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Chinese Chemical Letters 2021年第7期32卷 2309-2312页

作者： Liqiang Hao Hongyan Liu Zheng Zhang fuqiang wen Chengcai Xia Zengfen Pang Institute of Pharmacology Pharmacy CollegeShandong First Medical University&Shandong Academy of Medical SciencesTai'an 271016China Shandong Cancer Hospital and Institute Shandong First Medical University&Shandong Academy of Medical SciencesJi'nan 250117China

A novel route for tandem C-C/C-N formation,annulation and aromatization of hydrazones with 1,2-dichloroethane to synthesize 1 H-pyrazoles has been ***,the 1,2-dichloroethane serves as alkylation reagent in good to excellent *** methodology features mild reaction conditions and good functional group tolerance,providing a direct approach for the preparation of 1 Hpvrazoles.

关键词： Tandem Hydrazones 1,2-Dichloroethane 1H-Pyrazoles Annulation

Incorporation of a Toll-like receptor 2/6 agonist potentiates mRNA vaccines against cancer and infectious diseases

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3806-3817页

作者： Yangzhuo Gu Jingyun Yang Cai He Tingmei Zhao Ran Lu Jian Liu Xianming Mo fuqiang wen Huashan Shi Department of Biotherapy State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengduSichuan 610041China Division of Pulmonary Diseases State Key Laboratory of Biotherapy and Department of Respiratory and Critical Care MedicineWest China HospitalSichuan UniversityChengduSichuan 610041China Laboratory of Stem Cell Biology and Department of Pediatric Surgery State Key Laboratory of BiotherapyWest China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengduSichuan 610041China

mRNA vaccines have emerged rapidly in recent years as a prophylactic and therapeutic agent against various diseases including cancer and infectious *** of mRNA vaccines have been underway,among which boosting of efficacy is of great ***2Cys,a simple synthetic metabolizable lipoamino acid that signals through Toll-like receptor(TLR)2/6 pathway,eliciting both humoral and cellular adaptive immune responses,is an interesting candidate *** investigate the enhancement of the efficacies of mRNA vaccines by Pam2Cys,the adjuvant was incorporated into mRNA-lipid nanoparticles(LNPs)to achieve co-delivery with *** with the resulting mRNA-LNPs(Pam2Cys)shaped up the immune milieu in the draining lymph nodes(dLNs)through the induction of IL-12 and IL-17,among other *** presentation was carried out mainly by migratory and dLNresident conventional type 2 DCs(cDC2s)and significantly more potent antitumor responses were triggered in both prophylactic and therapeutic tumor models in a CD4^(+) and CD8^(+) T cell-dependent *** memory antitumor immunity was also ***,the vaccine also stimulated much more robust humoral and cellular immunity in a surrogate COVID-19 prophylactic *** but not the least,the new vaccines exhibited good preliminary safety profiles in murine *** facts warrant future development of Pam2Cys-incorporated mRNA vaccines or relevant mRNA therapeutics for clinical application.

关键词： vaccines immunity diseases

DNA of neutrophil extracellular traps promote NF-κBdependent autoimmunity via cGAS/TLR9 in chronic obstructive pulmonary disease

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3040-3055页

作者： Jun Chen Tao Wang Xiaoou Li Lijuan Gao Ke Wang Mengxin Cheng Zijian Zeng Lei Chen Yongchun Shen fuqiang wen Department of Respiratory and Critical Care Medicine West China HospitalWest China School of Medicineand Division of Pulmonary DiseasesState Key Laboratory of BiotherapySichuan UniversityChengduSichuan 610041China

Chronic obstructive pulmonary disease(COPD)is characterised by persistent airway inflammation even after cigarette smoking *** extracellular traps(NETs)have been implicated in COPD severity and acute airway inflammation induced by short-term cigarette smoke(CS).However,whether and how NETs contribute to sustained airway inflammation in COPD remain *** study aimed to elucidate the immunoregulatory mechanism of NETs in COPD,employing human neutrophils,airway epithelial cells(AECs),dendritic cells(DCs),and a long-term CS-induced COPD mouse model,alongside cyclic guanosine monophosphate-adenosine monophosphate synthase and toll-like receptor 9 knockout mice(cGAS-^(−/−)TLR9^(−/−));Additionally,bronchoalveolar lavage fluid(BALF)of COPD patients was *** from COPD patients released greater cigarette smoke extract(CSE)-induced NETs(CSE-NETs)due to mitochondrial respiratory chain *** CSE-NETs,containing oxidatively-damaged DNA(NETs-DNA),promoted AECs proliferation,nuclear factor kappa B(NF-κB)activation,NF-κB-dependent cytokines and type-I interferons production,and DC maturation,which were ameliorated/reversed by silencing/inhibition of cGAS/*** the COPD mouse model,blocking NETs-DNA-sensing via cGAS^(−/−)and TLR9^(−/−)mice,inhibiting NETosis using mitoTEMPO,and degrading NETs-DNA with DNase-I,respectively,reduced NETs infiltrations,airway inflammation,NF-κB activation and NF-κBdependent cytokines,but not type-I interferons due to IFN-α/βreceptor *** NETs components(myeloperoxidase and neutrophil elastase activity)in BALF of COPD smokers correlated with disease severity and NF-κB-dependent cytokine levels,but not type-I interferon *** conclusion,NETs-DNA promotes NF-κB-dependent autoimmunity via cGAS/TLR9 in long-term CS exposure-induced ***,targeting NETs-DNA and cGAS/TLR9 emerges as a potential strategy to alleviate persistent airway inflammation in COPD.

关键词： inflammation TLR9 neutrophil

从指南变迁看吸入性糖皮质激素在慢性阻塞性肺疾病稳定期治疗中的地位

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中华医学杂志 2021年第6期101卷 383-387页

作者：文富强四川大学华西医院呼吸科成都610041

在慢性阻塞性肺疾病(慢阻肺)稳定期治疗中,国际指南对吸入性糖皮质激素(ICS)治疗的推荐依据临床证据积累而不断更新,经过从“争议”到“肯定”的认识深入过程,直到最新指南中的ICS推荐策略:考虑到临床特征将患者分为呼吸困难和急性加重... 详细信息

在慢性阻塞性肺疾病(慢阻肺)稳定期治疗中,国际指南对吸入性糖皮质激素(ICS)治疗的推荐依据临床证据积累而不断更新,经过从“争议”到“肯定”的认识深入过程,直到最新指南中的ICS推荐策略:考虑到临床特征将患者分为呼吸困难和急性加重两类来进行治疗方案调整,对前一年急性加重发生较频繁患者,结合其外周血嗜酸性粒细胞计数,推荐相应的含ICS的个体化给药。

关键词：肺疾病,阻塞性吸入性糖皮质激素

Hydrogen gas:a novel antioxidant for chronic obstructive pulmonary disease?

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Journal of Medical Colleges of PLA(China) 2011年第2期26卷 94-97页

作者： Shen Yongchun Yang Ting Wang Tao wen fuqiang Division of Pulmonary Diseases State Key Laboratory of Biotherapy of China and Department of Respiratory Medicine West China Hospital of Sichuan University Chengdu 610041 China

Oxidative stress therapy targeted on ox plays idativ critical role in the pathogenesis of chronic obstructive e stress is of great importance for COPD. However, since pu the lmonary disease （COPD）, so current used antioxidants are not satisfying, scientists have to find more effective antioxidants for COPD. Hydrogen, the most abundant chemical element in the universe, was recently discovered as a novel therapeutic medical gas, and has shown great antioxidant potential in a series of recent published researches for its feature of selectively reducing toxic reactive oxygen species. Based on these findings, we hypothesize that hydrogen gas therapy might be a novel, effective, safe, and economic treatment for COPD patients in one day

关键词： Hydrogen Chronic obstructive pulmonary disease

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中国慢性阻塞性肺疾病诊疗的现存问题与思考

中华医学杂志 2020年第2期100卷 81-84页

作者：文富强陈磊四川大学华西医院呼吸与危重症医学科生物治疗国家重点实验室呼吸病学研究室成都610041

慢性阻塞性肺疾病(简称慢阻肺)在我国呈高发态势,最新的数据显示40岁以上人群慢阻肺患病率高达13.7%,预计到2020年将成为疾病负担之首。然而,我国慢阻肺的防治体系和能力建设严重滞后,医生和患者对该病认知不足,肺功能测定尚未普及,治... 详细信息

慢性阻塞性肺疾病(简称慢阻肺)在我国呈高发态势,最新的数据显示40岁以上人群慢阻肺患病率高达13.7%,预计到2020年将成为疾病负担之首。然而,我国慢阻肺的防治体系和能力建设严重滞后,医生和患者对该病认知不足,肺功能测定尚未普及,治疗并不规范,疾病管理有待加强。本文阐述我国慢阻肺诊疗方面的现存问题并思考"破解之道"。

关键词：肺疾病,慢性阻塞性诊断治疗

Resolvin-D1 inhibits interleukin-8 and hydrogen peroxide production induced by cigarette smoke extract in 16HBE cells via attenuating NF-κB activation

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Chinese Medical Journal 2014年第3期127卷 511-517页

作者： Dong Jiajia Zhang Mingke Liao Zenglin Wu Wei Wang Tao Chen Lei Yang Ting Guo Lingli Xu Dan wen fuqiang Division of Pulmonary Diseases State Key Laboratory of Biotherapy of China and Department of Respiratory Medicine West China Hospital of Sichuan University Chengdu Sichuan 610041 China Department of Hospital Internal Medicine Northwest A&F University Yangling Shaanxi 712100 China

Background Cigarette smoke induced airway inflammation plays a role in pathogenesis of airway ***-D1 derived from omega-3 polyunsaturated fatty acids is an endogenous anti-inflammatory and proresolving lipid ***-D1 ameliorated inflammatory responses in lung injury,asthma,peritonitis and *** investigated whether resolvin-D1 suppressed the productions of chemokines and oxidative stress induced by cigarette smoke extract （CSE） in vitro and its possible *** We examined the proinfiammatory chemokine interleukin-8 and hydrogen peroxide （H2O2）productions induced by CSE in 16 human bronchial epithelial （16HBE）cells after resolvin-D1 treatment and their mechanisms.16HBE cells were treated with resolvin-D1 at up to 10 nmol/L,for 30 minutes before CSE up to 16％（v/v） *** of interlukin-8 proteins was assessed by enzyme linked immunosort assay （ELISA） and its mRNA level by *** evaluated extracellular H2O2 expression in the *** of NF-KB/p65 and degradation of Ⅰ-KB in 16HBE cells were determined by Westem blotting analysis and NF-KB DNA binding activity by electrophoretic mobility shift assay （EMSA）.Results 16HBE cells treated with 8％ CSE showed significantly higher interlukin-8 ***-D1 pretreatment inhibited CSE induced intedukin-8 production （mRNA and protein） in a dose and time dependent *** H2O2 level decreased after resolvin-D1 ***-D1 attenuated CSE triggered Ⅰ-KB degradation and NF-KB/p65 activation dose dependently and inhibited NF-KB DNA binding *** Resolvin-D1 inhibits CSE induced interlukin-8 and H2O2 production in 16HBE cells by modulating NF-KB activation and has therapeutic potential for pulmonary inflammation.

关键词： resolvins airway inflammation oxidative stress interleukin-8 NF-κB

甘草酸二铵抑制慢性哮喘模型小鼠气道平滑肌增生

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南方医科大学学报 2013年第10期33卷 1416-1420页

作者：肖敏朱涛汪涛文富强四川大学华西医院呼吸病学研究室/呼吸内科四川成都610041

目的评价甘草酸二铵(DG)对气道重构的影响及可能的作用途径。方法 30只雄性BALB/C小鼠随机平均分为3组,既空白组、卵清蛋白+甘草酸二铵组(OVA+DG组)和卵清蛋白组(OVA组)。在干预75 d后处死小鼠获得肺组织标本,并进行HE染色和Masson染色... 详细信息

目的评价甘草酸二铵(DG)对气道重构的影响及可能的作用途径。方法 30只雄性BALB/C小鼠随机平均分为3组,既空白组、卵清蛋白+甘草酸二铵组(OVA+DG组)和卵清蛋白组(OVA组)。在干预75 d后处死小鼠获得肺组织标本,并进行HE染色和Masson染色及气道上皮基底膜下胶原沉积测量。使用RT-PCR和Western blotting对α-SMA和PPARγ的mRNA和蛋白表达进行测定。结果 HE染色发现OVA致敏和激发75 d后小鼠肺组织出现明显的病理改变,且OVA组较OVA+DG组更加明显。Masson染色和基底膜下胶原沉积分析发现OVA干预后小鼠基底膜下胶原沉积明显增加,且OVA组较OVA+DG组增加更显著。RT-PCR和Western blotting分析发现OVA干预后小鼠肺组织α-SMA表达明显增加,而PPARγ表达则明显下降,但与OVA+DG组相比较OVA组α-SMA表达增加和PPARγ表达下降更明显。结论 DG可能通过上调PPARγ的表达减轻OVA诱导的慢性哮喘导致的气道肌成纤维细胞的增殖和基底膜下的胶原沉积。

关键词：甘草酸二铵支气管哮喘气道平滑肌过氧化物酶体增殖激活受体γ α-SMA

肺黏膜相关淋巴组织淋巴瘤临床特征及预后分析

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中国肿瘤临床 2012年第3期29卷 149-152页

作者：李琳李晓欧文富强四川大学华西医院呼吸内科成都市610041

目的:分析肺黏膜相关淋巴组织(MALT)淋巴瘤的发病情况、临床病理特征、影像学表现和治疗、预后情况,探讨肺MALT淋巴瘤诊治中的相关问题。方法:回顾性分析14例肺MALT淋巴瘤患者的临床资料、治疗反应及预后因素。结果:14例肺MALT淋巴瘤患... 详细信息

目的:分析肺黏膜相关淋巴组织(MALT)淋巴瘤的发病情况、临床病理特征、影像学表现和治疗、预后情况,探讨肺MALT淋巴瘤诊治中的相关问题。方法:回顾性分析14例肺MALT淋巴瘤患者的临床资料、治疗反应及预后因素。结果:14例肺MALT淋巴瘤患者发病年龄为33～73岁,平均发病年龄为(52.36±13.08)岁,高峰年龄段40～60岁,占50%。男女比例为1:1。其中92.86%(13/14)患者为Ⅰ～Ⅱ期病变,50.00%(7/14)患B症状,64.29%(9/14)有结外受累。2例患者行手术治疗,4例行利妥昔单抗联合化疗,3例患者行未含利妥昔单抗的化疗,1例患者行利妥昔单抗单药化疗,1例患者间断使用干扰索2年,3例患者未接受任何化疗。随访15～75个月,平均随访时间(37.86±19.52)个月,总生存率100%,总无进展生存率57.14%(8/14)。预后分析提示结外侵犯数≥2枚、Ann Arhor分期≥Ⅲ、血乳酸脱氢酶(LDH)、IgM水平升高为不良预后因素。结论:肺MALT淋巴瘤是一种惰性淋巴瘤,进展缓慢,临床表现不典型,影像学改变缺乏特异性,诊断主要依靠病理活检。联合利妥昔单抗的免疫化疗效果好,可作为肺MALT淋巴瘤的标准治疗。

关键词：肺黏膜相关淋巴组织淋巴瘤临床特征预后

A case of miss-diagnosed pulmonary hamartomas with atypical radiology findings

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Chinese Medical Journal 2014年第1期127卷 113-113页

作者： Li Min Shen Yongchun wen fuqiang Department of Respiratory Medicine West China Hospital of Sichuan UniversityChengdu Sichuan 610041 China

To the editor： Pulmonary hamartoma is one of the most common benign tumour-like lesions of the lung with the characteristic radiograph appearance of a well-defined, solitary, smooth or slightly lobulated, peripheral pulmonary nodule with the presence of popcorn-like calcification. We report a case of multiple pulmonary hamartomas in a patient with unusual radiology perfomlance.

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