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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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Prevention of ventilator-associated pneumonia with inhaled antibiotics

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World Journal of Emergency Medicine 2024年第3期15卷 165-168页

作者： Stephan Ehrmann Jie Li Intensive Care Medicine INSERM CIC 1415CRICS-TriggerSep FCRIN research networkUniversity Hospital Center in ToursTours 37044France respiratory Pathology Research Center National Institute of Health and Medical ResearchTours 37000France Department of Cardiopulmonary Sciences Division of Respiratory CareRush UniversityChicago 60612USA

The direct delivery of inhaled antibiotics to the respiratory tract has been a subject of enduring interest among medical practitioners and researchers due to the associated favorable *** interest has been particularly pronounced in the context of critically illpatients,wherehealthcare-associatedpulmonary infections represent a significant challenge,driving continued exploration of inhaled antibiotics for intubated *** high-level evidence has shown a very promising application in the field of ventilator-associated pneumonia (VAP) prevention.^([1]).

关键词： pneumonia ventilator respiratory

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Aryl hydrocarbon receptor:Linking environment to aging process in elderly patients with asthma

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Chinese Medical Journal 2024年第4期137卷 382-393页

作者： Tianrui Yang Rongjun Wan Wei Tu Sai Nithin Avvaru Peisong Gao division of Allergy and Clinical Immunology Department of MedicineJohns Hopkins University School of MedicineBaltimoreMD 21224USA Department of Geriatric Medicine The First People’s Hospital of Yunnan ProvinceKunmingYunnan 650032China Department of respiratory Medicine Xiangya HospitalCentral South UniversityChangshaHunan 410008China The State Key Laboratory of respiratory Disease for Allergy Shenzhen Key Laboratory of Allergy and ImmunologyShenzhen University School of MedicineShenzhenGuangdong 518055China

Aging is a significant risk factor for various diseases,including asthma,and it often leads to poorer clinical outcomes,particularly in elderly *** is recognized that age-related diseases are due to a time-dependent accumulation of cellular damage,resulting in a progressive decline in cellular and physiological functions and an increased susceptibility to chronic *** effects of aging affect not only the elderly but also those of younger ages,posing significant challenges to global ***,understanding the molecular mechanisms associated with aging in different diseases is *** intriguing factor is the aryl hydrocarbon receptor(AhR),which serves as a cytoplasmic receptor and ligand-activated transcription factor and has been linked to the aging ***,we review the literature on several major hallmarks of aging,including mitochondrial dysfunction,cellular senescence,autophagy,mitophagy,epigenetic alterations,and microbiome ***,we provide an overview of the impact of AhR on these hallmarks by mediating responses to environmental exposures,particularly in relation to the immune ***,we explore how aging hallmarks affect clinical characteristics,inflammatory features,exacerbations,and the treatment of *** is suggested that AhR signaling may potentially play a role in regulating asthma phenotypes in elderly populations as part of the aging process.

关键词： Aging Environment Reactive oxygen species Senescence Aryl hydrocarbon receptor Asthma

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Effect of early stepwise cardiopulmonary rehabilitation on function and quality of life in sepsis patients

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World Journal of Clinical Cases 2024年第4期12卷 729-736页

作者： Ming-Hui Zheng Wen-Jun Liu Juan Yang division of Cardiovascular First Ward Departments of Internal Medicine Liyuan HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430077Hubei ProvinceChina Department of respiratory Medicine PuRen Hospital Affiliated to Wuhan University of Science and Technology/Respiratory MedicineWuhan 430000Hubei ProvinceChina Department of Cardiology Huanggang Central HospitalHuanggang 438000Hubei ProvinceChina

BACKGROUND Sepsis,as a non-limiting host infection disease,can be accompanied by serious complications such as organ failure,which seriously threatens patient quality of *** To investigate the effect of early stepwise cardiopulmonary rehabilitation on cardiopulmonary function and quality of life in patients evacuated from mechanical ventilation with *** A total of 80 patients with sepsis who were hospitalized in our hospital from January 2021 to January 2022 were selected and divided into the observation group(n=40)and the control group(n=40)according to the random number table *** observation group was treated with early stepwise cardiopulmonary rehabilitation,and the control group was treated with a conventional treatment *** function indexes(central venous pressure,cardiac troponin I,B-type brain natriuretic peptide),lung function indicators(diaphragmatic mobility,changes in central venous oxygen saturation,oxygenation index),and quality of life(Quality of Life Evaluation Scale)were compared between the two groups after *** After treatment,the central venous pressure,diaphragm mobility,central venous oxygen saturation,oxygenation index,and Quality of Life Evaluation Scale scores in the observation group were higher than those in the control group,and the differences were statistically significant(P<0.05).The observation group was less than that of the control group for other parameters,and the differences were statistically significant(P<0.05).CONCLUSION Early stepwise cardiopulmonary rehabilitation can effectively enhance cardiac and pulmonary function and improve the quality of life in patients evacuated from mechanical ventilation with sepsis.

关键词： Stepwise cardiopulmonary rehabilitation Sepsis Evacuation of mechanical ventilation Cardiopulmonary function Quality of life

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Investigation of Nasal Mucosal IgA Responses in the Population Following COVID-19 Pandemic — China, September 2022–August 2023

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China CDC weekly 2024年第15期6卷 312-317,I0005页

作者： Boyang Li Lei Zhou Zhilong Chen Yanhan Wen Qian Wang Tao Huang Si Chen Wei Wu Mengxuan Wang Lina Sun Mifang Liang Shiwen Wang Ling Chen Qun Li National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijingChina National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases Chinese Center for Disease Control and PreventionBeijingChina Xiamen United Institute of respiratory Health Xiamen CityFujian ProvinceChina Guangzhou Laboratory Guangzhou CityGuangdong ProvinceChina State Key Laboratory of respiratory Disease Guangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou CityGuangdong ProvinceChina

What is already known about this topic?Mucosal IgA plays a crucial role in host immunity against respiratory *** studies suggest that it has the potential to mitigate the transmission of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron ***,a comprehensive population-based analysis examining mucosal IgA levels following the winter 2022 wave of the coronavirus disease 2019(COVID-19)pandemic is yet to be *** is added by this report?In our study involving 3,421 participants,we documented IgA responses subsequent to SARS-CoV-2 infection.A significant proportion of individuals sustained increased levels of IgA for over six *** levels were also observed in individuals with prior infections who underwent asymptomatic reinfections,indicating an active production of IgA ***,individuals with multiple vaccinations or severe symptoms tended to display elevated IgA levels after *** are the implications for public health practice?IgA in the nasal mucosa is crucial for defense against SARS-CoV-2 *** insights can enhance our knowledge of immune responses following infection and have provided certain reference values for disease prevention and control strategies.

关键词： prevention sustained immunity

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Elucidating regulatory processes of intense physical activity by multi-omics analysis

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Military Medical Research 2024年第4期 479-499页

作者： Ernesto S.Nakayasu Marina A.Gritsenko Young-Mo Kim Jennifer E.Kyle Kelly G.Stratton Carrie D.Nicora Nathalie Munoz Kathleen M. Navarro Daniel Claborne Yuqian Gao Karl K.Weitz Vanessa L. Paurus Kent J. Bloodsworth Kelsey A. Allen Lisa M. Bramer Fernando Montes Kathleen A. Clark Grant Tietje Justin Teeguarden Kristin E.Burnum-Johnson Biological Sciences division Pacific Northwest National Laboratory Environmental and Molecular Sciences division Pacific Northwest National Laboratory Centers for Disease Control and Prevention National Institute for Occupational Safety and Health Western States Division Computational Analytics division Pacific Northwest National Laboratory National Security Directorate Pacific Northwest National Laboratory Los Angeles County Fire Department Centers for Disease Control and Prevention National Institute for Occupational Safety and Health Respiratory Health Division Environmental and Molecular Toxicology Oregon State University

Background: Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations, such as firefighting, law enforcement, military, and sports. A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work ***: To study regulatory processes in intense physical activity simulating real-life conditions, we performed a multi-omics analysis of 3 biofluids(blood plasma, urine, and saliva) collected from 11 wildland firefighters before and after a 45 min, intense exercise regimen. Omics profiles post-vs. pre-exercise were compared by Student's t-test followed by pathway analysis and comparison between the different omics ***: Our multi-omics analysis identified and quantified 3835 proteins, 730 lipids and 182 metabolites combining the 3 different types of samples. The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands. The urine analysis showed a strong, concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites, reabsorption of nutrients and maintenance of fluid balance. In saliva, we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides. A systematic literature review identified 6 papers that support an altered susceptibility to respiratory ***: This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility, suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.

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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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Pulmonary alveolar proteinosis induced by X-linked agammaglobulinemia:A case report

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World Journal of Clinical Cases 2024年第9期12卷 1644-1648页

作者： Ting Zhang Ming Li Li Tan Xin Li Department of respiratory Medicine Kunming Children´s HospitalKunming 650228Yunnan ProvinceChina Department of Emergency Kunming Children's HospitalKunming 650228Yunnan ProvinceChina

BACKGROUND Pulmonary alveolar proteinosis(PAP)and X-linked agammaglobulinemia(XLA)are rare diseases in *** theories infer that immunodeficiency can induce PAP,but these reports are almost all review articles,and there is little clinical *** report the case of a child with both PAP and *** SUMMARY A 4-month-old boy sought medical treatment due to coughing and difficulty in breathing for>2 *** had been hospitalized multiple times due to respiratory infections and *** computed tomography and alveolar lavage fluid showed typical PAP-related *** testing confirmed that the boy also had *** total lung alveolar lavage and intravenous immunoglobulin replacement therapy,the boy recovered and was *** the follow-up period,the number of respiratory infections was significantly reduced,and PAP did not *** XLA can induce PAP and improving immune function contributes to the prognosis of children with this type of PAP.

关键词： Pulmonary alveolar proteinosis X-linked agammaglobulinemia Children Immunodeficiency Alveolar lavage Case report

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Discussion of the Composition of Jaboticaba in Different Processes

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Food and Nutrition Sciences 2024年第1期15卷 101-112页

作者： Ching-Hu Tsai Yi-Chun Lin Chih-Ta Liu Yo-Ju Chen Department of Long-Term Care Kang Ning University Taipei Department of respiratory Therapy En Chu Kong Hospital New Taipei City Department of Thoracic Surgery division En Chu Kong Hospital New Taipei City

This study discusses the composition analysis and comparison of Jaboticaba under different processing conditions for fermented liquid, jam, fruit powder, and fruit vinegar. The differences and comparison of the contents of total polyphenols, anthocyanins, resveratrol, superoxide dismutase, small molecular peptides and ellagic acid in their products were analyzed. After analysis and comparison of results, the content of total polyphenols was found to be the highest 44.82 ± 0.89 (mg/g) after being fermented directly from fresh fruit. The fresh fruit was dried at low temperature and ground into powder, with a maximum ellagic acid content of 12.799 ± 0.12 (mg/g). Fresh fruit was then made into jam, with the highest anthocyanin content of 57.39 ± 1.20 (mg/g). The fruit vinegar was produced by fermentation. Except for the content of small molecule peptides, which was similar to the content of fermentation broth and fruit powder, they were 20.63 ± 1.61, 23.84 ± 2.51 and 20.52 ± 1.21 (mg/g), and the rest of the composition was not as good as other samples. In the fresh fruit fermentation broth samples, resveratrol was produced and detected, and its content was 2.14 (mg/L), while it was not detected in other samples, and a superoxide dismutase (SOD)-like enzyme was detected in the fresh fruit fermentation broth. The highest activity was 49002.5 units/mL. Jaboticaba is prepared using a fermentation broth processing method with fresh fruit, and its total polyphenol content is higher than that of fruit powder, jam, and fruit vinegar. The commercial value of Jaboticaba and the establishment of composition content data are relatively improved, which is more promising for the future.

关键词： Jaboticaba Total Polyphenols Anthocyanins Resveratrol Small Molecule Peptides

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TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization

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Neuroscience Bulletin 2024年第1期40卷 17-34页

作者： Siying Qu Shengfeng Hu Huiting Xu Yongjian Wu Siqi Ming Xiaoxia Zhan Cheng Wang Xi Huang Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000China The State Key Laboratory of respiratory Disease Guangdong Provincial Key Laboratory of Allergy and Clinical ImmunologyThe Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510260China Department of Laboratory Medicine The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China division of Nephrology Department of Medicinethe Fifth Affliated Hospital of Sun Yat-sen UniversityZhuhai 519000China

Multiple sclerosis(MS)is a neuroinflammatory demyelinating disease,mediated by pathogenic T helper 17(Th17)***,the therapeutic effect is accompa-nied by the fluctuation of the proportion and function of Th17 cells,which prompted us to find the key regulator of Th17 differentiation in ***,we demonstrated that the triggering receptor expressed on myeloid cells 2(TREM-2),a modulator of pattern recognition receptors on innate immune cells,was highly expressed on pathogenic CD4-positive T lymphocyte(CD4^(+)T)cells in both patients with MS and experimental autoimmune encephalomyelitis(EAE)mouse *** knockout of Trem-2 in CD4^(+)T cells significantly alleviated the disease activity and reduced Th17 cell infiltration,activation,differentiation,and inflammatory cytokine production and secretion in EAE ***,with Trem-2 knockout in vivo experiments and in vitro inhibitor assays,the TREM-2/zeta-chain associated protein kinase 70(ZAP70)/signal transducer and activator of transcription 3(STAT3)signal axis was essential for Th17 activation and differentiation in EAE *** conclusion,TREM-2 is a key regulator of pathogenic Th17 in EAE mice,and this sheds new light on the potential of this therapeutic target for MS.

关键词： Multiple sclerosis Experimental autoimmune encephalomyelitis T helper 17 Triggering receptor expressed on myeloid cells 2

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