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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

PKHD1L1 blocks the malignant behavior of lung adenocarcinoma cells and restricts tumor growth by regulating CBX7

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BIOCELL 2024年第8期48卷 1209-1221页

作者： KEWEI CHENG LEI SHI CAIWEN SHI SHUANSHUAN XIE CHANGHUI WANG Department of pulmonary and critical care medicine The Affiliated Changzhou Second People’s Hospital of Nanjing Medical UniversityChangzhou213004China Department of pulmonary and critical care medicine Shanghai Tenth Clinical Medical College of Nanjing Medical UniversityShanghai200072China

Objective:To explore the role of polycystic kidney and hepatic disease 1-like 1(PKHD1L1)in lung adenocarcinoma(LUAD).Methods:Bioinformatics tools were utilized to examine the clinical profile of PKHD1L1 and chromobox protein homolog 7(CBX7)in *** Cell Counting Kit-8,colony formation,terminal deoxynucleotidyl transferase dUTP nick end labeling,Transwell,and wound-healing assays were carried out to assess the proliferative,apoptotic,invasive,and migrative capacities of the ***,the interrelation between PKHD1L1 and CBX7 was validated using a co-immunoprecipitation assay.A LUAD mice model was constructed by subcutaneous injection of A549 ***,immunohistochemical staining was performed to evaluate CBX7 and Ki67 ***:PKHD1L1 was downregulated in LUAD and predicted dismal outcomes in patients with ***1L1 upregulation repressed the proliferative,invasive,and migrative capabilities of A549 cells and exacerbated the apoptotic ***,PKHD1L1 may bind to CBX7 and positively modulate CBX7 ***7 deletion partly abrogated the effects of PKHD1L1 upregulation on the cellular biological activities in A549 ***,the PKHD1L1/CBX7 axis regulates the Hippo signaling pathway in A549 ***1L1 restricted tumor growth in LUAD xenograft mice;this was partly abolished by CBX7 ***:PKHD1L1 can hinder LUAD progression by regulating CBX7-mediated Hippo signaling.

关键词： Lung adenocarcinoma Polycystic kidney and hepatic disease 1-like 1 CBX7 Hippo signaling

Research progress of viral sepsis:etiology,pathophysiology,diagnosis,and treatment

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Emergency and critical care medicine 2024年第2期4卷 74-81页

作者： Jianping Li Yiqi Luo Hao Li Yunhong Yin Yi Zhang Department of pulmonary and critical care medicine Qilu Hospital of Shandong UniversityJinanShandongChina

Sepsis is a common systemic disease characterized by various physiological and pathological *** can result from infection by various pathogens,such as bacteria,viruses,and *** rate of culture-negative sepsis is almost 42%,indicating that most patients may have nonbacterial *** the outbreak of coronavirus disease 2019,viral sepsis has attracted growing attention because many critically ill patients develop *** sepsis can be caused by viral infections and combined with,or secondary to,bacterial *** the common types of viral sepsis and the main characteristics of its pathogenesis will be helpful for effective diagnosis and treatment,thereby reducing *** identification of the causative agent of viral sepsis can help reduce the overuse of broad-spectrum *** this article,we reviewed the common viruses of sepsis,their potential pathophysiology,targets of diagnosis,and remedies for viral sepsis.

关键词： Acute gastrointestinal injury Acute kidney injury Acute lung injury Cytokine storm Diagnosis Treatment of viral sepsis Viral sepsis

Reflections on COPD comorbidities

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Chinese Medical Journal 2024年第12期137卷 1504-1506页

作者： Zhenming He Yue Wang Lin Shan Yan Mou Yunhuan Liu Guanhua Ma Yanxu Wu Huili Zhu Jeffrey L.Curtis Shilei Cui Haiyan Ge Department of pulmonary and critical care medicine Huadong HospitalFudan UniversityShanghai 200040China Medical Service VA Ann Arbor Healthcare SystemAnn ArborMI 48105USA pulmonary&critical care medicine division Department of Internal MedicineUniversity of MichiganAnn ArborMI 48109USA Graduate Program in Immunology University of MichiganAnn ArborMI 48109USA

To the Editor:Chronic obstructive pulmonary disease(COPD)is a common disease among the elderly,affecting over one-third of the elderly population *** progressive decline in lung function characteristic of COPD significantly impacts the quality of life and employability of affected individuals,resulting in a substantial direct and indirect socioeconomic *** frequently has comorbidities involving other organ *** all elderly COPD patients present with one or more comorbid conditions,collectively exacerbating health and economic *** viral and bacterial infections remain the most common triggers for COPD exacerbations(ECOPD).

关键词： morbid lung collective

Bronchoalveolar lavage fluid metagenomic next-generation sequencing assay for identifying pathogens in lung cancer patients

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BIOCELL 2024年第4期48卷 623-637页

作者： JIYU WANG HUIXIA LI DEYUAN ZHOU LIHONG BAI KEJING TANG division of pulmonary and critical care medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Institute of pulmonary Diseases Sun Yat-sen UniversityGuangzhouChina Department of Pharmacy The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

Background:For patients with lung cancer,timely identiﬁcation of new lung lesions as infectious or non-infectious,and accurate identiﬁcation of pathogens is very important in improving OS of *** a new auxiliary examination,metagenomic next-generation sequencing(mNGS)is believed to be more accurate in diagnosing infectious diseases in patients without underlying diseases,compared with conventional microbial tests(CMTs).We designed this study toﬁnd out whether mNGS has better performance in distinguishing infectious and non-infectious diseases in lung cancer patients using bronchoalveolar lavageﬂuid(BALF).Materials and Methods:This study was a real-world retrospective review based on electronic medical records of lung cancer patients with bronchoalveolar lavage(BAL)and BALF commercial mNGS testing as part of clinical care from 1 April 2019 through 30 April 2022 at The First Afﬁliated Hospital of Sun Yat-sen University.164 patients were included in this *** were categorized into the pulmonary non-infectious disease(PNID)group(n=64)and the pulmonary infectious disease(PID)group(n=100)groups based onﬁnal ***:BALF mNGS increased the sensitivity rate by 60%compared to CMTs(81%vs.21%,p0.1).Among the patients with PID,bacteria were the most common cause of *** infections occurred in 32%of patients,and Pneumocystis Yersini was most *** with Tyrosine kinase inhibitors(TKIs)therapy possess longer overall survival(OS)than other anti-cancer agents,the difference between TKIs and immuno-checkpoint inhibitors(ICIs)was insigniﬁcant(median OS TKIs *** ***-angiogenic *** ***=76 vs.84 vs.61 vs.58 vs.60).Conclusions:our study indicates that BALF mNGS can add value by improving overall sensitivity in lung cancer patients with potential pulmonary infection,and was outstanding in identifying Pneumocystis *** could be able

关键词： Lung cancer Bronchoalveolar lavage fluid Metagenomic next-generation sequencing Infectious diseases

lmpact of non-canonical ALK fusion on the efficacy of targeted therapy in non-small cell lung cancer

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Chinese Medical Journal 2024年第12期137卷 1468-1470页

作者： Hao Zeng Qi Wei Yuan Tang Yuanyuan Zhang Sihan Tan Qin Huang Xin Pu Yalun Li Panwen Tian Department of pulmonary and critical care medicine West China HospitalSichuan UniversityChengduSichuan 610041China Department of Pathology West China HospitalSichuan UniversityChengduSichuan 610041China Department of pulmonary and critical care medicine Lung Cancer CenterWest China HospitalSichuan UniversityChengduSichuan 610041China Department of pulmonary and critical care medicine State Key Laboratory of Respiratory Health and MultimorbidityPrecision Medicine Key Laboratory of Sichuan ProvinceWest China HospitalSichuan UniversityChengduSichuan 610041China

To the Editor:With the wide application of next-generation sequencing(NGS),a number of EML4-ALK fusion partners or coexisting(non)-EML4-ALK and non-EML4-ALK have been detected in non-small cell lung cancer(NSCLC).Although targeted therapies for patients with metastatic NSCLC and actionable mutations dramatically change how these patients are treated,studies have demonstrated differences in progression-free survival(PFS)among patients based on different ALK fusion partners.

关键词： targeted lung NSCLC

Whole-exome sequencing identified novel DNAH5 homozygous variants in two consanguineous families with primary ciliary dyskinesia

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中华医学杂志(英文版) 2024年第1期137卷 115-116页

作者： Yang Binyi Lei Cheng Xu Yingjie Yang Danhui Lu Chenyang Liu Ying Guo Ting Luo Hong Department of pulmonary and critical care medicine The Second Xiangya Hospital 3. Central South University 4. Changsha 5. Hunan 410011 6. China

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive inherited disease characterized by dysfunction of the motile cilia. DNAH5, the most frequently mutated gene in PCD, encodes a heavy chain of the ciliary outer dynein arms (ODAs). Herein, we report two patients with Kartagener syndrome (sinusitis, bronchiectasis, and situs inversus) in two consanguineous families carrying two novel homozygous DNAH5 variants [Supplementary Figures 1A and 1B, http://***/CM9/B598].

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Secular trends of asthma mortality in China and the United States from 1990 to 2019

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Chinese Medical Journal 2024年第3期137卷 273-282页

作者： Xiaochen Li Mingzhou Guo Yang Niu Min Xie Xiansheng Liu Department of pulmonary and critical care medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China NHC Key Laboratory of Respiratory Diseases WuhanHubei 430030China

Background:Asthma imposes a large healthcare burden in China and the United States(US).However,the trends of asthma mortality and the relative risk factors have not been comparatively analyzed between the *** aim of this study was to compare the mortality and risk factors between China and the ***:The deaths,and mortality rates of asthma in China and the US during 1990–2019 were obtained from the Global Burden of Disease Study *** age–period–cohort model was used to estimate these mortality rates based on a log-linear scale with additive age,period,and cohort *** population attributable fractions of risk factors for asthma were ***:In 1990–2019,the asthma mortality rate was higher in China than in the *** crude and age-standardized asthma mortality rates trended downward in both China and the US from 1990 to *** decline in mortality was more obvious in *** gap between the two countries was narrowing.A sex difference in asthma mortality was observed with higher mortality in males in China and females in the *** age effects showed that mortality increased with age in adults older than 20 years,particularly in the *** trends were generally observed in the period and cohort rate ratios in both countries,with China experiencing a more obvious *** and high body mass index(BMI)were the leading risk factors for asthma mortality in China and the US,*** attributable to occupational asthmagens and smoking decreased the most in China and the US,***:In 1990–2019,the asthma mortality rate was higher in China than in the US;however,the mortality gap has *** increased with age in *** improvements in asthma death risk with period and birth cohort were more obvious in China than in the ***,high BMI,and aging are major health problems associated with asthma *** role of occupational asthmagens in asthma mortality under

关键词： Asthma Mortality Global disease burden China the United States Age–period–cohort model

Omics methods predict the prognosis and treatment efficacy of chronic obstructive pulmonary disease

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Chinese Medical Journal 2024年第3期137卷 356-358页

作者： Yan Huang Juanjuan Xu Guanzhou Ma Sufei Wang Xiaojuan Yan Yang Jin Jiafu He Department of Respiratory and critical care medicine Xiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and ScienceXiangyangHubei 441000China Department of Respiratory and critical care medicine NHC Key Laboratory of Pulmonary DiseasesUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China

To the Editor:Chronic obstructive pulmonary disease(COPD)is a condition that severely endangers human *** 2018,Wang et al^([1])reported that there are approximately 100 million patients with COPD in China,with a 13.7%prevalence in people aged over 40 *** disease severity,frequency of exacerbations,and comorbidities,which are commonly(30–57%)observed in patients with COPD,are the three most crucial elements affecting the economic and societal consequences of COPD.^([2])Hospitalizations for exacerbations are the main contributors to health care *** reduce the clinical and financial burden of COPD,interventions are needed to slow the disease course,avoid exacerbations,and reduce comorbidities,such as approaches for improving the prognosis and treatment efficacy in COPD.

关键词： obstructive prognosis treatment