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Formulation of international standards of chinese medicine technology:clinical practice guide of chinese medicine for cough

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Journal of traditional chinese medicine 2024年第2期44卷 396-402页

作者： FANG Hanyu HONG Zheng LI Deming ZHANG Hongchun SHI Yihang LI Xiaojuan SUN Zengtao CHEN Wei ZHANG Chuchu ZU Yaqi Beijing University of chinese medicine Beijing 100029China department of traditional chinese medicine for pulmonary diseases Center of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029 national center for respiratory medicine Beijing 100029China department of traditional chinese medicine for pulmonary diseases Center of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Tianjin University of traditional chinese medicine Tianjin 301617China Second Teaching Hospital of Tianjin University of traditional chinese medicine Tianjin 300250China center for Evidence-based medicine Beijing University of Chinese MedicineBeijing 100029China Institute of Information on traditional chinese medicine China Academy of Chinese Medical SciencesBeijing 100700China

OBJECTIVE:To formulate the first clinical practice guideline for the treatment of cough using chinese medicine based on the grading of recommendations assessment,development,and evaluation(GRADE)systematic approach,including clinical evidence,evaluation of ancient literature,and expert ***:In the process of development,the regulation of"evidence-based,consensus-assisted,and empirical"was followed,and a comprehensive systematic approach of recommendation assessment,GRADE,evidence-based evaluation,expert consensus,and the Delphi method was *** the process of guideline development,evidence-based evaluation of ancient literature was included for the first time,and clinical evidence was fully integrated with clinical expert ***:The clinical practice guidelines for the treatment of cough with chinese herbal medicine were developed after a comprehensive consideration of evidence-based evaluation and expert *** guideline recommendations focused on recommending herbal compound decoctions and chinese patent medicines for cough in different *** on the GRADE systematic approach,we conducted an evidence-based evaluation of the recommended chinese patent medicines one by one;meanwhile,the expert consensus method was used to unify the recommendations of ***:Based on clinical evidence,ancient literature evaluation,and expert consensus,a clinical practice guideline for traditional chinese medicine(TCM)in the treatment of cough was developed,providing the first current clinical practice guideline for domestic and foreign TCM and Western medicine practitioners,especially respiratory professionals at home and abroad.

关键词： medicine chinese traditional clinical practice cough practice guide international standard

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Real-World Treatment Adherence to Smoking Cessation Medications and Association with Treatment Outcome—27 centers,China,2017–2022

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China CDC weekly 2024年第22期6卷 522-529,I0001-I0003页

作者： Anqi Cheng Zhao Liu Xinmei Zhou Zheng Su Dan Xiao Chen Wang the China national Tobacco Cessation Cohort Study(CNTCCS)Study Group department of Tobacco Control and Prevention of respiratory Disease Center of Respiratory MedicineChina-Japan Friendship Hospital/WHO Collaborating Center for Tobacco Cessation and Respiratory Diseases Prevention/National Center for Respiratory Medicine/National Clinical Research Center for Respiratory Diseases/Institute of Respiratory MedicineChinese Academy of Medical SciencesBeijingChina department of pulmonary and Critical Care medicine Center of Respiratory MedicineChina-Japan Friendship Hospital/WHO Collaborating Center for Tobacco Cessation and Respiratory Diseases Prevention/China National Center for Respiratory Medicine/China National Clinical Research Center for Respiratory DiseasesBeijingChina chinese Academy of Medical Sciences and Peking Union Medical College BeijingChina 不详

What is already known about this topic?Medication non-adherence significantly impedes smoking cessation *** effective smoking cessation medications are accessible in China,realworld adherence and its correlation with treatment outcomes remain largely *** is added by this report?From December 2017 to January 2022,1,120 participants were recruited from 27 centers in all seven geographical regions of *** revealed that only 38.2%of smokers adhered to the prescribed 12-week smoking cessation treatment and those with a higher education level were more likely to be *** addition,smokers with good adherence were more likely to successfully quit *** are the implications for public health practice?The data obtained could enhance our understanding of smoking cessation practices in *** adherence is a crucial strategy to enhance the effectiveness of smoking cessation treatments and management provided to smokers.

关键词： China. smoke likely

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Influenza and pneumococcal vaccination coverage and associated factors in patients hospitalized with acute exacerbations of COPD in China:Findings from real-world data

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chinese Medical Journal 2024年第10期137卷 1179-1189页

作者： Ruoxi He Xiaoxia Ren Ke Huang Jieping Lei Hongtao Niu Wei Li Fen Dong Baicun Li Ye Wang Ting Yang Chen Wang School of Population medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China department of respiratory medicine National Key Clinical SpecialtyBranch of National Clinical Research Center for Respiratory DiseaseXiangya HospitalCentral South UniversityChangshaHunan 410008China department of pulmonary and Critical Care medicine Center of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Institute of respiratory medicine Chinese Academy of Medical SciencesBeijing 100029China national center for respiratory medicine Beijing 100029China national clinical research center for respiratory diseases Beijing 100029China department of clinical research and Data Management Center of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China

Background:Influenza and pneumococcal vaccination are a priority in patients with chronic obstructive pulmonary disease(COPD).However,limited information is available on vaccination coverage among patients with acute exacerbations of COPD(AECOPD)in *** study aimed to determine the rates and associated factors of influenza and pneumococcal vaccination in patients hospitalized with ***:Baseline data from a national,multicenter,hospital-based study that included adult inpatients with AECOPD between 2017 and 2021 were *** outcomes of interest were the influenza vaccination in the past year and the pneumococcal vaccination in the past 5 *** ensure national representativeness,rates were weighted according to the distribution of hospital levels and types enrolled in this *** Poisson regression based on mixed-effects models were used to determine the associated *** independent variables included the region and hospital features where the participants were located,sociodemographic characteristics(age,sex,rural/urban residence,education,etc.),and clinical indicators(COPD disease history,lung function parameters,comorbidities,etc.).The treatment profiles of the vaccinated and unvaccinated participants were ***:Of 6949 eligible participants,the weighted rates of influenza/pneumococcal,influenza,and pneumococcal vaccination were 2.72%(95%confidence interval[CI]:2.34%-3.10%),2.09%(95%CI:1.76%-2.43%),and 1.25%(95%CI:0.99%-1.51%),*** multivariable models,age≥60 years(60-69 years,odds ratio[OR]:1.90,95%CI:1.11-3.25;≥80 years,OR:2.00,95%CI:1.06-3.78),geographical regions(Northern China relative to Eastern China,OR:5.09,95%CI:1.96-13.21),urban residence(OR:1.69,95%CI:1.07-2.66),a higher education level(junior high school,OR:1.77,95%CI:1.21-2.58;senior high school or above,OR:2.61,95%CI:1.69-4.03),former smoking(OR:1.79,95%CI:1.15-2.79),and regular inhaled medication treatment(OR:3.28,95%CI:2.29-4.70)were

关键词： Chronic obstructive pulmonary disease Influenza Pneumococcal Vaccine AECOPD

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评价散寒化湿颗粒与奈玛特韦-利托那韦对照治疗轻型/中型新型冠状病毒感染有效性和安全性的随机、开放、多中心临床研究

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Science Bulletin 2024年第12期69卷 1954-1963页

作者：邹晓辉常康范国辉郑欢伟神和正唐亮杨映映王业明赵林华吕红周昕沈小明陈利强仝小林曹彬 national center for respiratory medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesLaboratory of Clinical Microbiology and Infectious DiseasesDepartment of Pulmonary and Critical Care MedicineCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China national center for respiratory medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesDepartment of Clinical Research and Data Management Center of Respiratory MedicineCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Shijiazhuang Hospital of traditional chinese medicine Shijiazhuang 050051China Linyi traditional chinese medicine Hospital Linyi 276000China Wuxi traditional chinese medicine Hospital Wuxi 214071China national center for respiratory medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesDepartment of Traditional Chinese Medicine for Pulmonary DiseasesCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Institute of Metabolic diseases Guang’anmen Hospital of ChinaAcademy of Chinese Medical SciencesBeijing 100053China Taicang traditional chinese medicine Hospital Taicang 215400China The First Hospital of Qiqihar Qiqihar 161005China The Second Affiliated Hospital of Jiaxing University Jiaxing 314000China Huizhou First Hospital Huizhou 516003China national center for Integrated traditional chinese medicine and Western medicine China-Japan Friendship HospitalBeijing 100029China

Sanhan Huashi granules(SHG)demonstrated therapeutic effects against coronavirus disease 2019(COVID-19)in observational *** order to compare the effectiveness and safety of SHG and nirmatrelvir–ritonavir in treating adults with mild-to-moderate COVID-19,we conducted a randomized,activecontrolled,open-label,multi-center trial conducted between February and July in *** patients were randomized in a 1:1 ratio to the SHG group and the nirmatrelvir–ritonavir group.A total of 400participants were randomized,among which 200 participants ultimately received SHG and 198 received nirmatrelvir–*** primary outcome was time to sustained clinical recovery through day *** significantly shortened the median time to sustained clinical recovery compared to nirmatrelvir–ritonavir(6.0(95%CI,5.0 to 6.0)vs.8.0(95%CI,6.0 to 9.0)d;P=0.001),particularly for individual symptoms including fever,sore throat,cough and *** participants in either group died and incidence of severe COVID-19 showed no difference between two *** who received nirmatrelvir–ritonavir demonstrated a higher rate of virus clearance on day 5 compared to those received SHG(46.4%(95%CI,39.1 to 53.7)vs.65.6%(95%CI,58.3 to 72.4);Pclinical recovery in participants with mild-to-moderate COVID-19,despite a lower virus clearance rate observed after 5 d of treatment(chinese clinical Trial Registry Identifier:Chi CTR2300067872).

关键词： traditional chinese medicine COVID-19 Nirmatrelvir-Ritonavir Sustained clinical recovery

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Experts’Consensus on the Management of respiratory Disease Syndemic

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China CDC weekly 2024年第8期6卷 131-138页

作者： Weizhong Yang Zhongjie Li Ting Yang Yanming Li Zhengde Xie Luzhao Feng Zhibin Peng Jue Liu School of Population medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina State Key Laboratory of respiratory Health and Multimorbidity BeijingChina Key Laboratory of Pathogen Infection Prevention and Control Peking Union Medical CollegeMinistry of EducationBeijingChina national center for respiratory diseases State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesDepartment of Pulmonary and Critical Care MedicineCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijingChina department of pulmonary and Critical Care medicine National Center of GerontologyBeijing HospitalInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory of Pediatric respiratory Infection diseases Key Laboratory of Major Diseases in ChildrenMinistry of EducationNational Clinical Research Center for Respiratory DiseasesResearch Unit of Critical Infection in ChildrenChinese Academy of Medical Sciences2019RU016National Key Discipline of Pediatrics(Capital Medical University)Beijing Pediatric Research InstituteBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina chinese center for Disease Control and Prevention BeijingChina department of Epidemiology and Biostatistics School of PublicHealthKey Laboratory of Epidemiology of Major DiseasesMinistry of EducationPeking University Health Science Center-Weifang Joint Research Center for Maternal and Child HealthPeking UniversityBeijingChina

The global burden of respiratory diseases is a significant and increasing threat to individuals *** 2017,there were 544.9 million cases of chronic respiratory diseases,a 39.8%increase since 1990(1).These diseases were the third leading cause of global mortality in 2017,accounting for 7.0%of all deaths,an 18.0%increase compared to 1990.

关键词： diseases respiratory mortality

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A machine learning model for diagnosing acute pulmonary embolism and comparison with Wells score,revised Geneva score,and Years algorithm

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chinese Medical Journal 2024年第6期137卷 676-682页

作者： Linfeng Xi Han Kang Mei Deng Wenqing Xu Feiya Xu Qian Gao Wanmu Xie Rongguo Zhang Min Liu Zhenguo Zhai Chen Wang Capital Medical University Beijing 100069China national center for respiratory medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesDepartment of Pulmonary and Critical Care MedicineCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Institute of Advanced research Infervision Medical Technology Co.Ltd.Beijing 100025China department of Radiology China-Japan Friendship HospitalBeijing 100029China chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730China department of Radiology Peking University China-Japan Friendship School of Clinical MedicineBeijing 100191China

Background:Acute pulmonary embolism(APE)is a fatal cardiovascular disease,yet missed diagnosis and misdiagnosis often occur due to non-specific symptoms and signs.A simple,objective technique will help clinicians make a quick and precise *** population studies,machine learning(ML)plays a critical role in characterizing cardiovascular risks,predicting outcomes,and identifying *** work sought to develop an ML model for helping APE diagnosis and compare it against current clinical probability assessment ***:This is a single-center retrospective *** with suspected APE were continuously enrolled and randomly divided into two groups including training and testing sets.A total of 8 ML models,including random forest(RF),Naïve Bayes,decision tree,K-nearest neighbors,logistic regression,multi-layer perceptron,support vector machine,and gradient boosting decision tree were developed based on the training set to diagnose ***,the model with the best diagnostic performance was selected and evaluated against the current clinical assessment strategies,including the Wells score,revised Geneva score,and Years ***,the ML model was internally validated to assess the diagnostic performance using receiver operating characteristic(ROC)***:The ML models were constructed using eight clinical features,including D-dimer,cardiac troponin T(cTNT),arterial oxygen saturation,heart rate,chest pain,lower limb pain,hemoptysis,and chronic heart *** eight ML models,the RF model achieved the best performance with the highest area under the curve(AUC)(AUC=0.774).Compared to the current clinical assessment strategies,the RF model outperformed the Wells score(P=0.030)and was not inferior to any other clinical probability assessment *** AUC of the RF model for diagnosing APE onset in internal validation set was ***:Based on RF algorithm,a novel prediction model was finally constructed for AP

关键词： Acute pulmonary embolism Machine learning Wells score Revised Geneva score Years algorithm

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Efficacy and Safety of Bufei Jiedu Granules in Treating Multidrug-Resistant pulmonary Tuberculosis:A Multi-center,Double-Blinded and Randomized Controlled Trial

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chinese Journal of Integrative medicine 2024年第7期30卷 579-587页

作者： ZHANG Shao-yan QIU Lei ZHANG Shun-xian XIAO He-ping CHU Nai-hui ZHANG Xia ZHANG Hui-qiang ZHENG Pei-yong ZHANG Hui-yong LU Zhen-hui Institute of respiratory diseases Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai200032China clinical research center Shanghai University of Traditional Chinese MedicineShanghai200032China department of Tuberculosis Shanghai Pulmonary HospitalTongji UniversityShanghai200433China department of Tuberculosis Beijing Chest HospitalCapital Medical UniversityBeijing101100China department of Tuberculosis the Second Hospital of NanjingNanjing210003China department of Tuberculosis the First Hospital Affiliated to Xinxiang Medical CollegeXinxiangHenan Province453100China

Objective: To assess the efficacy and safety of Bufei Jiedu(BFJD) Granules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis(MDR-PTB). Methods: A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups(1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months(6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto). Meanwhile, patients in both groups also received BFJD Granules or placebo twice a day for a total of 18 months, respectively. The primary outcome was cure rate. The secondary outcomes included time to sputum-culture conversion, changes in lung cavities and quality of life(QoL) of patients. Adverse reactions were monitored during and after the trial. Results: A total of 216 cases completed the trial, 111 in the BFJD Granules group and 105 in the placebo group. BFJD Granules, as adjuvant treatment, increased the cure rate by 13.6% at the end of treatment, compared with the placebo(58.4% vs. 44.8%, P=0.02), and accelerated the median time to sputum-culture conversion(5 months vs. 11 months). The cavity closure rate of the BFJD Granules group(50.6%, 43/85) was higher than that of the placebo group(32.1%, 26/81;P=0.02) in patients who completed the treatment. At the end of the intensive treatment, according to the 36-item Short Form, the BFJD Granules significantly improved physical functioning, general health, and vitality of patients relative to the placebo group(all P<0.01). Overall, the death rates in the two groups were not significantly different;5.1%(8/156) in the BFJD Granules group and 2.6%(4/156) in the placebo group. Conclusions: Supplementing BFJD Granules with the long-course chemotherapy regimen significantly increased the cure rate and cavity closure rate, and rapidly improved QoL of pati

关键词： alternative medicine chinese herbal formula Bufei Jiedu Granules multidrug-resistant tuberculosis long-course chemotherapy regimen randomized controlled trial

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Pathogens of first-episode pulmonary infection in 141 children with chronic granulomatous disease

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chinese Medical Journal 2024年第4期137卷 502-504页

作者： Hui Liu Shunying Zhao Haiming Yang Jinrong Liu Hui Xu Xiaolei Tang Yuelin Shen Xiaoyan Zhang Xiaohui Wen Yuhong Zhao Ping Chu Huimin Li department of Second respiratory medicine National Clinical Research Center for Respiratory DiseasesBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijing 100045China Office of Scientific research Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijing 100045China

To the Editor:Chronic granulomatous disease(CGD)is an inherited primary immunodeficiency disease characterized by recurrent life-threatening bacterial or fungal infection and tissue granuloma formation.^([1])pulmonary infection is the most frequent manifestation,affecting nearly 80%of patients,[2]and remains the major cause of morbidity and mortality in patients with *** of the pathogenic microorganisms responsible for first-episode pulmonary infection provide information on the spectrum of infection in patients with CGD,help guide the empirical choice of antibiotics or antifungal therapy,and contribute to the early identification and management of *** is the commonest causative agent of pulmonary infection,but the distribution of other pathogens varies among countries.^([2–5])Few studies have investigated the etiology of pulmonary infection in CGD in a large cohort in China.

关键词： granuloma infection mortality

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Impact of corticosteroids on initiation and half-year durability of humoral response in COVID-19 survivors

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chinese Medical Journal pulmonary and Critical Care medicine 2024年第1期2卷 48-55页

作者： Yeming Wang Li Guo Guohui Fan Yang Han Qiao Zhang Lili Ren Hui Zhang Geng Wang Xueyang Zhang Tingxuan Huang Weiyang Wang Lan Chen Lixue Huang Xiaoying Gu Xinming Wang Jingchuan Zhong Ying Wang Hui Li Jiapei Yu Zhibo Liu Chaolin Huang Bin Cao Jianwei Wang national center for respiratory medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesChina-Japan Friendship HospitalBeijing 100029China national Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 102629China Key Laboratory of respiratory Disease Pathogenomics Chinese Academy of Medical SciencesBeijing 100029China School of Population medicine and Public Health Chinese Academy of Medical Sciences&Peking Union Medical CollegeState Key Laboratory of Respiratory Health and MultimorbidityKey Laboratory of Pathogen Infection Prevention and Control(Peking Union Medical College)Ministry of EducationBeijing 100730China national center for respiratory medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesDepartment of Clinical research and Data managementCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Jin Yin-tan Hospital WuhanHubei 430023China department of pulmonary and Critical Care medicine West China HospitalSichuan UniversityChengduSichuan 610041China department of Rheumatology and clinical Immunology Chinese Academy of Medical Sciences&Peking Union Medical CollegeNational Clinical Research Center for Dermatologic and Immunologic Diseases(NCRC-DID)Ministry of Science&TechnologyState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College Hospital(PUMCH)Key Laboratory of Rheumatology and Clinical ImmunologyMinistry of EducationBeijing 100730China department of pulmonary and Critical Care medicine Center of Respiratory MedicineChina-Japan Friendship HospsitalInstitute of Respiratory MedicineChinese

Background:The impact of corticosteroids on humoral responses in coronavirus disease 2019(COVID-19)sur-vivors during the acute phase and subsequent 6-month period remains *** study aimed to determine how the use of corticosteroids influences the initiation and duration of humoral responses in COVID-19 survivors 6 months after infection ***:We used kinetic antibody data from the lopinavir-ritonavir trial conducted at Jin Yin-Tan Hospital in January 2020,which involved adults hospitalized with severe COVID-19(LOTUS,ChiCTR2000029308).Anti-body samples were collected from 192 patients during hospitalization,and kinetic antibodies were monitored at all available time points after ***,plasma samples were collected from 101 COVID-19 survivors for comprehensive humoral immune measurement at the half-year follow-up *** main focus was comparing the humoral responses between patients treated with systemic corticosteroid therapy and the non-corticosteroid ***:From illness onset to day 30,the median antibody titre areas under the receiver operating characteristic curve(AUCs)of nucleoprotein(N),spike protein(S),and receptor-binding domain(RBD)immunoglobulin G(IgG)were significantly lower in the corticosteroids *** AUCs of N-,S-,and RBD-IgM as well as neutralizing antibodies(NAbs)were numerically lower in the corticosteroids group compared with the non-corticosteroid ***,peak titres of N,S,RBD-IgM and-IgG and NAbs were not influenced by *** 6-month follow-up,we observed a delayed decline for most binding antibodies,except N-IgM(𝛽−0.05,95%CI[−0.10,0.00])in the corticosteroids group,though not reaching statistical *** significant difference was observed for ***,for the half-year seropositive rate,corticosteroids significantly accelerated the decay of IgA and IgM but made no difference to N-,S-,and RBD-IgG or ***,corticosteroids group showed a trend towards d

关键词： COVID-19 Corticosteroid Immunity Antibody Humoral response

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Endothelial phosphodiesterase 4B inactivation ameliorates endothelial-to-mesenchymal transition and pulmonary hypertension

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1726-1741页

作者： Yanjiang Xing Yangfeng Hou Tianfei Fan Ran Gao Xiaohang Feng Bolun Li Junling Pang Wenjun Guo Ting Shu Jinqiu Li Jie Yang Qilong Mao Ya Luo Xianmei Qi Peiran Yang Chaoyang Liang Hongmei Zhao Wenhui Chen Jing Wang Chen Wang State Key Laboratory of respiratory Health and Multimorbidity Institute of Basic Medical SciencesChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100005China department of Lung Transplantation National Center for Respiratory MedicineNational Clinical Research Center for Respiratory DiseasesChina–Japan Friendship HospitalInstitute of Respiratory MedicineChinese Academy of Medical SciencesBeijing 100029China Haihe Laboratory of Cell Ecosystem Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300051China The State Key Laboratory of Complex Severeand Rare DiseasesInstitute of Basic Medical SciencesChinese Academy of Medical SciencesDepartment of PathophysiologyPeking Union Medical CollegeBeijing 100005China department of Pharmacy West China HospitalSichuan UniversityChengdu 610044China

pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A–D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH;however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA–CREB–BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.

关键词： Phosphodiesterase 4B pulmonary hypertension Endothelial-to-mesenchymal transition

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