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Antitumor effect of RNA interference on non-small- cell lung cancer in vivo

The Chinese-German Journal of Clinical Oncology 2009年第8期8卷 463-466页

作者： Min Zhang Chunxue Bai Xin Zhang Ling Mao Yuehong Wang Department of pulmonary disease Shandong Provincial Hospital affiliated to Shandong University Jinan 250021 China institute of pulmonary disease Zhongshan Hospital Fudan University Shanghai 200032 China

Objective： Lung cancer has emerged as a leading cause of cancer death in the world. Current therapies are ineffective, thus new approaches are needed to improve the therapeutic ratio. RNA interference （RNAi） has shown promise in gene silencing in vitro, the potential of which in developing new methods for the therapy of non-small-cell lung cancer （NSCLC） needs to be further tested in vivo. In this study, chemically synthesized double-stranded RNA （dsRNA） targeting epidermal growth factor receptor （EGFR） was transfected into NSCLC cell line SPC-A1 cells and established the tumor burdened athymic nude mice model to investigate whether dsRNA could induce gene silencing in NSCLC cells in vivo. Methods： SPC-A1 was transfected with EGFR sequence-specific dsRNA formulated with Lipofectamine 2000. SPC-A1 cells （1 × 107/ mL） in 200 pL were injected s.c. into the left flank area of the mice to establish the tumor burdened athymic nude mice model. Calculate the tumor growth inhibition rate by measuring the diameter and the weight of the tumor. Immunohistochemistry and Westem blot were used to monitor the reduction in the production of the EGFR protein. Realtime RT-PCR was used to detect the silencing of the EGFR mRNA level. Results： It displayed that EGFR sequence specific dsRNA （dsRNA-EGFR） significantly inhibited the tumor growth in vivo. The tumor growth inhibition rate was 75.03%. The dsRNA-EGFR sequence specifically silenced EGFR with 53.6% of down-regulation of EGFR protein production and 32.3% of silencing of EGFR mRNA level. Conclusion： DsRNA-EGFR showed a blockbuster effect in downregulation of EGFR mRNA level and protein production, and inhibition of tumor growth in vivo.

关键词： epidermal growth factor receptor (EGFR) RNA interference (RNAi) double-stranded RNA (dsRNA) non-small-cell lung cancer (NSCLC)

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When smoke meets gut:deciphering the interactions between tobacco smoking and gut microbiota in disease development

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Science China(Life Sciences) 2024年第5期67卷 854-864页

作者： Bo Chen Guangyi Zeng Lulu Sun Changtao Jiang Center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191China Department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China Center for Obesity and Metabolic disease Research School of Basic Medical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Women’s Reproductive Health and Fertility Promotion Peking UniversityBeijing 100191China Department of Endocrinology and Metabolism Peking University Third HospitalBeijing 100191China

Tobacco smoking is a prevalent and detrimental habit practiced worldwide,increasing the risk of various diseases,including chronic obstructive pulmonary disease(COPD),cardiovascular disease,liver disease,and *** previous research has explored the detrimental health effects of tobacco smoking,recent studies suggest that gut microbiota dysbiosis may play a critical role in these *** tobacco smoke components,such as nicotine,are found in the gastrointestinal tract and interact with gut microbiota,leading to lasting impacts on host health and *** review delves into the ways tobacco smoking and its various constituents influence gut microbiota composition and *** also summarize recent advancements in understanding how tobacco smoking-induced gut microbiota dysbiosis affects host ***,this review introduces a novel perspective on how changes in gut microbiota following smoking cessation may contribute to withdrawal syndrome and the degree of health improvements in smokers.

关键词： tobacco smoking gut microbiota dysbiosis nicotine smoking cessation

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Effect of mycobacteriophage to intracellular mycobateria in vitro

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Chinese Medical Journal 2006年第8期119卷 692-695页

作者： PENG Li CHEN Bao-wen LUO Yong-ai WANG Guo-zhi Department of pulmonary disease First Affiliated Hospital of Chongqing University of Medical Sciences Chongqing 400016 China National institute for the Control of Pharmaceutical and Biological Products Beijing 100020 China

Mycobacterium tuberculosis （ M. tuberculosis） is a pathogen associated with the deaths of millions of people worldwide annually. Although tuberculosis is a treatable disease, the emergence and increasing prevalence of multi-drug resistant bacterial pathogens emphasizes the need for new and innovative anti-microbial strategies. Effective therapeutic regimens, which have existed, are limited by the emergence of drug resistance and the inability of antibiotics to kill dormant or intracellular organisms.

关键词： mycobacterium mycobacteriophage D29 macrophage infection phagocyte

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Effects of traditional Chinese medicine on treatment outcomes in severe COVID-19 patients:a single-centre study

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Chinese Journal of Natural Medicines 2024年第1期22卷 89-96页

作者： XIAO Yongjiu LI Binbin LIU Chang HUANG Xiuyu MA Ling QIAN Zhirong ZHANG Xiaopeng ZHANG Qian LI Dunqing CAI Xiaoqing YAN Xiangyong LUO Shuping XIANG Dawei XIAO Kun Emergency Department the 940th Hospital of Jiont Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Scientific Research Center the Seventh Affiliated HospitalSun Yat-sen UniversityShenzhen 518000China School of Medicine Nankai universityTianjin 300000China Department of Cardiology the 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Department of Radiation Oncology Fujian Medical University Union HospitalFuzhou 350000China Department of Traditional Chinese Medicine the 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Department of Geriatric diseases the Seventh Medical Center of Chinese PLA General HospitalBeijing 100700China Health and Sport Administration Muskingum UniversityOhioanUSA Laboratory of Vaccine and Antibody Engineering Beijing Institute of BiotechnologyBeijing 100071China Department of pulmonary and Critical Care Medicine the 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Center of pulmonary&Critical Care Medicine Chinese People’s Liberation Army(PLA)General HospitalBeijing 100853China

As the search for effective treatments for COVID-19 continues,the high mortality rate among critically ill patients in Intensive Care Units(ICU)presents a profound *** study explores the potential benefits of traditional Chinese medicine(TCM)as a supplementary treatment for severe COVID-19.A total of 110 critically ill COVID-19 patients at the Intensive Care Unit(ICU)of Vulcan Hill Hospital between Feb.,2020,and April,2020(Wuhan,China)participated in this observational *** patients received standard supportive care protocols,with a subset of 81 also receiving TCM as an adjunct *** characteristics during the treatment period and the clinical outcome of each patient were closely monitored and *** findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group(16 of 81 vs 24 of 29;0.3 vs 2.3 person/month).In the adjusted Cox proportional hazards models,TCM treatment was associated with improved survival odds(P<0.001).Furthermore,the analysis also revealed that TCM treatment could partially mitigate inflammatory responses,as evidenced by the reduced levels of proinflammatory cytokines,and contribute to the recovery of multiple organic functions,thereby potentially increasing the survival rate of critically ill COVID-19 patients.

关键词： COVID-19 Pneumonia Novel coronavirus Critically ill Traditional Chinese medicine Clinical outcome

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Effects of Nω-nitro-L-arginine methyl ester and aminoguanidine on lipopolysaccharide-induced airway hyperresponsiveness in guinea pigs

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Chinese Medical Journal 2008年第17期121卷 1693-1697页

作者： JIANG Hong-ni QU Jie-ming HE Li-xian CHEN Xue-hua PAN Jue LI Li ZHU Da-nian CAO Yin-xiang SHEN Lin-lin Department of pulmonary Medicine Research Institute of Respiratory Disease Zhongshan Hospital Fudan University Shanghai 200032 China Department of pulmonary Medicine Huadong Hospital FudanUniversity Shanghai 200040 China Department of Physiology and Pathophysiology Medical Collegeof Fudan University Shanghai 200032 China

Background The down-regulation of constitutive nitric oxide synthase （cNOS） and up-regulation of inducible nitric oxide synthase （iNOS） are associated with the allergen-provocated airway hyperresponsiveness （AHR）. This study aimed to determine whether their alteration also plays an important role in the AHR induced by lipopolysaccharide （LPS）. Methods Hartley male guinea pigs, weighing between 250 g and 350 g, were injected with LPS at a dose of 1 mg/kg every 24 hours for three days. A non-selective NOS inhibitor, N^-nitro-L-arginine methyl ester （L-NAME）, or a selective inducible NOS inhibitor, aminoguanidine （AG）, were used thirty minutes before each injection of LPS. Airway reactions, nitric oxide （NO） production and inflammatory changes were detected 24 hours after the last dose of LPS. Results AG significantly decreased the NO production in the bronchoalveolar lavage fluid （BALF） and sharply reduced the intensity of bronchoconstdction to histamine challenge. L-NAME also significantly decreased the NO production in the BALF, but had no effect on airway reactions or, perhaps, a tendency to enhance the intensity of AHR. Conclusions The data suggest that inducible NOS contributes to the AHR induced by repetitive intraperitoneal LPS, and constitutive NOS was also involved.

关键词： airway hyperresponsiveness lipopolysaccharide nitric oxide nitric oxide synthase

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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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Genomic correlates of the response to first-line PD-1 blockade plus chemotherapy in patients with advanced non-small-cell lung cancer

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中华医学杂志(英文版) 2024年第18期

作者： Jiang Tao Chen Jian Wang Haowei Wu Fengying Chen Xiaoxia Su Chunxia Zhang Haiping Zhou Fei Yang Ying Zhang Jiao Sun Huaibo Zhang Henghui Zhou Caicun Ren Shengxiang Department of Medical Oncology Shanghai Pulmonary Hospital &amp Thoracic Cancer institute Tongji University School of Medicine Shanghai China Department of Thoracic Surgery Shanghai Pulmonary Hospital &amp Genecast Biotechnology Co. Ltd Wuxi Jiangsu China Biomedical Innovation Center Beijing Shijitan Hospital Capital Medical University Beijing China School of Oncology Capital Medical University Beijing China

Background: Programmed death 1 (PD-1) blockade plus chemotherapy has become the new first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC). Yet not all NSCLC patients benefit from this regimen. This study aimed to investigate the predictors of PD-1 blockade plus chemotherapy in untreated advanced ***: We integrated clinical, genomic, and survival data from 287 patients with untreated advanced NSCLC who were enrolled in one of five registered phase 3 trials and received PD-1 blockade plus chemotherapy or chemotherapy alone. We randomly assigned these patients into a discovery cohort (n = 125), a validation cohort (n = 82), and a control cohort (n = 80). The candidate genes that could predict the response to PD-1 blockade plus chemotherapy were identified using data from the discovery cohort and their predictive values were then evaluated in the three cohorts. Immune deconvolution was conducted using transcriptome data of 1014 NSCLC patients from The Cancer Genome Atlas ***: A genomic variation signature, in which one or more of the 15 candidate genes were altered, was correlated with significantly inferior response rates and survival outcomes in patients treated with first-line PD-1 blockade plus chemotherapy in both discovery and validation cohorts. Its predictive value held in multivariate analyses when adjusted for baseline parameters, programmed cell death ligand 1 (PD-L1) expression level, and tumor mutation burden. Moreover, applying both the 15-gene panel and PD-L1 expression level produced better performance than either alone in predicting benefit from this treatment combination. Immune landscape analyses revealed that tumors with one or more variation in the 15-gene panel were associated with few immune infiltrates, indicating an immune-desert tumor ***: These findings indicate that a 15-gene panel can serve as a negative prediction biomarker for first-line PD-1 blockade plus ch

关键词： Non-small-cell lung cancer (NSCLC) Programmed death 1 (PD-1) blockade Gene panel Prediction Biomarker

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Effect of low-molecular-weight heparin and urokinase on pulmonary arteries involved in pulmonary embolism

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Chinese Medical Journal 2013年第12期126卷 2254-2259页

作者： WU Jun-ping SUN Xin WU Qi DU Zhong-zhen LI Li WU Qian SUN Hong-fen Graduate School of Tianjin Medical University Tianjin 300070 China Division of pulmonary and Critical Care Medicine Duke University Medical Center Durham NC27710 USA Division of pulmonary Medicine Tianjin Haihe Hospital Tianjin 300350 China Tianjin institute of Respiratory disease Tianjin 300350 China

Background Recent studies have shown that T helper type-2 （Th2） cells can induce the apoptosis of CD4＋CD25＋ Treg cells or resist the immunosuppressive effect of Treg *** hypothesize that an imbalance of Th2/Treg is present in patients with allergic *** Twenty-two patients with mild asthma,17 patients with moderate to severe asthma,and 20 healthy donors were *** patients were allergic to house dust *** proportion of peripheral blood CD4＋CD25＋ Treg cells and Th2 cells were determined by flow *** concentration of interleukin （IL）-10,transforming growth factor （TGF）-β and IL-4 in plasma was determined by enzyme linked immunosorbent *** these subjects,peripheral blood mononuclear cells from 17 mild asthmatic patients,13 moderate to severe asthmatic patients and 14 healthy donors were acquired and expression of forkhead box P3 （Foxp3） and GATA-3 mRNA was detected by reverse-transcriptase polymerase chain *** Compared with healthy donors and patients with mild asthma,the percent of CD4＋CD25＋ Treg cells and plasma IL-10 levels were decreased in patients with moderate to severe *** were no significant differences in Foxp3 mRNA expression among three groups,but a downward trend seen among patients with ***,the percent of Th2 cells,IL-4 levels and expression of GATA-3 mRNA was markedly higher in patients with mild and moderate to severe asthma than in the control *** ratio of Th2/Treg and their cytokines was increased in allergic asthma,especially for moderate to severe *** ratio of GATA-3/Foxp3 mRNA was also increased in allergic *** patients with moderate to severe asthma,the percentage of peripheral blood Treg cells was negatively correlated to the percentage of Th2 cells and IL-4 *** The decline of CD4＋CD25＋ Treg cells in patients with moderate to severe asthma may play an important role in progress of the ***,the deficiency of CD4＋CD25＋ Treg cel

关键词： pulmonary embolism low-molecular-weight heparin urokinase interleukin-β transforming growth factor-β monocyte chemoattractant protein-1

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Comparison of the early curative effect in patients undergoing mechanical vs. bioprosthetic aortic valve replacement with concomitant annuloplasty by the Nicks procedure

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South China Journal of Cardiology 2024年第1期25卷 29-37页

作者：吴浩向鸿谟王露朱平 Guangdong Cardiovascular institute Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510100China Guangdong Provincial Key Laboratory of Pathogenesis Targeted Prevention and Treatment of Heart DiseaseGuangzhou Key Laboratory of Cardiac Pathogenesis and PreventionGuangzhouGuangdong 510100China

Background The probability of prosthesis-patient mismatch(PPM)is high in aortic valve replacement surgery for small aortic valve annulus,which increases the postoperative prosthetic valve transvalvular pressure *** aortic annuloplasty is a commonly applied surgical procedure,but there is currently no uniform standard or guideline on the type of prosthetic valve that should be used during ***,this study aimed to analyze whether there was any difference in the short-term prognosis between the choice of mechanical valves and bioprosthetic valves during aortic valve replacement surgery with concomitant aortic annuloplasty by the Nicks *** A retrospective analysis was conducted based on the clinical data from 55 patients undergoing aortic valve replacement surgery with concomitant annuloplasty by the Nicks procedure at the Cardiac Surgery Department of Guangdong Provincial People’s Hospital from November 2021 to December *** this study,all patients received aortic annuloplasty by the Nicks *** these patients,30 were in the mechanical valve group,while the other 25 were in the bioprosthetic valve *** including left ventricular end-diastolic/endsystolic diameters,left ventricular ejection fraction,interventricular septal thickness,left ventricular posterior wall thickness,transvalvular pressure gradient,left ventricular fractional shortening,and left ventricular mass index were collected 1 week preoperatively and 1 week and 3 months *** on gender,age,body surface area,types of perioperative complications,operation time,complication rates,and outcomes was also *** Among the 55 patients enrolled in this study,4 *** main causes of death included postoperative low cardiac output syndrome,severe pulmonary infection,and multi-organ ***,there was a statistically significant difference in left ventricular end-diastolic diameter between the mechanical valv

关键词： Valve replacement Small aortic annulus Nicks procedure Prosthesis-patient mismatch Mechani-cal valve Bioprosthetic valve

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GRK2-YAP signaling is implicated in pulmonary arterial hypertension development

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Chinese Medical Journal 2024年第7期137卷 846-858页

作者： Peng Ye Yunfei Deng Yue Gu Pengfei Liu Jie Luo Jiangqin Pu Jingyu Chen Yu Huang Nanping Wang Yong Ji Shaoliang Chen Division of Cardiovascular Molecular Laboratory Third Clinical CollegeNanjing Medical UniversityNanjingJiangsu 210006China Division of Cardiovascular Laboratory Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu 210006China Division of Cardiology Shanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200080China Division of pulmonary Surgery Wuxi People’s HospitalNanjing Medical UniversityWuxiJiangsu 300247China institute of Vascular Medicine The Chinese University of Hong KongHongkong 999077China Health Science Center East China Normal UniversityShanghai 200241China School of Pharmacy Nanjing Medical UniversityNanjingJiangsu 210004China Division of Cardiology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu 210006China

Background:pulmonary arterial hypertension(PAH)is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells(PASMCs),endothelial dysfunction,and extracellular matrix remodeling.G protein-coupled receptor kinase 2(GRK2)plays an important role in the maintenance of vascular tone and blood ***,the role of GRK2 in the pathogenesis of PAH is ***:GRK2 levels were detected in lung tissues from healthy people and PAH patients.C57BL/6 mice,vascular smooth muscle cell-specific Grk2-knockout mice(Grk2^(∆SM22)),and littermate controls(Grk2^(flox/flox))were grouped into control and hypoxia mice(n=8).pulmonary hypertension(PH)was induced by exposure to chronic hypoxia(10%)combined with injection of the SU5416(cHx/SU).The expression levels of GRK2 and Yes-associated protein(YAP)in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence *** mRNA expression levels of Grk2 and Yes-associated protein(YAP)in PASMCs were quantified with real-time polymerase chain reaction(RT-PCR).Wound-healing assay,3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT)assay,and 5-Ethynyl-2′-deoxyuridine(EdU)staining were performed to evaluate the proliferation and migration of ***,the interaction among proteins was detected by immunoprecipitation ***:The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH ***,cHx/SU-induced PH was attenuated in Grk2^(∆SM22) mice compared with littermate *** amelioration of PH in Grk2^(∆SM22) mice was accompanied by reduced pulmonary vascular *** vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration,whereas this effect was severely intensified by overexpression of *** also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs,resulting in excessive PA

关键词： pulmonary arterial hypertension GRK2 YAP pulmonary artery smooth muscle cell Hypoxia

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