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| 1 | Incidence trends and survival prediction of hepatoblastoma in children:a population-based study显示文摘Background:Hepatoblastoma is a rare disease that nevertheless accounts for the majority of liver malignancies in children.Due to limited epidemiological data,therapy for hepatoblastoma tends to be individualized.This study aimed to evaluate incidence trends of hepatoblastoma and to develop a nomogram to predict the survival of children with newly diagnosed hepatoblastoma on a population-based level.Methods:Individuals up to 18 years of age with hepatoblastoma recorded in 18 registries of the Surveillance,Epi-demiology,and End Results(SEER)database between 2004 and 2015 were examined.Joinpoint regression analyses were applied to assess incidence trends in annual percentage change(APC).Multivariable Cox regression was used to identify factors associated with overall survival(OS).A nomogram was constructed to predict OS in individual cases based on independent predictors.Concordance index(C-index)and calibration curves were used to evaluate predic-tive performance.Results:Between 2004 and 2015,hepatoblastoma incidence increased significantly(APC,2.2%;95%confidence interval[CI]0.5%to 3.8%,P<0.05).In particular,this increase was observed among 2-to 4-year-old patients,males,and African-Americans.The 5-and 10-year OS rates were 81.5%and 81.0%,respectively.Age of 2 to 4 years,Afri-can-American ethnicity,and no surgery were independent predictors for short OS.Distant disease at presentation was found not to be an independent factor of survival.The nomogram had a C-index of 0.79(95%CI 0.74-0.84)with appropriate calibration curve fitting.Conclusions:We constructed a nomogram that integrates common factors associated with survival for hepatoblas-toma patients.It provides accurate prognostic prediction for children with hepatoblastoma. | Jincheng Feng Georgios Polychronidis Ulrike Heger Giovanni Frongia Arianeb Mehrabi Katrin Hoffmann | 2019 | Cancer Communications2019，39，1： | 10 |
| 2 | Antibacterial photodynamic therapy:overview of a promising approach to fight antibiotic-resistant bacterial infections显示文摘Antibacterial photodynamic therapy(APDT)has drawn increasing attention from the scientific society for its potential to effectively kill multidrug-resistant pathogenic bacteria and for its low tendency to induce drug resistance that bacteria can rapidly develop against traditional antibiotic therapy.The review summarizes the mechanism of action of APDT,the photosensitizers,the barriers to PS localization,the targets,the in vitro-,in vivo-,and clinical evidence,the current developments in terms of treating Gram-positive and Gram-negative bacteria,the limitations,as well as future perspectives.Relevance for patients:A structured overview of all important aspects of APDT is provided in the context of resistant bacterial species.The information presented is relevant and accessible for scientists as well as clinicians,whose joint effort is required to ensure that this technology benefits patients in the post-antibiotic era. | Yao Liu Rong Qin Sebastian A.J.Zaat Eefjan Breukink Michal Heger | 2015 | Journal of Clinical & Translational Research2015，1，3： | 8 |
| 3 | Expression of the oxygen-sensitive transcription factor subunit HIF-1α in patients suffering from secondary Raynaud syndrome显示文摘Anti-ischemic therapy remains a challenge due to the complexity of hypoxia response pathways. Hypoxia-inducible factor (HIF)-1 is a heterodimer tran scription factor con sisti ng of 2 sub units, HIF-1α and HIF-1β. Hypoxia-depe ndent activatio n of HIF-1α regulates cellular 02 homeostasis. Raynaud syndrome (RS), as a comorbidity of the autoimmune disease systemic sclerosis (SS), is characterized by vasospasms that limit blood flow to the limbs, resulting in hypoxia. A single-center randomized study was con ducted to compare prostagla ndin E1 (PgEI) therapy with a treatme nt combi ning PgE1 and an en dotheli n-1 blocker, bosentan. A total of 30 patients suffering from SS with RS were enrolled. We examined the regulation of HIF-1α, its target heme oxygenase-1 (HMOX-1), and the serum levels of the HIF-1α protein in a subset of patients as well as in ten healthy individuals. The expression of HIF-1α and HMOX-1 in monocytes was measured using absolute plasmid-based quantitative real-time PCR, whereas serum HIF-1α levels were measured with ELISA. Samples were taken at the time of randomization and after 24 weeks. We found that HIF-1α and HMOX-1 mRNA expression in monocytes and serum HIF-1α protein levels were significantly higher in the SS/RS patients compared to the healthy control group. Single-drug therapy significantly increased HIF-1α and HMOX-1 mRNA expression in monocytes and serum HIF-1α protein levels in the SS/RS patients compared to those at the time of randomization, whereas combining PgE1 with an en dotheli n-1 blocker preve nted the further in creases in HIF-1α and HMOX-1 expressi on. We propose HIF-1α and HMOX-1 as novel markers for anti-ischemic therapy in RS. | Lukas Andreas Heger Mark Kerber Marcus Hortmann Samuel Robinson Maximilian Mauler Daniela Stallmann Daniel Duerschmied Christoph Bode Christoph Hehrlein Ingo Ahrens | 2019 | Acta Pharmacologica Sinica2019，40，4： | 5 |
| 4 | Chip-based digital PCR as a novel detection method for quantifying microRNAs in acute myocardial infarction patients显示文摘miRNAs 为尖锐心肌的梗塞(AMI ) 作为潜在的 biomarkers 显示出诺言。然而,当前的使用的量的即时 PCR (qRT-PCR ) 完全为 nucleic 酸的相对表示允许,它产生日常可变性,它限制了把 miRNAs 用作 biomarkers 的有效性。在这研究,我们探索了技术质量和一种新技术的诊断潜力,基于薄片的数字 PCR,在确定在有 AMI 和 ischaemia-reperfusion 损害(I/R ) 的病人的 miRNAs。在合成 C.elegans-miR-39 的一个冲淡系列,基于薄片的数字 PCR 与 qRT-PCR 相比显示了变化(8.9% 对 46.3%) 和察觉(0.2 copies/L 对 1.1 copies/L ) 的更低的限制的一个更低的系数。在从有圣举起心肌的梗塞( STEMI )的 24 个病人和有稳定的冠的动脉疾病( CAD )的 20 个病人镇定的浆液在经皮的冠的干预(一种总线标准)以后的病人,我们使用了 qRT-PCR 和多路的基于薄片的数字 PCR 确定他们在优先的研究在 AMI 被验证了的 miRNA-21 和 miRNA-499 的浆液层次。在 STEMI, I/R 损害经由圣片断分辨率(ST-R ) 的测量被估计。基于薄片的数字 PCR 处于在稳定的 CAD 和 STEMI 组之间的 miR-21 层次的差别揭示了统计意义(118.8 copies/L 对 59 copies/L;P=0.0300 ) ,而 qRT-PCR 是不能的到达意义(136.4 copies/L 对 122.8 copies/L;P=0.2273 ) 。为 miR-499 层次,基于薄片的数字 PCR 和 qRT-PCR 揭示了稳定的 CAD 和 STEMI 组之间的统计上重要的差别(2 copies/L 对 8.5 copies/L, P=0.0011;0 copies/L 对 19.4 copies/L;P < 0.0001 ) 。在 miR-21/499 层次和 ST-R 之间没有协会一种总线标准以后。我们的结果证明基于薄片的数字 PCR 展出优异技术质量和诺言是一个优异方法因为确定的 miRNA 在发行量铺平,它可以为直接确定成为一个更精确、可再现的方法 miRNAs,特别地为在大多中心的使用临床的试用。 | Samuel ROBINSON Marie FOLLO David HAENE Maximilian MAULER Daniela STALLMANN Lukas Andreas HEGER Thomas HELBING Daniel DUERSCHMIED Karlheinz PETER Christoph BODE Ingo AHRENS Marcus HORTMANN | 2018 | Acta Pharmacologica Sinica2018，39，7： | 5 |
| 5 | Site-specific pharmaco-laser therapy:A novel treatment modality for refractory port wine stains显示文摘Despite extensive efforts to optimize laser therapy,i.e.,the current gold standard treatment,a majority of port wine stain(PWS)patients responds suboptimally to laser therapy.This paper describes the niceties of a novel PWS treatment modality termed site-specific pharmaco-laser therapy(SSPLT).In contrast to the classic approach of enhancing the extent of intravascular photocoagulation(the photothermal response),SSPLT focuses on optimization of post-irradiation thrombus formation(i.e.,the hemodynamic response)by combining conventional laser therapy with the administration of thermosensitive drug delivery systems that encapsulate prothrombotic and antifibrinolytic drugs.The aim of SSPLT is to instill complete lumenal occlusion in target vessels,which has been linked to optimal PWS blanching.Relevance for patients:The current treatment options for PWS patients are limited in efficacy.Novel therapeutic modalities are needed to more effectively treat patients with recalcitrant PWSs.SSPLT is an experimental-stage treatment modality that could serve as an adjuvant to pulsed dye laser therapy for a selected group of patients whose PWS is ill-responsive to standard treatment.The expected clinical result of SSPLT is improved lesional blanching. | M.Ingmar van Raath Jojanneke E.van Amesfoort Martin Hermann Yasin Ince Maurice J.Zwart Agustina V.Echague Yan Chen Baoyue Ding Xuan Huang Gert Storm Michal Heger | 2019 | Journal of Clinical & Translational Research2019，5，1： | 4 |
| 6 | Inhibition of hypoxia-inducible factor 1 with acriflavine sensitizes hypoxic tumor cells to photodynamic therapy with zinc phthalocyanine-encapsulating cationic liposomes显示文摘光力学的治疗(太平洋夏季时间) 是 tumorlocalized photosensitizer 与光是激动的一种肿瘤治疗在形式,它导致反应的氧种类,肿瘤 vasculature 的破坏,肿瘤组织缺氧,肿瘤房间死亡,和反肿瘤免疫者回答的正式就职的本地生产。然而,先存在肿瘤组织缺氧可以减少肿瘤到由激活组织缺氧可诱导的因素的太平洋夏季时间 1 (HIF-1 ) 幸存小径。因此,我们与吖啶黄(ACF ) 假设了 HIF-1 的那抑制将在人的表皮状的癌(A431 ) 加重房间死亡房间。A431 肿瘤房间的太平洋夏季时间用包含 photosensitizer 锌酞毒(ZnPC ) 的最新发达并且优化的 PEGylated cationic liposomes 被执行。分子的停靠表明 ACF 绑在 HIF-1 的 dimerization 领域,并且共焦的显微镜学在组织缺氧下面从 cytosol 证实了 ACF 的 translocation 到原子核。HIF-1 在 hypoxic,然而并非 normoxic 被稳定, A431 房间列在后面太平洋夏季时间。有 ACF 的 HIF-1 的抑制在 hypoxic 条件下面增加了导致太平洋夏季时间的房间死亡的程度并且减少了 HIF-1 目标基因 VEGF, PTGS2,和 EDN1 的表示。而且,在包含 ZnPC liposomes 的水的核心的 ACF 的合作封装在比得上非包含的 ACF 的太平洋夏季时间功效上产出辅助效果。在结论, HIF-1 与 liposomal ZnPC 贡献 A431 肿瘤房间幸存追随者太平洋夏季时间。HIF-1 与的抑制免费或 liposomal ACF 改进太平洋夏季时间功效。 | Mans Broekgaarden Ruud Weijer Massis Krekorian Bas van den IJssel Milan Kos Lindy K. Alles Albert C. van Wijk1 Zsolt Bikadi Eszter Hazai Thomas M. van Gulik Michal Heger | 2016 | Nano Research2016，9，6： | 4 |
| 7 | Progress of Jinping Underground laboratory for Nuclear Astrophysics(JUNA)显示文摘Jinping Underground laboratory for Nuclear Astrophysics(JUNA) will take the advantage of the ultra-low background of CJPL lab and high current accelerator based on an ECR source and a highly sensitive detector to directly study for the first time a number of crucial reactions occurring at their relevant stellar energies during the evolution of hydrostatic stars. In its first phase, JUNA aims at the direct measurements of^(25)Mg(p,γ)^(26)Al,^(19)F(p,α)^(16)O,^(13)C(α,n)^(16)O and ^(12)C(α,γ)^(16)O reactions. The experimental setup,which includes an accelerator system with high stability and high intensity, a detector system, and a shielding material with low background, will be established during the above research. The current progress of JUNA will be given. | WeiPing Liu ZhiHong Li JiangJun He XiaoDong Tang Gang Lian Zhu An JianJun Chang Han Chen QingHao Chen XiongJun Chen ZhiJun Chen BaoQun Cui XianChao Du ChangBo Fu Lin Gan Bing Guo GuoZhu He Alexander Heger SuQing Hou HanXiong Huang Ning Huang BaoLu Jia LiYang Jiang Shigeru Kubono JianMin Li KuoAng Li Tao Li YunJu Li Maria Lugaro XiaoBing Luo HongYi Ma ShaoBo Ma DongMing Mei YongZhong Qian JiuChang Qin Jie Ren YangPing Shen Jun Su LiangTing Sun WanPeng Tan Isao Tanihata Shuo Wang Peng Wang YouBao Wang Qi Wu ShiWei Xu ShengQuan Yan LiTao Yang Yao Yang XiangQing Yu Qian Yue Sheng Zeng HuanYu Zhang Hui Zhang LiYong Zhang NingTao Zhang QiWei Zhang Tao Zhang XiaoPeng Zhang XueZhen Zhang ZiMing Zhang Wei Zhao Zuo Zhao Chao Zhou | 2016 | Science China(Physics,Mechanics & Astronomy)2016，59，4： | 3 |
| 8 | Importance of intellectual property generated by biomedical research at universities and academic hospitals显示文摘Biomedical research has many different facets.Researchers and clinicians study disease biology and biochemistry to discover novel therapeutic targets,unravel biochemical pathways and identify biomarkers to improve diagnosis,or devise new approaches to clinically manage diseases more effectively.In all instances,the overall goal of biomedical research is to ensure that results thereof(such as a therapy,a device,or a method which may be broadly referred to as“inventions”)are clinically implemented.Most of the researchers’efforts are centered on the advance of technical and scientific aspects of an invention.The development and implementation of an invention can be arduous and very costly.Historically,it has proven to be crucial to protect intellectual property rights(IPR)to an invention(i.e.,a patent)to ensure that companies can obtain a fair return on their investment that is needed to develop an academic invention into a product for the benefit of patients.However,the importance of IPR is not generally acknowledged among researchers at academic institutions active in biomedical research.Therefore this paper aims to(1)raise IP awareness amongst clinical and translational researchers;(2)provide a concise overview of what the patenting trajectory entails;and(3)highlight the importance of patenting for research and the researcher.Importance for patients:Adequate patent protection of inventions generated through biomedical research at academic institutions increases the probability that patients will benefit from these inventions,and indirectly enables the financing of clinical studies,mainly by opening up funding opportunities(e.g.specific grants aimed at start-ups,pre-seed and seed capital)that otherwise would not be accessible.As a consequence,patented inventions are more likely to become clinically tested and reach the market,providing patients with more treatment options. | Joris J.Heus Elmar S.de Pauw Mirjam Leloux Margherita Morpurgo Michael R Hamblin Michal Heger | 2017 | Journal of Clinical & Translational Research2017，3，2： | 3 |
| 9 | Physiological and Biochemical Basis of Clinical Liver Function Tests: A Review显示文摘 | Lisette T. Hoekstra Wilmar de Graaf Geert A. A. Nibourg Michal Heger Roelof J. Bennink Bruno Stieger Thomas M. van Gulik | 2013 | Annals of Surgery2013，，1： | 3 |
| 10 | Is Preoperative Chemotherapy Followed by Surgery the Appropriate Treatment for Signet Ring Cell Containing Adenocarcinomas of the Esophagogastric Junction and Stomach?显示文摘 | Ulrike Heger Susanne Blank Christiane Wiecha Rupert Langer Wilko Weichert Florian Lordick Thomas Bruckner Martin Dobritz Maria Burian Christoph Springfeld Lars Grenacher J?rg-Rüdiger Siewert Markus Büchler Katja Ott | 2014 | Annals of Surgical Oncology2014，，5： | 2 |
| 11 | Platelet aggregation but not activation and degranulation during the acute post-ischemic reperfusion phase in livers with no underlying disease显示文摘Background:Platelets and P-selectin(CD62P)play an unequivocal role in the pathology of hepatic ischemia/reperfusion(I/R)injury.Inhibition or knock-out of P-selectin or immunodepletion of platelets results in amelioration of post-ischemic inflammation,reduced hepatocellular damage,and improved survival.However,P-selectin expression on platelets and endothelial cells,which concurs with platelet activation,has never been clearly demonstrated in I/R-subjected livers.Aims:To determine whether platelets become activated and degranulate in the acute phase of liver I/R and whether the platelets interact with neutrophils.Methods:Hepatic I/R was induced in male C57BL/6J mice(N=12)using 37.5-min ischemia time.Platelets,endothelial cells,and neutrophils were fluorescently labeled by systemic administration of non-blocking antibodies.Cell kinetics were monitored by intravital spinning disk confocal microscopy during 90 min of reperfusion.Image analysis and quantification was performed with dedicated software.Results:Platelets adhered to sinusoids more extensively in post-ischemic livers compared to livers not subjected to I/R and formed aggregates,which occurred directly after ischemia.Platelets and endothelial cells did not express P-selectin in post-ischemic livers.There was no interaction between platelets and neutrophils.Conclusions:Platelets aggregate but do not become activated and do not degranulate in post-ischemic livers.There is no platelet-neutrophil interplay during the early reperfusion phase in a moderate model of hepatic I/R injury.The mechanisms underlying the biological effects of platelets and P-selectin in this setting warrant further investigation.Relevance for patients:I/R in surgical liver patients may compromise outcome due to post-ischemic oxidative stress and sterile inflammation.Both processes are mediated in part by platelets.Understanding platelet function during I/R is key to developing effective interventions for I/R injury and improving clinical outcomes. | Rowan F.van Golen Katarzyna M.Stevens Pina Colarusso Hartmut Jaeschke Michal Heger | 2015 | Journal of Clinical & Translational Research2015，1，2： | 2 |
| 12 | Editor’s inaugural issue foreword: perspectives on translational and clinical research显示文摘1. Introduction The efficacy with which human maladies can be treated by medical intervention generally depends on the extent of translational and clinical research conducted on the given illness before the diagnosis. This may be the reason why, for example, human immunodeficiency virus infections (~300,000 studies on “human immunodeficiency virus” indexed on PubMed) can nowadays be controlled with a cocktail of well-tolerated antiviral medication, while Ebola virus infections (~4,000 studies on “Ebola” indexed on PubMed) still kill ~50% of the infected individuals. | Michal Heger | 2015 | Journal of Clinical & Translational Research2015，1，1： | 2 |
| 13 | Potential therapeutic benefits stemming from the thermal nature of irreversible electropora tion of solid cancers显示文摘To the Editor:Irreversible electroporation(IRE)is a CE-and FDAapproved treatment modality for pancreatic and liver tumors that is based on the site-confined destruction of tumor tissue by multiple short,high-intensity electrical pulses.^([1])Currently there is a heated debate about whether the therapy is thermal or non-thermal.The'non-thermal proponents'advocate | Michal Heger Allard C van der Wal Gert Storm Martin J van Gemert | 2015 | Hepatobiliary & Pancreatic Diseases International2015，14，3： | 2 |
| 14 | Post-hepatectomy liver regeneration in the context of bile acid homeostasis and the gut-liver signaling axis显示文摘Background:Liver regeneration following partial hepatectomy(PHx)is a complicated process involving multiple organs and several types of signaling networks.The bile acid-activated metabolic pathways occupy an auxiliary yet important chapter in the entire biochemical story.PHx is characterized by rapid but transient bile acid overload in the liver,which constitutes the first wave of proliferative signaling in the remnant hepatocytes.Bile acids trigger hepatocyte proliferation through activation of several nuclear receptors.Following biliary passage into the intestines,enterocytes reabsorb the bile acids,which results in the activation of farnesoid X receptor(FXR),the consequent excretion of fibroblast growth factor(FGF)19/FGF15,and its release into the enterohepatic circulation.FGF19/FGF15 subsequently binds to its cognate receptor,fibroblast growth factor receptor 4(FGFR4)complexed withβ-klotho,on the hepatocyte membrane,which initiates the second wave of proliferative signaling.Because some bile acids are toxic,the remnant hepatocytes must resolve the potentially detrimental state of bile acid excess.Therefore,the hepatocytes orchestrate a bile acid detoxification and elimination response as a protective mechanism in concurrence with the proliferative signaling.The response in part results in the excretion of(biotransformed)bile acids into the canalicular system,causing the bile acids to end up in the intestines.Relevance for patients:Recently,FXR agonists have been shown to promote regeneration via the gut-liver axis.This type of pharmacological intervention may prove beneficial for patients with hepatobiliary tumors undergoing PHx.In light of these developments,the review provides an in-depth account of the pathways that underlie post-PHx liver regeneration in the context of bile acid homeostasis in the liver and the gut-liver signaling axis. | Lianne de Haan Sarah Jvan der Lely Anne-Loes K.Warps Quincy Hofsink Pim B.Olthof Mark J.de Keijzer Daniel A.Lionarons Lionel Mendes-Dias Bote G.Bruinsma Korkut Uygun Hartmut Jaeschke Geoffrey C.Farrell Narci Teoh Rowan Fvan Golen Tiangang Li Michal Heger | 2018 | Journal of Clinical & Translational Research2018，4，1： | 2 |
| 15 | Effect of essential: Total N ratio on endogenous amino acid losses and N retention in growing pigs显示文摘 | Nitrayov6 S Heger J Patrfg P | 2010 | Livest Sci2010，134，13： | 1 |
| 16 | Percutaneousnephrolithotomy with ultrasonography guided renal ac- cess:experience from over 300 cases显示文摘 | Osman M Wendt-nordahl G Heger K | 2005 | BJU2005，96，6： | 1 |
| 17 | Threonine and crude protein responses in broiler chicks显示文摘 | Kidd M T Gerard P D Heger J | 2001 | Animal Feed Science and Technology2001，94，： | 1 |
| 18 | Longterm outcome of pa- tiens with ventricular septal defect considered not to require surgical cloure during childhood显示文摘 | Gabriel HM Heger M Innerhofer P | 2002 | J Am Coil Cardiol2002，39，： | 1 |
| 19 | Clinical use and phanmacology lxf Amjodarone 显示文摘 | HEGER J J PRYSTOWSKY E N | 1984 | Am Nclinmed1984，68，5： | 1 |
| 20 | Percutaneous nephrolithoto my with ultrasonography-guided renal access:experience from over 300cases显示文摘 | Osman M Wendt Nordahl G Heger K | 2005 | BJU Int2005，96，： | 1 |
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