A prospective study of nerve-sparing radical hysterectomy for uterine cervical carcinoma in Taiwan

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初级纤毛相关基因KIF3A通过Hedgehog信号通路影响口腔鳞状细胞癌增殖研究

延边大学医学学报　２０２２年３月　第４５卷　第１期与疾病报告２０２０概要［Ｊ］．中国循环杂志，２０２１，３６（６）：５２１－５４５．［２］　ＭＥＤＩＮＡ－ＬＥＹＴＥ　ＤＪ，ＺＥＰＥＤＡ－ＧＡＲＣíＡ　Ｏ，ＤＯＭíＮＧ－ＵＥＺＰéＲＥＺ　Ｍ，ｅｔ　ａｌ．．Ｅｎｄｏｔｈｅｌｉａｌ　ｄｙｓｆｕｎｃｔｉｏｎ，ｉｎｆｌａｍ－ｍａｔｉｏｎ　ａｎｄ　ｃｏｒｏｎａｒｙ　ａｒｔｅｒｙ　ｄｉｓｅａｓｅ：ｐｏｔｅｎｔｉａｌ　ｂｉｏｍａｒｋ－ｅｒｓ　ａｎｄ　ｐｒｏｍｉｓｉｎｇ　ｔｈｅｒａｐｅｕｔｉｃａｌ　ａｐｐｒｏａｃｈｅｓ［Ｊ］．Ｉｎｔ　ＪＭｏｌ　Ｓｃｉ，２０２１，２２（８）：３８５０．［３］　ＨＵＡＮＧ　Ｃ，ＨＵＡＮＧ　ＷＨ，ＷＡＮＧ　Ｒ，ｅｔ　ａｌ．．Ｕｌｉｎａｓｔａｔｉｎｉｎｈｉｂｉｔｓ　ｔｈｅ　ｐｒｏｌｉｆｅｒａｔｉｏｎ，ｉｎｖａｓｉｏｎ　ａｎｄ　ｐｈｅｎｏｔｙｐｉｃｓｗｉｔｃｈｉｎｇ　ｏｆ　ＰＤＧＦ－ＢＢ－ｉｎｄｕｃｅｄ　ＶＳＭＣｓ　ｖｉａ　Ａｋｔ／ｅＮＯＳ／ＮＯ／ｃＧＭＰ　ｓｉｇｎａｌｉｎｇ　ｐａｔｈｗａｙ［Ｊ］．Ｄｒｕｇ　Ｄｅｓ　Ｄｅｖｅｌ　Ｔｈｅｒ，２０２０，１４：５５０５－５５１４．［４］　赵高峰．延边地区朝鲜族ＳＭＡＲＣＡ４基因ＳＮＰｒｓ１１２２６０８与冠心病相关性研究［Ｄ］．延吉：延边大学，２０２０．［５］　ＩＭ　ＰＫ，ＭＩＬＬＷＯＯＤ　ＩＹ，ＫＡＲＴＳＯＮＡＫＩ　Ｃ，ｅｔ　ａｌ．．Ａｌ－ｃｏｈｏｌ　ｄｒｉｎｋｉｎｇ　ａｎｄ　ｒｉｓｋｓ　ｏｆ　ｔｏｔａｌ　ａｎｄ　ｓｉｔｅ－ｓｐｅｃｉｆｉｃ　ｃａｎｃ－ｅｒｓ　ｉｎ　Ｃｈｉｎａ：Ａ　１０－ｙｅａｒ　ｐｒｏｓｐｅｃｔｉｖｅ　ｓｔｕｄｙ　ｏｆ　０．５ｍｉｌｌｉｏｎａｄｕｌｔｓ［Ｊ］．Ｉｎｔ　Ｊ　Ｃａｎｃｅｒ，２０２１，１４９（３）：５２２－５３４．［６］　ＲＯＳＣＨ　ＰＪ．Ｃｏｕｌｄ　ｔｈｅ　ｂｅｎｅｆｉｔｓ　ｏｆ　ｄｒｉｎｋｉｎｇ　ａｌｃｏｈｏｌ　ｏｕｔ－ｗｅｉｇｈ　ａｌｌ　ｉｔｓ　ｒｉｓｋｓ［Ｊ］．Ｓｔｒｅｓｓ　Ｈｅａｌｔｈ，２０１３．［７］　ＷＡＬＬＥＲＡＴＨ　Ｔ，ＰＯＬＥＯ　Ｄ，ＬＩ　Ｈ，ｅｔ　ａｌ．．Ｒｅｄ　ｗｉｎｅ　ｉｎ－ｃｒｅａｓｅｓ　ｔｈｅ　ｅｘｐｒｅｓｓｉｏｎ　ｏｆ　ｈｕｍａｎ　ｅｎｄｏｔｈｅｌｉａｌ　ｎｉｔｒｉｃ　ｏｘｉｄｅｓｙｎｔｈａｓｅ：ａ　ｍｅｃｈａｎｉｓｍ　ｔｈａｔ　ｍａｙ　ｃｏｎｔｒｉｂｕｔｅ　ｔｏ　ｉｔｓ　ｂｅｎｅ－ｆｉｃｉａｌ　ｃａｒｄｉｏｖａｓｃｕｌａｒ　ｅｆｆｅｃｔｓ［Ｊ］．ＪＡＣＣ，２００３，４１（３）：４７１－４７８．［８］　ＺＨＡＯ　Ｆ，ＪＩ　Ｚ，ＣＨＩ　Ｊ，ｅｔ　ａｌ．．Ｅｆｆｅｃｔｓ　ｏｆ　Ｃｈｉｎｅｓｅ　ｙｅｌｌｏｗｗｉｎｅ　ｏｎ　ｎｉｔｒｉｃ　ｏｘｉｄｅ　ｓｙｎｔｈａｓｅ　ａｎｄ　ｉｎｔｅｒｃｅｌｌｕｌａｒ　ａｄｈｅｓｉｏｎｍｏｌｅｃｕｌｅ－１ｅｘｐｒｅｓｓｉｏｎｓ　ｉｎ　ｒａｔ　ｖａｓｃｕｌａｒ　ｅｎｄｏｔｈｅｌｉａｌ　ｃｅｌｌｓ［Ｊ］．Ａｃｔａ　Ｃａｒｄｉｏｌｏｇｉｃａ，２０１６，７１（１）：２７－３４．［９］　金春花，刘文博，关宏锏，等．一氧化氮合酶各种亚型的信号通路对心力衰竭的作用机制与治疗的研究进展［Ｊ］．中国循环杂志，２０１７，３２（８）：８３０－８３２．［１０］ＷＡＧＮＥＲ　ＭＣ，ＹＥＬＩＧＡＲ　ＳＭ，ＬＯＵ　ＡＢ，ｅｔ　ａｌ．．ＰＰＡＲγｌｉｇａｎｄｓ　ｒｅｇｕｌａｔｅ　ＮＡＤＰＨ　ｏｘｉｄａｓｅ，ｅＮＯＳ，ａｎｄ　ｂａｒｒｉｅｒｆｕｎｃｔｉｏｎ　ｉｎ　ｔｈｅ　ｌｕｎｇ　ｆｏｌｌｏｗｉｎｇ　ｃｈｒｏｎｉｃ　ａｌｃｏｈｏｌ　ｉｎｇｅｓｔｉｏｎ［Ｊ］．Ａｌｃｏｈｏｌ　Ｃｌｉｎ　Ｅｘｐ　Ｒｅｓ，２０１２，３６（２）：１９７－２０６．［１１］ＴＩＲＡＰＥＬＬＩ　ＣＲ，ＬＥＯＮＥ　ＡＦ，ＹＯＧＩ　Ａ，ｅｔ　ａｌ．．Ｅｔｈａｎｏｌｃｏｎｓｕｍｐｔｉｏｎ　ｉｎｃｒｅａｓｅｓ　ｂｌｏｏｄ　ｐｒｅｓｓｕｒｅ　ａｎｄ　ａｌｔｅｒｓ　ｔｈｅ　ｒｅ－ｓｐｏｎｓｉｖｅｎｅｓｓ　ｏｆ　ｔｈｅ　ｍｅｓｅｎｔｅｒｉｃ　ｖａｓｃｕｌａｔｕｒｅ　ｉｎ　ｒａｔｓ［Ｊ］．Ｊ　Ｐｈａｒｍ　Ｐｈａｒｍａｃｏｌ，２００８，６０（３）：３３１－３４１．［１２］ＣＨＥＮ　ＳＳ，ＷＡＮＧ　ＺＹ，ＺＨＯＵ　Ｈ，ｅｔ　ａｌ．．Ｉｃａｒｉｉｎ　ｒｅ－ｄｕｃｅｓ　ｈｉｇｈ　ｇｌｕｃｏｓｅ－ｉｎｄｕｃｅｄ　ｅｎｄｏｔｈｅｌｉａｌ　ｐｒｏｇｅｎｉｔｏｒ　ｃｅｌｌｄｙｓｆｕｎｃｔｉｏｎ　ｖｉａ　ｉｎｈｉｂｉｔｉｎｇ　ｔｈｅ　ｐ３８／ＣＲＥＢ　ｐａｔｈｗａｙ　ａｎｄａｃｔｉｖａｔｉｎｇ　ｔｈｅ　Ａｋｔ／ｅＮＯＳ／ＮＯ　ｐａｔｈｗａｙ［Ｊ］．Ｅｘｐ　ＴｈｅｒＭｅｄ，２０１９，１８（６）：４７７４－４７８０．■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■［基金项目］　国家自然科学基金项目（编号：８１５６０１７９）．［收稿日期］　２０２２－０１－０３［作者简介］　黄银珠（１９９５—），女，硕士，研究方向为口腔颌面外科．［通信作者］　金成日，Ｅｍａｉｌ：ｊｃｒ１１０５＠１６３．ｃｏｍ．初级纤毛相关基因ＫＩＦ３Ａ通过Ｈｅｄｇｅｈｏｇ信号通路影响口腔鳞状细胞癌增殖研究黄银珠，李京旭，金成日（延边大学附属医院口腔科，吉林延吉１３３０００）［摘要］　［目的］探讨初级纤毛相关基因ＫＩＦ３Ａ通过Ｈｅｄｇｅｈｏｇ信号通路对口腔鳞状细胞癌增殖能力产生的影响．［方法］选择人舌鳞癌Ｔｃａ８１１３细胞株作为研究对象，分为ＫＩＦ３Ａ－ｓｉＲＮＡ转染组和对照组．采用蛋白印迹实验和实时荧光定量实验检测各组ＫＩＦ３Ａ、Ｓｈｈ、Ｇｌｉ１蛋白及ｍＲＮＡ的相对表达水平；利用ＭＴＴ细胞增殖实验观察Ｔｃａ８１１３细胞增殖能力的变化．［结果］蛋白印迹实验结果显示，与对照组比较，ＫＩＦ３Ａ－ｓｉＲＮＡ转染组ＫＩＦ３Ａ、Ｓｈｈ、Ｇｌｉ１蛋白表达水平均明显下调（Ｐ＜０．０５）；实时荧光定量实验结果显示，与对照组比较，ＫＩＦ３Ａ－ｓｉＲＮＡ转染组ＫＩＦ３Ａ、Ｓｈｈ、Ｇｌｉ１ｍＲＮＡ表达水平均明显下调（Ｐ＜０．０１）；ＭＴＴ细胞增殖实验结果显示，细胞培养２４ｈ时两组细胞增殖间差异无统计学意义（Ｐ＞０．０５），细胞培养４８、７２ｈ时ＫＩＦ３Ａ－ｓｉＲＮＡ转染组增殖率较对照组明显降低（Ｐ＜０．０１）．［结论］沉默初级纤毛相关基因ＫＩＦ３Ａ可能通过调控Ｈｅｄｇｅｈｏｇ信号通路抑制口腔鳞癌的增殖能力．［关键词］　口腔鳞状细胞癌；初级纤毛；ＫＩＦ３Ａ；Ｈｅｄｇｅｈｏｇ信号通路ＤＯＩ：１０．１６０６８／ｊ．１０００－１８２４．２０２２．０１．００２［中图分类号］　Ｒ　７３９．８［文献标志码］　Ａ［文章编号］　１０００－１８２４（２０２２）０１－０００７－０４·７·■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■Ｊｏｕｒｎａｌ　ｏｆ　Ｍｅｄｉｃａｌ　Ｓｃｉｅｎｃｅ　Ｙａｎｂｉａｎ　Ｕｎｉｖｅｒｓｉｔｙ　Ｍａｒ．２０２２　Ｖｏｌ．４５　Ｎｏ．１Ｅｆｆｅｃｔｓ　ｏｆ　ｐｒｉｍａｒｙ　ｃｉｌｉｕｍ－ａｓｓｏｃｉａｔｅｄ　ｇｅｎｅ　ＫＩＦ３Ａｏｎ　ｏｒａｌ　ｓｑｕａｍｏｕｓ　ｃｅｌｌｃａｒｃｉｎｏｍａ　ｐｒｏｌｉｆｅｒａｔｉｏｎ　ｂｙ　Ｈｅｄｇｅｈｏｇ　ｓｉｇｎａｌｉｎｇ　ｐａｔｈｗａｙＨＵＡＮＧ　Ｙｉｎｚｈｕ，ＬＩ　Ｊｉｎｇｘｕ，ＪＩＮ　Ｃｈｅｎｇｒｉ（Ｄｅｐａｒｔｍｅｎｔ　ｏｆ　Ｓｔｏｍａｔｏｌｏｇｙ，Ａｆｆｉｌｉａｔｅｄ　Ｈｏｓｐｉｔａｌ　ｏｆ　Ｙａｎｂｉａｎ　Ｕｎｉｖｅｒｓｉｔｙ，Ｙａｎｊｉ　１３３０００，Ｊｉｌｉｎ，Ｃｈｉｎａ）ＡＢＳＴＲＡＣＴ：ＯＢＪＥＣＴＩＶＥＴｏ　ｅｘｐｌｏｒｅ　ｔｈｅ　ｅｆｆｅｃｔ　ｏｆ　ｐｒｉｍａｒｙ　ｃｉｌｉｕｍ－ａｓｓｏｃｉａｔｅｄ　ｇｅｎｅ　ＫＩＦ３Ａｏｎ　ｏｒａｌ　ｓｑｕａｍｏｕｓｃｅｌｌ　ｃａｒｃｉｎｏｍａ　ｐｒｏｌｉｆｅｒａｔｉｏｎ　ｔｈｒｏｕｇｈ　Ｈｅｄｇｅｈｏｇ　ｓｉｇｎａｌｉｎｇ　ｐａｔｈｗａｙ．ＭＥＴＨＯＤＳ　Ｈｕｍａｎ　ｔｏｎｇｕｅ　ｓｑｕａｍｏｕｓ　ｃｅｌｌｃａｒｃｉｎｏｍａ　Ｔｃａ８１１３ｃｅｌｌ　ｌｉｎｅ　ｗａｓ　ｓｅｌｅｃｔｅｄ　ａｎｄ　ｄｉｖｉｄｅｄ　ｉｎｔｏ　ＫＩＦ３Ａ－ｓｉＲＮＡ　ｔｒａｎｓｆｅｃｔｉｏｎ　ｇｒｏｕｐ　ａｎｄ　ｃｏｎｔｒｏｌｇｒｏｕｐ．Ｗｅｓｔｅｒｎ　ｂｌｏｔ　ａｎｄ　ｒｅａｌ－ｔｉｍｅ　ｑＰＣＲ　ｗｅｒｅ　ｕｓｅｄ　ｔｏ　ｄｅｔｅｃｔ　ｔｈｅ　ｒｅｌａｔｉｖｅ　ｅｘｐｒｅｓｓｉｏｎ　ｌｅｖｅｌｓ　ｏｆ　ＫＩＦ３Ａ，Ｓｈｈａｎｄ　Ｇｌｉ１ｐｒｏｔｅｉｎｓ　ａｎｄ　ｍＲＮＡ　ｉｎ　ｅａｃｈ　ｇｒｏｕｐ．ＭＴＴ　ｃｅｌｌ　ｐｒｏｌｉｆｅｒａｔｉｏｎ　ａｓｓａｙ　ｗａｓ　ｕｓｅｄ　ｔｏ　ｏｂｓｅｒｖｅ　ｔｈｅｐｒｏｌｉｆｅｒａｔｉｏｎ　ｏｆ　Ｔｃａ８１１３ｃｅｌｌｓ．ＲＥＳＵＬＴＳ　Ｗｅｓｔｅｒｎ　ｂｌｏｔ　ｒｅｓｕｌｔｓ　ｓｈｏｗｅｄ　ｔｈａｔ　ｃｏｍｐａｒｅｄ　ｗｉｔｈ　ｔｈｅ　ｃｏｎｔｒｏｌ　ｇｒｏｕｐ，ｔｈｅ　ｐｒｏｔｅｉｎ　ｅｘｐｒｅｓｓｉｏｎ　ｌｅｖｅｌｓ　ｏｆ　ＫＩＦ３Ａ，Ｓｈｈ　ａｎｄ　Ｇｌｉ１ｉｎ　ｔｈｅ　ＫＩＦ３Ａ－ＳｉＲＮＡ　ｔｒａｎｓｆｅｃｔｉｏｎ　ｇｒｏｕｐ　ｗｅｒｅｓｉｇｎｉｆｉｃａｎｔｌｙ　ｄｏｗｎ－ｒｅｇｕｌａｔｅｄ（Ｐ＜０．０５）．Ｒｅａｌ－ｔｉｍｅ　ｑＰＣＲ　ｒｅｓｕｌｔｓ　ｓｈｏｗｅｄ　ｔｈａｔ　ｃｏｍｐａｒｅｄ　ｗｉｔｈ　ｔｈｅ　ｃｏｎｔｒｏｌｇｒｏｕｐ，ｔｈｅ　ｍＲＮＡ　ｅｘｐｒｅｓｓｉｏｎ　ｌｅｖｅｌｓ　ｏｆ　ＫＩＦ３Ａ，Ｓｈｈ　ａｎｄ　Ｇｌｉ１ｉｎ　ｔｈｅ　ＫＩＦ３Ａ－ＳｉＲＮＡ　ｔｒａｎｓｆｅｃｔｉｏｎ　ｇｒｏｕｐ　ｗｅｒｅｓｉｇｎｉｆｉｃａｎｔｌｙ　ｄｏｗｎ－ｒｅｇｕｌａｔｅｄ（Ｐ＜０．０１）．ＭＴＴ　ｃｅｌｌ　ｐｒｏｌｉｆｅｒａｔｉｏｎ　ａｓｓａｙ　ｓｈｏｗｅｄ　ｔｈａｔ　ｔｈｅｒｅ　ｗａｓ　ｎｏ　ｓｉｇｎｉｆｉｃａｎｔｄｉｆｆｅｒｅｎｃｅ　ｉｎ　ｃｅｌｌ　ｐｒｏｌｉｆｅｒａｔｉｏｎ　ｂｅｔｗｅｅｎ　ｔｈｅ　ｔｗｏ　ｇｒｏｕｐｓ　ａｆｔｅｒ　２４ｈｃｅｌｌ　ｃｕｌｔｕｒｅ（Ｐ＞０．０５）．Ｔｈｅ　ｐｒｏｌｉｆｅｒａｔｉｏｎｒａｔｅ　ｏｆ　ｔｈｅ　ＫＩＦ３Ａ－ＳｉＲＮＡ　ｔｒａｎｓｆｅｃｔｉｏｎ　ｇｒｏｕｐ　ｗａｓ　ｓｉｇｎｉｆｉｃａｎｔｌｙ　ｌｏｗｅｒ　ｔｈａｎ　ｔｈａｔ　ｏｆ　ｔｈｅ　ｃｏｎｔｒｏｌ　ｇｒｏｕｐ　ａｆｔｅｒ　ｃｅｌｌｃｕｌｔｕｒｅ　ｆｏｒ　４８ａｎｄ　７２ｈ（Ｐ＜０．０１）．ＣＯＮＣＬＵＳＩＯＮＳｉｌｅｎｃｉｎｇ　ｐｒｉｍａｒｙ　ｃｉｌｉｕｍ－ａｓｓｏｃｉａｔｅｄ　ｇｅｎｅ　ＫＩＦ３Ａｍａｙｉｎｈｉｂｉｔ　ｔｈｅ　ｐｒｏｌｉｆｅｒａｔｉｏｎ　ｏｆ　ｏｒａｌ　ｓｑｕａｍｏｕｓ　ｃｅｌｌ　ｃａｒｃｉｎｏｍａ　ｂｙ　ｒｅｇｕｌａｔｉｎｇ　Ｈｅｄｇｅｈｏｇ　ｓｉｇｎａｌｉｎｇ　ｐａｔｈｗａｙ．Ｋｅｙｗｏｒｄｓ：ｏｒａｌ　ｓｑｕａｍｏｕｓ　ｃｅｌｌ　ｃａｒｃｉｎｏｍａ；ｐｒｉｍａｒｙ　ｃｉｌｉａ；ＫＩＦ３Ａ；Ｈｅｄｇｅｈｏｇ　ｓｉｇｎａｌｉｎｇ　ｐａｔｈｗａｙ口腔癌人数约占全世界罹患恶性肿瘤人数的３％，其中鳞状细胞癌比例超过９０％．２００５年，ＷＨＯ将口腔鳞状细胞癌（ＯＳＣＣ）定义为一种具有不同分化程度和侵袭性的肿瘤，早期可出现广泛的淋巴结转移，好发于４０～７０岁的烟酒爱好者［１］．口腔癌患者５年生存率约为５０％［２］，患者术后预后差和５年生存率低的主要原因为患者未及时就诊、淋巴结转移及复发［３］．控制ＯＳＣＣ的侵袭转移能力对预后至关重要，认为可偿试从分子水平出发找出更好的治疗方法［４］．初生纤毛属于一种细胞表面的细胞器，在脊椎动物发育和人类遗传疾病中发挥着重要作用．纤毛对发育信号的响应是必需的，而越来越多的证据表明初级纤毛是专属于Ｈｅｄｇｅｈｏｇ信号传导的［５］，而Ｈｅｄｇｅｈｏｇ信号传导对肿瘤的发生发展起着重要作用．研究［６］结果显示，多种肿瘤组织中均存在Ｈｅｄｇｅｈｏｇ信号的异常激活，如肺小细胞癌、胰腺癌、前列腺癌、乳腺癌、恶性胶质瘤、髓母细胞瘤及多发性骨髓瘤等．ＫＩＦ３Ａ属于初级纤毛内运输系统，具有维持和发挥初级纤毛正常功能的作用［７］．本研究探讨了初级纤毛相关基因ＫＩＦ３Ａ通过Ｈｅｄｇｅｈｏｇ信号通路对ＯＳＣＣ增殖能力产生的影响．１　材料与方法１．１　细胞　人舌鳞癌细胞株Ｔｃａ８１１３购自美国菌种保藏中心（ＡＴＣＣ），置于延边大学附属医院中心实验室封存．１．２细胞培养与转染　取Ｔｃａ８１１３细胞置于温度３７℃、二氧化碳体积分数５％、饱和湿度９５％的恒温孵育箱中，用含１０％（质量分数）ＦＢＳ、青链霉素的ＤＭＥＭ高糖型培养基传代培养．在转染前１ｄ，将Ｔｃａ８１１３细胞分为对照组和ＫＩＦ３Ａ－ｓｉＲＮＡ转染组后接种至６孔板中，待生长至８０％时进行细胞转染．ＫＩＦ３Ａ－ｓｉＲＮＡ转染组转染ＫＩＦ３Ａ－ｓｉＲＮＡ，对照组未进行转染．转染操作按照ＬｉｐｏｆｅｃｔａｍｉｎｅＴＭ２０００Ｒｅ－ａｇｅｎ转染说明书进行．ＫＩＦ３Ａ－ｓｉＲＮＡ序列（５′－３′）：ＵＡＡ　ＧＧＡ　ＡＵＧ　ＣＵＧ　ＡＡＧ　ＡＡＧ　ＡＣＧ　ＡＧＵ　Ｃ．１．３　蛋白印迹实验　转染２４ｈ后分别收集两组细胞，并加入ＲＩＰＡ与ＰＭＳＦ混合（１００:１）冰上裂解细胞，提取细胞总蛋白，采用ＢＣＡ试剂盒测定总蛋白水平．取各组标本行８％（质量分数）十二烷基硫酸钠聚丙烯酰胺凝胶（ＳＤＳ－ＰＡＧＥ）电泳，转膜，室温下用５％（质量分数）脱脂奶粉封闭２ｈ．ＴＢＳＴ洗涤３·８·■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■延边大学医学学报　２０２２年３月　第４５卷　第１期次，每次１０ｍｉｎ，加入兔抗人Ｋｉｆ３ａ一抗（１:１　０００）、兔抗人Ｓｈｈ一抗（１:２　０００）、兔抗人Ｇｌｉ１（１:１　０００）及兔抗人ＧＡＰＤＨ（１:１　０００）后置于湿盒中，于４℃冰箱中孵育过夜；次日ＴＢＳＴ洗涤３次，每次１０ｍｉｎ，分别加入山羊抗兔ＩｇＧ二抗（１:１０　０００）后置于湿盒中室温孵育２ｈ；ＴＢＳＴ洗涤３次，每次１０ｍｉｎ，加入增强型化学发光剂ＥＣＬ显影．以ＧＡＰＤＨ为内参，采用Ｉｍａｇｉｎｅ　Ｊ软件分析蛋白条带灰度值．１．４　实时荧光定量实验　转染２４ｈ后分别收集两组细胞，采用ＴＲＮｚｏｌ法提取细胞中的总ＲＮＡ，反转录为ｃＤＮＡ，按照ＲＴ－ＰＣＲ试剂盒说明书以ｃＤＮＡ为模板进行扩增．测定循环阈值（Ｃｔ），采用２－△△Ｃｔ法进行统计．实验重复３次．引物序列，ＫＩＦ３Ａ－正向：５′－ＡＧＡ　ＧＣＧ　ＴＣＡ　ＡＣＧ　ＡＧＧ　ＴＧＴ　ＴＴ－３′；ＫＩＦ３Ａ－反向：５′－ＴＡＴ　ＴＧＡ　ＴＣＧ　ＧＣＡ　ＴＣＴ　ＴＧＧ　ＣＣＣ－３′；Ｓｈｈ－正向：５′－ＣＴＣ　ＧＣＴ　ＧＣＴ　ＧＧＴ　ＡＴＧ　ＣＴＣ　Ｇ－３′；Ｓｈｈ－反向：５′－ＡＴＣ　ＧＣＴ　ＣＧＧ　ＡＧＴ　ＴＴＣ　ＴＧＧＡＧＡ－３′；Ｇｌｉ１－正向：５′－ＡＧＣ　ＧＴＧ　ＡＧＣ　ＣＴＧ　ＡＡＴＣＴＧ　ＴＧ－３′；Ｇｌｉ１－反向：５′－ＣＡＧ　ＣＡＴ　ＧＴＡ　ＣＴＧＧＧＣ　ＴＴＴ　ＧＡＡ－３′；ＧＡＰＤＨ－正向：５′－ＧＧＡ　ＧＣＧＡＧＡ　ＴＣＣ　ＣＴＣ　ＣＡＡ　ＡＡＴ－３′；ＧＡＰＤＨ－反向：５′－ＧＧＣ　ＴＧＴ　ＴＧＴＣＡＴＡＣＴ　ＴＣＴＣＡＴＧＧ－３′．１．５　ＭＴＴ细胞增殖实验　转染２４ｈ后分别收集两组细胞，以５　０００个／孔接种于９６孔板中，每组设置５个复孔．培养２４、４８、７２ｈ后弃去旧培养液，每孔加入１００μＬ　ＭＴＴ（５　ｇ／Ｌ），于３７℃、５％（体积分数）二氧化碳、９５％饱和湿度的恒温孵育箱中培养４　ｈ，弃去上清液终止反应，每孔加入１００μＬ　ＤＭＳＯ，置于振荡器３　ｍｉｎ溶解结晶后在酶标仪波长４９０　ｎｍ处测定各孔的光密度（ＯＤ）值，计算相对细胞增殖率．相对细胞增殖率（％）＝（实验组ＯＤ值／对照组ＯＤ值）×１００％．１．６　统计学分析　采用Ｇｒａｐｈｐａｄ　Ｐｒｉｓｍ　７．０软件进行数据分析．计量数据以均数±标准偏差（ｘ±ｓ）表示，进行两个样本均数的ｔ检验，以Ｐ＜０．０５为差异有统计学意义．２　结果２．１　沉默ＫＩＦ３Ａ基因后对Ｔｃａ８１１３细胞Ｈｅｄｇｅｈｏｇ信号通路中Ｓｈｈ、Ｇｌｉ１蛋白表达水平的影响　与对照组比较，ＫＩＦ３Ａ－ｓｉＲＮＡ转染组２４ｈ时ＫＩＦ３Ａ、Ｓｈｈ及Ｇｌｉ１蛋白表达水平均明显降低，差异均具有统计学意义（Ｐ＜０．０５），见Ｆｉｇｕｒｅ　１．ｃｏｍｐａｒｅｄ　ｗｉｔｈ　ｃｏｎｔｒｏｌ，＊Ｐ＜０．０５．Ｆｉｇｕｒｅ　１　Ｔｈｅ　ｐｒｏｔｅｉｎ　ｅｘｐｒｅｓｓｉｏｎ　ｌｅｖｅｌｓ　ｏｆ　ＫＩＦ３Ａ，Ｓｈｈａｎｄ　Ｇｌｉ１ｄｅｃｒｅａｓｅｄ　ｓｉｇｎｉｆｉｃａｎｔｌｙ　ａｆｔｅｒｔｒａｎｓｆｅｃｔｉｏｎ　ｏｆ　Ｔｃａ８１１３ｃｅｌｌｓ２．２　沉默ＫＩＦ３Ａ基因后对Ｔｃａ８１１３细胞中Ｈｅｄｇｅｈｏｇ信号通路Ｓｈｈ、Ｇｌｉ１ｍＲＮＡ表达水平的影响　与对照组比较，ＫＩＦ３Ａ－ｓｉＲＮＡ转染２４ｈ组ＫＩＦ３Ａ、Ｓｈｈ及Ｇｌｉ１ｍＲＮＡ表达水平均显著降低，差异均具有统计学意义（Ｐ＜０．０１），见Ｆｉｇｕｒｅ　２．ｃｏｍｐａｒｅｄ　ｗｉｔｈ　ｃｏｎｔｒｏｌ，＊＊Ｐ＜０．０１．Ｆｉｇｕｒｅ　２　Ｔｈｅ　ｍＲＮＡ　ｅｘｐｒｅｓｓｉｏｎ　ｌｅｖｅｌｓ　ｏｆ　ＫＩＦ３Ａ，Ｓｈｈａｎｄ　Ｇｌｉ１ｄｅｃｒｅａｓｅｄ　ｓｉｇｎｉｆｉｃａｎｔｌｙ　ａｆｔｅｒｔｒａｎｓｆｅｃｔｉｏｎ　ｏｆ　Ｔｃａ８１１３ｃｅｌｌｓ２．３　沉默ＫＩＦ３Ａ基因后对Ｔｃａ８１１３细胞增殖能力的影响　ＭＴＴ检测结果显示，细胞培养２４ｈ时ＫＩＦ３Ａ－ｓｉＲＮＡ转染组与对照组细胞增殖间差异无统计学意义（Ｐ＞０．０５）；细胞培养４８、７２ｈ时，ＫＩＦ３Ａ－ｓｉＲＮＡ转染组与对照组比较增殖显著受到抑制（Ｐ＜０．０１），见Ｆｉｇｕｒｅ　３．·９·■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■Ｊｏｕｒｎａｌ　ｏｆ　Ｍｅｄｉｃａｌ　Ｓｃｉｅｎｃｅ　Ｙａｎｂｉａｎ　Ｕｎｉｖｅｒｓｉｔｙ　Ｍａｒ．２０２２　Ｖｏｌ．４５　Ｎｏ．１ｃｏｍｐａｒｅｄ　ｗｉｔｈ　ｃｏｎｔｒｏｌ，＊＊Ｐ＜０．０１．Ｆｉｇｕｒｅ　３　Ｔｈｅ　ｐｒｏｌｉｆｅｒａｔｉｏｎ　ｒａｔｅ　ｏｆ　Ｔｃａ８１１３ｃｅｌｌｓ　ａｆｔｅｒｔｒａｎｓｆｅｃｔｉｏｎ３　讨论初级纤毛为多数分化型细胞表面上的感觉附属物，具有化学感觉和机械感觉功能，在细胞周期控制中具有重要的作用．以往的研究认为初级纤毛在快速增殖的细胞上是找不到的，如癌症细胞，但ＫＯＷＡＬ等［８］通过一种初级纤毛标志物Ａｒｌ１３ｂ在ＨｅＬａ和ＭＧ６３细胞中发现了初级纤毛．未在ＯＳＣＣ中查看是否存在初级纤毛是本研究的不足之处．ＫＩＦ３Ａ属于初级纤毛内运输系统，在维持和发挥初级纤毛功能中起重要作用．ＨＯＡＮＧ－ＭＩＮＨ等［９］的研究结果显示，沉默ＫＩＦ３Ａ基因表达后可降低胶质母细胞瘤中初级纤毛的数量，最终促进肿瘤的发生．玄云泽等［１０］首次在ＯＳＣＣ中发现有初级纤毛，后来有学者亦在口腔白斑与ＯＳＣＣ组织中发现了初级纤毛，ＥＧＦＲ－Ａｕｒｏｒａ　Ａ异常信号被激活后，口腔黏膜癌变过程中原发性纤毛逐渐减少［１１］．本研究结果显示，利用ｓｉＲＮＡ技术沉默ＫＩＦ３Ａ基因后ｍＲＮＡ和蛋白表达水平明显降低，提示初级纤毛的检出率降低．Ｈｅｄｇｅｈｏｇ信号通路对胚胎发育及肿瘤的发生发展具有重要意义．研究［１２－１３］结果显示，Ｈｅｄｇｅｈｏｇ信号通路的异常激活与皮肤、乳腺、肺及消化道等多种恶性肿瘤的发生、增殖密切相关．程志芬等［１２］利用Ｈｅｄｇｅｈｏｇ信号通路特异性抑制剂环巴胺处理Ｔｃａ８１１３细胞株后，Ｓｍｏｏｔｈｅｎｅｄ的ｍＲＮＡ和蛋白表达明显减少，且细胞增殖受到抑制．ＫＵＲＯＤＡ等［１４］的研究结果显示，给予Ｈｅｄｇｅｈｏｇ信号通路抑制剂可抑制肿瘤前沿血管内皮细胞的增殖、迁移，进而抑制肿瘤的增殖和迁移．在小细胞肺癌中，沉默ＫＩＦ３Ａ后初级纤毛明显减少，且Ｓｈｈ信号通路介导的Ｇｌｉ１ｍＲＮＡ表达水平明显降低［１５］，此结果与本研究结果相符．研究［１６］结果显示，Ｈｅｄｇｅｈｏｇ信号通路转录因子Ｇｌｉ１的激活是恶性肿瘤的一个不良预后因素，利用环巴胺阻断Ｈｅｄｇｅｈｏｇ信号通路可抑制Ｇｌｉ１激活，并增强头颈部鳞癌对放疗的敏感性，提示Ｈｅｄｇｅｈｏｇ信号通路影响头颈部鳞癌的放疗预后．总之，本研究揭示了初级纤毛相关基因ＫＩＦ３Ａ在人舌鳞癌Ｔｃａ８１１３细胞Ｈｅｄｇｅｈｏｇ信号通路中的作用，初步解释了沉默ＫＩＦ３Ａ后可能通过抑制Ｈｅｄｇｅｈｏｇ信号通路影响ＯＳＣＣ细胞的增殖能力，为ＯＳＣＣ患者的靶向治疗提供了理论依据．［参　考　文　献］［１］　ＤＩ　ＰＡＲＤＯ　ＢＪ，ＢＲＯＮＳＯＮ　ＮＷ，ＤＩＧＧＳ　ＢＳ，ｅｔ　ａｌ．．Ｔｈｅｇｌｏｂａｌ　ｂｕｒｄｅｎ　ｏｆ　ｅｓｏｐｈａｇｅａｌ　ｃａｎｃｅｒ：ａ　ｄｉｓａｂｉｌｉｔｙ－ａｄｊｕｓｔｅｄｌｉｆｅ－ｙｅａｒ　ａｐｐｒｏａｃｈ［Ｊ］．Ｗｏｒｌｄ　Ｊ　Ｓｕｒｇ，２０１６，４０（２）：３９５－４０１．［２］　ＢＲＯＣＫＬＥＨＵＲＳＴ　ＰＲ，ＢＡＫＥＲ　ＳＲ，ＳＰＥＩＧＨＴ　ＰＭ．Ｏｒａｌｃａｎｃｅｒ　ｓｃｒｅｅｎｉｎｇ：ｗｈａｔ　ｈａｖｅ　ｗｅ　ｌｅａｒｎｔ　ａｎｄ　ｗｈａｔ　ｉｓ　ｔｈｅｒｅｓｔｉｌｌ　ｔｏ　ａｃｈｉｅｖｅ［Ｊ］．Ｆｕｔｕｒｅ　Ｏｎｃｏｌ，２０１０，６（２）：２９９－３０４．［３］　ＢＡＶＬＥ　ＲＭ，ＶＥＮＵＧＯＰＡＬ　Ｒ，ＫＯＮＤＡ　Ｐ，ｅｔ　ａｌ．．Ｍｏ－ｌｅｃｕｌａｒ　ｃｌａｓｓｉｆｉｃａｔｉｏｎ　ｏｆ　ｏｒａｌ　ｓｑｕａｍｏｕｓ　ｃｅｌｌ　ｃａｒｃｉｎｏｍａ［Ｊ］．ＪＣＤＲ，２０１６，１０（９）：Ｚ１８－Ｚ２１．［４］　陈新，徐文华，周健，等．口腔鳞状细胞癌现状［Ｊ］．口腔医学，２０１７，３７（５）：４６２－４６５．［５］　ＧＯＥＴＺ　ＳＣ，ＡＮＤＥＲＳＯＮ　ＫＶ．Ｔｈｅ　ｐｒｉｍａｒｙ　ｃｉｌｉｕｍ：ａ　ｓｉｇｎａｌｌｉｎｇ　ｃｅｎｔｒｅ　ｄｕｒｉｎｇ　ｖｅｒｔｅｂｒａｔｅ　ｄｅｖｅｌｏｐｍｅｎｔ［Ｊ］．Ｎａｔ　Ｒｅｖ　Ｇｅｎｅ，２０１０，１１（５）：３３１－３４４．［６］　那玉岩，刘万林．纤毛相关疾病：细胞学机制及转化应用进展［Ｊ］．中国组织工程研究，２０１６，２０（２４）：３６４２－３６４８．［７］　ＮＩＥＷＩＡＤＯＭＳＫＩ　Ｐ，ＮＩＥＤＺＩółＫＡ　ＳＭ，ＭＡＲＫＩＥＷＩＣＺŁ，ｅｔ　ａｌ．．Ｇｌｉ　ｐｒｏｔｅｉｎｓ：ｒｅｇｕｌａｔｉｏｎ　ｉｎ　ｄｅｖｅｌｏｐｍｅｎｔ　ａｎｄｃａｎｃｅｒ［Ｊ］．Ｃｅｌｌｓ，２０１９，８（２）：１４７．［８］　ＫＯＷＡＬ　ＴＪ，ＦＡＬＫ　ＭＭ．Ｐｒｉｍａｒｙ　ｃｉｌｉａ　ｆｏｕｎｄ　ｏｎ　ＨｅＬａａｎｄ　ｏｔｈｅｒ　ｃａｎｃｅｒ　ｃｅｌｌｓ［Ｊ］．Ｃｅｌｌ　Ｂｉｏｌ　Ｉｎｔ，２０１５，３９（１１）：１３４１－１３４７．［９］　ＨＯＡＮＧ－ＭＩＮＨ　ＬＢ，ＤＥＬＥＹＲＯＬＬＥ　ＬＰ，ＳＩＥＢＺＥＨ－ＮＲＵＢＬ　Ｄ，ｅｔ　ａｌ．．Ｄｉｓｒｕｐｔｉｏｎ　ｏｆ　ＫＩＦ３Ａｉｎ　ｐａｔｉｅｎｔ－ｄｅ－ｒｉｖｅｄ　ｇｌｉｏｂｌａｓｔｏｍａ　ｃｅｌｌｓ：ｅｆｆｅｃｔｓ　ｏｎ　ｃｉｌｉｏｇｅｎｅｓｉｓ，ｈｅｄｇｅ－ｈｏｇ　ｓｅｎｓｉｔｉｖｉｔｙ，ａｎｄ　ｔｕｍｏｒｉｇｅｎｅｓｉｓ［Ｊ］．Ｏｎｃｏｔａｒｇｅｔ，２０１６，７（６）：７０２９－７０４３．［１０］玄云泽，李书进，金成日，等．初级纤毛相关基因ＫＩＦ３Ａ通过调控ＥＭＴ过程在口腔鳞状细胞癌中的作用机制研究［Ｊ］．重庆医学，２０２０，４９（１）：７－１２．［１１］ＹＩＮ　Ｆ，ＣＨＥＮ　Ｑ，ＳＨＩ　Ｙ，ｅｔ　ａｌ．．Ａｃｔｉｖａｔｉｏｎ　ｏｆ　ＥＧＦＲ－Ａｕ－ｒｏｒａ　Ａ　ｉｎｄｕｃｅｓ　ｌｏｓｓ　ｏｆ　ｐｒｉｍａｒｙ　ｃｉｌｉａ　ｉｎ　ｏｒａｌ　ｓｑｕａｍｏｕｓ　ｃｅｌｌｃａｒｃｉｎｏｍａ［Ｊ］．Ｏｒａｌ　Ｄｉｓ，２０２２，２８（３）：６２１－６３０．［１２］程志芬，崔演，玄延花．Ｐｔｃｈ和Ｓｍｏ在舌鳞状细胞癌Ｔｃａ８１１３细胞中的表达及其意义［Ｊ］．口腔医学研究，２０１５，３１（５）：４３３－４３６．［１３］ＫＯＮＳＴＡＮＴＩＮＯＵ　Ｄ，ＢＥＲＴＡＵＸ－ＳＫＥＩＲＩＫ　Ｎ，ＺＡＶＲＯＳＹ．Ｈｅｄｇｅｈｏｇ　ｓｉｇｎａｌｉｎｇ　ｉｎ　ｔｈｅ　ｓｔｏｍａｃｈ［Ｊ］．Ｃｕｒｒ　ＯｐｉｎＰｈａｒｍａｃｏｌ，２０１６，３１：７６－８２．［１４］ＫＵＲＯＤＡ　Ｈ，ＫＵＲＩＯ　Ｎ，ＳＨＩＭＯ　Ｔ，ｅｔ　ａｌ．．Ｏｒａｌ　ｓｑｕａｍｏｕｓｃｅｌｌ　ｃａｒｃｉｎｏｍａ－ｄｅｒｉｖｅｄ　ｓｏｎｉｃ　ｈｅｄｇｅｈｏｇ　ｐｒｏｍｏｔｅｓ　ａｎｇｉｏｇｅｎｅ－ｓｉｓ［Ｊ］．Ａｎｔｉｃａｎｃｅｒ　Ｒｅｓ，２０１７，３７（１２）：６７３１－６７３７．［１５］ＣＯＣＨＲＡＮＥ　ＣＲ，ＶＡＧＨＪＩＡＮＩ　Ｖ，ＳＺＣＺＥＰＮＹ　Ａ，ｅｔ　ａｌ．．Ｔｒｐ５３ａｎｄ　Ｒｂ１ｒｅｇｕｌａｔｅ　ａｕｔｏｐｈａｇｙ　ａｎｄ　ｌｉｇａｎｄ－ｄｅｐｅｎｄｅｎｔＨｅｄｇｅｈｏｇ　ｓｉｇｎａｌｉｎｇ［Ｊ］．Ｊ　Ｃｌｉｎ　Ｉｎｖｅｓｔ，２０２０，１３０（８）：４００６－４０１８．［１６］ＧＡＮ　ＧＮ，ＥＡＧＬＥＳ　Ｊ，ＫＥＹＳＡＲ　ＳＢ，ｅｔ　ａｌ．．Ｈｅｄｇｅｈｏｇｓｉｇｎａｌｉｎｇ　ｄｒｉｖｅｓ　ｒａｄｉｏｒｅｓｉｓｔａｎｃｅ　ａｎｄ　ｓｔｒｏｍａ－ｄｒｉｖｅｎｔｕｍｏｒ　ｒｅｐｏｐｕｌａｔｉｏｎ　ｉｎ　ｈｅａｄ　ａｎｄ　ｎｅｃｋ　ｓｑｕａｍｏｕｓ　ｃａｎｃｅｒｓ［Ｊ］．Ｃａｎｃｅｒ　Ｒｅｓ，２０１４，７４（２３）：７０２４－７０３６．■·０１·■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■。

0._1_mg

- 64 -[8]刘海兵，唐丹，曹海燕，等.温哥华瘢痕量表的信度研究[J].中国康复医学杂志，2006，21（3）：240-242.[9]周峰，虞慧婷，范和玉，等.2003-2020年上海市剖宫产率趋势及归因分析[J].实用预防医学，2022，29（8）：948-951.[10]韩娜，林力孜，金楚瑶，等.2013年—2018年基于改良版Robson 分级系统的北京通州区剖宫产率变化情况[J].中国生育健康杂志，2022，33（1）：8-13.[11]叶鹏海，王书捷.剖宫产术中因素对术后腹部切口脂肪液化的影响[J].中国妇幼保健，2021，36（5）：1033-1036.[12]周玲，王莉，陈秀芳，等.剖宫产手术腹部切口愈合不良的相关因素分析[J].中华医院感染学杂志，2018，28（14）：2169-2172.[13]程家乐，孟优，包兆康，等.无创皮肤吻合器应用于甲状腺手术切口的效果分析[J].医药前沿，2021，11（15）：1-3.[14] FREED J S，KO J.An innovative advance in non-invasive woundclosure: a new paradigm[J].Mil Med，2018，183（suppl 1）：472-480.[15]杨欢，钟琴，李俊强，等.心形缝合预防妇科恶性肿瘤患者开腹手术切口愈合不良的效果观察[J].实用医院临床杂志，2022，19（6）：119-122.[16]陈佳佳，赵慎之，董克，等.楔形切除与改良全埋入式垂直褥式缝合在二次剖宫产腹壁切口中的应用[J].医学研究杂志，2020，49（4）：57-61.[17]李嫦，陈苑红，黄力力，等.改良埋没垂直褥式缝合技术在腹部伤口的应用及术后切口愈合的效果评价[J].广西医科大学学报，2020，37（2）：277-281.[18] NGAAGE M，AGIUS M.The psychology of scars: a mini-review[J].Psychiatr Danub，2018，30（Suppl 7）：633-638.[19] LIU Z，TANG Z，HAO X，et al.Modified buried verticalmattress suture versus buried intradermal suture: a prospective split-scar study[J].Dermatol Surg，2021，47（3）：75-80.[20]宋海峰，董高宏，魏凯军，等.张力促进瘢痕疙瘩纤维化的初步研究[J].中华皮肤科杂志，2021，54（3）：196-200.[21]郭娇娇，罗恒，马雯雯，等.剖宫产切口心形减张美容缝合的愈合效果评价[J].中国现代手术学杂志，2022，26（4）：294-298.[22]张强，冯有支，郭军，等.心形缝合法联合无创皮肤吻合器在面部软组织损伤修复中的应用效果[J].中国美容医学，2021，30（5）：29-32.（收稿日期：2023-08-25）　（本文编辑：张爽）①泉州市第一医院麻醉科　福建　泉州　362002②福建医科大学附属协和医院麻醉科　福建　福州　350001通信作者：林小玲0.1 mg/kg纳布啡对腰-硬联合麻醉剖宫产产妇血流动力学、术后疼痛及寒战的影响林小玲①　杨丽萍①　陈强②【摘要】　目的：探讨0.1 mg/kg 纳布啡对腰-硬联合麻醉剖宫产产妇血流动力学、术后疼痛及寒战的影响。

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Primary extramedullary plasmacytoma: similarities with and differences from multiple myeloma revealed by interphase cytogeneticsKarin Bink,1Eugenia Haralambieva,2Marcus Kremer,3German Ott,4Christine Beham-Schmid,5 Laurence de Leval,6Suat Cheng Peh,7Hubert R. Laeng,8Uta Jütting,9Peter Hutzler,1Leticia Quintanilla-Martinez,1and Falko Fend31Institutes of Pathology,Helmholtz Center Munich,German Research Center for Environmental Health,Neuherberg, Oberschleissheim; 2University of Würzburg;3Technical University of Munich; 4Robert Bosch Hospital,Stuttgart, Germany; 5University of Graz,Austria;6University of Liège,Belgium;7University of Malaya,Malaysia;8Kantonsspital Aarau,Switzerland; 9Institute of Biomathematics and Biometry,Helmholtz Center Munich,German Research Center for Environmental Health,Neuherberg,Oberschleissheim,GermanyBrief ReportABSTRACTPrimary extramedullary plasmacytoma is an indolent neoplasm that infrequently converts to multiple myeloma.Since cytogenetic data on extramedullary plasmacytoma are lacking,we studied 38 cases of this type of neoplasm by fluorescence in situ hybridization.Fourteen cases (37%) contained IGH breaks,including six with a t(4;14) translocation.No translocations t(11;14),t(14;16),t(8;14),nor breaks involving MALT1,BCL6or FOXP1were found.Loss of 13q (40%),as well as chromosomal gains (82%) were common.There was no cor-relation between chromosomal alterations and clinical features or local relapse.Cytogenetically,extramedullary plasmacytoma and multi-ple mueloma are closely related.However,the distribution of IGH translocation partners,with the notable absence of t(11;14),is different. Key words: extramedullary plasmacytoma,multiple myeloma,cytogenetics,IGH translocation,fluorescence in situ hybridization.Citation:Bink K,Haralambieva E,Kremer M,Ott G,Beham-Schmid C,de Leval L,Peh SC,Laeng HR,Jütting U,Hutzler P,Quintanilla-Martinez L,and Fend F.Primary extramedullary plasmacytoma: similarities with and differences from multiple myeloma revealed by interphase cytogenetics.Haematologica 2008 Apr; 93(4):623-626.doi: 10.3324/haematol.12005©2008 Ferrata Storti Foundation.This is an open-access paper.IntroductionPrimary extramedullary plasmacytoma (EMP) is defined as an extraosseous proliferation of neoplastic plasma cells without evidence of bone or bone marrow involvement as evidenced by morphological bone marrow examination and radiographic studies.1EMP accounts for about 4% of plasma cell tumors, and more than 80% occur in the upper aerodigestive tract. EMP usually shows an indolent clinical course with good response to local radiotherapy, a tendency to local relapse and infrequent conversion to multiple myeloma (MM).2-4Despite these marked differences in clinical presentation and prognosis, infiltrates of EMP are morphologically indistinguishable from MM spreading to extramedullary locations,5and there are no well defined parameters predicting which patients with EMP are at risk of developing MM. On the other hand, some authors have specu-lated that EMP may represent a form of extranodal marginal zone B-cell lymphoma (MALT-type lymphoma) with extreme plasmacytic differentiation.6In recent years, the introduction of interphase fluorescence in situ hybridization (FISH)has enabled identification of clinically and prognostically relevant MM subgroups defined by recurrent chromosomal aberrations.7,8Fifty to 70% of cases of MM have translocations involving the immunoglobulin heavy chain (IGH) gene locus at 14q32. In contrast to most translocations in non-Hodgkin’s lymphoma, a large number of different chromosomal partners of 14q32 have been identified in MM, including the t(11;14)(q13;q32) involving the CCND1(cyclin D1) locus in 15-25% of patients, and the t(4;14)(p16;q32) involving the fibroblast growth factor receptor 3 (FGFR3) locus in 10-15% of cases.8,9A frequent numerical aberration is loss of chromosome 13 or parts of its long arm, which occurs in about half of MM patients.8 Furthermore, about half of MM patients exhibit hyperdiploidy, characterized by non-random chromosomal gains. Based on these data, two main types of MM of prognostic relevance have been defined, namely hyperdiploid cases with lower frequencies of recurrent 14q32 translocations or chromosome 13 abnormal-ities, and pseudo- or hypodiploid cases with a high incidence ofAcknowledgments: we would like to thank all the clinicians who contributed clinical data.The skilful technical assistance of Ulrike Buchholz is gratefully acknowledged.We thank Dr.Mark Raffeld for providing the KMS11,KMS12,KMS18 and OPM-2 cell lines.Funding:this study was supported in part by grant FE 597-1/1-2 from the Deutsche Forschungsgemeinschaft (DFG) to FF,LQ-M and MK.Manuscript received July 18,2007.Revised version arrived on September 28,2007.Accepted October 29,2007.Correspondence:Falko Fend,M.D.,Institute of Pathology,University Hospital Tuebingen,Eberhard-Karls-University,Liebermeisterstrasse 8,72076 Tuebingen,Germany.E-mail: falko.fend@med.uni-tuebingen.deThe online version of this article contains a supplemental appendix.haematologica | 2008; 93(4) | 623|K. Bink et al.| 624| haematologica | 2008; 93(4)FISH in extramedullary plasmacytomahaematologica | 2008; 93(4) | 625|K. Bink et al.| 626| haematologica | 2008; 93(4)References1.Kyle RA. Criteria for the classification of monoclonal gammopathies, multi-ple myeloma and related disorders: a report of the international myeloma working group. Br J Haematol 2003;121:749-57.2.Galieni P , Cavo M, Pulsoni A, Avvisati G, Bigazzi C, Neri S, et al. Clinical out-come of extramedullary plasmacy-toma. Haematologica 2000;8547-51.3.Batsakis JG , Medeiros JL, Luna MA,El-Naggar AK. Plasma cell dyscrasias and the head and neck. Ann Diagn Pathol 2002;6:129-40.4.Alexiou C, Kau RJ, Dietzfelbinger H,Kremer M, Spiess JC, Schratzenstaller B, et al. Extramedullary plasmacy-toma: tumor occurrence and thera-peutic concepts. Cancer 1999; 85:2305-14.5.Kremer M, Ott G, Nathrath M, Specht K, Stecker K, Alexiou C, et al. Primary extramedullary plasmacytoma and multiple myeloma: phenotypic differ-ences revealed by immunohisto-chemical analysis. J Pathol 2005;205:92-101.6.Hussong JW, Perkins SL, Schnitzer B,Hargreaves H, Frizzera G . Extra-medullary plasmacytoma. A form of marginal zone cell lymphoma? Am J Clin Pathol 1999; 111:111-6.7.Avet-Loiseau H, Facon T, Grosbois B,Magrangeas F , Rapp MJ, Harousseau JL, et al. Oncogenesis of multiple myeloma: 14q32 and 13q chromoso-mal abnormalities are not randomly distributed, but correlate with natural history, immunological features, and clinical presentation. Blood 2002;99:2185-91.8.Fonseca R, Barlogie B, Bataille R,Bastard C, Bergsagel PL, Chesi M, et al. Genetics and cytogenetics of mul-tiple myeloma: a workshop report.Cancer Res 2004;64:1546-58.9.Chesi M, Nardini E, Brents LA,Schrock E, Ried T, Kuehl WM, et al.Frequent translocation t(4;14) (p16.3;q32.3) in multiple myeloma is associ-ated with increased expression and activating mutations of fibroblast growth factor receptor 3. Nat G enet 1997;16:260-4.10.Chng WJ, Santana-Davila R, Van Wier SA, Ahmann G J, Jalal SM, Bergsagel PL, et al. Prognostic factors for hyper-diploid-myeloma: effects of chromo-some 13 deletions and IgH transloca-tions. Leukemia 2006; 20:807-13.11.Fonseca R, Blood E, Rue M,Harrington D, Oken MM, Kyle RA, et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood 2003; 101:4569-75.12.Avet-Loiseau H, Facon T, Daviet A,Godon C, Rapp MJ, Harousseau JL, et al. 14q32 translocations and mono-somy 13 observed in monoclonal gammopathy of undetermined signif-icance delineate a multistep process for the oncogenesis of multiple myeloma. Intergroupe Francophone du Myelome. Cancer Res 1999;59:4546-50.13.Bartl R, Frisch B, Fateh-Moghadam A,Kettner G , Jaeger K, Sommerfeld W.Histologic classification and staging of multiple myeloma: a retrospective and prospective study of 674 cases.Am J Clin Pathol 1987; 87:342-55.14.Haralambieva E, Adam P , Ventura R,Katzenberger T, Kalla J, Höller S, et al.Genetic rearrangement of FOXP1 is predominantly detected in a subset of diffuse large B-cell lymphomas with extranodal presentation.Leukemia 2006;20:1300-3.15.Specht K, Haralambieva E, Bink K,Kremer M, Mandl-Weber S, Koch I, et al. Different mechanisms of cyclin D1overexpression in multiple myeloma revealed by fluorescence in situ hybridization and quantitative analy-sis of mRNA levels. Blood 2004;104:1120-6.16.Perfetti V, Coluccia AM, Intini D,Malgeri U, Vignarelli MC, Casarini S,et al. Translocation t(4;14) (p16.3;q32)is a recurrent genetic lesion in primary amyloidosis. Am J Pathol 2001;158:1599-603.17.Shaughnessy J Jr., G abrea A, Qi Y,Brents L, Zhan F , Tian E, et al. Cyclin D3 at 6p21 is dysregulated by recur-rent chromosomal translocations to immunoglobulin loci in multiple myeloma. Blood 2001;98:217-23.18.Avet-Loiseau H, G erson F , Magran-geas F , Minvielle S, Harousseau JL,Bataille R. Rearrangements of the c-myc oncogene are present in 15% of primary human multiple myeloma tumors. Blood 2001;98:3082-6.19.Konigsberg R, Ackermann J,Kaufmann H, Zojer N, Urbauer E,Kromer E, et al. Deletions of chromo-some 13q in monoclonal gammopa-thy of undetermined significance.Leukemia 2000;14:1975-9.20.Chng WJ, Van Wier SA, Ahmann GJ,Winkler JM, Jalal SM, Bergsagel PL, et al. A validated FISH trisomy index demonstrates the hyperdiploid and nonhyperdiploid dichotomy in MGUS. Blood 2005;106:2156-61.21.Ott G , Katzenberger T, G reiner A,Kalla J, Rosenwald A, Heinrich U, et al. The t(11;18)(q21;q21) chromo-some translocation is a frequent and specific aberration in low-grade but not high-grade malignant non-Hodgkin's lymphomas of the mucosa-associated lymphoid tissue (MALT-) type. Cancer Res 1997; 57:3944-8.22.Streubel B, Lamprecht A, Dierlamm J,Cerroni L, Stolte M, Ott G , et al.T(14;18)(q32;q21) involving IG H and MALT1 is a frequent chromosomal aberration in MALT lymphoma.Blood 2003;101:2335-9.23.Streubel B, Vinatzer U, Lamprecht A,Raderer M, Chott A. t(3;14)(p14.1;q32) involving IGH and FOXP1is a novel recurrent chromosomal aberration in MALT lymphoma.Leukemia 2005;19:652-8.。

Jpn. J. Clin. Oncol.-2012-Kotake-29-35

Number of Lymph Nodes Retrieved is an Important Determinant of Survival of Patients with Stage II and Stage III Colorectal CancerKenjiro Kotake 1,2,*,Satoshi Honjo 2,Kenichi Sugihara 2,Yojiro Hashiguchi 2,Tomoyuki Kato 2,Susumu Kodaira 2,Tetsuichiro Muto 2and Yasuo Koyama 21Department of Surgery,Tochigi Cancer Center and 2Registry Committee,Japanese Society for Cancer of the Colon and Rectum,Tochigi-ken,Japan*For reprints and all correspondence:Kenjiro Kotake,Department of Surgery,Tochigi Cancer Center,4-9-13Yohnan,Utsunomiya,Tochigi-ken 320-0834,Japan.E-mail:kkotake@tcc.pref.tochigi.lg.jpReceived June 30,2011;accepted October 21,2011Objective:The number of lymph nodes retrieved is recognized to be a prognostic factor of Stage II colorectal cancer.However,the prognostic signiﬁcance of the number of lymph nodes retrieved in Stage III colorectal cancer remains controversial.Methods:The relationship between the number of lymph nodes retrieved and clinical and pathological factors,and signiﬁcance of the number of lymph nodes retrieved for prognosis of Stage II and III colorectal cancer were investigated.A total of 16865patients with T3/T4colo-rectal cancer who had R0resection were analysed.Results:The arithmetic mean of the number of lymph nodes retrieved of all cases was 20.0.The number of lymph nodes retrieved were varied according to several clinical and patho-logical variables with signiﬁcant difference,and the greater difference was observed in scope of nodal dissection.Survival of Stages II and III was signiﬁcantly associated with the number of lymph nodes retrieved.Five-year overall survival of the patients with 9of the number of lymph nodes retrieved and those with .27differed by 6.4%for Stage II colon cancer,8.8%for Stage III colon cancer,12.5%for Stage II rectal cancer and 10.6%for Stage III rectal cancer.With one increase in the number of lymph nodes retrieved,the mortality risk was decreased by 2.1%for Stage II and by 0.8%for Stage III,respectively.The cut-off point of the number of lymph nodes retrieved was not obtained.Conclusions:The number of lymph nodes retrieved was shown to be an important prognos-tic variable not only in Stage II but also in Stage III colorectal cancer,and it was most promin-ently determined by the scope of nodal dissection.A cut-off value for the number of lymph nodes retrieved was not found,and it is necessary to carry out appropriate nodal dissection and examine as many lymph nodes as possible.Key words:colorectal cancer –number of lymph nodes retrieved –lymph node dissectionINTRODUCTIONLymph node metastasis is the most important determinant of survival in localized colorectal cancer (CRC),and it has been used as an indicator for postoperative adjuvant chemo-therapy.In recent years,it has been recognized that in add-ition to lymph node metastasis,the number of lymph nodes retrieved (NLNR)is closely related to prognosis of Stage II CRC (1–4).Some clinical guidelines recommendpostoperative adjuvant chemotherapy in Stage II CRC with a small NLNR to prevent recurrence (5,6).However,the precise mechanism how the NLNR works on prognosis has not been clariﬁed,because the NLNR is thought to be de-pendent on the scope of lymph node dissection,quality of pathologic examination and individual differences in the number of lymph node present.Signiﬁcance of the NLNR in Stage III CRC remains controversial (1,7–10).Clinical#The Author 2011.Published by Oxford University Press.All rights reserved.For Permissions,please email:journals.permissions@Jpn J Clin Oncol 2012;42(1)29–35doi:10.1093/jjco/hyr164Advance Access Publication 18November2011at United Arab Emirates University on May 9, 2014/Downloaded fromevidence on the NLNR should be formulated,also allowing for the fact that laparoscopic surgery has been rapidly spreading in Japan since the late 1990s (11).The aim of this study is not only to investigate the rela-tionship between the NLNR and clinical and pathological factors,but also to clarify signiﬁcance of the NLNR on prog-nosis of Stage II and III CRC,using the database for the Japanese Society for Cancer of the Colon and Rectum (JSCCR),which contains information of a large number of patients with CRC recorded in accordance with the clinical and pathological classiﬁcation of the JSCCR (12).PATIENTS AND METHODSThe JSCCR has a registration system which has started in 1980.The member institutions which are located all over Japan voluntarily have been registering the clinical and pathological information of patients with CRC who were treated in each institute.The database currently contains in-formation about 140000CRC patients treated between 1974and 2002(13).A total of 16865patients who had T3or T4colorectal adenocarcinoma and underwent R0resection accompanied by D2or D3lymph node dissection between 1985and 1994were extracted from the database.Because laparoscopic surgery for CRC was introduced in 1992(11),nearly all the cases in the present study were treated with open surgery.During this period,chemotherapeutic regimens of neither 5-ﬂuorouracil and leucovorin nor oxaliplatin were available in Japan.In colon cancer,D2dissection means removal of peri-colic nodes and intermediate nodes,and D3dissection means removal of main lymph nodes at the root of the re-gional artery in addition to D2dissection.In rectal cancer,D2dissection is removal of both peri-rectal nodes locating in the mesorectum and lymph nodes along the middle rectal artery between the proper rectal fascia and the pelvic nerve plexus,and D3dissection includes removal of the main nodes around the inferior mesenteric artery and lateral nodes dissection which means removal of internal iliac and obtur-ator lymph nodes in addition to D2dissection.The classiﬁ-cation of JSCCR clearly states the scope of dissection (12).Exclusion criteria were as follows:unspeciﬁed age,syn-chronous multiple cancers,no pathologic examination of lymph nodes,unknown followed-up status and receiving perioperative radiotherapy.To eliminate possible data entry errors at the time of registration,patients with 100or more lymph nodes retrieved were also excluded.The correlation between the histologically proven NLNR and the following variables were investigated:year of treat-ment,age,gender,tumour site,histological grade,depth of tumour invasion,degree of lymph node metastasis,tumour size,scope of lymph node dissection,postoperative adjuvant chemotherapy and the number of patients registered per insti-tution.The depth of tumour invasion and degree of lymph node metastasis described by the JSCCR classiﬁcation (12),which is not translated into the UICC-TNM classiﬁcation system,is given in Table 1.S TATISTICAL M ETHODSFirst,the NLNR was investigated in relation to age,gender,tumour site,depth of tumour invasion,stage and other clinic-al and pathological characteristics using multiple linear re-gression with mutual adjustment of these factors to calculate adjusted means due to each level of them (14).Secondly,an association of the NLNR in Stage III with the number of metastasized lymph nodes was investigated by the Kruskal–Wallis test for the categorized NLNR and by the use of Spearman’s correlation coefﬁcient for the NLNR treated as continuous variable.Thirdly,survival analysis was done according to the quartiles of the NLNR for patients with Stages II and III by the Kaplan–Meier methods,and statis-tical signiﬁcance for the difference was tested by log-rank test with length of the follow-up period being truncated at 5years.Fourthly,the Cox proportional hazard model was employed to examine an effect of the NLNR on survival adjusted for other clinical variables in multivariate analyses.Table 1.Classiﬁcation of depth of tumour invasion and lymph node metastasis according to the rules by the JSCCR Depth of tumour invasion a sm Invasion beyond the mucosa but within the submucosa mpInvasion beyond the submucosa but within the proper muscle layerFor further invasion of cancers arising from the intestine covered with the serosa ss Invasion beyond the proper muscle layer but not exposed on the serosal surfacese Invasion exposed on the serosal surface siInvasion to other organs or structuresFor further invasion of cancers arising from the intestine not covered with the serosa a1Invasion beyond the proper muscle layer but penetrating not deeplya2Invasion beyond the proper muscle layer and penetrating deeply ai Invasion to other organs or structures Lymph node metastasisn0No lymph node metastasisn1Metastasis to lymph nodes that are located along the marginal artery and adjacent to the colonn2Metastasis to lymph nodes that are located along the course of the major vessels supplying the arean3Metastasis to lymph nodes that are located around the superior or inferior mesenteric vessels,and/or metastasis to lateral lymph nodes for some cases with rectal cancern4Metastasis to lymph node more distant than that for n3JSCCR,Japanese Society for Cancer of the Colon and Rectum.asm,mp,a group consisting of ss,a1and a2,another group consisting of se,ai and si are corresponding to the UICC pT1,pT2,pT3and pT4,respectively.30Number of lymph nodes retrievedat United Arab Emirates University on May 9, 2014/Downloaded fromDummy variables in the models were assigned to levels of relevant variables other than a reference category of each variable.Interactions between the NLNR and degree of lymph node metastasis (presence or absence),scope of lymph node dissection and tumour site (colon vs.rectum)on the risk for death due to CRC were examined by comparing the full model with the model having also the interaction terms;the likelihood ratio statistics obtained from 22times difference in log-likelihood between the two models was tested as x 2statistics.Because the interaction between the NLNR and the lymph node metastasis was statistically sig-niﬁcant as shown in the latter,the multivariate analysis by the Cox model was performed for the Stage II and III cancers separately.Finally,martingale residuals (15)were computed based on the model including the year of treat-ment,age,gender,depth of tumour invasion,histological grade,tumour site,tumour size,lymph node dissection,post-operative chemotherapy (done vs.not done)and the number of registrations from institution.The residuals were plotted against the NLNR for Stages II and III,separately.All statis-tical analyses were performed using STATA Statistical Software (STATA Corporation,College Station,TX,USA),and P ,0.05was regarded as denoting statistical signiﬁ-cance otherwise speciﬁed.RESULTSFigure 1shows the distribution of the NLNR for 16865patients.A total of 336857lymph nodes were retrieved,with a median of 17.0,an arithmetic mean of 20.0with a standard deviation of 14.0and a mode of 10.Because the NLNR was distributed with the right skewness,a log-transformed value of the NLNR was used in most statistical analyses and the geometric mean was calculated instead of the arithmetic mean in the following section.As shown in Table 2,the NLNR was varied according to categories of selected variables including age,gender,degree of tumour invasion,histological grade,tumour site,tumour size,scope of lymph node dissection,degree of lymph node metastasis and number of registration per insti-tute.The greater difference in the NLNR was observed in scope of lymph node dissection.The NLNR was divided into four subgroups (quartiles): 9,10–16,17–26and 27.The number of metastatic nodes for each subgroup is shown in Table 3.The number of positive lymph nodes was increased with the increasing NLNR.The same was observed in each site.Even when handling the both number as continuous variables,the two were weakly correlated to each other (Spearman’s correlation coefﬁcient ¼0.0813,P ,0.01).Overall survival of Stages II and III was signiﬁcantly asso-ciated with the NLNR.The same results were observed even if it was investigated according to tumour sites (Table 4).When comparison was made between patients with 9of the NLNR and those with 27,the 5-year overall survival differed by 6.4%for Stage II colon cancer,8.8%for Stage III colon cancer,12.5%for Stage II rectal cancer and 10.6%for Stage III rectal cancer.The 5-year disease-speciﬁc survival differed similarly between those with 9of the NLNR and with 27(P ,0.001,data not shown).Scope of the lymph node dissection and tumour site did not inﬂuence the effect of the NLNR on the risk for death (P for interaction ¼0.91and 0.58,respectively,when the NLNR was categorized;and 0.19and 0.84,respectively,when the NLNR was treated as a continuous variable),but lymph node metastasis inﬂuenced the effect of the NLNR (P ,0.01when the NLNR was categorized or treated as con-tinuous).Therefore,the Cox proportional hazard model was employed for the Stage II and III CRC separately examining CRC mortality risk due to the increasing NLNR adjusted for age,sex,scope of the dissection and other factors (Table 5).Stages II and III with 27of the NLNR had the decreased risk by 54and 25%when compared with those with 9,re-spectively.With one increase in the NLNR,CRC mortality risk was decreased by 2.1%for Stage II and by 0.8%for Stage III,respectively.For both Stages II and III,the cut-off point was not obtained because the plots of the martingale residuals were fairly linear (data not shown).DISCUSSIONIn the present study,it was shown that the NLNR was a crit-ical prognosticator for not only Stage II but also Stage III CRC.The arithmetic average of the NLNR in our study was comparable to the reports based on data from single institu-tion (16–18).On the other hand,the NLNR was around 10in the studies that examined large-scale database,such as the NCDB and SEER (2,10,19,20).Theoretically,the NLNR may be inﬂuenced by the extent of surgery or scope of lymph node dissection,technique of pathologic examination and individual difference intheFigure 1.Number of lymph nodes retrieved per patient in 16865colorectal cancer patients using the JSCCR database.JSCCR,Japanese Society for Cancer of the Colon and Rectum.Jpn J Clin Oncol 2012;42(1)31at United Arab Emirates University on May 9, 2014/Downloaded fromTable 2.Adjusted means of the number of lymph nodes retrieved (NLNR)according to clinical and pathological variables Variables Number of cases Adjusted means of NLNR 95%conﬁdence interval P value1985148315.52Reference 1986167815.3614.5916.160.6891987165115.0714.3215.870.2631988167914.7013.9615.480.0391989185815.0514.3215.820.2311990194815.3214.5816.100.6151991164115.3314.5516.140.6361992156316.3015.4717.170.0671993155416.4015.5617.280.0401994181015.7915.0016.610.510Trend0.001Age (years)16–4054220.5219.2421.88,0.00141–54348717.2416.7117.78,0.00155–64549915.54Reference 65–74480514.7214.3115.15,0.00175þ253213.5913.1214.08,0.001Trend,0.001Sex Male 971615.13Reference Female 714915.9215.5716.28,0.001Depth of invasion ss/a1989215.14Reference s/a2606716.0015.6316.39,0.001si/ai 90615.3514.5916.150.600Trend0.001HistologyWell differentiated 841516.00Reference Moderately differentiated 714314.9914.6515.34,0.001Others 130714.6914.0615.35,0.001SiteRight colon 481717.60Reference Left colon 528113.5713.1813.97,0.001Rectum 676715.6015.1716.04,0.001Diameter (mm)10–1915910.859.6912.14,0.00120–2982710.9610.3911.58,0.00130–39221512.6212.1513.11,0.00140–49332414.18Reference 50–59332115.8515.3216.40,0.00160–69249117.2216.6017.87,0.00170–79150118.1017.3318.90,0.00180–8997119.0018.0520.00,0.001Continued32Number of lymph nodes retrievedat United Arab Emirates University on May 9, 2014/Downloaded fromnumber of nodes present.The present study clearly showed that the scope of lymph node dissection affected the NLNR. More lymph nodes are to be harvested for D3than for D2 dissection if the pathological examination technique is con-stant.The NLNR was dependent on factors other than scope of lymph node dissection in the present investigation,and theﬁndings on several factors were comparable with those from previous studies including gender,age,degree of lymph node metastasis,grade of differentiation,tumour site, depth of tumour invasion and size(2,3,9,10,17,19,21).Associations of those factors with the NLNR may be explained as follows:(i)the reported association between the NLNR and lymph node metastasis may be possibly related to the larger size of metastatic nodes than that of non-metastatic ones(19,22),(ii)proliferation of lymph tissue around the ileocecal region and the longer removed bowel may be associated with the larger NLNR for the right than for the left colon and(iii)lateral dissection for rectal cancer should be associated with the increased NLNR.Although we have no direct evidence showing the contribution ofTable2.ContinuedVariables Number of cases Adjusted means of NLNR95%conﬁdence interval P value90–9954219.5518.3220.87,0.001 100–19972919.3018.2020.48,0.001Trend,0.001 Scope of lymph node dissectionD2624412.31ReferenceD3*******.6617.2518.08,0.001 Grade of lymph node metastasisn0914315.00Referencen1461515.9615.5516.38,0.001 n2260116.4315.9016.97,0.001 n350614.6013.6715.600.429Trend,0.001 Reported chemotherapyNo587015.61ReferenceYes1099515.3815.0115.750.219 Number of registrations per institution1–1957512.2611.5013.07,0.001 20–49139714.9314.3115.590.518 50–99337414.7814.3315.250.806 100–199603014.72Reference200þ548917.2716.8117.75,0.001Trend,0.001Table3.Number of lymph node retrieved and that of metastatic lymph nodesNLNR Total Number of metastatic lymph nodes(mean)Right colon Left colon Rectum1–9 2.1 2.2 1.9 2.110–16 2.9 3.2 2.7 2.717–26 3.4 3.9 2.9 3.127þ 4.1 4.8 3.4 3.6 Overall 3.2 3.6 2.65 3.03Table4.Five-year overall survival rates of the patients with Stage II and III colorectal cancer according to the number of lymph nodes retrievedNLNR Stage II Stage IIIColon Rectum Colon Rectum1–981.071.664.253.910–1684.379.468.155.817–2684.682.968.854.827þ87.484.173.064.5Log-rank0.0006,0.00010.0003,0.0001Jpn J Clin Oncol2012;42(1)33at United Arab Emirates University on May 9, 2014/Downloaded frompathological technique to the NLNR (2),it is difﬁcult to ﬁnd other speculation other than differentiated precision of patho-logical examination for the variation in the NLNR by insti-tute (23).It remains unknown why age and gender were related to the NLNR as shown not only in the present but also in other studies (2,3,10).Studies have reported that the NLNR is inﬂuenced also by inﬂammation (21),diverticulum (21)and obesity (19,23,24).In this manner,the NLNR is determined most prominently by the extent of surgery,but is inﬂuenced to some degree by other factors.In the present study,patients with the larger NLNR had a signiﬁcantly better prognosis,and the increased NLNR was associated with decreased risk of death.Furthermore,there was a positive correlation between the NLNR and the number of lymph node metastases (16).When more lymph nodes are examined,the opportunity for discovering a meta-static lymph node is believed to increase and the likelihood of under-staging may decrease.However,the ﬁnding that patients with the larger NLNR may have the better chance for survival,regardless of the number or metastasized nodes,should be more important (10).This cannot be explained based solely on stage migration.Because the present study is retrospective,a residual confounding effect from other related clinical factors should remain after statistical adjust-ment for those.We found no clear statistical evidence for interaction between the scope of lymph node dissection and the NLNR on the risk for death while the NLNR was signiﬁ-cantly larger for D3than for D2.This ﬁnding may explain not only the valid staging but also a possible resection of occult metastasis to lymph nodes is potentially related to im-provement in prognosis.The effects of the NLNR on prognosis,however,cannot be explained based solely on the extent of surgery and pathological examination.The reason for this is that few surgeons would alter the extent of surgery and few patholo-gists would modify examination techniques based on gender,age and histological grade.Thus,a third factor,such as individual differences in lymph nodes as deﬁned by host –tumour relationships,may be considered to be involved.Leibl et al.(21)hypothesized that ‘lymph node neo-formation’established by micro-vessels and peri-capillary lymphocyte accumulation may contribute to indi-vidual variation in the NLNR.Further studies are required to explain the association of individual difference in lymph node and prognosis.For proper assessment of resection and staging,the NLNR is a critical clinical issue to solve.With UICC and AJCC TNM classiﬁcation,based on the recommendation by the Working Party Report to the World Congress of Gastroenterology in 1999(25,26),at least 12lymph nodes should be examined to ensure N0.However,this recommen-dation has few pieces of evidence.Swanson et al.(2)com-mented that 13or more of lymph nodes should be examined to be judged as N0,Wong (17)and Tepper (1)reported 14,Goldstein did 17(16)and Le Voyer et al.(10)did 20.In these studies,no coherent logic leading to the proper NLNR has been established.In the present study,a cut-off value for the NLNR was not determined.This ﬁnding was comparable to a large-scale SEER study (4),as well as a study conducted by individual institution (16).In addition to the NLNR,recent studies demonstrate that a ratio of metastatic lymph node to NLNR (i.e.lymph node ratio)has prognostic signiﬁcance for estimating overall survival for the patients with colon cancer (27–29),although the cut-off value of the ratio remains undetermined.Therefore,at the present,it is required to dissect and examine as many regional lymph nodes as possible for reliable staging.Patients with the small NLNR following proper dissection and pathological examination should be considered at high risk of recurrence.The mainstay of treatment against CRC is surgery.Local control with proper surgery and appropriate adjuvant therapy based on reliable pathological staging are essential.The NLNR may be a potential indicator for postoperative adju-vant therapy.Table 5.Hazard ratio of patients with Stage II and III colorectal cancer according to NLNR analysed by Cox’s proportional model NLNRStage II Stage III Number of casesHazard ratio a 95%CI P valueNumber of cases Hazard ratio 95%CI P value1–92294 1.00Reference 1758 1.00Reference 10–1623330.630.530.76,0.0119490.910.80 1.030.1417–2622900.590.490.72,0.0119690.920.81 1.050.2327þ22260.460.370.57,0.0120460.750.650.86,0.01Trend ,0.01Trend ,0.01Increase by 1node0.9790.9720.985,0.010.9920.9890.996,0.01CI,conﬁdence interval.aHazard ratio of patients with Stage II and III CRC according to NLNR analysed by Cox’s proportional model.34Number of lymph nodes retrievedat United Arab Emirates University on May 9, 2014/Downloaded fromFinally,we should mention the limitations of the study. Since the present study was retrospectively done and infor-mation on cases without follow-up was not used for the ana-lyses,the effect of the NLNR on the survival in the present study is possibly over-or underestimated. CONCLUSIONSIn the present analysis of a database containing information on patients with20lymph nodes retrieved on average,the NLNR was shown to be an important prognostic variable in Stage II and III CRC,especially in patients with Stage III, as well as the number of metastatic nodes.The NLNR was determined most prominently by the scope of lymph node dissection and by other patient’s proﬁle and characteristics of tumour.A cut-off value for the NLNR was not found,and it is necessary to carry out proper dissection and examine as many lymph nodes as possible(4,9).Basic and clinical studies investigating the relation between the varying NLNR across individuals and oncological outcome should be reinforced.FundingJapanese Society for Cancer of the Colon and Rectum. Grant-in-Aid from the Ministry of Health,Labour and Welfare of Japan.Conﬂict of interest statementNone declared.References1.Tepper JE,O’Connell MJ,Niedzwiecki D,Hollis D,Compton C,Benson AB,3rd,et al.Impact of number of nodes retrieved on outcome in patients with rectal cancer.J Clin Oncol2001;19:157–63.2.Swanson RS,Compton CC,Stewart AK,Bland KI.The prognosis ofT3N0colon cancer is dependent on the number of lymph nodes examined.Ann Surg Oncol2003;10:65–71.3.Sarli L,Bader G,Iusco D,Salvemini C,Mauro DD,Mazzeo A,et al.Number of lymph nodes examined and prognosis of TNM stage II colorectal cancer.Eur J Cancer2005;41:272–9.4.Cserni G,Vinh-Hung V,Burzykowski T.Is there a minimum number oflymph nodes that should be histologically assessed for a reliable nodal staging of T3N0M0colorectal carcinomas?J Surg Oncol2002;81: 63–9.5.NCCN Clinical Practice Guidelines in Oncology.Colon Cancer.V.3.2010./professionals/physician_gls/PDF/colon.pdf6.National Cancer Institute.Colon Cancer(PDQ)./cancertopics/pdq/treatment/colon/healthprofessional7.Prandi M,Lionetto R,Bini A,Francioni G,Accarpio G,Anfossi A,et al.Prognostic evaluation of stage B colon cancer patients is improved by an adequate lymphadenectomy:results of a secondary analysis of a large scale adjuvant trial.Ann Surg2002;235:458–63.8.Caplin S,Cerottini JP,Bosman FT,Constanda MT,Givel JC.Forpatients with Dukes’B(TNM Stage II)colorectal carcinoma, examination of six or fewer lymph nodes is related to poor prognosis.Cancer1998;83:666–72.9.Johnson PM,Porter GA,Ricciardi R,Baxter NN.Increasing negativelymph node count is independently associated with improved long-termsurvival in stage IIIB and IIIC colon cancer.J Clin Oncol2006;24:3570–5.10.Le Voyer TE,Sigurdson ER,Hanlon AL,Mayer RJ,Macdonald JS,Catalano PJ,et al.Colon cancer survival is associated with increasingnumber of lymph nodes analyzed:a secondary survey of intergroup trialINT-0089.J Clin Oncol2003;21:2912–9.11.Inomata M,Yasuda K,Shiraishi 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快速康复外科理念在妇科手术中的应用研究

基层医学论坛2021年3月第25卷第7期快速康复外科理念在妇科手术中的应用研究刘文利（苍梧县人民医院，广西苍梧543100）随着近年来医疗卫生事业的发展，以及临床对围术期患者病理生理认知理念的深入，快速康复外科（FTS ）理念应运而生。

FTS 理念最先由丹麦的外科医生Kehlet 提出的，有相关研究表明，该理念对降低患者术后并发症，促进术后快速恢复等方面具有一定作用[1~3]。

围术期给予患者积极有效的治疗与护理有助于促进患者机体尽快康复与降低并发症发生率。

FTS 是运用循证医学的优化措施，减少患者生理和心理应激反应，减少术后并发症，加速术后康复和节省住院费用及医疗资源[4，5]。

FTS作用主要表现在从围术期至患者机体达到康复指标期，是麻醉、护理、康复、营养等多学科协同合作的过程。

FTS 以促进患者康复，降低手术应激和并发症发生率为目的，也被称为促进术后康复措施[6-8]。

本文就FTS 理念在妇科手术中的应用效果及进展综述如下。

1FTS 理念及在妇科手术中的应用现状FTS 是指为了使患者在围术期减少生理及心理方面的应激创伤，采取具有循证医学依据的优化措施，达到快速出院的目的[9，10]。

具体措施包括术前、术中及术后的处理。

FTS 作为一种具创新性理念与优化的外科模式,国外学者Moller 等初次在子宫肌瘤术中应用并取得了成功，开创了FTS 模式应用于临床外科的先河。

随之而来，国内外大量相关研究证实了应用FTS 模式较常规模式对患者术后疼痛、住院时间以及并发症发生率与安全性等效果更令人满意。

国内黄雪霞、周维艳等[11，12]在研究中认为将FTS 应用于临床具有良好效果。

经多项研究显示，FTS 及对应的护理模式在降低妇科手术患者术后并发症发生率、加快术后康复、减少住院时间与经费等方面均较常规方法理想。

国际快速康复外科协会于2016年发布了应用于妇科的FTS 指南，首次将FTS 在妇科的应用予以了规范化总结。

艾宾浩斯遗忘曲线应用于手术室护理人员操作技能培训的学习曲线分析

艾宾浩斯遗忘曲线应用于手术室护理人员操作技能培训的学习曲线分析瞿田星天津医科大学肿瘤医院,国家恶性肿瘤临床医学研究中心;天津市恶性肿瘤临床医学研究中心;天津市肿瘤防治重点实验室,天津300060A n a l y s i s o f l e a r n i n g c u r v e o f E b i n g h a u s f o r g e t t i n g c u r v e a p p l i e d t o o p e r a t i o n s k i l l t r a i n i n g o f n u r s i n g p e r s o n n e l i no p e r a t i n g r o o mQ UT i a n x i n gT i a n j i n M e d i c a lU n i v e r s i t y C a n c e r I n s t i t u t e&H o s p i t a l,N a t i o n a lC l i n i c a lR e s e a r c hC e n t e r f o rC a n c e r;T i a n j i n's C l i n i c a lR e s e a r c hC e n t e r f o rC a n c e r;K e y L a b o r a t o r y o fC a n c e rP r e v e n t i o na n dT h e r a p y,T i a n j i n300060C h i n a C o r r e s p o n d i n g A u t h o r Q UT i a n x i n g,E-m a i l:707753689@q q.c o mK e y w o r d s E b b i n g h a u s;f o r g e t t i n g c u r v e;L e o n a r d oD aV i n c i r o b o t;o p e r a t i o n s k i l l;l e a r n i n g c u r v e摘要目的:探讨基于艾宾浩斯遗忘曲线原理在手术室护士学习并掌握达芬奇机器人手术系统操作中的应用效果㊂方法:选取2020年1月 2021年6月某三级甲等医院手术室参与达芬奇机器人手术的护理人员40名,使用在线随机发生器随机分为试验组与对照组,各20名㊂试验组基于艾宾浩斯遗忘曲线原理进行教学方案设计,并绘制学习曲线㊂对照组按照传统模式进行教学后自行练习,并绘制学习曲线㊂两组均采用达芬奇机器人手术配合考核表进行考核㊂结果:试验组理论考核成绩优于对照组(P< 0.05)㊂试验组达芬奇机器人手术系统操作中单支无菌器械臂罩装置时间㊁参数设置时间㊁人机对接次数㊁术后系统处理时间4项指标的学习曲线,进入熟练掌握期操作次数均短于对照组㊂结论:将艾宾浩斯遗忘曲线原理融入到达芬奇机器人手术系统的操作教学中,可有效缩短被培训人员的学习曲线,并能提高其理论知识掌握程度㊂关键词艾宾浩斯;遗忘曲线;达芬奇机器人;操作技能;学习曲线d o i:10.12102/j.i s s n.2095-8668.2024.07.022达芬奇机器人手术系统作为人工智能领域与现代生物医学结合发展的新生代设备,凭借其三维立体高分辨率㊁高达720ʎ的可转腕手术器械以及无延迟的同步操控技术等优势,在手术方面具有精确度更高㊁操作更加灵活㊁适用范围更广等优势,广泛应用于多种外科领域[1]㊂而随着国内各所医疗机构的不断引入,达芬奇机器人手术的开展量也在飞速地增加㊂因此,对于配合该类手术的手术室专科护士的需求量也随之增加㊂达芬奇机器人手术系统的操作作为专科护士所必须学习掌握的内容,具有涉及学科广㊁个性化需求多㊁操作量大㊁易遗忘等特点㊂达芬奇机器人厂商和国内定点的培训机构所提供的培训内容较多集中于达芬奇机器人操作理论㊁单病种手术专科练习㊁常见错误排查等[2]㊂需要对配合达芬奇机器人手术的护士进行临床再培训,才能减少临床操作知识盲点,培训出合格的临基金项目天津市医学重点学科(专科)建设项目,编号: T J Y X Z D X K-011A作者简介瞿田星,主管护师,本科,E-m a i l:707753689@q q.c o m 引用信息瞿田星.艾宾浩斯遗忘曲线应用于手术室护理人员操作技能培训的学习曲线分析[J].循证护理,2024,10(7): 1257-1261.床达芬奇机器人专科护士[3]㊂学习过程中最大的障碍在于遗忘,遗忘是指不能或错误地再认或回忆识记的内容[4]㊂德国心理学家艾宾浩斯(E b b i n g h a u s)证实,遗忘存在一定的规律曲线即艾宾浩斯遗忘曲线,间隔1d的遗忘率最高,2~31d遗忘率稳定在72%~ 79%[5]㊂学习曲线是指在对于一项新生事物不断学习中,逐渐熟练掌握该新生事物相关操作的过程[6]㊂本研究结合艾宾浩斯遗忘曲线原理进行教学方案的设计,制定出符合遗忘规律的操作技能培训方案,并通过绘制研究对象的学习曲线,对整个学习过程可实现针对性指导,对于临床教学具有一定的实际意义㊂1对象与方法1.1研究对象选取2020年1月 2021年6月某三级甲等医院手术室参与达芬奇机器人手术的护理人员40名,使用在线随机发生器随机分为试验组和对照组,各20名㊂纳入标准:1)独立配合各专科开放手术;2)独立配合各专科腔镜手术;3)从未接触过达芬奇机器人手术㊂排除标准:1)未完成教学;2)因各种原因退出研究者㊂两组护理人员在性别㊁年龄㊁学历等一般资料方面比较,差异无统计学意义(P>0.05),具有可比性㊂见表1㊂表1 两组护理人员一般资料比较组别人数性别(人) 男女工作年限(x ʃs ,年) 职称(人)护士护师主管护师学历(人)专科本科对照组205159.63ʃ3.554610218试验组206148.21ʃ2.92569119统计值χ2=0.326t =1.382χ2=0.418 χ2=0.568P0.7480.1580.6800.5761.2 方法1.2.1 对照组采用传统的教学方法进行培训,由科室制定的专业组长及带教人员担任培训员,采用一对一带教,连续带教7d (培训次数为每日1次)后,被带教人员通过科室制定的达芬奇机器人手术配合资质考核后独立操作,记录其15台手术的操作数据,绘制学习曲线㊂1.2.2 试验组根据艾宾浩斯遗忘曲线的规律,刚刚记忆完毕的记忆量为100.0%,20m i n 后的记忆量为58.2%,1h 后的记忆量为44.2%,8~9h 的记忆量为35.8%,1d 后的记忆量为33.7%,2d 后的记忆量为27.8%,15d后的记忆量为21.0%㊂结合达芬奇机器人手术系统操作技能内容设计培训程序卡(见表2),并根据规律确定培训的时间及相应的内容㊂试验组培训周期严格按照艾宾浩斯遗忘曲线进行,第2次培训内容是在结束第1次培训后20m i n 后进行,第3次培训是在第2次培训结束后1h 进行,第4次培训由于时间间隔的原因,按照8~9h 的计划时间,安排在当日工作时间最后阶段进行,后续培训计划严格按照艾宾浩斯遗忘曲线进行㊂试验组第1次和第2次培训的培训内容与对照组一样,培训内容包括培训程序卡全部内容,第3次培训内容以项目1~3为主,第4次培训内容以项目4~6为主,第5次培训项目以项目7和8为主,循环往复,每次培训突出相应重点,在培训之前评价上次培训的结果㊂对于被培训人员掌握程度较差的项目,由培训人员进行讲解并提出合适的解决方法㊂根据被培训人员每次培训中易发生错误的内容,在突出本次培训重点的同时,强化培训上次培训中易发生的错误㊂培训次数与对照组一致,同样为7次㊂培训结束后,被培训人员通过科室制定的达芬奇机器人手术配合资质考核后,独立配合手术,记录其15台手术的操作数据,绘制学习曲线㊂表2 达芬奇机器人手术系统操作技能培训程序卡培训项目培训内容机器臂摆放①掌握机械臂的控制方法②掌握无菌器械臂套的装置方法③掌握关机状态和备用状态机械臂标准摆放位置④掌握机械臂的收放和摆放方法⑤掌握无菌器械臂套装置过程中的无菌原则器械的识别及作用①电钩㊁电剪刀(单极做功)②马里兰㊁双极圆头(双极做功)③心包钳㊁强力抓钳(抓持作用)④大针持㊁强力针持(缝合作用)⑤大号㊁中号锁扣钳(闭合作用)⑥胸腔牵拉钳㊁腹腔牵拉钳(牵拉作用)⑦超声刀的组装及注意事项(切割作用)⑧特殊器械的识别⑨穿刺器及配件使用⑩器械相关配件的使用机器人用物的识别器械臂套㊁镜头臂套㊁镜头套㊁剪刀帽㊁封堵帽㊁0ʎ镜头㊁30ʎ镜头㊁穿刺器(普通㊁加长㊁一次性)㊁单极线㊁双极线器械及镜头装机①掌握器械臂安装在穿刺器的方法②掌握正确放入和取出器械臂上器械的方法③掌握镜头白平衡设置和3D 校准的方法④掌握镜头与光源线对接方法⑤掌握装机后甜蜜点位置(s w e e t s po t )㊁器械臂位置㊁镜头臂高度㊁病人皮肤检查方法机器人系统连接及开㊁关机方法和注意事项①掌握正确连接电源,开㊁关机方法②掌握机器人自检过程中指示灯含义及故障处理(续表)培训项目培训内容床旁机械臂系统与手术床位置摆放①掌握头颈手术床旁机械臂系统及手术床的位置②掌握胸部手术床旁机械臂系统及手术床的位置③掌握下腹部手术床旁机械臂系统及手术床的位置④掌握上腹部手术床旁机械臂系统及手术床的位置⑤熟练掌握床旁机械臂系统的手动模式功能识别机械臂指示灯的含义及手术过程中出现紧急情况的检查顺序①蓝灯或白灯不闪动,器械已固定,主刀医生可操控②白灯闪动,器械未固定,提示助手医生操作③绿灯闪动表示器械的记忆功能存在,可将器械臂直接放入④黄灯报警表示问题可解决,看屏幕提示⑤红灯表示出现系统错误,应立即停止任何手术操作,首先将系统静音,然后检查错误项目,根据屏幕进行相关操作⑥系统屏幕常见的各种英文提示的含义㊁各种报警提示的含义及处理方法正确处理所有术后用物掌握镜头㊁机械臂㊁穿刺器㊁线缆术后预处理方法1.3评价指标1.3.1理论成绩两组护理人员培训结束后,采用科室设计的达芬奇机器人手术配合资质考核表进行理论成绩考核㊂考核内容根据临床手术中实际操作归类并分别赋予相应分值,包括:机械臂摆放(20分);器械的识别及作用(10分);机器人用物的识别(10分);器械及镜头装机(10分);机器人系统连接及开㊁关机方法和注意事项(10分);床旁机械臂系统与手术床位置摆放(10分);识别机械臂指示灯的含义及手术过程中出现紧急情况的检查顺序(20分);正确处理所有术后用物(10分),共8项,满分为100分㊂1.3.2单支无菌器械臂罩装置时间㊁参数设置时间㊁人机对接次数㊁术后系统处理时间收集两组护理人员的单支无菌器械臂罩装置时间(δ1)㊁参数设置时间(δ2)㊁人机对接次数(δ3)㊁术后系统处理时间(δ4),采用累积和分析法(C U S UM)绘制两组护理人员在独立配合手术时15台手术的学习曲线㊂C U S UM最早应用工业生产以评价劳动工人的生产技能,后逐渐被用于医学专业临床技术等方面关于学习曲线等研究[7],其评价指标计算公式为δ=X i-X0,其中δ为操作水平的量化值,X0为评价指标所设目标值的失败率㊂当初学者评价指标达到目标值时X i=0,若未达到所设目标值则X i=1㊂依照C U S UM 计算公式ði=δ1+δ2+δ3+δ4㊂绘制学习曲线,横坐标(X)为手术例数,纵坐标(Y)为ði(依次累加值),首例病例的C U S U M值是4项量化指标的和;第2例的C U S U M值是第2例的4项量化指标的和,再加上第1例的C U S U M值,以此类推至第15例[8-9]㊂1.4统计学方法采用S P S S21.0软件进行统计分析,符合正态分布的定量资料用均数ʃ标准差(xʃs)表示,行t检验㊂应用S P S S21.0软件曲线拟合方法刻画X轴与Y 轴的曲线关系,其中横坐标(X)为手术配合例数,纵坐标(Y)为累积和值ði㊂拟合模型检验以P值判断,P< 0.05曲线拟合成功㊂以系数R2判断拟合优度,R2越接近于1,曲线拟合优度越高,R2最高的模型,即为最佳拟合模型㊂根据学习曲线函数公式计算学习曲线斜率K,当K值在逐渐减小至负值时,其所对应的手术例数即为掌握该项技能所需要的最小手术例数[10]㊂以P<0.05为差异有统计学意义㊂2结果2.1理论成绩(见表3)表3两组护理人员理论成绩比较(xʃs)单位:分考核项目对照组(n=20)试验组(n=20)t值P 机器臂摆放13.16ʃ2.6116.00ʃ2.75-4.342<0.001器械的识别及作用6.30ʃ0.868.60ʃ1.05-6.744<0.001机器人用物的识别5.90ʃ0.858.30ʃ0.92-8.718<0.001器械及镜头装机5.60ʃ1.397.70ʃ1.49-5.688<0.001机器人系统连接及开㊁关机方法和注意事项6.10ʃ0.918.00ʃ1.03-7.292<0.001床旁机械臂系统与手术床位置摆放5.60ʃ1.547.60ʃ1.79-4.156<0.001识别机械臂指示灯的含义及手术过程中出现紧急情况的检查顺序13.30ʃ2.0616.55ʃ2.16-5.143<0.001正确处理所有术后用物6.15ʃ1.047.90ʃ1.45-4.837<0.0012.2学习曲线试验组学习曲线函数为Y=-10.34+13.09X-1.55X2+0.05X3,函数决定系数R2=0.983;对照组学习曲线函数为Y=-0.59+4.40X-0.97X2-0.01X3,函数R2=0.968㊂通过分析学习曲线,对照组与试验组学习曲线累积和值斜率开始变为负值时对应的操作次数分别为7次和11次,两组护理人员学习曲线出现拐点,试验组人员在4项评价指标的学习曲线进入熟练掌握期的时间均短于对照组,见图1~图5㊂图1两组护理人员总体学习曲线比较图图2两组护理人员单支无菌器械臂罩装置累积时间比较图图3两组护理人员参数设置累积时间比较图图4两组护理人员人机对接累积次数比较图图5两组护理人员术后系统处理累积时间比较图3讨论3.1达芬奇机器人手术系统操作技能规范化培训的必要性随着国内医疗机器人的迅速引进,达芬奇机器人手术开展呈大幅度增长趋势,因此对于配合相应手术的护理人员的需求量也迅速增长㊂达芬奇机器人手术系统设备组成复杂㊁技术操作指标多㊁涉及学科广泛,对于初学者来说,短时间内接受大量的知识,其掌握的程度不牢固,同时在培训接受后短时间内未独立操作,不能将学到的理论知识熟练掌握并转化为实际操作能力㊂因此,手术护理人员需要通过规范化的专科护理培训才能为病人提供高效的护理服务,使病人达到更佳的术后恢复效果[11]㊂本研究基于艾宾浩斯遗忘曲线设计教学培训内容,根据遗忘曲线的规律制定培训的时间节点和相应需掌握的内容,将学习重点和学习细节有效结合进行培训,根据时间节点匹配培训内容,将全部培训内容按阶段有序进行㊂被培训人员在易于掌握培训内容的基础上,可实现对培训重点和目标的深度理解㊂同时,采用在培训之前强化上次培训重点的模式,可将已经掌握的知识进行印象加深㊂3.2艾宾浩斯遗忘曲线在达芬奇机器人手术系统操作技能培训中的应用结果显示,试验组经过基于艾宾浩斯遗忘曲线设计的教学培训后,对于达芬奇机器人手术系统操作技能相关的理论水平明显高于对照组㊂对照组人员虽然培训次数等同于试验组,但其在培训结束后存在短时间内未独立实际操作㊁操作重点内容未强化练习㊁操作细节遗忘等情况,符合艾宾浩斯遗忘曲线所呈现出来的先快后慢规律[12],因此,在操作技能考核的8项内容中,对照组得分明显低于试验组,差异有统计学意义(P< 0.05)㊂高峰等[8-10,13]已经证明在临床手术领域中短时间内提高操作的频数㊁缩短操作的间隔时间能够明显帮助初学者记忆和熟悉操作流程,掌握操作的重点环节和细节的理解,协助初学者迅速进入熟练掌握的状态㊂这也佐证了本研究采用的方法有正确的科学意义,针对操作复杂的达芬奇机器人手术系统,基于艾宾浩斯遗忘曲线设计教学培训可帮助初学者迅速度过学习曲线,提前进入熟练掌握阶段㊂同时根据遗忘曲线的规律,适时地对机器人教学内容中的重点和难点进行合理的巩固和重复,能够使记忆保持得更长久㊁更完整[14],巩固和重复的同时将容易培训中易发生错误的内容进行有目标的强化,更利于将未完全掌握的知识进一步提高和确认㊂3.3基于艾宾浩斯遗忘曲线原理对学习曲线相关研究的探讨艾宾浩斯遗忘曲线自提出以来,广泛应用于教育行业等,针对护理方面技能的培训少有研究㊂严加洁等[15]将其引入针对病人的糖尿病健康教育等方面,杨京晶等[5]采用该曲线针对护理人员进行相关技能的培训,均取得了良好的效果,证明采用艾宾浩斯遗忘曲线原理对人员进行技能相关培训是有一定的优势㊂在临床医学领域,学习曲线的研究方法已广泛应用于某一类技术或者手术的学习过程研究,在护理领域的相关研究则处于刚刚起步的阶段㊂姚轶超等[16]证明在手术护理相关领域内,应用学习曲线的方法也可以将某项护理技术的学习过程进行数据化研究㊂本研究基于艾宾浩斯遗忘曲线的原理,制定培训目标和计划,将达芬奇机器人手术系统操作技能的培训内容进行细化㊂同时基于学习曲线的评价方法,收集培训结束后独立配合手术时的相应数据,绘制单支无菌器械臂罩装置时间㊁参数设置时间㊁人机对接次数㊁术后系统处理时间4条学习曲线㊂图2~图5显示,4项评价指标随着配合次数的增加而逐渐降低,并且在一定次数之后,该项指标的数据进入相对稳定阶段即熟练掌握期㊂同时,通过比较学习曲线,试验组进入熟练掌握期的次数少于对照组,说明两组护理人员虽经过同样的培训次数,但试验组对于培训内容的接受㊁理解及实际应用的效果要优于对照组,基于艾宾浩斯遗忘曲线原理设计操作技能培训可以使被培训人员更快㊁更高效地掌握培训内容㊂4小结本研究通过基于艾宾浩斯遗忘曲线设计教学培训计划,将培训重点和培训细节有效结合进行,根据时间节点匹配培训内容,将全部培训内容按阶段进行有序进行,高效地培训出具有合格手术配合能力的护士的同时为手术室制定新的培训模式提供参考㊂同时,本研究可扩大适用范围,将该模式应用于具有相似类型的人员培训中㊂本研究不足之处在于,此次教学培训计划仅适用于当前的手术机器人,时代在不断发展,随着更多高科技的手段出现,必须与时俱进,进一步更新和探索㊂同时,本研究所包含的样本量较小,仅针对1所医院进行了院内研究,在样本量和选择范围上具有一定的狭隘㊂今后的工作必将开展不同医院间的合作,通过交流㊁比较㊁总结来不断发现问题,探讨问题,为进一步开展达芬奇机器人手术夯实基础㊂参考文献:[1]饶兰,张培茗,柴岗,等.基于真实世界数据的达芬奇机器人手术系统安全性研究[J].中国医学物理学杂志,2020,37(3):326-331.[2]唐鲁,郭志红,朱国雄,等.香港达芬奇机器人手术护士培训课程介绍[J].护理学杂志,2015,30(14):15-17.[3]李莎,余文静,曹婷,等.达芬奇机器人手术专科护士培训模式构建[J].全科护理,2018,16(31):3946-3947.[4]姚春红,李雪梅,张莉.遗忘规律在静脉留置针健康教育中的应用[J].护理研究,2014,28(33):4199-4200.[5]杨京晶,李曼都,杜文碧.艾宾浩斯遗忘曲线应用于糖尿病健康教育的效果分析[J].华南国防医学杂志,2014,28(12):1237-1239.[6]张葳,肖春秀.尿路造口患者家属造口护理技术的学习曲线分析[J].护理学杂志,2015,30(22):1-3.[7]B I S WA S P,K A L B F L E I S C H J D.A r i s k-a d j u s t e d C U S UM i nc o n t i n u o u st i m e b a s ed o n t he C o x m o d e l[J].S t a t i s t i c s i nM e d i c i n e,2008,27(17):3382-3406.[8]高峰,许李力.C U S UM绘制在心外科住院医师临床培养中的应用[J].中华医学教育探索杂志,2015,14(4):397-400.[9] B O L S I N S,C O L S O N M.T h eu s eo ft h eC u s u m t e c h n i q u ei nt h ea s s e s s m e n t o f t r a i n e e c o m p e t e n c e i nn e w p r o c e d u r e s[J].I n t e r n a t i o n a lJ o u r n a l f o rQ u a l i t y i nH e a l t hC a r e,2000,12(5):433-438. [10]廉波,李勍,陈彧,等.股动静脉途径插管体外膜式氧合循环辅助的学习曲线[J].中国微创外科杂志,2018,18(3):209-212. [11]王喆,王春灵,郭呈瑶.达芬奇机器人手术专科护士培训体系的构建[J].护理实践与研究,2023,20(15):2355-2359. [12]崔秀丽,陈元元,李欣.基于艾宾浩斯遗忘曲线的记忆康复训练对阿尔茨海默病患者记忆力水平及事件相关电位的影响[J].医学理论与实践,2024,37(1):151-154.[13]任镜清,刘少杰,罗辉兴,等.以C U S UM法分析手辅助腹腔镜结直肠癌根治术的学习曲线[J].暨南大学学报(自然科学与医学版),2020,41(3):235-240.[14]濮怀芳,朱莹莹.基于艾宾浩斯遗忘曲线实施延续性护理对脑出血患者术后自我管理能力影响[J].国际护理学杂志,2022,41(11):2105-2108.[15]严加洁,何金爱,黄果花,等.经外周静脉留置中心静脉导管术学习曲线的前瞻性研究[J].护士进修杂志,2015,30(2):100-103.[16]姚轶超,张麒,滕海茂.巡回护士掌握天玑机器人辅助脊柱手术设备操作技能的学习曲线[J].护理研究,2023,37(17):3192-3196.(收稿日期:2023-04-13;修回日期:2024-03-15)(本文编辑薛佳)。

T2WI-FS序列影像组学诊断宫颈癌转移及脉管间隙浸润的价值

标签在诊断宫颈癌淋巴转移及 LVSI 中的价值，基于以上背景，我院开展如下研究。
1 材料与方法 1.1 一般资料
回顾性分析我院 2017 年 6 月至 2020 年 6 月间收治的 66 例宫颈癌患者临床资料。(1)纳入标准：患者均接受全子宫切除术联合盆腔淋巴结清扫；经病理检查证实淋巴结转移及 LVSI；术前均行包括轴位 T2WI-FS 在内的 MRI 扫描。(2)排除标准：影像学检查前行放化疗等相关治疗者；MR 图像质量差，影响结果判断者；合并其他恶性肿瘤者。(3)病例资料： 66 例宫颈癌患者年龄 45～63 (50.46±12.03)岁，病理类型：鳞癌 49 例，腺癌 13 例，腺鳞癌 4 例。分化程度：高分化 7 例，中分化 33 例，低分化 26 例。LVSI 阳性 27 例，阴性 39 例。淋巴结转移阳性 22 例，阴性 44 例。本研究经过本单位医学伦理委员会批准(批准文号：20170515) ，免除受试者知情同意。 1.2 方法 1.2.1 MRI 检查及图像处理方法
Value of T2WI-FS based radiomics features in the diagnosis of cervical cancer metastasis and lymph vascular space invasion
ZHOU Xiaoling, LAI Hua*, WEN Xilin, LIU Chunying Department of Radiology, Women and Children's Hospital Affiliated to School of Medicine, University of Electronic Science and Technology of China, Chengdu Women and Children's Central Hospital, Chengdu 611731, China *Correspondence to: Lai H, E-mail: 449535176@ Received 29 Jan 2021, Accepted 25 Mar 2021; DOI:10.12015/issn.1674-8034.2021.07.014 Cite this article as: Zhou XL, Lai H, Wen XL, et al. Value of T2WI-FS based radiomics features in the diagnosis of cervical cancer metastasis and lymph vascular space invasion[J]. Chin J Magn Reson Imaging, 2021, 12(7): 69-71, 76.

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OriginalArticleAprospectivestudyofnerve-sparingradicalhysterectomyforuterinecervicalcarcinomainTaiwan

Chih-JenTsenga,b,*,Huang-PinShena,b,Yu-HsiangLina,b,Chung-YuanLeec,WillWei-ChengChiud,e

aDepartmentofObstetricsandGynecology,ChungShangMedicalUniversityHospital,Taiwan

bChungShangMedicalUniversity,Taiwan

cDepartmentofObstetricsandGynecology,Chia-YiChristianHospital,Taiwan

dDepartmentofObstetricsandGynecology,Tai-YiMaternalandChildHospital,Taiwan

eDepartmentofObstetricsandGynecology,ChangBingShowChwanMemorialHospital,Taiwan

Accepted3October2011

AbstractObjective:Surgicaltherapyforcervicalcarcinomacarriesasigniﬁcantriskoffunctionalimpairmenttothebladder.Thisstudyevaluatesthefeasibilityandcomplicationsofnerve-sparingradicalhysterectomy(NRH)inTaiwan.Methods:BetweenMarch2010andMarch2011,consecutivepatientsdiagnosedwithearlystagecervicalcancer(FIGOstageIa2toIb1)andtumorsize<3cmwererecruitedprospectivelytoundergoNRHorconventionalradicalhysterectomy(RH).Patientswithhistoriesofurinarystressincontinenceorbladderdysfunctiondiseasewereexcluded.AmodiﬁedTokyonerve-sparingradicalhysterectomywasperformed.Results:Atotalof30patientswereenrolled.Amongthese,18patientsunderwentNRHwithsuccessfulbilaterallynerve-sparingproceduresin15cases(83%),unilaterallynerve-sparingproceduresin2cases(11%),andafailurein1case(6%).Theindwellingcatheterwasremovedonpostoperativeday6.ThemeanÆSDdurationfromoperationtospontaneousvoidingwas6.8Æ1.5daysforwomenwhounderwentNRH;thecorrespondingdurationforwomenwhounderwentRHorfailedNRHwas20.6Æ3days.NoneofthepatientswhounderwentNRHrequiredintermittentcatheterization.All12patientswhounderwentRHneededself-catheterizationafterdischarge.Therewasasigniﬁcantreductionintheincidenceofpostoperativeself-catheterization(p<0.01)andbladderdysfunction(p<0.006).AveragesatisfactionscoreanalyzedbytheLikert-scalequestionnairewas4.5fortheNRHgroupand1.9forRHgroup(p<0.0001).Conclusions:WeconcludedthatthenewtechniqueofNRHcanreducepostoperativebladderdysfunctions.CopyrightÓ2012,TaiwanAssociationofObstetrics&Gynecology.PublishedbyElsevierTaiwanLLC.Allrightsreserved.

Keywords:nerve-sparingradicalhysterectomy;cervicalcarcinoma;bladderfunction;Taiwan

IntroductionIn1969,Hanleyﬁrstproposedthatradicalhysterectomy(RH)mighthaveaneffectonbladderfunction[1].SeverallargeepidemiologicalstudieshaveaddressedtherelationshipbetweenRH,urinaryincontinenceandbladderdysfunction

[2e4].TheincidenceoflowerurinarytractdysfunctionafterRHhasbeenreportedtobe12%e40%[5,6].Thiscomplica-tionisthoughttobecausedbydamagetothepelvicnerveplexus[7].TheseverityofbladderdysfunctionafterRHappearedtoberelatedtotheextentoftheprocedure.Benedetti-Panicietalhavesuggestedthattheincidenceoflowerurinarytractdysfunctionisrelatedtotheextentofresectionoftherectovaginalligamentsandvaginaltissue[8].Resectionofthesetissueswouldinterrupttheautonomicﬁbersinnervatingthebladder,aswouldtheresectionofthepara-metrium,cardinalligament,andutero-sacralligament[9].

*Correspondingauthor.DepartmentofObstetricsandGynecology,ChungShangMedicalUniversityHospital,Number110,Section1,Chien-KuoNorthRoad,Taichung402,Taiwan.E-mailaddress:tsengcj@gmail.com(C.-J.Tseng).

Availableonlineatwww.sciencedirect.comTaiwaneseJournalofObstetrics&Gynecology51(2012)55e59www.tjog-online.com

1028-4559/$-seefrontmatterCopyrightÓ2012,TaiwanAssociationofObstetrics&Gynecology.PublishedbyElsevierTaiwanLLC.Allrightsreserved.doi:10.1016/j.tjog.2012.01.011Bycontrast,anyoperativeproceduresforinvasivecancersshouldallowsufﬁcientradicalityforanoptimaloutcome.Extensivepelvicdissectionwouldmeangreaterneurovasculardisruptionwithincreasedurinarytractcomplications.Hence,achievingmaximaltherapeuticbeneﬁtinthesurgicaltreat-mentofinvasivecervicalcarcinoma,withminimalcompli-cations,remainsachallengeforgynecologiconcologists.Severalstudieshavedemonstratedanewnerve-sparingsurgicaltechniquethatpermitspreservationofthehypogas-tricandsplenicnervesduringradicalhysterectomy,withfewerlowerurinarytractcomplications[10e19].Thesestudieshaveshownthefeasibilityofanerve-sparingradicalhysterectomy(NRH)andhavedocumentedfewercomplicationsascomparedtotheconventionalprocedureforRH,inwhichthepelvicnervesarenotpreserved.Moreover,NRHdoesnotappeartoinﬂuencethedisease-freesurvivalofinvasivecervicalcancer[20,21].CervicalcarcinomaisstilloneofthemostimportantfemalecancersinTaiwan.WiththeintroductionoftheuniversalPapanicolaoucervicalsmearscreeningprogram,earlystagecervicalcarcinomasareincreasinglydetectedatanearlierage.Surgicaltherapyisindicatedintheseyoungpatientswithearlystagecervicalcancer,assurgerycouldhelppreservesexualfunction.However,traditionalRHmayinducelowerurinarytractdysfunctionandurinaryincontinence,andaffectthequalityoflife.NRHwasdevelopedasanalternativetotraditionalRHormodiﬁedRH.NRHcanreducecompli-cationsassociatedwithtraditionalRHandmayholdaplaceinthetherapeuticchoicesfortreatingearlystagecervicalcarcinomainTaiwan.Unfortunately,thereisnodataregardingthisnewtechniqueanditsrelatedlowerurinarytractmorbidityinTaiwan.Thisstudywasaprospectivepreliminarystudytoevaluatetheeffectofnerve-sparingRHversustraditionalRHonlowerurinarytractfunctiononTaiwanesepatientswithearlycervicalcarcinoma.