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RAMAN SPECTROSCOPY FOR IN VIVO TISSUE ANALYSIS AND DIAGNOSIS,FROM INSTRUMENT DEVELOPMENT TO CLINICAL APPLICATIONS

Journal of Innovative Optical Health Sciences 2008年第1期1卷 95-106页

作者： HAISHAN ZENG JIANHUA ZHAO MICHAEL SHORT DAVID I.MCLEAN stephen lam ANNETTE MCWILLIAMS HARVEY LUI Laboratory for Advanced Medical Photonics(lamP)Cancer Imaging Department British Columbia Cancer Research Centre 675 West 10th Avenue Vancouver BCV5Z 1L3Canada Photomedicine Institute Department of Dermatology and Skin Science University of British Columbia and Vancouver Coastal Health Research Institute 835 West 10th Avenue VancouverBCV5Z 4E8Canada

Raman spectroscopy is a noninvasive,nondestructive analytical method capable of determining the biochemical constituents based on molecular *** does not require sample preparation or ***,the use of Raman spectroscopy for in vivo clinical applications will depend on the feasibility of measuring Raman spectra in a relatively short time period(a few seconds).In this work,a fast dispersive-type nearinfrared(NIR)Raman spectroscopy system and a skin Raman probe were developed to facilitate real-time,noninvasive,in vivo human skin *** image aberration was corrected by a parabolic-line fiber array,permitting complete CCD vertical binning,thereby yielding a 16-fold improvement in signal-to-noise *** quality in vivo skin NIR Raman spectra free of interference from fiber fluorescence and silica Raman scattering can be acquired within one second,which greatly facilitates practical noninvasive tissue characterization and clinical ***,we are conducting a large clinical study of various skin diseases in order to develop Raman spectroscopy into a useful tool for non-invasive skin cancer *** data analysis results are ***,we have also successfully developed a technically more challenging endoscopic Laser-Raman probe for early lung cancer *** in vivo results from endoscopic lung Raman measurements are discussed.

关键词： Rapid Raman system in vivo skin Raman in vivo lung Raman endoscopic Raman probe early cancer detection

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中国香港地区的医学遗传学发展(英文)

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北京大学学报（医学版） 2006年第1期38卷 17-20页

作者： stephen TS lam Hong Kong Society of Medical Genetics Hong KongChina

As a geographically integral part of south China, the population mix of Hong Kong is largely influenced by itslocation. In the past150 years, its population has increased from a fewthousand to 5.7 million. This is the resultof episodic influxes of a great mass of people from China, often associated with political upheavals or economic cri-sis. It explains a population structure of95% Chinese. This structure is also reflected in the finding of genetic vari-ants in this population, which bears resemblance to neighbouring regions in China. For example, the thalassaemiasand lactose intolerance are common. However, the impact of migration from other parts of China cannot be neglec-ted, particulary for the last half century. This is evident from studies of glucose-6-phosphate dehydrogenase(G6PD) variants and other protein polymorphisms. The quick change in political situation has also promoted moreinflux of people from central and northern part of China. They bring with them a diversity of genetic constituent,mutations and diseases. However, as an international city, Hong Kong has significantinputfrommostethnic groupsin the world. Hence, the remaining 5% of its population is a heterogeneous group of minorities including Europe-ans, Indians, Japanese, and south-east Asians. Although their contribution to the cultural and economic growth inHong Kong is phenomenal, their impact on the genetic load is small. However, since their genetic makeup, andhence diseases, vary somewhatfromsouthern Chinese, they also poses specific needs to the provision of clinical ge-netic services.

关键词：遗传学医学遗传学服务香港中国发展

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Novel biomarkers GEP/ABCB5 regulate response to adjuvant transarterial chemoembolization after curative hepatectomy for hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2018年第6期17卷 524-530页

作者： Charing Ching-Ning Chong Siu Tim Cheung Yue-Sun Cheung Anthony Wing-Hung Chan stephen lam Chan Simon Chun-Ho Yu Paul Bo-San Lai Department of Surgery Prince of Wales HospitalThe Chinese University of Hong Kong4/F Clinical Science Building30-32 Ngan Shing StreetShatinHong KongChina Department of Anatomical and Cellular Pathology State Key Laboratory in Oncology in South ChinaPrince of Wales HospitalThe Chinese University of Hong Kong30-32 Ngan Shing StreetShatinHong KongChina Department of Clinical Oncology Prince of Wales HospitalThe Chinese University of Hong Kong30-32 Ngan Shing StreetShatinHong KongChina Department of Imaging and Interventional Radiology Prince of Wales HospitalThe Chinese University of Hong Kong30-32 Ngan Shing StreetShatinHong KongChina

Background: Transarterial chemoembolization(TACE) is the most commonly used adjuvant therapy for hepatocellular carcinoma(HCC) after curative resection. Responses to TACE are variable due to tumor and patient heterogeneity. We had previously demonstrated that expression of Granulin-epithelin precursor(GEP) and ATP-dependent binding cassette(ABC)B5 in liver cancer stem cells was associated with chemoresistance. The present study aimed to evaluate the association between GEP/ABCB5 expression and response to adjuvant TACE after curative resection for HCC. Methods: Patients received adjuvant TACE after curative resection for HCC and patients received curative resection alone were identified from a prospectively collected database. Clinical samples were retrieved for biomarker analysis. Patients were categorized into 3 risk groups according to their GEP/ABCB5 status for survival analysis: low(GEP-/ABCB5-), intermediate(either GEP +/ABCB5-or GEP-/ABCB5 +) and high(GEP +/ABCB5 +). Early recurrence(recurrence within 2 years after resection) and disease-free survival were analyzed. Results: Clinical samples from 44 patients who had followed-up for more than 2 years were retrieved for further biomarker analysis. Among them, 18 received adjuvant TACE and 26 received surgery alone. Patients with adjuvant TACE in the intermediate risk group was associated with significantly better overall survival and 2-year disease-free survival than those who had surgery alone( P = 0.036 and P = 0.011, respectively). Adjuvant TACE did not offer any significant differences in the early recurrence rate, 2-year disease-free survival and overall survival for patients in low and high risk groups. Conclusions: Adjuvant TACE can only provide survival benefits for patients in the intermediate risk group(either GEP +/ABCB5-or GEP-/ABCB5 +). A larger clinical study is warranted to confirm its role in patient selection for adjuvant TACE.

关键词： Adjuvant therapy Hepatocellular carcinoma Drug transporter Transarterial chemoembolisation Granulin-epithelin precursor

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A different spectrum of DMD gene mutations in local Chinese patients with Duchenne/Becker muscular dystrophy

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Chinese Medical Journal 2006年第13期119卷 1079-1087页

作者： Ivan Fai-man Lo Kent Keung-san Lai Tony Ming-for Tong stephen Tak-sum lam Clinical Genetic Service Department of HealthHong KongChina

Background Duchenne muscular dystrophy （DMD） and Becker muscular dystrophy （BMD） are X-linked recessive, allelic disorders. This study was conducted to look into the spectrum of DMD gene mutations in Hong Kong Chi... 详细信息

关键词： Duchenne muscular dystrophy Becker muscular dystrophy Chinese DMD mutation deletion duplication

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Delayed diagnosis of 22q11.2 deletion syndrome in an adult Chinese lady

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Chinese Medical Journal 2012年第16期125卷 2945-2947页

作者： SHEA Yat-fung LEE Chi-ho Harinder Gill CHOW Wing-sun lam Yui-ming LUK Ho-ming lam stephen Tak-sum CHU Leung-wing Department of Medicine Queen Mary Hospital the University ofHong Kong Hong Kong China Clinical Genetic Service Department of Health The Government of Hong Kong Special Administrative Region Hong Kong China

We report a 32 year-old Chinese lady with history of tetralogy of Fallot, presented to us with chest pain due to hypocalcemia secondary to hypoparathyroidism. With her dysmerphic facial features and intellectual disability 22q11.2 deletion was suspected and confirmed by genetic study. Clinicians should consider the diagnosis of DiGeorge syndrome in adult patient with past medical history of congenital heart disease, facial dysmorphism, intellectual disability and primary hypoparathyroidism.

关键词： hypocalcemia DiGeorge syndrome adult

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PHOX2B mutations in three Chinese patients with congenital central hypoventilation syndrome

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Chinese Medical Journal 2006年第20期119卷 1749-1752页

作者： Siu-Fong June Or Ming-for Tony Tong Fai-Man Ivan Lo Chi-Wai Law Ting-Yat Miu Delphine Trochet Tak-Sum stephen lam Clinical Genetic Service Department of Health Hong Kong SAR China Department of Paediatrics Queen Elizabeth Hospital Hong Kong SAR China Department de Genetique Hospital Necker-Enfants Malades Paris France

Congenital central hypoventilation syndrome （CCHS, OMIM #209880） is a rare autosomal dominant disorder of the autonomic nervous system （ANS） characterized by an abnormal autonomic ventilatory response to progressive hypercarbia and sustained hypoxemia. Patients typically present in the newborn period with hypoventilation or apnea asleep, awake, or both, without any associated cardiac, pulmonary, neuromuscular or brainstem lesions. Rarely, some patients may present at a later age and are diagnosed to have late onset central hypoventilation syndrome （LOCHS）.1 Other features of ANS dysfunction such as feeding difficulty due to oesophageal dysmotility, severe constipation in the absence of Hirschsprung disease, poor regulation of basal body temperature, episodes of profuse sweating, pupillary and ocular abnormalities, decreased beat-to-beat variability of heart rate, attenuated response of heart rate to exercise, abnormal fluctuation of blood pressure, decreased perception to pain, and decreased perception to anxiety may be variably present but not essential for diagnosis Furthermore, this central hypoventilation can occur as an isolated feature or in association with a number of neurocristopathies, notably Hirschsprung disease （Haddad syndrome, OMIM #209880） and tumours of the sympathetic nervous system particularly neuroblastoma, ganglioneuro- blastoma, and ganglioneuroma, which were found in 20% and 5%--10% of CCHS patients, respectively.2 Studies of genes pertinent to the early embryologic development of the neural crest cells, specifically the endothelin and the RET-GDNF signaling pathways, have recently led to the identification of PHOX2B as the major disease causing gene for CCHS.2-6 PHOX2B was mapped to chromosome 4p12 and consists of 3 exons. It encodes a highly conserved paired-like homeobox transcription factor of 314 amino acids linked to the RET-GDNF signaling

关键词： congenital central hypoventilation syndrome PHOX2B Chinese mutation

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优化检测制程设计加速改善65nm芯片的良率

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电子工业专用设备 2008年第3期37卷 38-42页

作者： Sang Chong Eric Rying Alexa Perry stephen lam Mary Ann St Lawrence IBM微电子部Hopewell Junction PDF Solutions KLA-Tencor Corporation Hopewell Junction

描述一种广泛应用于探索制程设计方面的系统性及随机性故障的短流程测试芯片与先进的检测工具平台相结合的综合方法,以对在65nm技术节点上的关键性缺陷进行特征化描述和监控,借此加速基于缺陷的良率学习。通过独特的快速电性测试方案、... 详细信息

描述一种广泛应用于探索制程设计方面的系统性及随机性故障的短流程测试芯片与先进的检测工具平台相结合的综合方法,以对在65nm技术节点上的关键性缺陷进行特征化描述和监控,借此加速基于缺陷的良率学习。通过独特的快速电性测试方案、快速分析软件以及优化的检测效果,可缩短快速制程开发的学习周期。通过将在一个领先的300mm晶片厂得到的CV检测设置知识经验成功运用于制造过程,优化了产品的关键缺陷(DOI)检测。

关键词：特征化载具测试芯片缺陷检测缺陷叠置分析 S/N分析 KLA—Tencor 2800 制程-设计互动

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Cellular & Molecular Immunology 2021年第4期18卷 1005-1015页

作者： Xuezhen Zeng Jingying Zhou Zhewen Xiong Hanyong Sun Weiqin Yang Myth T.S.Mok Jing Wang Jingqing Li Man Liu Wenshu Tang Yu Feng Hector Kwong-Sang W ang Shun-Wa Tsang King-Lau Chow Philip Chun Yeung John Wong Paul Bo-San Lai Anthony Wing-Hung Chan Ka Fai To stephen lam Chan Qiang Xia Jing Xue Xiao Chen Jun Yu Sui Peng Joseph Jao-Yiu Sung Ming Kuang Alfred Sze-Lok Cheng School of Biomedical Sciences The Chinese University of Hong KongHong Kong SARChina lnstitute of Precision Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Liver Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Pharmacy The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Anatomical and Cellular Pathology The Chinese University of Hong KongHong Kong SARChina Department of Liver Surgery Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Gastroenterology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Division of Life Science Hong Kong University of Science and TechnologyHong Kong SARChina Department of Surgery The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Translational Oncology The Chinese University of Hong KongHong Kong SARChina Department of Clinical Oncology The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Oncogenes and Related Genes Stem Cell Research CenterRen Ji HospitalSchool of MedicineShanghai Cancer InstituteShanghai Jiao Tong UniversityShanghaiChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong Kong SARChina Clinical Trial Unit The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Cancer Center The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

The liver is an immunologically tolerant organ and a common metastatic site of multiple cancer *** a role for cancer cell invasion programs has been well characterized,whether and how liver-intrinsic factors drive metastatic spread is incompletely ***,we show that aberrantly activated hepatocyte-intrinsic cell cycle-related kinase(CCRK)signaling in chronic liver diseases is critical for cancer metastasis by reprogramming an immunosuppressive *** an inducible liverspecific transgenic model,we found that CCRK overexpression dramatically increased both B16F10 melanoma and MC38 colorectal cancer(CRC)metastasis to the liver,which was highly infiltrated by polymorphonuclear-myeloid-derived suppressor cells(PMNMDSCs)and lacking natural killer T(NKT)*** of PMN-MDSCs in CCRK transgenic mice restored NKT cell levels and their interferon gamma production and reduced liver metastasis to 2.7% and 0.7%(metastatic tumor weights)in the melanoma and CRC models,***,CCRK activated nuclear factor-kappa B(NF-κB)signaling to increase the PMN-MDSC trafficking chemokine C-X-C motif ligand 1(CXCL1),which was positively correlated with liver-infiltrating PMN-MDSC levels in CCRK transgenic ***,CRC liver metastasis patients exhibited hyperaaivation of hepatic CCRK/NF-κB/CXCL1 signaling,which was associated with accumulation of PMN-MDSCs and paucity of NKT cells compared to healthy liver transplantation *** summary,this study demonstrates that immunosuppressive reprogramming by hepatic CCRK signaling undermines antimetastatic *** findings offer new mechanistic insights and therapeutic targets for liver metastasis intervention.

关键词： Cell cycle related kinase liver metastasis liver immune microenvironment myeloid-derived suppressor cell natural killer T cell

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Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma

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Frontiers of Medicine 2021年第2期15卷 275-291页

作者： Na Qin Yuancheng Li Cheng Wang Meng Zhu Juncheng Dai Tongtong Hong Demetrius Albanes stephen lam Adonina Tardon Chu Chen Gary Goodman Stig EBojesen Maria Teresa Landi Mattias Johansson Angela Risch H-Erich Wichmann Heike Bickeboller Gadi Rennert Susanne Arnold Paul Brennan John KField Sanjay Shete Loic Le Marchand Olle Melander Hans Brunnstrom Geoffrey Liu Rayjean JHung Angeline Andrew lambertus AKiemeney Shan Zienolddiny Kjell Grankvist Mikael Johansson Neil Caporaso Penella Woll Philip Lazarus Matthew BSchabath Melinda CAldrich Victoria LStevens Guangfu Jin David CChristiani Zhibin Hu Christopher IAmos Hongxia Ma Hongbing Shen Department of Epidemiology Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166China State Key Laboratory of Reproductive Medicine Center for Global HealthNanjing Medical UniversityNanjing 211166China Department of Bioinformatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjing 211166China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer MedicineNanjing Medical UniversityNanjing 211166China China International Cooperation Center for Environment and Human Health School of Public HealthNanjing Medical UniversityNanjing 211166China Division of Cancer Epidemiology and Genetics National Cancer InstituteBethesdaMD 20892-9304USA Department of Integrative Oncology British Columbia Cancer AgencyVancouverBC V5Z 1L3Canada Faculty of Medicine University of Oviedo and CIBERESPOviedo 33006Spain Program in Epidemiology Public Health Sciences DivisionFred Hutchinson Cancer Research CenterSeattleWA 98109-1024USA Public Health Sciences Division Swedish Cancer InstituteSeattleWA 98026USA Department of Clinical Biochemistry Copenhagen University HospitalCopenhagen DK-1017Denmark National Cancer Institute BethesdaMD 20892-9304USA Genetic Epidemiology Group International Agency for Research on CancerLyon 69372France Cancer Center Cluster Salzburg at PLUS Department of Molecular BiologyUniversity of SalzburgHeidelberg 5020Austria Institute of Medical Informatics Biometry and EpidemiologyChair of EpidemiologyLudwig Maximilians UniversityMunichBavaria 80539Germany Department of Genetic Epidemiology University Medical Center GoettingenGoettingen 37075Germany Technion Faculty of Medicine Carmel Medical CenterHaifa 3448516Israel Markey Cancer Center University of KentuckyLexingtonKY 40506-0054USA Department of Molecular and Clinical Cancer Medicine Roy Castle Lung Cancer Research ProgrammeThe University of Liverpool Institute of Translational MedicineLiverpool L697Z

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely *** integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility *** identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive *** factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was *** annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency *** results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

关键词： lung cancer genome-wide association study function annotation immune homologous recombination repair deficiency genetic heterogeneity

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TRMT6 and TRMT61A facilitated acute pancreatitis severity via regulation of neutrophil function

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Science China Life Sciences 2025年

作者： Yuan Dong Li Su Sin Man lam Cen Yan Yalan Deng Guotao Lu Jinkui Yang Guanghou Shui Yingmei Feng Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Department of Science and Development Beijing Youan HospitalCapital Medical University Laboratory for Clinical Medicine Capital Medical University Neuroscience Research Institute Peking University Center of Medical and Health AnalysisPeking University State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of Sciences Pancreatic Center Department of GastroenterologyAffiliated Hospital of Yangzhou UniversityYangzhou University Beijing Key Laboratory of Diabetes Research and Care Department of EndocrinologyBeijing Tongren HospitalCapital Medical University

Dear Editor,Type 2 diabetes mellitus (T2DM) has been identified as a risk factor for increased severity in acute pancreatitis (AP)(Mikóet al,2018).However,to date,no studies have simultaneously included healthy individuals,T2DM patients,and AP patients to investigate which diabetes-associated metabolites are linked to AP severity.

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