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aerosolized immunotherapeutic nanoparticle inhalation potentiates PD-L1 blockade for locally advanced lung cancer

Nano Research 2023年第4期16卷 5300-5310页

作者： Yang Liu William N.Crowe Lulu Wang W.Jeffrey Petty Amyn A.Habib Dawen Zhao Department of Biomedical Engineering Wake Forest University School of MedicineWinston-SalemNC 27157USA Department of Medicine Section on Hematology and OncologyWake Forest University School of MedicineWinston-SalemNC 27157USA Department of Neurology University of Texas Southwestern Medical Center and VA North Texas Medical CenterDallasTX 75390USA Department of Cancer Biology Wake Forest University School of MedicineWinston-SalemNC 27157USA

Despite therapeutic advancements,the prognosis of locally advanced non-small cell lung cancer(LANSCLC),which has invaded multiple lobes or the other lung and intrapulmonary lymph nodes,remains poor.The emergence of immunotherapy with immune checkpoint blockade(ICB)is transforming cancer treatment.However,only a fraction of lung cancer patients benefit from ICB.Significant clinical evidence suggests that the proinflammatory tumor microenvironment(TME)and programmed death-ligand 1(PD-L1)expression correlate positively with response to the PD-1/PD-L1 blockade.We report here a liposomal nanoparticle loaded with cyclic dinucleotide and aerosolized(AeroNP-CDN)for inhalation delivery to deep-seated lung tumors and target CDN to activate stimulators of interferon(IFN)genes in macrophages and dendritic cells(DCs).Using a mouse model that recapitulates the clinical LANSCLC,we show that AeroNP-CDN efficiently mitigates the immunosuppressive TME by reprogramming tumor-associated macrophage from the M2 to M1 phenotype,activating DCs for effective tumor antigen presentation and increasing tumor-infiltrating CD8+T cells for adaptive anticancer immunity.Intriguingly,activation of interferons by AeroNP-CDN also led to increased PD-L1 expression in lung tumors,which,however,set a stage for response to anti-PD-L1 treatment.Indeed,anti-PD-L1 antibody-mediated blockade of IFNs-induced immune inhibitory PD-1/PD-L1 signaling further prolonged the survival of the LANSCLC-bearing mice.Importantly,AeroNP-CDN alone or combination immunotherapy was safe without local or systemic immunotoxicity.In conclusion,this study demonstrates a potential nano-immunotherapy strategy for LANSCLC,and mechanistic insights into the evolution of adaptive immune resistance provide a rational combination immunotherapy to overcome it.

关键词： locally advanced non-small cell lung cancer(LANSCLC) nanoparticle immunotherapeutic aerosol inhalation stimulator of interferon genes programmed death 1/programmed death-ligand 1(PD-1/PD-L1)blockade

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Effects of Budesonide aerosol inhalation on Perioperative Lung Function in Patients Undergoing Cardiopulmonary Bypass Valve Replacement

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Medicinal Plant 2021年第5期12卷 97-99页

作者： Yongliang CHEN Jing XUE Daguang FANG Xiaoli YAN Xuefei TIAN Shulei XU Affiliated Hospital of Chengde Medical College Chengde 067000 China Chengde Medical College Chengde 067000 China

[Objectives]To explore the effects of budesonide aerosol inhalation on the perioperative pulmonary function of patients undergoing cardiopulmonary bypass valve replacement.[Methods]A total of 82 patients who underwent cardiopulmonary bypass valve replacement during January 2018 and May 2019 in the Affiliated Hospital of Chengde Medical College were selected.They were divided into blank control group(group A,n=28),aerosol control group(group B,n=27,normal saline aerosol treatment),and experimental group(group C,n=27,budesonide aerosol treatment)by the random number table method.Corresponding treatments were given 5 d before surgery and 5 d after surgery,and the treatment effects of the 3 groups were compared.[Results]The clinical symptom scores of the patients in the experimental group were significantly lower than those in the blank control group and the aerosol control group,and the total effective rate of treatment was significantly higher than that in the blank control group.[Conclusions]Perioperative application of budesonide aerosol inhalation can effectively improve the clinical symptoms,treatment effect,and clinical prognosis of patients undergoing cardiopulmonary bypass valve replacement.

关键词： Cardiopulmonary bypass Valve replacement aerosol inhalation Lung function

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喘乐宁联合爱喘乐雾化吸入治疗哮喘急性发作的效果分析及护理

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中国实用护理杂志 2010年第18期26卷 1-2页

作者：莫月清林向荣海南省人民医院急诊科

哮喘急性发作是指喘息、气促、咳嗽、胸闷等症状突然发生,或原有症状急剧加重,常有呼吸困难,以呼吸道流量降低为特征,常因接触变应原等刺激物或治疗不当等所致。其病情重,变化快,复杂,若处理不及时,短时间内进入危重状态,病死率高。我... 详细信息

哮喘急性发作是指喘息、气促、咳嗽、胸闷等症状突然发生,或原有症状急剧加重,常有呼吸困难,以呼吸道流量降低为特征,常因接触变应原等刺激物或治疗不当等所致。其病情重,变化快,复杂,若处理不及时,短时间内进入危重状态,病死率高。我院急诊科2007年1月至2009年1月采用喘乐宁联合爱喘乐雾化吸入治疗哮喘急性发作取得满意疗效,现报道如下。临床资料1.一般资料。本组共64例哮喘急性发作患者。将采用喘乐宁联合爱喘乐雾化吸入治疗的32例列为治疗组,其中男20例,女12例,年龄15～84岁;另随机抽取我科用舒喘灵口服平喘治疗哮喘急性发作的32例列为对照组,其中男17例,女15例,年龄16～78岁。所有病例既往均有哮喘发作史,符合

关键词：喘乐宁爱喘乐雾化吸入治疗哮喘急性发作效果分析护理 treatment aerosol inhalation 现报道如下接触变应原治疗不当症状危重状态急剧加重呼吸困难急诊科呼吸道刺激物病死率胸闷

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