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Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

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Cancer Biology & Medicine 2024年第2期21卷 144-162页

作者： Yang Song Harry CH lau Xiang Zhang Jun Yu Institute of Digestive Disease and Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong KongChina Department of Gastroenterology Zhongshan Hospital Xiamen UniversityXiamen 361004China

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver *** interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and *** normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and *** gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal *** note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC ***,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying *** this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in ***,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered *** summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

关键词： Bile acid gut microbiota hepatocellular carcinoma therapeutics microbiota modulation

Martin boundary and exit space on the Sierpinski gasket

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Science China Mathematics 2012年第3期55卷 475-494页

作者： lau ka-sing NGAI Sze-Man Department of Mathematics The Chinese University of Hong Kong Department of Mathematical Sciences Georgia Southern University

We define a new Markov chain on the symbolic space representing the Sierpinski gasket (SG),and show that the corresponding Martin boundary is homeomorphic to the SG while the minimal Martin boundary is the three vertices of the *** addition,the harmonic structure induced by the Markov chain coincides with the canonical one on the *** suggests another approach to consider the existence of Laplacians on those self-similar sets for which the problem is still not settled.

关键词： Martin boundary Markov chain Green function harmonic function fractal Sierpinski gasket

Comparing 11 early warning scores and three shock indices in early sepsis prediction in the emergency department

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World Journal of Emergency Medicine 2024年第4期15卷 273-282页

作者： Rex Pui Kin Lam Zonglin Dai Eric Ho Yin lau Carrie Yuen Ting Ip Ho Ching Chan Lingyun Zhao Tat ChiTsang Matthew Sik Hon Tsui Timothy Hudson Rainer Department of Emergency Medicine School of Clinical MedicineLi Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina School of Public Health Li Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina Accident and Emergency Department Queen Mary HospitalHong KongChina

BACKGROUND:This study aimed to evaluate the discriminatory performance of 11 vital sign-based early warning scores(EWSs)and three shock indices in early sepsis prediction in the emergency department(ED).METHODS:We performed a retrospective study on consecutive adult patients with an infection over 3 months in a public ED in Hong *** primary outcome was sepsis(Sepsis-3 definition)within 48 h of ED *** c-statistics and the DeLong test,we compared 11 EWSs,including the National Early Warning Score 2(NEWS2),Modified Early Warning Score,and Worthing Physiological Scoring System(WPS),etc.,and three shock indices(the shock index[SI],modified shock index[MSI],and diastolic shock index[DSI]),with Systemic Inflammatory Response Syndrome(SIRS)and quick Sequential Organ Failure Assessment(qSOFA)in predicting the primary outcome,intensive care unit admission,and mortality at different time ***:We analyzed 601 patients,of whom 166(27.6%)developed ***2 had the highest point estimate(area under the receiver operating characteristic curve[AUROC]0.75,95%CI 0.70-0.79)and was significantly better than SIRS,qSOFA,other EWSs and shock indices,except WPS,at predicting the primary ***,the pooled sensitivity and specificity of NEWS2≥5 for the prediction of sepsis were 0.45(95%CI 0.37-0.52)and 0.88(95%CI 0.85-0.91),*** discriminatory performance of all EWSs and shock indices declined when used to predict mortality at a more remote time ***:NEWS2 compared favorably with other EWSs and shock indices in early sepsis prediction but its low sensitivity at the usual cut-off point requires further modification for sepsis screening.

关键词： Sepsis Emergency department Clinical prediction rule Early warning score Shock index

MULTIFRACTAL STRUCTURE AND PRODUCT OF MATRICES

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Analysis in Theory and Applications 2003年第4期19卷 289-311页

作者： lau ka-sing Department of Mathematics Chinese University of Hong Kong

There is a well established multifractal theory for self-similar measures generated by non-overlapping contractive similutudes. Our report here concerns those with overlaps. In particular we restrict our attention to the important classes of self-similar measures that have matrix representations. The dimension spectra and the L q -spectra are analyzed through the product of matrices. There are abnormal behaviors on the multifractal structure and they will be discussed in detail.

关键词： multifractal self-similar measure iterated function system dimension spectra

Multiomics approaches to uncover endometrial receptivity in embryo implantation: a mini-review

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REPRODUCTIVE AND DEVELOPMENTAL MEDICINE 2024年第3期8卷 178-185页

作者： Fernando, Sudini R. Yan, Yang Kumar, Manish Lai, Hoi-Lam Lee, Yin-lau Ng, Ernest H. Y. Yeung, William S. B. Lee, kai-Fai Univ Hong Kong Li Ka Shing Fac Med Dept Obstet & Gynaecol L7-49Lab Block21 Sassoon Rd Hong Kong 999077 Peoples R China Uva Wellassa Univ Fac Anim Sci & Export Agr Dept Anim Sci Badulla Sri Lanka Univ Hong Kong Shenzhen Hosp Shenzhen Key Lab Fertil Regulat Shenzhen 518053 Peoples R China

Successful implantation requires concerted interactions during the apposition, adhesion, and invasion of the embryo into a receptive endometrium. However, the embryo implantation rate for assisted reproduction remains low despite the transfer of good quality embryos. Changes in endometrial transcriptomics, proteomics, lipidomics, and even microbiota all play important roles in embryo implantation. Specifically, the expression of steroid hormone-regulated adhesive and anti-adhesive molecules during the embryo implantation window is becoming an area of increasingly intense research. This review (a) summarizes the different molecules expressed in the receptive endometrium and (b) proposes the use of surface protein markers to predict pregnancy outcomes from assisted reproduction.

关键词： Cell surface proteins Steroid regulation Endometrial receptivity Receptivity marker Infertility PROTEIN DISULFIDE-ISOMERASE UTERINE EPITHELIAL-CELLS PLASMA-MEMBRANE TRANSFORMATION HEAT-SHOCK PROTEINS L-SELECTIN DIFFERENTIAL EXPRESSION ADHESION MOLECULES IN-VITRO INTEGRINS PREGNANCY

片仔癀通过调节小鼠的肠道菌群和代谢物抑制非酒精性脂肪性肝炎

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Engineering 2024年第4期35卷 257-269页

作者： Xianyi Zeng Xiang Zhang Hao Su Hongyan Gou Harry Cheuk-Hay lau Xiaoxu Hu Ziheng Huang Yan Li Jun Yu Shenzhen Research Institute The Chinese University of Hong KongShenzhen 518057China Department of Medicine and Therapeutics Institute of Digestive DiseaseState Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong 999077China

Non-alcoholic steatohepatitis(NASH)is a severe form of non-alcoholic fatty liver disease without effective *** traditional Chinese medicine formulation Pien Tze Huang(PTH)can suppress inflammatory ***,we evaluate the effects of PTH on the evolution of NASH and its underlying *** found that PTH prevented the development of steatohepatitis induced by various dietary models,including a high-fat high-cholesterol(HFHC)diet,choline-deficient high-fat diet(CD-HFD),and methionine-and choline-deficient(MCD)diet,along with significant suppression of liver injury,hepatic triglyceride,and lipid ***,ten days of PTH treatment after the onset of NASH significantly ameliorated MCD diet-induced steatosis and liver injury in *** the metagenomic sequencing of stool samples,we found that PTH administration restored the gut microbiota with enrichment of probiotics including Lactobacillus acidophilus(***),Lactobacillus plantarum,Lactococcus lactis,and Bacillus *** enriched *** prevented MCD diet-induced *** addition,PTH restored the gut barrier function in mice with steatohepatitis,as evidenced by reduced intestinal permeability,decreased serum lipopolysaccharides(LPS)level,and increased epithelial tightjunction protein E-cadherin *** metabolomic analysis via liquid chromatography-mass spectrometry profiling identified the alteration in the metabolism of bile acids in the portal vein of PTHtreated *** further confirmed that an intact gut microbiota is necessary for PTH to exhibit antisteatohepatitis *** conclusion,PTH protects against steatohepatitis development by modulating the gut microbiota and *** is a potential promising prophylactic and therapeutic option for patients with NASH.

关键词： Pien Tze Huang Non-alcoholic steatohepatitis Gut barrier function Gut microbiota

Residential building performance analysis at near extreme weather conditions in Hong Kong through a thermal-comfort-based strategy

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Building Simulation 2023年第1期16卷 13-25页

作者： K.F.Fong C.K.Lee Kevin ka-Lun lau Edward Yan Yung Ng Division of Building Science and Technology College of EngineeringCity University of Hong KongHong KongChina Department of Civil Engineering and Natural Resources Lulea University of TechnologySweden School of Architecture The Chinese University of Hong KongHong KongChina

The precise building performance assessment of residential housings in subtropical regions is usually more difficult than that for the commercial premises due to the much more complicated behavior of the occupants with regard to the change in indoor *** conventional use of a fixed schedule for window opening,clothing insulation and cooling equipment operation cannot reflect the real situation when the occupants respond to the change in thermal comfort,thus affecting the appropriateness of the assessment *** rectify the situation,a new modeling strategy in which the modification of the various operation schedules was based on the calculated thermal comfort(TC),was developed in this *** this new TC-based strategy,the realistic building performances under different cooling provision scenarios applied to a high-rise residential building under the near extreme weather conditions were investigated and *** was found that sole provision of ventilation fans could not meet the zone thermal comfort by over 68%of the time,and air-conditioning was *** optimal use of ventilation fans for cooling could only help reduce the total cooling energy demand by less than 12%at best which could only be realistically evaluated by adopting the present *** studies were conducted which revealed that some design factors could offer opportunities for reducing the total cooling energy under the near extreme weather conditions.

关键词： predicted mean vote thermal comfort ventilation potential building performance simulation residential housings

B-cell-targeted therapies in systemic lupus erythematosus

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Cellular & Molecular Immunology 2013年第2期10卷 133-142页

作者： Vera Sau-Fong Chan Helen Hoi-Lun Tsang Rachel Chun-Yee Tam Liwei Lu Chak-sing lau Department of Medicine Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong China Department of Pathology Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong China

Autoreactive B cells are one of the key immune cells that have been implicated in the pathogenesis of systemic lupus erythematosus （SLE）. In addition to the production of harmful auto-antibodies （auto-Abs）, B cells prime autoreactive T cells as antigen-presenting cells and secrete a wide range of pro-inflammatory cytokines that have both autocrine and paracrine effects. Agents that modulate B cells may therefore be of potential therapeutic value. Current strategies include targeting B-cell surface antigens, cytokines that promote B-cell growth and functions, and B- and T-cell interactions. In this article, we review the role of B cells in SLE in animal and human studies, and we examine previous reports that support B-cell modulation as a promising strategy for the treatment of this condition. In addition, we present an update on the clinical trials that have evaluated the therapeutic efficacy and safety of agents that antagonize CD20, CD22 and B-lymphocyte stimulator （BLyS） in human SLE. While the results of many of these studies remain inconclusive, belimumab, a human monoclonal antibody against BLyS, has shown promise and has recently been approved by the US Food and Drug Administration as an indicated therapy for patients with mild to moderate SLE. Undoubtedly, advances in B-cell immunology will continue to lead us to a better understanding of SLE pathogenesis and the development of novel specific therapies that target B cells.

关键词： Systemic lupus erythematosus B-cell autoimmunity therapy

Substitute of Expensive Pt with Improved Electrocatalytic Performance and Higher Resistance to CO Poisoning for Methanol Oxidation: the Case of Synergistic Pt-Co_3O_4 Nanocomposite

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Nano-Micro Letters 2013年第4期5卷 296-302页

作者： Hongxiao Zhao Zhi Zheng Jing Li Huimin Jia ka-wai Wong Yidong Zhang Woon Ming lau Key Laboratory of Micro-Nano Materials for Energy Storage and Conversion of Henan Province Institute of Surface Micro and Nano Materials Xuchang University Chengdu Green Energy and Green Manufacturing R&D Center

In this paper, Pt-Co_3O_4 nanocomposite was synthesized by a sol gel process combined with electrodeposition method. Its electrocatalytic activity towards methanol oxidation was investigated at room temperature using cyclic voltammetry(CV), electrochemical impedance spectroscopy(EIS) and current density time curve. It is found that the resultant Pt-Co_3O_4 catalysts with minute amount of Pt exhibite attractive electrocatalytic activity for methanol oxidation reaction(MOR) but with a high resistance CO poisoning due to the synergistic effects from Pt and Co_3O_4. Together with the low manufacturing cost of Co_3O_4, the reported nanostructured Pt-Co_3O_4 catalyst is expected to be a promising electrode material for direct methanol fuel cells(DMFC).

关键词： Pt-Co3O4 nanocomposite MOR Electrocatalytic activity