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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

Fe65-engineered neuronal exosomes encapsulating corynoxine-B ameliorate cognition and pathology of Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5481-5494页

作者： Ashok Iyaswamy Abhimanyu Thakur Xin-Jie Guan Senthilkumar Krishnamoorthi Tsz Yan Fung Kejia Lu Isha Gaurav Zhijun Yang Cheng-Fu Su Kwok-Fai Lau Kui Zhang Roy Chun-Laam Ng Qizhou Lian King-Ho cheung Keqiang Ye Huanhuan Joyce Chen Min Li Mr.&Mrs.Ko Chi-Ming Centre for Parkinson’s Disease Research School of Chinese MedicineHong Kong Baptist UniversityHong Kong SARChina Pritzker School of Molecular Engineering The University of ChicagoChicagoILUSA Ben May Department for Cancer Research The University of ChicagoChicagoILUSA School of Chinese Medicine Hong Kong Baptist UniversityHong Kong SARChina School of Life Sciences The Chinese University of Hong KongHong Kong SARChina Division of Neuroscience School of Biological SciencesFaculty of BiologyMedicine and HealthManchester Academic Health Science CentreUniversity of ManchesterManchesterUnited Kingdom Department of Medicine Li Ka Shing Faculty of MedicineThe University of Hong KongPok Fu LamHong Kong SARChina Prenatal Diagnostic Center and Cord Blood Bank Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhouChina HKUMed Laboratory of Cellular Therapeutics the University of Hong KongPok Fu LamHong Kong SARChina Faculty of Life and Health Sciences Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina

Alzheimer’s disease(AD)is a neurodegenerative disorder characterized by the predominant impairment of neurons in the hippocampus and the formation of amyloid plaques,hyperphosphorylated tau protein,and neurofibrillary tangles in the *** overexpression of amyloid-βprecursor protein(APP)in an AD brain results in the binding of APP intracellular domain(AICD)to Fe65 protein via the C-terminal Fe65-PTB2 interaction,which then triggers the secretion of amyloid-βand the consequent pathogenesis of ***,targeting the interaction between APP and Fe65 can offer a promising therapeutic approach for ***,exosome,a type of extracellular vesicle with diameter around 30–200 nm,has gained much attention as a potential delivery tool for brain diseases,including AD,due to their ability to cross the blood–brain barrier,their efficient uptake by autologous cells,and their ability to be surface-modified with target-specific receptor ***,the engineering of hippocampus neuron cell-derived exosomes to overexpress Fe65,enabled the development of a novel exosome-based targeted drug delivery system,which carried Corynoxine-B(Cory-B,an autophagy inducer)to the APP overexpressed-neuron cells in the brain of AD *** Fe65-engineered HT22 hippocampus neuron cell-derived exosomes(Fe65-EXO)loaded with Cory-B(Fe65-EXO-Cory-B)hijacked the signaling and blocked the natural interaction between Fe65 and APP,enabling APP-targeted delivery of ***,Fe65-EXO-Cory-B induced autophagy in APP-expressing neuronal cells,leading to amelioration of the cognitive decline and pathogenesis in AD mice,demonstrating the potential of Fe65-EXO-Cory-B as an effective therapeutic intervention for AD.

关键词： Alzheimer gained loaded

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

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 Ca^(2+) signaling during the early differentiation of h ESCs into cardiomyocytes and avoid some of the inherent problems associated with using fluorescent reporters, we expressed the bioluminescent Ca^(2+) reporter, apo-aequorin, in HES2 cells and then reconstituted active holo-aequorin by incubation with f-coelenterazine. The temporal nature of the Ca^(2+) 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 Ca^(2+) transients(generated by release from intracellular stores) were detected in 1–12-day-old cardiospheres but transients were generated in cardiospheres following stimulation with KCl or Ca Cl_2, indicating that holo-f-aequorin was functional in these cells. Furthermore, following the addition of exogenous ATP, an inositol trisphosphate receptor(IP_3R) agonist, small Ca^(2+) transients were generated from day 1 onward. That ATP was inducing Ca^(2+) release from functional IP_3 Rs was demonstrated by treatment with 2-APB, a known IP_3 R antagonist. In contrast, following treatment with caffeine, a ryanodine receptor(Ry R) agonist, a minimal Ca^(2+) response was observed at day 8 of differentiation only. Thus, our data indicate that unlike Ry Rs, IP_3 Rs 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

Efficacy of vasopressin, steroid, and epinephrine protocol for in-hospital cardiac arrest resuscitation: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis

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Journal of Geriatric Cardiology 2022年第9期19卷 705-711页

作者： Danish Iltaf Satti Yan Hiu Athena Lee Keith Sai Kit Leung Jeremy Man Ho Hui Thompson ka Ming Kot Arslan Babar Gauranga Mahalwar Abraham KC Wai Tong Liu Leonardo Roever Gary Tse Jeffrey Shi kai Chan International Health Informatics Study(IHIS)Network Cardiovascular Analytics Group Hong KongChina-UK Collaboration Emergency Medicine Unit Li Ka Shing Fac-ulty of MedicineThe University of Hong KongHong KongChina Aston Medical School Faculty of Health&Life SciencesAston UniversityBirminghamUnited Kingdom Li ka shing Faculty of Medicine The University of Hong KongHong KongChina Department of Anaesthesia and Pain Service Princess Margaret HospitalLai Chi KokKowloonHong KongChina Department of Medicine Cleveland Clinic FoundationClevelandUSA Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease Department of CardiologyTianjin Institute of Cardi-ologySecond Hospital of Tianjin Medical UniversityTianjinChina Department of Clinical Research Federal Uni-versity of UberlândiaUberlândiaBrazil Kent and Medway Medical School CanterburyKentUnited Kingdom 不详

OBJECTIVES To assess the effect of vasopressin,steroid and epinephrine(VSE)combination therapy on return of spontan-eous circulation(ROSC)after in-hospital cardiac arrest(IHCA),and test the conclusiveness of evidence using trial sequential ana-lysis(TSA).METHODS The systematic search included PubMed,EMBASE,Scopus,and Cochrane Central Register of Controlled *** controlled trials(RCTs)that included adult patients with IHCA,with at least one group receiving combined VSE therapy were *** was extracted independently by two *** main outcome of interest was *** out-comes included survival to hospital discharge or survival to 30 and 90 days,with good neurological *** We included a total of three RCTs(n=869).Results showed that VSE combination therapy increased ROSC(risk ra-tio=1.41;95%CI:1.25-1.59)as compared to *** demonstrated that the existing evidence is *** was also validated by the alpha-spending adjusted relative risk(1.32[1.16,1.49],P<0.0001).Other outcomes could not be meta-analysed due to differences in timeframe in the included *** VSE combination therapy administered in cardiopulmonary resuscitation led to improved rates of ***-ture trials of VSE therapy should evaluate survival to hospital discharge,neurological function and long-term survival.

关键词： resuscitation analysis return

Mutations of t-complex testis expressed gene 5 transcripts in the testis of sterile t-haplotype mutant mouse

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Asian Journal of Andrology 2008年第2期10卷 219-226页

作者： Yibing Han Xue-Xiong Song Huai-Liang Feng Che-Kwok cheung Po-Mui Lam Chi-Chiu Wang Christophe John Haines Department of Obstetrics and Gynaecology Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong China Department of Animal Sciences Laiyang Agricultural College Qingdao Shandong 266109 China Center for Human Reproduction North Shore University Hospital NYU School of Medicine Manhasset NY 11030 USA Li ka shing Institute of Health Sciences Faculty of Medicine The Chinese University of Hong Kong Hong Kong China

Aim： To determine the possible roles of the t-complex testis expressed gene 5 （Tctex5） on sperm functions, the fulllength sequence of mRNA was studied and compared in the testis between the normal wild-type and the sterile t-haplotype mutant mice. Methods： We applied rapid amplification of cDNA ends, Northern blot and reverse transcription polymerase chain reaction to analyze the full length of Tctex5 mRNAs isolated from testes of the wild-type and the t-haplotype mice. Reverse transcription polymerase chain reaction was used to semi-quantitatively compare expression of Tctex5 transcripts in the 16 tissues and 9.5 day stage embryos in the wild-type mice. E-translation was applied to estimate the amino acid sequences. Results： One long and one short transcript of Tctex5 mRNA were discovered in mouse testis of wild-type （Tctex5^long-＋ and Tctex5^short-＋） and t-haplotype （Tctex5^long-＋ and Tctex5^short-＋） mice, respectively. Being enhanced only in the testis, Tctex5^long-＋ had 17 point mutations and one 15-bp-deletion in the exon 1 region, comparing with the Tctex5^long-＋, whereas the Tctex5^short-＋ was similar to the Tctex5^short-＋. The short isoforms of Tctex5 mRNAs in the two models encoded exactly the same peptides, but the long isoforms did not. The estimated peptide encoded by Tctex5^long-＋ had significant mutations on putative sites of phosphorylation and PP1 binding. Conclusion： We established that mutations that occur in the Tctex5 long transcript of the t-haplotype mice are important for normal sperm function, whereas the short transcript of Tctex5 might have a conserved function among different tissues. （Asian J Androl 2008 Mar; 10： 219-226）

关键词： t-complex testis expressed gene 5 transcripts testis mice

Rapid quantification of semen hepatitis B virus DNA by real-time polymerase chain reaction

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World Journal of Gastroenterology 2005年第34期11卷 5385-5389页

作者： Wei-Ping Qian Yue-Qiu Tan Ying Chen Ying Peng Zhi Li Guang-Xiu Lu Made C. Liu Hsiang-Fu Kung Ming-Ling He Li-ka shing Luofu Hospital Shenzhen 518033 Guangdong Province China Institute of Reproduction and Stem Cell Engineering Xiangya School of Medicine Central South University Changsha 410008 Hunan Province China The Institute of Molecular Biology The University of Hong Kong Hong Kong Special AdministrativeRegion China Department of Neurology The Second AffiliatedHospital Sun Yat-Sen University Guangzhou 510120 Guangdong Province China The Center for Emerging Infectious Diseases The Chinese University ofHong Kong Hong Kong Special Administrative Region China

AIM: To examine the sensitivity and accuracy of real-time polymerase chain reaction (PCR) for the quantification of hepatitis B virus (HBV) DNA in ***: Hepatitis B viral DNA was isolated from HBV carriers' semen and sera using phenol extraction method and QTAamp DNA blood mini kit (Qiagen, Germany). HBV DNA was detected by conventional PCR and quantified by TaqMan technology-based real-time PCR (quantitative polymerase chain reaction (qPCR)). The detection threshold was 200 copies of HBV DNA for conventional PCR and 10 copies of HBV DNA for real time PCR per ***: Both methods of phenol extraction and QIAamp DNA blood mini kit were suitable for isolating HBV DNA from semen. The value of the detection thresholds was 500 copies of HBV DNA per mL in the semen. The viral loads were 7.5×107 and 1.67×107 copies of HBV DNA per mL in two HBV infected patients' sera, while 2.L4×105 and 3.02×105 copies of HBV DNA per mL in the ***: Real-time PCR is a more sensitive and accurate method to detect and quantify HBV DNA in the semen.

关键词：精液检查乙型肝炎病毒病毒DNA 聚合酶链反应

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

From skeleton to cytoskeleton:osteocalcin transforms vascular fibroblasts to myofibroblasts via angiotensin Ⅱ and Toll-like receptor 4

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中国病理生理杂志 2012年第11期 2002-2002页

作者： HUANG Yu(Institute of Vascular Medicine and Li ka shing Institute of Health Sciences,Chinese University of Hong Kong,Hong Kong SAR,China)

In contrast to the traditional belief of an"inside-out"progression of vascular dysfunction,recent evidence suggests an"outsidein"hypothesis,proposing that inflammation can originate from the adventitia and develop towards the intima,resulting in vascularwall *** remodeling such as neointima formation is signified by the acquisition of migratory and proliferative ability of

关键词： Toll From skeleton to cytoskeleton and Toll-like receptor 4

P21-activated kinase 1 (PAK1)-mediated cytoskeleton rearrangement promotes SARS-CoV-2 entry and ACE2 autophagic degradation

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5353-5367页

作者： Ming Liu Bingtai Lu Yue Li Shuofeng Yuan Zhen Zhuang Guangyu Li Dong Wang Liuheyi Ma Jianheng Zhu Jinglu Zhao Chris Chung-Sing Chan Vincent Kwok-Man Poon Kenn ka-Heng Chik Zhiyao Zhao Huifang Xian Jingxian Zhao Jincun Zhao Jasper Fuk-Woo Chan Yuxia Zhang Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical CentreState Key Laboratory of Respiratory DiseasesGuangzhou Medical University510623 GuangzhouGuangdongChina Medical Research Institute Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangdongChina State Key Laboratory of Emerging Infectious Diseases Carol Yu Centre for InfectionDepartment of MicrobiologySchool of Clinical MedicineLi Ka Shing Faculty of MedineThe University of Hong KongPokfulamHong KongChina Department of Clinical Microbiology and Infection Control The University of Hong Kong Shenzhen HospitalShenzhenGuangdongChina Centre for Virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong KongChina State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affliated Hospital of Guangzhou Medical UniversityGuangzhouChina The Third Afliated Hospital of Zhengzhou University 450052 ZhengzhouChina Guangzhou Laboratory GuangzhouGuangdong ProvinceChina Chongqing International Institute for Immunology ChongqingChina

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of coronavirus disease 2019(COVID-19),has had a significant impact on healthcare systems and economies *** continuous emergence of new viral strains presents a major challenge in the development of effective antiviral *** that possess broad-spectrum antiviral activities are desirable to control SARS-CoV-2 ***2,an angiotensin-containing enzyme that prevents the overactivation of the renin angiotensin system,is the receptor for ***2 interacts with the spike protein and facilitates viral attachment and entry into host ***,SARS-CoV-2 infection also promotes ACE2 *** restoring ACE2 surface expression has an impact on SARS-CoV-2 infection is yet to be ***,we show that the ACE2-spike complex is endocytosed and degraded via autophagy in a manner that depends on clathrin-mediated endocytosis and PAK1-mediated cytoskeleton *** contrast,free cellular spike protein is selectively cleaved into S1 and s2 subunits in a lysosomal-dependent ***,we show that the pan-PAK inhibitor FRAX-486 restores ACE2 surface expression and suppresses infection by different SARS-CoV-2 ***-486-treated Syrian hamsters exhibit significantly decreased lung viral load and alleviated pulmonary inflammation compared with untreated *** summary,our findings have identified novel pathways regulating viral entry,as well as therapeutic targets and candidate compounds for controlling the emerging strains of SARS-CoV-2 infection.

关键词： ACE2 inflammation rearrangement