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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

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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

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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

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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

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Alectinib-Induced Immune Hemolytic Anemia in a Patient with Lung Adenocarcinoma: Case Report and Literature Review

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Case Reports in Clinical medicine 2024年第8期13卷 321-327页

作者： Chai Young Lee Yon Ju Ryu division of pulmonary and critical Care medicine College of Medicine Ewha Womans University Seoul Republic of Korea

Alectinib is a selective Anaplastic Lymphoma Kinase (ALK) tyrosine kinase inhibitor used as standard therapy for ALK-rearranged lung adenocarcinoma. Hemolytic anemia is considered a rare but significant adverse event of alectinib. Here, we report the case of a 78-year-old female with advanced ALK rearrangement-positive lung adenocarcinoma who developed grade 4 drug-induced hemolytic anemia after receiving alectinib as first-line therapy. We discontinued alectinib treatment and switched to brigatinib. As a result, anemia improved without recurrence of lung adenocarcinoma over one year.

关键词： Non-Small Cell Lung Cancer Alectinib Brigatinib Hemolytic Anemia Drug-Induced Hemolytic Anemia

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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

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Severe aspiration pneumonia in the elderly

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Journal of Intensive medicine 2024年第3期4卷 307-317页

作者： Sebastian Ocrospoma Marcos I.Restrepo division of pulmonary Diseases&critical Care medicine University of Texas Health San AntonioSan AntonioTXUSA Section of pulmonary&critical Care medicine South Texas Veterans Health Care SystemSan AntonioTXUSA

The global population is aging at an unprecedented rate,resulting in a growing and vulnerable elderly population in need of efficient comprehensive healthcare services that include long-term care and skilled nursing *** this context,severe aspiration pneumonia,a condition that carries substantial morbidity,mortality,and financial burden,especially among elderly patients requiring admission to the intensive care unit,has attracted greater *** pneumonia is defined as a pulmonary infection related to aspiration or dysphagia in *** episodes of coughing on food or liquid intake,a history of relevant underlying conditions,abnormalities on videofluoroscopy or water swallowing,and gravity-dependent shadow distribution on chest imaging are among the clues that suggest *** with aspiration pneumonia tend to be elderly,frail,and suffering from more comorbidities than those without this ***,we comprehensively address the epidemiology,clinical characteristics,diagnosis,treatment,prevention,and prognosis of severe aspiration community-acquired pneumonia in the elderly to optimize care of this high-risk demographic,enhance outcomes,and minimize the healthcare costs associated with this *** preventive measures and effective management strategies is vital in ensuring the well-being of our aging population.

关键词： Aspiration pneumonia Aged critical illness Swallowing disorders Frailty Antibacterial agents

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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

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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

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A pilot study on Paxlovid therapy for hemodialysis patients with severe acute respiratory syndrome coronavirus 2 infections

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Frontiers of medicine 2024年第1期18卷 169-179页

作者： Xu Hao Zhiyao Bao Ranran Dai Xiaojing Wu Xin Li Muyin Zhang Hao Li Lili Xu Panpan Qiao Xuefei Liu Weiting Hu Ze Zhang Jie Fang Min Zhou Weiming Wang Jieming Qu Department of Nephrology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Department of pulmonary and critical Care medicine Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Institute of Respiratory Diseases Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Pharmacy Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China

We aimed to investigate the safety and efficacy of nirmatrelvir/ritonavir(Paxlovid)therapy for hemodialysis-dependent patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** hemodialysis patients infected with the Omicron variant of SARS-CoV-2 from April 3 to May 30,2022,were *** parameters and chest CT(computed tomography)imaging were *** treatment group included six patients who received 150 mg/100 mg of Paxlovid orally once daily for 5 days,whereas the control group included seven patients who received basic *** serious adverse reactions or safety events were *** control patients progressed to moderate disease,and none in the treatment group showed progression of chest CT findings(P<0.05).Paxlovid therapy tended toward early viral clearance and low viral load on Day ***,83.3%of the patients in the treatment group and 57.1%of the patients in the control group turned negative within 22 *** the Paxlovid treatment group,we found significantly increased levels of lymphocytes(P=0.03)and eosinophils(P=0.02)and decreased levels of D-dimer on Day 8 compared with those on Day *** therapy showed a potential therapeutic effect with good tolerance in hemodialysis *** optimal dose and effectiveness evaluation must be further investigated in a largeer cohort.

关键词： Paxlovid hemodialysis SARS-CoV-2 viral load chest CT scan

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