Exploring the potential of exosomes in diagnosis and drug delivery for pancreatic ductal adenocarcinoma

Pancreatic cancer (PC) is a cancer of the digestive system, and pancreatic ductal adenocarcinoma (PDAC) accounts for approximately 90% of all PC cases. Exosomes derived from PDAC (PDAC-exosomes) promote PDAC development and metastasis. Exosomes are nanoscale vesicles secreted by most cells, which can carry biologically active molecules and mediate communication and cargo transportation among cells. Recent studies have focused on transforming exosomes into good drug delivery systems (DDSs) to improve the clinical treatment of PDAC. This review considers PDAC as the main research object to introduce the role of PDAC-exosomes in PDAC development and metastasis. This review focuses on the following two themes: (a) the great potential of PDAC-exosomes as new diagnostic markers for PDAC, and (b) the transformation of exosomes into potential DDSs.     

早产儿体位管理的最佳证据总结

目的 检索、评价并整合国内外早产儿体位管理的相关证据,为临床实践提供参考。方法 计算机检索国际指南网、英国国家健康与临床优化研究所网站、苏格兰学院指南网、美国指南网、加拿大安大略注册护士协会网站、乔安娜布里格斯研究所循证卫生保健中心数据库、BMJ Best Practice、PubMed、Embase、OVID、万方数据库、中国知网、医脉通等网站或数据库中关于早产儿体位管理的所有证据,包括指南、证据总结、最佳临床实践手册、临床决策及系统评价,检索时限为建库至2020年8月31日。结果 共纳入10篇文献,其中指南3篇、系统评价5篇、技术报告1篇、临床决策1篇。从体位评估、体位摆放、体位辅助工具及使用、特殊疾病或情境下的体位管理4个方面总结了21条证据。结论 该研究总结了早产儿体位管理的最佳证据,为规范早产儿体位管理提供了循证依据,建议护理人员在应用证据时综合考虑临床实际情况选择性应用最佳证据,促进早产儿健康。     

脂质纳米粒-mRNA递送系统及其在嵌合抗原受体T细胞治疗中的应用

尽管嵌合抗原受体（CAR）T细胞治疗在血液系统恶性肿瘤患者中取得了显著的临床疗效，但需要进一步优化。脂质纳米粒（LNP）-信使核糖核酸（mRNA）递送系统作为一种非病毒性基因载体运用于CAR-T细胞治疗研究中，一方面通过LNP将密封蛋白-6 mRNA靶向递送至抗原提呈细胞，从而实现抗原提呈细胞辅助性增强密封蛋白-6靶向的CAR-T细胞的功能，以进一步诱导对实体瘤的清除；另一方面，通过LNP将成纤维细胞激活蛋白（FAP）CARmRNA靶向递送至T细胞，实现体内FAP靶向的CAR-T细胞的制备，以通过阻断心脏纤维化过程达到治疗急性心肌损伤的目的。在CAR-T细胞研究和治疗中，LNP-mRNA递送系统具有不与细胞基因组整合、价格便宜、毒副作用小及可修饰等优点，亦存在蛋白瞬时表达导致调控细胞功能的持久性不足及制备等方面的技术局限性。本文综述了LNP-mRNA递送系统及其在CAR-T细胞治疗中的应用研究。     

Fourteen years of the Pregnancy Registry on maternal immunisation with a reduced-antigen-content tetanus-diphtheria-acellular pertussis (Tdap) vaccine

BackgroundGSK initiated a Pregnancy Registry in the United States (US) for the reduced-antigen-content tetanus-diphtheria-acellular pertussis (Tdap; Boostrix, GSK) vaccine with the aim to detect and describe pregnancy outcomes in women vaccinated with Boostrix 28 days before estimated conception or during pregnancy.MethodsVoluntary reports of pregnancy exposure to Boostrix received from spontaneous and post-marketing surveillance sources in the US were assessed. Reports were classified as prospective or retrospective based on the knowledge of pregnancy outcomes at the time of reporting. For completeness, reports of exposure to Boostrix or to the Tdap-inactivated poliovirus vaccine (Boostrix-IPV, GSK) reported to the global safety database from countries outside the US were also evaluated.ResultsFrom May 2005 to August 2019, 1517 (1455 prospective and 62 retrospective) pregnancy reports were received in the Boostrix US Pregnancy Registry. Of the prospective reports, 250 had known outcomes: 244 live infants with no apparent birth defects (BDs), three live infants with BDs, and three spontaneous abortions with no apparent BDs. Of the retrospective reports, 55 had known outcomes: 33 live infants with no apparent BDs, 16 live infants with BDs, one spontaneous abortion with no apparent BDs, four stillbirths with no apparent BDs, and one stillbirth with BDs. Cumulatively, 1321 pregnancy reports (1006 for Boostrix; 315 for Boostrix-IPV) were received from countries outside the US. Of these, 163 prospective reports and 551 retrospective reports had known outcomes. Results were in line with those from the Boostrix US Pregnancy Registry.ConclusionsData currently available from the Boostrix US Pregnancy Registry and from countries outside the US suggested that exposure to Boostrix or Boostrix-IPV during pregnancy does not raise safety concerns related to adverse pregnancy outcomes or BDs.     

Repurposing of parenterally administered active substances used to treat pain both systemically and locally

Pain is a constant in our lives. The efficacy of drug therapy administered by the parenteral route is often limited either by the physicochemical characteristics of the drug itself or its adsorption–distribution–metabolism–excretion (ADME) mechanisms. One promising alternative is the design of innovative drug delivery systems that can improve the pharmacokinetics |(PK) and/or reduce the toxicity of traditionally used drugs. In this review, we discuss several products that have been approved by the main regulatory agencies (i.e., nano- and microsystems, implants, and oil-based solutions), highlighting the newest technologies that govern both locally and systemically the delivery of drugs. Finally, we also discuss the risk assessment of the scale-up process required, given the impact that this approach could have on drug manufacturing.Teaser: The management of pain by way of the parenteral route can be improved using complex drug delivery systems (e.g., micro- and nanosystems) which require high-level assessment and shorten the regulatory pathway.     

Local magnetic delivery of adeno-associated virus AAV2(quad Y-F)-mediated BDNF gene therapy restores hearing after noise injury

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Static and dynamic postural control of postpartum women of different delivery methods

ObjectiveThe aim of this study was to determine whether there is a difference in postural control between nulligravida women and women who have given birth by vaginal or cesarean section.MethodsWomen who had only vaginal delivery in the previous 1–3 years were included in the vaginal delivery group (n = 27), those who had only cesarean delivery in the previous 1–3 years were included in the cesarean section group (n = 28), and those who had never given birth were included in the control group (n = 32). Evaluations were administered 6–8 days after the ovulation phase. Postural control of the participants was evaluated with the computerized dynamic posturography device.ResultsA total of 87 women with a mean age of 29.4 ± 4 years and a mean body mass index of 24.1 ± 3.1 kg/m² were included in the study. Antero-posterior somatosensory organization test values of the vaginal delivery group were lower than the control group (p = 0.0016). The cesarean delivery group had statistically lower antero-posterior somatosensory (p < 0.001 and p = 0.0013) and medio-lateral somatosensory (p = 0.002 and p = 0.017, respectively) test scores compared to the control group and the vaginal delivery group.ConclusionsIt was observed that women who birthed with vaginal or cesarean delivery had impaired somatosensory postural control. There is definitely a need for further studies with a long-term follow-up examining the effects of postural control during pregnancy and the postpartum period.