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Psycho-Oncologie 2023年第3期17卷 195-199页

作者： Sylvie Faiderbe Nadège Berlioz patient-Researcher Regnéville-Sur-Mer50590France patient-Researcher Paris75000France

Two patients relate their experience as co-researchers in a research project in the human and social *** the genesis of the research project to the results,they detail their participation in each stage of this project alongside care professionals and researchers:their difficulties,their contributions,their pleasure,and speculations on the conditions for improving this type of active collaboration in a participative research project.

关键词： Participative research patient researcher patient expert patient partner care pathway

Estimation of Cancer Progression Based Clinical Trial Subgroups

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Journal of Mathematics and System Science 2019年第5期9卷 124-129页

作者： Shankar Srinivasan Lihua Yue Weiyuan Chung partner Resource Tepee LLC and DirectorCelgene Corporation Associate Director BiostatisticsCelgene Corporation.

Cancer trials often start investigational therapy at diagnosis or after a selected number of *** are the usual core inclusion criteria in clinical *** it is helpful when planning a trial to know the likely percentages of patients receiving standard therapy at clinics and hospitals who meet this key inclusion criteria of being newly diagnosed during a period or having just had their first,second or third relapse during an anticipated enrollment time *** regulatory agencies will have approvals tied to the use of a therapy in a relapsed context or in a newly diagnosed *** provide details on calculations to help those in clinical trial operations make realistic assessments on the number of sites and likely enrollment at clinical trial sites,and the enrollment time frames that might be needed to complete planned total patient *** estimates complement site feasibility questionnaires which are often sent to gauge patient availability and site interest.

关键词： Clinical trial enrollment site feasibility progression/relapse based subgroups.

Hepatitis B virus subgenotype F3 reactivation with vaccine escape mutations:A case report and review of the literature

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World Journal of Hepatology 2018年第7期10卷 509-516页

作者： Stefan Schlabe Kathrin van Bremen Souhaib Aldabbagh Dieter Glebe Corinna M Bremer Tobias Marsen Walter Mellin Veronica Di Cristanziano Anna M Eis-Hübinger Ulrich Spengler German Center of Infectious Diseases Research(DZIF) Partner-Site Cologne-BonnBonn-Cologne35392Germany Department of Internal Medicine I University Hospital of BonnBonn 53127Germany Institute of Virology University Hospital of BonnBonn 53127Germany Institute of Medical Virology Justus Liebig University GiessenNational Reference Center for Hepatitis B and D VirusesBiomedical Research Center SeltersbergGiessen 35392Germany German Center of Infectious Diseases Research(DZIF) Partner-Site GiessenGiessen 35392Germany Practice of Nephrology and Dialysis Nephrological Center Cologne-LindenthalCologne 50937Germany Practice of Pathology and Cytology Cologne 50931Germany Institute of Virology University Hospital of CologneCologne 50935Germany

Hepatitis B represents a global health threat because its chronic course and sequelae contribute to a high morbidity and mortality. Hepatitis B virus(HBV) infection can be controlled by vaccines, antiviral treatment, and by interrupting transmission. Rare vaccine escape mutants are serious because they eliminate vaccine protection. Here, we present a 74-year-old vaccinated patient with HBV reactivation 11 years after kidney transplantation. The patient was HBV-positive but HBs Ag-negative prior to vaccination 6 years before transplantation. The reactivated virus was HBV genotype F3 with vaccine escape mutations G145 R, P120 Q, and Q129 P. The patient was successfully treated with entecavir. The epidemiological reasons for this subgenotype, which is extremely rare in Western Europe, were unclear. This case illustrates that second-generation vaccines are not always effective in a specific group of patients.

关键词： Entecavir Hepatitis B virus Subgenotype F3 Kidney transplantation Vaccine escape mutant G145R

Diagnosis and management of ischemic cardiomyopathy: Role of cardiovascular magnetic resonance imaging

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World Journal of Cardiology 2014年第11期6卷 1166-1174页

作者： Christina Doesch Theano Papavassiliu 1~(st) Department of Medicine Cardiology University Medical Center Mannheim Medical Faculty Mannheim University of Heidelberg 68167 Mannheim Germany DZHK (German Centre for Cardiovascular Research) partner site Mannheim 69117 Heidelberg Germany

Coronary artery disease(CAD) represents an important cause of mortality. Cardiovascular magnetic resonance(CMR) imaging evolved as an imaging modality that allows the assessment of myocardial function, perfusion, contractile reserve and extent of fibrosis in a single comprehensive exam. This review highlights the role of CMR in the differential diagnosis of acute chest pain by detecting the location of obstructive CAD or necrosis and identifying other conditions like stress cardiomyopathy or myocarditis that can present with acute chest pain. Besides, it underlines the prognostic implication of perfusion abnormalities in the setting of acute chest pain. Furthermore, the review addresses the role of CMR to detect significant CAD in patients with stable CAD. It elucidates the accuracy and clinical utility of CMR with respect to other imaging modalitieslike single-photon emission computed tomography and positron emission tomography. Besides, the prognostic value of CMR stress testing is discussed. Additionally, it summarizes the available CMR techniques to assess myocardial viability and describes algorithm to identify those patient who might profit from revascularization those who should be treated medically. Finally, future promising imaging techniques that will provide further insights into the fundamental disease processes in ischemic cardiomyopathy are discussed.

关键词： Coronary artery disease Cardiovascular magnetic resonance imaging Prognostic value Stress testing Viability

Current understanding of thermo(dys)regulation in severe burn injury and the pathophysiological influence of hypermetabolism,adrenergic stress and hypothalamic regulation-a systematic review

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Burns & Trauma 2022年第1期10卷 272-282页

作者： Viktoria Mertin Patrick Most Martin Busch Stefan Trojan Christian Tapking Valentin Haug Ulrich Kneser Gabriel Hundeshagen Department of Hand Plastic and Reconstructive SurgeryBurn Trauma CenterBG Trauma Center LudwigshafenUniversity of Heidelberg67071 Ludwigshafen am RheinGermany Division of Molecular and Translational Cardi-ology Department of Internal MedicineⅢUniversity Hospital Heidelberg69120 HeidelbergGermany Deutsches Zentrum für Herz-und Kreislaufforschung(GCCR) Partner site Heidelberg/MannheimGermany Department of Anesthesiology and Intensive Care Medicine Merheim Medical CenterHospitals of CologneUniversity of Witten/Herdecke51109 CologneGermany

Background:In this systematic review,we summarize the aetiology as well as the current knowl-edge regarding thermo(dys)regulation and hypothermia after severe burn trauma and aim to present key concepts of pathophysiology and treatment *** burn injuries with>20%total body surface area(TBSA)affected commonly leave the patient requiring several surgical procedures,prolonged hospital stays and cause substantial changes to body composition and metabolism in the acute and long-term *** in severely burned patients,the loss of intact skin and the dysregulation of peripheral and central thermoregulatory processes may lead to substantial ***:A systematic and protocol-based search for suitable publications was conducted fol-lowing the PRISMA *** were screened and included if deemed *** encompasses animal-based in vivo studies as well as clinical studies examining the control-loops of thermoregulation and metabolic stability within burn patients Results:Both experimental animal studies and clinical studies examining thermoregulation and metabolic functions within burn patients have produced a general understanding of core concepts which are,nonetheless,lacking in *** describe the wide range of pathophysiological alterations observed after severe burn trauma and highlight the association between thermoregulation and hypermetabolism as well as the interactions between nearly all organ ***,the current clinical standards of mitigating the negative effects of thermodysregulation and hypothermia are summarized,as a comprehensive understanding and implementation of the key concepts is critical for patient survival and long-term ***:The available in vivo animal models have provided many insights into the interwoven pathophysiology of severe burn injury,especially concerning *** offer an outlook on concepts of altered central thermoregulation from non-burn research

关键词： Animal model Burn shock Hypothermia Thermoregulation Temperature management Burn injury Hypermetabolism

钠-葡萄糖共转运蛋白-2抑制剂或胰高血糖素样肽-1受体激动剂治疗成人2型糖尿病:临床实践指南

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英国医学杂志中文版 2021年第9期24卷 523-531页

作者： Sheyu Li Per Olav Vandvik Lyubov Lytvyn Gordon H Guyatt Suetonia C Palmer Rene Rodriguez-Gutierrez Farid Foroutan Thomas Agoritsas Reed A C Siemieniuk Michael Walsh Lawrie Frere David J Tunnicliffe Evi V Nagler Veena Manja Bjφrn Olav Asvold Vivekanand Jha Mieke Vermandere Karim Gariani Qian Zhao Yan Ren Emma Jane Cartwright Patrick Gee Alan Wickes Linda Fems Robin Wright Ling Li Qiukui Hao Reem A Mustafa 无郭鹤鸣(译) Chengdu China Chinese Evidencebased Medicine Center Cochrane China Center and MAGIC China CenterWest China HospitalSichuan UniversityChengduChina University of Oslo OsloNorway MAGIC Evidence Ecosystem Foundation Department of Health Research Methods Evidence and ImpactMcMaster UniversityHamiltonONCanada Department of Medicine McMaster UniversityHamiltonONCanada Department of Medicine University of OtagoChristchurchNew Zealand Plataforma INVEST Medicina UANL-KER Unit(KER Unit Mexico) Subdireccion de InvestigacionUniversidad Autonoma de Nuevo LeonMonterrey64460Mexico Knowledge and Evaluation Research Endocrinology Mayo ClinicRochesterMN55905USA Endocrinology Division Department of Internal MedicineUniversity Hospital"Dr.Jose E.Gonzalez"Universidad Autonoma de Nuevo LeonMonterrey64460Mexico Ted Rogers Center for Heart Research Canada Service of Endocrinology DiabetesNutrition and Patient Therapeutic EducationGeneva University HospitalsGenevaSwitzerland Newbridge Surgery BathUK Sydney School of Public Health The University of SydneySydneyAustralia Centre for Kidney Research The Children's Hospital at WestmeadSydneyAustralia Renal Division Ghent University HospitalBelgium University of California Davis USA Department of Endocrinology Clinic of MedicineSt Olavs HospitalTrondheim University HospitalTrondheimNorway K.G.Jebsen Center for Genetic Epidemiology Department of Public Health and NursingNTNUNorwegian University of Science and TechnologyTrondheimNorway The George Institute for Global Health UNSWIndia School of Public Health Imperial CollegeLondonUK Prasanna School of Public Health Manipal Academy of Higher EducationManipalIndia Department of Public Health and Primary Care KU LeuvenLeuvenBelgium International Medical Center/Ward of General Practice West China HospitalSichuan UniversityChengduChina London UK Founder&CEHD iAdvorateInc.VirginiaPatient partner patient partner The Center of Gerontology and Geriatrics/National Clinical Research Center for Geriatr

临床问题对于存在不同心血管风险及肾脏结局的2型糖尿病患者,在原有生活方式干预和/或其他降糖药物的基础上加用钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂的获益及风险是什么?现行做法几十年来,2型糖尿病... 详细信息

临床问题对于存在不同心血管风险及肾脏结局的2型糖尿病患者,在原有生活方式干预和/或其他降糖药物的基础上加用钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂的获益及风险是什么?现行做法几十年来,2型糖尿病的治疗决策都以控制血糖为主导。SGLT-2抑制剂和GLP-1受体激动剂在传统观念中常被用于二甲双胍治疗后血糖仍控制不佳的患者。目前这一现状已经发生了改变,这得益于多项临床研究结果。研究显示SGLT-2抑制剂和GLP-1受体激动剂拥有独立于药物降糖作用之外的对于动脉粥样硬化性心血管病(CVD)和慢性肾脏病(CKD)的获益。建议本指南阐述了针对不同风险分层的成人2型糖尿病患者使用SGLT-2抑制剂或GLP-1受体激动剂的建议。•伴有3种或更少的心血管风险因素且不存在CVD或CKD:不建议启动SGLT-2抑制剂或GLP-1受体激动剂治疗。(推荐等级:弱)•伴有3种以上心血管风险因素且不存在CVD或CKD:建议启动SGLT-2抑制剂治疗,不建议启动GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD或CKD:建议启动SGLT-2抑制剂治疗和GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD和CKD:建议启动SGLT-2抑制剂治疗(推荐等级:强)和GLP-1受体激动剂治疗。(推荐等级:弱)•对于那些想要进一步降低CVD和CKD结局风险的患者:推荐优先启用SGLT-2抑制剂治疗而非GLP-1受体激动剂治疗。(推荐等级:弱)这项指南是如何制订的一个由患者、临床医生和方法学家共同组成的国际小组提出了这些推荐意见。这些推荐意见基于可信度较高的指南的标准,并使用GRADE分级方法进行评估。该小组采用了息者个体化的观点。证据一项关于获益与风险的系统综述和网络meta分析(764项随机对照研究,包括421346例参与者)发现SGLT-2抑制剂和GLP-1受体激动剂可以降低总体死亡率、心肌梗死发生率、终末期肾病或肾衰竭的发生率(中等至高等质量的证据)。在不同的亚组中这些药物对卒中、因心力衰竭所致住院和其他主要不良事件有不同的影响。药物绝对获益的程度因患者个体风险的不同有很大的差异。(例如,对于接受了超过5年药物治疗的1000例患者,在最低风险人群中死亡人数减少了5人,在最高风险人群中死亡人数减少了48人)。一项关于预后的综述确认了14种风险预测模型,其中一种(RECODe)在证据总结中报告了大部分基线风险评估数据,小组利用该模型以支持风险分层的建议。考虑到患者的价值观及个体差异,指南推荐的支撑证据包括一项对已发表论文的系统综述、一项患者焦点小组研究、一项临床问题总结,以及一项指南调查。指南解读我们依据不同的CVD和CKD风险水平,综合考虑获益、风险和其他因素的平衡,以及每一个风险组别的实际问题,来对推荐意见进行分层。本指南强烈建议CVD和CKD患者使用SGLT-2抑制剂治疗,这说明专家组认为其具有显著的获益。而对于其他成人2型糖尿病患者,推荐等级较弱,这说明专家组想要在获益、风险及治疗花费上取得一个更好的平衡。临床医生通过该指南可以使用可靠的风险计算模型,如RECODe,来明确其患者的个体心血管和肾脏疾病风险。医患交互式总结临床证据和制订决策有助于患者知晓治疗选择,包括进行共同决策。2型糖尿病人群(全球患病率不断增长1-2)正面临着不断增加的心血管疾病、肾脏病和其他并发症的风险3。数十年来,2型糖尿病的管理始终以控制血糖及糖化血红蛋白(HbA1c)为治疗目标4-5,但是,最近的高质量随机对照研究已经对这种以血糖为中心的治疗模式发起了挑战。研究结果显示,强化血糖控制未必会降低大血管不良事件,它还可能带来不利影响监管机构现在要求新型糖尿病药物必须证明其具有心血管和肾脏获益才能获得批准。对两类新药--钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂(见框图1)的临床试验结果显示,在现有治疗方案(常规治疗)之上加用这些药物,对死亡、心肌梗死、卒中、心力衰竭和肾脏的结局(如进展为终末期肾病)都有获益8-12。

关键词：胰高血糖素样肽1 终末期肾病临床研究结果心血管风险 meta分析临床试验结果临床证据控制血糖

Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods

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Cellular & Molecular Immunology 2021年第4期18卷 936-944页

作者： Berislav Bosnjak Saskia Catherina Stein Stefanie Willenzon Anne Katrin Cordes Wolfram Puppe Gunter Bernhardt Inga Ravens Christiane Ritter Christian R.Schultze-Florey Nina Godecke Jorg Martens Hannah Kleine-Weber Markus Hoffmann Anne Cossmann Mustafa Yilmaz Isabelle Pink Marius M.Hoeper Georg M.N.Behrens Stefan Pohlm ann Rainer Blasczyk Thomas F.Schulz Reinhold Forster Institute of Immunology Hannover Medical SchoolHannoverGermany lnstitute of Virology Hannover Medical SchoolHannoverGermany Department of Hematology HemostasisOncology and Stem Cell TransplantationHannover Medical SchoolHannoverGermany Institute of Transfusion Medicine and Transplant Engineering Hannover Medical SchoolHannoverGermany German Primate Center-Leibniz Institute for Primate Research GottingenGermany Faculty of Biology and Psychology University GottingenGottingenGermany Department of Rheum atology and Immunology Hannover Medical SchoolHannoverGermany Public Health Department HannoverGermany Department of Pneumology and German Centre of Lung Research(DZL) Hannover Medical SchoolHannoverGermany German Center for Infection Research(DZIF) partner site Hannover-BraunschweigHannoverGermany Cluster of Excellence RESIST(EXC 2155) Hannover Medical SchoolHannoverGermany

Neutralizing antibodies targeting the receptor-binding domain(RBD)of the SARS-CoV-2 spike(S)block severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry into cells via surface-expressed angiotensin-converting enzyme 2(ACE2).We used a surrogate virus neutralization test(sVNT)and SARS-CoV-2 S protein-pseudotyped vesicular stomatitis virus(VSV)vector-based neutralization assay(pVNT)to assess the degree to which serum antibodies from coronavirus disease 2019(COVID-19)convalescent patients interfere with the binding of SARS-CoV-2 S to *** tests revealed neutralizing anti-SARS-CoV-2 S antibodies in the sera of ~90% of mildly and 100% of severely affected COVID-19 convalescent ***,sVNT and pVNT results correlated strongly with each other and to the levels of anti-SARS-CoV-2 S1 IgG and IgA ***,levels of neutralizing antibodies correlated with the duration and severity of clinical symptoms but not with patient *** to pVNT,sVNT is less sophisticated and does not require any biosafety *** this assay is also much faster and cheaper,sVNT will not only be important for evaluating the prevalence of neutralizing antibodies in a population but also for identifying promising plasma donors for successful passive antibody therapy.

关键词： COVID-19 SARS-CoV-2 Neutralizing antibody Serum ELISA

Rescue of p53 functions by in vitro-transcribed mRNA impedes the growth of high-grade serous ovarian cancer

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Cancer Communications 2024年第1期44卷 101-126页

作者： Monika Raab Izabela Kostova Samuel Peña-Llopis Daniela Fietz Monika Kressin Seyed Mohsen Aberoumandi Evelyn Ullrich Sven Becker Mourad Sanhaji Klaus Strebhardt Department of Gynecology Medical SchoolGoethe-UniversityFrankfurt am MainGermany Translational Genomics in Solid Tumors West German Cancer CenterUniversity HospitalEssenGermany German Cancer Consortium(DKTK) EssenGermany German Cancer Research Center(DKFZ) HeidelbergGermany Histology and Embryology Institute for Veterinary AnatomyGiessenGermany Franfurt Cancer Institute(FCI) Goethe UniversityFrankfurt am MainGermany German Cancer Consortium(DKTK) Partner site Frankfurt/Mainza partnership between DKFZ and University Hospital FrankfurtFrankfurt am MainGermany Experimental Immunology Department for Children and Adolescents MedicineUniversity Hospital FrankfurtGoethe UniversityFrankfurt am MainGermany

Background:The cellular tumor protein p53(TP53)is a tumor suppressor gene that is frequently mutated in human *** various cancer types,the very aggressive high-grade serous ovarian carcinoma(HGSOC)exhibits the high-est prevalence of TP53 mutations,present in>96%of *** intensive efforts to reactivate p53,no clinical drug has been approved to rescue p53 *** this study,our primary objective was to administer in vitro-transcribed(IVT)wild-type(WT)p53-mRNA to HGSOC cell lines,primary cells,and ortho-topic mouse models,with the aim of exploring its impact on inhibiting tumor growth and dissemination,both in vitro and in ***:To restore the activity of p53,WT p53 was exogenously expressed in HGSOC cell lines using a mammalian vector ***,IVT WT p53 mRNA was delivered into different HGSOC model systems(primary cells and patient-derived organoids)using liposomes and studied for proliferation,cell cycle progression,apoptosis,colony formation,and chromosomal *** alterations induced by p53 mRNA were analyzed using RNA sequencing in OVCAR-8 and primary HGSOC cells,followed by ingenuity path-way *** vivo effects on tumor growth and metastasis were studied using orthotopic xenografts and metastatic intraperitoneal mouse ***:Reactivation of the TP53 tumor suppressor gene was explored in differ-ent HGSOC model systems using newly designed IVT mRNA-based *** introduction of WT p53 mRNA triggered dose-dependent apoptosis,cell cycle arrest,and potent long-lasting inhibition of HGSOC cell *** analysis of OVCAR-8 cells upon mRNA-based p53 reactivation revealed significant alterations in gene expression related to p53 signaling,such as apoptosis,cell cycle regulation,and DNA *** p53 function concurrently reduces chromosomal instability within the HGSOC cells,under-scoring its crucial contribution in safeguarding genomic integrity by moderating the baselin

关键词： apoptosis cell cycle chromosomal instability HGSOC metastatic intraperitoneal mouse model HGSOC orthotopic Xenograft model high-grade serous ovarian cancer in vitro-transcribed p53-mRNA liposomal IVT mRNA delivery system patient-derived organoid patient-derived primary cancer cell

Multi-scale analysis of schizophrenia risk genes, brain structure, and clinical symptoms reveals integrative dues for subtyping schizophrenia patients

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Journal of Molecular Cell Biology 2019年第8期11卷 678-687页

作者： Liang Ma Edmund T.Rolls Xiuqin Liu Yuting Liu Zeyu Jiao Yue Wang Weikang Gong Zhiming Ma Fuzhou Gong Lin Wan CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100101 China National Center of Mathematics and Interdisciplinary Sciences Academy of Mathematics and Systems Science Chinese Academy of Sciences Beijing 100190 China Department of Computer Science University of Warwick Coventry CV4 7AL UK Oxford Centre for Computational Neuroscience Oxford 0X2 7JF UK School of Mathematics and Physics University of Science and Technology Beijing Beijing 100083 China School of Science Beijing Jiaotong University Beijing 100044 China Centre for Computational Systems Biology School of Mathematical Sciences Fudan University Shanghai 200433 China CAS-MPG partner Institute for Computational Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China University of Chinese Academy of Sciences Beijing 100049 China

Analysis Unking directly genomics, neuroimaging phenotypes and clinical measurements is crucial for understanding psychiatric disorders, but remains ***, we describe a multi-scale analysis using genome-wide SNPs, gene expression, grey matter volume (GMV), and the positive and negative syndrome scale scores (PANSS) to explore the etiology of schizophrenia. With 72 drug-naive schizophrenic first episode patients (FEPs) and 73 matched heathy controls, we identified 108 genes, from schizophrenia risk genes, that correlated significantly with GMV, which are highly co-expressed in the brain during development. Among these 108 candidates, 19 distinct genes were found associated with 16 brain regions referred to as hot clusters (HCs), primarily in the frontal cortex, sensory-motor regions and temporal and parietal *** patients were subtyped into three groups with distinguishable PANSS scores by the GMV of the identified HCs. Furthermore, we found that HCs with common GMV among patient groups are related to genes that mostly mapped to pathways relevant to neural signaling, which are associated with the risk for *** results provide an integrated view of how genetic variants may affect brain structures that lead to distinct disease *** method of multi-scale analysis that was described in this research, may help to advance the understanding of the etiology of schizophrenia.

关键词： Schizophrenia PANSS multi-scale analysis hot cluster grey matter volume pathway

How to Diagnose the State of a Dynamic System

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Journal of Acupuncture and Tuina Science 2008年第5期6卷 265-265页

作者： Andreas Dress CAS-MPG partner Institute of Computational Biology Shanghai Institutes of Biological Sciences(CAS)Shanghai 200040P.R.China

When analyzing a system,it is not only the easily quantified parameters (like where an item,*** location of a planet in the planetary system or the weight,the temperature。

关键词：动力学系统诊断方法经络研究中医治疗