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Characterization and validation of somatic mutation spectrum to reveal heterogeneity in gastric cancer by single cell sequencing

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Science Bulletin 2019年第4期64卷 236-244页

作者： Lihua Peng Rui Xing Dongbing Liu Li Bao Wenxiang Cheng Hongyi Wang Yuan Yu Xiaofeng Liu Lu Jiang Yan Wu Zhongxue An Qiaoyi Liang Ryong nam Kim Young kee Shin Huanming Yang Jian Wang Jun Yu Xiuqing Zhang Xun Xu Jiaan Yang Kui Wu Shida Zhu Youyong Lu BGI-Shenzhen China National GeneBank-Shenzhen BGI-Shenzhen Laboratory of Molecular Oncology Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Peking University Cancer Hospital & Institute Department of Drug Design and Pharmacology University of Copenhagen Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Department of Histology and Embryology Inner Mongolia Medical University Department of Medicine and Therapeutics State Key Laboratory of Digestive Disease Institute of Digestive Disease and Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong Department of Pharmacy College of Pharmacy Seoul National University James D. Watson Institute of Genome Sciences Micro Pharmatech Ltd Department of Biology University of Copenhagen

Gastric cancer(GC) is a highly heterogeneous disease with multiple cellular types and poor ***, the cellular evolution and molecular basis of GC at the individual intra-tumor level has not been well demonstrated. We performed single-cell whole exome sequencing to detect somatic singlenucleotide variants(SNVs) and significantly mutated genes(SMGs) among 34 tumor cells and 9 normal cells from a patient with GC. The Complete Prediction for Protein Conformation(CPPC) approach directly predicting the folding conformation of the protein 3D structure with Protein Folding Shape Code, combined with functional experiments were used to confirm the characterization of mutated SMGs in GC cells. We identified 201 somatic SNVs, including 117 non-synonymous mutations in GC cells. Further analysis identified 24 significant mutated genes(SMGs) in single cells, for which a single amino acid change might affect protein conformation. Among them, two genes(CDC27 and FLG) that were mutated only in single cells but not in the corresponding tumor tissue, were recurrently present in another GC tissue cohort, and may play a potential role to promote carcinogenesis, as confirmed by functional characterization. Our findings showed a mutational landscape of GC at intra-tumor level for the first time and provided opportunities for understanding the heterogeneity and individualized target therapy for this disease.

关键词： Gastric cancer Single-cell whole exome sequencing SNV Signi-cell mutated gene Heterogeneity

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Neutron Irradiation of Electronic Materials at HANARO

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Journal of Applied Mathematics and Physics 2014年第9期2卷 837-842页

作者： kee-nam Choo Man-Soon Cho Byung-Hyuk Jun Chan-Joong Kim Sang-Jun Park Department of Research Reactor Utilization Korea Atomic Energy Research Institute Daejeon South Korea

HANARO, a 30 MW open-pool type multipurpose research reactor, has been operated as a platform for nuclear researches in Korea, and irradiation facilities have been mainly utilized for various nuclear material irradiation tests requested by users. Although most irradiation tests have been related to national R&D relevant to nuclear power, demand for neutron irradiation of electro-magnetic materials is increasing rapidly at HANARO. Another research reactor, which is named the KIJANG research reactor (KJRR), is under construction in Korea. KJRR is dedicated to increasing the national radio-isotopes supply capacity and to the irradiation facilities including Neutron Transmutation Doping (NTD) facilities for power semiconductor production in a large scale and fast neutron irradiation (FNI) facility for fast neutron irradiation. The NTD and FNI facilities in the KJRR reactor can be effectively utilized on the study of separated effect of thermal and fast neutron irradiations on the properties of electro-magnetic materials. HANARO will also specialize more on irradiation research, including neutron irradiation of electronic materials. The research status and possibility of new electro-magnetic materials using neutron irradiation at HANARO are surveyed to ascertain the utilization of neutron irradiation technology in electro-magnetic material researches.

关键词： HANARO Neutron Irradiation Electro-Magnetic Material

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WNT5A drives interleukin-6-dependent epithelial-mesenchymal transition via the JAK/STAT pathway in keloid pathogenesis

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Burns & Trauma 2022年第1期10卷 200-215页

作者： Young In Lee Jung Eun Shim Jihee Kim Won Jai Lee Jae Woo Kim kee Hyun nam Ju Hee Lee Department of Dermatology Severance HospitalCutaneous Biology Research InstituteYonsei University College of MedicineSeoul 03722Korea Bioinformatics Collaboration Unit Yonsei University College of MedicineSeoul 03722Korea Department of Plastic and Reconstructive Surgery Severance HospitalYonsei University College of MedicineSeoul 03722Korea Scar Laser and Plastic Surgery Center Yonsei Cancer HospitalYonsei University College of MedicineSeoul 03722Korea Department of Biochemistry and Molecular Biology Chronic Intractable Disease for Systems Medicine Research CenterYonsei University College of MedicineSeoul 03722Korea Department of Surgery Severance HospitalYonsei University College of MedicineSeoulKorea

Background:Keloid scarring is a fibroproliferative disease caused by aberrant genetic activation with an unclear underlying *** predisposition,aberrant cellular responses to environmental factors,increased inflammatory cytokines and epithelial-mesenchymal transition(EMT)phenomena are known as major *** this study,we aimed to identify the molecular drivers that initiate keloid ***:Bulk tissue RNA sequencing analyses of keloid and normal tissues along with ex vivo and in vitro tests were performed to identify the contributing genes to keloid *** animal model of inflammatory keloid scarring was reproduced by replication of a skin fibrosis model with intradermal bleomycin injection in C57BL/6 ***:Gene set enrichment analysis revealed upregulation of Wnt family member 5A(WNT5A)expression and genes associated with EMT in keloid ***,human keloid tissues and the bleomycin-induced skin fibrosis animal model showed significantly increased expression ofWNT5A and EMT *** activation of the interleukin(IL)-6/Janus kinase(JAK)/signal transducer and activator of transcription(STAT)pathway and subsequent elevation of EMT markerswas also observed in keratinocytes co-cultured withWNT5A-activated fibroblasts or keloid ***,WNT5A silencing and the blockage of IL-6 secretion via neutralizing IL-6 antibody reversed hyperactivation of the STAT pathway and EMT markers in ***,STAT3 silencing significantly reduced the EMT-like phenotypes in both keratinocytes and IL-6-stimulated ***:Intercellular communication via the WNT5A and STAT pathways possibly underlies a partial mechanism of EMT-like phenomena in keloid ***-6 secreted from WNT5A-activated fibroblasts or keloid fibroblasts activates the JAK/STAT signaling pathway in adjacent keratinocytes which in turn express EMT markers.A better understanding of keloid development and the

关键词： Keloid Wnt family member 5A Interleukin-6 JAK/STAT pathway Epithelial-mesenchymal transition Scar Epithelial mesenchymal transition

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Photodynamic therapy-mediated modulation of inflammatory cytokine production by Epstein–Barr virus-infected nasopharyngeal carcinoma cells

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Cellular & Molecular Immunology 2010年第4期7卷 323-326页

作者： Ho-kee Koon Kwok-Wai Lo Kwok-nam Leung Maria Li Lung Chris Chi-Kwong Chang Ricky Ngok-Shun Wong Wing-Nang Leung Nai-Ki Mak Department of Biology Hong Kong Baptist UniversityKowloonHong Kong Department of Anatomical and Cellular Biology and State Key Laboratory in Oncology in South China Prince of Wales HospitalShatinHong Kong Department of Biochemistry and Food and nutritional Sciences Programme The Chinese University of Hong KongShatinHong Kong Department of Biology Hong Kong University of Science and TechnologyHong Kong Department of Chemistry Hong Kong University of Science and TechnologyKowloonHong Kong School of Chinese Medicine The Chinese University of Hong KongShatinHong Kong

Nasopharyngeal carcinoma(NPC)is a malignant disease associated with Epstein–Barr virus(EBV)*** study aims to examine the effects of EBV infection on the production of proinflammatory cytokines in NPC cells after the Zn-BC-AM photodynamic therapy(PDT)*** were treated with the photosensitiser Zn-BC-AM for 24 h before light *** ELISA was used to evaluate the production of *** the same experimental condition,HK-1-EBV cells produced a higher basal level of IL-1a(1561 pg/ml),IL-1b(16.6 pg/ml)and IL-8(422.9 pg/ml)than the HK-1 *** the light dose of 0.25–0.5 J/cm2,Zn-BC-AM PDT-treated HK-1-EBV cells were found to produce a higher level of IL-1a and IL-1b than the HK-1 *** production of IL-1b appeared to be mediated via the IL-1b-converting enzyme(ICE)-independent *** contrast,the production of angiogenic IL-8 was downregulated in both HK-1 and HK-1-EBV cells after Zn-BC-AM *** results suggest that Zn-BC-AM PDT might indirectly reduce tumour growth through the modulation of cytokine production.

关键词： Photodynamic therapy nasopharyngeal carcinoma cytokines Epstein-Barr virus

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Impact of statin usage patterns on outcomes after percutaneous coronary in-tervention in acute myocardial infarction：Korea Working Group on Myocar-dial Infarction registry （KorMI） study

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Journal of Geriatric Cardiology 2014年第2期11卷 93-99页

作者： Chan-Hee Lee Sang-Hee Lee Jong-Seon Park Young-Jo Kim kee-Sik Kim Shung-Chull Chae Hyo-Soo Kim Dong-Ju Choi Myeong-Chan Cho Seung-Woon Rha Myung-Ho Jeong Department of Cardiology Yeungnam University Hospital 170 Hyeonchung-ro Nam-gu Daegu 705-717 South Korea Department of Internal Medicine Daegu Catholic University Hospital 33 Duryugongwon-ro 17-gil Nam-gu Daegu 705-718 South Korea Department of Internal Medicine Kyungpook National University Hospital 130 Dongdeok-ro Jung-gu Daegu 700-721 South Korea Department of Internal Medicine Seoul National University Hospital 101 Daehak-ro Jongno-gu Seoul 110-744 South Korea Department of Internal Medicine Seoul National University Bundang Hospital 82 Gumi-ro 173-gil Bundang-gu Seongnam 463-707 South Korea Department of Internal Medicine Chungbuk National University Hospital 776 1sunhwan-ro Heungdeok-gu Cheongju 361-711 South Korea Department of Internal Medicine Korea University Guro Hospital 148 Gurodong-ro Guro-gu Seoul 152-703 South Korea Department of Internal Medicine Chonnam National University Hospital 42 Jebong-ro Dong-gu Gwangju 501-757 South Korea

Background The benefit of statin use after acute ST-segment elevation myocardial infarction （STEMI） has been well established, however, the influence of the timing of statin administration has not been elucidated. The objective of this study focused on early clinical outcomes after percutaneous coronary intervention （PCI）. Methods This analysis of the Korea Working Group on Myocardial Infarction registry （KorMI） study included 3,584 STEMI patients （mean age, 63 ±13 years;male, 2,684, 74.9%） undergoing PCI from January 2008 to June 2009. Rates of major adverse cardiac events （MACE：all-cause death, recurrent MI, and target lesion revascularization） were compared among patients grouped according to statin therapy timing：I, both during and after hospitalization （n=2,653, 74%）;II, only during hospita-lization （n=309, 8.6%）;III, only after discharge （n=157, 4.4%）;and IV, no statin therapy （n=465, 13%）. Mean follow-up duration was 234 ± 113 days. Results Multivariate factors of statin use during hospitalization included prior statin use, multiple diseased vessels, final thrombolysis in myocardial infarction flow grade III, and low-density lipoprotein cholesterol level. At 6-month follow-up, groups Ⅲ and Ⅳ had the highest MACE rates （2.3%, 3.9%, 5.1%, and 4.9%for groups I-IV, respectively, P=0.004）. After adjusting for confounders, groups Ⅱ-Ⅳ had a higher MACE risk than group Ⅰ [hazard ratio （HR）：3.20, 95%confidence interval （95%CI）：1.31-7.86, P=0.011;HR：3.84, 95%CI：1.47-10.02, P=0.006;and HR：3.17, 95%CI：1.59-6.40, P=0.001;respectively]. Conclusions This study, based on the national registry database, shows early and continuous statin therapy improvs early outcomes of STEMI patients after PCI in real-world clinical prac-tice.

关键词： Statins Acute myocardial infarction Treatment omcome

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亚洲近视管理共识

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中华眼视光学与视觉科学杂志 2022年第3期24卷 161-169页

作者： Monica Jong Serge Resnikoff Kah Ooi Tan 吕帆 Kah Meng Chung 胡楚南 Ian Morgan Oliver Kam Tong Woo 蓝卫忠齐备瞿佳杨智宽樊志诚吴佩昌 Ian Flitcroft Murphy Hian kee Chan Thok Chuan Tan Charlie Ho David Chai Wong Chong Liang Hwee Koh Olivia Qian Ru Cheng 机构不详亚洲眼视光管理协会(AOMA)与亚洲视光大会(AOC)合作项目

指南的目标本指南是从国际近视研究所(IMI)白皮书中提取出来的有关近视管理方面的建议[1,2]。本指南所提供的内容都是根据现有最新数据(截至2022年3月)而来,其治疗可行性和执业范围因地区而异,应根据实际情况做调整。眼保健专家组通过... 详细信息

指南的目标本指南是从国际近视研究所(IMI)白皮书中提取出来的有关近视管理方面的建议[1,2]。本指南所提供的内容都是根据现有最新数据(截至2022年3月)而来,其治疗可行性和执业范围因地区而异,应根据实际情况做调整。眼保健专家组通过对现有最优科学数据进行分析诠释,从而形成了本指南。在工作中,近视管理从业者应该将患者需求放在首位,全面考虑患者具体情况后再提出合适的处理意见。

关键词：执业范围科学数据处理意见患者需求眼保健新数据近视白皮书

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