Baloxavir marboxil (baloxavir), a cap-dependent endonuclease inhibitor, has been proven safe and efficacious against influenza and approved for the treatment of influenza in children aged ≥ 5 years in China. There were limited data on baloxavir in Chinese pediatric patients aged 1 to < 5 years with influenza. This study aimed to evaluate the safety, clinical efficacy, and virologic outcomes of baloxavir for treating influenza in this younger age group. In this single-arm, multicenter trial, patients received a single oral dose of baloxavir (2 mg/kg for participants weighing < 20 kg, or 40 mg for participants weighing ≥ 20 kg to < 80 kg). The primary endpoint was safety. Efficacy, virology, and palatability endpoints were also assessed. All 100 enrolled children completed the study and received baloxavir. Adverse events were reported in 29 (29.0

目的 分析中国儿科人群干细胞临床研究现状,为国内研究者提供儿科人群干细胞临床研究参考.方法 通过检索美国临床试验数据库网站进行我国儿科人群干细胞临床研究登记信息的采集,对临床研究每年新增项目数、临床阶段、适应症、应用干细胞类型、申报者、资金来源、研究设计等方面进行统计分析.结果 截至2021-11-30,网站共登记包含儿科人群的干细胞临床研究共89项;我国儿科人群干细胞临床研究在2013年和2019年开展项目数最多,可能与我国近些年陆续出台政策相关;我国儿科人群干细胞临床研究多处于早期探索阶段,以间充质干细胞临床研究为主,研究疾病类型涉及广泛,以血液系统疾病为主;临床研究多由医疗机构发起,以科研探索为主;临床研究类型主要是干预性研究,少数研究设盲,涉及预计样本量例数较少.结论 我国儿科人群干细胞临床研究近年来发展平稳,技术仍处于早期发展水平,临床应用前景十分广阔.

Objective:To help clinical pharmacists clearly position themselves, seize the opportunity, and actively participate in pediatric clinical research projects.Methods:Through SWOT analysis, this study analyzed the advantages and disadvantages of clinical pharmacists of Beijing Children's Hospital participating in drug clinical research from four aspects: superiority (S), weak (W), opportunity (O), and threat (T), so as to form development suggestions for pediatric clinical pharmacists in drug clinical research.Results:Pediatric clinical pharmacists could take advantage of external opportunities to initiate drug clinical studies and participate in drug clinical trials as the principal investigator, and participate in the formulation of clinical research protocols and drug safety incident management as a research team member. Relying on internal advantages, pediatric clinical pharmacists could strengthen popular science education, reduce irrational drug use, and promote clinical research. Seizing the external opportunities, they could improve their professional quality, play a role in drug management for clinical research and drug clinical research quality control to increase clinical research practice experience. Overcoming internal disadvantages, they could play a role in protecting subjects' rights and interests and provide consulting services to improve subjects' compliance.Conclusion:Pediatric clinical pharmacists should clearly position themselves, seize the opportunity of children's drug research and development, participate in drug clinical research, and provide better pharmaceutical services for children.

Objective:To analyze the status quo of clinical trials of rare disease drugs in China and abroad, to provide reference for further promoting the development of clinical research of rare disease drugs in China.Methods:By extracting the data of clinical trials of rare disease drugs in China's "drug clinical trial registration and information publicity platform", weanalyzedthe characteristics of clinical trials of rare disease drugs in China from the aspects of project registration, test type and stage, involved diseases, and scheme design, and comparedthem with the registration data of foreign clinical trials of rare disease drugs.Results:As of March 31, 2022, there were a total of 337 clinical trials of rare disease drugs in China's "drug clinical trial registration and information publicity platform", involving 37 diseases and 125 experimental drugs. Among them, there were 127 bioequivalence tests, accountingfor 37.6%; 278 domestic projects, accountingfor 82.4%; and 103 projects involving children, accountingfor about 37.0%.Compared with those in other countries, clinical trials of rare disease drugs in China had the following characteristics: (1) the number of clinical trialsshowedan obviously increasing trend; (2) there were few clinical trials of innovative drugs but many bioequivalence tests of generic drugs; and (3) the proportion of trials involving children was high.Conclusion:The clinical research on innovative drugs for rare diseases is still a weak link in China, and we need to improve legislation, increase financial support, enhance personnel training, and improve innovative research paths and methods.

目的:探讨儿科医疗机构研究型病房的运行和管理模式.方法:通过查阅文献资料和实地考察,对北京市第一批示范性研究型病房建设单位不同的病房运行模式和管理模式进行分析比较,并结合儿科医疗机构自身特点,提出一种研究型病房新型运行和管理模式.结果:参考成人综合医院和专科医院两种不同的研究型病房运行模式和管理模式,分析儿科机构自身特点,结合研究型病房建设目标及功能定位,探索出一套具有儿科特色的研究型病房高效高质量运行的管理模式——"平急结合"模式,并提出进一步改进和完善建议.结论:儿科临床研究有其特殊性,不能照搬成人医疗机构研究型病房已有的运行和管理模式,需结合儿科临床研究现状和医院自身需求,建立适合自身的发展模式,并在临床研究管理体系、支撑平台、信息化系统以及人才梯队等方面加强建设.

近年来,随着系列改革政策的出台,儿童用药的研发越发受到重视,儿童用药的科学监管力度也越发增强,但是药品说明书中儿童用药信息的缺失或不完善问题依然突出,尚缺乏有效措施予以规范.本文介绍了我国目前存在的药品说明书中儿童用药信息缺失或不完善问题,梳理了美国、欧洲和我国的法规制定历程,介绍了《化学药品和治疗用生物制品说明书中儿童用药相关信息撰写的技术指导原则(试行)》的起草背景,最后详细介绍了该指导原则及要点内容.

随着国家创新药物研发产业的迅猛发展,医疗机构内研究者开展研究者发起的临床研究(investigator-initiated trial,IIT)的积极性日益增加.一个高质量的IIT项目不仅依靠研究团队,更需要管理部门对其进行规范化管理.在我国IIT监管政策和规范指南尚不完善的情况下,梳理医疗机构内IIT项目的管理现状、探讨管理中易出现的问题、分析总结管理要点,可为医疗机构内IIT项目的规范化管理提供建议和参考.通过文献调研,整理出医疗机构内IIT管理相关的5个要素,并对每个管理要素中较突出的问题进行分析和汇总.根据国家对IIT管理的规范要求,咨询北京某三甲医院临床研究管理部门对IIT项目的管理经验,并结合本院既往临床研究管理实践,提出建议和对策,力求为制定和完善国家有关IIT研究的监管政策,规范医疗机构对IIT项目的管理提供参考.

The Fuyou (Fy) formula is an in-hospital preparation consisting of traditional Chinese medicine (TCM) that has been used for treating precocious puberty (PP) for more than 20 years. In this study, we aimed to clarify the effect of the Fy formula and its major components on PP. To confirm the effect of the Fy formula on the release of hypothalamic gonadotropin-releasing hormone (GnRH), GT1-7 cells were treated with estrogen to build the model group and subsequently treated with the Fy formula and its major components to explore their effects on the secretion of GnRH. The level of GnRH in GT1-7 cells was determined using enzyme-linked immunosorbent assay. The results illustrated that, compared to the model group, the Fy formula inhibited the release of GnRH. In addition, the expression levels of proteins related to GnRH secretion, including GnRH, gonadotropin-releasing hormone receptor (GnRHR), Kiss-1 metastasis-suppressor (Kiss1), G-protein coupled receptor 54 (GPR54), estrogen receptor α (ERα), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-1 receptor (IGF-1R), were detected by real-time polymerase chain reaction (RT-qPCR). The results demonstrated that the Fy formula significantly reduced the level of GnRH secretion in the GT1-7 cell lines compared with the model group. Moreover, it significantly downregulated the expression of GnRH, GnRHR, Kiss1, GPR54, ERα, IGF-1, and IGF-1R. In summary, our results indicate that the Fy formula and its major components may inhibit the effects of estrogen, which alleviates PP through transcriptional regulation of target genes.

Research ward construction is one of the important carriers to promote the transformation from traditional hospital to research hospital. Since the launch of the research ward construction project in Beijing in 2020, 30 medical institutions have been incorporated into the construction system in three batches, including grade-A general hospitals and specialty hospitals. Pediatric clinical research has its particularity, which determines that the construction of research ward in pediatric medical institutions cannot copy the construction idea of general hospitals. Referring to the experience of research hospital and research ward construction both at home and abroad, Beijing Children's Hospital explored and practiced a way of operation and management of research wards with pediatric characteristics based on the current situation of domestic pediatric medical institutions. In this paper, we put forward some suggestions and measures for further improvement of such construction, such as strengthening the service capacity of clinical research support departments and the comprehensive capacity construction of research team, in order to standardize the management of clinical research, improve the quality of clinical research, and promote the hospital to develop into a research-oriented innovative hospital.

目的 回顾性调查与分析我国儿童常用药品说明书中儿童药物代谢动力学(简称药动学)标注现状,以期为规范和完善我国儿童药品说明书信息提供参考.方法 总结和比较美国食品药品管理局、欧洲药品管理局及国家药品监督管理局发布的药品说明书相关指导原则对药动学标注内容和数据结构的要求,收集我国8家儿童医院常用药品说明书,从疾病种类、药动学数据来源、药动学参数标注情况等维度分析药品说明书儿童药动学标注情况.结果 共收集有效药品说明书1719份,说明书信息中标注有成人药动学信息的品种数有914种,标注率53.17％;标注有儿童药动学信息的品种数150种,标注率8.73％,来源于儿童临床试验的数据占70.67％.药动学参数中半衰期标注率88.00％,达峰时间标注率76.00％,达峰浓度标注率47.30％,蛋白结合率、表观分布容积、清除率、生物利用度以及血药浓度曲线下面积标注较少,标注率不超过33.30％.结论 药品说明书中儿童药动学信息缺乏现象普遍存在,标注格式不规范、内容不完整、质量不高,建议通过建立药动学数据库及儿童药动学研究方法优化体系等为完善儿童药品说明书儿童药动学信息提供方向.

新技术在儿童疾病的临床诊断、治疗和预防中发挥着重要作用,为解决儿童健康问题提供了更多的选择.是否在儿童群体开展新技术,开展研究和应用过程中如何保证儿童的最大利益是临床医生和研究者面临的重要问题.分别对基因技术、人类干细胞技术和人体器官移植三种现代技术在儿童群体研究或应用的特殊伦理问题进行探讨,为临床医生和研究者提供参考建议和应对策略,以期保障儿童权益.

论述了儿科人群多中心临床试验伦理协作审查模式的建立背景、适用范围、相关定义,参与协作审查的伦理委员会资格要求、协作审查的流程,以及参与协作审查的各方伦理委员会的职责.依据国家相关法规及文件的规定,以签订"互认协议"的方式构建儿科人群多中心临床试验伦理审查结论互认的协作审查模式,推进儿科人群多中心临床试验的规范、高效开展.

目的:建设高质量、专业化的临床试验研究者团队,提升团队人员研究能力和水平,推动我国临床研究快速健康发展.方法:通过分析临床试验核查中发现的问题,查找问题产生的原因,提出建设稳定、高效、高质量的临床试验研究者团队的重要性和必要性,并进一步探讨临床试验研究者团队建设的策略.结果 与结论:多数临床研究中出现的问题和缺陷均与研究者团队人员遵循《药物临床试验质量管理规范》(GCP)的原则性不强、研究能力不足有关.只有加强临床试验研究者团队建设,才能从根本上推动临床研究高质高效发展.主要研究者作为临床试验研究者团队的总指挥,在临床试验实施过程中起关键作用,是临床试验质量的保证者.笔者建议可以通过宣教培训转变研究者观念,完善配套政策和措施,激发研究者承担临床试验的积极性和主动性,壮大研究者队伍;通过搭建临床研究平台,构建长效培训体系和多层次教育体系,稳定临床研究人才梯队;通过开展多学科、跨领域协作,锻炼团队人员专业水平和协作能力,提升我国临床试验研究者团队质量.

规范临床试验机构试验药物管理是提高受试者安全性、确保试验数据准确与完整性的重要保证.美国卫生系统药师协会于2018年出台了《临床试验药物管理指南》,对临床试验药物管理的6个关键环节,即临床试验药房的意义及管理模式、存储基础设施、人员管理、文件管理、过程管理、监查工作等作了详细规定.我国目前尚缺乏较全面的关于临床试验药物管理的相关规范,该文对该指南的关键内容进行详细解读和介绍,以期为我国临床试验药物管理提供参考和借鉴.

Chemotherapy post cancer surgery has important clinical significance for reducing the chance of recurrent-metastasis. However, postoperative chemotherapy efficacy is hampered by poor targeting capability and dose-limiting toxicity of chemo-drugs. Herein, we report a bio-mimetic platelet membrane-cloaked paclitaxel nano-crystal system (PPNCs), which consists of spherical paclitaxel nanocrystals (PNCs) as a high-dose drug core, polyethylene glycol-conjugated paclitaxel (PEG-PTX) as an amphiphilic molecule to adjust the surface hydrophilicity of PNCs and the shell of platelet membrane that can target surgical coagulation site. The in vitro characterization of PPNCs exhibited uniform particle size distribution, high drug loading, and good stability, which are crucial for effective drug delivery. At cell levels, PPNCs showed greater cellular uptake and higher cytotoxicity in 4T1 breast cancer cells than bare PNCs. In vivo, the nanoparticles could deliver high-dose chemodrugs and target the coagulation site caused by surgery or vascular disrupting agents, resulting in enhanced antitumor efficacy and reduced systemic toxicities. In general, the PPNCs system can be served as a promising and efficient drug delivery system for postoperative chemotherapy.