109/L, 用药第14天PLT为17×109/L, 血小板相关免疫球蛋白检测结果阳性, 考虑为奥拉帕利所致免疫性血小板减少症。患者未再服用奥拉帕利。先后给予血小板生成素、艾曲波帕、甲泼尼龙及输注血小板等治疗, 但患者反复出现PLT回升和降低, 最高为67×109/L, 最低为4×109/L。     

奥拉帕利单药维持治疗新诊断晚期BRCA基因突变上皮性卵巢癌、输卵管癌或原发性腹膜癌患者的药物经济学评价

目的 本研究基于医保支付方角度,评估奥拉帕利用于BRCA基因突变的晚期上皮性卵巢癌、输卵管癌或原发性腹膜癌初治成人患者在接受了一线含铂化疗后达到完全缓解或部分缓解的维持治疗的经济性.方法 在Excel中构建分区生存模型,代入SOL01研究亚洲人群的临床数据、效用数据和中国本土成本数据,评估患者接受了一线含铂化疗,达到完...     

局限期食管小细胞癌20例治疗临床分析

目的分析局限期原发性食管小细胞癌（PESC）的临床特点及其诊治与预后。方法回顾性分析2004年6月至2012年2月厦门大学附属第一医院收治的20例局限期原发性食管小细胞癌临床资料,并对其治疗手段、生存预后进行分析。结果全组20例患者中位无进展生存（PFS）5.7个月（3.9～7.5个月,95%CI）,中位生存（OS）16.1个月（9.3～23.0个月,95%CI）。15例曾接受化学治疗（术前新辅助化疗、放疗中同步化疗或术后辅助化疗）患者的PFS显著高于未接受化学治疗的患者（9.9月vs 3.7月,P=0.02）,但化疗与否并不影响总生存。结论食管小细胞癌目前尚无标准治疗模式。但包含了化学治疗的综合治疗可能是一种值得进一步探讨和推荐的治疗方式。     

晚期非小细胞肺癌应用吉西他滨维持治疗的疗效分析

目的比较晚期非小细胞肺癌行4周期一线含铂方案联合化疗后,单药吉西他滨维持治疗与最佳支持治疗两组之间无进展生存期（PFS）和总生存（OS）之间的差别。方法选择经过一线化疗后获得疾病控制的Ⅲb期或Ⅳ期非小细胞肺癌（NSCLC）患者62例,随机分为维持治疗组和对照观察组,维持治疗组给予吉西他滨按1g.m^-2d1、d8维持化疗,三周重复一次,直至疾病进展;对照观察组只给予最佳支持治疗,观察两组患者的PFS和OS的差别。结果维持治疗组的中位PFS为4．2月,明显优于对照观察组的2．9月,两组比较差异有显著性意义（P〈0．05）;维持治疗组和对照观察组的中位OS分别为13．7个月和11．4个月,两组比较差异无显著性意义（P〉0．05）。结论非小细胞肺癌4周期一线含铂方案联合化疗后采用单药吉西他滨维持治疗能改善PFS,副作用轻微,耐受性好。     

雷替曲塞联合奥沙利铂治疗晚期胃癌的疗效及安全性研究

目的：研究雷替曲塞联合奥沙利铂治疗晚期胃癌的疗效及安全性。方法选取苏州大学附属常州肿瘤医院2011年8月—2013年8月一线氟尿嘧啶类药物化疗失败后的23例晚期胃癌患者,予雷替曲塞联合奥沙利铂为二线方案化疗。观察患者的治疗效果。结果23例患者中完全缓解（CR）1例（4.3%）,部分缓解（PR）6例（26.8%）,病情稳定（SD）8例（34.9%）,疾病进展（PD）8例（34.9%）,中位无进展生存时间3.5个月。18例患者产生毒副作用。结论雷替曲塞联合奥沙利铂二线治疗晚期胃癌疗效较好,毒副作用较小。     

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.