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Characteristics of Proinflammatory Cytokines and Chemokines in Airways of Asthmatics： Relationships with Disease Severity and Infiltration of Inflammatory Cells

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Chinese Medical Journal 2017年第17期130卷 2033-2040页

作者： Ting Yang Yan Li Zhe Lyu Kewu Huang Chris J Corrigan Sun Ying Wei Wang Chen Wang National Clinical Research Center for respiratory Diseases Center for Respiratory Diseases China-Japan Friendship Hospital Capital Medical University Beijing 100029 China Department of Immunology School of Basic Medical Sciences Capital Medical University Beijing 100069 China Department of respiratory and Critical Care Medicine Beijing Chao-Yang Hospital Capital Medical University and Beijing Institute of Respiratory Medicine Beijing 100020 China MRC and Asthma UK Centre in Allergic Mechanisms of Asthma Division of Asthma Allergy and Lung Biology King&#39 s College London London UK

Background：Increased proinflammatory cytokines and chemokines might contribute to infiltration of inflammatory cells and remodeling in airways of *** these molecules may be associated with asthma,there is lack of systemic evidence showing which and how important these events are in the *** aimed to analyze the concentrations of these molecules in the airways and relationships with disease severity and with airway infiltration of inflammatory cells in a large cohort of asthmatics （n =70,including 37 mild and 33 moderate/severe asthmatics） compared with controls （n =30）.Methods：Meso scale discovery system and commercial ELISA kits were used to measure the concentrations ofproinflammatory cytokines interleukin （IL）-1 β;tumor necrosis factor-alpha （TNF-α）;IL-6;and IL-17 and CC and CXC chemokines CCL2,CCL4,CCL 11,CCL 13,CCL17,CCL22,and CCL26 and CXCL8,CXCL9,CXCL10,and CXCL1 1 in bronchoalveolar lavage fluid of asthmatics and ***：The concentrations ofIL-1,TNF-α,IL-6,CXCL8 and CXCL 10,and CCL4,CCL 11,CCL 17,and CCL22 were significantly elevated in asthmatics compared with controls （P 〈 0.05）.The concentrations of TNF-α and CXCL8,but not others,were negatively correlated with severity of disease （lung function forced expiratory volume in 1 s）（TNF-α ***：r =-0.359,P =0.002 ***/severe：r =-0.541,P =0.001;CXCL8 ***：r =-0.327,P =0.006 ***/severe：r =-0.625,P =0.0001,respectively）.In addition,concentrations of these two molecules were also correlated with the absolute numbers of infiltrating eosinophils and neutrophils in asthmatic ***：Increased concentrations of TNF-α and CXCL8 are associated with pathogenesis of *** these molecules might provide an alternative therapeutic for this disease.

关键词： Asthma Bronchoalveolar Lavage Chemokine Proinflammatory Cytokines

Cytokine storm and translating IL-6 biology into effective treatments for CoVID-19

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Frontiers of Medicine 2023年第6期17卷 1080-1095页

作者： Tiantian Li Dongsheng Wang Haiming Wei Xiaoling Xu Department of Geriatric Medicine The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China respiratory and Critical Care Medicine The First Afiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease School of Life Science and Medical CenterUniversity of Science and Technology of ChinaHefei 230001China Hefei National Laboratory for Physical Sciences at Microscale University of Science and Technology of ChinaHefei 230001China

As of May 3,2023,the Coronavirus disease 2019(COVID-19)pandemic has resulted in more than 760 million confirmed cases and over 6.9 million *** patients have developed pneumonia,which can deteriorate into acute respiratory distress *** primary etiology may be attributed to cytokine storm,which is triggered by the excessive release of proinflammatory cytokines and subsequently leads to immune *** that high levels of interleukin-6(IL-6)have been detected in several highly pathogenic coronavirus-infected diseases,such as severe acute respiratory syndrome in 2002,the Middle East respiratory syndrome in 2012,and COVID-19,the IL-6 pathway has emerged as a key in the pathogenesis of this hyperinflammatory ***,we review the history of cytokine storm and the process of targeting IL-6 signaling to elucidate the pivotal role played by tocilizumab in combating COVID-19.

关键词： SARS-CoV-2 COVID-19 cytokine storm interleukin-6 tocilizumab

Promoting Health Wellness——The Essentials of Chinese Medicine

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Chinese Journal of Integrative Medicine 2015年第8期21卷 563-568页

作者：边灵杰刘志国李光熙 Department of respiratory Guang'anmen HospitalChina Academy of Chinese Medical Sciences Mayo Epidemiology and Translational Research in Intensive Care Division of Pulmonary and Critical Care Medicine

Chinese medicine is a healing medicine which respect the power of human body itself. The essentials of Chinese medicine is promoting health wellness instead of disease management. Modern medicine just realized the limits of its theory. P4 medicine （personalized, predictive, preventive, and participatory/precision） similar to Chinese medicine theory is beginning to representing the pioneer in the Western world. In this review, we summarized different domains of Chinese medicine. Based on the basic of promoting health wellness, we compared the fundamental theory of Chinese medicine to the new merging P4 medicine idea of Western medicine. We also discussed the potential for using modern computational medicine technique to integrate Chinese medicine theory and Western medicine theory.

关键词： Chinese medicine health wellness P4 medicine

Uncommon late presentation of platypnea-orthodeoxia syndrome

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Journal of Geriatric Cardiology 2015年第6期12卷 687-689页

作者： Laura Toffetti Marco Centola Laura Massironi Cristina Pipia Fabiano Di Marco Alessandro Colombo Emanuela Piccaluga division of Cardiology Ospedale San Paolo University of Milan Italy Divison of Internal Medicine Ospedale San Paolo Italy division of respiratory Medicine University of Milan Italy division of Cardiology Azienda Ospedaliera 'Luigi Sacco ' Milan Italy

A 79-year-old man presented with progressive dyspnea,gradually worsening over a period of several weeks. His past medical history included hypertension, chronic hepatitis C without cirrhosis, ischemic stroke occurred at the age of 68 and chronic obstructive pulmonary disease (COPD) caused by long-term cigarette smoking. The patient was alert and oriented and not in acute distress. The physical examination of the chest revealed decreased breath sounds at the bases of the lungs, without crackles or wheezes. Heart sounds were regular without murmurs. The respiration rate was normal. Extremities had no cyanosis, clubbing or oedema. The 12-lead electrocardiogram showed sinus rhythm with normal heart rate and non-specific T wave changes in D1, D2 and V5-V6. The chest radiograph revealed bilateral hilar prominence. Baseline peripheral capillary oxygen saturation (SpO_2) measured by standard pulse oximetry was 89%. A face mask was placed, delivering oxygen at 6 L/min. The subsequent arterial blood gas analysis provided information on the following parameters: pH 7.41, PaCO_2 34 mmHg, PaO_2 64 mmHg, SaO_2 91%. The full blood examination was normal, except for elevated C-reactive protein(50 mL/L, normal range < 10 mg/L) and D-dimer (782 ng/mL, normal range ≤ 270 ng/mL). A pulmonary embolism was suspected and a computed tomography pulmonary angiogram was then performed. No filling defects within the lumen of the pulmonary arterial branches were detected,neither were pleural effusion or pulmonary inflammatory infiltrates. A transthoracic echocardiogram (TTE) showed normal left ventricular ejection fraction, grade I diastolic dysfunction, normal heart valves, normal pulmonary pressure(systolic pulmonary artery pressure of 27 mmHg) and moderate enlargement of the ascending aorta (sinuses of Valsalva diameter of 49 mm). The patient was treated with a standard therapy for the acute exacerbation of COPD. Serum inflammatory markers progressively decreased. Nevertheless,episodes of dy

关键词：慢性阻塞性肺病综合征慢性阻塞性肺疾病晚期血症低氧呼吸困难丙型肝炎

Corticosteroid resistance in chronic obstructive pulmonary disease： new uses of theophylline

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Chinese Medical Journal 2013年第5期126卷 965-970页

作者： WU Jun-ping WU Qi SUN Xin SUN Hong-fen division of Pulmonary Medicine Tianjin Haihe Hospital TianjinInstitute of Respiratory Disease Tianjin 300350 China division of Pulmonary and Critical Care Medicine Duke University Medical Centre Durham NC27710 USA

Chronic obstructive pulmonary disease （COPD） is a major global health problem with a rising morbidity and mortality, which is expected to account for about 27% of tobacco related deaths and is anticipated to move from the fifth to the fourth leading cause of death worldwide from 2002 to 2030.1 COPD is characterized by the abnormal and chronic inflammation induced by cigarette smoking and other inflammatory insults in both small airway and lung parenchyma.2＇3 Glucocorticosteroids （also called glucocorticoids, corticosteroids or steroids） are the most effective anti-inflammatory drugs available for the treatment of many chronic inflammatory and immune diseases.

关键词： dimethylxanthine histone deacetylase neutrophil apoptosis chronic obstructive pulmonary disease corticosteroid resistance

Characteristics and Prognosis of Microscopic Polyangiitis Patients with Diffuse Alveolar Hemorrhage and Interstitial Lung Disease

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Chinese Medical Sciences Journal 2022年第4期37卷 293-302页

作者： Yu Gu Ting Zhang Min Peng Juhong Shi Department of respiratory and Critical Care Medicine Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100037China

Objective To evaluate the clinical characteristics and prognostic predictors of patients with diffuse alveolar hemorrhage(DAH)and/or interstitial lung disease(ILD)secondary to microscopic polyangiitis(MPA)in a Chinese general *** We retrospectively reviewed the medical records of MPA patients admitted to internal medicine departments between the year 2002 and *** patients were divided into the ILD,DAH,DAH combined with ILD(DAHILD),and no pulmonary involvement(NPI)groups according to pulmonary involvement *** clinical characteristics at diagnosis were *** risk factors associated with short-term death and long-term death were identified with Logistic regression and Cox *** Of 193 newly diagnosed MPA patients,181 patients were enrolled in the research,of which 19 had DAH alone,96 had ILD alone,18 had DAH and DAH concurrently,and 48 had *** median of serum creatine level in the DAH group was 449μmol/L,significantly higher than that in the ILD group(123μmol/L,Nemenyi=-35.215,P=0.045)and DAHILD group(359μmol/L,Nemenyi=-43.609,P=0.007).The median follow-up time was 67(range:1-199)*** in the ILD group were older than those in the DAH group(median:69 years vs.57 years,Nemenyi=43.853,P=0.005).The patients with both DAH and ILD had combined features of the two subtypes,and the highest mortality(72.2%at the end of follow-up).The elevated white blood cell count was a risk factor for short-term death(OR=1.103,95%CI:1.008-1.207,P=0.032 for one month;OR=1.103,95%CI:1.026-1.186,P=0.008 for one year).Old age(HR=1.044,95%CI:1.023-1.066,Pinfections(38/54)were the leading causes of death,especially for the patients with ***,49 patients suffered from pulmonary infections in the first year after *** MPA patients who prese

关键词： microscopic polyangiitis diffuse alveolar hemorrhage interstitial lung disease mortality risk factors

SARS-CoV-2 Nsp8 induces mitophagy by damaging mitochondria

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Virologica Sinica 2023年第4期38卷 520-530页

作者： Shan Zong Yan Wu Weiling Li Qiang You Qian Peng Chenghai Wang Pin Wan Tao Bai Yanling Ma Binlian Sun Jialu Qiao Wuhan Institute of Biomedical Sciences School of MedicineJianghan UniversityWuhan430056China State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China Hubei Key Laboratory of Wudang Local Chinese Medicine Research Hubei University of MedicineShiyan442000China division of Gastroenterology Tongji Medical CollegeHua Zhong University of Science and TechnologyWuhan430030China Department of respiratory and Critical Care Medicine Hubei Province Clinical Research Center for Major Respiratory DiseasesNHC Key Laboratory of Pulmonary DiseasesUnion HospitalTongji Medical CollegeHua Zhong University of Science and TechnologyWuhan430030China

Autophagy plays an important role in the interaction between viruses and host ***-CoV-2 infection can disrupt the autophagy process in target ***,the precise molecular mechanism is still *** this study,we discovered that the Nsp8 of SARS-CoV-2 could cause an increasing accumulation of autophagosomes by preventing the fusion of autophagosomes and *** further investigation,we found that Nsp8 was present on mitochondria and can damage mitochondria to initiate *** results of experiments with immunofluorescence revealed that Nsp8 induced incomplete ***,both domains of Nsp8 orchestrated their function during Nsp8-induced mitophagy,in which the N-terminal domain colocalized with mitochondria and the C-terminal domain induced auto/*** novel finding expands our understanding of the function of Nsp8 in promoting mitochondrial damage and inducing incomplete mitophagy,which helps us to understand the etiology of COVID-19 as well as open up new pathways for creating SARS-CoV-2 treatment methods.

关键词： SARS-CoV-2 Nsp8 Autophagy Mitophagy Mitochondrial damage

流感与COVID-19患者的免疫球蛋白G糖基化差异（英文）

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Engineering 2023年第7期 54-62页

作者： Marina Kljakovi?-Ga?pi? Batinjan Tea Petrovi? Frano Vu?kovi? Irzal Had?ibegovi? Barbara Radovani Ivana Jurin Lovorka Derek Eva Huljev Alemka Markoti? Ivica Luk?i? Irena Trbojevi?-Akma?i? Gordan Lauc Ivan Gudelj Rok ?ivljak University Hospital Centre Zagreb Genos Glycoscience Research Laboratory Department of Cardiology University Hospital Dubrava Faculty of Dental Medicine and Health Josip Juraj Strossmayer University Department of Biotechnology University of Rijeka Department for Laboratory Diagnostics University Hospital Dubrava Department for Acute respiratory infections University Hospital for Infectious Diseases “Dr. Fran Mihaljevi?” 8. Department for Urogenital Infections University Hospital for Infectious Diseases “Dr. Fran Mihaljevi?” 9. Department for Infectious Diseases School of Medicine Catholic University of Croatia Postdoctoral Study Faculty of Medicine University of Rijeka Department of Maxillofacial Surgery University of Zagreb School of Medicine Dubrava University Hospital Faculty of Pharmacy and Biochemistry University of Zagreb Department of Infectious Diseases University of Zagreb School of Medicine

The essential role of immunoglobulin G(IgG) in immune system regulation and combatting infectious diseases cannot be fully recognized without an understanding of the changes in its N-glycans attached to the asparagine 297 of the fragment crystallizable(Fc) domain that occur under such *** glycans impact the antibody stability, half-life, secretion, immunogenicity, and effector ***, in this study, we analyzed and compared the total IgG glycome—at the level of individual glycan structures and derived glycosylation traits(sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine(GlcNAc))—of 64 patients with influenza, 77 patients with coronavirus disease 2019(COVID-19), and 56 healthy controls. Our study revealed a significant decrease in IgG galactosylation, sialylation, and bisecting GlcNAc(where the latter shows the most significant decrease) in deceased COVID-19 patients, whereas IgG fucosylation was increased. On the other hand, IgG galactosylation remained stable in influenza patients and COVID-19 survivors. IgG glycosylation in influenza patients was more time-dependent: In the first seven days of the disease, sialylation increased and fucosylation and bisecting GlcNAc decreased; in the next 21 days, sialylation decreased and fucosylation increased(while bisecting GlcNAc remained stable). The similarity of IgG glycosylation changes in COVID-19 survivors and influenza patients may be the consequence of an adequate immune response to enveloped viruses, while the observed changes in deceased COVID-19 patients may indicate its deviation.

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Paraneoplastic syndromes associated with lung cancer

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World Journal of Clinical Oncology 2014年第3期5卷 197-223页

作者： Nobuhiro Kanaji Naoki Watanabe Nobuyuki Kita Shuji Bandoh Akira Tadokoro Tomoya Ishii Hiroaki Dobashi Takuya Matsunaga Department of Internal Medicine Division of Endocrinology and Metabolism Hematology Rheumatology and Respiratory MedicineFaculty of MedicineKagawa University

Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases. Paraneoplastic syndromes associated with lung cancer can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy(Trousseau's syndrome). The histological type of lung cancer is generally dependent on the associated syndrome, the two most common of which are humoral hypercalcemia of malignancy in squamous cell carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. The symptoms often precede the diagnosis of the associated lung cancer, especially when the symptoms are neurologic or dermatologic. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators, such as hormones and hormone-like peptides, cyto-kines, and antibodies. Treating the underlying cancer is generally the most effective therapy for paraneoplastic syndromes, and treatment soon after symptom onset appears to offer the best potential for symptom improvement. In this article, we review the diagnosis, potential mechanisms, and treatments of a wide variety of paraneoplastic syndromes associated with lung cancer.

关键词： Paraneoplastic syndrome Small cell lung cancer Non-small cell lung cancer Symptom Diagnosis Treatment Endocrine Neurologic Hematologic Trousseau’s syndrome