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Updated developments on molecular imaging and therapeutic strategies directed against necrosis

Acta Pharmaceutica Sinica B 2019年第3期9卷 455-468页

作者： Dongjian Zhang Meng Gao Qiaomei Jin yicheng ni Jian Zhang Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese MedicineNanjing210028China Laboratories of Translational Medicine Jiangsu Province Academy of Traditional Chinese MedicineNanjing210028China Theragnostic Laboratory Campus GasthuisbergKU LeuvenLeuven3000Belgium

Cell death plays important roles in living organisms and is a hallmark of numerous disorders such as cardiovascular diseases, sepsis and acute pancreatitis. Moreover, cell death also plays a pivotal role in the treatment of certain diseases, for example, cancer. Noninvasive visualization of cell death contributes to gained insight into diseases, development of individualized treatment plans, evaluation of treatment responses, and prediction of patient prognosis. On the other hand, cell death can also be targeted for the treatment of diseases. Although there are many ways for a cell to die, only apoptosis and necrosis have been extensively studied in terms of cell death related theranostics. This review mainly focuses on molecular imaging and therapeutic strategies directed against necrosis. Necrosis shares common morphological characteristics including the rupture of cell membrane integrity and release of cellular contents, which provide potential biomarkers for visualization of necrosis and necrosis targeted therapy. In the present review, we summarize the updated joint efforts to develop molecular imaging probes and therapeutic strategies targeting the biomarkers exposed by necrotic cells. Moreover, we also discuss the challenges in developing necrosis imaging probes and propose several biomarkers of necrosis that deserve to be explored in future imaging and therapy research.

关键词： Necrosis avid agents Exposed DNA Molecular imaging Targeted therapy Solid tumor Myocardial infarction

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What is the purpose of launching the World Journal of Methodology？

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World Journal of Methodology 2011年第1期1卷 1-3页

作者： yicheng ni Department of Radiology University Hospitals KU Leuven Herestraat 49 B-3000 Leuven Belgium

Congratulations to the publisher, members of the editorial board of the journal, all the authors and readers for launching the World Journal of Methodology (WJM) as a new member of the World series journal family! Scientific advances and important breakthroughs have been facilitated by well developed methodologies or techniques and any misleading findings and theories are exclusively attributable to certain methodological defects. Thus, the role of appropriate methodologies in the development of science and technology cannot be overemphasized and the need for inaugurating this new journal is self-evident. The WJM is a peer-reviewed open-access periodical centered in biomedical sciences but with multidisciplinary coverage. If you want to share any new methodologies, any experiences of the application or improvement of such methodologies and any methodology-related academic issues with your peers, you will find the WJM a good media to publish your papers!

关键词： Methodology Biomedical sciences Peer-reviewed Open-access Journal

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应用于新型环路热管的两相引射器数值模拟

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化工学报 2024年第1期75卷 268-278页

作者：周尧杨小平倪一程刘继平魏进家严俊杰西安交通大学热流科学与工程教育部重点实验室陕西西安710049 西安交通大学化学工程与技术学院陕西西安710049 西安交通大学动力工程多相流国家重点实验室陕西西安710049

环路热管是一种高效被动式相变传热装置,广泛应用于高热流电子器件散热等领域。前期研究发现将小型两相引射器与平板式环路热管耦合,可大幅提高传热性能。然而,小型两相引射器内部流动及传热机理尚不清晰,难以对新型环路热管进行正向设... 详细信息

环路热管是一种高效被动式相变传热装置,广泛应用于高热流电子器件散热等领域。前期研究发现将小型两相引射器与平板式环路热管耦合,可大幅提高传热性能。然而,小型两相引射器内部流动及传热机理尚不清晰,难以对新型环路热管进行正向设计与理论建模。通过数值模拟研究了汽水参数和混合腔结构对两相引射器性能及内部流场分布的影响。结果表明,喉部下游存在凝结激波,随着背压增加,其位置逐渐向喉部移动;其强度与背压、蒸汽产量、混合腔长度呈正相关,与水温呈负相关。引射器最大工作背压在40~125 kPa,与蒸汽产量和水温呈正相关,与混合腔长度呈负相关。通过大量模拟,得到了设计功率下水温和混合腔长度对引射器工作模式和压比的影响规律。

关键词：环路热管引射器传热两相流凝结激波数值模拟

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Everolimus halts hepatic cystogenesis in a rodent model of polycystic-liver-disease

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World Journal of Gastroenterology 2017年第30期23卷 5499-5507页

作者： Frederik Temmerman Feng Chen Louis Libbrecht Ingrid Vander Elst Petra Windmolders Yuanbo Feng yicheng ni Humbert De Smedt Frederik Nevens Jos van Pelt Laboratory of Hepatology Department of Clinical and Experimental Medicine Faculty of Medicine University of Leuven Department of Gastroenterology and Hepatology University Hospitals KU Leuven Department of Radiology The first Affiliated Hospital School of Medicine Zhejiang University Department of Pathology Ghent University Hospital Department of Imaging and Pathology Faculty of Medicine Laboratory of Molecular and Cellular Signalling Unit of Clinical Digestive Oncology Department of Oncology KU Leuven and Leuven Cancer Institute (LKI)

AIM To develop a MRI-based method for accurate determination of liver volume(LV) and to explore the effect of long-term everolimus(EVR) treatment on LV in PCK rats with hepatomegaly. METHODS Thirty-one female PCK rats(model for polycystic-liverdisease: PCLD) were randomized into 3 groups and treatment was started at 16 wk, at the moment of extensive hepatomegaly(comparable to what is done in the human disease). Animals received: controls(n = 14), lanreotide(LAN: 3 mg/kg per 2 wk)(n = 10) or everolimus(EVR: 1 mg/kg per day)(n = 7). LV was measured at week 16, 24, 28. At week 28, all rats were sacrificed and liver tissue was harvested. Fibrosis was evaluated using quantitative image analysis. In addition, gene(quantitative RT-PCR) and protein expression(by Western blot) of the PI3K/Ak T/m TOR signaling pathway was investigated. RESULTS LV determination by MRI correlated excellent with the ex vivo measurements(r = 0.99, P nificantly halt of LV progression compared with controls(respectively, P = 0.01 and P = 0.04). Furthermore, EVR significantly reduced the amount of liver fibrosis(P = 0.004) thus might also prevent the development of portal hypertension. There was no difference in phosphorylation of Akt(Threonine 308) between LAN-treated PCK rats control PCK rats, whereas S6 was significantly more phosphorylated in the LAN group. Phosphorylation of Akt was not different between controls and EVR treated rats, however, for S6 there was significantly less phosphorylation in the EVR treated rats. Thus, both drugs interact with the PI3K/Ak T/m TOR signaling cascade but acting at different molecular levels.CONCLUSION Everolimus halts cyst growth comparable to lanreotide and reduces the development of fibrosis. m TORinhibition should be further explored in PCLD patients especially those that need immunosuppression.

关键词： Fibrocystic 肝疾病 mTOR 禁止者 Somatostatin 类似物肝体积测量磁性的回声成像

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Evaluation of necrosis avidity of radioiodinated 5-hydroxytryptophan and its potential applications in myocardial infarction imaging

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Chinese Chemical Letters 2019年第1期30卷 83-86页

作者： Lin Ma Lingqiao Cai Qiaomei Jin Jiajia Liang Dongjian Zhang Wei Liu yicheng ni Zhiqi Yin Jian Zhang Ke Pan Department of Natural Medicinal Chemistry & Department of TCMs Pharmaceuticals School of Traditional Chinese Pharmacy China Pharmaceutical University Affliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine Laboratories of Translational Medicine Jiangsu Province Academy of Traditional Chinese Medicine College of Pharmacy Nanjing University of Chinese Medicine Department of Nuclear Medicine The First Affiliated Hospital of Nanjing Medical University Theragnostic Laboratory Campus Gasthuisberg

This study aimed to seek necrosis avid agents with high safety from DNA binding agents. The interaction of 5-hydroxytryptophan(5-HTP) with DNA was investigated by a series of spectroscopic studies. Then, 5-HTP was labeled with iodine-131([^(131)I]5-HTP) and the necrosis avidity of [^(131)I]5-HTP was evaluated by in vitro cell binding assays, in vivo biodistribution experiments and blocking experiment. Finally, the potential of [^(131)I]5-HTP to image necrotic myocardium was explored in rat models with myocardial infarction by SPECT/CT imaging. Results showed that 5-HTP bound to DNA in groove binding mode and the binding constant was 1.69×10~4 L/mol. [~(^(131))I]5-HTP showed specific affinity to necrotic A549 cells,which might be related to cell nucleus. Biodistribution and autoradiography results showed preferential accumulation of [^(131)I]5-HTP in necrotic muscle(necrotic/viable muscle ratio: 6.95 ? 0.68 at 3 h postinjection(p.i.)), which could be blocked by 5-HTP with 66.7% decline, indicating that [^(131)I]5-HTP might share the same necrotic targets with 5-HTP. On SPECT/CT images, a hotspot was clearly observed at 3h p.***.in the necrotic myocardium while not in the control myocardium. In conclusion, [^(131) I]5-HTP is a novel necrosis avid agent and can rapidly visualize necrotic myocardium at 3 h p.i. The necrosis avidity mechanism of [^(131) I]5-HTP may be attributed to its interactions with exposed DNA in the necrotic tissues.

关键词： Radioiodinated 5-hydroxytryptophan Necrosis avidity DNA Groove binding Necrotic myocardium imaging

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An overview of translational(radio)pharmaceutical research related to certain oncological and non-oncological applications

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World Journal of Methodology 2013年第4期3卷 45-64页

作者： Marlein Miranda Cona Peter de Witte Alfons Verbruggen yicheng ni Department of Imaging and Pathology Faculty of MedicineBiomedical Sciences GroupKU LeuvenB-3000 LeuvenBelgium Molecular Small Animal Imaging Centre/Mo SAIC Faculty of MedicineBiomedical Sciences GroupKU LeuvenB-3000 LeuvenBelgium Faculty of Pharmaceutical Sciences Biomedical Sciences GroupKU LeuvenB-3000 LeuvenBelgium

Translational medicine pursues the conversion of scientific discovery into human health improvement.It aims to establish strategies for diagnosis and treatment of diseases.Cancer treatment is difficult.Radiopharmaceutical research has played an importantrole in multiple disciplines,particularly in translational oncology.Based on the natural phenomenon of necrosis avidity,Onco Ci Dia has emerged as a novel generic approach for treating solid malignancies.Under this systemic dual targeting strategy,a vascular disrupting agent first selectively causes massive tumor necrosis that is followed by iodine-131 labeled-hypericin(123IHyp),a necrosis-avid compound that kills the residual cancer cells by crossfire effect of beta radiation.In this review,by emphasizing the potential clinical applicability of Onco Ci Dia,we summarize our research activities including optimization of radioiodinated hypericin Hyp preparations and recent studies on the biodistribution,dosimetry,pharmacokinetic and,chemical and radiochemical toxicities of the preparations.Myocardial infarction is a global health problem.Although cardiac scintigraphy using radioactive perfusion tracers is used in the assessment of myocardial viability,searching for diagnostic imaging agents with authentic necrosis avidity is pursued.Therefore,a comparative study on the biological profiles of the necrosis avid 123I-Hyp and the commercially available 99mTc-Sestamibi was conducted and the results are demonstrated.Cholelithiasis or gallstone disease may cause gallbladder inflammation,infection and other severe complications.While studying the mechanisms underlying the necrosis avidity of Hyp and derivatives,their naturally occurring fluorophore property was exploited for targeting cholesterol as a main component of gallstones.The usefulness of Hyp as an optical imaging agent for cholelithiasis was studied and the results are presented.Multiple uses of automatic contrast injectors may reduce costs and save resources.However,cross-contaminations with bloodborne pathogens

关键词： Translational medical research Cancer treatment OncoCiDia Vascular disrupting agent Hy-pericin Myocardial infarction Gallstone Transfux

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Pancreatic imaging:Current status of clinical practices and small animal studies

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World Journal of Methodology 2017年第3期7卷 101-107页

作者： Ting Yin Yewei Liu Ronald Peeters Yuanbo Feng yicheng ni Department of Imaging and Pathology Biomedical Sciences Group KU Leuven Department of Radiology University Hospitals KU Leuven

Different causative factors acting on the pancreas can result in diseases such as pancreatitis, diabetes and pancreatic tumors. The high incidence and mortality of pancreatic diseases have placed diagnostic imaging in a crucial position in daily clinical practice. In this minireview article different pancreatic imaging techniques are discussed, from the standard clinical imaging modalities and state of the art clinical magnetic resonance imaging techniques to current situations in pre-clinical pancreatic imaging studies. In particular, the challenges of pre-clinical rodent pancreatic imaging are addressed, with both the image acquisition techniques and the post-processing methods for rodent pancreatic imaging elaborated.

关键词： Pancreatic imaging Rats State of the art clinical magnetic resonance imaging 3.0T scanner Quantitative magnetic resonance imaging

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Bifunctional staining for ex vivo determination of area at risk in rabbits with reperfused myocardial infarction

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World Journal of Methodology 2013年第3期3卷 27-38页

作者： Yuanbo Feng Zhan-Long Ma Feng Chen Jie Yu Marlein Miranda Cona Yi Xie Yue Li yicheng ni Theragnostic Laboratory Department of Imaging and Pathology Biomedical Sciences Group 3000 KU Leuven Belgium Departments of Radiology the First Affiliated Hospital Nanjing Medical University Nanjing 210029 Jiangsu Province China Departments of Electronics and Information System (ELIS) Ghent University Sint-Pietersnieuwstraat 25 9000 Gent Belgium Lab of Translational Medicine Jiangsu Academy of Traditional Chinese Medicine nanjing 210028 Jiangsu Province China Radiology Section University Hospitals 3000 Leuven Belgium

AIM: To develop a method for studying myocardial area at risk(AAR) in ischemic heart disease in correlation with cardiac magnetic resonance imaging(c MRI). METHODS: nine rabbits were anesthetized, intubated and subjected to occlusion and reperfusion of the left circumflex coronary artery(LCx) to induce myocardial infarction(MI). ECG-triggered c MRI with delayed en-hancement was performed at 3.0 T. After euthanasia, the heart was excised with the LCx re-ligated. Bifunctional staining was performed by perfusing the aorta with a homemade red-iodized-oil(RIO) dye. The heart was then agar-embedded for ex vivo magnetic resonance imaging and sliced into 3 mm-sections. The AAR was defined by RIO-staining and digital radiography(DR). The perfusion density rate(PDR) was derived from DR for the AAR and normal myocardium. The MI was measured by in vivo delayed enhancement(i DE) and ex vivo delayed enhancement(e DE) c MRI. The AAR and MI were compared to validate the bifunctional straining for cardiac imaging research. Linear regression with Bland-Altman agreement, one way-ANOVA with Bonferroni's multiple comparison, and paired t tests were applied for statistics.RESULTS: All rabbits tolerated well the surgical procedure and subsequent c MRI sessions. The openchest occlusion and close-chest reperfusion of the LCx, double suture method and bifunctional staining were successfully applied in all animals. The percentage MI volumes globally(n = 6) and by slice(n = 25) were 36.59% ± 13.68% and 32.88% ± 12.38% on i DE, and 35.41% ± 12.25% and 32.40% ± 12.34% on e DE. There were no significant differences for MI determination with excellent linear regression correspondence(r global = 0.89; r slice = 0.9) between i DE and e DE. The percentage AAR volumes globally(n = 6) and by slice(n = 25) were 44.82% ± 15.18% and 40.04% ± 13.64% with RIO-staining, and 44.74% ± 15.98% and 40.48% ± 13.26% by DR showing high correlation in linear regression analysis(r global = 0.99; r slice = 1.0). The mean differences of the two AAR measurements on Bl

关键词： Reperfused Acute myocardial infarction Rabbit model Cardiac magnetic resonance imaging Oil-red-o dye Iodized oil

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Review on prevention of falls in hospital settings

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Chinese Nursing Research 2016年第1期3卷 7-10页

作者： Yuan-Yuan Gu Koen Balcaen yicheng ni Jan Ampe Jan Goffin Department of Geriatric Medicine The First Hospital Affiliated to Nanjing Medical University300 Guangzhou AvenueNanjingJiangsu210000China Faculty of Medicine KU LeuvenHerestraat 49B-3000LeuvenBelgium University Hospitals Leuven Herestraat 49B-3000LeuvenBelgium

This review will first cover the root causes of falls, identify preventive measures associated with these falls, and provide an overview of best practice of fall prevention at leading institutions. There is signif- icant benefit in instituting a comprehensive program to reduce falls. After analyzing the results from many successful programs, it is apparent that an integrative program that consists of patient evaluations, environmental modification, and staff training can lead to a significant reduction in the overall preva- lence of falls. Such programs can be implemented at a low cost and therefore represent an improvement in care with a high return on investment.

关键词： Hospital settingsFallFall preventionintervention

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靶向放疗药物碘-131-金丝桃素的研究

靶向放疗药物碘-131-金丝桃素的研究

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2012年华东地区六省一市核医学学术会议

作者：孙自平张健邵海波 yicheng ni 山东省医科院江苏省中医药研究院中国医科大学比利时鲁汶大学

本文介绍了一种新型靶向放疗药物——碘--金丝桃素(I-MIH)及以该药为基础建立的全新的肿瘤治疗方法——肿瘤梯次靶向治疗技术。金丝桃素是一种小分子天然化合物,曾被用于动物的病毒疫病防治及治疗抑郁症等。我们发现该化合物具有很强的...

本文介绍了一种新型靶向放疗药物——碘--金丝桃素(I-MIH)及以该药为基础建立的全新的肿瘤治疗方法——肿瘤梯次靶向治疗技术。金丝桃素是一种小分子天然化合物,曾被用于动物的病毒疫病防治及治疗抑郁症等。我们发现该化合物具有很强的坏死组织亲和性且易于进行放射性碘标记,因此我们制备了碘-131-金丝桃素标记物并进行了详尽的实验研究。结果表明,I-MIH在靶区的药物浓度,是对应组织的几倍甚至几十倍,且在重要脏器无明显蓄积,是一种理想的靶向药物。I-MIH的靶标是坏死

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