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具有TSC2基因突变的儿童嗜酸性实性和囊性肾细胞癌临床病理学观察

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中华病理学杂志 2020年第7期49卷 693-698页

作者：杨文萍 Kenneth Tou En Chang 徐红艳 chik hong kuick Eileen Hui Qi Ng 黄慧熊枫吴艳曾松涛樊金星 Xinyi Loh 江西省儿童医院病理科南昌330006 KK Women′s and Children′s Hospital Singapore 229899Singapore

目的:探讨具有TSC2基因突变的儿童嗜酸性实性和囊性肾细胞癌(ESC RCC)临床病理特征、免疫组织化学及分子遗传学特征和预后。方法:收集2017年至2018年2例ESC RCC临床资料,HE和免疫组织化学染色(EnVision)法进行形态学观察;荧光原位杂交检... 详细信息

目的:探讨具有TSC2基因突变的儿童嗜酸性实性和囊性肾细胞癌(ESC RCC)临床病理特征、免疫组织化学及分子遗传学特征和预后。方法:收集2017年至2018年2例ESC RCC临床资料,HE和免疫组织化学染色(EnVision)法进行形态学观察;荧光原位杂交检测TFE3、TFEB断裂重排基因;分子基因检测,PCR扩增,二代测序。结果:2例ESC RCC为男性,年龄分别9岁8个月和13岁,均发生在右肾。肿瘤大小5~7 cm,切面囊实性,灰红、灰白鱼肉样。显微镜下肿瘤具有纤维性包膜,肿瘤细胞突破胞膜。肿瘤细胞弥漫分布,圆形、多边性,胞质丰富,嗜伊红,可见大小不一的空泡,呈透明细胞样;部分区域类似乳头样结构,可见纤维轴心。细胞核圆形、泡状核,易见多核及巨核细胞,核分裂象未见;少量大小不一的囊样结构,囊壁可见单层瘤细胞被覆呈钉突样。间质见厚壁血管,灶状淋巴细胞浸润;较多嗜伊红坏死,可见钙化和胆固醇结晶。免疫组织化学阳性表达:PAX8(弥漫)、细胞角蛋白(CK)20、广谱细胞角蛋白(CKpan,局灶)、CD10(1例局灶/1例弥漫)、INI1、波形蛋白、CD68阳性,Ki-67阳性指数5%~10%。HMB45、S-100蛋白、Melan A、p53、结蛋白、TFE3、CK7、CK19、上皮细胞膜抗原(EMA)、CD56、嗜铬粒素A(CgA)、突触素、CD30、CD117、WT1、平滑肌肌动蛋白(SMA)阴性。分子遗传学检测:TFE3、TFEB断裂重排阴性。二代测序:例1,TSC2 ***574Ter(0.198);例2,TSC2 ***406Ter(0.355)。结论:ESC RCC儿童发病比较罕见,容易误诊,其具有独特的病理形态学特征、免疫表型和分子遗传学改变,预后较好。

关键词：肾肿瘤儿童免疫组织化学基因测定

儿童NTRK重排间叶源性肿瘤临床病理学观察

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中华病理学杂志 2020年第7期49卷 675-680页

作者：殷敏智马靖何巧沈萍陈洁枫金晓婷张忠德 chik hong kuick Chen Huiyi Eileen Hui Qi Ng Sze Jet Aw Kenneth Tou En Chang 上海交通大学医学院附属上海儿童医学中心病理科 200127 Department of Pathology and Laboratory Medicine KK Women′s and Children′s HospitalSingapore 229899Singapore

目的:探讨儿童NTRK重排间叶源性肿瘤临床和病理学特征,以提高对该类疾病的认识。方法:收集上海交通大学医学院附属上海儿童医学中心及新加坡KK Women′s and Children′s Hospital从2017年1月至2019年9月5例手术切除标本,采用EnVision... 详细信息

目的:探讨儿童NTRK重排间叶源性肿瘤临床和病理学特征,以提高对该类疾病的认识。方法:收集上海交通大学医学院附属上海儿童医学中心及新加坡KK Women′s and Children′s Hospital从2017年1月至2019年9月5例手术切除标本,采用EnVision法检测免疫组织化学表型,荧光原位杂交(FISH)检测相关基因并对NTRK基因重排进行克隆性分析。结果:该组5例患儿,3例男性,2例女性。年龄从3个月到13岁,部位包括软组织(膝、胸腔、腹壁)和肾,肿瘤大小为4.5~12.5 cm。组织学检查主要呈梭形细胞肿瘤,浸润性生长,可伴有炎性细胞。免疫表型上,肿瘤细胞阳性表达Pan-TRK,分子检测均存在NTRK基因重排,包括DCTN1-NTRK1的发现。除2例目前接受靶向药物治疗,其余均为无疾病进展病例,随访时间9~29个月。结论:NTRK重排间叶源性肿瘤,其肿瘤发生部位广泛,组织学图像多变。免疫组织化学Pan-TRK可以帮助诊断,NTRK基因检测确认其存在重排是诊断的金标准,对不能完整切除或有复发、转移病例建议靶向药物治疗。

关键词：儿童免疫组织化学分子靶向治疗间叶源性肿瘤

Identification of novel small-molecule inhibitors of SARS-CoV-2 by chemical genetics

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4028-4044页

作者： Chris Chun-Yiu Chan Qian Guo Jasper Fuk-Woo Chan Kaiming Tang Jian-Piao Cai Kenn Ka-Heng chik Yixin Huang Mei Dai Bo Qin Chon Phin Ong Allen Wing-Ho Chu Wan-Mui Chan Jonathan Daniel Ip Lei Wen Jessica Oi-Ling Tsang Tong-Yun Wang Yubin Xie Zhenzhi Qin Jianli Cao Zi-Wei Ye Hin Chu Kelvin Kai-Wang To Xing-Yi Ge Tao Ni Dong-Yan Jin Sheng Cui Kwok-Yung Yuen Shuofeng Yuan State Key Laboratory of Emerging Infectious Diseases Carol Yu Centre for InfectionDepartment of MicrobiologySchool of Clinical MedicineLi Ka Shing Faculty of Medicinethe University of Hong KongPokfulamHong Kong SAR 999077China Department of Infectious Diseases and Microbiology the University of Hong Kong-Shenzhen HospitalShenzhen 518000China Centre for Virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong Kong SAR 999077China Academician Workstation of Hainan Province Hainan Medical University-the University of Hong Kong Joint Laboratory of Tropical Infectious DiseasesHaikou 571100China School of Biomedical Sciences Li Ka Shing Faculty of Medicinethe University of Hong KongPokfulamHong Kong SAR 999077China NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen Biology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China College of Biology Hunan Provincial Key Laboratory of Medical VirologyHunan UniversityChangsha 410082China

There are only eight approved small molecule antiviral drugs for treating *** them,four are nucleotide analogues(remdesivir,JT001,molnupiravir,and azvudine),while the other four are protease inhibitors(nirmatrelvir,ensitrelvir,leritrelvir,and simnotrelvir-ritonavir).Antiviral resistance,unfavourable drug‒drug interaction,and toxicity have been reported in previous *** there is a dearth of new treatment options for *** this work,a three-tier cell-based screening was employed to identify novel compounds with anti-SARS-CoV-2 *** compound,designated 172,demonstrated broad-spectrum antiviral activity against multiple human pathogenic coronaviruses and different SARS-CoV-2 variants of *** studies validated by reverse genetics showed that compound 172 inhibits the 3-chymotrypsin-like protease(3CLpro)by binding to an allosteric site and reduces 3CLpro dimerization.A drug synergistic checkerboard assay demonstrated that compound 172 can achieve drug synergy with nirmatrelvir in *** vivo studies confirmed the antiviral activity of compound 172 in both Golden Syrian Hamsters and K18 humanized ACE2 ***,this study identified an alternative druggable site on the SARS-CoV-23CLpro,proposed a potential combination therapy with nirmatrelvir to reduce the risk of antiviral resistance and shed light on the development of allosteric protease inhibitors for treating a range of coronavirus diseases.

关键词： SARS-CoV-2 High throughput screening Broad-spectrum antiviral treatment 3CLpro inhibitor Allosteric-site inhibitor Animal models Chemical genetics Reverse genetics

Gene-switch therapy for beta-hemoglobinopathies a genetic disease linked with malaria

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Gene-switch therapy for beta-hemoglobinopathies a genetic di...

P21-activated kinase 1 (PAK1)-mediated cytoskeleton rearrangement promotes SARS-CoV-2 entry and ACE2 autophagic degradation

全国寄生虫学与热带医学学术研讨会

作者： Ming Chiu FUNG~1,Ki Wai chik~2 and hong Tao XING~1 1 Department of Biology,2 Department of Paediatrics,The Chinese University of hong Kong,Shatin,hong Kong

The long history of epidemic of malaria forcing the selection of a mutated beta-globin gene in ***-nopathies such as the sickle cell anemia and thalassemias become the most prevalent serious genetic disorders affecting human populations and represent a major health burden *** sickle cell anmeia is not common in China, the prevalence of beta-thalassemia is 3.4%in hong Kong and 2.16%in *** of defected globin genes results in a clinical *** red cell transfusions and iron chelating therapy remain the basis of therapy for this disease for the majority of ***,in most of these patients,the upstream globin genes are intact and fully *** these could be reactivated,functional hemoglobin synthesis could be maintained during adulthood, ameliorating the severity of the *** many years,the search for treatment aimed at reduction of globin chain imbalance in patients with thalassemia has focused on the pharmacological manipulation of fetal hemoglobin(22;HbF).

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5353-5367页

作者： Ming Liu Bingtai Lu Yue Li Shuofeng Yuan Zhen Zhuang Guangyu Li Dong Wang Liuheyi Ma Jianheng Zhu Jinglu Zhao Chris Chung-Sing Chan Vincent Kwok-Man Poon Kenn Ka-Heng chik Zhiyao Zhao Huifang Xian Jingxian Zhao Jincun Zhao Jasper Fuk-Woo Chan Yuxia Zhang Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical CentreState Key Laboratory of Respiratory DiseasesGuangzhou Medical University510623 GuangzhouGuangdongChina Medical Research Institute Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangdongChina State Key Laboratory of Emerging Infectious Diseases Carol Yu Centre for InfectionDepartment of MicrobiologySchool of Clinical MedicineLi Ka Shing Faculty of MedineThe University of Hong KongPokfulamHong KongChina Department of Clinical Microbiology and Infection Control The University of Hong Kong Shenzhen HospitalShenzhenGuangdongChina Centre for Virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong KongChina State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affliated Hospital of Guangzhou Medical UniversityGuangzhouChina The Third Afliated Hospital of Zhengzhou University 450052 ZhengzhouChina Guangzhou Laboratory GuangzhouGuangdong ProvinceChina Chongqing International Institute for Immunology ChongqingChina

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of coronavirus disease 2019(COVID-19),has had a significant impact on healthcare systems and economies *** continuous emergence of new viral strains presents a major challenge in the development of effective antiviral *** that possess broad-spectrum antiviral activities are desirable to control SARS-CoV-2 ***2,an angiotensin-containing enzyme that prevents the overactivation of the renin angiotensin system,is the receptor for ***2 interacts with the spike protein and facilitates viral attachment and entry into host ***,SARS-CoV-2 infection also promotes ACE2 *** restoring ACE2 surface expression has an impact on SARS-CoV-2 infection is yet to be ***,we show that the ACE2-spike complex is endocytosed and degraded via autophagy in a manner that depends on clathrin-mediated endocytosis and PAK1-mediated cytoskeleton *** contrast,free cellular spike protein is selectively cleaved into S1 and s2 subunits in a lysosomal-dependent ***,we show that the pan-PAK inhibitor FRAX-486 restores ACE2 surface expression and suppresses infection by different SARS-CoV-2 ***-486-treated Syrian hamsters exhibit significantly decreased lung viral load and alleviated pulmonary inflammation compared with untreated *** summary,our findings have identified novel pathways regulating viral entry,as well as therapeutic targets and candidate compounds for controlling the emerging strains of SARS-CoV-2 infection.

关键词： ACE2 inflammation rearrangement

A NFW LINK BETWEEN NERVOUS SYSTEM AND BLOOD

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A NFW LINK BETWEEN NERVOUS SYSTEM AND BLOOD

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作者：杨默 Li K Xia WJ Pong NH chik KW Li CK Fok TF Department of Paediatrics The Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong. Department of Paediatrics The Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong. Department of Paediatrics The Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong. Department of Paediatrics The Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong. Department of Paediatrics The Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong. Department of Paediatrics The Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong. Department of Paediatrics The Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong.

＜正＞ Neurotransmitter 5-HT is a growth factor for hematopoiesis:Serotonin（5-hydroxytryptamine,5-HT） hasrecently been recognized not only as a neurotransmitter and vasoactive agent,but also as a growth *** study has firstly shown that serotonin significantly stimulates megakaryocytopoiesis via 5-HT2receptors （Yang et al,Blood Coagul Fibrin 1996）.In this study, we further investigated the new functions ofthe old molecule on hematopoietic stem and progenitor *** results showed that:（1）Serotonin（200 nM）significantly enhanced TPO,SCF plus FL-induced the ex vivo expansion of CD34+ cells,CD34+38-cells andCD41+61+cells from cord *** also had a promoting effect on megakaryocyte differentiation.

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香港科学园GIFT绿色建筑

现代装饰 2015年第7期 104-107页

作者： Eugene Kiang Jennifer chik 白骐鸣

这是一个名为＂给香港一个GIFT＂的比赛,要求为香港科学园设计一座标志性的绿色建筑,并鼓励可持续发展的生活方式。该地点三期开发致力于将高科技初创企业和中小型企业培养成可持续发展的企业。第三期开发展示了最新的绿色技术和可持续... 详细信息

这是一个名为＂给香港一个GIFT＂的比赛,要求为香港科学园设计一座标志性的绿色建筑,并鼓励可持续发展的生活方式。该地点三期开发致力于将高科技初创企业和中小型企业培养成可持续发展的企业。第三期开发展示了最新的绿色技术和可持续发展的建筑设计,并以零碳排放标准为目标。这并不是强调运用最新的绿色技术和先进的绿色建筑设计,设计师建议回到＂绿色设计＂的基本含义。设计师认为,绿色设计的基本原则应该是认识自然,欣赏自然的力量之美和连接人造与自然,让建筑与自然充分的融合与发展。

关键词：科学园 GIFT 绿色技术认识自然绿色建筑设计建筑形态中小型企业碳排放吐露港地面升起

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晚古生代冈瓦纳的演化:长逾13500km的基墨利超级地体的裂离及其向亚洲的漂移(英文)

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地球学报 2012年第S1期33卷 2-3页

作者： Jason R.ALI Jonathan C.AITCHISON Haz M.C.CHEUNG Sam S.Y.chik SUN Ya-dong Department of Earth Sciences University of Hong KongPokfulam Road School of Geosciences University of SydneySydneyNSW 2006Australia Faculty of Earth Sciences China University of Geosciences School of Earth and Environment University of LeedsLeeds LS2 9JTUK

The Cimmerian terrane forms an almost unbroken chain stretching >13,500 km,from central southern Europe to western Indonesia,via SE Europe,the Middle East,Afghanistan,Tibet,SW China and ***,it is Earth’s most spectac... 详细信息

关键词： Cimmerian terrane Paleomagnetism Baoshan Block Sibumasu Block

Application of hematopoietic growth factor TPO to the protection and repair of the central nervous system

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Application of hematopoietic growth factor TPO to the protec...