检索结果-南通市图书馆

World Journal of Gastroenterology 2024年第16期30卷 2209-2219页

作者： Na Cui Ting Dai Yang Liu Ya-Yu Wang Jia-Yu Lin Qing-Fan Zheng Dong-Dong Zhu Xue-Wei Zhu Department of Otorhinolaryngology Head and Neck Surgery China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina Department of Ultrasound China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina Department of Gastroenterology China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina

Laryngopharyngeal reflux disease(LPRD)is an inflammatory condition in the laryngopharynx and upper aerodigestive tract mucosa caused by reflux of stomach contents beyond the esophagus.LPRD commonly presents with symptoms such as hoarseness,cough,sore throat,a feeling of throat obstruction,excessive throat mucus.This complex condition is thought to involve both reflux and reflex mechanisms,but a clear understanding of its molecular mechanisms is still lacking.Currently,there is no standardized diagnosis or treatment protocol.Therapeutic strategies for LPRD mainly include lifestyle modifications,proton pump inhibitors and endoscopic surgery.This paper seeks to provide a comprehensive overview of the existing literature regarding the mechanisms,pathophysiology and treatment of LPRD.We also provide an in-depth exploration of the association between LPRD and gastroesophageal reflux disease.

关键词： Laryngopharyngeal reflux Gastroesophageal reflux Head neck surgery Laryngitis Otolaryngology

Relationship between Helicobacter pylori infection and colorectal polyp/colorectal cancer

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastrointestinal Surgery 2024年第4期16卷 1008-1016页

作者： Ying Liu Ding-Quan Yang Jun-Nan Jiang Yan Jiao Department of General Surgery The Affiliated Hospital to Changchun University of Chinese MedicineChangchun 130021Jilin ProvinceChina Department of Gastrointestinal and Colorectal Surgery China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina Department of Hepatobiliary and Pancreatic Surgery General Surgery CenterThe First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina

Helicobacter pylori(H.pylori)plays an important role in the development of gastric cancer,although its association to colorectal polyp(CP)or colorectal cancer(CRC)is unknown.In this issue of World Journal of Gastrointestinal Surgery,Zhang et al investigated the risk factors for H.pylori infection after colon polyp resection.Importantly,the researchers used R software to create a prediction model for H.pylori infection based on their findings.This editorial gives an overview of the association between H.pylori and CP/CRC,including the clinical significance of H.pylori as an independent risk factor for CP/CRC,the underlying processes of H.pylori-associated carcinogenesis,and the possible risk factors and identification of H.pylori.

关键词： Helicobacter pylori Colorectal polyp Colorectal cancer Risk factor

Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 89-101页

作者： Yunhan Zhang Zhulin Zou Shuang Liu Fangfang Chen Minglu Li Haoyang Zou Haiyan Liu Jianxun Ding Key Laboratory of Pathobiology Ministry of Education Department of AnatomyCollege of Basic Medical SciencesJilin UniversityChangchun 130061China Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Department of Gastrointestinal Colorectaland Anal SurgeryChina-Japan Union Hospital of Jilin UniversityChangchun 130033China

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

关键词： Poly(amino acid)nanogel Controlled drug delivery Inhibition of ferroptosis Neuroprotection Cerebral ischenia injury therapy

Continuous ward monitoring and intensive postoperative management

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Medical Journal 2024年第6期137卷 631-632页

作者： Kai Li Jiayi Wang Daniel I.Sessler Department of Anesthesiology China-Japan Union HospitalJilin UniversityChangchunJilin 130031China Outcomes Research Consortium ClevelandOhio 44195USA Department of Anesthesiology Shanghai Ninth People’s HospitalShanghai JiaoTong University School of MedicineShanghai 201999China Department of Outcomes Research Cleveland ClinicClevelandOhio 44195USA

When patients having major surgery reach the post-anaesthesia care unit,families naturally assume that they have survived the most dangerous part of the perioperative experience.Their assumption is wrong.Mortality in the 30 days after surgery is 140 times higher than intraoperative mortality.^([1,2])In fact,if the month after surgery were considered a disease,it would be the world’s third leading cause of death.^([3])

关键词： assume dangerous wrong

Long-term tadalafil once daily in Chinese men witherectile dysfunction:a 2-year final analysis of apost-marketing,multicenter,randomized,open-labeltrial

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Asian Journal of Andrology 2024年第3期26卷 282-287页

作者： Hui Jiang Lian-Ming Zhao Su Yan Ji-Hong Liu Zhao-Hui Zhu Jin-Dan Luo Yu-Tian Dai Fu-Biao Li Hao-Cheng Lin Zhi-Chao Zhang Department of Urology Peking University First HospitalBeijing 100000China Department of Urology Peking University Third HospitalBeijing 100191China Department of Urology Peking Union Medical College HospitalBeijing 100730China Department of Urology Tongji HospitalTongji Medical CollegeHuazhongUniversity of Science and TechnologyWuhan 430030China Department of Urology Union Hospital of Tongji Medical CollegeHuazhong University of Science andTechnologyWuhan 430022China Department of Urology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Departmentof Andrology Nanjing Drum Tower HospitalNanjing 210008China Department of Andrology The First Hospital of Jilin UniversityChangchun 130021China Andrology Center Department of UrologyPeking University First HospitalBeijing 100034China.

The long-term safety and effectiveness of once-daily tadalafil is crucial,but limited data are available in Chinese patients witherectile dysfunction(ED).In this post-marketing,multicenter,randomized,open-label trial with 2-year follow-up,635 ED caseswere randomized to receive daily oral tadalafil 2.5 mg or 5 mg for 3 months,of whom 580 continued once-daily tadalafil 5 mg for21 months.Treatment-emergent adverse events in the 12-month and 24-month period were similar,with the most common beingviral upper respiratory tract infection,upper respiratory tract infection,and headache.Significant improvement from baseline inthe International Index of Erectile Function-Erectile Function(IIEF-EF)score was detected at month 12(least squares mean[LSM]change:7.9,95%confidence interval[CI]:7.5–8.4,P<0.001)and was maintained to month 24(LSM change:8.6,95%CI:8.1–9.0,P<0.001).The proportions of patients regaining normal erectile function(IIEF-EF score≥26)were 43.7%and 48.0%at months 12 and 24,respectively.Global Assessment Questionnaire results showed improved erection function in 97.5%ofpatients and improved ability to engage in sexual activity in 95.9%of patients at month 12;these values were 96.1%and 95.0%at month 24,respectively.The quality of sexual life score based on the Sexual Life Quality Questionnaire(SLQQ)was increased by52.2%at month 12 and by 55.3%at month 24(both P<0.001).The treatment satisfaction score determined by SLQQ(mean±standard deviation)was 62.4±21.0 at month 12 versus 65.9±20.2 at month 24.Two-year daily application of tadalafil 5mg in Chinese men with ED showed a favorable safety profile and durable improvement in sexual performance and satisfaction.

关键词： clinical trial erectile dysfunction long-term safety once-daily dosing tadalafil

Clinical manifestation,lifestyle,and treatment patterns of chronic erosive gastritis:A multicenter real-world study in china

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2024年第9期30卷 1108-1120页

作者： Ying-Yun Yang Ke-Min Li Gui-Fang Xu Cheng-Dang Wang Hua Xiong Xiao-Zhong Wang Chun-Hui Wang Bing-Yong Zhang Hai-Xing Jiang Jing Sun Yan Xu Li-Juan Zhang Hao-Xuan Zheng Xiang-Bin Xing Liang-Jing Wang Xiu-Li Zuo Shi-Gang Ding Rong Lin Chun-Xiao Chen Xing-Wei Wang Jing-Nan Li Department of Gastroenterology Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100730China Department of Gastroenterology Nanjing Drum Tower HospitalNanjing 21000Jiangsu ProvinceChina Department of Gastroenterology The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005Fujian ProvinceChina Department of Gastroenterology Renji HospitalShanghai 200127China Department of Gastroenterology Union Hospital of Fujian Medical UniversityFuzhou 350000Fujian ProvinceChina Department of Gastroenterology West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Gastroenterology and Hepatology The People’s Hospital of Zhengzhou UniversityThe Henan Provincial People’s HospitalZhengzhou 450003Henan ProvinceChina Department of Gastroenterology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Ruijin hospital Shanghai Jiaotong university School of Medicine Shanghai Jiao Tong UnivesrityRuijin HospitalSchool MedicineShanghai 200025China Department of Gastroenterology and Hepatology China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina Department of Gastroenterology Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina Department of Gastroenterology Nanfang HospitalGuangzhou 510080Guangdong ProvinceChina Department of Gastroenterology The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080Guangdong ProvinceChina Department of Gastroenterology The Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina Department of Gastroenterology Shandong University Qilu HospitalJinan 250012Shandong ProvinceChina Department of Gastroenterology Peking University Third HospitalBeijing 100191China Department of Gastroenterology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022Hubei Pr

BACKGROUND Although chronic erosive gastritis(CEG)is common,its clinical characteristics have not been fully elucidated.The lack of consensus regarding its treatment has resulted in varied treatment regimens.AIM To explore the clinical characteristics,treatment patterns,and short-term outcomes in CEG patients in china.METHODS We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology.Patients and treating physicians completed a questionnaire regarding history,endoscopic findings,and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment.RESULTS Three thousand five hundred sixty-three patients from 42 centers across 24 cities in china were included.Epigastric pain(68.0%),abdominal distension(62.6%),and postprandial fullness(47.5%)were the most common presenting symptoms.Gastritis was classified as chronic non-atrophic in 69.9%of patients.Among those with erosive lesions,72.1%of patients had lesions in the antrum,51.0%had multiple lesions,and 67.3%had superficial flat lesions.In patients with epigastric pain,the combination of a mucosal protective agent(MPA)and proton pump inhibitor was more effective.For those with postprandial fullness,acid regurgitation,early satiety,or nausea,a MPA appeared more promising.CONCLUSION CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms.Gastroscopy may play a major role in its detection and diagnosis.Treatment should be individualized based on symptom profile.

关键词： Chronic erosive gastritis Symptom Endoscopic findings Treatment pattern Real-world

Associations of sleeping patterns and isotemporal substitution of other behavior with the prevalence of CKD in Chinese adults

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Frontiers of Medicine 2024年第2期18卷 303-314页

作者： Yi Ding Xiaoli Xu Zhuojun Xin Qiuyu Cao Jiaojiao Huang Xianglin Wu Yanan Huo Qin Wan Yingfen Qin Ruying Hu Lixin Shi Qing Su Xuefeng Yu Li Yan Guijun Qin Xulei Tang Gang Chen Min Xu Tiange Wang Zhiyun Zhao Zhengnan Gao Guixia Wang Feixia Shen Zuojie Luo Li Chen Qiang Li Zhen Ye Yinfei Zhang Chao Liu Youmin Wang Tao Yang Huacong Deng Lulu Chen Tianshu Zeng Jiajun Zhao Yiming Mu Shengli Wu Yuhong Chen Jieli Lu Weiqing Wang Guang Ning Yu Xu Yufang Bi Mian Li Department of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Shanghai National Clinical Research Center for Metabolic Diseases Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of ChinaShanghai Key Laboratory for Endocrine TumorState Key Laboratory of Medical GenomicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Jiangxi Provincial People’s hospital Affiliated to Nanchang UniversityNanchang330000China Department of Endocrinology The Affiliated Hospital of Southwest Medical UniversityLuzhou646000China Department of Endocrinology The First Affiliated Hospital of Guangxi Medical UniversityNanning530000China Zhejiang Provincial Center for Disease Control and Prevention Hangzhou310000China Department of Endocrinology Affiliated Hospital of Guiyang Medical UniversityGuiyang550000China Xinhua hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200000China Tongji hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430000China Sun Yat-sen Memorial hospital Sun Yat-sen UniversityGuangzhou510000China Department of Endocrinology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450000China Department of Endocrinology The First Hospital of Lanzhou UniversityLanzhou730000China Fujian Provincial hospital Fujian Medical UniversityFuzhou350000China Dalian Municipal Central hospital Affiliated of Dalian Medical UniversityDalian116000China Department of Endocrinology The First Hospital of Jilin UniversityChangchun130000China Department of Endocrinology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou325000China Qilu hospital of Shandong university Jinan250000China Department of Endocrinology The Second Affiliated Hospital of Harbin Medical UniversityHarbin150000China Department of Endocrinology Cen

Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD.We included 104538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals:A Longitudinal Study,with self-reported time of daily-life behavior.Using isotemporal substitution models,we found that substituting 1 h of sleeping with sitting,walking,or moderate-to-vigorous physical activity was associated with a lower CKD prevalence.Leisure-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working population.In stratified analysis,a lower CKD prevalence related to substitution toward physical activity was found in long sleepers.More pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes,and they benefited from other behavior substitutions toward a more active way.The U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys,in which the pernicious link with oversleep could be reversed by time reallocation to physical activity.The divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.

关键词： sleep physical activity chronic kidney disease isotemporal substitution behavioral pattern

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

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

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 diagnosis.In population studies,machine learning(ML)plays a critical role in characterizing cardiovascular risks,predicting outcomes,and identifying biomarkers.This work sought to develop an ML model for helping APE diagnosis and compare it against current clinical probability assessment models.Methods:This is a single-center retrospective study.Patients 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 APE.Thereafter,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 algorithm.Eventually,the ML model was internally validated to assess the diagnostic performance using receiver operating characteristic(ROC)analysis.Results: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 failure.Among 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 strategy.The AUC of the RF model for diagnosing APE onset in internal validation set was 0.726.Conclusions:Based on RF algorithm,a novel prediction model was finally constructed for APE diagnosis.When compared to the current clinica

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

Non-invasive imaging of pathological scars using a portable handheld two-photon microscope

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Chinese Medical Journal 2024年第3期137卷 329-337页

作者： Yang Han Yuxuan Sun Feili Yang Qingwu Liu Wenmin Fei Wenzhuo Qiu Junjie Wang Linshuang Li Xuejun Zhang Aimin Wang Yong Cui Graduate School Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100730China Department of Dermatology China-Japan Friendship HospitalBeijing 100029China College of Engineering Peking UniversityBeijing 100871China School of Chemical Biology and Biotechnology State Key Laboratory of Chemical OncogenomicsPeking University Shenzhen Graduate SchoolShenzhenGuangdong 518055China Department of Dermatology The First Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China Academy for Advanced Interdisciplinary Studies Peking UniversityBeijing 100871China College of Future Technology Peking UniversityBeijing 100871China Beijing Transcend Vivoscope Biotech Beijing 100085China Department of Dermatology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230001China Institute of Dermatology Anhui Medical UniversityHefeiAnhui 230001China School of Electronics Peking UniversityBeijing 100871China

Background:Pathological scars are a disorder that can lead to various cosmetic,psychological,and functional problems,and no effective assessment methods are currently available.Assessment and treatment of pathological scars are based on cutaneous manifestations.A two-photon microscope(TPM)with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo.This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients.Methods:Fifteen patients with pathological scars and three healthy controls were recruited.Imaging was performed using a portable handheld TPM.Five indexes were extracted from two dimensional(2D)and three dimensional(3D)perspectives,including collagen depth,dermo-epidermal junction(DEJ)contour ratio,thickness,orientation,and occupation(proportion of collagen fibers in the field of view)of collagen.Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images.We assessed index differences between scar and normal skin and changes before and after treatment.Results:Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers.Five indexes were employed to distinguish between normal skin and scar tissue.Statistically significant differences were found in average depth(t=9.917,P<0.001),thickness(t=4.037,P<0.001),occupation(t=2.169,P<0.050),orientation of collagen(t=3.669,P<0.001),and the DEJ contour ratio(t=5.105,P<0.001).Conclusions:Use of portable handheld TPM can distinguish collagen from skin tissues;thus,it is more suitable for scar imaging than reflectance confocal microscopy.Thus,a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.

关键词： Scars Two-photon microscope Two-photon excitation fluorescence Second harmonic generation microscopy

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

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

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