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运动皮质的塑性:多巴胺的神经分布(英文)

中国药理学与毒理学杂志 2016年第10期30卷 1001-1002页

作者： YUNG wing-ho School of Biomedical Sciences Faculty of Medicine & Gerald Choa Neuroscience CenterThe Chinese University of Hong Kong

The motor cortex plays a key role in motor control as its output directly generates ***,it is known that the motor cortex also exhibits a high degree of plasticity that may be important in both health and *** I provide evidence to support that dopaminergic innervation arising from the midbrain plays critical roles in the process of acquiring novel motor skills as well as recovery of motor functions after ischemic *** on extracel ular multi-unit recordings from conscious freely moving rats,we investigated the dynamics of neurons in the output layer 5b(L5b)of the primary motor cortex during the training of a forelimb reaching for food *** found a subpopulation of task-recruited layer 5b neurons that not only became more movement-encoding during motor learning,but their activities were also more temporally aligned to motor *** phenomena were accompanied by the emergence of reproducibleneurodynamics of the L5b neuronal ensemble and traininginduced long-term synaptic plasticity of inputs to these neurons,but were highly disrupted by local denervation of dopaminergic inputs originating from the ventral tegmental *** another series of experiments based on rodent models of focal ischemic stroke,administration of L-DOPA,the precursor of dopamine,significantly promoted motor function *** and biochemical examination of the perilesioned area provided evidence that neuroplasticity markers,dendritic arborisation and synaptic plasticity were increased by the *** examination of neuronal activity through in vivo recording revealed that motor cortical regions adjacent to the infarct had restored capability for synaptic ***,pharmacological blockade of either D1 or D2 receptors at the perilesioned region abolished the beneficial ***,our findings highlight the importance of the plasticity of the motor cortex in health and disease that are mediated by the mesocortical dopaminer

关键词： plasticity cortex synaptic 神经分布 neuronal conscious 运动皮质 administration aligned dopamine

LRRK2, GBA and their interaction in the regulation of autophagy: implications on therapeutics in Parkinson’s disease

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Translational Neurodegeneration 2022年第1期11卷 869-882页

作者： Shirley Yin-Yu Pang Rachel Cheuk Nam Lo Philip wing-Lok ho Hui-Fang Liu Eunice Eun Seo Chang Chi-Ting Leung Yasine Malki Zoe Yuen-Kiu Choi wing Yan Wong Michelle Hiu-Wai Kung David Boyer Ramsden Shu-Leong ho Division of Neurology Department of MedicineQueen Mary HospitalUniversity of Hong KongHong KongChina School of Biomedical Sciences Li Ka Shing Faculty of MedicineUniversity of Hong KongHong KongChina Institute of Metabolism and Systems Research University of BirminghamBirminghamUK.

Mutations in leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA) represent two most common genetic causes of Parkinson’s disease (PD). Both genes are important in the autophagic-lysosomal pathway (ALP), defects of which are associated with α-synuclein (α-syn) accumulation. LRRK2 regulates macroautophagy via activation of the mitogen activated protein kinase/extracellular signal regulated protein kinase (MAPK/ERK) kinase (MEK) and the calcium-dependent adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathways. Phosphorylation of Rab GTPases by LRRK2 regulates lysosomal homeostasis and endosomal trafficking. Mutant LRRK2 impairs chaperone-mediated autophagy, resulting in α-syn binding and oligomerization on lysosomal membranes. Mutations in GBA reduce glucocerebrosidase (GCase) activity, leading to glucosylceramide accumulation, α-syn aggregation and broad autophagic abnormalities. LRRK2 and GBA influence each other: GCase activity is reduced in LRRK2 mutant cells, and LRRK2 kinase inhibition can alter GCase activity in GBA mutant cells. Clinically, LRRK2 G2019S mutation seems to modify the effects of GBA mutation, resulting in milder symptoms than those resulting from GBA mutation alone. however, dual mutation carriers have an increased risk of PD and earlier age of onset compared with single mutation carriers, suggesting an additive deleterious effect on the initiation of PD pathogenic processes. Crosstalk between LRRK2 and GBA in PD exists, but its exact mechanism is unclear. Drugs that inhibit LRRK2 kinase or activate GCase are showing efficacy in pre-clinical models. Since LRRK2 kinase and GCase activities are also altered in idiopathic PD (iPD), it remains to be seen if these drugs will be useful in disease modification of iPD.

关键词： Parkinson’s disease Interaction LRRK2 GBA GCase Mutation Autophagy α-Synuclein

Impact of small-for-size liver grafts on medium-term and long-term graft survival in living donor liver transplantation: A meta-analysis

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World Journal of Gastroenterology 2019年第36期25卷 5559-5568页

作者： Ka wing Ma Kelly Hiu Ching Wong Albert Chi Yan Chan Tan To Cheung wing Chiu Dai James Yan Yue Fung Wong hoi She Chung Mau Lo Kenneth Siu ho Chok Department of Surgery Queen Mary Hospital Hong Kong China Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong China Department of Surgery The University of Hong Kong Hong Kong China Department of Medicine Queen Mary Hospital Hong Kong China

BACKGROUND Small-for-size grafts (SFSGs) in living donor liver transplantation (LDLT) could optimize donor postoperative outcomes and also expand the potential donor pool. Evidence on whether SFSGs would affect medium-term and long-term recipient graft survival is lacking. AIM To evaluate the impact of small-for-size liver grafts on medium-term and longterm graft survival in adult to adult LDLT. METhoDS A systematic review and meta-analysis were performed by searching eligible studies published before January 24, 2019 on PubMed, EMBASE, and Web of Science databases. The primary outcomes were 3-year and 5-year graft survival. Incidence of small-for-size syndrome and short term mortality were also extracted. RESULTS This meta-analysis is reported according to the guidelines of the PRISMA 2009 Statement. Seven retrospective observational studies with a total of 1821 LDLT recipients were included in the meta-analysis. SFSG is associated with significantly poorer medium-term graft survival. The pooled odds ratio for 3-year graft survival was 1.58 [95% confidence interval 1.10-2.29, P = 0.014]. On the other hand, pooled results of the studies showed that SFSG had no significant discriminatory effect on 5-year graft survival with an odds ratio of 1.31 (95% confidence interval 0.87-1.97, P = 0.199). Furthermore, incidence of small-for-size syndrome detected in recipients of SFSG ranged from 0-11.4% in the included studies. CONCLUSION SFSG is associated with inferior medium-term but not long-term graft survival. Comparable long-term graft survival based on liver graft size shows that smaller grafts could be accepted for LDLT with appropriate flow modulatory measures. Close follow-up for graft function is warranted within 3 years after liver transplantation.

关键词： Living donor liver transplantation Small-for-size grafts Small-for-size syndrome Graft survival

The interplay of aging,genetics and environmental factors in the pathogenesis of Parkinson’s disease

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Translational Neurodegeneration 2019年第1期8卷 279-289页

作者： Shirley Yin-Yu Pang Philip wing-Lok ho Hui-Fang Liu Chi-Ting Leung Lingfei Li Eunice Eun Seo Chang David Boyer Ramsden Shu-Leong ho Division of Neurology Department of MedicineQueen Mary HospitalUniversity of Hong KongHong KongPeople’s Republic of China Institute of Metabolism and Systems Research University of BirminghamBirminghamUK

Background:Parkinson’s disease(PD)is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta and intracellular inclusions called Lewy bodies(LB).During the course of disease,misfoldedα-synuclein,the major constituent of LB,spreads to different regions of the brain in a prion-like fashion,giving rise to successive non-motor and motor *** is likely multifactorial,and involves interplay among aging,genetic susceptibility and environmental *** body:The prevalence of PD rises exponentially with age,and aging is associated with impairment of cellular pathways which increases susceptibility of dopaminergic neurons to cell ***,the majority of those over the age of 80 do not have PD,thus other factors in addition to aging are needed to cause *** of neurotoxins which can result in parkinsonism led to efforts in identifying environmental factors which may influence PD ***,the causality of most environmental factors is not conclusively established,and alternative explanations such as reverse causality and recall bias cannot be *** lack of geographic clusters and conjugal cases also go against environmental toxins as a major cause of *** mutations as well as common variants in genes such as SNCA,LRRK2 and GBA are associated with risk of PD,but Mendelian causes collectively only account for 5%of PD and common polymorphisms are associated with small increase in PD *** of PD has been estimated to be around 30%.Thus,aging,genetics and environmental factors each alone is rarely sufficient to cause PD for most ***:PD is a multifactorial disorder involving interplay of aging,genetics and environmental *** has implications on the development of appropriate animal models of PD which take all these factors into *** converging pathways likely include mitochondrial dysfunction,impaired autophagy,oxidative stress and neuroinflammation,which are

关键词： Parkinson’s disease Genetics Aging Environmental toxins

Integrative Multi-omics Analyses of Barley Rootzones under Salinity Stress Reveal Two Distinctive Salt Tolerance Mechanisms

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Plant Communications 2020年第3期1卷 107-123页

作者： William wing ho ho Camilla B.Hill Monika S.Doblin Megan C.Shelden Allison van de Meene Thusitha Rupasinghe Antony Bacic Ute Roessner School of BioSciences The University of MelbourneParkvilleVIC 3010Australia School of Veterinary and Life Sciences Murdoch UniversityMurdochWA 6150Australia La Trobe Institute for Agriculture&Food Department of AnimalPlant and Soil ScienceLa Trobe UniversityBundooraVIC 3086Australia ARC Centre of Excellence in Plant Energy Biology School of AgricultureFood and WineUniversity of AdelaideGlen OsmondSA 5064Australia Metabolomics Australia The University of MelbourneParkvilleVIC 3010Australia

The mechanisms underlying rootzone-localized responses to salinity during early stages of barley development remain *** this study,we performed the analyses of multi-root-omes(transcriptomes,metabolomes,and lipidomes)of a domesticated barley cultivar(Clipper)and a landrace(Sahara)that maintain and restrict seedling root growth under salt stress,*** generalized linear models were designed to determine differentially expressed genes(DEGs)and abundant metabolites(DAMs)specific to salt treatments,genotypes,or rootzones(meristematic Z1,elongation Z2,and maturation Z3).Based on pathway over-representation of the DEGs and DAMs,phenylpropanoid biosynthesis is the most statistically enriched biological pathway among all salinity responses *** with histological evidence,an intense salt-induced lignin impregnation was found only at stelic cell wall of Clipper Z2,compared with a unique elevation of suberin deposition across Sahara *** suggests two differential salt-induced modulations of apoplastic flow between the *** on the global correlation network of the DEGs and DAMs,callose deposition that potentially adjusted symplastic flow in roots was almost independent of salinity in rootzones of Clipper,and was markedly decreased in *** together,we propose two distinctive salt tolerance mechanisms in Clipper(growth-sustaining)and Sahara(salt-shielding),providing important clues for improving crop plasticity to cope with deteriorating global soil salinization.

关键词： barley root transcriptomics metabolomics lipidomics omics integration salinity stress

Parentage testing anomalies in hong Kong SAR of China

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Chinese Medical Journal 2003年第5期116卷 708-711页

作者： Richard A Collins wing See Wu Lok-Ting lau Albert CH Yu hong Kong DNA Chips Limited 1805-6 18/F Lu Plaza 2 Wing Yip Street Kowloon Hong Kong SAR ChinaHong Kong DNA Chips Limited 1805-6 18/F Lu Plaza 2 Wing Yip Street Kowloon Hong Kong SAR ChinaHong Kong DNA Chips Limited 1805-6 18/F Lu Plaza 2 Wing Yip Street Kowloon Hong Kong SAR ChinaHong Kong DNA Chips Limited 1805-6 18/F Lu Plaza 2 Wing Yip Street Kowloon Hong Kong SAR China

Objective To determine if there are any differences in the number of exclusions from paternity of men using an anonymous parentage testing service compared with that of men using an in-person parentage testing service provided by the same company in hong Kong SAR of China. Methods Comparable numbers of consecutive anonymous and in-person parentage tests conducted by the same company were analyzed. Results Men using an anonymous parentage testing service were excluded from paternity at a significantly greater rate (Phorities should acknowledge and address.

关键词： parentage testing short tandem repeat combined probability index polymerase chain reaction

Hepatic venous outflow obstruction after piggyback liver transplantation by an unusual mechanism:Report of a case

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World Journal of Gastroenterology 2006年第33期12卷 5416-5418页

作者： Simon Siu-Man Ng Simon Chun-ho Yu Janet Fung-Yee Lee Paul Bo-San Lai Wan-Yee lau Departments of Surgery and Diagnostic Radiology & Organ Imaging Chinese University of Hong Kong Prince of Wales Hospital Shatin Hong Kong China

Hepatic venous outflow obstruction after piggyback liver transplantation is a very rare complication. An unusual mechanism aggravating it is reported. A 33-year-old man with end-stage hepatitis B liver cirrhosis underwent a piggyback orthotopic liver transplantation using a full-size cadaveric graft. Two months after transplantation, he developed gross ascites refractory to maximal diuretic therapy. Doppler ultrasound showed patent portal and hepatic veins. Serial computed tomography scans revealed a hypoperfused right posterior segment of the liver which subsequently underwent atrophy. Hepatic venography demonstrated a high-grade stenosis with an element of torsion of venous drainage at the anastomosis. The stenosis was successfully treated with repeated percutaneous balloon angioplasty. The patient remained asymptomatic six months afterwards with complete resolution of ascites and peripheral edema. We postulate that liver allograft segmental hypoperfusion and atrophy may aggravate or result in a hepatic venous outflow problem by the mechanism of torsion effect. Percutaneous balloon angioplasty is a safe and effective treatment modality for anastomotic stenosis.

关键词： Hepatic venous outflow obstruction Piggyback Liver transplantation Percutaneous balloon angioplasty

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

Liver transplantation:would it be the best and last chance of cure for hepatocellular carcinoma with major venous invasion?

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Hepatobiliary Surgery and Nutrition 2021年第3期10卷 308-314页

作者： Ka wing Ma Albert Chi Yan Chan Kenneth Siu ho Chok Wong hoi She Tan To Cheung wing Chiu Dai James Yan Yue Fung Chung Mau Lo Department of Surgery The University of Hong KongHong KongChina Department of Medicine The University of Hong KongHong KongChina

Background:Hepatocellular carcinoma(HCC)with portal vein tumour thrombus(PVTT)signifies advanced disease,whether LT confers any survival superiority over resection remains ***:A propensity score matched(PSM)analysis of liver transplantation(LT)and liver resection(LR)for HCC with PVTT was ***:A consecutive series of 88 patients who received either LT(10 DDLTs and 3 LDLTs)or LR(n=75)respectively were *** PSM,the LT group has a higher MELD score(17.3 vs.7.8,Phould be considered.

关键词： Liver transplantation(LT) portal vein tumour thrombus liver resection(LR)Submitted Aug 10,2019.Accepted for publication Oct 15,2019.