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| 1 | 食物过敏的定义、流行性、诊断及治疗显示文摘食物过敏是异质性群体相关疾病,会通过一种或多种方式对多个器官造成影响。其反应的严重程度可从轻度的局部反应到全身性的过敏反应。从机制上来看,食物过敏是Th2细胞驱动的免疫紊乱疾病,食物特异性IgE是这种速发型不良反应的基础。过敏的部位和症状并不一定相同。食物过敏常会与自身免疫性(如乳糜泻)和非免疫性(如乳糖不耐受)的其他食物不良反应相混淆。为了正确诊断食物过敏,需要详细了解患者病史,检测特异性IgE,并进行经口激发试验来确诊。一些辅助因素(如运动、药物和酒精)有助于诱发食物过敏,会进一步增加诊断的复杂性。以食物提取物为基础的诊断试验并不能反映症状的严重程度,而检测单个食物致敏原IgE的新一代分子诊断技术,则能够为临床医生和患者提供可靠的症状严重程度依据。分子诊断还有助于确定食物过敏是直接源于对食物的暴露还是间接源于花粉过敏(交叉反应)。流行病学调查表明,桃过敏在欧洲主要是源于对桃的食用,而在中国则是源于对艾蒿花粉的初级致敏。但这两种情况都是由来自同一家族的致敏原分子介导的。流行病学调查深入揭示了食物过敏的病因、流行性及其所包含的风险因素,为预防食物过敏提供了循证策略。过去的十年中,食物过敏在发达国家盛行。经济发展和城市化进程都被认为会导致食物过敏流行性的增加,而且饮食习惯不同,过敏的食物也不同。目前,分子变态反应学和生物技术正在开发安全的免疫治疗方法,有望能够减轻日益加重的食物过敏负担。一种使用低致敏性突变重组分子的免疫疗法已经开始进行第一阶段临床试验的评估。食物致敏原名单的不断完善为转基因食品致敏性的评估提供了坚实基础。 | Ronald van Ree Lars K. Poulsen Gary WK Wong Barbara K. Ballmer-Weber 高中山 贾旭东 | 2015 | 中华预防医学杂志2015，49，1： | 28 |
| 2 | Intracellular signaling mechanisms regulating the activation of human eosinophils by the novel Th2 cytokine IL-33:implications for allergic inflammation显示文摘The novel interleukin(IL)-1 family cytokine IL-33 has been shown to activate T helper 2(Th2)lymphocytes,mast cells and basophils to produce an array of proinflammatory cytokines,as well as to mediate blood eosinophilia,IgE secretion and hypertrophy of airway epithelium in mice.In the present study,we characterized the activation of human eosinophils by IL-33,and investigated the underlying intracellular signaling mechanisms.IL-33 markedly enhanced eosinophil survival and upregulated cell surface expression of the adhesion molecule intercellular adhesion molecule(ICAM)-1 on eosinophils,but it suppressed that of ICAM-3 and L-selectin.In addition,IL-33 mediates significant release of the proinflammatory cytokine IL-6 and the chemokines CXCL8 and CCL2.We found that IL33-mediated enhancement of survival,induction of adhesion molecules,and release of cytokines and chemokines were differentially regulated by activation of the nuclear factor(NF)-KB,p38 mitogen-activated protein kinase(MAPK)and extracellular signal-regulated kinase(ERK)pathways.Furthermore,we compared the above IL-33 activities with two structurally and functionally related cytokines,IL-1 B and IL-18.IL-1β,but not IL-18,markedly upregulated cell surface expression of ICAM-1.IL-1βand IL-18 also significantly enhanced eosinophil survival,and induced the release of IL-6 and chemokines CXCL8 and CCL2 via the activation of the NF-κB,p38 MAPK and ERK pathways.Synergistic efects on the release of IL-6 were also observed in combined treatment withIL-1B,IL-18 and IL-33.Taken together,our findings provide insight into IL-33-mediated activation of eosinophils via differential intracellular signaling cascades in the immunopathogenesis of allergic inflammation. | Joyce YS Chow Chun K Wong Phyllis FY Cheung Christopher WK Lam | 2010 | Cellular & Molecular Immunology2010，7，1： | 22 |
| 3 | Multivariate statistical analysis of clinicopathologic factors influencing survival of patients with bile duct carcinoma显示文摘AIM: To evaluate the influence of various clinicopathologicfactors on survival of patients with bile duct carcinoma aftercurative resection.METHODS: A retrospective analysis was made for 86 casesof bile duct carcinoma treated from January 1981 toSeptember 1995. Fifteen clinicopathologic factors possiblyinfluencing survival were selected. Independent variableswere first analyzed by univariate methods. Survival forvariable was estimated by the method of Kaplan and Meier.The variables that were statistically significant by univarlateanalysis were included in a multivariate analysis, which wereconfirmed using the Cox stepwise proportion hazard modelwith the help of SPSS 10.0 for Windows software.RESULTS: The overall cumulative survival rate was 72.6 %at 1 year, 32.4 % at 3 years, and 18.7 % at 5 years. Theresults of univariate analysis showed that the majorsignificant prognostic factors influencing survival of thesepatients were histological type of lesion, lymph nodemetastasis, pancreatic invasion, duodenal invasion, pedneuralinvasion, macroscopic vessel involvement, resected surgicalmargin and depth of cancer invasion (P=0.02, 0.02, 0.004,0.005, 0.01, 0.43, 0.03 and 0.04). Age, sex, location of tumor,size of tumor, macroscopic type of lesions, hepaticmetastasis, and hepatic invasion were not significantlyassociated with prognosis (P>0.05). Pancreatic invasion,perineural invasion and lymph node metastases were thethree most important prognostic factors by multivariateanalysis using the Cox proportional hazards model.CONCLUSION: Pancreatic invasion, pedneural invasion andlymph node metastases are the most important prognosticfactors for bile duct carcinoma after curative resection. | He, P Shi, JS Chen, WK Wang, ZR Ren, H Li, H | 2002 | World Journal of Gastroenterology2002，8，5： | 10 |
| 4 | Formation of disinfection byproducts in typical Chinese drinking water显示文摘Eight typical drinking water supplies in China were selected in this study.Both source and tap water were used to investigate the occurrence of chlorinated disinfection byproducts(DBPs),and seasonal variation in the concentrations of trihalomethanes(THMs) of seven water sources was compared.The results showed that the pollution level for source water in China,as shown by DBP formation potential,was low.The most encountered DBPs were chloroform,dichloroacetic acid,trichloroacetic acid,and chlorodibromoacetic acid.The concentration of every THMs and haloacetic acid(HAA) compound was under the limit of standards for drinking water quality.The highest total THMs concentrations were detected in spring. | Wenbo Liu Yanmei Zhao Christopher WK Chow Dongsheng Wang | 2011 | Journal of Environmental Sciences2011，23，6： | 7 |
| 5 | Quality of life and palliative care needs of elderly patients with advanced heart failure显示文摘 | Helen YL Chan Doris SF Yu Doris YP Leung Aileen WK Chan Elsie Hui | 2016 | Journal of Geriatric Cardiology2016，13，5： | 7 |
| 6 | 胶质瘤干细胞对替莫唑胺敏感性的研究显示文摘目的探讨胶质瘤干细胞(GSC)对替莫唑胺(TMZ)的敏感性及耐药机制。方法新鲜多形性胶质母细胞瘤(GBM)标本培养后获得GSC。免疫荧光技术检测未分化GSC的CD133及分化生长GSC的GFAP的表达,MTS法检测对替莫唑胺的敏感性,流式细胞技术对CD133阳性细胞的比例进行定量,荧光标记的甲基化特异性PCR分析MGMT启动子区域的甲基化状态,Western blot检测抑癌基因PTEN的表达。结果(1)5例GBM标本中成功获得GSC,符合肿瘤干细胞定义。(2)5个GSC细胞株多数对TMZ不敏感。其中,T509的半数抑制浓度(IC50)为22.3μmol/L(敏感),T411的IC50为286.3μmol/L(中度敏感),其余3个细胞株T402,T405及T509的IC50皆大于1000μmol/L(不敏感)。(3)CD133阳性细胞比例大于10%的GSC细胞株对TMZ不敏感。(4)MGMT启动子区域呈去甲基化状态的GSC对TMZ不敏感或仅为中度敏感。(5)5个GSC细胞株中,PTEN表达水平差异大,与GSC对TMZ的敏感性无明显关联。结论GSC对TMZ普遍耐药,与MGMT启动子区域甲基化状态及CD133阳性细胞有关,而与PTEN蛋白表达水平无明显关联。 | 赛克 WANG Shu-zhen Popoff S Yung WK Colman H 陈忠平 | 2009 | 中华神经外科杂志2009，25，10： | 7 |
| 7 | 血清HBV RNA和HBsAg水平在判断亚洲慢性乙型肝炎患者是否适合停用恩替卡韦中的作用显示文摘【据Gut 2020年8月报道】题:血清HBV RNA和HBsAg水平在判断亚洲慢性乙型肝炎患者是否适合停用恩替卡韦中的作用(作者Seto WK等)来自中国香港的Seto等研究显示,在HBsAg血清清除前,慢性HBV感染的某些亚群患者可能已经停止治疗了。血清HBV RNA在决定停止治疗适宜性方面的作用中尚未得到很好的研究。 | SETO WK LIU KS MAK LY 徐晓桐 金晶兰 | 2020 | 临床肝胆病杂志2020，36，11： | 7 |
| 8 | Increasing incidence of colorectal cancer in Asia: implications for screening显示文摘 | Joseph JY Sung James YW Lau KL Goh WK Leung | 2005 | Lancet Oncology2005，，11： | 7 |
| 9 | Receptor activator of NF-κB Ligand (RANKL) expression is associated with epithelial to mesenchymal transition in human prostate cancer cells显示文摘 | Valerie A Odero-Marah Ruoxiang Wang Gina Chu Majd Zayzafoon Jianchun Xu Chunmeng Shi Fray F Marshall Haiyen E Zhau Leland WK Chung | 2008 | Cell Research2008，18，8： | 6 |
| 10 | Activation of human fibroblast-like synoviocytes by uric acid crystals in rheumatoid arthritis显示文摘Hyperuricemia-mediated uric acid crystal formation may cause joint inflammation and provoke the destruction of joints through the activation of inflammasome-mediated innate immune responses.However,the immunopathological effects and underlying intracellular regulatory mechanisms of uric acid crystal-mediated activation of fibroblast-like synoviocytes(FLS)in rheumatoid arthritis(RA)have not been elucidated.Therefore,we investigated the in vitro effects of monosodium urate crystals,alone or in combination with the inflammatory cytokines tumor-necrosis factor(TNF)-a or interleukin(IL)-1b,on the activation of human FLS from RA patients and normal control subjects and the underlying intracellular signaling mechanisms of treatment with these crystals.Monosodium urate crystals were able to significantly increase the release of the inflammatory cytokine IL-6,the chemokine CXCL8 and the matrix metalloproteinase(MMP)-1 from both normal and RA-FLS(all P,0.05).Moreover,the additive or synergistic effect on the release of IL-6,CXCL8 and MMP-1 from both normal and RA-FLS was observed following the combined treatment with monosodium urate crystals and TNF-a or IL-1b.Further experiments showed that the release of the measured inflammatory cytokine,chemokine and MMP-1 stimulated by monosodium urate crystals were differentially regulated by the intracellular activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase pathways but not the p38 mitogen-activated protein kinase pathway.Our results therefore provide a new insight into the uric acid crystal-activated immunopathological mechanisms mediated by distinct intracellular signal transduction pathways leading to joint inflammation in RA. | Da P Chen Chun K Wong Lai S Tam Edmund K Li Christopher WK Lam | 2011 | Cellular & Molecular Immunology2011，8，6： | 5 |
| 11 | Emerging radiotherapy technologies and trends in nasopharyngeal cancer显示文摘AbTechnology has always driven advances in radiotherapy treatment.In this review,we describe the main technological advances in radiotherapy over the past decades for the treatment of nasopharyngeal cancer(NPC)and highlight some of the pressing issues and challenges that remain.We aim to identify emerging trends in radiation medicine.These include advances in personalized medicine and advanced imaging modalities,standardization of planning and delineation,assessment of treatment response and adaptive re-planning,impact of particle therapy,and role of artificial intelligence or automation in clinical care.In conclusion,we expect significant improvement in the therapeutic ratio of radiotherapy treatment for NPC over the next decade. | Michelle Tseng Francis Ho Yiat Horng Leong Lea ChoungWong Ivan WK Tham Timothy Cheo Anne WM Lee | 2020 | Cancer Communications2020，40，9： | 5 |
| 12 | sonic hedgehog信号通路蛋白在人胚胎前列腺发育不同阶段的表达及意义显示文摘目的:探明sonic hedgehog信号通路中几个关键的效应蛋白sonic hedgehog(SHH)、Patchedl(PTC1)、Smoothened(SMO)及GLI1在人胚胎前列腺组织中的定位表达及变化.方法:应用免疫组织化学方法研究SHH、PTC1、SMO及GLI1在不同胎龄(10~39周)人胚胎前列腺组织中的表达变化情况.结果:随胎龄增大,SHH、PTC1、SMO及GLI1在前列腺组织中的表达水平呈由弱变强,由强渐弱,又由弱转强的双峰变化趋势.SHH和SMO仅表达在胚胎前列腺上皮细胞中;而PTC1和GLI1主要表达在上皮细胞外,也可表达在腺体周围的间质中.结论:SHH信号通路参与了人胚胎前列腺发育的调控过程,可能对于腺体发育初期的诱导发生,以及后期的增殖、分化都具有重要的调控作用. | 朱国栋 贺大林 何辉 张林琳 王新阳 Zhau E Haiyen Chung Leland WK | 2006 | 中华男科学杂志2006，12，10： | 4 |
| 13 | C-reactive protein activates complement in infarcted human myocardium显示文摘 | Nijmeijer R Lagrand WK Lubbers YT | 2003 | Am J Pathol2003，163，1： | 3 |
| 14 | 新型STAT3信号转导通路抑制剂WP1193在体外对脑肿瘤干细胞生物学特性影响的研究显示文摘背景与目的:恶性脑胶质母细胞瘤(glioblastoma Multiforme,GBM)是最常见的成人原发性脑肿瘤,预后仍不理想。近年来,肿瘤干细胞理论认为脑肿瘤干细胞是GBM进展及治疗耐受的主要原因,只有针对脑肿瘤干细胞的靶向治疗才能更加有效的治疗GBM。本研究旨在探讨新型STAT3信号转导通路抑制剂WP1193在体外对脑肿瘤干细胞生物学特性的影响。方法:从新鲜手术切除的GBM标本中,分离、培养及鉴定脑肿瘤干细胞。采用Western blot及RT-PCR法检测WP1193给药后,STAT3信号转导通路的变化。使用神经球形成实验评估WP1193对GBM干细胞形成神经球能力的影响。利用RT-PCR及流式细胞技术检测WP1193对CD133阳性细胞的影响。采用MTS及PI染色结合流式细胞技术检测WP1193对GBM干细胞增殖及细胞周期的影响。采用AnnexinV流式细胞术分析WP1193对GBM干细胞的凋亡诱导效应。结果:WP1193抑制GBM干细胞STAT3磷酸化及下游基因的表达。WP1193有效抑制GBM干细胞形成神经球的能力及增殖,并可将细胞阻滞于G1期。WP1193在体外通过改变Bax/Bcl-2比例诱导GBM干细胞凋亡。结论:WP1193通过抑制STAT3信号转导通路,有效的抑制GBM干细胞的增殖及形成神经球的能力,并能诱导凋亡。STAT3信号转导通路可作为GBM干细胞的治疗靶点。 | 赛克 WK Alfred Yung Fred Lang Waldemar Priebe Howard Colman 陈忠平 | 2009 | 中国神经肿瘤杂志2009，7，3： | 3 |
| 15 | Matching perspective views of a polyhedron using circuits显示文摘 | Gu WK Yang JY Huang TS | 1987 | IEEE Transaction on Pattern Analysis and Machine Intelligence1987，9，3： | 2 |
| 16 | Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer:a randomised phase Ⅲ noninferiority trial显示文摘 | Kang YK Kang WK Shin DB | | Annals of Oncology0，，： | 2 |
| 17 | STAT3信号转导通路抑制剂诱导胶质瘤干细胞产生自噬的研究显示文摘背景与目的:胶质瘤干细胞(glioma stem cell,GSC)在胶质瘤发展及治疗抗拒中发挥重要作用。我们以往的研究表明,新型STAT3信号转导通路抑制剂(STAT3 inhibitor,STI)WP1193能够诱导GSC产生细胞周期阻滞及凋亡。本研究旨在探讨STI是否能在体外诱导GSC产生自噬现象。方法:从手术切除的胶质母细胞瘤中分离及培养GSC。使用STI处理GSC。利用细胞计数法检测STI对GSC增殖的影响。使用Western blot检测自噬相关蛋白LC3的表达情况。吖啶橙染色后,利用荧光显微镜及流式细胞技术检测酸性自噬小体。使用透射电镜检测GSC中自噬小体。结果:STI剂量依赖性的抑制GSC的增殖。STI处理后,GSC中出现LC3表达的切换。STI处理后,GSC中出现自噬小体,且出现自噬小体细胞的比例增加。结论:STI能够在GSC中诱导自噬现象的产生。自噬在STI治疗中的意义及调节机制需要进一步的研究。 | 赛克 WK Alfred Yung Howard Colman Waldemar Priebe 陈忠平 | 2011 | 中国神经肿瘤杂志2011，9，2： | 2 |
| 18 | Interracial differences in prostate cancer progression among patients from the United States, China and Japan显示文摘 | Haiyen E Zhau Qinlong Li Leland WK Chung | 2013 | Asian Journal of Andrology2013，15，6： | 2 |
| 19 | Feasibility and efficacy of routine PCR screening of blood donations for hepatitis virus and HIV-1 in a blood bank setting 显示文摘 | Roth WK Weber M Seifried E | 1999 | Lancet1999，353，9150： | 2 |
| 20 | Selective activation of NF-kappa B subunits in human breast cancer: potential roles for NF-kappa B2/p52 and for Bcl-3显示文摘 | Cogswell PC Guttridge DC Funkhouser WK | 2000 | Oncogene2000，19，9： | 2 |
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