托珠单抗致不良反应文献分析

目的:分析托珠单抗致不良反应(adverse drug reactions,ADRs)发生情况及临床特点,为临床安全用药提供参考。方法:检索Web of Science、PubMed、维普数据库、中国知网数据库和万方数据库关于托珠单抗不良反应的文献并进行分析。结果:托珠单抗致ADRs的个案报道共51例,患者年龄分布以51~80岁年龄段较多(36例,70.6%);多发生在用药后的12个月内(41例,80.4%);托珠单抗致ADR主要以皮肤及其附件损害(11例,21.6%)和胃肠道损害(11例,21.6%)较多;49例经停药和(或)对症支持治疗后症状治愈或好转。ADRs好转后9例(17.7%)再次给予托珠单抗治疗,出现与之前相同的ADR。10例(19.6%)在ADRs好转或痊愈后重新恢复托珠单抗治疗未出现ADR。用药后重点监测时间段为3个月。结论:临床使用托珠单抗时应慎重评估患者相关的利益风险,综合考虑患者的各项实际情况,以防不良反应导致的严重损伤。对发生的不良反应要做到及时发现,及时治疗。还需要开展药物警戒调查阐明托珠单抗的长期安全性。     

帕博利珠单抗致不良反应文献分析

目的 分析帕博利珠单抗不良反应的发生情况及相关因素,以供临床安全用药参考。方法 检索CNKI、万方、维普、PubMed、Embase、ScienceDirect数据库收载的帕博利珠单抗致不良反应的个案报道,检索时间为建库至2023年3月15日,对纳入病例信息资料,包括性别、年龄、原患疾病、用法剂量、ADR发生时间、累及系统、临床表现、预后和转归等进行回顾性分析。结果 收集到帕博利珠单抗致ADR的案例报道171篇,共189例个案,其中60～79岁的患者（123例）占比最高;原患疾病以肺癌占比最高（75例）;给药后21 d和42～63 d内患者ADR发生频率较高;ADR表现以神经系统、呼吸系统为主;经治疗后,157例好转,32例死亡。结论 帕博利珠单抗ADR潜伏期长,且可损害全身多个系统,即使在停用后较长一段时间内,临床上均应及时识别和发现ADR的早期信号,确保患者用药安全。     

卡瑞利珠单抗致药品不良反应的文献病例分析

摘要：目的:探讨卡瑞利珠单抗所致药品不良反应（ADR）的类型和临床特点,为临床安全用药提供参考。方法:检索国内主要中文文献数据库,收集2019年6月～2022年4月卡瑞利珠单抗所致ADR病例报道文献,统计分析病例的年龄性别、原患疾病、联合用药,以及ADR发生时间、临床表现、分级和治疗转归等情况。结果:检索到卡瑞利珠单抗ADR病例报道的相关文献32篇,共35例病例,其中男24例,女11例,年龄35～76（58.62±10.18）岁;原患疾病以肺癌居多（14例,40.0%）;联合用药病例19例（54.3%）,联用最多的药物是紫杉醇;ADR诱导期≤30 d有19例（54.3%）,＞30 d有16例（45.7%）;ADR发生在免疫治疗第1周期有14例（31.4%）;ADR主要累及皮肤及其附件（16例,41.0%）、循环系统（7例,17.9%）和呼吸系统（5例,12.8%）。结论:临床医生在应用卡瑞利珠单抗时应准确把握用药指征,严格按照说明书,熟悉其ADR常见类型和发生时间,加强ADR监测,确保患者用药安全。     

坤泰胶囊致不良反应的文献分析

目的对坤泰胶囊致不良反应(ADR)的文献进行调研,为临床合理用药提供参考。方法检索中国学术期刊(网络版)、万方数字化期刊全文库、中文科技期刊全文数据库(维普)及Pub Med等数据库,收集报道坤泰胶囊致不良反应的文献进行统计和分析。结果共筛选出56篇文献,涉及病例2 140例,其中ADR病例232例;ADR病例年龄集中在46~55岁;用药2 d内出现ADR的例数最多;原患疾病为更年期综合征者最多(153例,65.95%);报道的ADR病例主要为单独使用坤泰胶囊产生的,且单用药156例(67.24%),联合用药76例(32.76%);ADR累及器官或系统主要为消化系统(256例次,42.95%),主要临床表现有胃肠道不适、腹胀、恶心、呕吐,且未见严重ADR发生;大部分发生ADR的患者未做任何处理,部分产生ADR的患者主要处理方法为饭后服药或停药处理,且处理后均好转。结论目前未发现坤泰胶囊致严重的ADR,但仍需分析已经报道的ADR产生原因,挖掘潜在的用药风险,进一步加强对其ADR的监测,探索行之有效的应对措施。     

帕博利珠单抗致免疫相关性不良反应文献回顾性分析

目的：分析帕博利珠单抗药品不良反应(Adverse Drug Reactions,ADR)的发生情况和临床特点,为临床合理用药提供参考。方法：检索中国知网、万方、维普、PubMed、Springer及Wiley中关于帕博利珠单抗的ADR个案报道,对其进行统计和分析。结果：帕博利珠单抗致ADR个案报道共41篇53例。 患者的年龄主要为51~70岁(54.71%)。ADR多发生在用药3个月后(47.37%),以皮肤系统(47.37%) 损害多见。ADR主要表现为大疱性类天疱疮(8例次)和视力下降(5例次)等。结论：在临床使用帕博利珠单抗时应注意监测和防治其ADR,避免严重的ADR发生。     

贝伐珠单抗治疗恶性肿瘤相关不良反应回顾性分析

摘 要 目的：探讨贝伐珠单抗治疗恶性肿瘤的相关不良反应（ADR）发生情况及特点,为临床安全使用贝伐珠单抗提供参考。方法：采用回顾性分析方法,收集2016年10月~2018年4月使用贝伐珠单抗治疗而出现ADR的94例恶性肿瘤病例,统计患者年龄、性别、所患疾病,贝伐珠单抗剂量、联合化疗方案,ADR发生时间、症状、严重程度等。 结果：患者原患疾病主要为结直肠癌、非小细胞肺癌（NSSCLC）和乳腺癌,其中化疗一线治疗53例,二线治疗41例。本组患者中贝伐珠单抗所致ADR发生在6个月内,≤3个月者64例,3~5个月者30例,其中导致出血、贫血、高血压比例分别为29.79%,29.79%,25.53%,明显高于其他ADR占比（P<0.05）。高血糖、肠穿孔等特殊ADR比例分别为7.45%,1.06%。结论：贝伐珠单抗严重ADR比例较低,临床使用贝伐珠单抗时,应密切关注发生概率较高及特殊的ADR,做到定期监测、及时处理。     

硫唑嘌呤不良反应文献分析

目的探讨硫唑嘌呤不良反应(ADR)发生情况及相关因素。方法检索中国期刊全文数据库(CNKI)、万方数据库和中文科技期刊全文数据库(VIP)的临床研究及ADR报告。提取纳入文献中ADR患者的原患疾病、性别、年龄及ADR类型。结果627篇文献中最终纳入98篇,其中不良反应报告(A类)文献42篇报告中有55例ADR,临床研究(B类)文献56篇(449例ADR),回顾性研究共13篇(317例ADR患者)。ADR患者女性略多于男性,主要为30~59岁。A类文献中,ADR主要表现为骨髓抑制、粒细胞缺乏、白细胞减少及脱发,原患疾病主要为系统性红斑狼疮、溃疡性结肠炎、重症肌无力;ADR患者中有13例死亡。B类文献中,ADR主要表现为肝功能异常、胃肠道反应、白细胞减少、骨髓抑制、感染;原患疾病为炎症性肠病、克罗恩病、视神经性脊髓炎、溃疡性结肠炎、重症肌无力。结论硫唑嘌呤主要的ADR为血液系统损害、肝功能损害,其中骨髓抑制严重者可致命。临床可通过用药前硫代嘌呤甲基转移酶基因检测、实验室指标监测及患者用药后的密切监护,避免或减少严重ADR的发生。     

亮丙瑞林药品不良反应文献分析

目的 促进临床合理使用亮丙瑞林.方法 计算机检索中国期刊全文数据库(CNKI)、万方数据库及PubMed,Embase数据库,收集自建库起至2020年12月31日关于亮丙瑞林药品不良反应(ADR)的报道,对患者年龄、性别、原患疾病、使用药物、联合用药,ADR发生时间、分布、临床表现、治疗与转归等数据进行统计与分析.结果...     

奥马珠单抗不良反应文献分析

目的:分析奥马珠单抗致不良反应(adverse drug reaction,ADR)的临床表现和特点,为临床安全用药提供参考。方法:检索中国知网、万方、维普、Web of Science、PubMed、Embase等数据库关于奥马珠单抗致ADR的个案报道并进行分析。结果:收集奥马珠单抗致ADR的个案报道26篇,共35例,其中男性9例(25.71%)、女性26例(74.29%),年龄分布以30~69岁居多(82.86%),发生时间大多在用药后1年内(87.27%),过敏反应主要集中在用药3个月内(66.67%),ADR以皮肤及其附件损害(48.78%)、呼吸系统损害(14.63%)和循环系统损害(12.19%)为主。多数患者对症处理后均好转,仅1例死亡,4例发生过敏反应的患者接受脱敏治疗并成功脱敏。结论:临床应用奥马珠单抗应加强ADR监测,防范严重ADR的发生,确保用药安全。     

727例银杏达莫注射液不良反应报告分析

目的:了解银杏达莫注射液不良反应(ADR)发生的特点和一般规律,为临床合理用药提供参考。方法:以"银杏达莫注射液""不良反应"为主题词,检索中国学术期刊全文数据库2005年1月1日-2016年6月28日收载的期刊文献,对患者性别、年龄、原患疾病、过敏史、用药情况、ADR发生时间、累及器官/系统及临床表现等进行统计、分析。结果:检索得到有效文献14篇,共计727例患者。其中,女性多于男性(57.63%vs.42.37%),年龄多在50岁以上,原患疾病以血栓栓塞性疾病、冠心病为主;ADR多在用药30 min内发生(268例,36.86%);累及器官/系统以神经系统(254例,28.60%)、皮肤及其附件(228例,25.68%)和消化系统(187例,21.06%)为主,严重者可致过敏性休克;新的严重的ADR 18例(2.48%);所有ADR均好转,无死亡病例。结论:临床应严格掌握银杏达莫注射液的适应证,辨证施治、合理用药,对用药过程严密观察,警惕ADR的发生。     

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.