Semantic Caching in Ontology-based Mediator Systems
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第 50 卷第 1 期2024年 1 月吉林大学学报(医学版)Journal of Jilin University(Medicine Edition)Vol.50 No.1Jan.2024DOI:10.13481/j.1671‑587X.20240103PD-L1对人口腔鳞状细胞癌细胞增殖、迁移和侵袭的影响曾洁1, 俞雪燕2, 罗婷3, 徐江1(1. 石河子大学第一附属医院口腔科,新疆石河子832000;2. 石河子大学第一附属医院病理科,新疆石河子832000;3. 新疆维吾尔自治区儿童医院检验科,新疆乌鲁木齐830000)[摘要]目的目的:探讨程序性细胞死亡配体1(PD-L1)在口腔鳞状细胞癌(OSCC)细胞中的表达及其对OSCC CAL27细胞生物学行为的影响,阐明其可能的作用机制。
方法方法:采用Western blotting法检测口腔上皮HOK细胞和OSCC CAL27、TCA8113和SCC15细胞中PD-L1蛋白表达水平。
免疫荧光染色法检测CAL27细胞中PD-L1蛋白表达和定位情况。
将CAL27细胞分为对照组(转染si-NC)和si-PD-L1组(转染si-PD-L1),Western blotting法检测2组细胞干扰效率,CCK-8法检测不同时间点2组细胞增殖活性,平板克隆实验检测2组细胞克隆形成数,细胞划痕愈合实验检测2组细胞划痕愈合率,Transwell小室实验检测2组细胞中迁移和侵袭细胞数。
结果结果:OSCC细胞中PD-L1蛋白表达水平均高于HOK细胞(P<0.05或P<0.01),PD-L1在CAL27细胞的细胞质和细胞核中均有表达。
CCK-8法和平板克隆实验,与对照组比较,不同时间点si-PD-L1组CAL27细胞增殖活性明显降低(P<0.05或P<0.01),克隆形成数明显减少(P<0.01)。
细胞划痕愈合实验,与对照组比较,si-PD-L1组CAL27细胞划痕愈合率明显降低(P<0.05或P<0.01)。
㊃理论探讨㊃作者单位:056001 河北省邯郸市第二医院中医科(王振海);河北工程大学文学院(王蕾)作者简介:王振海(1950-),大专,副主任医师㊂研究方向:天人相应思想理论和中医临床㊂E⁃mail:wang_zhenhai@天人相应是中医学的理论基础和指导思想王振海 王蕾【摘要】 针对有关中医学的理论基础和指导思想存在着 天人相应” 天人合一”和 整体观”表述上的混乱,从 天人相应”一语的语源, 天人相应”与 天人合一”的联系与区别, 天人相应”与整体观,新老中医药专家学者的论证,现代科学的研究,及便于当代理解㊁把握和传承㊁交流等几个方面出发,认为应把中医学的理论基础和指导思想表述为 天人相应”思想㊂【关键词】 中医药学; 理论基础; 天人相应; 天人合一; 天人相分; 黄帝内经; 整体观【中图分类号】 R221 【文献标识码】 A doi:10.3969/j.issn.1674⁃1749.2015.07.012 Correspondence of human body and natural environment ”theory was the theoretical basis and guiding ideology of TCM WANG Zhen⁃hai ,WANG Lei. Department of traditional Chinese medicine of No.2hospital in Handan ,Handan 056001,ChinaCorresponding author :WANG Zhen⁃hai ,E⁃mail :wang_zhenhai@【Abstract 】 This paper concluded that correspondence of human body and natural environment”theory was the theoretical basis and guiding ideology of traditional Chinese medicine (TCM)due to the following reasons:the etymology of correspondence of human body and natural environment”theory,difference and connection between theory of correspondence of human body and natural environment”and theory of man was an integral part of nature”,theory of correspondence of human body and natural envi⁃ronment”and holism,demonstrations of young and old Chinese medicine scholars,modern scientific researches,and the convenience in understanding,inheritance and communication based on the confusionstate of TCM guiding ideology descriptions such as correspondence of human body and natural environment”, man was an integral part of nature”and holism.【Key words 】 Traditional Chinese medicine; Theoretical basis; Correspondence of human bodyand natural environment; Man was an integral part of nature; Separation of nature and man; InnerCanon of Huangdi; Holism 有关中医学的理论基础和指导思想,存在着 整体观” 天人相应”和 天人合一”表述上的混乱㊂表述上的不一致,反映了理论上的不明确㊂而理论上的不明确,必然导致人们对中医认识理解上的困惑㊂笔者认为,应把中医学的理论基础和指导思想表述为天人相应思想㊂1 天人相应的语源‘黄帝内经“没有明确记载 天人合一”一词,而是从生命和医学角度择取㊁倡导了 人与日月相应”人与天地相参”的天人相应思想, 上合于天,下合于地,中合于人事”,经历了 应于人” 验于今”的实践检验,从而为中医学奠定了坚实的理论基础㊂2 天人相应与天人合一的联系与区别2.1 对 天”的含义不同天人合一说的天,有多重含义,众说纷纭㊂有一义说,认为 天”即大自然(季羡林);二义说,认为 天”一指有意志的天神,一指自然的天体(王明);三义说,以张岱年㊁宋志明为代表,张岱年认为 天”一指最高主宰,二指广大自然,三指最高原理㊂宋志明说 天有主宰㊁自然㊁义理三种涵义”;四义说,认为 天”指意志之天㊁无为之天㊁道德之天㊁自然之天(康中乾);五义说,以冯友兰㊁任继愈为代表,冯友兰认为 天”有五义:物质之天㊁主宰之天㊁运命之天㊁自然之天㊁义理之天㊂任继愈也主张 天”有五义:主宰之天㊁运命之天㊁义理之天㊁自然之天㊁人格之天;六义说:天地之天㊁自然之天㊁皇天之天㊁天命之天㊁天道之天㊁天理之天(傅伟勋);混沌说,认为天”是一个混沌概念,神㊁本体㊁本原㊁自然㊁必然㊁命运㊁心性等均在其中(刘泽华),林俊义则根据历史顺序,抽出天有人格神,天象或气象及其规律(天道)㊁天命㊁自然㊁天然㊁天志,群物之祖,天理㊁天性㊁天心㊁天气和宇宙空间等12种涵义[1]㊂而‘黄帝内经“中的天不止包含天象㊁天气㊁气候等,也包含了 地”和环境中的各种因素;既包含直接的 象”,也包含 象”后面所蕴含的 道” 变化的规律,既有 形而下”的,也有 形而上”的[2]㊂也就是说不但包含产生人和对人发生影响的自然之天,也包含了人事社会之天㊂‘上经“曰 夫道者,上知天文,下知地理,中知人事,可以长久 ”(‘素问㊃气交变大论“),人事与天地并列,属于社会意义的天㊂中医学很早就注意到人的社会属性,认为社会环境的优劣或剧烈变化等因素会影响到人体健康,从而把人事社会之天与天地自然之天并列㊂‘素问㊃移精变气论和汤液醪醴论“中,岐伯在回答古人和今世疗效的差别问题时,就强调这是社会之天变了,生活条件和生活方式变了,病情也和古人不一样,所以治疗方法也随着发生变化而疗效还不满意㊂‘素问㊃阴阳应象大论“在谈到 生乃不固”的两个原因时,就指出一是自然之天的方面,一是社会之天 人的方面, 故喜怒伤气,寒暑伤形, 喜怒不节,寒暑过度,生乃不固”,因此在诊治过程中不要忽略 故贵脱势” 始贵后贫”的社会因素㊂2.2 对 人”的含义有别人”的涵义既指单个的人,也指整体的人㊂天人合一说的 人”不是指普通的平民大众,而是大人㊁君子,如‘周易㊃文言“ 夫大人者,与天地合其德”,‘荀子㊃五制“ 故天地生君子,君子礼天地”㊂‘黄帝内经“中的 人”是不带任何社会属性的全体,是普遍意义上的人的总体,全书对人使用的是 民” 万民” 百姓” 众子”这样的概念[3]㊂2.3 目的不同天人合一主要目的不在于关注自然界的规律,而是为寻求现实世界的道德原则和人类政治生活的普遍原则,寻求政治存在的意义,是指君主要遵守天道,效法天道,体道而治㊂如‘吕氏春秋㊃圜道“ 天道圜,地道方,圣王法之,所以立上下 主执圜,臣执方,方圜不易,其国乃昌”㊂‘黄帝内经“天人相应思想的目的是为了寻求掌握自然规律以及研究天人相应规律和运用天人相应规律为人类健康服务,为人类寻找更适当的生存生活方式和防治疾病的原则与方法㊂‘素问㊃金匮真言论“指出 所以欲知阴中之阴阳中之阳者何也?为冬病在阴,夏病在阳, 皆视其所在,为施针石也”,‘素问㊃阴阳应象大论“更指出 故治不法天之纪,不用地之理,则灾害至矣”㊂2.4 内涵不同古人对天人关系的探索经历了漫长的历程, 天人合一”包含了诸如 天人合德” 天人相分” 天人相通” 天人感应” 天人相应” 天人不相预” 天人交相胜” 天人合一” 天人同性” 天人同体” 天人同类” 天人一气” 天人一心” 天人一理”等多种学说,概括起来可归约为 天人相分” 天人相应” 天人合一”三类㊂ 天人合一”观念,其本义并非直接讨论人与自然的关系,虽然 天人合一”的理论也涉及人与自然生态的关系,但这种关系是以政治㊁伦理和精神境界为本位的㊂ 天人合一”理论所关注的重点,更多体现在其社会㊁政治㊁道德㊁伦理㊁价值㊁认识论㊁人格修养方面的意义[4]㊂ 夫礼,天之经,地之义也”(‘左传㊃昭公二十五年“), 诚者天道也,诚之者人之道也”(‘中庸㊃十九章“),天人合一说把礼㊁性㊁德㊁诚提高到天的地位,然后反过来要人去合天,只是为了说明人类社会道德原则的客观性㊁天道性㊂面对天人关系的诸多提法,‘黄帝内经“从生命和医学角度择取㊁倡导并发挥了 人与日月相应” 人与天地相参”的天人相应思想㊂天人相应思想既承认天与人的区别,又承认天与人的联系,同时还认为 参’是相互的,人法天地而也可以参赞造化”[5]㊂天的变化影响着人,人又通过自身的活动影响着天[6]㊂既包含了 天人相分”区分主客的内涵,而不致听其走向片面和极端;另一方面又把 天人合一”所体现的社会㊁政治㊁道德㊁伦理㊁价值㊁认识论㊁人格修养方面的意义及孜孜以求的最高精神境界,包摄在天人相应思想中而不致使其流于玄远㊂天人合一追求的是最高精神境界,天人相应注重的是客观自然规律㊂天人合一反映的是理想状态,天人相应反映的是现实状态㊂因此, 天人相应”显然要比 天人合一”更明白更确切地反映了天人关系㊂2.5 ‘黄帝内经“继承发展了天人相应相参思想天人相应相参说在先秦诸子著作中是零散的,范蠡㊁子思㊁荀子都提到了天人相参相应,但都没有展开论述,形成系统㊂如 夫人事必将与天地相参,然后可以成功”(‘左传㊃国语“); 唯天下之至诚,为能尽其性; 能尽物之性,则可以赞天地之化育;可以赞天地之化育,则可以与天地参矣”(‘中庸㊃第二十一章“); 故天地生君子,君子礼天地,君子者,天地之参也 ”(‘荀子㊃五制“); 天行,有常 故应之以治则吉,应之以乱则凶”(‘荀子㊃天论“)㊂面对天人关系的诸多提法,‘黄帝内经“注重的不是抽象的论辩,而是如何运用天人相应思想处理实际问题㊂‘黄帝内经“继承发展了天人相应相参思想,并将之系统化㊂‘黄帝内经“以天人相应相参思想为指导,融汇诸子各家学说,对成书之前的医学资料和各家学说进行了全面整理和继承,构建了一个贯通天地人的理论体系㊂3 天人相应与整体观对中医学理论体系的理解,长期以来一般是以整体观和辨证论治来加以概括㊂这显然难以涵盖和体现这一体系的丰富内涵㊁内在联系及其特色,也就难以具体有效地指导临床㊁科研和教学[7]㊂通常认为,一个科学理论体系,起码包括作为体系基本元素的基本概念,和联系这些基本概念的基本关系做出的推论㊂天人相应理论的基本概念就是 天” 人”㊂ 人”包括个体的人和群体的人㊂人类生活在地球上,吃穿行住产生的社会关系,及社会环境与自然环境构成了从单个人到群体人生活在其中的天㊂每个人对他自己来说是人,相对于另一个人来讲又属于天㊂毫无疑问,人作为一个独立的实体,有着自己生命运动变化的轨迹,但人是 天”的产物和组成部分,所以生命运动变化的轨迹必然要服从㊁受控于 天”运动变化的规律㊂天的变化产生和影响着人,人又通过自身的活动影响着天,天人之间相互作用,人天相应,这就是天人之间的基本关系[6]㊂可以看出,中医整体观主要包括的三个方面:人体本身是一个有机整体;人与自然环境是一个有机整体;人与社会环境是一个有机整体,归根到底依然是 天”(自然环境和社会环境) 人”两个概念,也就自然而然包括在天人相应思想理论中㊂事实上,中医整体观就是从‘黄帝内经“关于天人相应的论述中概括出来的,是建立在天人相应思想方法基础上的㊂天人相应思想理论提供了天人相应的思想方法[8]㊂医学就是伴随着对天的认识㊁对人的认识和对天人关系的认识而发展的㊂天人相应思想方法不仅指导古人创建了中医理论体系,同样可以指导今人,像复杂性理论㊁系统论㊁控制论㊁模糊理论㊁信息论㊁全息论㊁协同论就可以运用于医学领域,用来阐明对人的认识㊂同样,自然科学的方法㊁社会科学的方法㊁数学的方法㊁观察的方法㊁实验的方法㊁逻辑的方法㊁猜想的方法㊁理性思维的方法㊁非理性思维的方法等,都可以用来研究人及其健康与疾病问题㊂显而易见,天人相应方法论不仅包含了整体观的方法,还包含了其它方法,从而体现出开放性㊁包容性和与时消息性㊂4 新老中医药专家学者的论证老一代中医药专家早就指出了天人相应思想在中医学中的理论基础地位这个问题㊂ 气或精气学说,阴阳学说,都以天人相应思想为基础”(岳美中),天人相应思想是 中医学理论的渊源所在”,是 贯穿整个‘内经“的指导思想”(方药中),是‘内经“理论的精髓, 中医学中的阴阳学说㊁五行学说㊁藏象学说㊁经络学说㊁精气神学说㊁运气学说等,几乎无不根据天人相参的原理而阐明其所具有的规律性”(裘沛然),是 贯穿整个中医学理论和临床的最核心㊁最根本的思想”(陆干甫㊁谢永新)㊂新一代中医药学者通过对‘内经“及其时代,对中医基础理论,对天人相应思想的深入研究,进一步明确了‘内经“体系的最重要的逻辑起点是天人相应,‘内经“体系,主要是天人相应的体系[9]㊂中医理论要还其本原 人与天地相参[10],认为天人相应思想不仅仅是传统中医学的理论基础,也应该成为现代医学的理论基础[6]㊂5 现代科学的研究一种生物生存在什么条件下,是环境因子综合作用的结果,也是生物适应的结果,生物的进化过程也就是天人相应的过程㊂从人类基因组计划到克隆羊,从生态学到微生态学,从宇宙飞船载人航天飞行到蛟龙号深潜,天人相应思想经过了现代科学从宏观㊁中观㊁微观以至宇观的检验,证明了天人相应的正确性和科学性[6,8,11⁃13]㊂天人相应不仅是中医学关于天人关系的基本看法,而且是生物界的一条基本规律㊂要想真正认识人类本身与人类疾病,就必须把人与其生活在其中的天联系在一起㊂因此,把天人相应思想作为医学的理论基础,也是逻辑的必然㊂6摇便于当代理解把握和传承交流如何完善中医学理论体系的框架结构,建立与中医学理论体系的丰富内涵相适应,便于当代理解㊁把握㊁传承㊁交流的理论框架与结构,是中医学理论继承与创新的重要课题[14⁃15]㊂而明确了天人相应思想的理论基础地位,就理顺了中医体系的逻辑结构,这就是:用对天的认识说明对人的认识;用认识天的方法去认识人;从人和天的相互关系中去研究人;研究天人相应规律和运用天人相应规律[8]㊂同时,也就明确了中医体系 道㊁理㊁法㊁术”四个层次结构㊂ 道”就是中医学的理论基础 天人相应思想㊂ 理”属于第二层次 在天人相应思想的指导下,综合对天的认识,对人的认识,形成适用于预防㊁诊断㊁治疗各方面的基础理论,如气血津液㊁阴阳五行㊁升降出入㊁藏象经络㊁寒热虚实等㊂ 法”属于第三层次,是用基础理论研究具体的天与具体的人相互作用产生相应变化的规律,总结归纳形成如六淫辨证㊁伤寒辨证㊁温病辨证㊁杂病辨证㊁摄生㊁经络㊁以及 汗吐下和温清消补”等的临床应用理论㊂ 术”是第四个层次,就是在以上基础上产生的对某一具体病种㊁证治㊁药物㊁方法提出的具体的理论见解和治疗方法,如伤寒护阳,温病存阴等㊂正因为中医理论是用天人相应思想方法建构起来的,随着对天的认识,对人的认识的发展和深入,对养生及疾病防治实践经验的积累和总结,中医理论不但可以根据时代和需要对原有理论进行部分的修正和改造,补充和发展,还可以在条件具备的时候,以现代自然观㊁宇宙观为参照系,用天人相应思想方法建构起新的理论大厦㊂也就是说,天人相应思想使中医理论具备自我更新的内动力㊂天人相应思想既为理解㊁把握和传承交流中医理论提供了方法,也为中医走向世界打开了方便之门㊂笔者相信,只要从天人相应思想出发,就如高屋建瓴,一通百通[16],从而应对和解决中医学面临的困惑㊁危机和挑战㊂参考文献[1] 林俊义.从中国传统哲学中的 天人合一论”,寻觅 自然与人的和谐”[J].自然辩证法研究,2000,16(9):4⁃8. [2] 杨光.正确看待 天人相应”[N].中国中医药报,2010⁃05⁃05(8).[3] 申咏秋,鲁兆麟.‘黄帝内经“的医学人文精神探析[J].中国医学伦理学,2006,19(6):108⁃109.[4] 耿云志.近代文化与儒学[N].人民日报,1988⁃03⁃21(5).[5] 裘沛然.裘沛然选集[M].上海:世纪出版集团上海辞书出版社,2004:180⁃184.[6] 淮辉先,王振海.试论天人相应思想的科学性[J].中国医药学报,1988,3(1):9⁃13.[7] 许家松.把根留住 继往开来 中医理论现代发展战略研究之我见[N].中国中医药报,2004⁃09⁃13(3). [8] 王振海,淮辉先.从‘黄帝内经“谈天人相应思想的方法论[J].中国医药学报,1998,13(3):20⁃23.[9] 赵洪均.内经时代[M].北京:学苑出版社,2012:293.[10] 张效霞.回归中医 对中医基础理论的重新认识[M].青岛:青岛出版社,2006:57.[11] 周鹏,高学敏,张建军,等.从中医天人相应理论看人体太空生理紊乱[J].中华中医药杂志,2008,23(6):472⁃475. [12] 刘焕兰,谈博.天人相应理论的发展及其意义[J].广州中医药大学学报,2010,27(4):407⁃410.[13] 熊德鑫.微生态学研究的重要意义和实际应用[J].中国微生态学杂志,2001,13(5):252⁃253.[14] 潘桂娟.中医学理论体系框架结构之研讨[J].中国中医基础医学杂志,2005,11(7):481⁃483.[15] 王耘,颜素容,乔延江.中医理论建模的天人相应形式化方法[J].北京中医药大学学报,2009,32(7):437⁃439. [16] 王振海,王蕾.高屋建瓴 一通百通 关于天人相应思想研究问答[J].按摩与康复医学,2011,27(60):181⁃183.(收稿日期:2015⁃04⁃22)(本文编辑:董历华)。
第十八章流行病学与循证医学循证医学(evidence-based medicine)可以说是20世纪90年代以来医学界最炙手可热的话题,媒体称它为一项震荡世界的构想,一场发生在医学实践里的革命,正如抗生素的发现对医学的冲击一样,循证医学正在彻底改变着沿袭千古的医学实践模式。
20世纪中叶诞生的现代流行病学及其以后几十年的发展、成熟、应用和取得的成果,是这场变革的原始动因。
如果说DNA结构的发现揭开了生命最深的奥秘,那么流行病学给研究医学实践中的各种问题提供了科学方法论,而循证医学则引发了一场医学实践模式的革命。
流行病学与循证医学息息相关。
如果说流行病学是一种研究方法论,循证医学则是关于如何利用流行病学研究结果进行医学实践与决策的学问。
本章将首先回顾从现代流行病学到循证医学的发展轨迹,然后简单介绍循证医学的概念、范畴、意义、方法,以及发展循证医学需要的文化和基础建设,并对循证医学时代流行病学在医学教育、科学研究和医疗卫生实践中的地位和作用进行探索性的讨论。
教科书的目的是介绍一个领域的知识、原理、方法和技能。
然而,在知识飞速更新和世界互联网高速传播信息的今天,一本教科书的使用寿命也变得越来越短。
因此,本章也希望通过对历史的回顾和未来的展望,为读者打开一个更宽广的视窗,使读者在学好基本知识的同时,能够体味科学变革的重要性和必然性,用发展的眼光看待流行病学这门科学,不断跟上知识更新的步伐。
本章还采用一种鲜明的个性化的分析和讨论,希望能鼓励一种敢于怀疑知识和勇于独立思考的精神。
歌德说:“怀疑随知识的增加而增加”。
任何知识都是不完善的,怀疑是一种必然,怀疑也是一种必要,怀疑是新知识产生的开端,而独立思考正是怀疑的开端。
另外,循证医学作为一个新生事物,它的内涵和外延还在不断发展和完善,因此,我们也希望读者能够以发展的眼光看待循证医学,把握甚至主动地影响它的发展,而不是简单地学习一些僵硬的概念和技能。
第一节从流行病学到循证医学一、早期的流行病学探索(一)流行病学产生和发展的背景直到20世纪,威胁人类健康和生命的主要疾病是传染性疾病,如天花,鼠疫和霍乱,它们是造成人类死亡的主要病因。
头颈部鳞癌的研究趋势及新进展张洪瑞,苏本香,庞艳,孙月茹呼伦贝尔职业技术学院口腔教研室,内蒙古呼伦贝尔021000[摘要]头颈部鳞癌(Head and Neck Squamous Cell Carcinoma, HNSCC)为发生于口腔、咽、喉黏膜上皮的鳞癌,吸烟、酗酒与促进口腔及喉部鳞癌形成存在相关性,咽部鳞癌与人类乳头状瘤病毒感染有关。
头颈部鳞癌有多种治疗方式,特别是以分子靶向治疗为代表的药物治疗快速发展。
本文具体探讨与分析了头颈部鳞癌的流行病学状况,阐述了头颈部鳞癌的形成机制,综述了头颈部鳞癌的分子靶向治疗进展:西妥昔单抗、免疫检查点分子抑制剂、贝伐珠单抗。
[关键词]头颈部鳞癌;分子靶向治疗;免疫检查点分子抑制剂;贝伐珠单抗;西妥昔单抗[中图分类号]R739.91 [文献标识码]A [文章编号]2096-1782(2024)01(b)-0194-05 Research Trends and New Advances in Head and Neck Squamous Cell CarcinomaZHANG Hongrui, SU Benxiang, PANG Yan, SUN YueruStomatology Department, Hulunbuir Vocational Technical College, Hulunbuir, Inner Mongolia Autonomous Region, 021000 China[Abstract] Head and neck squamous cell carcinoma (HNSCC) is a squamous carcinoma that occurs in the mucosal epithelium of the oral cavity, pharynx and larynx. Smoking and alcohol abuse are associated with the formation of squa‐mous carcinoma of the oral cavity and larynx, and squamous cell carcinoma of the pharynx is associated with human papillomavirus infection. There are various treatment modalities for head and neck squamous cell carcinoma, espe‐cially the rapid development of drug therapy represented by molecular targeted therapy. This article specifically dis‐cusses and analyzes the epidemiological status of head and neck squamous cell carcinoma, describes the formation mechanism of head and neck squamous cell carcinoma, and reviews the progress of molecular targeted therapy for head and neck squamous cell carcinoma: cetuximab, immune checkpoint molecular inhibitors, and bevacizumab. [Key words] Head and neck squamous cell carcinoma; Molecular targeted therapy; Immune checkpoint molecular inhibitors; Bevacizumab; Cetuximab头颈部鳞癌(Head and Neck Squamous Cell Car‐cinoma, HNSCC)是一组起源于口腔、咽、喉的鳞状上皮细胞的异质性肿瘤,当前其发病率逐年增加,且病死率一直居高不下[1]。
血清残余胆固醇水平对冠心病的影响及临床意义陈翠1,2,杨莉婷3,唐陶1,2,徐浩2,刘茂41.川北医学院附属医院遗传与产前诊断中心,四川南充637000;2.川北医学院检验医学院,四川南充637000;3.南充市中心医院检验科,四川南充637000;4.川北医学院附属医院心血管内科,四川南充637000【摘要】目的探讨血清残余胆固醇(RC)水平对冠心病的影响及其临床意义。
方法回顾性分析2019年6月至2020年6月因胸闷胸痛于川北医学院附属医院心内科住院行冠脉造影检查的230例患者的临床资料,根据冠脉造影结果分为冠心病组190例和非冠心病组40例(CON 组),根据临床诊断标准又将冠心病患者分为稳定性心绞痛组(SAP 组)70例和急性冠脉综合征组(ACS 组)120例。
比较三组患者的一般资料和RC 水平,采用Spearman 秩相关分析RC 水平与Gensini 评分的相关性,采用多因素Logistic 回归分析影响冠心病发生的风险因素,绘制受试者工作特征曲线(ROC)分析RC 对冠心病发生的预测价值。
结果ACS 组、SAP 组和CON 组患者的性别、年龄、吸烟史、高血压史、LP(a)比较差异均无统计学意义(P >0.05),但ACS 组和SAP 组患者的总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A (ApoA)、载脂蛋白B (ApoB)水平明显高于CON 组,而高密度脂蛋白胆固醇(HDL-C)水平明显低于CON 组,且ACS 组患者的TC 、LDL-C 、ApoB 水平明显高于SAP 组,差异均有统计学意义(P <0.05);ACS 组和SAP 组患者的RC 水平分别为(0.98±0.37)mmol/L 、(0.86±0.23)mmol/L ,明显高于CON 组的(0.68±0.16)mmol/L ,且ACS 组的RC 水平明显高于SAP 组,差异均具有统计学意义(P <0.05);经Spearman 秩相关分析结果显示,RC 水平与Gensini 评分呈正相关(P <0.05);经多因素Logistic 回归分析结果显示,年龄、吸烟、RC 、LDL-C 、ApoA 为冠心病的独立危险因素(P <0.05);经ROC 分析结果显示,血清RC 预测冠心病发生的曲线下面积(AUC)为0.755,灵敏性和特异性分别为53.20%和87.50%。
机械专业论⽂参考⽂献机械专业论⽂参考⽂献 参考⽂献要注意精选国内外的最新的相关⽂献,按顺序编码制组织,即各篇⽂献要按正⽂标注的序号依次列表于⽂后。
以下是yjbys⼩编为您整理的机械专业论⽂参考⽂献,希望能提供帮助。
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Semantic Caching in Ontology-based Mediator SystemsMarcel Karnstedtmarcel@ University of Halle-Wittenberg 06099Halle/Saale,Germany Kai-Uwe Sattler Ingolf Geist Hagen Höpfner∗{kus|geist|hoepfner}@iti.cs.uni-magdeburg.deUniversity of MagdeburgP.O.Box4120,39016Magdeburg,GermanyAbstract:The integration of heterogenous web sources is still a big challenge.Oneapproach to deal with integration problems is the usage of domain knowledge in formof vocabularies or ontologies during the integration(mapping of source data)as wellas during query processing.However,such an ontology-based mediator system stillhave to overcome performance issues because of high communication costs to thelocal sources.Therefore,a global cache can reduce the response time significantly.In this work we describe the semantic cache of the ontology-based mediator systemY ACOB.In this approach the cache entries are organized by semantic regions and thecache itself is tightly coupled with the ontology on the concept level.Furthermore,thecache-based query processing is shown as well as the advantages of the global conceptschema in the creation of complementary queries.1IntroductionMany autonomous,heterogeneous data sources exists in the Web on various topics.Pro-viding an integrated view to the data of such sources is still big challenge.In this scenario several problems arise because of autonomy and heterogeneity of the sources as well as scalability and adaptability with regard to a great number of–possibly changing–data sources.Approaches to overcome these issues are for instance metasearch engines,ma-terialized approaches and mediator systems,which answer queries on a global schema by decomposing them,forwarding the sub-queries to the source systems and combining the results to a global answer.First generation mediators achieve integration mainly on a structural level,i.e.data from different sources are combined based on structural cor-respondences,e.g.the existence of common classes and attributes.Newer approaches of mediators use semantic information,such as vocabularies,concepts hierarchies or ontolo-gies to integrate different sources.In this paper,we use the Y ACOB mediator system which uses domain knowledge modeled as concepts as well as their properties and relationships. The system supports the mapping of the data from the local sources to a global concept schema.The semantic information are not only used to overcome the problems resulting from heterogeneity and autonomy of the different sources but also during query processing and optimization.However,response times and scalability are still problems because of high communication ∗Research supported by the DFG under grant SA782/3-2costs to the local sources.One approach to reduce the response times and improve the scal-ability of the system is the introduction of a cache which holds results of previous queries. Thus,queries can be answered(partially)from the cache saving communication costs. As page or tuple based cache organizations are not useful in distributed,heterogeneous environments,the Y ACOB mediator supports a semantic cache,i.e.,the cache entries are identified by queries that generated them.This approach promises to be particularly useful because of the typical behavior of the user during the search:starting with afirst,relatively inexact query the users want to get an overview of the contained objects.Subsequently, the user iteratively refines the query by adding conjuncts or disjuncts to the original query. Therefore,it is very likely that a cache contains a(partial)data set to answer the refined query.The contribution of this paper is the description of the caching component of the Y ACOB mediator.We discuss different possibilities of the organization of cache according to the ontology model as well as the retrieval of matching cache entries based on a modified query containment determination.Furthermore,the paper shows the generation of com-plementary queries using the global concept model as well as the efficient inclusion of the cache into the query processing.The remainder of the paper is structured as following:Section2gives a brief overview of the Y ACOB mediator system and its data model and query processing.In Section3the structure of the cache as well as replacement strategies and cache management with help of semantic regions is described.The query processing based on the cache is discussed in Section4.After a comparison with the related work in Section5we conclude the paper with some preliminary performance results and give an outlook to our future work in Section6.2The Y ACOB Mediator SystemThe Y ACOB mediator is a system that uses explicitly modeled domain knowledge for in-tegrating heterogeneous data from the Web.Domain knowledge is represented in terms of concepts,properties and relationships.Here,concepts act as terminological anchors for the integration beyond structural aspects.One of the scenarios where Y ACOB is applicable and for which it was originally developed is the(virtual)integrated access to Web databases on cultural assets that where lost or stolen during World War II.Examples of such databases–which are in fact integrated by our system–are www.lostart.de,www.herkomstgezocht.nl and www.restitution-art.cz.The overall architecture of the system is shown in Fig.1.The sources are connected via wrappers which process simple XPath query(e.g.,by translating them according the proprietary query interface of the source)and return the result as an XML document of an arbitrary DTD.The mediator accesses the wrappers using services from the access component which for-wards XPath queries via SOAP to the wrappers.The wrappers work as Web services and therefore can be placed at the mediator’s site,at the source’s site,or at a third place.An-Figure1:Architecture of the Y ACOB mediatorother part of the access component is the semantic cache which stores results of queries in a local database and in this way allow to use it for answering subsequent queries.This part of the system is subject of this paper and described in the following sections.Fur-ther components are the concept management component providing services for storing and retrieving metadata(concepts as well as their mapping)in terms of a RDF graph, the query planning and execution component which processes global queries as well as the transformation component responsible for transforming result data retrieved from the sources according the global schema.Architecture and implementation of this system are described in[SGHS03].Thus,we omit further details.Exploiting domain knowledge in a data integration system requires ways for modeling this knowledge and for relating concepts to source data.For this purpose,we use a two-level model in our approach:the instance level comprises the data managed by the sources and is represented using XML,the metadata or concept level describes the semantics of the data and is based on RDF Schema(RDFS).Here,we provide•concepts which are classes in the sense of RDFS and for which extensions(set of instances)are available in the sources,•properties(attributes)of concepts,•relationships which are modeled as properties,too,•as well as categories which represent abstract property values used for semantic grouping of objects.These primitives are used for annotating local schemas,i.e.,mappings between the global concept level and the local schema are specified in a Local-as-View manner[SGHS03].In this way,a source supports a certain concept,if it provides a subset of the extension (either with all properties or only with a subset).For each supporting concept,a source mapping specified the local element and an optionalfilter restricting the instance set.Such a mapping is used both for rewriting queries as well as transforming source data in the transformation component.In the Y ACOB mediator queries are formulate in CQuery–an extension of XQuery. CQuery provides additional operators applicable to the concept level such as selecting concepts,traversing relationships,computing the transitive closure etc.as well as for ob-taining the extension of a concept.Concept-level operators are processed always at the global mediator level,whereas instance-level operators(filter,join,set operations)can be performed both in the mediator as well as by the source.For a detailed description of CQuery we refer again to[SGHS03,SGS03].For the remainder of this paper,it is only important to know that a global CQuery is rewritten and decomposed into several source queries in the form of XPath expressions which can be delegated to the sources via the wrappers.Because we are aware that for the average user of our application domain(historians, lawyers etc.)CQuery is much too complex,we hide the query language behind a graphical Web user interface combining browsing and structured querying.The browsing approach implements a navigation along the relationships(e.g.subClass)and properties defined in the concept level.The user can pick concepts and categories in order to refine the search. In each step the defined properties are presented as inputfields allowing to specify search values for exact and fuzzy matching.From the discussion of the architecture as well as the user interface the necessity of a cache should be obviously:•First,accessing sources over the Web and encapsulating sources using wrappers(i.e.translating queries and extracting data from HTML pages)result in poor per-formance compared to processing queries in a local DBMS.•Second,a user interface paradigm involving browsing allows to refine queries.That means,the user can restrict a query by removing queried concepts or by conjunc-tively adding predicates and he/she can expand a query by adding concepts or by disjunctively adding predicates.In thefirst case,the restricted query could be com-pletely answered from the cache(assuming the result of the initial query was already added to the cache).In the latter case,at least portions of the query can be answered from the cache and quickly presented to the user,but additional complementary queries have to executed retrieving the remaining data from the sources.Based on these observations,we will present in the following our caching approach that uses concepts of the domain model as anchor points for cache items and exploits–to a certain degree–domain knowledge for determining complementary queries.3Cache ManagementThe cache is designed to store result data,which is received as XML documents,and the corresponding queries,which are the semantic description of those results.If a new query arrives it has to be matched against the cached queries and possibly a(partial)result has to be extracted from the cache’s physical storage(see Section4).In order to realize the assumed behavior a simple and effective way of storing XML data persistently and fail-safe is needed.One way of storing is the usage of a native XML database solution which is Apache’s X INDICE in this work.The open source database X INDICE stores XML documents into containers called collections.These collections are organized hierarchically,comparable to the organization of folders in afile system.The cache is placed below the ontology level,which means the cached entries are collected regarding to the queried concepts.All entries corresponding to a concept are stored in a collection named after that concept’s name.The actual data is stored as it is received from the sources in a sub-collection“results”,the describing data,namely the calculated “ranges”(see Section4),the query string decomposed to the single sub-goals and a ref-erence to the corresponding result document,are stored in another sub-collection called “entries”(Fig.2(a)).During query matching the XML encoded entries are read from the database and the match type for the currently handled query is determined.If an entry matches,a part of or the whole result document is added to the global result data.If only a part of the cached result is needed,i.e.if the two queries overlap in some way,the part corresponding to the processed query has to be extracted.Here another advantage of using a native XML database becomes apparent:X INDICE supports XPath as its query language. In order to retrieve the required data we simply have to execute the current query against the data of the entry.An important decision is the level of caching:we can store query results either at con-cept level or at source level.The difference is the form of the queries and correspond-ing result documents.Caching at concept level means caching queries formulated at the global schema.The queries will be transformed according to the local source schemas after processing them in the cache.The retrieved result documents stored to the cache are already transformed back to the global schema,too.Caching at source level is placed below of the transformation component.There are sep-arate entries for each source,because the stored queries and results are formulated in the specific schema of a source.An evident advantage of the source level cache is thefiner granularity of the cached items,e.g.enabling the detection of temporarily offline sources by the cache manager.The main disadvantages–which are the benefits of using concept level caching–are the increased management overhead because of the rising amount of entries and a loss of performance at cache hit.Caching at concept level does not require any transformations at cache hit:the result is returned immediately.Additionally,a query matching making use of the global ontology,including a smart way of building a comple-mentary query,is supported.Fig.2(b)shows a part of the global ontology together with an associated cache entry.This entry is created by executing the following query and storing the result in the cache://Graphics[Artist=’van Gogh’and Motif=’People’](a)Cache entry(b)Cache structure Figure2:Structure of the semantic cacheUsing a storage strategy as described above,the cached data is grouped together into se-mantically related sets called semantic regions.Every cache entry represents one semantic region,where the sub-goals of the predicate are conjunctive expressions.Disjunctive parts of a query get an own entry.The containment of a query is decided between the cached entries and every single conjunction of the disjunctive normal form of the query pred-icate.The decision algorithm is explained in detail in Section4.The regions have to be disjoint,so each cached item is associated with exactly one semantic region.This is useful for getting a maximum of cached data when processing a query,in contrast other works let the regions overlap and avoid data redundancy using reference counters ([LC98,LC99,LC01,KB96]).There arise certain problems and open questions if the re-gions have to be disjoint and are forbidden to overlap.Different strategies are possible if a processed query overlaps with a cached query,more exactly their result sets are overlap-ping.In this case,the part of the result data already stored in the cache is extracted and a corresponding complementary query is sent to the sources.The data received as result of this query and the data found in cache form a large semantic region.Now,it have to be decided whether keeping this region or splitting it or coalescing the separate parts in some way.Because putting all data in one region will result in bad granularity and lead to stor-age usage problems,the regions are stored separately.There are still some remaining ways of how to split/coalesce the single parts,all effecting the query answering mechanism and possible replacement strategies.In our approach the data for the complementary query forms a new semantic region and is inserted into the cache(inclusive the query representing the semantic description).Here, the semantic region holding the cached part of the result data is unchanged.Another possi-ble way is to collect cached data and send the original query instead of the complementary query to the sources.The last approach is useful in the case,that matching all cached en-tries to a processed query results in a complementary query which causes multiple source queries or which is simply not answerable at all,e.g.due to unsupported operations such as“<>”.Details of building a complementary query and related issues are described inSection 4.In order to keep the semantic regions disjunct,it is important to store only that part in the cache which corresponds to the complementary query created before.Both ways guarantee that the semantic regions do not overlap,which is one of the formu-lated constraints to the cache.Collecting the data in such disjoint regions allows a simple replacement strategy:replacement on region level,i.e.if a region has to be replaced,its complete represented data is deleted from the physical storage.This replacement strategy requires the following cache characteristics:At first,the cached regions may not be too large.On the one hand,replacing large regions means deleting a big part of the cached data and results into inefficient storage usage.On the other hand,a large amount of relatively small semantic regions leads to bad performance of the query processing.Small regions may enable a replacement based on a much finer granularity,but the cost of query process-ing will rise,because many regions have to be considered.Additionally,complementary queries will become very complex and last but not least because small regions mean long query strings that have to be combined when creating the complementary query.Currently,our implemented replacement strategy is very simple.Timestamps referring to the date of collection and last reference are kept enabling a replacement strategy based on the age and referencing frequency of a cached entry.Entries are removed from the cache together with the corresponding result data,if either its cache holding time expires or if an entry has to be replaced in order to make room for a new entry.Other conceivable strategies could make use of some kind of semantic distance (like in [DFJ +96])or other locality aspects.The timestamp strategy is sufficient for the Y ACOB mediator system because the main concern is to support an efficient interactive query refinement by the cache.(Dis-)advantages of other strategies have to be the subject of future work.4Cache-based Query AnsweringCache lookup is an integral part of the query processing approach used in the Y ACOB mediator.Thus,we will sketch in the following first the overall process before describing the cache lookup procedure.In general,a query in CQuery consists of two kind of expressions:a concept level expres-sion CExpr for computing a set of concepts,e.g.by specifying certain concepts,apply filter,traversal or set operations and an instance level expression IExpr(c )consisting of operators such as selection which are applied to the extension of each concept c com-puted with CExpr .The results of the evaluation of IExpr(c )for each c are combined by a union operator,which we denote extensional union .Thus,we can formulate a query as follows: c ∈CExpr IExpr (c ).For example,in the following query:FOR $c IN concept[name=’Paintings’]LET $e :=extension($c)WHERE $e/artist =’van Gogh’RETURN <picture><title>$e/title</title><artist_name>$e/artist</artist_name></picture>CExpr corresponds to the FOR clause and IExpr corresponds to the WHERE clause.If a query contains additional instance level operators involving more than one extension (e.g.a join)these are applied afterwards but are not considered here because they are not affected by the caching approach.Based on this,a query is processed as follows.The first step is the evaluation of the concept level expression.For each of the selected concept we try to answer the instance level expression by first translating it into an XPath query and applying this to the extension.Basically,this means to send the XPath query to the source system.However,using the cache we can try to answer the query from the cache.For this purpose,the function cache-lookup returns a (possibly partial)result set satisfying the query condition,i.e.,if necessary additional filter operations are applied to the stored cache entries,as well as a (possibly empty)complementary XPath query.In case of an non-empty complementary query or if no cache entry was found,the XPath query is further processed by translating it according to the concept mapping CM (c )and send this translated query to the corresponding source s .Finally,the results of calling cache-lookup and/or process-source-query are combined.Input :query expression in the form of U c ∈CExpr IExpr (c )result set R :={}1compute concept set C :=CExpr2forall c ∈C do3/*translate query into XPath */4q :=toXPath (IExpr (c ))5/*look for the query q in the cache →result is denoted by R c ,6q is returned as complementary query for q */7R c :=cache-lookup (q,q )8if R c ={}then9/*found cache entry */10R :=R U R c11q :=q12fi13if q =empty then14q s :=translate-for-source (q ,CM (c ))15R s :=process-source-query (q s ,s )16R :=R U R s17fi18odFigure 3:Steps of Query ProcessingNote that in this context complementary queries are derived at two points:•First,because a global query is decomposed into a set of single concept related queries,complementary queries are derived implicitly.This means,if one wants to retrieve in query q the extension ext (c )of a concept c with two sub-concepts c 1and c 2where it holds ext (c )=ext (c 1)∪ext (c 2)and ext (c 1)is already stored in thematch type situation cached part of complementary(Q,C)result data queryexact data to Q and C identical C’s data nonecontaining C containing Q Q on C’s data nonecontained C contained in Q C’s data Q∧¬Coverlapping data to C and Q overlaps Q on C’s data Q∧¬Cdisjoint C’s data is no part of result data none Q Table1:Possible match types between processed query Q and cached entry C cache,two queries q1(for ext(c1))and q2(for ext(c2))have to be processed.How-ever,because we can answer q1from the cache,only the complementary query q2 needs to be executed(i.e.,q2=q),which is achieved by iterating over all concepts of the set C(line2).•Secondly,if the cache holds only a subset of ext(c1)restricted by a certain predicate p we have to determine q1with¬p during the cache lookup.Because thefirst issue is handled as part of the query decomposition,we focus in the following only on cache lookup.We will use the example started in Section3to picture this step.Let us assume,we are in a very early(almost starting)state of the cache,where the query//Graphics[Artist=’van Gogh’and Motif=’People’]is the only stored query referencing the resultfile data.xml.Now,the new query has to be processed://Graphics[(Artist=’van Gogh’or Artist=’Monet’)and Date=’1600’] During the cache lookup every conjunction found in the disjunctive normal form of the processed query is matched against each cache entry in no special order.As mentioned in Section3the semantic regions do not overlap.Thus,independent from the order of processing cache entries,all available parts of the result can be found in cache.In other words,if an entry contains a part of the queried data no other one will contain this data, e.g.if an exact match to the query exists,there will be no other containing match and the exact match will be detected independent of any entries observed before.There arefive possible match types that may occur which are summarized in Tbl.1.The match types are listed top down in the order of their quality.Obviously,the exact match is the best one,because the query can be answered simply by returning the all data of the entry.If no exact match can be found,a containing match would be the next best. In this case,a superset of the needed data is cached and can be extracted by applying the processed query Q to the cached documents.The cases of contained and disjoint match type require to process a complementary query.Only a portion of the required data is stored and the complementary query retrieves the remaining part from the source. Considering our example the disjunctive normal form of the new query is://Graphics[(Artist=’van Gogh’and Date=’1600’)or(Artist=’Monet’and Date=’1600’)]The two parts in brackets are the conjunctions we have to handle separately during the cache lookup.The algorithm in Fig.4displays the procedure of cache lookup in pseudo code.Input:Query qOutput:result set R:={}complementary query q:=1q =disjunctive-normal-form(q);2E=get-cache-entries(get-concept(q));5forall conjunction Conj of q do6CC={Conj};/*current conjunctions(still to check)*/7forall cache entry C∈E do8NC:=∅;/*new conjunctions(to check)*/9forall conjunctions Conj ∈CC do10M:=match-type(Conj ,C);11switch(M)do12case’disjoint’:break;13case’exact’:R:=R∪C→Data;14CC:=CC\{Conj };15break;16case’containing’:R:=R∪Conj (C→Data);17CC:=CC\{Conj };18break;19case’contained’:R:=R∪C→Data;20CC:=CC\{Conj };21NC:=NC∪{(Conj ∧¬C)};22break;23case’overlapping’:R:=R∪Conj (C→Data);24CC:=CC\{Conj };25NC:=NC∪{(Conj ∧¬C)};26break;27od28od29CC:=CC∪NC;30if CC={}then break;31od32if CC={}then q:=q+CC;33od34return R,q;Figure4:Procedure cache-lookupThe match type between the processed and the cached query is determined by callingthe procedure match-type(line10).This procedure implements a solution to the query containment problem and is discussed later in this section.Running over all cached entries we only have to match the query remaining from the step before instead of having to match the original query again each time.This reflects a part of the result data already been found.This data cannot occur in the semantic regions described by other entries and is not needed to retrieved from the sources.In cases of exact and containing matches there will no query remain,because all of the data can be found in the cache and therefore the cache lookup isfinished(lines13to18).In all other cases, we still have to match against the remaining entries.If we encounter a disjoint match, the currently checked conjunction has to be matched against the next entry(line12).In contrast,if a part of the result data is found,only the complementary query is to process further on.In order to avoid checks of conjunctions created during the generation of the complementary query,wefirst collect them separately(lines21and25)and add them to the set of later checked conjunctions(line29).The query remaining after checking all (possibly new created)conjunctions against all entries is built in q(line32).Here,the operation’+’denotes a concatenation of the existing query q and all conjunctions in CC by a logical OR.If all entries belonging to the queried concept are checked,a possibly remaining query have to be used to fetch data which could not be found in the cache.The procedure returns a set of all collected references to parts of the result stored in cache as well as the complementary query(34).This query is sent to the sources and–in parallel–the cached data are extracted from physical storage.In the simple example introduced above only one cache entry is created which we have to check for a match.Here,we get an overlapping match between the cached query and the first of the two conjunctions.Thus,the complementary query looks as follows://Graphics[Artist=’van Gogh’and Date=’1600’and Motif!=’People’] This expression is added to the global complementary query,because no further entry is left that we could check and therefore,we cannotfind any further parts of the result data in paring the second query conjunction we receive a disjoint match,because the query predicates together are unsatisfiable in the attribute Artist.After checking against all existing entries this conjunction becomes part of the complementary query unchanged. Thefinal complementary query is://Graphics[(Artist=’van Gogh’and Date=’1600’and Motif!=’People’) or(Artist=’Monet’and Date=’1600’)]The cached part of the result data is extracted from the cache database by applying//Graphics[Artist=’van Gogh’and Date=’1600’]to the result document data.xml,which is done using the XPath query service provided by X INDICE.Match Type Determination.In order to determine the match type between processed and cached query the problem of query containment has to be solved,symbolized in the pseudo code by calling method match-type.We can restrict the general problem to a。