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Cancer stem-like cells in Epstein-Barr virus-associated nasopharyngeal carcinoma

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Chinese Journal of Cancer 2014年第11期33卷 529-538页

作者： Samantha Wei-Man Lun Siu-Tim cheung Kwok-Wai Lo Department of Anatomical and Cellular Pathology State Key Laboratory in Oncology in South ChinaPrince of Wales Hospital Department of Surgery The University of Hong Kong Li ka shing Institute of Health Science The Chinese University of Hong Kong

Although the Epstein-Barr virus(EBV) has spread to all populations in the world, EBV-associated nasopharyngeal carcinoma(NPC) is prevalent only in South China and Southeast Asia. The role of EBV in the malignant transformation of nasopharyngeal epithelium is the main focus of current researches. Radiotherapy and chemoradiotherapy have been successful in treating early stage NPC, but the recurrence rates remain high. Unfortunately, local relapse and metastasis are commonly unresponsive to conventional treatments. These recurrent and metastatic lesions are believed to arise from residual or surviving cells that have the properties of cancer stem cells. These cancer stem-like cells(CSCs) have the ability to selfrenew, differentiate, and sustain propagation. They are also chemo-resistant and can form spheres in anchorage-independent environments. This review summarizes recent researches on the CSCs in EBVassociated NPC, including the findings regarding cell surface markers, stem cell-related transcription factors, and various signaling pathways. In particular, the review focuses on the roles of EBV latent genes [latent membrane protein 1(LMP1) and latent membrane protein 2A(LMP2A)], cellular microRNAs, and adenosine triphosphate(ATP)-binding cassette chemodrug transporters in contributing to the properties of CSCs, including the epithelial-mesenchymal transition, stem-like transition, and chemo-resistance. Novel therapeutics that enhance the efficacy of radiotherapy and chemoradiotherapy and inhibitors that suppress the properties of CSCs are also discussed.

关键词：肿瘤干细胞 EB病毒鼻咽癌潜伏膜蛋白1 上皮细胞东南亚地区三磷酸腺苷 EBV

Brain delivering RNA-based therapeutic strategies by targeting mTOR pathway for axon regeneration after central nervous system injury

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Neural Regeneration Research 2022年第10期17卷 2157-2165页

作者： Ming-Xi Li Jing-Wen Weng Eric S.Ho shing Fung Chow Chi Kwan Tsang Clinical Neuroscience Institute The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina Department of Pharmacology and Pharmacy Li Ka Shing Faculty of MedicineUniversity of Hong KongHong Kong Special Administrative RegionChina Department of Biology and Department of Computer Science Lafayette CollegeEastonPAUSA

Injuries to the central nervous system(CNS)such as stroke,brain,and spinal cord trauma often result in permanent disabilities because adult CNS neurons only exhibit limited axon *** brain has a surprising intrinsic capability of recovering itself after ***,the hostile extrinsic microenvironment significantly hinders axon *** advances have indicated that the inactivation of intrinsic regenerative pathways plays a pivotal role in the failure of most adult CNS neuronal ***,substantial evidence has convincingly demonstrated that the mechanistic target of rapamycin(mTOR)signaling is one of the most crucial intrinsic regenerative pathways that drive axonal regeneration and sprouting in various CNS *** this review,we will discuss the recent findings and highlight the critical roles of mTOR pathway in axon regeneration in different types of CNS ***,we will demonstrate that the reactivation of this regenerative pathway can be achieved by blocking the key mTOR signaling components such as phosphatase and tensin homolog(PTEN).Given that multiple mTOR signaling components are endogenous inhibitory factors of this pathway,we will discuss the promising potential of RNA-based therapeutics which are particularly suitable for this purpose,and the fact that they have attracted substantial attention recently after the success of coronavirus disease 2019 *** specifically tackle the blood-brain barrier issue,we will review the current technology to deliver these RNA therapeutics into the brain with a focus on nanoparticle *** will propose the clinical application of these RNA-mediated therapies in combination with the brain-targeted drug delivery approach against mTOR signaling components as an effective and feasible therapeutic strategy aiming to enhance axonal regeneration for functional recovery after CNS injury.

关键词： axon sprouting axon regeneration brain targeted drug delivery CNS injury ischemic stroke mTOR nanoparticle neural circuit reconstruction PTEN RNA-based therapeutics

Optimization of nanofiber scaffold properties towards nerve guidance channel design

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Neural Regeneration Research 2018年第7期13卷 1179-1180页

作者： Graham ka-Hon Shea Francis Mok Department of Orthopaedics and Traumatology The University of Hong Kong Li ka shing Faculty of Medicine The University of Hong Kong

Nerve guidance channels are limited by lack of topographical guidance：Treatment of sizeable nerve gaps remains problematic following peripheral nerve *** outcomes are good when neurorrhaphy,or direct end-to-end suture repair,is *** problem arises when there is significant segmental loss,which can occur following trauma as well as oncological procedures.

关键词： Optimization of nanofiber scaffold properties towards nerve guidance channel design

Simultaneous portohepatic vein embolization a radiological:a short cut to associating liver partition and portal vein ligation for staged hepatectomy?

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Hepatobiliary Surgery and Nutrition 2021年第3期10卷 373-375页

作者： ka Wing Ma Albert Chi Yan Chan Department of Surgery Li Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina

Insufficient future liver remnant(FLR)represented one of the most common contraindications for major hepatectomy as post-hepatectomy liver failure(PHLF)was associated with high mortality with no effective *** the description of portal vein embolization(PVE)by Makucchi in 1984(1),FLR volumetric modulation was made *** of PVE before major hepatectomy for patients with insufficient FLR(i.e.,<30%of estimated standard liver volume)had greatly improved resectability.

关键词： hepatectomy mortality liver

Diagnostic accuracy of Focused Abdominal Sonography for Trauma in blunt abdominal trauma patients in a trauma centre of Hong Kong

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Chinese Journal of Traumatology 2012年第5期15卷 273-278页

作者： cheung Kent Shek Wong Hay Tai Leung Ling Pong Tsang Tat Chi Leung Gilberto ka Kit Department of Accident and Emergency Queen Mary Hospital 102 Pokfulam Road Pokfulam Hong Kong China Department of Surgery Li Ka Shing Faculty of Medicine University of Hong Kong Hong Kong China

Objective： Focused Abdominal Sono graphy for Trauma （FAST） is widely used for the detection of intraperitoneal free fluids in patients suffering from blunt abdominal trauma （BAT）. This study aimed at assessing the diagnostic accuracy of this investigation in a designated trauma centre. Methods： This was a retrospective study of BAT pa tients over a 6 year period seen in a trauma centre in Hong Kong. FAST findings were compared with laparotomy, ab dominal computed tomography or autopsy findings, which served as the gold standard for presence of intraperi toneal free fluids. The patients who did not have FAST or gold standard confirmatory test performed, had preexisting peritoneal fluid, died at resuscitation or had imcomplete docu mentation of FAST findings were excluded. The performance of FAST was expressed as sensitivity, specificity, predictive values （PV）, likelihood ratios （LR） and accuracy. Results： FAST was performed in 302 patients and 153 of them were included in this analysis. The sensitivity, specificity, positive PV, negative PV, positive LR, negative LR and accuracy for FAST were respectively 50.0%, 97.3%, 87.0%, 84.6%, 18.8, 0.5 and 85.0%. FAST was found to be more sensitive in less severely injured patients and more specific in more severely injured patients. Conclusion： FAST is a reliable investigation in the initial assessment of BAT patients. The diagnostic values of FAST could be affected by the severity of injury and staff training is needed to further enhance its effective use.

关键词： Laparotomy Autopsy Tomography, X-ray computed Tomography, spiral computed Ultra-sonography

Traditional Chinese medicine poisoning in the emergency departments in Hong Kong: Trend, clinical presentation and predictors for poor outcome

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World Journal of Emergency Medicine 2021年第2期12卷 143-150页

作者： Rex Pui Kin Lam Eric Ho Yin Lau Wai Lam Yip Joe kai shing Leung Matthew Sik Hon Tsui Emergency Medicine Unit Li Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina Accident and Emergency Department Queen Mary HospitalHong KongChina Accident and Emergency Department Pamela Youde Nethersole Eastern HospitalHong KongChina School of Public Health Li Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina

Dear editor,Traditional Chinese medicine (TCM) is popular in many countries,especially in the Chinese population.^([1,2]) In Hong Kong,it has been estimated that around 15%of the population consumed Chinese medicine products/herbs in the preceding *** reasons for consumption include regulating bodily functions,curing disease,and building up health.

关键词： has editor curing

The D253N Mutation in the Polymerase Basic 2 Gene in Avian Influenza(H9N2) Virus Contributes to the Pathogenesis of the Virus in Mammalian Hosts

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Virologica Sinica 2018年第6期33卷 531-537页

作者： Jinfeng Zhang Rong Su Xiaoyun Jian Hongliang An Ronbing Jiang Chris ka Pun Mok Laboratory Medicine Center Foshan Hospital of Traditional Chinese Medicine Guangzhou University of Chinese Medicine Department of Respiratory Medicine Foshan Hospital of Traditional Chinese Medicine Guangzhou University of Chinese Medicine State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University HKU-Pasteur Research Pole School of Public Health HKU Li Ka Shing Faculty of Medicine The University of Hong Kong

Mutations in the polymerase basic 2(PB2) gene of avian influenza viruses are important signatures for their adaptation to mammalian hosts. Various adaptive mutations have been identified around the 627 and nuclear localization sequence(NLS) domains of PB2 protein, and these mutations contribute to the replicative ability of avian influenza ***, few studies have focused on adaptive mutations in other regions of PB2. In this study, we investigated the functional roles of the D253N mutation in PB2 in an H9N2 virus. This mutation was found to affect an amino acid residue in the middle domain of the PB2 protein. The virus with the D253N mutation showed higher polymerase activity and transiently increased viral replication in human cells. However, the mutant did not show significant differences in viral replication in the respiratory tract of mice upon infection. Our results supported that the D253N mutation in the middle domain of PB2, similar to mutations at the 627 and NLS domains, specifically contributed to the replication of avian influenza viruses in human cells.

关键词： Avian influenza virus Mammalian adaptation D253N Polymerase basic 2(PB2) H9N2

A machine learning model for colorectal liver metastasis post-hepatectomy prognostications

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Hepatobiliary Surgery and Nutrition 2023年第4期12卷 495-506,I0007-I0016页

作者： Cynthia Sin Nga Lam Alina Ashok Bharwani Evelyn Hui Yi Chan Vernice Hui Yan Chan Howard Lai Ho Au Margaret kay Ho Shireen Rashed Bernard Ming Hong Kwong Wentao Fang ka Wing Ma Chung Mau Lo Tan To cheung Li ka shing Faculty of Medicine The University of Hong KongHong Kong SARChina Department of Surgery Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina

Background:Currently,surgical resection is the mainstay for colorectal liver metastases(CRLM)management and the only potentially curative treatment *** tools can support patient selection for surgical resection to maximize therapeutic *** study aimed to develop a survival prediction model using machine learning based on a multicenter patient sample in Hong ***:Patients who underwent hepatectomy for CRLM between 1 January 2009 and 31 December 2018 in four hospitals in Hong Kong were included in the *** analysis was performed using Cox proportional hazards(CPH).A stepwise selection on Cox multivariable models with Least Absolute Shrinkage and Selection Operator(LASSO)regression was applied to a multiply-imputed dataset to build a prediction *** model was validated in the validation set,and its performance was compared with that of Fong Clinical Risk Score(CRS)using concordance ***:A total of 572 patients were included with a median follow-up of 3.6 *** full models for overall survival(OS)and recurrence-free survival(RFS)consist of the same 8 established and novel variables,namely colorectal cancer nodal stage,CRLM neoadjuvant treatment,Charlson Comorbidity Score,pre-hepatectomy bilirubin and carcinoembryonic antigen(CEA)levels,CRLM largest tumor diameter,extrahepatic metastasis detected on positron emission-tomography(PET)-scan as well as KRAS *** CRLM Machine-learning Algorithm Prognostication model(CMAP)demonstrated better ability to predict OS(C-index=0.651),compared with the Fong CRS for 1-year(C-index=0.571)and 5-year OS(C-index=0.574).It also achieved a C-index of 0.651 for ***:We present a promising machine learning algorithm to individualize prognostications for patients following resection of CRLM with good discriminative ability.

关键词： Machine-learning colorectal liver metastasis(CRLM) prognostic model survival analysis hepatectomy outcome

Expression and reconstitution of the bioluminescent Ca2+reporter aequorin in human embryonic stem cells,and exploration of the presence of functional IP3 and ryanodine receptors during the early stages of their differentiation into cardiomyocytes

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Science China(Life Sciences) 2016年第8期59卷 811-824页

作者： Harvey Y.S.Chan Man Chun cheung Yi Gao Andrew L.Miller Sarah E.Webb Division of Life Science&State Key Laboratory of Molecular Neuroscience HKUSTClear Water BayHong KongChina Stem Cell&Regenerative Medicine Consortium Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong KongChina Marine Biological Laboratory Woods Hole MA 02543USA

In order to develop a novel method of visualizing possible Ca2＋ signaling during the early differentiation of hESCs into cardi- omyocytes and avoid some of the inherent problems associated with using fluorescent reporters, we expressed the biolumines- cent Ca2＋ reporter, apo-aequorin, in HES2 cells and then reconstituted active holo-aequorin by incubation withf-coelenterazine. The temporal nature of the Ca2＋ signals generated by the holo-f-aequorin-expressing HES2 cells during the earliest stages of differentiation into cardiomyocytes was then investigated. Our data show that no endogenous Ca2＋ transients （generated by re- lease from intracellular stores） were detected in 1-12-day-old cardiospheres but transients were generated in cardiospheres following stimulation with KC1 or CaC12, indicating that holo-f-aequorin was functional in these cells. Furthermore, following the addition of exogenous ATP, an inositol trisphosphate receptor （IP3R） agonist, small Ca2＋transients were generated from day 1 onward. That ATP was inducing Ca2＋ release from functional IP3Rs was demonstrated by treatment with 2-APB, a known IP3R antagonist. In contrast, following treatment with caffeine, a ryanodine receptor （RyR） agonist, a minima/Ca2＋ response was observed at day 8 of differentiation only. Thus, our data indicate that unlike RyRs, IP3Rs are present and continually functional at these early stages of cardiomyocyte differentiation.

关键词： Ca2+ signaling apo-aequorin expression bioluminescence HES2 human embryonic stem cells hESC-derived cardiospheres IP3 and ryanodine receptors