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Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Signal Transduction and Targeted Therapy 2024年第1期9卷 105-149页

作者： Yumin Wang Jing Hu Shuang Wu Joshua S.Fleishman Yulin Li Yinshi Xu Wailong Zou Jinhua Wang Yukuan Feng Jichao Chen Hongquan Wang department of respiratory and critical care Medicine Aerospace Center HospitalPeking University Aerospace School of Clinical MedicineBeijing 100049PR China department of Pathogen Biology School of Basic Medical SciencesTianjin Medical UniversityTianjin 300060PR China department of Neurology Zhongnan Hospital of Wuhan UniversityWuhan 430000PR China department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNY 11439USA department of Outpatient Aerospace Center HospitalPeking University Aerospace School of Clinical MedicineBeijing 100049PR China Beijing Key Laboratory of Drug Target and Screening Research Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050PR China department of Pancreatic Cancer Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060PR China

Ferroptosis,a unique modality of cell death with mechanistic and morphological differences from other cell death modes,plays a pivotal role in regulating tumorigenesis and offers a new opportunity for modulating anticancer drug *** epigenetic modifications and posttranslational modifications(PTMs)promote anticancer drug resistance,cancer progression,and *** studies indicate that epigenetic modifications can transcriptionally and translationally determine cancer cell vulnerability to ferroptosis and that ferroptosis functions as a driver in nervous system diseases(NSDs),cardiovascular diseases(CVDs),liver diseases,lung diseases,and kidney *** this review,we first summarize the core molecular mechanisms of ***,the roles of epigenetic processes,including histone PTMs,DNA methylation,and noncoding RNA regulation and PTMs,such as phosphorylation,ubiquitination,SUMOylation,acetylation,methylation,and ADP-ribosylation,are concisely *** roles of epigenetic modifications and PTMs in ferroptosis regulation in the genesis of diseases,including cancers,NSD,CVDs,liver diseases,lung diseases,and kidney diseases,as well as the application of epigenetic and PTM modulators in the therapy of these diseases,are then discussed in *** the mechanisms of ferroptosis regulation mediated by epigenetic modifications and PTMs in cancer and other diseases will facilitate the development of promising combination therapeutic regimens containing epigenetic or PTM-targeting agents and ferroptosis inducers that can be used to overcome chemotherapeutic resistance in cancer and could be used to prevent other *** addition,these mechanisms highlight potential therapeutic approaches to overcome chemoresistance in cancer or halt the genesis of other diseases.

关键词： diseases epigenetic overcome

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Prediction of sepsis within 24 hours at the triage stage in emergency departments using machine learning

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World Journal of Emergency Medicine 2024年第5期15卷 379-385页

作者： Jingyuan Xie Jiandong Gao Mutian Yang Ting Zhang Yecheng Liu Yutong Chen Zetong Liu Qimin Mei Zhimao Li Huadong Zhu Ji Wu department of Electronic Engineering Tsinghua UniversityBeijing 100084China Center for Big Data and Clinical Research Institute for Precision MedicineTsinghua UniversityBeijing 100084China Institute of Medical Technology Peking University Health Science CenterBeijing 100091China Emergency department State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100005China department of Health care Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China

BACKGROUND:Sepsis is one of the main causes of mortality in intensive care units(ICUs).Early prediction is critical for reducing *** approximately 36%of sepsis occur within 24 h after emergency department(ED)admission in Medical Information Mart for Intensive care(MIMIC-IV),a prediction system for the ED triage stage would be *** methods such as the quick Sequential Organ Failure Assessment(qSOFA)are more suitable for screening than for prediction in the ED,and we aimed to fi nd a light-weight,convenient prediction method through machine ***:We accessed the MIMIC-IV for sepsis patient data in the *** dataset comprised demographic information,vital signs,and synthetic *** Gradient Boosting(XGBoost)was used to predict the risk of developing sepsis within 24 h after ED ***,SHapley Additive exPlanations(SHAP)was employed to provide a comprehensive interpretation of the model's *** percent of the patients were randomly selected as the testing set,while the remaining patients were used for training with 10-fold ***:For 10-fold cross-validation on 14,957 samples,we reached an accuracy of 84.1%±0.3%and an area under the receiver operating characteristic(ROC)curve of 0.92±*** model achieved similar performance on the testing set of 1,662 *** values showed that the fi ve most important features were acuity,arrival transportation,age,shock index,and respiratory ***:Machine learning models such as XGBoost may be used for sepsis prediction using only a small amount of data conveniently collected in the ED triage *** may help reduce workload in the ED and warn medical workers against the risk of sepsis in advance.

关键词： Sepsis Machine learning Emergency department Triage Informatics

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Risk factors for intracranial hemorrhage and mortality in adult patients with severe respiratory failure managed using veno-venous extracorporeal membrane oxygenation

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Chinese Medical Journal 2022年第1期135卷 36-41页

作者： Xiaojing Wu Min Li Ying Cai Tianshu Zhai Yi Zhang Qingyuan Zhan Sichao Gu department of Pulmonary and critical care Medicine Center for Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China National Clinical Research Center for respiratory diseases Beijing 100029China

Background: Intracerebral hemorrhage (ICH) is one of the most severe complications during veno-venous extracorporeal membrane oxygenation (VV-ECMO). This study aimed to determine the risk factors for ICH and mortality in such ***: We analyzed the clinical data of 77 patients who received VV-ECMO due to severe respiratory failure from July 2013 to May 2019 at China-Japan Friendship Hospital. Demographical data, laboratory indices, imaging characteristics, and other clinical information were collected. Multivariable logistic regression analyses were performed to identify risk factors for ICH and ***: Of 77 patients, 11 (14.3%) suffered from ICH, and 36 (46.8%) survived. The survival rate was significantly lower (18.2% [2/11]vs. 51.5% [34/66],P = 0.040) in patients with ICH than in those without ICH. Multivariable analysis revealed that factors independently associated with ICH were diabetes mellitus (adjusted odds ratio [aOR]: 12.848, 95% confidence interval [CI]: 1.129-146.188,P = 0.040) and minimum fibrinogen during ECMO (aOR: 2.557, 95% CI: 1.244-5.252,P = 0.011). Multivariable analysis showed that factors independently associated with mortality were acute hepatic failure during ECMO (aOR: 9.205, 95% CI: 1.375-61.604,P = 0.022), CO2 retention before ECMO (aOR: 7.602, 95% CI: 1.514-38.188,P = 0.014), and minimum platelet concentration during ECMO (aOR: 0.130, 95% CI: 0.029-0.577,P = 0.007).Conclusions: Diabetes mellitus and minimum fibrinogen concentration during ECMO are risk factors for ICH in patients with severe respiratory failure managed using VV-ECMO. This indicated that anticoagulants use and nervous system monitoring should be performed more carefully in patients with diabetes when treated with VV-ECMO due to severe respiratory failure.

关键词： Veno-venous extracorporeal membrane oxygenation Severe respiratory failure Intracranial hemorrhage Mortality Risk factors

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Novel mutations in RSPH4A and TTN genes lead to primary ciliary dyskinesia-hereditary myopathy with early respiratory failure overlap syndrome

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Genes & diseases 2023年第3期10卷 743-745页

作者： Mengjie Feng Xiu Yu Yongjian Yue Jiacheng Zhong Lingwei Wang department of respiratory and critical care Medicine Shenzhen Key Laboratory of Respiratory DiseasesShenzhen Respiratory Disease Prevention CenterShenzhen Institute of Respiratory DiseasesShenzhen People's Hospital(Second Clinical Medical College of Jinan University&First Affiliated Hospital of Southern University of Science and Technology)ShenzhenGuangdong 518020China

Primary ciliary dyskinesia(PCD)is an autosomal recessive disease caused by defects in motile cilia and clinically characterized by bronchiectasis,situs inversus,nasosinusitis,recurrent respiratory infections,tympanitis,and/or male *** PCD,impaired function or structure of motile cilia leads to abnormality of mucociliary clearance。

关键词： respiratory impaired Primary

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Venopulmonary ECMO Improved Hypoxemia and Supported the Right Ventricle in a Patient with Decompensated Eisenmenger Syndrome

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World Journal of Cardiovascular Surgery 2024年第1期14卷 7-19页

作者： Daniel Manzur-Sandoval Gian Manuel Jiménez-Rodríguez Edgar García-Cruz Ramón Espinosa-Soto Erika Yamali Ramirez-Marcano Yessenia Máyory Téllez-López José Luis Elizalde-Silva Gustavo Rojas-Velasco Cardiovascular critical care unit Ignacio Ch&#225vez National Institute of Cardiology Mexico City Mexico Adult Congenital Heart Disease unit Ignacio Ch&#225vez National Institute of Cardiology Mexico City Mexico Cardiology department Ignacio Ch&#225vez National Institute of Cardiology Mexico City Mexico

Mechanical circulatory and/or respiratory assistance with extracorporeal membrane oxygenation (ECMO) has become a standard of care for patients with circulatory (venoarterial) and/or respiratory (venovenous) failure refractory to standard therapies. Adult patients with congenital heart disease are an increasingly recognized and growing population and include various groups, such as undiagnosed cases in childhood and palliated and/or corrected cases, which require subsequent care because of residual lesions, cardiac arrest/insufficiency, and arrhythmias, among other conditions. In addition, these patients are prone to developing pathologies that are typical of adulthood with a generally increased risk of morbidity and mortality because of their low reserves and organic damage associated with the underlying heart disease, which makes them candidates for ECMO. These patients represent an additional challenge in this therapy because malformations and the presence of a shunt can generally affect the usual cannulation methods and hemodynamic and oximetry monitoring. Thus, the configuration decision must be made on a case-by-case basis. Here, we present a cannulation method, venopulmonary artery ECMO, which provides hemodynamic and respiratory support, and may be ideal for patients with shunts and/or right ventricular dysfunction. To our knowledge, this is the first report of this configuration in patients with congenital heart diseases.

关键词： Eisenmenger Syndrome Venopulmonary Artery ECMO Refractory Hypoxemia Right Ventricular Dysfunction

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Two methods of lung biopsy for histological confirmation of acute fibrinous and organizing pneumonia:A case report

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World Journal of Clinical Cases 2022年第36期10卷 13381-13387页

作者： Wen-Juan Liu Shuang Zhou Yan-Xia Li department of respiratory and critical care Medicine Institute of Respiratory DiseasesThe First Affiliated Hospital of Dalian Medical UniversityDalian 116011Liaoning ProvinceChina department of Internal Medicine Dalian Medical UniversityDalian 116044Liaoning ProvinceChina

BACKGROUND Acute fibrinous and organizing pneumonia(AFOP)is a rare,noninfective lung disease,histologically characterized by a patchy distribution of intra-alveolar fibrin“balls”and organizing *** clinical manifestations of AFOP are *** depends on *** lung biopsy is optimal for tissue sampling to diagnose ***,many patients have no tolerance to the operation,including mentally and *** is still no standard therapy for AFOP and the methods remain ***,further clinical attention and discussion are *** SUMMARY A 53-year-old woman presented with fever,cough and dyspnea for 15 *** therapy was *** computed tomography showed bilateral patchy consolidation,especially in the lower *** performed both ultrasound-guided transbronchial lung biopsy and ultrasound-guided percutaneous fine needle puncture at different lung lesion *** samples supported the diagnosis of *** patient had a good clinical course after treatment with methylprednisolone,and no side effects of *** Percutaneous needle biopsy combined with transbronchial lung biopsies may be a good choice in the absence of surgical *** alone is effective in the treatment of idiopathic AFOP.

关键词： Acute fibrinous and organizing pneumonia Fibrin balls Percutaneous needle biopsy Transbronchial lung biopsies Methylprednisolone Case report

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Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis:An exploratory randomized controlled trial

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Journal of Integrative Medicine 2023年第6期21卷 543-549页

作者： Jian-sheng Li Hai-long Zhang Wen Guo Lu Wang Dong Zhang Li-min Zhao Miao Zhou Co-construction Collaborative Innovation Center for Chinese Medicine and respiratory diseases by Henan&Education Ministry of China Henan Key Laboratory of Chinese Medicine for Respiratory DiseasesHenan University of Chinese MedicineZhengzhou 450046Henan ProvinceChina respiratory department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou 450000Henan ProvinceChina department of respiratory and critical care Medicine Henan Provincial People’s HospitalZhengzhou 463599Henan ProvinceChina respiratory department the Third Affiliated Hospital of Henan University of Chinese MedicineZhengzhou 450003Henan ProvinceChina

Background:Acute exacerbation of idiopathic pulmonary fibrosis(AE-IPF)is an important occurrence in the natural history of idiopathic pulmonary fibrosis(IPF),associated with high hospitalization rates,high mortality and poor *** present,there is no effective treatment for *** herbal medicine has some advantages in treating IPF,but its utility in AE-IPF is ***:The treatment of AE-IPF with Kangxian Huanji Granule(KXHJ),a compound Chinese herbal medicine,lacks an evidence-based *** study explores the efficacy and safety of KXHJ in patients with ***,setting,participants and interventions:Wedesigned a randomized,double-blind,placebo-controlled,exploratory clinical trial.A total of 80 participants diagnosed with AE-IPF were randomly assigned to receive KXHJ or a matching placebo;the treatment included a 10 g dose,administered twice daily for 4 weeks,in addition to conventional *** were followed up for 12 weeks after the *** outcome measures:The primary endpoints were treatment failure rate and all-cause *** endpoints included the length of hospitalization,overall survival,acute exacerbation rate,intubation rate,the modified British Medical Research Council(mMRC)score,and the St George’s respiratory Questionnaire for IPF(SGRQ-I)***:The rate of treatment failure at 4 weeks was lower in the intervention groupcompared to the control group(risk ratio[RR]:0.22;95%confidence interval[CI]:0.051 to 0.965,P=0.023).There was no significant difference in all-causemortality at 16 weeks(RR:0.75;95%CI:0.179 to 3.138;P>0.999)or in the acute exacerbation rate during the 12-week follow-up period(RR:0.69;95%CI:0.334 to 1.434;P=0.317).The intervention group had a shorter length of hospitalization than the control group(mean difference[MD]:–3.30 days;95%CI,–6.300 to–0.300;P=0.032).Significant differences in the mean change from baseline in the mMRC(between-group difference:–0.67;

关键词： Idiopathic pulmonary fibrosis Acute exacerbation Chinese herbal medicine Integrative medicine Randomized controlled trial

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Long-term outcomes in COVID-19 patients who recovered from the first wave of the pandemic

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National Science Review 2022年第11期9卷 87-96页

作者： Dan Cui Simiao Chen Luzhao Feng Mengmeng Jia Yeming Wang Weijun Xiao Yanxia Sun Qiangru Huang Libing Ma Zhiwei Leng Hao Wang Bin Cao Weizhong Yang Juntao Yang Chen Wang department of Pulmonary and critical care Medicine The Second Affiliated Hospital of Harbin Medical UniversityHarbin Medical University department of Pulmonary and critical care Medicine National Center for Respiratory Medicine Center of Respiratory MedicineNational Clinical Research Center for Respiratory Diseases China-Japan Friendship Hospital Heidelberg Institute of Global Health Faculty of Medicine and University Hospital Heidelberg University School of Population Medicine and Public Health Chinese Academy of Medical Sciences &Peking Union Medical College department of respiratory and critical care Medicine the Affiliated Hospital of Guilin Medical University Institute of respiratory Medicine Chinese Academy of Medical Science State Key Laboratory of Medical Molecular Biology Department of Biochemistry and Molecular BiologyInstitute of Basic Medical Sciences Chinese Academy of Medical Sciences & Peking Union Medical College

This cross-sectional study evaluated the long-term health effects of coronavirus disease 2019(COVID-19)in Jianghan District(Wuhan, China). The results showed that 61.4% of COVID-19 patients reported at least one symptom and 8.8% had depressive symptoms at the 17-month follow-up. The proportion of patients with chest radiographic abnormalities in Fangcang shelter hospitals and designated COVID-19hospitals was 31.6% and 41.1%, respectively, and the proportion of patients with impaired pulmonary diffusion capacity in these hospitals was 52.8% and 60.9%, respectively. Female sex(odds ratio[OR] = 1.48, 95% confidence interval [CI]: 1.16–1.88), severe disease(OR = 1.46, 95% CI: 1.01–2.10)and a higher number of initial symptoms(OR = 1.31, 95% CI: 1.23–1.40) were associated with the development of sequelae symptoms at 17 months. This study involving community-dwelling COVID-19adults may help determine the long-term effects of COVID-19 during the first pandemic ***, larger follow-up studies are needed to characterize the post-COVID-19 condition.

关键词： SARS-CoV-2 post-COVID-19 syndrome follow-up studies

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Response to dacomitinib in advanced non-small-cell lung cancer harboring the rare delE709_T710insD mutation:A case report

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World Journal of Clinical Cases 2022年第17期10卷 5916-5922页

作者： Fei Xu Meng-Ling Xia Hui-Yun Pan Jiong-Wei Pan Yi-Hong Shen department of respiratory diseases The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina department of Day care Ward The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina department of respiratory diseases Lishui City People’s HospitalLishui 323000Zhejiang ProvinceChina

BACKGROUND Tyrosine kinase inhibitors(TKI)have been the standard first-line therapy for advanced non-small cell lung cancer(NSCLC)of epidermal growth factor receptor(EGFR)sensitive *** EGFR mutations are increasingly reported with the development of next-generation ***,their sensitivity to TKIs is variable with limited clinical *** SUMMARY Here,we report a patient with the rare delE709_T710insD mutation,who showed the favorable efficacy of dacomitinib and achieved a partial response with a progression-free survival of 7.0 *** To our knowledge,this is the first report displaying the clinical efficacy of dacomitinib for patients with delE709_T710insD,which may help to provide alternatives in non-classical variant NSCLC *** studies are warranted to make the optimal choice of EGFR-TKI for rare mutations.

关键词： Next-generation sequencing DelE709_T710insD Non-small-cell lung cancer Dacomitinib Uncommon EGFR mutation Case report

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Clinical characteristics of hypersensitivity pneumonitis:non-fibrotic and fibrotic subtypes

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Chinese Medical Journal 2023年第23期136卷 2839-2846页

作者： Xueying Chen Xiaoyan Yang Yanhong Ren Bingbing Xie Sheng Xie Ling Zhao Shiyao Wang Jing Geng Dingyuan Jiang Sa Luo Jiarui He Shi Shu Yinan Hu Lili Zhu Zhen Li Xinran Zhang Min Liu Huaping Dai department of Pulmonary and critical care Medicine Center of Respiratory MedicineChina-Japan Friendship HospitalNational Center for Respiratory MedicineNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100029China department of Pulmonary and critical care Medicine Center of Respiratory MedicineChina-Japan Friendship HospitalCapital Medical UniversityBeijing 100029China department of Radiology China-Japan Friendship HospitalBeijing 100029China department of Pathology China-Japan Friendship HospitalBeijing 100029China Institute of Clinical Medical Sciences Center of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China

Background:The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis(HP)*** present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis(NFHP)and fibrotic hypersensitivity pneumonitis(FHP)and explore factors associated with the presence of ***:In this prospective cohort study,patients diagnosed with HP through a multidisciplinary discussion were *** data included demographic and clinical characteristics,laboratory findings,and radiologic and histopathological *** regression analyses were performed to explore factors related to the presence of ***:A total of 202 patients with HP were enrolled,including 87(43.1%)NFHP patients and 115(56.9%)FHP *** with FHP were older and more frequently presented with dyspnea,crackles,and digital clubbing than patients with *** levels of carcinoembryonic antigen,carbohydrate antigen 125,carbohydrate antigen 153,gastrin-releasing peptide precursor,squamous cell carcinoma antigen,and antigen cytokeratin 21-1,and count of bronchoalveolar lavage(BAL)eosinophils were higher in the FHP group than in the NFHP *** lymphocytosis was present in both groups,but less pronounced in the FHP *** regression analyses revealed that older age,<20%of lymphocyte in BAL,and≥1.75%of eosinophil in BAL were risk factors for the development of *** patients developed adverse outcomes,with a median survival time of 12.5 months,all of whom had ***:Older age,<20%of lymphocyte in BAL,and≥1.75%of eosinophil in BAL were risk factors associated with the development of *** of patients with NFHP was better than that of patients with *** results may provide insights into the mechanisms of fibrosis in HP.

关键词： Interstitial lung disease Hypersensitivity pneumonitis Clinical characteristics Fibrosis Prognosis

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