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Semiparametric Quantile Modelling of Hierarchical Data

Acta Mathematica Sinica,English Series 2009年第4期25卷 597-616页

作者： Mao Zai TIAN Man Lai TANG ping shing chan School of Statistics Renmin University of China Beijing 100872 P. R. China Center for Applied Statistics Renmin University of China Beijing 100872 P. R. China Department of Mathematics Hong Kong Baptist University Kowloon Hong Kong Department of Statistics The Chinese University of Hong Kong Shatin N.T. Hong Kong

The classic hierarchical linear model formulation provides a considerable flexibility for modelling the random effects structure and a powerful tool for analyzing nested data that arise in various areas such as biology, economics and education. However, it assumes the within-group errors to be independently and identically distributed （i.i.d.） and models at all levels to be linear. Most importantly, traditional hierarchical models （just like other ordinary mean regression methods） cannot characterize the entire conditional distribution of a dependent variable given a set of covariates and fail to yield robust estimators. In this article, we relax the aforementioned and normality assumptions, and develop a so-called Hierarchical Semiparametric Quantile Regression Models in which the within-group errors could be heteroscedastic and models at some levels are allowed to be nonparametric. We present the ideas with a 2-level model. The level-1 model is specified as a nonparametric model whereas level-2 model is set as a parametric model. Under the proposed semiparametric setting the vector of partial derivatives of the nonparametric function in level-1 becomes the response variable vector in level 2. The proposed method allows us to model the fixed effects in the innermost level （i.e., level 2） as a function of the covariates instead of a constant effect. We outline some mild regularity conditions required for convergence and asymptotic normality for our estimators. We illustrate our methodology with a real hierarchical data set from a laboratory study and some simulation studies.

关键词： hierarchical models quantile regression robustness

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NHE7 upregulation potentiates the uptake of small extracellular vesicles by enhancing maturation of macropinosomes in hepatocellular carcinoma

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Cancer Communications 2024年第2期44卷 251-272页

作者： Yue Yao Yi Xu Liang Yu Ting-Mao Xue Zhi-Jie Xiao Pui-Chi Tin Hiu-Ling Fung Hoi-Tang Ma Jing-ping Yun Judy Wai ping Yam Department of Pathology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongP.R.China Department of Endocrinology and Metabolism Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjingP.R.China Department of Hepatopancreatobiliary Surgery Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjingP.R.China State Key Laboratory of Oncology in South China Cancer Center of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Hepatobiliary Surgery II Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China Scientific Research Center The Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdongP.R.China State Key Laboratory of Liver Research The University of Hong KongHong KongP.R.China Department of Pathology Cancer Center of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China

Background:Small extracellular vesicles(sEVs)mediate intercellular commu-nication that contributes to hepatocellular carcinoma(HCC)progression via multifaceted *** success of cell entry determines the effect of sEV on recipient ***,we aimed to delineate the mechanisms underlying the uptake of sEV in ***:AF,Alexa Fluor;ANOVA,analysis of variance;ATP9A,ATPase Phospholipid Transporting 9A;BCECF-AM,2’,7’-bis-(2-barboxyethyl)-5-(and-6)-carboxyfluorescein,acetoxymethyl ester;BSA,bovine serum albumin;CCMR,Centre for Comparative Medicine Research;CRISPR,clustered regularly interspaced short palindromic repeats;CTL,ctrl;CXCR4,C-X-C Chemokine Receptor Type 4;DAPI,4′,6-diamidino-2-phenylindole;DFS,disease-free survival;DMEM,Dulbecco’s Modified Eagle Medium;DMSO,dimethyl sulfoxide;Dox,doxycycline;EEA1,early endosome antigen 1;EIPA,5-(N-ethyl-N-isopropyl)-amiloride;FBS,fetal bovine serum;FITC,fluorescein isothiocyanate;GAPDH,glyceraldehyde-3-phosphate dehydrogenase;GM130,Golgi matrix protein 130;HCC,hepatocellular carcinoma;HEPES,4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid;HPRT1,hypoxanthine phosphoribosyltransferase 1;H-score,histoscore;IAA,indole-3-acetic acid;KD,knockdown;KO,knockout;mAID,mini-auxin-inducible degron;MTT,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide;NHE7,Na(+)/H(+)exchanger 7;ns,non-significant;OD,optical density;OS,overall survival;PBS,phosphate-buffered saline;PCR,polymerase chain reaction;pHe,endosomal pH;pHi,intracellular pH;PKH67,Paul Karl Horan 67;Rab21,Ras-associated binding protein 21;RIPA,radioimmunoprecipitation assay;SAM,synergistic activation mediator;SEMs,standard error of the means;sEVs,small extracellular vesicles;sgRNA,single-guide RNA;shRNA,short-hairpin RNA;SLC9,solute carrier gene 9;SLiCE,Seamless Ligation Cloning Extract;TCGA,The Cancer Genome Atlas;TCL,total cell lysates;TGN,trans-Golgi network;TMA,tissue microarray;TMR,tetramethyl rhodamine;TSG101,tumor susceptibility gene *** Yao an

关键词： hepatocellular carcinoma small extracellular vesicles macropinocytosis pH regulation sodium-hydrogen exchanger

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Cold-Induced Reprogramming of Subcutaneous White Adipose Tissue Assessed by Single-Cell and Single-Nucleus RNA Sequencing

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Research 2024年第1期2023卷 763-778页

作者： Qing Liu Qiaoyun Long Jiayu Zhao Wenjie Wu Zexin Lin Wei Sun ping Gu Tuo Deng Kerry Martin Loomes Donghai Wu Alice P.S.Kong Jingying Zhou Alfred S.Cheng Hannah Xiaoyan Hui School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Department of Pharmacology and Pharmacy The University of Hong KongHong KongChina Guangzhou Institute of Biomedicine and Health Chinese Academy of SciencesGuangzhouChina China-New Zealand Joint Laboratory on Biomedicine and Health Chinese Academy of SciencesGuangzhouChina Department of Endocrinology Jinling HospitalNanjing UniversitySchool of MedicineNanjingChina National Clinical Research Center for Metabolic Diseases and Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaChina Key Laboratory of Diabetes Immunology Ministry of Educationand Metabolic Syndrome Research CenterThe Second Xiangya Hospital of Central South UniversityChangshaChina Clinical Immunology Center The Second Xiangya Hospital of Central South UniversityChangshaChina School of Biological Sciences and Maurice Wilkins Centre University of AucklandAucklandNew Zealand Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina Hong Kong Institute of Diabetes and Obesity The Chinese University of Hong KongPrince of Wales HospitalShatinHong KongChina Li Ka shing Institute of Health Sciences The Chinese University of Hong KongPrince of Wales HospitalShatinHong KongChina

Adipose browning has demonstrated therapeutic potentials in several ***,by conducting transcriptomic profiling at the single-cell and single-nucleus resolution,we reconstituted the cellular atlas in mouse inguinal subcutaneous white adipose tissue(iWAT)at thermoneutrality or chronic cold *** major nonimmune cells within the iWAT,including adipose stem and progenitor cells(ASPCs),mature adipocytes,endothelial cells,Schwann cells,and smooth muscle cells,were recovered,allowing us to uncover an overall and detailed blueprint for transcriptomes and intercellular cross-talks and the dynamics during white adipose tissue brown *** findings also unravel the existence of subpopulations in mature adipocytes,ASPCs,and endothelial cells,as well as new insights on their interconversion and reprogramming in response to *** adipocyte subpopulation competent of major histocompatibility complex class Ⅱ(MHCⅡ)antigen presentation is ***,a subcluster of ASPC with CD74 expression was identified as the precursor of this MHCⅡ^(+)*** adipocytes are transdifferented from preexisting lipid generating adipocytes,which exhibit developmental trajectory from de novo differentiation of amphiregulin cells(Aregs).Two distinct immune-like endothelial subpopulations are present in iWAT and are responsive to *** data reveal fundamental changes during cold-evoked adipose browning.

关键词： evoked programming generating

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Protein surface recognition of the novel tetra-carboxylphenyl calix[4]arene to cytochrome c

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Chinese Chemical Letters 2008年第11期19卷 1341-1344页

作者： Wen Ting An Yong Jiao Xiao Hua Sun Chuan Dong Shao Min Shuang ping Fang Xia Man shing Wong Research Center of Environmental Science and Engineering School of Chemistry and Chemical Engineering Shanxi University Taiyuan 030006 China Department of Chemistry Hong Kong Baptist University Kowloon Tong Hongkong S.A.R. China

The interaction of the novel tetra-carboxylphenyl calix[4]arene （TCPC） with the bovine heart cytochrome c （Cc） was first investigated by fluorescence spectroscopy and molecular modeling methods. The formation of a stable 1：1 complex was monitored by fluorescence titration, and its binding constant is 1.916 ×10^7 L mol^-1. Molecular modeling reveals the recognition mechanism of TCPC to the Cc surface, that is, the electrostatic interaction drives TCPC to the Cc surface, and the van der Waals interaction orientates TCPC parallel to the cleft of Cc.

关键词： Tetra-carboxylphenyl calixarene Cytochromc c Protein surface recognition Fluorescence spectroscopy Molecular modeling

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Transradial versus transfemoral rotablation for heavily calcified coronary lesions in contemporary drug-eluting stent era

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Journal of Geriatric Cardiology 2015年第5期12卷 489-496页

作者： Wei-Hsian Yin Chin-Kun Tseng Tien-ping Tsao Hsu-Lung Jen Wen-Pin Huang Chien-Lung Huang Jiann-Jong Wang Mason shing Young Division of Cardiology Heart Center Cheng Hsin General Hospital Taipei Taiwan China Faculty of Medicine National Yang-Ming University Taipei Taiwan China Institute of Clinical Medicine National Yang-Ming University Taipei Taiwan China Cardiovascular Research Centre School of Medicine National Yang-Ming University Taipei Taiwan China

Background Although radial access for drug-eluting stent （DES） combined with rotational atherectomy （RA） in patients with calcified coronary lesions may be associated with a lower risk of major bleeding complications and obtain favorable clinical results compared with femoral access, the long-term outcome data of this approach were limited in contemporary DES era. Methods ＆ Results This retrospective study sought to compare in-hospital and long-term outcomes for patients undergoing RA via the transradial （TR） and transfemoral （TF） route in 126 consecutive patients （59 radial, 67 femoral） from 2009 to 2014. TR RA procedures were performed in 44/62 （71%） by the three TR operators, compared with 15/64 （23%） by the four TF operators in the present study. Significantly smaller diameter guide catheters and burrs （1.39 ± 0.16 mm vs. 1.53 ± 0.24 mm, P = 0.001） were used in the TR group. Procedural success rates were similar in both TR and TF groups. There was a significantly less major access site bleeding complications in favor of radial artery access （2% vs. 16%, P = 0.012）. The incidence of in-hospital death or myocardial infarction was low in both groups. Although a trend of lower adverse event rate was demonstrated in the TR group compared with the TF one, no statistical significance （21% vs. 27%, P = 0.135） was detected. Conclusions Radial access, a useful alternative to femoral access for RA and DES, can be safely and successfully performed on up to 71% of the patients with heavily calcified coronary lesions needing RA by experienced TR operators.

关键词： Calcified lesion Drug-eluting stent Rotablation Transfemoral Transradial

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Forensic examination of plastic drinking straws based on their physical characteristics and manufacturing marks

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Forensic Sciences Research 2020年第1期5卷 64-73页

作者： Alaric C.W.Koh Suat ping Oh shing Min Lim Sok Yee Yew Jean Chen Vicky Y.S.Chow Forensic Chemistry and Physics Laboratory Health Sciences AuthoritySingapore

This work highlights the evidential value of examining plastic drinking straws to establish linkages between multiple sources for forensic intelligence,investigative or prosecution *** drinking straws are commonly encountered in drug cases,either as inhalational paraphernalia or as packaging ***,to the best of our knowledge,systematic studies on the evidential value of straws have not previously been carried *** this study,over 80 packets of clear and colourless straws—most of which were visually similar—were purchased from various commercial outlets in *** physical characteristics(viz.,polarizing patterns,thickness,circumference and mass per unit length)and the manufactur-ing marks of these straws were examined to assess their potentials for discriminating straws from different *** of polarizing patterns yielded a discrimination of approximately 69%,while thickness,circumference,and mass per unit length measurements resulted in lower *** microscopy of manufacturing marks was found to be the most discriminating among all techniques employed herein,with a discrimination of about 95%,even among straws with similar polarizing patterns.

关键词： Forensic sciences drug packaging plastics manufacturing marks tool marks straw discrimination

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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 semen. METHODS： Hepatitis B viral DNA was isolated from HBV carriers＇ semen and sera using phenol extraction method and QIAamp 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 reaction. RESULTS： 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 7.5×10^7 and 1.67×10^7 copies of HBV DNA per mL in two HBV infected patients＇ sera, while 2.14×10^5 and 3.02×10^5 copies of HBV DNA per mL in the semen. CONCLUSION： Real-time PCR is a more sensitive and accurate method to detect and quantify HBV DNA in the semen.

关键词： Hepatitis B virus Semen Real-time polymerase chain reaction Viral load

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ER stress-mediated renal fibrosis is attenuated by chemical chaperon 4-phenylbutyrate in vitro and in vivo

ER stress-mediated renal fibrosis is attenuated by chemical ...

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第八届海峡两岸毒理学研讨会

作者： Chih-Kang Chiang Li-ping Chen shing-Hwa Liu Institute of Toxicology College of MedicineNational Taiwan University Department of Integrated Diagnostics & Therapeutics National Taiwan University Hospital Department of Dentistry Taipei Chang Gang Memorial HospitalChang Gang University

Renal tubule interstitial fibrosis is the common and final pathologic change of kidney in end-stage renal *** reticulum（ER）stress contributes to the pathophysiological mechanisms during the development of renal ***,we investigated the protective effect of chemical chaperon sodium 4-phenylbutyrate（4-PBA）on renal fibrosis in vivo and in *** a rat unilateral ureteral obstruction（UUO）model,4-PBA mimicked endogenous ER chaperonin the kidneys.4-PBA significantly attenuated UUO-increased renal GRP78,CHOP,ATF4,and phosphorylated JNK protein expressions and UUO-decreased renal splicing XBP1 protein expression.4-PBA also attenuated the increases of a-smooth muscle actin and connective tissue growth factor（CTGF）protein expressions in the kidneys of UUO *** tubule interstitial injury,fibrosis,and apoptosis in the kidneys of UUO rats could also be attenuated by the administration of ***,transforming growth factor（TGF）-p markedly increased the protein expressions of ER stress-related molecules,pro-fibrotic factors,and apoptosis-related markers in the normal rat kidney epithelial cells（NRK-52E）,which could be significantly attenuated by 4-PBA treatment.4-PBA treatment also attenuated TGF-P-increased CTGF-luciferase activity and CTGF mRNA expression in NRK-52E *** together,4-PBA acts as an ER chaperone to ameliorate ER stress and protect against renal tubular cell apoptosis and renal fibrosis.

关键词： 4-phenylbutyrate endoplasmic reticulum stress unilateral ureteral obstruction apoptosis renal fibrosis

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Analysis of inborn errors of metabolism： disease spectrum for expanded newborn screening in Hong Kong

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Chinese Medical Journal 2011年第7期124卷 983-989页

作者： Han-Chih Hencher Lee Chloe Miu Mak Ching-Wan Lam Yuet-ping Yuen, Angel On-Kei chan Chi-Chung Shek Tak-shing Siu Chi-Kong Lai Chor-Kwan Ching Wai-Kwan Siu Sammy Pak-Lam Chen Chun-Yiu Law Morris Hok-Leung Tai Sidney Tam Albert Yan-Wo chan Chemical Pathology Laboratory Department of Pathology Princess Margaret Hospital Hong Kong SAR China Division of Clinical Biochemistry Queen Mary Hospital Hong Kong SAR China Department of Pathology Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China Chemical Pathology Laboratory Department of Pathology Queen Elizabeth Hospital Hong Kong SAR China

Background Data of classical inborn errors of metabolism （IEM） of amino acids, organic acids and fatty acid oxidation are largely lacking in Hong Kong, where mass spectrometry-based expanded newborn screening for IEM has not been initiated. The current study aimed to evaluate the approximate incidence, spectrum and other characteristics of classical IEM in Hong Kong, which would be important in developing an expanded newborn screening program for the local area.

关键词： biochemical genetics chemical pathology expanded newborn screening Hong Kong," inborn errorsof metabolism tandem mass spectrometry

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Role of Small Extracellular Vesicles in Liver Diseases:Pathogenesis,Diagnosis,and Treatment

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Journal of Clinical and Translational Hepatology 2022年第6期10卷 1176-1185页

作者： Tingmao Xue Judy Wai ping Yam Department of Hepatobiliary Surgery II Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdongChina Department of Pathology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongChinaReceived

Extracellular vesicles(EVs)are vesicular bodies that bud off from the cell membrane or are secreted virtually by all cell *** EVs(sEVs or exosomes)are key mediators of cell-cell communication by delivering their cargo,including proteins,lipids,or RNAs,to the recipient cells where they induce changes in signaling pathways and phenotypic *** findings have revealed the pivotal involve-ment of sEVs in the pathogenesis of various *** the bright side,they are rich sources of biomarkers for diag-nosis,prognosis,treatment response,and disease *** have high stability,biocompatibility,targetability,low toxicity,and are immunogenic in *** intrinsic properties make sEVs an ideal delivery vehicle to be loaded with cargo for therapeutic *** diseases are a major global health *** review aims to focus on the roles and mechanisms of sEVs in the pathogenesis of liver diseases,liver injury,liver failure,and liver *** are released not only by hepatocytes but also by stromal and immune cells in the *** detection of liver disease determines the chance for cura-tive treatment and high survival of *** review focuses on the potential of circulating sEV cargo as specific and sensitive noninvasive biomarkers for the early detection and prognosis of liver *** addition,the therapeutic use of sEVs derived from various cell types is ***-though sEVs hold promise for clinical applications,there are still challenges to be overcome by further research to bring utilization of sEVs into clinical practice.

关键词： Small extracellular vesicles Liver injury Liver fibrosis Liver fail-ure Hepatocellular carcinoma Biomarkers.

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