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Molecular basis of von Hippel-Lindau syndrome in Chinese patients

Chinese Medical Journal 2011年第2期000卷 237-241页

作者： SIU Wai-kwan MA Ronald Ching-wan lam Ching-wan MAK Chloe Miu YUEN Yuet-ping LO Fai-man Ivan CHAN Kin-wan lam Siu-fung LING Siu-cheung TONG Sui-fan SO Wing-yee CHOW Chun-chung TANG Mary Hoi-yin TAM wing-hung CHAN Albert Yan-wo Department of Pathology Princess Margaret Hospital Hong Kong China Department of Medicine & Therapeutics The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong China Department of Pathology Li Ka Shing Faculty of Medicine The University of Hong Kong Queen Mary Hospital Hong Kong China Clinical Genetic Service Department of Health Hong Kong China Department of Medicine and Geriatrics Princess Margaret Hospital Hong Kong China Department of Paediatrics and Adolescent Medicine Princess Margaret Hospital Hong Kong China Department of Obstetrics & Gynaecology Tsan Yuk Hospital Hong Kong China Department of Obstetrics & Gynaecology The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong China

Background Von Hippel-Lindau （VHL） syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various *** genetic basis of VHL in Southern Chinese is largely *** this study,we characterized the mutation spectrum of VHL in nine unrelated Southern Chinese *** Nine probands with clinical features of VHL,two symptomatic and eight asymptomatic family members were included in this *** diagnosis was performed twice for one *** probands had only isolated bilateral *** VHL gene was screened for mutations by polymerase chain reaction,direct sequencing and multiplex ligation-dependent probe amplification （MLPA）.Results The nine probands and the two symptomatic family members carried heterozygous germline *** different VHL mutations were identified in the nine *** splicing mutation,NM_000551.2：c.463＋1G〉T,was *** other seven VHL mutations,c.233A〉G [***78Ser],c.239G〉T [***80lle],c.319C〉G [***107Gly],c.481C〉T [***161X],c.482G〉A [***161GIn],c.499C〉T [***167Trp] and an exon 2 deletion,had been previously *** asymptomatic family members were positive for the mutation and the other five tested *** prenatal diagnosis,the fetuses were positive for the *** Genetic analysis could accurately confirm VHL syndrome in patients with isolated tumours such as sporadic phaeochromocytoma or epididymal papillary *** detection in asymptomatic family members allows regular tumour surveillance and early intervention to improve their ***-based diagnosis can have an important impact on clinical management for VHL families.

关键词： von Hippel-Lindau syndrome VHL gene Chinese VHL mutations

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Single-cell transcriptomic analysis uncovers intratumoral heterogeneity and drug-tolerant persister in ALK-rearranged lung adenocarcinoma

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Cancer Communications 2023年第8期43卷 951-955页

作者： Hoi-Hin Kwok Huiyu Li Jiashuang Yang Junyang Deng Nerissa Chui-Mei Lee Timmy Wing-Kuk Au Alva Ko-Yung Sit Michael Kuan-Yew Hsin Stephanie Kwai-yee Ma LydiaWai-Ting Cheung Luc Girard Junya Fujimoto Ignacio Ivan Wistuba Boning Gao John Dorrance Minna David Chi-Leung lam Department of Medicine Li Ka Shing Faculty of MedicineUniversity of Hong KongHong Kong SARP.R.China Nancy B.and Jake L.Hamon Center for Therapeutic Oncology Research University of Texas Southwestern Medical CenterDallasTexasUSA Cardiothoracic Surgical Department Queen Mary HospitalHong Kong SARP.R.China School of Biomedical Sciences Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARP.R.China Department of Translational Molecular Pathology Division of Pathology/Lab MedicineUniversity of Texas MD Anderson Cancer CenterHoustonTexasUSA

Dear Editor,Non-small cell lung carcinoma(NSCLC)accounts for more than 85%of all lung cancers[1].Lung adenocarcinomas(ADCs)arising from never-smokers have been frequently found to be associated with oncogenic driver mutations,including anaplastic lymphoma kinase(ALK)*** microtubule-associated protein-like 4(EML4)is the most common fusion partner of the ALK gene[2].Tyrosine kinase inhibitors(TKIs)are currently the first-line treatment for advanced EML4-ALKrearranged lung ADC.

关键词： lung adenocarcinoma Lung

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Distinctive serotypes of SARS-related coronaviruses defined by convalescent sera from unvaccinated individuals

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hLife 2023年第1期1卷 26-34页

作者： Chee Wah Tan Feng Zhu Wan Ni Chia #Barnaby EYoung Aileen Ying Yan Yeoh Thomas Althaus Chee Fu Yung Wee Chee Yap Beng Lee Lim Mark I-C Chen Jinyan Zhang Yun Yan Mah Eric Voiglio Alex Sigal Jianxin Huo Shengli Xu yee Joo Tan Kong-Peng lam David Lye Lin-Fa Wang Programme in Emerging Infectious Diseases Duke-NUS Medical SchoolSingapore National Center of Infectious Diseases Singapore Tan Tock Seng Hospital Singapore Lee Kong Chian School of Medicine Nanyang Technology UniversitySingapore Centre Scientifique de Monaco Monaco Direction de I’Action Sanitaire de Monaco Monaco Infectious Disease Service Department of PediatricsKK Women’s and Children’s HospitalSingapore Duke-NUS Medical School Singapore African Health Research Institute DurbanSouth Africa Singapore Immunology Network Agency for ScienceTechnology and ResearchSingapore Department of Physiology Yong Loo Lin School of MedicineNational University of SingaporeSingapore Department of Microbiology and Immunology Yong Loo Lin School of MedicineNational University of SingaporeSingapore Infectious Diseases Translational Research Programme National University of SingaporeSingapore 14School of Biological SciencesNanyang Technological UniversitySingapore Singhealth Duke-NUS Global Health Institute Singapore

Multiple Omicron sub-lineages have emerged,with Omicron XBB and XBB.1.5 subvariants becoming the dominant variants globally at the time of this *** key feature of new variants is their ability to escape humoral immunity despite the fact that there are limited genetic changes from their preceding *** raises the question of whether Omicron should be regarded as a separate serotype from viruses serologically clustered with the ancestral severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)***,we present cross-neutralization data based on a pseudovirus neutralization test using convalescent sera from naïve individuals who had recovered from primary infection by SARS-CoV-1 and SARS-CoV-2 strains/variants including the ancestral virus and variants Beta,Delta,Omicron BA.1,Omicron BA.2 and Omicron *** results revealed no significant cross-neutralization in any of the three-way testing for SARS-CoV-1,ancestral SARS-CoV-2 and SARS-CoV-2 Omicron *** data argue for the assignment of three distinct serotypes for the currently known human-infecting SARS-related coronaviruses.

关键词： SARS-CoV-2 SARS-CoV-1 serotype Omicron primary infection convalescent sera

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A six-year descriptive epidemiological study of human coronavirus infections in hospitalized patients in Hong Kong

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Virologica Sinica 2016年第1期31卷 41-48页

作者： Cyril C.Y.Yip Carol S.F.lam Hayes K.H.Luk Emily Y.M.Wong Rodney A.Lee Lok-yee So Kwok-Hung Chan Vincent C.C.Cheng Kwok-Yung Yuen Patrick C.Y.Woo Susanna K.P.Lau Department of Microbiology The University of Hong Kong Department of Microbiology Pamela Youde Nethersole Eastern Hospital Department of Paediatrics and Adolescent Medicine Pamela Youde Nethersole Eastern Hospital Research Centre of Infection and Immunology The University of Hong Kong State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong

We conducted a six-year epidemiological study on human coronaviruses（HCoVs） circulating in Hong Kong, using 8275 nasopharyngeal samples from patients with acute respiratory tract infections. HCoVs were detected in 77（0.93%） of the samples by a pan-HCoV RT-PCR assay. The most frequently detected HCoV species was HCoV-OC43（0.58%）, followed by HCoV-229E（0.15%）,HCoV-HKU1（0.13%） and HCoV-NL63（0.07%）. HCoVs were detected throughout the study period（September 2008–August 2014）, with the highest detection rate from September 2010 to August2011（22/1500, 1.47%）. Different seasonal patterns of each HCoV species in Hong Kong were ***-OC43 was predominant in the fall and winter, whereas HCoV-HKU1 showed peak activity in winter, with a few cases occurred in spring and summer. HCoV-229 E mainly occurred in winter and spring, while HCoV-NL63 was predominant in summer and autumn. HCoVs most commonly infect the elderly and young children, with median age of 79.5 years（range, 22 days to 95 years）.Intriguingly, the detection rate of HCoV-OC43 in the age group of ＆gt; 80 years（26/2380, 1.09%） was significantly higher than that in the age group of 0–10 years（12/2529, 0.47%）（P 〈 0.05）. These data provides new insight into the epidemiology of coronaviruses.

关键词： epidemiology human coronaviruses respiratory tract infections

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Genomic,transcriptomic,and metabolomic analysis of Oldenlandia corymbosa reveals the biosynthesis and mode of action of anti-cancer metabolites

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Journal of Integrative Plant Biology 2023年第6期65卷 1442-1466页

作者： Irene Julca Daniela Mutwil-Anderwald Vaishnervi Manoj Zahra Khan Soak Kuan Lai Lay K.Yang Ing T.Beh Jerzy Dziekan Yoon P.Lim Shen K.Lim yee W.Low Yuen I.lam Seth Tjia Yuguang Mu Qiao W.Tan Przemyslaw Nuc Le M.Choo Gillian Khew Loo Shining Antony Kam James P.Tam Zbynek Bozdech Maximilian Schmidt Bjoern Usadel Yoganathan Kanagasundaram Saleh Alseekh Alisdair Fernie Hoi Y.Li Marek Mutwil School of Biological Sciences Nanyang Technological UniversitySingapore 639798Singapore Shared Analytics Singapore Institute of Food and Biotechnology Innovation(SIFBI)Agency for ScienceTechnology and Research(A*STAR)Singapore 138671Singapore Department of Biochemistry National University of SingaporeSingapore 117596Singapore Singapore Botanic Gardens Singapore 259569Singapore Department of Gene Expression Faculty of BiologyInstitute of Molecular Biology and BiotechnologyAdam Mickiewicz UniversityPoznan 61-614Poland IBG-4 Bioinformatics Forschungszentrum JülichJülich 52428Germany Max-Planck-Institut für Molekulare Pflanzenphysiologie Potsdam-Golm 14476Germany Center of Plant Systems Biology and Biotechnology Plovdiv 4000Bulgaria

Plants accumulate a vast array of secondary metabolites,which constitute a natural resource for *** corymbosa belongs to the Rubiaceae family,and has been used in traditional medicine to treat different diseases,including ***,the active metabolites of the plant,their biosynthetic pathway and mode of action in cancer are *** fill these gaps,we exposed this plant to eight different stress conditions and combined different omics data capturing gene expression,metabolic profiles,and anti-cancer *** results show that *** extracts are active against breast cancer cell lines and that ursolic acid is responsible for this ***,we assembled a high-quality genome and uncovered two genes involved in the biosynthesis of ursolic ***,we also revealed that ursolic acid causes mitotic catastrophe in cancer cells and identified three high-confidence protein binding targets by Cellular Thermal Shift Assay(CETSA)and reverse ***,these results constitute a valuable resource to further characterize the biosynthesis of active metabolites in the Oldenlandia group,while the mode of action of ursolic acid will allow us to further develop this valuable compound.

关键词： genome medicinal metabolomics mode of action transcriptome

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Potential Antiviral Target for SARS-CoV-2:A Key Early Responsive Kinase during Viral Entry

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CCS Chemistry 2022年第1期4卷 112-121页

作者： Siwen Liu Lin Zhu Guangshan Xie Bobo Wing-yee Mok Zhu Yang Shaofeng Deng Siu-Ying Lau Pin Chen Pui Wang Honglin Chen Zongwei Cai State Key Laboratory for Emerging Infectious Diseases Department of MicrobiologyThe University of Hong KongPok Fu LamHong Kong SAR 999077 State Key Laboratory of Environmental and Biological Analysis Department of ChemistryHong Kong Baptist UniversityKowloonHong Kong SAR 999077 HKBU Shenzhen Institute of Research and Continuing Education Shenzhen 518000 Beijing Normal University-Hong Kong Baptist University United International College Zhuhai 519087

Currently,there is no effective antiviral medication for coronavirus disease 2019(COVID-19)and the knowledge on the potential therapeutic target is in great *** by a time-course transmission electron microscope(TEM)imaging,we analyzed early phosphorylation dynamics within the first 15 min during severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)viral *** on alterations in the phosphorylation events,we found that kinase activities such as protein kinase C(PKC),interleukin-1 receptor-associated kinase 4(IRAK4),MAP/microtubule affinity-regulating kinase 3(MARK3),and TANK-binding kinase 1(TBK1)were affected within 15 min of *** of the corresponding kinase inhibitors of PKC,IRAK4,and p38 showed significant inhibition of SARS-CoV-2 ***,proinflammatory cytokine production was reduced by applying PKC and p38 *** an acquisition of a combined image data using positiveand negative-sense RNA probes,as well as pseudovirus entry assay,we demonstrated that PKC contributed to viral entry into the host cell,and therefore,could be a potential COVID-19 therapeutic target.

关键词： SARS-CoV-2 viral entry phosphoproteomics early responsive kinase antiviral target PKC

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Development of Saba (Musa“BBB” acuminata x balbisiana) Peel-Monggo [Vigna radiata(L.) R. Wilczek] Flours with Malunggay (Moringa oleiferalam.) Polvoron Bar

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Food and Nutrition Sciences 2020年第4期11卷 262-280页

作者： Welbert A.Ronquillo Marites Gatchalian-yee Lotis E.Mopera Aimee Sheree A.Barrion Department of Nutrition and Dietetics Adventist Medical Center CollegeIligan CityPhilippines Institute of Human Nutrition and Food College of Human EcologyUniversity of the Philippines Los BañosLagunaPhilippines Institute of Food Science and Technology College of Agriculture and Food ScienceUniversity of the Philippines Los BañosLagunaPhilippines

The study was designed to produce a nutrient-dense polvoron bar from the optimized mixture of Saba-peel, monggo, and malunggay using simplex lattice design (RSM-SLD). Polvoron bar was also evaluated analytically including proximate, iron, total dietary fiber (TDF), and vitamin A content. Shelf stability, consumer acceptability, and microbial assessment of the sample were determined. Results showed that the optimal combination of ingredients was 37%, 52%, and 11% for saba peel flour, monggo flour, and malunggay powder, respectively. Proximate composition revealed that a fresh sample can provide 66% of carbohydrates, 12.17% protein, and 17% of fats. Every 100 g has 1.43 mg Fe content, 1.78 g TDF, and 91.25 mg vitamin A. The optimized product can last up to 111, 98, and 54 days at 30°C, 40°C, and 50°C, respectively, while total aerobic bacteria, yeast and molds, and coliform count are within the acceptable limits of the FDA standards.

关键词： Malunggay Monggo Saba-Peel Polvoron

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香港地区汉族人视紫红质基因和视网膜色素变性1基因与视网膜色素变性的双基因关联分析

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中华医学杂志 2005年第23期85卷 1613-1617页

作者：王丹艺范宝剑陈伟民谭霭仙蒋蔚宜林顺潮彭智培香港中文大学眼科与视觉科学学系

目的研究视紫红质基因(RHO)和视网膜色素变性1(RP1)基因在香港地区汉族视网膜色素变性(RP)患者中的突变频率及特征,并进一步探讨它们在RP发病机理中潜在的相互作用。方法运用高通量构象敏感凝胶电泳和直接测序方法,对151例香港地区汉族R... 详细信息

目的研究视紫红质基因(RHO)和视网膜色素变性1(RP1)基因在香港地区汉族视网膜色素变性(RP)患者中的突变频率及特征,并进一步探讨它们在RP发病机理中潜在的相互作用。方法运用高通量构象敏感凝胶电泳和直接测序方法,对151例香港地区汉族RP先证者和150名对照者进行了RHO和RP1基因全编码区和邻近剪切位点的内含子区域序列突变的检测。对携带基因突变的12例RP先证者的46名亲属进一步作分离分析。运用单因素分析、多因素分析和基因型家系不平衡分析研究RHO和RP1基因对RP的作用。结果RHO基因和RP1基因的突变检出率各为1.3%。RHO基因中-26G>A可增高RP危险性,而RP1基因中R872H则可降低RP危险性。多因素Logistic回归分析揭示了RHO基因IVS423G>A分别与RP1基因N985Y和C2033Y之间存在相互作用。结论在香港地区汉族RP患者中,RHO和RP1基因的突变率比其他人群中RP患者的突变率低。除了致病性基因突变,非编码区的序列改变也可改变RP的易感性。部分RP患者由双基因突变引起,当然多基因共同作用也完全可能存在。

关键词：香港地区汉族人视紫红质基因视网膜色素变性1基因视网膜色素变性基因

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香港部分严重急性呼吸综合征病人的分析

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解放军检验医学杂志 2003年第2期2卷 133-137页

作者： KennethW.Tsang,M.D. PakL.Ho,M.D. GaikC.Ooi,M.D. WilsonK.yee,M.D. TeresaWang,M.D. MoiraChan-Yeung,M.D. WahK.lam,M.D. WingH.Seto,M.D. LorettaY.Yam,M.D. ThomasM.Cheung,M.D. PoonC.Wong,M.D. Binglam,M.D. MaryS.Ip,M.D. JaneChan,M.D. KwokY.Yuen,M.D. KarN.Lai,M.D.,D.Sc From the University Departments of Medicine the Department of Medicine Pamela Youde Nethersole Eastern Hospital From the University Departments of Medicine Clinical Microbiology Diagnostic Radiology University of Hong Kong the Department of Medicine Kwong Wah Hospital

背景对已确诊的严重急性呼吸综合征的病人临床特点进行总结，为以后疑似病例的治疗和护理提供参考价值。方法对香港从2003年2月22日到2003年3月22日被确诊的10名患者(5男5女，38～72岁)进行分析。结果：潜伏期从2天至ll天。所有的患... 详细信息

背景对已确诊的严重急性呼吸综合征的病人临床特点进行总结，为以后疑似病例的治疗和护理提供参考价值。方法对香港从2003年2月22日到2003年3月22日被确诊的10名患者(5男5女，38～72岁)进行分析。结果：潜伏期从2天至ll天。所有的患者都表现有发热(体温>38℃，超过24小时)，大多数的患者有寒战、干咳、呼吸困难、周身不适、头痛、缺氧症状。物理检查听诊可有肺泡音、叩诊浊音。9名患者出现淋巴细胞降低。大多数患者出现转氨酶升高。但血清肌酐值维持正常水平。连续进行胸部X线检查，提示进行性充气区减少。两名患者死于进行性呼吸功能衰竭。组织活检表明肺组织内广泛性肺泡损伤。但未找到肺衣原体、肺炎支原体和军团菌感染的迹象。所有的患者都接受了皮质激素和病毒唑治疗。有8位患者接受了β-内酰胺类与大环内酯类药物的治疗，临床症状及x线检查都无明显改善。结论 SARS为传染性疾病。发热及继发的进行性呼吸困难是其主要的症状。病原体有待进一步确定。2002年秋冬季，中国广东省报道了305例高传染性的严重呼吸道疾患，表现为在医护人员中的局部流行。2003年2月，美国CDC将其命名为SARS，确定了它的临床表现。2003年3月13日，由于SARS由中国向世界范围内扩散，世界卫生组织发出SARS爆发公告，在全世界范围内进行调查。

关键词：严重急性呼吸综合征香港地区临床特点治疗护理

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