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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

Malignant pleural mesothelioma:The disdained member of thoracic oncology!

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World Journal of Experimental medicine 2024年第3期14卷 1-10页

作者： Divya Khosla Pawan Kumar Singh Bharath A Chhabria Vaishali Kataria Navneet Singh Rakesh Kapoor Department of Radiotherapy and Oncology Postgraduate Institute of Medical Education and ResearchChandigarh 160012India Department of pulmonary and critical care medicine Pandit Bhagwat Dayal Sharma Postgraduate Institute of Medical SciencesRohtak 124001India Department of pulmonary and critical care medicine Ramaiah Memorial HospitalBengaluru 560054India Department of pulmonary medicine Postgraduate Institute of Medical Education and ResearchChandigarh 160012India

Pleural mesothelioma is a very aggressive malignancy that arises from the pleural mesothelial cell lining and is linked strongly to prior asbestos *** ban on asbestos has helped to lower the incidence,but in developing countries like India,it is expected to *** has an extended latency period usually progressing over decades and presents with nonspecific *** has a median survival ranging between 10-22 *** diagnosis of malignant pleural mesothelioma is challenging and is done using computed tomography(CT),magnetic resonance imaging,or positron emission tomography-CT,with the last two predicting the resectability of the tumor better than CT alone.A pleural biopsy along with an array of immunohistochemical markers,such as p16,BRCA1 associated protein 1,and claudin-4,are required for a definitive *** genetic alterations have prognostic significance as *** current histological subtype identification is indispensable for decision making because of the new therapeutic avenues being *** combination of nivolumab and ipilimumab-based immunotherapy outperformed platinum and pemetrexed-based chemotherapy in terms of survival benefit and improved quality of life especially for non-epithelioid ***,the latter continues to be a robust treatment option for patients with the epithelioid *** is recommended for resectable cases with radiotherapy being indicated in neoadjuvant,adjuvant,and palliative settings along with systemic *** review article provides an overview of epidemiology,etiology,clinical manifestations,diagnostic approaches(including immunohistochemical and genetic markers),staging,and multidisciplinary approaches to current treatment for malignant pleural mesothelioma using surgery,chemotherapy,immunotherapy,and *** also sheds light on some recent studies(EMPHACIS,CALGB30901,Checkmate-743,etc.)that have led to significant developments in recent years with clinically mean

关键词： Chemotherapy Diagnosis Immunotherapy Malignant pleural mesothelioma Radiotherapy

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

Clinical evolution of antisynthetase syndrome-associated interstitial lung disease after COVID-19 in a man with Klinefelter syndrome:A case report

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World Journal of Clinical Cases 2024年第6期12卷 1144-1149页

作者： Xiang-Xiang Wu Jian Cui Shi-Yao Wang Tian-Tian Zhao Ya-Fei Yuan Long Yang Wei Zuo Wen-Jian Liao Department of Respiratory and critical care The First Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina China-Japan Friendship Jiangxi Hospital Nanchang 330006Jiangxi ProvinceChina Department of pulmonary and critical care medicine Center of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China

BACKGROUND This study presents a case of rapidly developing respiratory failure due to antisynthetase syndrome(AS)following coronavirus disease 2019(COVID-19)in a 33-year-old man diagnosed with Klinefelter syndrome(KS).CASE SUMMARY A 33-year-old man with a diagnosis of KS was admitted to the Department of pulmonary and critical care medicine of a tertiary hospital in China for fever and shortness of breath 2 wk after the onset of *** tomography of both lungs revealed diffuse multiple patchy heightened shadows in both lungs,accompanied by signs of partial bronchial *** next-generation sequencing of the bronchoalveolar lavage fluid suggested absence of pathogen.A biopsy specimen revealed organizing pneumonia with alveolar septal ***,extensive auto-antibody tests showed strong positivity for anti-SSA,anti-SSB,anti-Jo-1,and *** multidisciplinary discussions,the patient received a final diagnosis of AS,leading to rapidly progressing respiratory *** This study underscores the clinical progression of AS-associated interstitial lung disease subsequent to viral infections such as COVID-19 in patients diagnosed with KS.

关键词： Antisynthetase syndrome COVID-19 Klinefelter syndrome Interstitial lung disease Anti-Jo-1 Case report

Cardiac rehabilitation after cardiac surgery:An important underutilized treatment strategy

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World Journal of Cardiology 2024年第2期16卷 67-72页

作者： Christos Kourek stavros Dimopoulos Medical School of Athens National and Kapodistrian University of AthensAthens 15772Greece Cardiac Surgery Intensive care Unit Onassis Cardiac Surgery CenterAthens 17674Greece Clinical Ergospirometry Exercise&Rehabilitation Laboratory1st Critical Care Medicine DepartmentEvangelismos HospitalNational and Kapodistrian University of AthensAthens 10676Greece

Physical inactivity remains in high levels after cardiac surgery,reaching up to 50%.Patients present a significant loss of functional capacity,with prominent muscle weakness after cardiac surgery due to anesthesia,surgical incision,duration of cardiopulmonary bypass,and mechanical ventilation that affects their quality of *** complications,along with pulmonary complications after surgery,lead to extended intensive care unit(ICU)and hospital length of stay and significant mortality *** the well-known beneficial effects of cardiac rehabilitation,this treatment strategy still remains broadly underutilized in patients after cardiac *** and ICU early mobilization have been both showed to be valid methods to improve exercise tolerance and muscle *** mobilization should be adjusted to each patient’s functional capacity with progressive exercise training,from passive mobilization to more active range of motion and resistance *** exercise testing remains the gold standard for exercise capacity assessment and optimal prescription of aerobic exercise *** the last decade,recent advances in healthcare technology have changed cardiac rehabilitation perspectives,leading to the future of cardiac *** incorporating artificial intelligence,simulation,telemedicine and virtual cardiac rehabilitation,cardiac surgery patients may improve adherence and compliance,targeting to reduced hospital readmissions and decreased healthcare costs.

关键词： Cardiac rehabilitation Cardiac surgery Cardiopulmonary exercise testing Early mobilization Treatment Technology

Heterogeneous hybrid immunity against Omicron variant JN.1 at 11 months following breakthrough infection

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3170-3172页

作者： Xuan He Jingyou Yu Jiajing Jiang Jinyuan Liu Qi Qi Dan Liu Weimin Li Department of pulmonary and critical care medicine Precision Medicine Key Laboratory of Sichuan ProvinceState Key Laboratory of Respiratory Health and MultimorbidityWest China HospitalSichuan UniversityChengduSichuanChina Guangzhou National Laboratory Bio-lslandGuangzhouGuangdongChina Sichuan Center for Disease Control and Prevention ChengduSichuanChina

Dear Editor,Due to the ongoing evolution of SARS-CoV-2 and waning immunity following COVID-19 vaccination,breakthrough infections have become common *** exposure to viral antigens during different COVID-19 waves and vaccination contribute to the unique"hybrid immunity"-immune protection conferred by the combined vaccination and natural infection in individuals.

关键词： immunity vaccination infection

Reimagining critical care:Trends and shifts in 21st century medicine

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World Journal of critical care medicine 2024年第3期13卷 5-10页

作者： Sai Doppalapudi Bilal Khan Muhammad Adrish Division of pulmonary and critical care medicine Department of MedicineBronxCare Health System/Icahn School of Medicine at Mount SinaiBronxNY 10467United States pulmonary William P.Clements High SchoolSugar LandTX 77479United States Section of pulmonary and critical care medicine Ben Taub Hospital/Baylor College of MedicineHoustonTX 77030United States

primarily driven by advancements in technology,changes in healthcare delivery,and a deeper understanding of disease *** in technology have revolutionized patient monitoring,diagnosis,and treatment in the critical care *** minimally invasive procedures to advances imaging techniques,clinicians now have access to a wide array of tools to assess and manage critically ill patients more *** this editorial we comment on the review article published by Padte S et al wherein they concisely describe the latest developments in critical care medicine.

关键词： Artificintelligenceial Ventilators Extracorporeal organ support Telemedicine critical care

HIF-1αpromotes virus replication and cytokine storm in H1N1 virus-induced severe pneumonia through cellular metabolic reprogramming

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Virologica Sinica 2024年第1期39卷 81-96页

作者： Xiaoxiao Meng Yong Zhu Wenyu Yang Jiaxiang Zhang Wei Jin Rui Tian Zhengfeng Yang Ruilan Wang Department of critical care medicine Shanghai General HospitalShanghai Jiaotong UniversitySchool of MedicineShanghai201620China Precision Research Center for Refractory Diseases Shanghai General HospitalShanghai Jiaotong UniversitySchool of MedicineShanghai201620China

The mortality of patients with severe pneumonia caused by H1N1 infection is closely related to viral replication and cytokine ***,the specific mechanisms triggering virus replication and cytokine storm are still not fully ***,we identified hypoxia inducible factor-1α(HIF-1α)as one of the major host molecules that facilitates H1N1 virus replication followed by cytokine storm in alveolar epithelial ***,HIF-1αprotein expression is upregulated after H1N1 *** of HIF-1αattenuates pulmonary injury,viral replication and cytokine storm in *** addition,viral replication and cytokine storm were inhibited after HIF-1αknockdown in ***,the invasion of H1N1 virus into alveolar epithelial cells leads to a shift in glucose metabolism to glycolysis,with rapid production of ATP and *** of glycolysis significantly suppresses viral replication and inflammatory *** analysis revealed that H1N1-induced HIF-1αcan promote the expression of hexokinase 2(HK2),the key enzyme of glycolysis,and then not only provide energy for the rapid replication of H1N1 virus but also produce lactate,which reduces the accumulation of the MAVS/RIG-I complex and inhibits IFN-α/β*** conclusion,this study demonstrated that the upregulation of HIF-1αby H1N1 infection augments viral replication and cytokine storm by cellular metabolic reprogramming toward glycolysis mainly through upregulation of HK2,providing a theoretical basis for finding potential targets for the treatment of severe pneumonia caused by H1N1 infection.

关键词： H1N1 Severe pneumonia Virus replication Hypoxia inducible factor-1α Glycolysis

Liver Characterization of a Cohort of Alpha-1 Antitrypsin Deficiency Patients with and without Lung Disease

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Journal of Clinical and Translational Hepatology 2024年第10期12卷 845-856页

作者： Naweed Mohammad Regina Oshins Tongjun Gu Virginia Clark Jorge Lascano Naziheh Assarzadegan George Marek Mark Brantly Nazli Khodayari Division of pulmonary Critical Care and Sleep MedicineCollege of MedicineUniversity of FloridaGainesvilleFLUSA Interdisciplinary Center for Biotechnology Research Bioinformatics CoreUniversity of FloridaGainesvilleFLUSA Division of Gastroenterology Hepatology and NutritionCollege of MedicineUniversity of FloridaGainesvilleFLUSA Division of Pathology Immunologyand Laboratory MedicineCollege of MedicineUniversity of FloridaGainesvilleFLUSA Division of Gastroenterology and Hepatology Mayo ClinicRochesterMNUSA

Background and Aims:Alpha-1 antitrypsin deficiency(AATD)is a genetic disorder characterized by the misfolding and accumulation of the mutant variant of alpha-1 antitrypsin(AAT)within hepatocytes,which limits its access to the circulation and exposes the lungs to protease-mediated tissue *** results in progressive liver disease secondary to AAT polymerization and accumulation,and chronic obstructive pulmonary disease(COPD)due to deficient levels of AAT within the *** goal was to characterize the unique effects of COPD secondary to AATD on liver disease and gene ***:A subcohort of AATD individuals with COPD(n=33)and AATD individuals without COPD(n=14)were evaluated in this study from our previously reported cross-sectional *** used immunohistochemistry to assess the AATD liver phenotype,and RNA sequencing to explore liver *** observed a distinct transcriptomic profile in liver tissues from AATD individuals with COPD compared to those ***:A total of 339 genes were differentially *** pathways related to fibrosis,extracellular matrix remodeling,collagen deposition,hepatocellular damage,and inflammation were significantly upregulated in the livers of AATD individuals with *** analysis also revealed higher levels of fibrosis and hepatocellular damage in these ***:Our data supports a relationship between the development of COPD and liver disease in AATD and introduces genes and pathways that may play a role in AATD liver disease when COPD is *** believe addressing lung impairment and airway inflammation may be an approach to managing AATD-related liver disease.

关键词： Alpha-1 antitrypsin deficiency Chronic obstructive pulmonary disease Liver fibrosis Liver biopsy Liver histology Transcriptomics