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The activity and immune dynamics of PD-1.inhibition on high-risk pulmonary ground glass opacity lesions:insights from a single-arm,phase II trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2202-2214页

作者： Bo Cheng Caichen li Jianfu li Longlong Gong Peng liang Ying Chen Shuting Zhan Shan Xiong Ran Zhong Hengrui liang Yi feng Runchen Wang Haixuan Wang Hongbo Zheng Jun liu Chengzhi Zhou Wenlong shao Yuan Qiu Jiancong Sun Zhanhong Xie Zhu liang Chenglin Yang Xiuyu Cai Chunxia Su Wei Wang Jianxing He Wenhua liang department of Thoracic Surgery and Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Medical department Genecast Biotechnology Co.LtdWuxiChina department of Radiation Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina department of Respiratory Medicine the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina department of Cardiothoracic Surgery Affiliated Hospital of Guangdong Medical UniversityZhanjiangChina department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenChina department of VIP Inpatient Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaSun Yat-sen UniversityGuangzhouChina department of Medical Oncology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Immune checkpoint inhibitors targeting the programmed cell death-1.PD-1.protein significantly improve survival in patients with advanced non-small-cell lung cancer(NSCLC),but its impact on early-stage ground-glass opacity(GGO)lesions remains *** is a single-arm,phase II trial(NCT04026841.using Simon’s optimal two-stage design,of which 4 doses of sintilimab(200 mg per 3 weeks)were administrated in 36 enrolled multiple primary lung cancer(MPLC)patients with persistent high-risk(Lung-RADS category 4 or had progressed within 6 months)*** primary endpoint was objective response rate(ORR).T/B/NK-cell subpopulations,TCR-seq,cytokines,exosomal RNA,and multiplexed immunohistochemistry(mIHC)were monitored and compared between responders and ***,two intent-to-treat(ITT)lesions(pure-GGO or GGO-predominant)showed responses(ORR:5.6%,2/36),and no patients had progressive disease(PD).No grade 3-5 TRAEs *** total response rate considering two ITT lesions and three non-intent-to-treat(NITT)lesions(pure-solid or solid-predominant)was 1..9%(5/36).The proportion of CD8^(+)T cells,the ratio of CD8^(+)/CD4^(+),and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over ***,the mIHC analysis showed more CD8^(+)T cells infiltrated in ***,responders’cytokine concentrations of EGF and CTLA-4 increased during *** exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among ***,PD-1.inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety *** effects were associated with specific T-cell re-distribution,EGF/CTLA-4 cytokine compensation,and regulation of metabolism pathways.

关键词： lesions metabolism doses

Engineering Shewanella-re duce d graphene oxide aerogel biohybrid to efficiently synthesize Au nanoparticles

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Journal of Materials Science & Technology 2024年第1期168卷 50-61页

作者： Baocai Zhang Shulin {1. Huan Yu Qijing liu Sicheng Shi Qingyuan Wu Zijie Wu Yiyu feng Yifei Wang Xi Sun Deguang Wu feng li Hao Song Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering(Ministry of Education) Tianjin UniversityTianjin 300072China Collaborative Innovation Center of Chemical Science and Engineering(Tianjin) School of Chemical Engineering and TechnologyTianjin UniversityTianjin 300072China beijing Advanced Innovation Center for Soft Matter Science and Engineering Beijing University of Chemical TechnologyBeijing 100029China School of Materials Science and Engineering Tianjin UniversityTianjin 300350China College of Biological Engineering Tianjin Agricultural UniversityTianjin 300384China department of Brewing Engineering Moutai InstituteLuban AveRenhuai 564507China

Biosynthesizing Au nanoparticles(AuNPs)from gold-bearing scraps provides a sustainable method to meet the urgent demand for ***,it remains challenging to efficiently biosynthesize AuNPs of which the diameter is less than 1. nm from a trace amount of Au^(3+)concentration at the level of tens ***,we constructed an exoelectrogenic cell(eCell)-conductive reduced-graphene-oxide aero-gel(rGA)biohybrid by assembling Shewanella sp.S1.SS1.as living biocatalyst and rGA as conductive ad-sorbent,in which Au^(3+)at trace concentrations would be enriched by the adsorption of rGA and reduced to AuNPs through the extracellular electron transfer(EET)of *** regulate the size of the synthe-sized AuNPs to 1. nm,the strain SS1.was engineered to enhance its EET,resulting in strain RS2(pYYD-P tac-ribADEHC&pHG1.-P_(bad)-omcC in SS1..Strain RS2 was further assembled with rGA to construct the RS2-rGA biohybrid,which could synthesize AuNPs with the size of 7.62±2.82 nm from 60 ppm Au^(3+)*** eCell-rGA biohybrid integrated Au^(3+)adsorption and reduction,which enabled AuNPs biosyn-thesis from a trace amount of Au^(3+).Thus,the required Au^(3+)ions concentration was reduced by one or two orders of magnitude compared with conventional methods of AuNPs *** work devel-oped an AuNPs size regulation technology via engineering eCell’s EET with synthetic biology methods,providing a feasible approach to synthesize AuNPs with controllable size from trace level of gold ions.

关键词： Au nanoparticles Exoelectrogenic cell(e-Cell) Shewanella Synthesis biology Extracellular electron transfer Reduced graphene oxide aerogel

Risk factors and predictive model of cerebral edema after road traffic accidents-related traumatic brain injury

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Chinese Journal of Traumatology 2024年第3期27卷 153-162页

作者： Di-You Chen Peng-Fei Wu Xi-Yan Zhu Wen-Bing Zhao Shi-feng {1. Jing-Ru Xie Dan-feng Yuan liang Zhang Kui li Shu-Nan Wang Hui Zhao Institute for Traffic Medicine Daping HospitalArmy Medical UniversityChongqing400042China department of Radiology Daping HospitalArmy Medical UniversityChongqing400042China Chongqing Key Laboratory of Traffic Injury and Vehicle Ergonomics Chongqing400042China Wound Trauma Medical Center State Key Laboratory of TraumaBurns and Combined InjuryInstitute of Surgery ResearchDaping HospitalArmy Medical UniversityChongqing.400042China

Purpose:Cerebral edema(CE)is the main secondary injury following traumatic brain injury(TBI)caused by road traffic accidents(RTAs).It is challenging to be predicted *** this study,we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of ***:This case-control study included 21. patients with TBI caused by *** cohort was divided into CE and non-CE groups,according to CT results within 7 *** data,imaging data,and clinical data were collected and *** variables that follow normal distribution were presented as mean±standard deviation,those that do not follow normal distribution were presented as median(Q1.Q3).Categorical variables were expressed as *** Chi-square test and logistic regression analysis were used to identify risk factors for *** curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of *** efficacy of the model was evaluated using the receiver operator characteristic ***:According to the study,almost half(47.3%)of the patients were found to have *** risk factors associated with CE were bilateral frontal lobe contusion,unilateral frontal lobe contusion,cerebral contusion,subarachnoid hemorrhage,and abbreviated injury scale(AIS).The odds ratio values for these factors were 7.27(95%confidence interval(CI):2.08-25.42,p=0.002),2.85(95%CI:1.1.-7.31.p=0.030),2.62(95%CI:1.1.-6.1.,p=0.027),2.44(95%CI:1.25-4.76,p=0.009),and 1.5(95%CI:1.1.-2.04,p=0.009),*** also observed that patients with mild/moderate TBI(AIS≤3)had a 50%probability of developing CE 1..7 h after injury(χ^(2)=1..82,adjusted R2=0.51.,while patients with severe TBI(AIS>3)developed CE after 1..5 h(χ^(2)=1..48,adjusted R2=0.54).Finally,we conducted a receiver operator characteristic curve analysis of CE time,which showed an area under the curve of 0

关键词： Road traffic accident Traumatic brain injury Cerebral edema Risk factors Time window

Utilization of a spiropyran derivative in a polymeric film optode for selective fluorescent sensing of zinc ion

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Science china Chemistry 2006年第3期49卷 246-255页

作者： ZHANG Ying1. shao Na1. YANG Ronghua1. {1. Ke’an1. {1.U feng1. CHAN Winghong2 & MO Tian2 1. College of Chemistry and Molecular Engineering, peking university, beijing 100871, china 2. department of Chemistry, Hong Kong Baptist university, Hong Kong, china College of Chemistry and Molecular Engineering Peking University Beijing China department of Chemistry Hong Kong Baptist University Hong Kong China

A new spiropyran derivative was synthesized and first utilized in a polymericfilm-based optical sensor for zinc ion. Spiropyrans, combining the characteristics of metal bindingand signal transduction, show potential function in the design of optical chemical sensors(optodes) toward metal ions. When embedded in a plasticized poly (vinyl chloride) (PVC) membrane,the newly synthesized spiropyran derivative 1.exhibits obvious fluorescence enhancement at 630 nm inthe presence of zinc ion in aqueous solution. With the optimum condition described, the optodemembrane responds to zinc ion over a dynamic range of 4.94x1.^(-7) to 4.1.x1.^(-4)mol·L^(-1., witha detection limit of 1.51.1.^(-7) mol·L^(-1.. The membrane not only displays excellentphotostability, reproducibility and reversibility, but also exhibits high selectivity toward zincion over transition metal ions including Hg^(2+), Cd^(2+), Pb^(2+), Cu^(2+), Fe^(3+) and commoncationic ions presented in the physiological fluids.

关键词： spiropyran, sensor, PVC membrane, zinc ion, fluorescent spectroscopy.

Dual-functional microneedle with programmatic regulation of macrophage for autoimmune psoriasis treatment

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Nano Research 2024年第8期17卷 7436-7448页

作者： Ze Qiang Zhao Bo Zhi Chen Jia li Gan Yun Hao {1. ling liang lingyun Yu Zi Yi Wang Samin Abbaszadeh Mohammad-Ali Shahbazi Ruixing Yu Xin Dong Guo State Key Laboratory of Organic-Inorganic Composites Beijing University of Chemical TechnologyBeijing 100029China beijing Laboratory of Biomedical Materials College of Materials Science and EngineeringBeijing University of Chemical TechnologyBeijing 100029China china-Japan Friendship Hospital Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100029China department of Dermatology China-Japan Friendship HospitalBeijing 100029China department of Pharmaceutical Biomaterials School of PharmacyZanjan University of Medical SciencesZanjan 45139-56184Iran department of Biomaterials and Biomedical Technology University Medical Center GroningenUniversity of GroningenAntonius Deusinglaan 19713 AV GroningenThe Netherlands W.J.Kolff Institute for Biomedical Engineering and Materials Science University of GroningenAntonius Deusinglaan 19713 AV GroningenThe Netherlands

Modulating the immune microenvironment to establish sustained positive feedback within immune pathways represents a promising avenue for the treatment of ***,the precise and efficient delivery of therapeutic systems to the subcutaneous basal layer to modulate immune disorders is a major challenge in the treatment of autoimmune *** this project,we introduce a dual-functional microneedle(DF-MN)designed to combine MNs with multiple release kinetics and immunotherapy,the programmed treatment is achieved through segmented design of the MN structure,realizing the unification of rapid and long-lasting treatment of autoimmune *** vivo imaging results showed that GelMA@M-CSF showed fluorescent signals after 5 days of delivery to subcutaneous tissues,whereas HA@IL-1. showed minimal fluorescent signals after 2 *** multistage release behavior of MNs and the diffusion mechanism of drugs were explained at the molecular level,in combination with coarse-grained molecular ***,DF-MN can successfully induce macrophage reprogramming in vitro and ameliorate overall symptoms in a psoriasis mice model,suggesting that it has the potential to be an effective strategy for the treatment of psoriasis and portends to be a transformative platform for the treatment of other autoimmune diseases.

关键词： microneedle psoriasis M2 macrophage immunoregulation

Establishment of a Multiplex Detection Method for Common Bacteria in Blood Based on Human Mannan-Binding Lectin Protein-Conjugated Magnetic Bead Enrichment Combined with Recombinase-Aided PCR Technology

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Biomedical and Environmental Sciences 2024年第4期37卷 387-398页

作者： ZHAO Zi Jin CHEN Xiao Ping HUA shao Wei {1. feng Yu ZHAO Meng XING Chen Hao WANG Jie TIAN feng Yu ZHANG Rui Qing LYU Xiao Na HAN Zhi Qiang WANG Yu Xin {1. Hong Yi SHEN Xin Xin MA Xue Jun TIE Yan Qing Graduate School Hebei North UniversityZhangjiakou 075000HebeiChina department of C{1.nical Laboratory Hebei General HospitalShijiazhuang 050051HebeiChina National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases NHC Key Laboratory of Medical Virology and Viral DiseasesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China National Institute for Communicable Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206China department of C{1.nical Laboratory Pathology Diagnostic Center Shiyan General HospitalShiyan 442000HubeiChina Graduate School Hebei Medical university Shijiazhuang 050031HebeiChina

Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification *** study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannanbinding lectin protein(M1.protein)-conjugated magnetic bead(M1.bead)enrichment of pathogens combined with *** Recombinant plasmids were used to evaluate the assay *** blood influenza bacteria were used for the specific *** and clinical plasma samples were enriched with M1.beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)*** analysis was used to evaluate the consistency between the two *** The M-RAP method had sensitivity rates of 1.1.,and 1.copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial *** M-RAP assay obtained results for1. CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.81.,and 0.856,respectively(Plizing M1.bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

关键词： Staphylococcus aureus Pseudomonas aeruginosa Acinetobacter baumannii Human Mannan-binding lectin protein Bloodstream infection Recombinase-aided PCR assay Multiple detection

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

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Military Medical Research 2024年第1期11卷 19-33页

作者： liang-Kun Guo Yi Su Yu-Ya-Nan Zhang Hao Yu Zhe Lu Wen-Qiang {1. Yong-feng Yang Xiao Xiao Hao Yan Tian-Lan Lu Jun {1. Yun-Dan {1.ao Zhe-Wei Kang {1.-Fang Wang Yue {1. Ming {1. Bing {1.u Hai-liang Huang Lu-Xian Lv Yin Yao Yun-Long Tan Gerome Breen Ian Everall Hong-Xing Wang Zhuo Huang Dai Zhang Wei-Hua Yue Institute of Mental Health Peking University Sixth HospitalBeijing 100191China National Clinical Research Center for Mental Disorders Peking University Sixth HospitalBeijing 100191China NHC Key Laboratory of Mental Health and Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder(201.RU006) Chinese Academy of Medical SciencesBeijing 100191China peking {1. Huilongguan Clinical Medical School Beijing Huilongguan HospitalBeijing 100096China department of Psychiatry Jining Medical UniversityJining 272067ShandongChina Henan Key Lab of Biological Psychiatry the Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang 435001HenanChina Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Institute of Psychiatry Psychology and NeuroscienceKing’s College LondonLondon WC2R 2LSUK State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal UniversityBeijing 100875China Analytic and Translational Genetics Unit Massachusetts General HospitalBostonMA 02114USA Stanley Center for Psychiatric Research the Broad Institute of MIT and HarvardCambridgeMA 02141USA department of Medicine Harvard Medical SchoolBostonMA 02115USA department of Biostatistics and Computational Biology School of Life SciencesFudan UniversityShanghai 200438China department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Natural and Biomimetic Drugs Key Laboratory for Neuroscience for Ministry of EducationSchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China PKU-IDG/McGovern Institute for Brain Research Peking UniversityBeijing 100871China Chinese Institute for Brain Research Beijing 102206China

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective *** studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been ***,further research is imperative to enhance precision medicine in SCZ ***:Participants with SCZ were recruited from two randomized *** discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)*** external validation cohort was recruited from the CAPEC trial(n=1.79),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole ***,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic *** genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,*** study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin *** learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve ***:Six risk genes for SCZ(liNC01.95,DDHD2,SBNO1.KCNG2,SEMA7A,and RUFY1.involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment *** developed and externally validated predictio

关键词： Schizophrenia Antipsychotic drug Treatment response Prediction model Genetics Epigenetics

life's essential 8 and risk of subclinical atherosclerosis progression: a prospective cohort study

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Journal of Geriatric Cardiology 2024年第7期21卷 751-759页

作者： Shi-Yu ZHOU Fang-Chao liU Shu-{1. CHEN Jian-Xin li Jie CAO Ke-Yong HUANG Zheng-Hao TANG {1.-Chao liang Dong-Sheng HU lian-Cheng ZHAO Ying li Jian-{1. HUANG Xiang-{1. LU Bin LU Dong-{1. GU department of Epidemiology&Key Laboratory of Cardiovascular Epidemiology State Key Laboratory of Cardiovas-cular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina School of Public Health and Emergency Management School of Medi-cineSouthern University of Science and TechnologyShenzhenChina department of Epidemiology and Health Stat-istics School of Public HealthZhengzhou UniversityZhengzhouChina department of Biostatistics and Epidemi-ology School of Public HealthShenzhen University Health Science CenterShenzhenChina department of Radi-ology State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

BACKGROUND Previous studies have demonstrated the benefits of ideal cardiovascular health(CVH) in reducing cardiovascular ***,its role in subclinical atherosclerosis(SA) progression remains *** aim to examine the association of CVH,estimated by the American Heart Association's new life's Essential 8(LE8),with the progression of *** This prospective cohort study was conducted among 972 asymptomatic Chinese participants and followed up for5.7 *** LE8 score(range,0–1.0) consisted of blood pressure,lipids,glucose,body mass index,smoking status,diet health,physical activity and sleep health was evaluated in 1.98 and 2008–*** of SA was determined by carotid plaque and coronary artery calcification(CAC) in 2008–2009 and 201.–***-binomial regression model was used to estimate the association of LE8 score with SA *** Each 1. points increment in LE8 score was associated with 1..2%(RR:0.848,95% CI:0.797–0.902),1..7%(RR:0.823,95% CI:0.766–0.884) and 1..0%(RR:0.880,95% CI:0.845–0.91.) lower risks of carotid plaque,CAC and overall SA progression,*** with participants with non-ideal CVH at both visits,the participants with ideal CVH at both visits had39.1.(RR:0.609,95% CI:0.494–0.752),41.0%(RR:0.590,95% CI:0.456–0.764) and 29.7%(RR:0.703,95% CI:0.598–0.825) lower risks of carotid plaque,CAC and overall SA progression,*** Higher LE8 scores were associated with lower risks of SA ***,long-term maintenance of optimal CVH was more beneficial to prevent SA progression.

关键词： atherosclerosis prospective cardiovascular

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