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Downregulation of Hes1 expression in experimental biliary atresia and its effects on bile duct structure

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World Journal of Gastroenterology 2018年第29期24卷 3260-3272页

作者： Rui-Zhong Zhang Xin-Hao Zeng Ze-Feng Lin Ming-Fu Yan-Lu Tong vincent CH lui Paul KH Tam Jonathan R Lamb Hui-Min Xia Yan Chen Department of Pediatric Surgery Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou 510623Guangdong ProvinceChina Department of Surgery and Pathology University of Hong KongHong KongChina Department of Life Sciences Faculty of Natural SciencesImperial College LondonLondon SW7 2AZUnited Kingdom

AIM To analyze the expression and function of the notchsignaling target gene Hes1 in a rhesus rotavirusinduced mouse biliary atresia model. METHODS The morphologies of biliary epithelial cells in biliary atresia patients and in a mouse model were examined by immunohistochemical staining. Then, the differential expression of Notch signaling pathway-related molecules was investigated. Further, the effects of the si RNAmediated inhibition of Hes1 expression were examined using a biliary epithelial cell 3 D culture *** Both immature(Ep CAM+) and mature(CK19+) biliary epithelial cells were detected in the livers of biliary atresia patients without a ductile structure and in the mouse model with a distorted bile duct structure. The hepatic expression of transcripts for most Notch signaling molecules were significantly reduced on day 7 but recovered to normal levels by day 14, except for the target molecule Hes1, which still exhibited lower m RNA and protein levels. Expression of the Hes1 transcriptional co-regulator, RBP-Jκ was also reduced. A 3 D gel culture system promoted the maturation of immature biliary epithelial cells, with increased expression of CK19+ cells and the formation of a duct-like structure. The administration of Hes1 si RNA blocked this process. As a result, the cells remained in an immature state, and no duct-like structure was *** Our data indicated that Hes1 might contribute to the maturation and the cellular structure organization of biliary epithelial cells, which provides new insight into understanding the pathology of biliary atresia.

关键词： Biliary atresia Rhesus rotavirus Hes1 EpCAM Epithelial cells 3D culture

Role of CD56-expressing immature biliary epithelial cells in biliary atresia

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World Journal of Gastroenterology 2016年第8期22卷 2545-2557页

作者： Rui-Zhong Zhang Jia-Kang Yu Jiao Peng Feng-Hua Wang Hai-Ying Liu vincent CH lui John M Nicholls Paul KH Tam Jonathan R Lamb Yan Chen Hui-Min Xia Department of Pediatric Surgery Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 Guangdong Province China Department of Pathology and Clinical Laboratory Guangzhou Women and Children's Medical Center Guangzhou 510623 Guangdong Province China Department of Surgery and Pathology University of Hong Kong Hong Kong China Department of Life Sciences Faculty of Natural Sciences Imperial College London London SW7 2AZ United Kingdom

AIM: To analyze the clinical and pathological parameters and expression of the neural cell adhesion molecule(CD56) in patients with biliary atresia(BA).METHODS: Established clinical laboratory markers of hepatic function, including enzyme activity, protein synthesis, and bilirubin metabolism, were evaluated in patients with BA and compared with those in patients with choledochal cysts and neonatal hepatitis. Pathological changes in tissue morphology and fibrosis were examined by histological and tissue collagen staining. Immunohistochemical staining for the biliary epithelial cell markers CD56 and CK19 together with the Notch signaling related molecules Notch1 and Notch2 was performed in the context of alterations in the structure of intrahepatic biliary ***: Differences in some clinical laboratoryparameters among the three diseases examined were observed, but they did not correlate with the pathological classification of fibrosis in BA. Immunohistochemical staining showed the presence of CD56-positive immature bile ducts in most patients(74.5%) with BA but not in patients with choledochal cysts or neonatal hepatitis. The number of CD56-expressing cells correlated with disease severity, with more positive cells present in the later stages of liver damage(81.8% vs 18.2%). Furthermore, bile plugs were mainly found in CD56-positive immature biliary ducts. Notch signaling was a key regulatory pathway in biliary duct formation and played a role in tissue fibrosis. Notch1 was co-expressed in CD56-positive cells, whereas Notch2 was found exclusively in blood vessels in the portal area of patients with BA. CONCLUSION: The maturation of biliary epithelial cells and the expression of Notch may play a role in the pathogenesis of BA.

关键词： Biliary atresia CD56 Epithelial cell adhesion molecule Cytokeratin 7 Biliary epithelial cells Liver fibrosis

Depletion of the IKBKAP ortholog in zebrafish leads to hirschsprung disease-like phenotype

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World Journal of Gastroenterology 2015年第7期21卷 2040-2046页

作者： William Wai-Chun Cheng Clara Sze-Man Tang Hong-Sheng Gui Man-Ting So vincent Chi-Hang lui Paul Kwong-Hang Tam Maria-Mercè Garcia-Barcelo Department of Surgery Li Ka Shing Faculty of Medicine the University of Hong Kong Department of Psychiatry Li Ka Shing Faculty of Medicine the University of Hong Kong Center for Genomic Sciences of the Li Ka Shing Faculty of Medicine the University of Hong Kong Centre for Reproduction Development and Growth Li Ka Shing Faculty of Medicine the University of Hong Kong

AIM:To investigate the role of IKBKAP(inhibitor of kappa light polypeptide gene enhancer in B-cells,kinase complexassociated protein)in the development of enteric nervous system(ENS)and Hirschsprung disease(HSCR).METHODS:In this study,we injected a morpholino that blocked the translation of ikbkap protein to 1-cell stage zebrafish *** phenotype in the ENS was analysed by antibody staining of the pan-neuronal marker Hu C/D followed by enteric neuron *** mean numbers of enteric neurons were compared between the morphant and the *** also studied the expressions of ret and phox2bb,which are involved in ENS development,in the ikbkap morpholino injected embryos by quantitative reverse transcriptase polymerase chain reaction and compared them with the ***:We observed aganglionosis(χ2,P<0.01)and a reduced number of enteric neurons(38.8±9.9 vs50.2±17.3,P<0.05)in the zebrafish embryos injected with ikbkap translation-blocking morpholino(morphant)when compared with the control *** of the morpholino was confirmed by similar results obtained using a second non-overlapping morpholino that blocked the translation of *** further studied the morphant by analysing the expression levels of genes involved in ENS development such as ret,phox2bb and sox10,and found that phox2bb,the ortholog of human PHOX2B,was significantly down-regulated(0.51±0.15 vs 1.00±0,P<0.05).Although we also observed a reduction in theexpression of ret,the difference was not ***:Loss of IKBKAP contributed to HSCR as demonstrated by functional analysis in zebrafish embryos.

关键词： Hirschsprung disease Enteric nervous system IKBKAP

Magnetic resonance imaging manifestations of cerebral small vessel disease:automated quantification and clinical application

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Chinese Medical Journal 2021年第2期134卷 151-160页

作者： Lei Zhao Allan Lee Yu-Hua Fan vincent C.T.Mok Lin Shi BrainNow Research Institute ShenzhenGuangdong 518000China Department of Neurology The First Affiliated HospitalSun Yat-sen UniversityGuangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological DiseasesNational Key Clinical Department and Key Discipline of NeurologyGuangzhouGuangdong 510080China Department of Medicine and Therapeutics The Chinese University of Hong KongHong Kong 999077China Gerald Choa Neuroscience Centre Margaret KL Cheung Research Centre for Management of ParkinsonismTherese Pei Fong Chow Research Centre for Prevention of DementiaLui Che Woo Institute of Innovative MedicineThe Chinese University of Hong KongHong Kong 999077China Department of Imaging and Interventional Radiology The Chinese University of Hong KongHong Kong 999077China

The common cerebral small vessel disease(CSVD)neuroimaging features visible on conventional structural magnetic resonance imaging include recent small subcortical infarcts,lacunes,white matter hyperintensities,perivascular spaces,microbleeds,and brain *** CSVD neuroimaging features have shared and distinct clinical consequences,and the automatic quantification methods for these features are increasingly used in research and clinical *** review article explores the recent progress in CSVD neuroimaging feature quantification and provides an overview of the clinical consequences of these CSVD features as well as the possibilities of using these features as endpoints in clinical *** added value of CSVD neuroimaging quantification is also discussed for researches focused on the mechanism of CSVD and the prognosis in subjects with CSVD.

关键词： Cerebral small vessel disease Neuroimaging manifestations Automated quantification Clinical relevance

Kidney health for all: bridging the gap in kidney health education and literacy

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肾脏病与透析肾移植杂志 2022年第1期31卷 1-8页

作者： Robyn G.Langham Kamyar Kalantar-Zadeh Ann Bonner Alessandro Balducci Li-Li Hsiao Latha A.Kumaraswami Paul Laffin Vassilios Liakopoulos Gamal Saadi Ekamol Tantisattamo Ifeoma Ulasi Siu-Fai lui for the World Kidney Day Joint Steering Committee St.vincent’s Hospital Department of MedicineUniversity of MelbourneMelbourneVictoriaAustralia Division of Nephrology Hypertension and Kidney TransplantationDepartment of MedicineUniversity of California IrvineOrangeCaliforniaUSA School of Nursing and Midwifery Griffith UniversitySouthportQueenslandAustralia Italian Kidney Foundation RomeItaly Brigham and Women’s Hospital Renal DivisionDepartment of MedicineBostonMassachusettsUSA Tamilnad Kidney Research(TANKER)Foundation The International Federation of Kidney Foundations-World Kidney Alliance(IFKF-WKA)ChennaiIndia International Society of Nephrology BrusselsBelgium Division of Nephrology and Hypertension 1st Department of Internal MedicineAHEPA HospitalAristotle University of ThessalonikiThessalonikiGreece Nephrology Unit Department of Internal MedicineFaculty of MedicineCairo UniversityGizaEgypt Renal Unit Department of MedicineCollege of MedicineUniversity of NigeriaItuku-OzallaEnuguNigeria International Federation of Kidney Foundations-World Kidney Alliance The Jockey Club School of Public Health and Primary CareThe Chinese University of Hong KongHong KongChina The World Kidney Day Joint Steering Committee is listed in the Appendix

The high burden of kidney disease,global disparities in kidney care,and poor outcomes of kidney failure bring a concomitant growing burden to persons affected,their families,and carers,and the community at *** literacy is the degree to which persons and organizations have or equitably enable individuals to have the ability to find,understand,and use information and services to make informed health⁃related decisions and actions for themselves and *** than viewing health literacy as a patient deficit,improving health literacy largely rests with health care providers communicating and educating effectively in codesigned partnership with those with kidney *** kidney policy makers,health literacy provides the imperative to shift organizations to a culture that places the person at the center of health *** growing capability of and access to technology provides new opportunities to enhance education and awareness of kidney disease for all *** in telecommunication,including social media platforms,can be leveraged to enhance persons’and providers’education;The World Kidney Day declares 2022 as the year of“Kidney Health for All”to promote global teamwork in advancing strategies in bridging the gap in kidney health education and *** organizations should work toward shifting the patient⁃deficit health literacy narrative to that of being the responsibility of health care providers and health policy *** engaging in and supporting kidney health-centered policy making,community health planning,and health literacy approaches for all,the kidney communities strive to prevent kidney diseases and enable living well with kidney disease.

关键词： educational gap empowerment health literacy health policy information technology kidney health partnership prevention social media

Pandemic of the aging society—sporadic cerebral small vessel disease

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Chinese Medical Journal 2021年第2期134卷 143-150页

作者： Alexander Yuk Lun Lau Bonaventure Yiu Ming Ip Ho Ko Bonnie Yin Ka Lam Lin Shi Karen Ka Yan Ma Lisa Wing Chi Au Yannie Oi Yan Soo Thomas Wai Hong Leung Adrian Wong vincent Chung Tong Mok Division of Neurology Department of Medicine and TherapeuticsThe Faculty of MedicineThe Chinese University of Hong KongHong KongChina Gerald Choa Neuroscience Centre Faculty of MedicineLui Che Woo Institute of Innovative MedicineThe Chinese University of Hong KongHong KongChina Faculty of Medicine School of Biomedical SciencesLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongChina Margaret Cheung K.L.Cheung Research Centre for Management of Parkinsonism Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Imaging and Interventional Radiology The Chinese University of Hong KongHong KongChina Shenzhen Research Institute The Chinese University of Hong KongShenzhenGuangdongChina.

Age-related sporadic cerebral small vessel disease(CSVD)has gained increasing attention over the past decades because of its increasing prevalence associated with an aging *** widespread application of and advances in brain magnetic resonance imaging in recent decades have significantly increased researchers’understanding in the in vivo evolution of CSVD,its impact upon the brain,its risk factors,and the mechanisms that explain the various clinical manifestation associated with sporadic *** this review,we aimed to provide an update on the pathophysiology,risk factors,biomarkers,and the determinants and spectrum of the clinical manifestation of sporadic CSVD.

关键词： Cerebral small vessel disease Clinical spectrum Pathophysiology

Overview of methodologies and statistical strategies in observational studies and meta-analyses on the risk of hepatocellular carcinoma in patients with chronic hepatitis B on entecavir or tenofovir therapy

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Hepatoma Research 2022年第1期8卷 143-156页

作者： Terry Cheuk-Fung Yip vincent Wai-Sun Wong Mandy Sze-Man Lai Vicki Wing-Ki Hui Yee-KitTse Grace Lai-Hung Wong Medical Data Analytics Centre Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics 9/F Lui Che Woo Clinical Sciences BuildingPrince of Wales Hospital30-32 Ngan Shing StreetShatinHong KongChina Institute of Digestive Disease The Chinese University of Hong KongHong KongChina

Entecavir(ETV)and tenofovir disoproxil fumarate(TDF)are first-line antiviral therapies for patients with chronic hepatitis B(CHB)and reduce the risk of disease progression and liver-related complications,as well as improve survival by effectively suppressing viral ***,since the first publication in 2019 on a lower risk of hepatocellular carcinoma(HCC)in Korean patients receiving TDF than those receiving ETV,the topic has remained a hot and unsettled *** studies and meta-analyses have yielded conflicting *** HCC takes time to develop,studies are mainly observational to benefit from a larger sample size and longer follow-up that provides a higher statistical power to compare the two ***,TDF was available to CHB patients a few years later than ETV in most countries,thus leading to a difference in follow-up ***,despite studying the same topic,the difference in data sources and available parameters,inclusion and exclusion criteria,and use of statistical methods complicated the interpretation and comparison of the findings and contributed to between-study heterogeneity in *** review describes some caveats in interpreting and comparing the results from these observational studies and *** studies should explore better designed observational studies with high-quality data sources,and aggregation of patient data in metaanalysis to tackle between-study heterogeneity.

关键词： Bias confounding hepatitis B virus hepatocellular carcinoma liver cancer nucleos(t)ide analogues propensity score