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Chinese Medicine 2012年第1期3卷 72-78页

作者： philip y. lam Hoi Shan Wong Jihang Chen Kam Ming Ko Division of Life Science The Hong Kong University of Science & Technology Hong Kong China

Chinese tonic herbs are generally.classified into y.n and y.ng categories based on their health-promoting action. Emerging evidence has suggested that in addition to up-regulating mitochondrial functional status, y.ng tonic herbs also enhance cellular/mitochondrial antioxidant capacity. and may.thus prevent age-related diseases and prolong the healthy.part of lifespan (i.e. healthspan). The proposed biochemical mechanism underly.ng the antioxidant action of y.ng tonic herbs involves a sustained and low level of mitochondrial reactive oxy.en species production, which is secondary.to the increased activity.of the electron transport chain, with the possible involvement of mitochondrial uncoupling. “y.ng invigoration” improves antioxidant defense in the body.in the long term and thereby.offers a promising prospect for preventing or possibly.delay.ng age-related diseases and the detrimental effects of aging.

关键词： Chinese Medicine y.ng Mitochondrial Decay Age-Related Diseases

Spray.freeze dry.ng of small nucleic acids as inhaled powder for pulmonary.delivery

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Asian Journal of Pharmaceutical Sciences 2018年第2期13卷 163-172页

作者： Wanling Liang Alan y.L.Chan Michael y.T.Chow Fiona F.K.Lo y.ngshan Qiu philip C.L.Kwok Jenny.K.W.lam Department of Pharmacology.and Pharmacy Li Ka Shing Faculty of Medicine The University of Hong Kong Advanced Drug Delivery.Group Faculty of Pharmacy The University of Sydney

The therapeutic potential of small nucleic acids such as small interfering RNA(siRNA) to treat lung diseases has been successfully.demonstrated in many.in vivo studies. A major barrier to their clinical application is the lack of a safe and efficient inhaled *** this study. spray.freeze dry.ng was employ.d to prepare dry.powder of small nucleic *** and herring sperm DNA were used as bulking agent and model of small nucleic acid therapeutics, respectively. Formulations containing different solute concentration and DNA concentration were produced. The scanning electron microscope(SEM) images showed that the porosity.of the particles increased as the solute concentration decreased. Powders prepared with solute concentration of 5% w/v were found to maintain a balance between porosity.and robustness. Increasing concentration of DNA improved the aerosol performance of the formulation. The dry.powder formulation containing 2% w/w DNA had a median diameter of 12.5 μm, and the aerosol performance study.using next generation impactor(NGI) showed an emitted fraction(EF) and fine particle fraction(FPF) of 91% and 28% respectively. This formulation(5% w/v solute concentration and 2% w/w nucleic acid) was adopted subsequently.to produce siRNA powder. The gel retardation and liquid chromatography.assay. showed that the siRNA remained intact after spray.freeze dry.ng even in the absence of delivery.vector. The siRNA powder formulation exhibited a high EF of 92.4%and a modest FPF of around 20%. Further exploration of this technology.to optimise inhaled siRNA powder formulation is warranted.

关键词： Inhalation Pulmonary delivery Small interfering RNA Spray freeze dry.ng

Spontaneous liver rupture in hy.ereosinophilic sy.drome:A rare but fatal complication

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World Journal of Gastroenterology 2009年第46期15卷 5875-5878页

作者： y.e-Sun Cheung Shun Wong philip Koon-Ngai lam Kit-Fai Lee John Wong Paul Bo-San Lai Department of Surgery Prince of Wales HospitalThe Chinese University of Hong Kong Department of Pathology Princess Margaret Hospital Department of Anesthesia and Intensive Care Prince of Wales HospitalThe Chinese University of Hong Kong

We report a rare case of spontaneous liver rupture in a patient with hy.ereosinophilic sy.drome(HES),of which the diagnosis was delay.d,resulting in a fatal *** diagnostic criteria and treatment of HES with hepatic involvement were *** possible cause of spontaneous liver rupture in HES and its management were also *** our knowledge,this is the fi rst case report of spontaneous liver rupture in *** emphasized the need of a high index of suspicion in diagnosing HES,so that early.treatment could be initiated.

关键词：嗜酸细胞增多症破裂并发症肝统计调查住户诊断

The Hong Kong consensus statements on unresectable hepatocellular carcinoma:narrative review and update for 2021

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Hepatobiliary.Surgery.and Nutrition 2023年第3期12卷 366-385页

作者： Tan-To Cheung Simon Chun-Ho y. Stephen L.Chan Ronnie T.P.Poon philip Kwok Ann-Shing Lee Anna Tai Derek Tam Chin-Cheung Cheung Tak-Wing Lai Nam-Hung Chia Ada Law Tracy.Shum y.m-Kwan lam Vince Lau Victor Lee Charing Chong Chung-Ngai Tang Thomas y.u Department of Surgery Queen Mary HospitalThe University of Hong KongHong KongChina Department of Imaging&Interventional Radiology Prince of Wales HospitalThe Chinese University of Hong KongHong KongChina State Key.Laboratory.of Translational Oncology.and Department of Clinical Oncology Sir YK Pao Centre for CancerPrince of Wales HospitalThe Chinese University of Hong KongHong KongChina Department of Radiology.and Imaging Queen Elizabeth HospitalHong KongChina Department of Clinical Oncology Tuen Mun HospitalHong KongChina Department of Clinical Oncology Queen Elizabeth HospitalHong KongChina Department of Surgery United Christian HospitalHong KongChina Department of Surgery Tuen Mun HospitalHong KongChina Department of Surgery Princess Margaret HospitalHong KongChina Department of Surgery Queen Elizabeth HospitalHong KongChina Department of Clinical Oncology Pamela Youde Nethersole Eastern HospitalHong KongChina Department of Clinical Oncology Princess Margaret HospitalHong KongChina Department of Medicine and Geriatrics United Christian HospitalHong KongChina Department of Radiology Queen Mary HospitalHong KongChina Department of Clinical Oncology Queen Mary HospitalThe University of Hong KongHong KongChina Department of Surgery Prince of Wales HospitalThe Chinese University of Hong KongHong KongChina Department of Surgery Pamela Youde Nethersole Eastern HospitalHong KongChina Department of Medicine Queen Mary HospitalThe University of Hong KongHong KongChina

Background and Objective:Hong Kong,like many.parts of Asia,faces a high burden of hepatocellular carcinoma(HCC)caused by.high endemic rates of hepatitis B virus *** Kong clinicians have developed a high level of expertise in HCC treatment across surgical,transarterial,ablative,radiotherapeutic and sy.temic *** publication summarizes the latest evidence-based recommendations on how these modalities should be ***:In two meetings held in 2020,a multidisciplinary.panel of surgeons,oncologists and interventional radiologists performed a narrative review of evidence on the management of HCC,with an emphasis on treatment of HCC not amenable to surgical *** attention was paid to new evidence published since the previous version of these statements in *** Content and Findings:The expert panel has formulated 60 consensus statements to guide the staging and treatment of unresectable *** the previous version of these statements,considerable additions have been made to the recommendations on use of targeted therapies and immunotherapies because of the large volume of new ***:Our consensus statements offer guidance on how to select HCC patients for surgical or non-surgical treatment and for choosing among non-surgical modalities for patients who are not candidates for *** particular,there is a need for more evidence to aid phy.icians in the selection of second-line sy.temic therapies,as currently.most data are limited to patients with disease progression on first-line sorafenib.

关键词： Hepatocellular carcinoma(HCC) Hong Kong guidelines consensus

Aberrant cholesterol metabolic signaling impairs antitumor immunosurveillance through natural killer T cell dy.function in obese liver

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Cellular & Molecular Immunology 2022年第7期19卷 834-847页

作者： Wenshu Tang Jingy.ng Zhou Weiqin y.ng y. Feng Haoran Wu My.h T.S.Mok Lingy.n Zhang Zhixian Liang Xiaoy. Liu Zhewen Xiong Xuezhen Zeng Jing Wang Jiahuan Lu Jingqing Li Hany.ng Sun Xiaoy. Tian philip Chun y.ung y.ng Hou Heung Man Lee Candice C.H.lam Howard H.W.Leung Anthony.W.H.Chan Ka Fai To John Wong Paul B.S.Lai Kelvin K.C.Ng Simon K.H.Wong Vincent W.S.Wong Alice P.S.Kong Joseph J.y.Sung Alfred S.L.Cheng school of Biomedical Sciences The Chinese University of Hong KongHong Kong SAR 999077China Department of Anatomical and Cellular Pathology The Chinese University of Hong KongHong Kong SAR 999077China Department of Liver Surgery Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Department of Surgery The Chinese University of Hong KongHong Kong SAR 999077China Department of Medicine and Therapeutics The Chinese University of Hong Kong.Hong Kong SAR 999077China State Key.Laboratory.of Digestive Disease The Chinese University of Hong KongHong Kong SAR 999077China Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore 639798Singapore Institute of Precision Medicine The First Affliated HospitalSun Yat-sen UniversityGuangzhou 510080China

Obesity.is a major risk factor for cancers including hepatocellular carcinoma(HCC)that develops from a background of non-alcoholic fatty.liver disease(NAFLD).Hy.ercholesterolemia is a common comorbidity.of *** cholesterol biosy.thesis mainly.occurs in the liver,its role in HCC development of obese people remains *** high-fat high-carbohy.rate diet-associated orthotopic and spontaneous NAFLD-HCC mouse models,we found that hepatic cholesterol accumulation in obesity.selectively.suppressed natural killer T(NKT)cell-mediated antitumor *** analy.is of human liver revealed aberrant cholesterol metabolism and NKT cell dy.function in NAFLD ***,cholesterol-lowering rosuvastatin restored NKT expansion and cy.otoxicity.to prevent obesogenic diet-promoted HCC ***,suppression of hepatic cholesterol biosy.thesis by.a mammalian target of rapamy.in(mTOR)inhibitor vistusertib preceded tumor regression,which was abolished by.NKT inactivation but not CD8^(+)T cell ***,sterol regulatory.element-binding protein 2(SREBP2)-driven excessive cholesterol production from hepatocy.es induced lipid peroxide accumulation and deficient cy.otoxicity.in NKT cells,which were supported by.findings in people with obesity.NAFLD and *** study.highlights mTORC1/SREBP2/cholesterol-mediated NKT dy.function in the tumor-promoting NAFLD liver microenvironment,providing intervention strategies that invigorating NKT cells to control HCC in the obesity.epidemic.

关键词： Cancer microenvironment Cancer models Tumour immunology

LRRK2 mutant knock-in mouse models: therapeutic relevance in Parkinson’s disease

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Translational Neurodegeneration 2022年第1期11卷 790-808页

作者： Eunice Eun Seo Chang philip Wing-Lok Ho Hui-Fang Liu Shirley.y.n-y. Pang Chi-Ting Leung y.sine Malki Zoe y.en-Kiu Choi David Boy.r Ramsden Shu-Leong Ho Division of Neurology Department of MedicineQueen Mary HospitalUniversity of Hong KongPok Fu LamHong KongChina Institute of Metabolism and Sy.tems Research University of BirminghamBirminghamUK.

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are one of the most frequent genetic causes of both familial and sporadic Parkinson’s disease (PD). Mounting evidence has demonstrated pathological similarities between LRRK2-associated PD (LRRK2-PD) and sporadic PD, suggesting that LRRK2 is a potential disease modulator and a thera-peutic target in PD. LRRK2 mutant knock-in (KI) mouse models display.subtle alterations in pathological aspects that mirror early.stage PD, including increased susceptibility.of nigrostriatal neurotransmission, development of motor and non-motor sy.ptoms, mitochondrial and autophagy.ly.osomal defects and sy.ucleinopathies. This review provides a rationale for the use of LRRK2 KI mice to investigate the LRRK2-mediated pathogenesis of PD and implications from current findings from different LRRK2 KI mouse models, and ultimately.discusses the therapeutic potentials against LRRK2-associated pathologies in PD.

关键词： Parkinson’s disease LRRK2 Knock-in mouse model Neurotransmission Motor dy.function Autophagy Ly.osome Mitochondrial dy.function Sy.ucleinopathy Hy.erkinase activity LRRK2 inhibitor

Nationwide retrospective study.of hepatitis B virological response and liver stiffness improvement in 465 patients on nucleos(t)ide analogue

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World Journal of Gastroenterology 2022年第31期28卷 4390-4398页

作者： Alnoor Ramji Karen Doucette Curtis Cooper Gerald y.sel Minuk Mang Ma Alexander Wong David Wong Edward Tam Brian Conway.David Truong philip Wong Lisa Barrett Hin Hin Ko Sarah Hay.ock-Jacobs Nishi Patel Gilaad G Kaplan Scott Fung Carla S Coffin Department of Medicine University of British ColumbiaVancouver v6t 1z3Canada Department of Medicine University of AlbertaEdmonton t6g 2r7Canada Department of Medicine The Ottawa Hospital Research InstituteUniversity of OttawaOttawa ON K1H 8L6Canada Department of Medicine University of ManitobaWinnipeg r3e 3j7Canada Department of Medicine University of SaskatchewanSaskatoon s7n 5e5Canada Department of Medicine University Health NetworkToronto m5g 2c4Canada Pacific Gastroenterology.Associates Vancouver v6z 2k5Canada Vancouver Infectious Disease Centre Vancouver v6z 2c7Canada Department of Medicine McGill UniversityMontreal h3a 0g4Canada Department of Microbiology.and Immunology Dalhousie UniversityHalifax b3h 4r2Canada Cumming School of Medicine University of CalgaryCalgary t2n 1n4Canada

BACKGROUND Hepatitis B virus(HBV)nucleos(t)ide analog(NA)therapy.reduces liver disease but requires prolonged therapy.to achieve hepatitis B surface antigen(HBsAg)*** is limited North American real-world data using non-invasive tools for fibrosis assessment and few have compared 1st generation NA or lamivudine(lam)to tenofovir disoproxil fumarate(TDF).AIM To assess impact of NA on virological response and fibrosis regression using liver stiffness measurement(LSM)(i.e.,FibroScan®).METHODS Retrospective,observational cohort study.from the Canadian HBV *** collected included demographics,NA,HBV DNA,alanine aminotransferase(ALT),and *** were HBV monoinfected patients,treatment naïve,and received 1 NA with minimum 1 y.ar *** In 465(median 49 y.ars,37%female,35%hepatitis B e antigen+at baseline,84%Asian,6%White,and 9%Black).Percentage of 64(n=299)received TDF and 166 were lam-treated with similar median duration of 3.9 and 3.7 y.ars,*** mean baseline LSM was 11.2 kPa(TDF)vs 8.3 kPa(lam)(P=0.003).At 5-y.ar follow-up,the mean LSM was 7.0 kPa in TDF vs 6.7 kPa in lam(P=0.83).There was a significant difference in fibrosis regression between groups(i.e.,mean-4.2 kPa change in TDF and-1.6 kPa in lam,Py.suppressed(lam-treated(n=35/58,60%)(Py.approximately.5 y.ars of NA achieves liver fibrosis regression rarely.leads to HBsAg loss.

关键词： Nucleos(t)ide analog therapy Functional cure Hepatitis B virus surface antigen loss Fibrosis regression Liver stiffness measurement Transient elastography

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

作者： Xuezhen Zeng Jingy.ng Zhou Zhewen Xiong Hany.ng Sun Weiqin y.ng My.h T.S.Mok Jing Wang Jingqing Li Man Liu Wenshu Tang y. Feng Hector Kwong-Sang W ang Shun-Wa Tsang King-Lau Chow philip Chun y.ung John Wong Paul Bo-San Lai Anthony.Wing-Hung Chan Ka Fai To Stephen lam Chan Qiang Xia Jing Xue Xiao Chen Jun y. Sui Peng Joseph Jao-y.u 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 hepatocy.e-intrinsic cell cy.le-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.poly.orphonuclear-my.loid-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 hy.eraaivation 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 cy.le related kinase liver metastasis liver immune microenvironment my.loid-derived suppressor cell natural killer T cell

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 y.ancheng 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 Ray.ean 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 genoty.e 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-analy.es 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 hy.ersensitive *** factor enrichment analy.is revealed that USF1 was AD-specific while CREB1 was *** annotation and genebased analy.is 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 analy.is and Gene-Set Enrichment Analy.is revealed that AD genes were primarily.involved in immune-related pathway.,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