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Metabolic memory:mechanisms and diseases

Signal Transduction and Targeted Therapy 2024年第3期9卷 1086-1114页

作者： Hao Dong Yuezhang Sun Lulingxiao Nie Aimin Cui Pengfei Zhao wai Keung leung Qi Wang State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengduChina Department of Prosthodontics West China Hospital of StomatologySichuan UniversityChengduChina Periodontology and Implant Dentistry Division Faculty of DentistryThe University of Hong KongHong KongChina

Metabolic diseases and their complications impose health and economic burdens *** from past experimental studies and clinical trials suggests our body may have the ability to remember the past metabolic environment,such as hyperglycemia or hyperlipidemia,thus leading to chronic inflammatory disorders and other diseases even after the elimination of these metabolic *** long-term effects of that aberrant metabolism on the body have been summarized as metabolic memory and are found to assume a crucial role in states of health and *** molecular mechanisms collectively participate in metabolic memory management,resulting in different cellular alterations as well as tissue and organ dysfunctions,culminating in disease progression and even affecting *** elucidation and expansion of the concept of metabolic memory provides more comprehensive insight into pathogenic mechanisms underlying metabolic diseases and complications and promises to be a new target in disease detection and ***,we retrace the history of relevant research on metabolic memory and summarize its salient *** provide a detailed discussion of the mechanisms by which metabolic memory may be involved in disease development at molecular,cellular,and organ levels,with emphasis on the impact of epigenetic ***,we present some of the pivotal findings arguing in favor of targeting metabolic memory to develop therapeutic strategies for metabolic diseases and provide the latest reflections on the consequences of metabolic memory as well as their implications for human health and diseases.

关键词： diseases metabolism alterations

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Cellular zinc metabolism and zinc signaling:from biological functions to diseases and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第2期9卷 401-441页

作者： Bonan Chen Peiyao Yu wai Nok Chan Fuda Xie Yigan Zhang Li Liang Kam Tong leung Kwok wai Lo Jun Yu Gary M.K.Tse Wei Kang Ka Fai To Department of Anatomical and Cellular Pathology State Key Laboratory of Translational OncologyPrince of Wales HospitalThe Chinese University of Hong KongHong KongChina State Key Laboratory of Digestive Disease Institute of Digestive DiseaseThe Chinese University of Hong KongHong KongChina CUHK-Shenzhen Research Institute The Chinese University of Hong KongShenzhenChina Department of Pathology Nanfang Hospital and Basic Medical CollegeSouthern Medical UniversityGuangdong Province Key Laboratory of Molecular Tumor PathologyGuangzhouChina Institute of Biomedical Research Taihe HospitalHubei University of MedicineShiyanChina Department of Pediatrics The Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina

Zinc metabolism at the cellular level is critical for many biological processes in the body.A key observation is the disruption of cellular homeostasis,often coinciding with disease *** an essential factor in maintaining cellular equilibrium,cellular zinc has been increasingly spotlighted in the context of disease *** research suggests zinc’s involvement in promoting malignancy and invasion in cancer cells,despite its low tissue *** has led to a growing body of literature investigating zinc’s cellular metabolism,particularly the functions of zinc transporters and storage mechanisms during cancer *** transportation is under the control of two major transporter families:SLC30(ZnT)for the excretion of zinc and SLC39(ZIP)for the zinc ***,the storage of this essential element is predominantly mediated by metallothioneins(MTs).This review consolidates knowledge on the critical functions of cellular zinc signaling and underscores potential molecular pathways linking zinc metabolism to disease progression,with a special focus on *** also compile a summary of clinical trials involving zinc *** the main localization of zinc transporters at the cell membrane,the potential for targeted therapies,including small molecules and monoclonal antibodies,offers promising avenues for future exploration.

关键词： metabolism invasion involvement

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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

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Prostate health index can stratify patients with Prostate Imaging Reporting and Data System score 3 lesions on magnetic resonance imaging to reduce prostate biopsies

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Asian Journal of Andrology 2024年第1期26卷 20-24页

作者： John Shung-Lai leung wai-Kit Ma Brian Sze-Ho Ho Stacia Tsun-Tsun Chun Rong Na Yongle Zhan Chi-Yuen Ng Chi-Ho Ip Ada Tsui-Lin Ng Yiu-Chung Lam Division of Urology Department of SurgeryQueen Mary HospitalUniversity of Hong KongHong KongChina Division of Urology Department of SurgeryPrincess Margaret HospitalHongKongChina

We aim to evaluate prostate health index as an additional risk-stratification tool in patients with Prostate Imaging Reporting and Data System score 3 lesions on multiparametric magnetic resonance *** with biochemical or clinical suspicion of having prostate cancer who underwent multiparametric magnetic resonance imaging in two tertiary centers(Queen Mary Hospital and Princess Margaret Hospital,hong Kong,China)between January 2017 and June 2022 were ***-magnetic resonance imaging fusion biopsies were performed after prostate health index *** who only had Prostate Imaging Reporting and Data System score 3 lesions were further stratified into four prostate health index risk groups and the cancer detection rates were *** of the 747 patients,47.3%had Prostate Imaging Reporting and Data System score 3 lesions *** detection rate of clinically significant prostate cancer in this group was 15.0%.The cancer detection rates of clinically significant prostate cancer had statistically significant differences:5.3%in prostate health index<25.0,7.4%in prostate health index 25.0-34.9,17.9%in prostate health index 35.0-54.9,and 52.6%in prostate health index≥55.0(P<0.01).Among the patients,26.9%could have avoided a biopsy with a prostate health index<25.0,at the expense of a 5.3%risk of missing clinically significant prostate *** health index could be used as an additional risk stratification tool for patients with Prostate Imaging Reporting and Data System score 3 *** could be avoided in patients with low prostate health index,with a small risk of missing clinically significant prostate cancer.

关键词： biopsy fusion biopsy magnetic resonance imaging prostate cancer prostate health index

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Within-Cluster Variability Exponent for Identifying Coherent Structures in Dynamical Systems

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Communications in Computational Physics 2023年第3期33卷 824-848页

作者： wai Ming Chau Shingyu leung Department of Mathematics The Hong Kong University of Science and TechnologyClear Water BayHong Kong

We propose a clustering-based approach for identifying coherent flow structuresin continuous dynamical systems. We first treat a particle trajectory over a finitetime interval as a high-dimensional data point and then cluster these data from differentinitial locations into groups. The method then uses the normalized standarddeviation or mean absolute deviation to quantify the deformation. Unlike the usualfinite-time Lyapunov exponent (FTLE), the proposed algorithm considers the completetraveling history of the particles. We also suggest two extensions of the method. To improvethe computational efficiency, we develop an adaptive approach that constructsdifferent subsamples of the whole particle trajectory based on a finite time interval. Tostart the computation in parallel to the flow trajectory data collection, we also developan on-the-fly approach to improve the solution as we continue to provide more measurementsfor the algorithm. The method can efficiently compute the WCVE over adifferent time interval by modifying the available data points.

关键词： Dynamical system visualization finite time Lyapunov exponent numerical methods for differential equations k-means clustering

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Development of a dual targeting scaffold of SET7/MLL inhibitor for castration-resistant prostate cancer treatment

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Genes & Diseases 2023年第6期10卷 2260-2262页

作者： Guodong Li Qi Huang Vincent Kam wai Wong Wanhe Wang Chung-Hang leung Institute of Chinese Medical Sciences and State Key Laboratory of Quality Research in Chinese Medicine University of MacaoMacao SAR 999078China Dr.Neher's Biophysics Laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao University of Science and TechnologyMacao SAR 999078China Institute of Medical Research Northwestern Polytechnical UniversityXi'anShaanxi 710072China Macao Centre for Research and Development in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SAR 999078China Department of Biomedical Sciences Faculty of Health SciencesUniversity of MacaoMacao SAR 999078China Zhuhai UM Science and Technology Research Institute ZhuhaiGuangdong 519000China

Histone methyltransferase enzyme SET7 and mixed-lineage leukemia protein(MLL)complex are crucial co-activators of androgen receptor(AR)and have recently emerged as potential therapeutic targets for advanced castration-resistant prostate cancer(CRPC).In this study,we described the identification of a rhodium-based hybrid complex(SM_1)as a potent blocker of AR activity via simultaneously inhibiting SET7 and MLL complex activity,which makes it a potential lead scaffold for CPRC drug development.

关键词： cancer inhibiting treatment

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伴有前后循环颅内动脉粥样硬化的缺血性卒中患者1年死亡和卒中复发的差异

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中华医学杂志 2018年第7期98卷 502-507页

作者：濮月华邹昕颖王伊龙潘岳松向祥龙苏霭欣梁慧康赵性泉王春雪黄家星王拥军刘丽萍首都医科大学附属北京天坛医院神经内科北京100050 首都医科大学附属北京天坛医院神经精神医学与临床心理科北京100050 香港中文大学内科与药物治疗学系

目的探讨伴有前循环和后循环颅内动脉粥样硬化狭窄或闭塞的缺血性卒中患者1年的死亡和卒中复发风险是否存在差异。方法在中国颅内动脉粥样硬化研究（2007年10月至2009年6月）的数据库中，剔除颅外动脉狭窄或闭塞的病例、头核磁弥散加权... 详细信息

目的探讨伴有前循环和后循环颅内动脉粥样硬化狭窄或闭塞的缺血性卒中患者1年的死亡和卒中复发风险是否存在差异。方法在中国颅内动脉粥样硬化研究（2007年10月至2009年6月）的数据库中，剔除颅外动脉狭窄或闭塞的病例、头核磁弥散加权成像未见急性梗死灶的病例和颅内前后循环联合病变的病例，将患者分为无明显颅内动脉病变组（n=964）、前循环动脉病变组（n=440）、后循环动脉病变组（n=233）。预后评估指标为发病后1年内任何原因所致的死亡、卒中复发。结果在纳入分析的1637例患者中，1年随访结果显示，任何原因所致死亡30例，卒中复发58例。与无明显颅内动脉病变组相比，前循环动脉病变组和后循环动脉病变组校正后的死亡风险比（95％可信区间）分别为1．349（0．311～5．851）、4．542（1．227～16．813）；卒中复发分别为1．663（0．620～4．460）、2．464（0．935—6．493）。结论伴有后循环颅内动脉粥样硬化的缺血性卒中患者1年死亡风险高于前循环者，而前后循环动脉病变卒中复发风险差异有待进一步评估。

关键词：缺血性卒中颅内动脉粥样硬化预后卒中复发

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X-reality for phantom limb management for amputees:A systematic review and meta-analysis

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再生工程(英文) 2023年第2期4卷 134-151页

作者： James Chung-wai Cheung Daphne Sze Ki Cheung Ming Ni Kam-wai Chen Ye-Jiao Mao Lin Feng Wing-Kai Lam Duo wai-Chi Wong Aaron Kam-Lun leung Department of Biomedical Engineering Faculty of EngineeringThe Hong Kong Polytechnic UniversityHong KongChina School of Nursing The Hong Kong Polytechnic UniversityHong KongChina Department of Orthopaedics Ruijin HospitalShanghai Jiao Tong UniversityShanghaiChina Department of Prosthetics and Orthotics Queen Mary HospitalHong KongChina Sports Information and External Affairs Centre Hong Kong Sports InstituteHong KongChina Research Institute for Sports Science and Technology The Hong Kong Polytechnic UniversityHong KongChina Department of Rehabilitation Science The Hong Kong Polytechnic UniversityHong KongChina

Phantom limb is a disabling neuropsychiatric condition among amputees resulting in pain and disturbance that impact their functions,quality of life,and *** pharmacological approaches appeared to be ineffec-tive,the emergence and integration of X-reality,including virtual reality,augmented reality,and mixed reality,might elevate the effectiveness of mirror therapy in managing phantom *** objective of this study is to review X-reality for managing phantom pain.A systematic search was conducted on PubMed,Scopus,Web of Science,PsycINFO,Embase,and ***(n=16)studies containing 66 lower-limb and 53 upper-limb amputees were included for the review over the thematic framework of amputee characteristics and intervention designs,while thirteen(n=13)studies were further proceeded for the *** found eleven studies on virtual reality(n=11),four studies on marker-based augmented reality(n=4)and one study on mixed reality(n=1)with a total of 40 game/task themes involving,motor skills,motor control,and ***,all these interventions adopted the movement representation strategies with different ***,the X-reality interventions reduced the pain level of the amputees(mean difference:-2.30,95%CI,-3.38 to-1.22),especially the virtual reality subgroup(mean difference:-2.83,95%CI,-4.43 to-1.22).However,there were substantial heterogeneity and partially explained by the subgroup analysis on publication *** strength of evidence was limited by case reports and case series in this review.

关键词： Extended reality Limb telescoping Phantom pain Phantom sensation

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Is artificial intelligence the final answer to missed polyps in colonoscopy?

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World Journal of Gastroenterology 2020年第35期26卷 5248-5255页

作者： thomas K L Lui wai K leung Department of Medicine Queen Mary HospitalUniversity of Hong KongHong KongChina

Lesions missed by colonoscopy are one of the main reasons for post-colonoscopy colorectal cancer,which is usually associated with a worse *** the adenoma miss rate could be as high as 26%,it has been noted that endoscopists with higher adenoma detection rates are usually associated with lower adenoma miss *** intelligence(AI),particularly the deep learning model,is a promising innovation in *** studies have shown that AI is not only accurate in colorectal polyp detection but can also reduce the miss ***,the application of AI in real-time detection has been hindered by heterogeneity of the AI models and study design as well as a lack of long-term ***,we discussed the principle of various AI models and systematically reviewed the current data on the use of AI on colorectal polyp detection and miss *** limitations and future prospects of AI on colorectal polyp detection are also discussed.

关键词： Artificial intelligence Adenoma Colonoscopy Colorectal cancer Polyps

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ABC/2 formula for"bedside"postoperative pneumocephalus volume measurement

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Chinese Neurosurgical Journal 2022年第4期8卷 284-291页

作者： David Yuen Chung Chan Eric Yuk hong Cheung Ka Ho Hui Cecelia Mei Sze leung Stephanie Chi Ping Ng wai Kit Mak George Kwok Chu Wong Tat Ming Danny Chan wai Sang Poon Division of Neurosurgery Department of SurgeryFaculty of MedicinePrince of Wales HospitalThe Chinese University of Hong KongHong KongSARChina

Background:Postoperative pneumocephalus is associated with a higher risk of recurrence of chronic subdural hematoma(cSDH).However,there is no verified simple way to measure the pneumocephalus volume at the bedside for daily clinical *** ABC/2 method was shown to be a simple and reliable technique to estimate volumes of intracranial lesions,such as intracranial *** study aims to evaluate the accuracy of the ABC/2 formula in estimating volumes of pneumocephalus,as compared to the gold standard with computer-assisted volumetric ***:A total of 141 postoperative computed tomographic(CT)brain scans of cSDH patients with burr-hole drainage were *** volume was measured independently by both the ABC/2 formula and the computer-assisted volumetric *** the computer-assisted measurement,the volume of the air was semiautomatically segmented and calculated by computer *** regression was used to determine the correlation between the ABC/2 method and computer-assisted ***:The postoperative pneumocephalus volume after bilateral burr-hole drainage was significantly larger than that of unilateral burr-hole drainage(29.34 ml versus 12.21 ml,p<0.001).The estimated volumes by the formula ABC/2 significantly correlated to the volumes as measured by the computer-assisted volumetric technique,with r=0.992(p<0.001).The Pearson correlation coefficient is very close to 1,which signifies a very strong positive correlation,and it is statistically ***:An excellent correlation is observed between the ABC/2 method and the computer-assisted *** study verified that the ABC/2 method is an accurate and simple"bedside"technique to estimate pneumocephalus volume.

关键词： ABC/2 Chronic subdural haematoma Burr-hole Pneumocephalus

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