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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

铜绿假单胞菌对肺血管内皮细胞功能的影响及其机制

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中国医学科学院学报 2024年第1期46卷 1-10页

作者：张雷王俊轶何翔吴敏李国平黄锦伟澳门科技大学中药质量研究国家重点实验室中国澳门999078 成都市第三人民医院呼吸健康研究所过敏与精准医学实验室成都610000 北达科他大学医学与健康科学院生物医学科学系美国北达科他州大福克斯58203 中国科学院大学温州研究院浙江温州325000

目的探究铜绿假单胞菌(PA)感染对肺血管内皮细胞功能的影响,并探讨其加重小鼠肺部炎症反应的可能机制。方法PAO1菌株感染人肺微血管内皮细胞HULEC-5a 2 h后,采用逆转录实时荧光定量PCR(RT-qPCR)检测自噬相关基因5(ATG5)、6-磷酸果糖-2-... 详细信息

目的探究铜绿假单胞菌(PA)感染对肺血管内皮细胞功能的影响,并探讨其加重小鼠肺部炎症反应的可能机制。方法PAO1菌株感染人肺微血管内皮细胞HULEC-5a 2 h后,采用逆转录实时荧光定量PCR(RT-qPCR)检测自噬相关基因5(ATG5)、6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶3(PFKFB3)和钙黏蛋白5(CDH5)的mRNA表达,免疫荧光检测ATG5、PFKFB3和血管内皮钙黏蛋白(VE-cadherin)的蛋白表达。采用小干扰RNA(siRNA)分别敲减ATG5、PFKFB3后,RT-qPCR检测ATG5、PFKFB3和CDH5的mRNA表达,免疫荧光检测PFKFB3和VE-cadherin的蛋白表达,并采用乳酸测定试剂盒检测细胞内乳酸的水平。采用PAO1菌株感染小鼠后,肺组织切片病理染色观察小鼠肺部炎症,激光共聚焦显微镜观察并分析荧光标记的内皮细胞PFKFB3和VE-cadherin的表达量。结果与对照组比较,PAO1感染HULEC-5a细胞后,PFKFB3 mRNA和蛋白表达均增加(P均<0.05),CDH5 mRNA表达减少(P=0.023),VE-cadherin蛋白表达减少(P<0.001),且连续性被破坏,乳酸含量升高(P=0.017)。与PAO1感染HULEC-5a细胞比较,PAO1感染敲减PFKFB3的HULEC-5a细胞后,CDH5 mRNA表达增加(P=0.043),VE-cadherin荧光连续性得到恢复,乳酸含量降低(P=0.047);PAO1感染敲减ATG5的HULEC-5a细胞后,PFKFB3 mRNA(P=0.013)和蛋白表达(P=0.003)均增加,CDH5 mRNA(P=0.020)和VE-cadherin蛋白表达(P=0.001)均减少,乳酸含量升高(P=0.015)。PAO1感染小鼠后,病理HE染色结果显示,肺泡内明显的红细胞渗漏,炎症细胞浸润,肺泡间隔增宽和部分血管内皮细胞脱落。免疫荧光染色结果显示,与正常小鼠比较,PAO1感染小鼠内皮细胞PFKFB3表达增加,VE-cadherin荧光减弱,且不连续。结论PA可能通过AGT5调控PFKFB3通路,破坏肺血管内皮细胞功能,进而加重小鼠肺部炎症反应。

关键词：铜绿假单胞菌肺血管内皮细胞 6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶3 自噬相关基因5 感染

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

Differing coping mechanisms, stress level and anorectal physiology in patients with functional constipation

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World Journal of Gastroenterology 2005年第34期11卷 5362-5366页

作者： Annie OO Chan Cecilia Cheng wai Mo Hui Wayne HC Hu Nina YH Wong KF lam wai Man Wong kam Chuen Lai Shiu Kum lam Benjamin CY Wong Department of Medicine the University of Hong Kong Hong Kong China Division of Social Science the Hong Kong University of Science and Technology Hong Kong China Department of Medicine the University of Hong Kong Hong Kong China Department of Statistics the University of Hong Kong Hong Kong China

AIM: To investigate coping mechanisms, constipation symptoms and anorectal physiology in 80 constipated subjects and 18 ***: Constipation was diagnosed by Rome Ⅱ *** ability and anxiety/depression were assessed by validated questionnaires. Transit time and balloon distension test were ***: 34.5% patients were classified as slow transit type of constipation. The total colonic transit time (56 h vs 10 h, P＜0.0001) and rectal sensation including urge sensation (79 mL vs 63 mL, P = 0.019) and maximum tolerable volume (110 mL vs95 mL, P = 0.03) differed in patients and controls. Constipated subjects had significantly higher anxiety and depression scores and lower SF-36 scores in all categories. They also demonstrated higher scores of'monitoring' coping strategy (14+6 vs9+3, P = 0.001),which correlated with the rectal distension sensation (P = 0.005), urge sensation (P=0.002), and maximum tolerable volume (P = 0.035). The less use of blunting strategy predicted slow transit constipation in both univariate (P = 0.01) and multivariate analysis (P = 0.03).CONCLUSION: Defective or ineffective use of coping strategies may be an important etiology in functional constipation and subsequently reflected in abnormal anorectal physiology.

关键词： Constipation Anorectal physiology Coping mechanism

Investigation into perturbed nucleoside metabolism and cell cycle for elucidating the cytotoxicity effect of resveratrol on human lung adenocarcinoma epithelial cells

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Chinese Journal of Natural Medicines 2019年第8期17卷 608-615页

作者： LI Zheng CHEN Qian-Qian lam Christopher wai Kei GUO Jian-Ru ZHANG Wei-Jia WANG Cai-Yun WONG Vincent kam wai YAO Mei-Cun ZHANG Wei State Key Laboratory of Quality Research in Chinese Medicines and Macao Institute for Applied Research in Medicine and Health Macao University of Science and Technology Macao 999078 China Faculty of Medicine Macao Institute for Applied Research in Medicine and Health Macao University of Science and TechnologyMacao 999078 China School of Pharmaceutical Sciences Sun Yat-sen University Guangzhou 510006 China

In an effort to understand the molecular events contributing to the cytotoxicity activity of resveratrol(RSV), we investigated its effects on human lung adenocarcinoma epithelial cell line A549 at different concentrations. Cellular nucleoside metabolic profiling was determined by an established liquid chromatography-mass spectrometry method in A549 cells. RSV resulted in significant decreases and imbalances of deoxyribonucleoside triphosphates(d NTPs) pools suppressing subsequent DNA synthesis. Meanwhile, RSV at high concentration caused significant cell cycle arrest at S phase, in which cells required the highest dNTPs supply than other phases for DNA replication. The inhibition of DNA synthesis thus blocked subsequent progression through S phase in A549 cells,which may partly contribute to the cytotoxicity effect of RSV. However, hydroxyurea(HU), an inhibitor of RNR activity, caused similar dNTPs perturbation but no S phase arrest, finally no cytotoxicity effect. Therefore, we believed that the dual effect of high concentration RSV, including S phase arrest and DNA synthesis inhibition, was required for its cytotoxicity effect on A549 cells. In summary,our results provided important clues to the molecular basis for the anticancer effect of RSV on epithelial cells.

关键词： Resveratrol LC-MS Deoxyribonucleotides DNA synthesis S phase arrest

Incidence and predictors of upper gastrointestinal bleeding in patients receiving low-dose aspirin for secondary prevention of cardiovascular events in patients with coronary artery disease

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World Journal of Gastroenterology 2006年第18期12卷 2923-2927页

作者： William Ng wai-Man Wong wai-Hong Chen Hung-Fat Tse Pui-Yin Lee kam-Chuen Lai Sheung-wai Li Matthew Ng Kwok-Fai lam Xi Cheng Chu-Pak Lau Division of Cardiology University Department of Medicine Queen Mary Hospital Hong Kong SAR China Division of Gastroenterology University Department of Medicine Queen Mary Hospital Hong Kong SAR China Division of Rehabilitation Medicine University Department of Medicine Queen Mary Hospital Hong Kong SAR China Department of Statistics and Actuarial Science University of Hong Kong Hong Kong SAR China

AIM： The use of low-dose aspirin to prevent cardiovascular disease events is well established. However, the incidence and predictors of upper gastrointestinal bleeding （UGIB） with its use are unknown. We studied prospectively the incidence and outcome of peptic ulceration in low-dose aspirin users. METHODS： A total of 991 patients with coronary artery disease （CAD） on low-dose aspirin were prospectively followed-up for two years for the occurrence and clinical features of first hospitalized episode of UGIB. RESULTS： UGIB had a bimodal presentation with 45% occurring within four months of aspirin initiation and had an overall prevalence of 1.5% per year. There was no UGIB-related death. Hypertension （OR = 4.6, 95%CI 1.5 - 14.7, P = 0.009）, history of peptic ulceration （OR = 3.1, 95%CI 1.1 - 9.0, P = 0.039）, tertiary education （OR = 3.08, 95%CI 1.1 - 9.0, P = 0.039） and higher lean body mass （P = 0.016） were independent factors associated with UGIB. Use of nitrate did not reduce UGIB. CONCLUSION： The incidence of UGIB in patients with CAD on long-term low-dose aspirin is low, but is accompanied with significant morbidity. With prolonged use of aspirin, UGIB continues to be a problem for those with risk factors and especially in patients with a history of peptic ulcers, in which UGIB tends to occur early after aspirin therapy.

关键词： Coronary artery disease, Aspidn Gastrointestinal bleeding

Intravenous fluid selection rationales in acute clinical management

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World Journal of Emergency Medicine 2018年第1期9卷 13-19页

作者： Wing Yan Shirley Cheung wai Kwan Cheung Chun Ho lam Yeuk wai Chan Hau Ching Chow Ka Lok Cheng Yau Hang Wong Chak Wah kam Accident and Emergency Department Tuen Mun Hospital

BACKGROUND: Intravenous fluid(IVF) is commonly used in acute clinical management. This study aimed to review the choice and primary considerations in IVF prescriptions and to evaluate the adequacy of guidelines and trainings on it in the New Territories West Cluster(NTWC) of Hong ***: This is a descriptive study based on data collected from an online survey. Data were processed by SPSS for statistical analysis. This study focused on a general description and doctor-nurse between group comparison. Participants were asked the choice of IVF for nine acute clinical scenarios and provide reason. A 1–10 scale was used to assess the sufficiency of guideline, training and information, and time for revision on IVF ***: 0.9% sodium chloride was the most familiar IVF(36%), followed by 5% Dextrose solution(26%). In the nine scenarios, the most chosen IVF was 0.9% sodium chloride(37%–61%). There was significant difference in the choice of IVF between doctors and nurses in 7 cases. The second most chosen IVF for doctors was Plasma-Lyte A while that for nurses was Gelofusine. Departmental practice was the most chosen reason to account for the prescription. The adequacy of guideline, information and training, and time for revision was rated 5. Doctors had significantly more time at work than nurses to update knowledge in IVF prescription(5.41 versus 4.57).CONCLUSION: 0.9% sodium chloride was mostly chosen. The choice of IVF was mainly based on departmental practice. Adequacy of guideline, information and training, and time for revision on IVF prescription were average, indicating significant training deficit.

关键词： Intravenous fluid Acute care Resuscitation

A Survey on Recent Advances and Challenges in Reinforcement Learning Methods for Task-oriented Dialogue Policy Learning

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Machine Intelligence Research 2023年第3期20卷 318-334页

作者： wai-Chung Kwan Hong-Ru Wang Hui-Min Wang kam-Fai Wong The Systems Engineering and Engineering Management Department The Chinese University of Hong KongHong Kong 999077China

Dialogue policy learning(DPL)is a key component in a task-oriented dialogue(TOD)*** goal is to decide the next action of the dialogue system,given the dialogue state at each turn based on a learned dialogue *** learning(RL)is widely used to optimize this dialogue *** the learning process,the user is regarded as the environment and the system as the *** this paper,we present an overview of the recent advances and challenges in dialogue policy from the perspective of *** specifically,we identify the problems and summarize corresponding solutions for RL-based dialogue policy *** addition,we provide a comprehensive survey of applying RL to DPL by categorizing recent methods into five basic elements in *** believe this survey can shed light on future research in DPL.

关键词： Dialogue policy learning(DPL) task-oriented dialogue system(TOD) reinforcement learning(RL) dialogue system Markov decision process

NOD2 and TLR2 ligands trigger the activation of basophils and eosinophils by interacting with dermal fibroblasts in atopic dermatitis-like skin inflammation

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Cellular & Molecular Immunology 2016年第4期13卷 535-550页

作者： Delong Jiao Chun-Kwok Wong Huai-Na Qiu Jie Dong Zhe Cai Man Chu kam-Lun Hon Miranda Sin-Man Tsang Christopher wai-Kei lam Department of Chemical Pathology The Chinese University of Hong Kong Prince of Wales Hospital Shatin NT Hong Kong China Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China The Chinese University of Hong Kong Hong Kong China Department of Paediatrics The Chinese University of Hong Kong Prince of Wales Hospital Shatin NT Hong Kong China State Key Laboratory of Quality Research in Chinese Medicine Macao institute for Applied Research in Medicine and Health Macao University of Science and Technology Taipa Macao People's Republic of China

The skin of patients with atopic dermatitis （AD） has a unique predisposition for colonization by Staphylococcus aureus （S. aureus）, which contributes to the inflammation and grim prognosis of AD. Although the mechanism underlying the S. aureus-induced exacerbation of AD remains unclear, recent studies have found a pivotal role for pattern recognition receptors in regulating the inflammatory responses in S. aureus infection. In the present study, we used a typical mouse model of AD-like skin inflammation and found that S. aureus-associated nucleotide-binding oligomerization domain-containing protein 2 （NOD2） and toll-like receptor 2 （TLR2） ligands exacerbated AD-like symptoms, which were further deteriorated by the in vivo expansion of basophils and eosinophils. Subsequent histological analyses revealed that dermal fibroblasts were pervasive in the AD-like skin lesions, Co-culture of human dermal fibroblasts with basophils and eosinophils resulted in a vigorous cytokine/chemokine response to the NOD2/TLR2 ligands and the enhanced expression of intercellular adhesion molecule-1 on the dermal fibroblasts. Basophils and eosinophils were primarily responsible for the AD-related cytokine/chemokine expression in the co-cultures. Direct intercellular contact was necessary for the crosstalk between basophils and dermal fibroblasts, while soluble mediators were sufficient to mediate the eosinophil-fibroblast interactions. Moreover, the intracellular p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and nuclear factor-kappa B signaling pathways were essential for NOD2/TLR2 ligand-mediated activation of basophils, eosinophils, and dermal fibroblasts in AD-related inflammation. This study provides the evidence of NOD2/TLR2-mediated exacerbation of AD through activation of innate immune cells and therefore sheds light on a novel mechanistic pathway bv which S. aureus contributes to the DathoDhvsiology of AD.

关键词： atopic dermatitis basophils, eosinophils NOD2 TLR2