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Chidamide,Decitabine,Cytarabine,Aclarubicin,and Granulocyte Colony-stimulating Factor Therapy for Patients with Relapsed/Refractory Acute Myeloid Leukemia:A Retrospective Study from a Single-center

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Current Medical Science 2023年第6期43卷 1151-1161页

作者： Fan-cong KONG Ling QI Yu-lan ZHOU Min YU Wen-feng HUANG Fei LI center of Hematology The First Affiliated Hospital of Nanchang UniversityNanchang330006China Jiangxi clinical research center for hematologic diseases Nanchang330006China

Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(Phematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.

关键词： relapsed/refractory acute myeloid leukemia histone deacetylase inhibitor DNA methyltransferase inhibitor salvage therapy

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Association between clustering of cardiovascular risk factors and resting heart rate in Chinese population:a cross-sectional study

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Journal of Geriatric Cardiology 2022年第6期19卷 418-427页

作者： Fu-Yu JING Xiu-Ling WANG Jia-Li SONG Yan GAO Jian-Lan CUI Wei XU Yang YANG Li-Juan SONG Hai-Bo ZHANG Jia-Peng LU Xi LI Xin ZHENG national clinical research center for Cardiovascular diseases NHC Key Laboratory of Clinical Research for Cardiovascular MedicationsState Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Center for Cardiovascular DiseasesBeijingChina national clinical research center for Cardiovascular diseases ShenzhenCoronary Artery Disease CenterFuwai Hospital Chinese Academy of Medical SciencesShenzhenChina

BACKGROUND Epidemiologic studies have explored the association between a single cardiovascular risk factor(CVRF)and resting heart rate(RHR),but the research on the relation of multiple risk factors with RHR remains scarce.This study aimed to explore the associations between CVRFs clustering and the risk of elevated RHR.METHODS In this cross-sectional study,adults aged 35-75 years from 31 provinces were recruited by the China PEACE Million Persons Projects from September 2015 to August 2020.We focused on seven risk factors:hypertension,diabetes mellitus,dyslipidemia,obesity,smoking,alcohol use,and low physical activity.Multivariate logistic regression was used to calculate odds ratios(OR)for elevated RHR(>80 beats/min).RESULTS Among 1,045,405 participants,the mean age was 55.67±9.86 years,and 60.4%of participants were women.The OR(95%CI)for elevated RHR for the groups with 1,2,3,4 and≥5 risk factor were 1.11(1.08-1.13),1.36(1.33-1.39),1.68(1.64-1.72),2.01(1.96-2.07)and 2.58(2.50-2.67),respectively(Ptrend<0.001).The association between the CVRFs clustering number and elevated RHR was much more pronounced in young males than in other age-sex subgroups.Clusters comprising more metabolic risk factors were associated with a higher risk of elevated RHR than those comprising more behavioral risk factors.CONCLUSIONS There was a significant positive association between the CVRFs clustering number and the risk of elevated RHR,particularly in young males.Compared clusters comprising more behavioral risk factors,clusters comprising more metabolic risk factors were associated with a higher risk of elevated RHR.RHR may serve as an indicator of the cumulative effect of multiple risk factors.

关键词： elevated cardiovascular sectional

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Blood pressure targets in patients with chronic kidney disease:Comments and controversies

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Chinese Medical Journal 2024年第3期137卷 270-272页

作者： Ying Zheng Guangyan Cai Xiangmei Chen Department of Nephrology First Medical Center of Chinese PLA General HospitalNational Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchBeijing 100853China

According to the Global Burden of Disease Study 2017,there are 132 million patients with chronic kidney disease(CKD)in China,^([1])and the prevalence of hypertension in Chinese patients with CKD(67.3%)is significantly higher than that in the general population(23.2%).^([2,3])CKD is both a cause and a consequence of hypertension,and these two conditions form a vicious cycle that leads to the high prevalence rate of hypertension in patients with CKD.Uncontrolled hypertension accelerates the deterioration of renal function,which significantly increases the risk of developing end-stage renal disease(ESRD),as well as cardiovascular and cerebrovascular diseases,leading to poor patient outcomes.

关键词： patients Blood hypertension

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China Stroke Statistics 2019:A Report From the national center for Healthcare Quality Management in Neurological diseases,China national clinical research center for Neurological diseases,the Chinese Stroke Association,national center for Chronic and Non-communicable Disease Control and Prevention,Chinese center for Disease Control and Prevention and Institute for Global Neuroscience and Stroke Collaborations

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Stroke & Vascular Neurology 2020年第3期5卷 211-239页

作者： Yong-Jun Wang Zi-Xiao Li Hong-Qiu Gu Yi Zhai Yong Jiang Xing-Quan Zhao Yi-Long Wang Xin Yang Chun-Juan Wang Xia Meng Hao Li Li-Ping Liu Jing Jing Jing Wu An-Ding Xu Qiang Dong David Wang Ji-Zong Zhao On behalf of China Stroke Statistics 2019 Writing Committee China national clinical research center for Neurological diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina national center for Healthcare Quality Management in Neurological diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina national center for Chronic and Non-communicable Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijingChina Department of Neurology and Stroke center The First Affiliated HospitalJinan UniversityGuangzhouGuangdongChina Department of Neurology Huashan HospitalFudan UniversityShanghaiChina Neurovascular Division Department of NeurologyBarrow Neurological InstituteSt.Joseph's Hospital and Medical CenterPhoenixArizonaUSA 不详

China faces the greatest challenge from stroke in the world.The death rate for cerebrovascular diseases in China was 149.49 per 100000,accounting for 1.57 million deaths in 2018.It ranked third among the leading causes of death behind malignant tumours and heart disease.The age-standardised prevalence and incidence of stroke in 2013 were 1114.8 per 100000 population and 246.8 per 100000 person-years,respectively.According to the Global Burden of Disease Study 2017,the years of life lost(YLLs)per 100000 population for stroke increased by 14.6%;YLLs due to stroke rose from third highest among all causes in 1990 to the highest in 2017.The absolute numbers and rates per 100000 population for all-age disability-adjusted life years(DALYs)for stroke increased substantially between 1990 and 2017,and stroke was the leading cause of all-age DALYs in 2017.The main contributors to cerebrovascular diseases include behavioural risk factors(smoking and alcohol use)and pre-existing conditions(hypertension,diabetes mellitus,dyslipidaemia and atrial fibrillation(AF)).The most prevalent risk factors among stroke survivors were hypertension(63.0%-84.2%)and smoking(31.7%-47.6%).The least prevalent was AF(2.7%-7.4%).The prevalences for major risk factors for stroke are high and most have increased over time.Based on the latest national epidemiological data,26.6%of adults aged≥15 years(307.6 million adults)smoked tobacco products.For those aged≥18 years,age-adjusted prevalence of hypertension was 25.2%;adjusted prevalence of hypercholesterolaemia was 5.8%;and the standardised prevalence of diabetes was 10.9%.For those aged≥40 years,the standardised prevalence of AF was 2.31%.Data from the Hospital Quality Monitoring System showed that 3010204 inpatients with stroke were admitted to 1853 tertiary care hospitals during 2018.Of those,2466785(81.9%)were ischaemic strokes(ISs);447609(14.9%)were intracerebral haemorrhages(ICHs);and 95810(3.2%)were subarachnoid haemorrhages(SAHs).The average age of patients admitted was 66 years old,and nearl

关键词： admitted smoke insurance

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Impact of baseline blood pressure on all-cause mortality in patients with atrial fibrillation:results from a multicenter registry study

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Chinese Medical Journal 2023年第6期136卷 683-689页

作者： Wei Xu Qirui Song Han Zhang Juan Wang Xinghui Shao Shuang Wu Jun Zhu Jun Cai Yanmin Yang Emergency center Fuwai HospitalState Key Laboratory of Cardiovascular Disease of ChinaNational Center for Cardiovascular DiseasesNational Clinical Research Center of Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Hypertension center Fuwai HospitalState Key Laboratory of Cardiovascular Disease of ChinaNational Center for Cardiovascular Diseases of ChinaNational Clinical Research Center of Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

Background:The ideal blood pressure(BP)target for patients with atrial fibrillation(AF)is still unclear.The present study aimed to assess the effect of the baseline BP on all-cause mortality in patients with AF.Methods:This registry study included 20 emergency centers across China and consecutively enrolled patients with AF from 2008 to 2011.All participants were followed for 1 year±1 month.The primary endpoint was all-cause mortality.Results:During the follow-up,276(13.9%)all-cause deaths occurred.Kaplan-Meier curves showed that a systolic blood pressure(SBP)110 mmHg or>160 mmHg was associated with a higher risk of all-cause mortality(log-rank test,P=0.014),and a diastolic blood pressure(DBP)<70 mmHg was associated with the highest risk of all-cause mortality(log-rank test,P=0.002).After adjusting for confounders,the multivariable Cox regression model suggested that the risk of all-cause mortality was increased in the group with SBP110 mmHg(hazard ratio[HR],1.963;95%confidence interval[CI],1.306-2.951),and DBP<70 mmHg(HR,1.628;95%CI,1.163-2.281).In the restricted cubic splines,relations between baseline SBP or DBP and all-cause mortality showed J-shaped associations(non-linear P<0.001 and P=0.010,respectively).The risk of all-cause mortality notably increased at a lower baseline SBP and DBP.Conclusions:Having a baseline SBP110 mmHg or DBP<70 mmHg was associated with a significantly higher risk of all-cause mortality in patients with AF.An excessively low BP may not be an optimal target for patients with AF.

关键词： All-cause death All-cause mortality Atrial fibrillation Blood pressure Diastolic blood pressure Hypertension Systolic blood pressure

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Monkeypox outbreak: a novel threat after COVID-19?

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Military Medical research 2023年第1期10卷 137-138页

作者： Yang Zhang Ji-Yuan Zhang Fu-Sheng Wang Senior Department of Infectious diseases the Fifth Medical Center of Chinese PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijing 100039China

Dear Editor,Monkeypox is a zoonosis caused by monkeypox virus (MPXV)infection first reported in Central and West Africa[1]. The first outbreak of monkeypox outside of Africa was reported in2003[2].Afterthat,Israel,theUnitedKingdom(UK),Singapore, and other countries have reported monkeypox cases among travelers back from Nigeria since 2018[3].

关键词： Monkeypox Outbreak Zoonosis Human-to-human transmission

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Neutrophils in liver diseases:pathogenesis and therapeutic targets

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Cellular & Molecular Immunology 2021年第1期18卷 38-44页

作者： Kai Liu Fu-Sheng Wang Ruonan Xu Peking University 302 clinical Medical School BeijingChina Treatment and research center for Infectious diseases The Fifth Medical Center of PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijingChina

Previously,it was assumed that peripheral neutrophils are a homogeneous population that displays antimicrobial functions.However,recent data have revealed that neutrophils are heterogeneous and are additionally involved in tissue damage and immune regulation.The phenotypic and functional plasticity of neutrophils has been identified in patients with cancer,inflammatory disorders,infections,and other diseases.Currently,neutrophils,with their autocrine,paracrine,and immune modulation functions,have been shown to be involved in liver diseases,including viral hepatitis,nonalcoholic steatohepatitis,alcoholic liver disease,liver fibrosis,cirrhosis,liver failure,and liver cancer.Accordingly,this review summarizes the role of neutrophils in liver diseases.

关键词： Liver disease Liver injury Neutrophil Innate immunity Immunotherapy

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Current assessment and management of measurable residual disease in patients with acute lymphoblastic leukemia in the setting of CAR-T-cell therapy

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Chinese Medical Journal 2024年第2期137卷 140-151页

作者： Minghao Lin Xiaosu Zhao Yingjun Chang Xiangyu Zhao Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China

Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell therapy.Common MRD detection methods include flow cytometry(FCM),polymerase chain reaction(PCR),and next-generation sequencing(NGS),and each method has advantages and limitations.It has been well documented that MRD positivity predicts a poor prognosis and even disease relapse.Thus,how to perform prognostic evaluations,stratify risk based on MRD status,and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical practice.This review assesses the common and novel MRD assessment methods.In addition,we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation(allo-HSCT),as well as other therapeutic strategies to improve treatment effect.Furthermore,this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.

关键词： Measurable/minimal residual disease Acute lymphoblastic leukemia Chimeric antigen receptor-modified T-cell therapy Allogeneic hematopoietic stem cell transplantation Relapse

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Reverse effect of Semaphorin-3F on rituximab resistance in diffuse large B-cell lymphoma via the Hippo pathway

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Chinese Medical Journal 2023年第12期136卷 1448-1458页

作者： Qiong Li Naya Ma Xinlei Li Chao Yang Wei Zhang Jingkang Xiong Lidan Zhu Jiali Li Qin Wen Lei Gao Cheng Yang Lingyi Rao Li Gao Xi Zhang Jun Rao Medical center of Hematology Xinqiao HospitalArmy Medical UniversityChongqing 400037China State Key Laboratory of Trauma Burns and Combined InjuryArmy Medical UniversityChongqing 400037China National Clinical Research Center for Hematologic Diseases the First Affiliated Hospital of Soochow UniversitySuzhou 215123China

Background:Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma(DLBCL).Here,we tried to identify the effects of the axon guidance factor semaphorin-3F(SEMA3F)on rituximab resistance as well as its therapeutic value in DLBCL.Methods:The effects of SEMA3F on the treatment response to rituximab were investigated by gain-or loss-of-function experiments.The role of the Hippo pathway in SEMA3F-mediated activity was explored.A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects.The prognostic value of SEMA3F and TAZ(WW domain-containing transcription regulator protein 1)was examined in the Gene Expression Omnibus(GEO)database and human DLBCL specimens.Results:We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen.Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity(CDC)activity induced by rituximab.We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20.Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter.Moreover,in patients with DLBCL,SEMA3F expression was negatively correlated with TAZ,and patients with SEMA3F^(low)TAZ^(high)had a limited benefit from a rituximab-based strategy.Specifically,treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo.Conclusion:Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.

关键词： Lymphoma,large B-cell,diffuse Rituximab resistance Apoptosis WW domain-containing transcription regulator protein 1

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Long-term outcome of percutaneous or surgical revascularization with and without prior stroke in patients with threevessel disease

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Journal of Geriatric Cardiology 2022年第8期19卷 583-593页

作者： Na XU Ce ZHANG Lin JIANG Jing-Jing XU Ru LIU Ying SONG Xue-Yan ZHAO Lian-Jun XU Run-Lin GAO Bo XU Jin-Qing YUAN Lei SONG center for Coronary Heart Disease National Clinical Research Center for Cardiovascular DiseasesNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

OBJECTIVE To determine whether high-risk patients with three-vessel disease(TVD)with and without prior stroke preferen-tially benefit from three strategies[percutaneous coronary intervention(PCI),coronary artery bypass grafting(CABG)and medical therapy(MT)].METHODS A total of 8943 patients with TVD were included in the study.Patients enrolled were stratified into two categories according to the presence or absence of prior stroke history.The primary endpoint was all-cause death.Secondary endpoints in-cluded stroke and major adverse cardiac and cerebrovascular event(MACCE),a composite of death,myocardial infarction(MI),unplanned revascularization and stroke.RESULTS Prior stroke was present in 888 patients(9.9%).These patients were older and had higher rates of comorbidities.Du-ring a median follow-up of 7.5 years,patients with prior stroke were strongly associated with increased risks of all-cause death,cardiac death,stroke and MACCE,even after adjusting for confounding variables and results been consistent across either treat-ment subgroup(PCI,CABG and MT)(all adjusted Pclinical outcomes.It is essential to balance benefit and risk when determining the optimal treatment strategy for TVD with and without prior stroke.

关键词： patients prior founding

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