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Identification of TWIST-interacting genes in prostate cancer

Science China(Life Sciences) 2017年第4期60卷 386-396页

作者： Peng Lyu Shu-Dong Zhang hiu-fung yuen Cian M.McCrudden Qing Wen Kwok-Wah Chan Hang Fai Kwok Faculty of Health Sciences University of Macao Avenida de Universidade Macao 999078 China Northern Ireland Centre for Stratified Medicine C-TRIC Building Altnagelvin Hospital Campus Ulster University Londonderry BT47 6SB UK Institute of Molecular and Cellular Biology Agency for Science Technology and Reseach Singapore 138673 Singapore School of Pharmacy Queen's University of Belfast Belfast BT9 7BL UK Centre for Cancer Research & Cell Biology School of Medicine Dentistry and Biomedical Sciences Queen's University Belfast Belfast BT9 7BL UK Department of Pathology Queen Mary Hospital University of Hong Kong Hong Kong 999077 China

Prostate cancer is one of the most common cancers in men worldwide, and the number of diagnosed patients has dramatically increased in recent years. Currently, the clinical parameters used to diagnose prostate cancer, such as Gleason score, pathological tumor staging, and prostate-specific antigen(PSA) expression level, are considered insufficient to inform recommendation to guide clinical practice. Thus, identification of a novel biomarker is necessary. TWIST is one of the well-studied targets and is correlated with cancer invasion and metastasis in several human cancers. We have investigated two largest prostate cancer patient cohorts available in GEO database and found that TWIST expression is positive correlated with Gleason score and associated with poorer survival. By using a prostate cancer cohort and a prostate cancer cell line dataset, we have identified three potential downstream targets of TWIST, PPM1 A, SRP72 and TBCB. TWIST's prognostic capacity is lost when the gene is mutated. Further investigation in the prostate cancer cohort revealed that gene expression of SERPINA, STX7, PDIA2, FMP5, GP1 BB, VGLL4,KCNMA1, SHMT2, SAA4 and DIDO1 influence the prognostic significance of TWIST and vice versa. Importantly, eight out of these ten genes are prognostic indicator by itself. In conclusion, our study has further confirmed that TWIST is a prognostic marker in prostate cancer, identified its potential downstream targets and genes that could possibly give additional prognostic value to predict TWIST-mediated prostate cancer progression.

关键词： Gleason prognostic staging cohort progression invasion downstream metastasis biomarker interacting

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NHE7 upregulation potentiates the uptake of small extracellular vesicles by enhancing maturation of macropinosomes in hepatocellular carcinoma

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Cancer Communications 2024年第2期44卷 251-272页

作者： Yue Yao Yi Xu Liang Yu Ting-Mao Xue Zhi-Jie Xiao Pui-Chi Tin hiu-Ling fung Hoi-Tang Ma Jing-Ping Yun Judy Wai Ping Yam Department of Pathology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongP.R.China Department of Endocrinology and Metabolism Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjingP.R.China Department of Hepatopancreatobiliary Surgery Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjingP.R.China State Key Laboratory of Oncology in South China Cancer Center of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Hepatobiliary Surgery II Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China Scientific Research Center The Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdongP.R.China State Key Laboratory of Liver Research The University of Hong KongHong KongP.R.China Department of Pathology Cancer Center of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China

Background:Small extracellular vesicles(sEVs)mediate intercellular commu-nication that contributes to hepatocellular carcinoma(HCC)progression via multifaceted *** success of cell entry determines the effect of sEV on recipient ***,we aimed to delineate the mechanisms underlying the uptake of sEV in ***:AF,Alexa Fluor;ANOVA,analysis of variance;ATP9A,ATPase Phospholipid Transporting 9A;BCECF-AM,2’,7’-bis-(2-barboxyethyl)-5-(and-6)-carboxyfluorescein,acetoxymethyl ester;BSA,bovine serum albumin;CCMR,Centre for Comparative Medicine Research;CRISPR,clustered regularly interspaced short palindromic repeats;CTL,ctrl;CXCR4,C-X-C Chemokine Receptor Type 4;DAPI,4′,6-diamidino-2-phenylindole;DFS,disease-free survival;DMEM,Dulbecco’s Modified Eagle Medium;DMSO,dimethyl sulfoxide;Dox,doxycycline;EEA1,early endosome antigen 1;EIPA,5-(N-ethyl-N-isopropyl)-amiloride;FBS,fetal bovine serum;FITC,fluorescein isothiocyanate;GAPDH,glyceraldehyde-3-phosphate dehydrogenase;GM130,Golgi matrix protein 130;HCC,hepatocellular carcinoma;HEPES,4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid;HPRT1,hypoxanthine phosphoribosyltransferase 1;H-score,histoscore;IAA,indole-3-acetic acid;KD,knockdown;KO,knockout;mAID,mini-auxin-inducible degron;MTT,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide;NHE7,Na(+)/H(+)exchanger 7;ns,non-significant;OD,optical density;OS,overall survival;PBS,phosphate-buffered saline;PCR,polymerase chain reaction;pHe,endosomal pH;pHi,intracellular pH;PKH67,Paul Karl Horan 67;Rab21,Ras-associated binding protein 21;RIPA,radioimmunoprecipitation assay;SAM,synergistic activation mediator;SEMs,standard error of the means;sEVs,small extracellular vesicles;sgRNA,single-guide RNA;shRNA,short-hairpin RNA;SLC9,solute carrier gene 9;SLiCE,Seamless Ligation Cloning Extract;TCGA,The Cancer Genome Atlas;TCL,total cell lysates;TGN,trans-Golgi network;TMA,tissue microarray;TMR,tetramethyl rhodamine;TSG101,tumor susceptibility gene *** Yao an

关键词： hepatocellular carcinoma small extracellular vesicles macropinocytosis pH regulation sodium-hydrogen exchanger

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A prospective cohort of men with localized prostate cancer on active surveillance protocol in Hong Kong,China:what did we learn?

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Asian Journal of Andrology 2024年第3期26卷 245-249页

作者： Xiaobo Wu Ivan Ching-Ho Ko Cindy Yeuk-Lam Hong Samuel Chi-Hang Yee Jeremy yuen-Chun Teoh Samson Yun-Sang Chan Ho-Man Tam Chi-Kwok Chan Chi-Fai Ng Peter Ka-fung Chiu SH Ho Urology Centre Department of SurgeryFaculty of MedicineThe Chinese University of Hong KongHong KongChina

This study aimed to report the outcomes of active surveillance(AS)in the management of low-risk prostate cancer(PCa).It recruited87 men who were prospectively followed up according to the Prostate Cancer Research International Active Surveillance(PRIAS)protocol with local adaptation at SH Ho Urology Centre,Prince of Wales Hospital,Hong Kong,*** investigated the predictorsof disease progression and found that baseline prostate-specific antigen density(PSAD)and the presence of the highest ProstateImaging-Reporting and Data System(PI-RADS)score 5 lesion on magnetic resonance imaging(MRI)are significantly correlatedwith disease ***,men with PSAD>0.2 ng ml^(−2)or PI-RADS 4 or 5 lesions had significantly worse upgradingfree survival compared to those with PSAD≤0.2 ng ml−2 and PI-RADS 2 or 3 *** study concludes that AS is a safe andeffective management strategy for selected patients to defer radical treatment and that most disease progression can be detectedafter the first repeated *** combination of PSAD>0.2 ng ml^(−2)and PI-RADS 4 or 5 lesions may serve as a useful predictorof early disease progression and provide a guide to optimize follow-up protocols for men in different risk groups.

关键词： active surveillance cohort localized prostate cancer

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Effects of SARS-CoV-2 infection on incidence and treatment strategies of hepatocellular carcinoma in people with chronic liver disease

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World Journal of Hepatology 2024年第2期16卷 211-228页

作者： Lung-Yi Mak Matthew Shing Hin Chung Xue Li Francisco Tsz Tsun Lai Eric Yuk Fai Wan Celine Sze Ling Chui Franco Wing Tak Cheng Esther Wai Yin Chan Ching Lung Cheung Ivan Chi Ho Au Xi Xiong Wai-Kay Seto Man-fung yuen Carlos King Ho Wong Ian Chi Kei Wong Department of Medicine The University of Hong KongHong KongChina State Key Laboratory of Liver Research The University of Hong KongHong KongChina Department of Pharmacology and Pharmacy The University of Hong KongHong KongChina Laboratory of Data Discovery for Health(D24H) Hong Kong Science and Technology ParkHong KongChina Department of Family Medicine and Primary Care The University of Hong KongHong KongChina School of Nursing The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina Research Department of Practice and Policy University College LondonLondon WC1E 6BTUnited Kingdom Aston School of Pharmacy Aston UniversityBirmingham B47ETUnited Kingdom

BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with *** A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in Hong *** with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient was followed up until death,outcome event,or November 15,*** outcome was incidence of *** outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to HCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 *** rate ratios(IRRs)were estimated by Poisson regression *** Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score *** 249-d median follow-up,COVID-19+CLD was not associated with increased risk of incident HCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for HCC(IRR:1.60,95%CI:1.46-1.75,P<0.001),compared to *** both acute and post-acute phases of infection,COVID-19+CLD were associated with increased risks of allcause mortality(acute:IRR:7.06,95%CI:5.78-8.63,P<0.001;post-acute:IRR:1.24,95%CI:1.14-1.36,P<0.001)and adverse hepatic outcomes(acute:IRR:1.98,95%CI:1.79-2.18,P<0.001;post-acute:IRR:1.24,95%CI:1.13-1.35,P<0.001),compared to *** Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they

关键词： SARS-CoV-2 infection Chronic liver disease Long COVID Post-COVID-19 syndrome Cirrhosis Hepatocellular carcinoma

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Management of chronic hepatitis B in severe liver disease

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World Journal of Gastroenterology 2014年第43期20卷 16053-16061页

作者： James fung Ching-Lung Lai Man-fung yuen Department of Medicine The University of Hong KongQueen Mary Hospital

In the past few decades,chronic hepatitis B(CHB)has evolved from a disease that was untreatable and progressive,to one that can be easily controlled with antiviral ***,patients with severe liver disease still remain difficult to treat despite the availability of highly potent nucleos(t)ide *** include those with underlying cirrhosis,severe flares of CHB,hepatocellular carcinoma(HCC),and for those undergoing liver *** those with established cirrhosis,antiviral therapy should be considered for all,as unpredictable flares can still occur,which can be fatal for those with advanced chronic liver ***,even with effective viral suppression,the development of HCC can still *** patients with severe flares of CHB,although the use of antiviral can improve long term outcomes,a significant proportion may still die without liver *** short term prognosis of these patients is dependent on both the severity of flare and underlying pre-existing liver *** patients with decompensated cirrhosis,liver failure secondary to severe flares,or those with HCC,liver transplantation may be *** liver transplantation,long term antiviral therapy is required to prevent graft loss from recurrent hepatitis B *** use of hepatitis B immune globulin(HBIG)in combination with an oral antiviral agent has been the mainstay of post-transplant antiviral regimen for over *** newer and more potent antiviral agents such as tenofovir and entecavir,use of these agents along with HBIG have demonstrated to be effective in preventing significant recurrence in the long term.

关键词： Antiviral therapy Cirrhosis Liver failure Liver transplantation Hepatocellular carcinoma

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Clinical application of liver stiffness measurement using transient elastography in chronic liver disease from longitudinal perspectives

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World Journal of Gastroenterology 2013年第12期19卷 1890-1900页

作者： Beom Kyung Kim James fung Man-fung yuen Seung Up Kim Department of Internal Medicine Institute of Gastroenterology Yonsei University College of Medicine Liver Cirrhosis Clinical Research Center Department of Medicine State Key Laboratory for Liver Research the University of Hong Kong

Accurate determination of the presence and degree of fibrosis in liver is of great importance, because the prognosis and management strategies for chronic liver disease depend mainly on these factors. To date, liver biopsy (LB) remains the "gold standard" for assessing the severity of liver fibrosis; however, LB is often limited by its invasiveness, sampling error, and intra/ inter-observer variability in histological interpretation. Furthermore, repeated LB examinations within a short time interval are indeed ineligible in a real clinical practice. Thus, due to the pressing need for non-invasive surrogates for liver fibrosis, transient elastography (TE),as a novel ultrasound based technology, has allowed a noninvasive measurement of liver stiffness and has gained in popularity over recent years. In the past few years, additional roles for transient TE beyond the initial purpose of a non-invasive surrogate for LB have included the prediction of the most two critical consequences of fibrosis progression: the development of portal hypertension-related complications and hepatocellular carcinoma. This indicates that the role of transient TE is not merely limited to reducing the need for LB, but transient TE can enable the establishment of tailored management strategies by providing more detailed prognostic information. In particular, under the concept in which the clinical course of liver fibrosis is dynamic and bidirectional, especially when appropriate intervention is commenced, transient TE can be used to track the dynamic changes in fibrotic burden during antiviral or antifibrotic treatment. This review discussed extended applications of transient TE in prediction of the development of real clinical endpoints from a longitudinal perspective.

关键词： Liver stiffness Transient elastography Fibroscan Fibrosis Longitudinal Outcome

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Economic analysis in product design——A case study of a TCM dietary supplement

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Chinese Journal of Chemical Engineering 2016年第1期24卷 202-214页

作者： yuen Shan Cheng Ka Yip fung Ka Ming Ng Christianto Wibowo Department of Chemical and Biomolecular Engineering The Hong Kong University of Science and Technology ClearWaterBay Technology Inc.

An approach for the economic analysis of chemical product design is proposed. It takes into account of customers' preference on product quality and economic considerations such as pricing, profit, market share, capital investment, and operating cost. The activities needed to support business decision making – identifying product quality, estimating product cost, calculating financial metrics, and performing make–buy analysis – are *** design of a Ganoderma lucidum dietary supplement, a traditional Chinese medicinal(TCM) product, is used to illustrate all the activities in this approach.

关键词： Product design Product conceptualization TCM dietary supplement Economic analysis Make–buy analysis

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Prediction of hepatocellular carcinoma development by aminotransferase to platelet ratio index in primary biliary cholangitis

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World Journal of Gastroenterology 2017年第44期23卷 7863-7874页

作者： Ka-Shing Cheung Wai-Kay Seto James fung Lung-Yi Mak Ching-Lung Lai Man-fung yuen Department of Medicine The University of Hong Kong Queen Mary Hospital State Key Laboratory for Liver Research The University of Hong Kong

AIM To investigate the usefulness of aspartate aminotransferase to platelet ratio index(APRI) in predicting hepatocellular carcinoma(HCC) risk in primary biliary cholangitis(PBC).METHODS We identified PBC patients between 2000 and 2015 by searching the electronic medical database of a tertiary center. The hazard ratio(HR) of HCC with different risk factors was determined by Cox proportional hazards model. RESULTS One hundred and forty-four PBC patients were recru-ited. Patients were diagnosed at a median age of 57.8 years [interquartile range(IQR): 48.7-71.5 years), and 41(28.5%) patients had cirrhosis at baseline. The median follow-up duration was 6.9 years(range: 1.0-26.3 years). Twelve patients developed HCC, with an incidence rate of 10.6 cases per 1000 patient-years. The overall 5-, 10-and 15-year cumulative incidences of HCC were 2.3% 95%CI: 0%-4.8%), 8.4%(95%CI: 1.8%-14.5%) and 21.6%(6.8%-34.1%), respectively. Older age(HR = 1.07), cirrhosis(HR = 4.38) and APRI at 1 year after treatment(APRI-r1) > 0.54(HR = 3.94) were independent factors for HCC development. APRI-r1, when combined with treatment response, further stratified HCC risk(log rank P < 0.05). The area under receiver operating curve of APRI-r1 in predicting HCC was 0.77(95%CI: 0.64-0.88).CONCLUSION APRI-r1 can be used to predict the development of HCC in PBC patients. Combination of APRI-r1 with treatment response can further stratify the HCC risk.

关键词： Aspartate aminotransferase Platelet ratio index Hepatocellular carcinoma Primary biliary cholangitis Ursodeoxycholic acid Cirrhosis

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Epidemiology and natural history of Wilson's disease in the Chinese: A territory-based study in Hong Kong between 2000 and 2016

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World Journal of Gastroenterology 2017年第43期23卷 7716-7726页

作者： Ka-Shing Cheung Wai-Kay Seto James fung Lung-Yi Mak Ching-Lung Lai Man-fung yuen Department of Medicine The University of Hong KongQueen Mary Hospital State Key Laboratory for Liver Research The University of Hong Kong

AIM To investigate the epidemiology and natural history of Wilson's disease in the *** Data were retrieved via electronic search of hospital medical registry of the Hong Kong Hospital Authority,which covers all the public healthcare services. We identified cases of Wilson's disease between 2000 and 2016 by the International Classification of Diseases(ICD)-9 code. We analyzed the incidence rate,prevalence and adverse outcomes of Wilson's *** We identified 211 patients(male cases 104; female cases 107; median age 27.2 years,IQR: 17.1-38.6 years; duration of follow-up 8.0 years,IQR: 5.0-14.0 years). The average annual incidence rate was 1.44 per million person-years while the prevalence was 17.93 per million. Between 2000 and 2016,there was a decrease in the annual incidence rate from 1.65 to 1.23 per million person-years(P = 0.010),whereas there was an increase in the annual prevalence from 7.80 to 25.20 per million(P < 0.001). Among the 176 cases with hepatic involvement,38(21.6%) had cirrhosis,three(1.7%) developed hepatocellular carcinoma,24(13.6%) underwent liver transplantations,and 26(14.8%) died. Seven patients had concomitant chronic viral hepatitis B or C. The 5-year and 10-years rates of overall survival were 92.6% and 89.5%,and for transplant-free survival rates 91.8% and 87.4%,respectively. Cirrhosis and possibly chronic viral hepatitis were associated with poorer overall survival. CONCLUSION There was a significant increase in the prevalence of Wilson's disease in Hong Kong. The prognosis was favorable except for those with cirrhosis or concomitant viral hepatitis.

关键词： Hepaticolenticular degeneration Cirrhosis Hepatocellular carcinoma Transplantation

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Study of Defect-Layers Effect in Ferroelectric Thin Film with Transverse Ising Model

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Communications in Theoretical Physics 2011年第12期56卷 1057-1062页

作者： WANG Chun-Dong TENG Bao-Hua Kwok So-Ying LU Zhen-Zhen yuen Muk-fung Center of Super-Diamond and Advanced Films （COSDAF） and Department of Physics and Materials Science City University of Hong Kong Hong Kong SAR China School of Physical Electronics University of Electronic Science and Technology of China Chengdu 610054 China

By taking into account the two-spin interaction in the transverse Ising model （TIM）, the influence of the defect layers （including JB and ΩB） on the polarization and Curie temperature are calculated numerically, within the framework of the decoupling approximation under Green＇s function. The numerical results show that the polarization and Curie temperature will both become large sensitively due to the large values of JB and the small value of ΩB of the defect layers. Meanwhile, the dependence of the crossover values of the exchange interaction JA, the transverse field ΩA of the bulk material on the exchange interaction JB and the transverse field ΩB of the defect layers are shown in 3-Dimensional （3-D） figures for the first time. Moreover, the transition features of the ferroelectric thin film with defect layers are presented.

关键词： ferroelectrics phase transitions defect-layer

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