第一代酪氨酸激酶抑制剂治疗中发生进展的非小细胞肺癌血浆表皮生长因子受体(EGFR)T790M突变提示了失败部位并预测了临床预后:一项前瞻性观察研究

背景与目的血浆循环肿瘤DNA(circulating tumor DNA,ctDNA)是检测表皮生长因子受体(epidermal growth factor receptor,EGFR)T790M突变的理想方法。T790M突变是第一代EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)耐药的主要机制。本研究旨在探讨ctDNA来源的T790M突变与非小细胞肺癌(non-small cell lung cancer,NSCLC)患者疾病失败部位及临床预后的关系。方法第一代TKI治疗发生进展的患者被分为局限胸内进展(chest limited,CF)、局限颅内进展(brain limited,BF)和其他部位进展(other,OF)组。采用扩增阻滞突变系统(amplification refractory mutation system,ARMS)和微滴式数字PCR(droplet digital PCR,ddPCR)对ctDNA中T790M突变进行了检测。采用Kaplan-Meier法分析了预后。结果 2种方法的总体一致性为78.3%。根据ARMS和ddPCR,OF组患者的T790M突变率明显高于BF组和CF组(P <0.001),OF组的T790M突变丰度也明显高于CF组和BF组(P <0.001)。AZD9291是T790M+患者最佳治疗选择,为EGFR-TKI治疗后进展的所有组中T790M+患者提供了最长的生存期;接受其他治疗的T790M-患者亚组的预后各不相同。结论本研究表明ctDNA中T790M突变与NSCLC患者EGFR-TKI治疗失败部位相关,失败部位和T790M突变状态对治疗选择和预后都有很大影响。

Application of extracorporeal membrane oxygenation in the endoscopic treatment of severe benign airway stenosis:A case report and literature review

Ventilation strategies in patients with severe tracheal stenosis should be tailored to the patient according to the underlying cause and narrowing location.This report is on a case of a 68-year-old male patient,who was admitted for radiotherapy because of esophageal cancer and then developed severe stenosis at the cervical trachea.We used venovenous extracorporeal membrane oxygenation to secure the airway and ensure adequate oxygenation.Then urgent endoscopic balloon dilation of airway stenosis was successfully performed under general anesthesia.This case shows that venovenous extracorporeal membrane oxygenation can be used in endoscopic tracheal procedures for patients with severe benign stenosis in the upper-trachea who are unable to tolerate conventional ventilation.

Interventional bronchoscopic treatment of lung cancer

Interventional bronchoscopy has developed rapidly in the management of lung cancer. Besides ablativeresection of various modalities and balloon dilation/stent placement, which have been widely used in themanagement of malignant central airway obstruction, bronchoscopic brachytherapy and transbronchoscopic local injection of drugs are also developing. For early-stage peripheral lung cancer,transbronchoscopic ablation and the assisted localization of preoperative peripheral lung nodules bybronchoscopy are the new techniques. In addition, interventional bronchoscopy can manage complications related to lung cancer. Overall, interventional bronchoscopy has been an indispensable componentin the treatment of lung cancer and has vast space for development. The review summarizes the recentupdates.

Emerging vaccine nanotechnology: From defense against infection to sniping cancer

Looking retrospectively at the development of humanity, vaccination is an unprecedented medical landmark that saves lives by harnessing the human immune system. During the ongoing coronavirus disease 2019(COVID-19) pandemic, vaccination is still the most effective defense modality. The successful clinical application of the lipid nanoparticle-based Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines highlights promising future of nanotechnology in vaccine development. Compared with conventional vaccines, nanovaccines are supposed to have advantages in lymph node accumulation,antigen assembly, and antigen presentation;they also have, unique pathogen biomimicry properties because of well-organized combination of multiple immune factors. Beyond infectious diseases, vaccine nanotechnology also exhibits considerable potential for cancer treatment. The ultimate goal of cancer vaccines is to fully mobilize the potency of the immune system as a living therapeutic to recognize tumor antigens and eliminate tumor cells, and nanotechnologies have the requisite properties to realize this goal.In this review, we summarize the recent advances in vaccine nanotechnology from infectious disease prevention to cancer immunotherapy and highlight the different types of materials, mechanisms, administration methods, as well as future perspectives.

Water-driven photoluminescence reversibility in CsPbBr_(3)/PDMSPUa composite

Strong ionic character endows all-inorganic perovskite nanocrystals(NCs)with particular optoelectronic features when interacting with common polar solvents,such as water.However,the interaction mechanism of water affecting perovskite NCs is still lack of in-depth understanding.This study systematically explores the roles of water on CsPbBr_(3) nanocrystals(CNCs)by finely controlling the polymer coating degree of polydimethylsiloxane-based polyurea(PDMS-PUa).Through this coating,the effect of water on CNCs is found to experience from“fluorescence quenching”owing to irreversible crystal decomposition towards“forward fluorescence reversibility”by crystal destruction and recrystallization.With gradually enhanced coating,a phenomenon of“reverse fluorescence reversibility”is further observed in that water begins to passivate the CNCs’defect states.Finally,“fluorescent balance”can be achieved with a thick enough coating,where water can hardly contact with the CNCs.Inspired by the fluorescence reversible mechanism discovered,a new wearable intelligent sensing skin is demonstrated by using the CsPbBr_(3)/PDMS-PUa composite as raw material.Both water contact and humidity change can be perceived through photoluminescence(PL)intensity,corresponding to stimuli-responsive sensory nerves of human skin.It is expected that these findings will shed some new lights on perovskite NCs.

Development and validation of a risk-prediction model for immune-related adverse events in patients with non-small-cell lung cancer receiving PD-1/PD-L1 inhibitors

Lung cancer remains the leading cause of cancer deaths worldwide and is the most common cancer in males.Immune-checkpoint inhibitors(ICIs)that target programmed cell death protein-1(PD-1)or programmed cell death-ligand 1(PD-L1)have achieved impressive efficacy in the treatment of non-small-cell lung cancer(NSCLC)(Pardoll,2012;Champiat et al.,2016;Gao et al.,2022).Although ICIs are usually well tolerated,they are often accompanied by immune-related adverse events(irAEs)(Doroshow et al.,2019).Non-specific activation of the immune system produces off-target immune and inflammatory responses that can affect virtually any organ or system(O'Kane et al.,2017;Puzanov et al.,2017).

Epidermal growth factor receptor (EGFR) T790M mutation identified in plasma indicates failure sites and predicts clinical prognosis in non-small cell lung cancer progression during first-generation tyrosine kinase inhibitor therapy: a prospective observational study

Introduction:Plasma circulating tumor DNA(ctDNA)is an ideal approach to detecting the epidermal growth factor receptor(EGFR)T790M mutation,which is a major mechanism of resistance to first-generation EGFR-tyrosine kinase inhibitor(TKI)therapy.The present study aimed to explore the association of ctDNA-identified T790M mutation with disease failure sites and clinical prognosis in non-small cell lung cancer(NSCLC)patients.Methods:Patients who progressed on first-generation TKIs were categorized into failure site groups of chest limited(CF),brain limited(BF)and other(OF).Amplification refractory mutation system(ARMS)and droplet digital PCR(ddPCR)were used to identify the T790M mutation in ctDNA.Prognosis was analyzed with Kaplan-Meier methods.Results:Overall concordance between the two methods was 78.3%.According to both ARMS and ddPCR,patients in the OF group had a significantly higher rate of T790M mutation than did patients in the BF and CF groups(P<0.001),and a significantly higher T790M mutation rate was also observed in OF-group patients than in those in the CF and BF groups(P<0.001).AZD9291 was found to be an excellent treatment option and yielded the longest survival for T790M+patients in all groups who had progressed on EGFR-TKIs;for other treatments,the prognosis of T790M−patient subgroups varied.Conclusions:The present study demonstrates that T790M mutation in ctDNA is associated with failure sites for NSCLC patients after EGFR-TKI therapy and indicates that both failure site and T790M mutational status greatly influ-ence treatment selection and prognosis.