《周处除三害 电影》免费观看-HD版完整版免费视频...App Store 上的“易演乾坤-专业排盘起名占卜算命”
关婷娜一出场，哪里还有心思看这几个男人？
2024年12月08日，我说你少提我弟，我弟公司关了躺在家里等死啊，他不得打工赚房贷，他们两口子为给我妈治病把房子抵押出去，这份情已经很重了，我还有脸让我弟媳养我爸啊。
《周处除三害 电影》免费观看-HD版完整版免费视频...App Store 上的“易演乾坤-专业排盘起名占卜算命”
第一轮
又一个挑战马斯克的人出现了抖音电商在今年的618大促中推出了“大促重点货品”的玩法，希望继续发挥平台优势，靠重点货品撬动品牌生意，借助大促的时机为品牌商家带来生意爆发增长。抖音电商根据商品的综合表现筛选重点货品，提供价格补贴和流量激励等，商城曝光、搜索推荐、达人合作等全面且丰富的资源无疑能为品牌商家赋予巨大的能量支持。
驳补辞虫颈补辞蝉丑颈蝉丑别苍驳“箩颈苍诲颈补苍锄颈”锄丑耻濒颈飞别苍丑耻补肠丑补苍测别测耻补苍蹿补锄丑补苍濒补辞蝉丑颈诲补颈办补苍濒颈补辞丑耻颈飞辞，肠丑耻辩耻濒颈补辞。
也(驰别)就(闯颈耻)是(厂丑颈)那(狈补)举(闯耻)手(厂丑辞耻)抬(罢补颈)足(窜耻)的(顿别)分(贵别苍)寸(颁耻苍)，
ershangbanzu，zhegeshihouhuanmeixiaban，youhuozhezhengzaitongqinba。feijiroujinrunxingrutouzhuangniaolushangpizhongliudeduocanshufenlei：jiehexingtaixue、biaoxinghefenzitezhengyigaijinfengxianfenceng2023-03-14 01:51·yixuejingjieSander P, Harland N, Serna-Higuita LM, Bonzheim I, B?smüller H, Stenzl A, Fend F. Multiparametric Classification of Non-Muscle Invasive Papillary Urothelial Neoplasms: Combining Morphological, Phenotypical, and Molecular Features for Improved Risk Stratification. Int J Mol Sci. 2022 Jul 23;23(15):8133. doi: 10.3390/ijms23158133. PMID: 35897708; PMCID: PMC9330009.yi、jianjiebangzuoaishishijieshangzuichangjiandeaizhengzhiyi，meinianyueyou 550,000 li [ 1 ]。jiezhizhenduanshi，dayue 75% debangzuoaishidijibie、feijicengjinrunxingrutouzhuangzhongliu，beichengweifeijicengjinrunxingbangzuoai (NMIBC) [2 ]。NMIBC baokuoqinfanguyoucenghejiedizuzhiderutouzhuangzhongliu，anzhao TNM fenleifenwei T1、Ta he Tis。genjuqixingtaitezheng，zhexiezhongliukejinyibufenweidijibiehegaojizhongliu。dijibiezhongliu Ta he T1 zai 5 niansuifangzhongjingchangfufa (31–78%) danhenshaojinzhanweijinrun (shaoyu 1% he 45%)，yinciyuhoulianghao [3 , 4 , 5 ]。lingyifangmian，gaojibierutouzhuangzhongliukenengfazhanweijicengjinrunxingbangzuoai (MIBC)，houzhetongchanghuifazhanweizhuanyi [ 6]]. yinci，zainiaolushangpiaidezhiliaozhong，binglifenjidequedingzhizaijiangzhongliufenweibutongdeyuhouzu，yipingguzhiliaojieguobingyouhuahuanzheguanli。zhenduibangzuofeiqinruxingrutouzhuangbingbiandebinglifenjitichuliaojizhongfenjixitong [ 7 ]。1973 niande WHO fenleijiangbangzuoniaolushangpiaifenwei G1、G2 he G3 ji；raner，youyuzhezaidingyi G2 zhongliufangmiancunzaiyixiejuxianxing，yincitabei 2004/2016 WHO fenleixitongsuoqudai [ 8]. gaixitongrujinguangfanyongyuduibutongzuzhixueyazuzhongdefeijiroujinrunxingniaolushangpiliuxingchengjinxingqiangyoulidefenlei，baokuodiduexingqiannengderutouzhuangniaolushangpiliu，chengwei PUN-LMP、dijibierutouzhuangfeijinrunxingniaolushangpiai (LG-PUC) hegaojibierutouzhuangfeijinrunxingai (HG-PUC)。raner，gaifanganyegeijieshidailailiaoyixiekunnan，daozhiguanchazhejiandebianyixingxiangduijiaogao，zai PUN-LMP binglizhongwei 12-39%，zai LG-PUC zhongwei 21-63%，zai HG-PUC zhongwei 18-56% .jinnianlaisuizhuoxinyidaicexujishudechuxian，bangzuoaidezhenduanbujinguanzhuxingtaixue，huanguanzhufenzitezheng。zai UROMOL yanjiuzhong，NMIBC zhongliugenjuqizhuanlutezhengfenweisanlei，xianshichuxibaozhouqijiyinhefenhuabiaozhiwubiaodadechayi [9 ]。ciwai，longdedaxuexiaozugenjukejihuodebaxianghezhuanluyinziquedingliaowugebutongdeshiti，baokuo Uro A、jiyinzubuwending、jinrunxing SCC yanghe Uro B yaxing [10]，tamendazhiduiyingyujidiheguanqiangbeikaluolainadaxuefenleizhongmiaoshudeyazu [ 11]. zhexiefenziyaqunyibiandefeichangzhongyao，yinweitamenyulinchuangyuhouzhijiexiangguan，danshangweijinrulinchuangshijian 。NMBIC huanzhedechangguizhiliaoshijingniaodaobangzuozhongliuqiechushu (TURBT)，lianhehuobulianhekajiemiao (BCG) bangzuoneizhiliaoyijiangdijinzhanfengxian。raner，jinguan BCG zhiliaoyouxiao，60% dehuanzhekenengzai 12 geyuehoufufa，20% dehuanzhekenengjinzhanwei MIBC。buchenggongde BCG zhiliaohuanzhexuyaogenzhixingbangzuoqiechushuhuohuaxueliaofahefangsheliaofa，zheliangzheduyuxiangdangdadefabinglvxiangguan。yinci，xuyaoqitaliaofa，rumianyijianchadianyizhijihejiyuqifenzipudeliaofalaigaishanbangzuoaidefabinglv 。zaizhexiangyanjiuzhong，womencongzuzhibinglixue、mianyibiaoxinghetubianzhuangtaidengsangebutongcengmianyanjiuliaofeiqinruxing PUC detezheng，zhizaijinxingzhunquehewenjiandefenlei。gaifenleibaokuoshiyongxingtaixuetezheng、baokuo CK20、p16、p21、p53、MIB-1、yousifenliebiaojiwu p-HH3 he FGFR3（chengxianweixibaoshengchangyinzishouti）demianyizuzhihuaxuezu，yijiyufufahefufaxiangguanjiyindebaxiangtubianfenxi。yuhou，baokuoFGFR3、TP53、PTEN、PIK3CA、ERCC2heSTAG2。2. jieguo2.1. duiliemiaoshubenyanjiugongnaru 45 lifeijinrunxingniaolushangpirutouzhuangliubianhuanzhe，zuichufenleiwei pTa，zuzhizhilianglianghao，shihejinyibufenxi。linchuangxinxizongjieyubiaoge1. nannvbiliwei 2.75:1，zhongweinianlingwei 75 sui（fanwei 50-95 sui）。genju TNM fenlei，39/45 (86.6%) huanzhebeiguileiweichun pTa，er 6/45 (13.3%) huanzhezailingyigebuweiyou pT1 bingbian。19 li (42.2%) zaibangzuodelianggehuogengduoquyuxianshiduogezhongliudingwei，er 26 lixianshidangebingbian。budaoyibandehuanzhefufa (48.4%)，zhiyou 52.6% dehuanzhezailiangniandesuifangzhongmeiyoufufa。genju 44 minghuanzhedexianyoulinchuangshuju，zhiyou 25/44 (56.8%) huanzhejieshouliaolijizhiliao，13/44 (29.5%) huanzhejieshouliaoliji MMC dizhu。suoyouzuzhixue HC-PUC zhenduandehuanzhe (12/44, 27.3%) junjieshouliaozai TUR-BT zhiliao，19 ming (19/44, 43.2%) huanzhejinjieshouyixueguanchadanweigeiyuzhiliao。biaoge1).biaoge1feijinrunxingniaolushangpirutouzhuangliubianbinglidelinchuangtezheng。n = 45 (%)zhongweinianling（fanwei） 75 sui (50–95)xingbie n (%)nanxing 33 (73.3)nvxing 12 (26.6)M:Fbilv 2.75:1zhongliufenqi，TNM n (%)pTa 39 (86.6)pTa he pT1 6 (13.3)zhongliudingwei2 gehuogengduoweizhi 19 (42.2)cebi 10 (22.2)houbi 6 (13.3)sanlengshu 3 (6.6)jingbu/dingdian 3 (6.6)bangzuoyuanding 2 (4.4)qianbi 2 (4.4)zuzhixuehuandengpianzhongdebiniaoji 30 (66.7)zhenduanhoulijizhiliao * ( n = 44) n (%)wuzhiliao 19 (43.2)lijibangzuoneidizhuMMC 12 (27.3)zhongxinTUR-BT 13 (29.5)liangniansuifangzhongdefufalv % * 48.4%linchuangguochengzhongdejinyibuzhiliaowuxujinyibuzhiliao 12 (27.3)jinyibude BCG huo MMC dizhu 10 (22.7)TUR-B 31 (70.5)bangzuoqiechushuhe TUR-B： 2 (4.5)bangzuoqiechushu、TUR-B he BCG zhiliao 2 (4.5)zaidandudechuangkouzhongdakaiMMC：siliemeisuC；BCG，kajiemiao（BCG）；TUR-BT，jingniaodaobangzuozhongliuqiechushu。* baifenbishizhendui 44 minghuanzhejisuande，yinwei 1 lihuanzhedeyixielinchuangshujubukeyong。2.2. zuzhixuefenleiduiyuanshizhenduanheyuanshizhenduanbaogao (ODR) buzhiqingdesanweibinglixuejiadezhenduanyizhixingshujubaogaoyubiao 2. PUN-LMP zhenduandeguanchazhejianbianyixingshizhong (57%)，LG-PUC binglilianghao (67%)，HG-PUC binglijihao (87%)。zaibijiao PUN-LMP he LG-PUC zhenduanshifaxianliaozuixianzhuodeguanchazhejianbianyixing，Fleiss Kappa zhishuxiangdangdi，wei 0.43 ( p= <0.001)，95% zhixinqujianzai 0.398–0.635 zhijian。dangzhishaoyouliangmingduliguanchayuandachengyizhiyijianshi，jiujianliliaogongshizhenduan。genjugongshi，zhiyou 18% debinglibeiguileiwei PUN-LMP，danyiban（51.1%）dehuanzheshuyu LG-PUC leibie，33.3% dehuanzhebeiguileiwei HG-PUC。zaihouxuxingdongzhong，ruyuqidenayang，zai HG-PUC binglizhongguanchadaogenggaodefufalv。yu LG he HG-PUC de 23 geyuehe 5 geyuexiangbi，PUN-LMP debinglixianshichugenggaodezhongweiwufufa（34 geyue）。liangnianfufafenxixianshi，yu LG-PUC (42.7%) he PUN-LMP (33.3%) xiangbi，HG-PUC defufalv (79.5%) genggao（p = 0.14，tu1). genjubuchongbiao S2zhongdegongshizhenduanmiaoshujixianlinchuangtezhenghesuifang。tu1zuzhixuefenjihewufufashengcun。（yi）。daibiaoxingzuzhixuetuxiangxianshibutongzhongliudengji（PUN-LMP、LG-PUC he HG-PUC）dezhuyaotezheng。（yi）。tongguogongshizhenduanbijiaozhongliufenjidewufufashengcunqide Kaplan-Meier fenxi。（bing）。bijiao TNM fenleihezhongliufenjidewufufashengcunqide Kaplan-Meier fenxi。PUN-LMP，diduexingqiannengderutouzhuangniaolushangpiliu；LG-PUC，dijibieniaolushangpirutouzhuangai；HG-PUC，gaojibieniaolushangpirutouzhuangai。biao 2WHO 2004/2016 zuzhixueleibiezhijiandeguanchazhejianbianyixing。nianji wangshangzhengyijiejue zhenduan P 1 zhenduan P 2 zhenduanP 3 gongshizhenduan guanchazhejianbianyixing (%) fulaisikapaPUN-LMP 18 (40%) 16 (35.6%) 8 (17.8%) 6 (13.3%) 8 (17.8%) 57% 0.43 **LG-PUC 14 (31.1%) 15 (33.3%) 22 (48.9%) 27 (60%) 23 (51.1%) 67% 0.41 **HG-PUC 13 (28.9%) 14 (31.1%) 15 (33.3%) 12 (26.7%) 14 (31.1%) 87% 0.81 **zaidandudechuangkouzhongdakaiPUN-LMP，diduexingqiannengderutouzhuangniaolushangpiliu；LG-PUC，dijibieniaolushangpirutouzhuangai；HG-PUC，gaojibieniaolushangpirutouzhuangai；P 1、2、3，binglixuejia 1、2 he 3。** pzhi < 0.001 Fleiss Kappa。2.3. mianyizuhuatezhengjiyuzhongliufenjidexiangguanxingSpearman dezuzhipingfendengjixiangguanjuzhenzaizhenduanleibiezhijianmeiyouzhengxiangguan，chuliaozengzhizhishu，tayu p-HH3 ransepinggudeyousifenliejishuchengzhengxiangguan（tu 2). CK20、p53 hezengzhilv (MIB-1) shishibiejuyoujiaogaozuzhixuefenjihebulianghouguodebinglideheshigongju。zhesangebiaozhiwuzai LG-PUC he HG-PUC binglizhongxianshichubi PUN-LMP bingligenggaodezuzhipingfen ( p < 0.05) (biao3hetu 2). zhongliuyizhiyinzi p53 zaisangeyazuzhongxianshiyizhiranse，danyu PUN-LMP xiangbi，zaifenleiwei LG-PUC he HG-PUC debinglizhongbiaoxianchugenggaodebiaoda ( p = 0.06)。ciwai，yu LG- huo HG-PUC binglixiangbi，guileiwei PUN-LMP debinglixianshi CK20、p53 ransejiaoruo，p-HH3 pinggudezengzhiheyousifenlielvjiaodi（p< 0.001)。yu HG-PUC zuxiangbi，LG-PUC binglixianshichuxiangside CK20 he p53 zuzhipingfen。xiangbizhixia，HG-PUC binglidezengzhilv (MIB-1) heyousifenliejishudefenjiaogao。yixie PUN-LMP he LG-PUC binglixianshiyousifenliejishujiaogao，danzaizhexiebinglizhong，yu HG-PUC xiangbi，yousifenliejinxianyujidiceng。xibaozhouqidanbai p21 he p16 zaibinglizhongransebujunyun，yuzuzhixuefenjiwuxiangguanxing。zonggongyou 28/37 (75.7%) gebinglixianshisuoyoubinglijunquefa FGFR3 ranse，danfenleiwei LG-PUC de 6 gebingli (6/20, 30%) xianshi FGFR3 guobiaoda。yibaneryan，zhiyou 16/25 (64%) debinglixianshiquefayuqitubianzhuangtaixiangguande FGFR3 biaoda，yinweiyixietubiankenengdaozhifeigongnengxingdanbaizhi。tu 2mianyizuzhihuaxuetezheng。（yi）。sipiermandengjixiangguanjuzhenhemianyizuzhihuaxuebianliangdexiangguanyiyi。zhixianshi Spearman paimingjieguo；lansebiaoshizhengxiangguan，hongsebiaoshifuxiangguan。（yi）。xiaotiqintubijiaoliaofeiqinruxing PUC leibiezhongyong p-HH3 ransede 10 gegaobeishiye (HPF) zhongdeyousifenliejishu。（bing）。mianyizuzhihuaxuebiaojiwudebutongzuzhipingfendexiaotiqintu，biaoshifeiqinruxing PUC shiti。duiyutongjifenxi，shiyongweipeiduitjianyan，ns= buxianzhuo，* p < 0.05，** p < 0.01，**** p < 0.0001。biao3genjuzuzhixuefenjidebinglidezuzhipingfen。CK20 MIB-1 p-HH3 * FGFR3 p16 p21 p53PUN-LMP 60(6–180) 3(3–30) 2(1–12) 9(1–40) 10(15–270) 150(60–170) 90(50–130)LG-PUC 202(110–270) 25(9–45) 10(5–15) 70(10–82.5) 85(17.5–180) 110(57.5–160) 127.5(100–182.5)HG-PUC 225(172–270) 90(57–97.5) 38.5(25.3–51.5) 26.3(10–82.5) 25(3–225) 97.5(6–191.3) 142.5(97.5–210)pzhi 0.027 <0.001 <0.001 0.032 0.065 <0.001 0.066zaidandudechuangkouzhongdakaizuzhipingfenzhongweishu (p25–p75)；PUN-LMP，diduexingqiannengderutouzhuangniaolushangpiliu；LG-PUC，dijibieniaolushangpirutouzhuangai；HG-PUC，gaojibieniaolushangpirutouzhuangai。* 10 gegaobeishiye (HPF) zhongdeyousifenlieshu。2.4. tubianjingguanzonggongyou 37 geanlishiyongbaxiang NGS jinxingliaofenxi。cexudepingjunduqushenduwei 6820 ciduqu (1141–23,628)。tubiandefenbumiaoshuyutu 3buchongbiao S1zhongzongjieliaoxiangxixinxi。zonggongjiandingchu 80 getubian，66/80 gecuoyidiantubian (82.5%)，9 gewuyitubian (11.25%) he 5 geyimatubian (6.25%)。SIFT、PolyPhen-2 he CADD defenxiyuceliaoduisuoyoubaogaodecuoyitubiandepohuaixingyingxiang。suoyoujiyintubiandebianyidengweijiyinpinlv (VAF) fanweiwei 3% zhi 93%（pingjun 34%）。tu 3（yi）。meigezhenduanleibiedetubianhemianyizuzhihuaxuejieguogaishu。（yi）。lianggehesangezizu（fenbieweiyoucehezuoce）dejuleifenxi。（bing）。shiyongjuleituzhongxianshidejuleifenxidewufufashengcunde Kaplan-Meier tu。yufenjiwuguan，FGFR3shigaixiliezhongshouyingxiangzuipinfandejiyin。guileiwei PUN-LMP debinglizhuyaoxianshiFGFR3gaibian (57%, 4/7) bingqiemeiyouTP53tubian。ciwai，zaiERCC2、PTENhePIK3CAzhongjiancedaodetubiandaduoshitongshifashengde，bingqiezongtishangbuchangjian (28.5%, 2/7)。dijibie PUC binglizai 17/20 (85%) binglizhongtongyangbiaoxianchupinfandeFGFR3tubian，11 libinglizaiPIK3CA (63.6%, 7/11)、STAG2 (54.5%, 6/11) heERCC2 (45.4%)zhongbiaoxianchubingfagaibian, 5/11). TP53tubiancunzaiyu 2/20 (10%) binglizhong。HG-PUC binglixianshijiaodipinlvdeFGFR3gaibian (40%, 4/10) hegengduoTP53gaibian (30%, 3/10)。TP53tubianbinglizongshixianshichugaoTP53zuzhipingfen，danxiangfan，bingfeisuoyoujuyougaozuzhipingfendebinglidubiaoxianchuTP53jiyingaibian。PTENtubianhenshaojian，dancunzaiyu PUN-LMP he HG-PUC binglizhong。zaisuoyoudiaochadejiyinzhong，zhiyouTP53tubianyuwufufashengcunxianzhuoxiangguan（p = 0.024，buchongtu S1）。2.5. zhenghexingtaixue、mianyibiaoxinghetubianzhuangtaidejuleifenxijuleifenxiqingchudijiangfeiqinruxingrutouzhuangniaolushangpizhongliufenweilianggebutongdeyazu。julei 1 daibiao PUN-LMP he LG-PUC binglidehunhe，xianshidizengzhilvheyousifenliejishu，yijipinfandeFGFR3he STAG2 tubian，erjulei 2 baohanjuyougaozengzhizhishuheyousifenliejishude HG-PUC，qiang CK20 biaoda, TP53tubiandanFGFR3 WT (biao 4). juleifenxiyulinchuangxingweimiqiexiangguan，bingxianshiyudi 1 zu（fenleiwei PUN-LMP he LG-PUC debingli）xiangbi，di 2 zu（fenleiwei HG-PUC debingli）dewufufashengcunlvjiaodi，( p = 0.029 ,tu 3gongyuanqian）。shiyongsangebutongdeyazujinxingewaidejuleifenxiyiqueding PUN-LMP he LG-PUC binglishifoukeyifenkai。(tu 3B，zuoce）。raner，zaidi 1 zuhedi 2 zuzhongfaxianliao PUN-LMP he LG-PUC hunhebingli，bingqiegaicuyuzuzhixuefenjiwuguan。jihusuoyouguileiwei HG-PUC debinglidubeishoujidaodi 3 zu（tu 3B、C，zuoce）。biao 4juleizhijiandanbaizhihetubianzhuangtaidebijiao。biaoji jiqun 1 jiqun 2 p -zhimianyizuzhihuaxue zhongweishu (p25–p75) zhongweishu (p25–p75) Wilcoxon zhihejianyanCK20 160 (80–240) 225 (172.5–270.0) 0.150p53 110 (80–160) 158.7 (107.5–212.5) 0.013MIB-1 15 (3–33.9) 90 (68.5–97.5) <0.001FGFR3 60 (1–80) 3 (1.0–65.0) 0.101p-HH3 * 8 (3–12) 38.5 (25.7–51.5) <0.001tubianzhuangtai n (%) n (%) χ2jianyan_FGFR3 18 (40.0%) 3 (6.0%) 0.028STAG2 8 (17.2%) 1 (2.2% 0.236TP53 2 (4.4%) 5 (11.1%) 0.023ERCC2 7 (15.5%) 4 (8.8%) 0.717PIK3CA 10 (22.2%) 3 (6.6%) 0.724zaidandudechuangkouzhongdakaimianyizuzhihuaxue：shujubiaoshiweizuzhipingfenzhidezhongweishu (p25–p75) huo (*) 10 HPF zhongdeyousifenlieshu。tubianzhuangtaiyoutubianbinglishu (%) biaoshi。Kaplan-Meier fenxixianshiyujiqunyouhenqiangdexiangguanxing，yinweidi 1 zuhedi 2 zudewufufashengcunlvshizhongjiaogao，LG-PUC he PUN-LMP zhijiancunzaizhongdie (p = 0.055 )。di 3 zushizhongxianshichujiaogaodefufalv（tu 3C，zuomianban）。zhixingbili Cox huiguimoxingyiguji RFS hejuleifenxizhijiandeguanlian。danbianliangheduobianliangfenxizhengshilinchuangtezhenghezhiliaobuyingxiang RFS。RE-TURB zhiliaobiaoshiyufufaxianzhuoxiangguan，danweikaolv，yinwei RE-TURB jinzai HG-PUC binglizhongjinxing（buchongbiao S4）。duobianliangfenxizhengshi，linchuangtezhenghezhiliaobuyingxiangwufufashengcun，bingqiefufayuyouzuzhixuetezheng、danbaizhibiaodahetubianzhuangtaichanshengdecuzudulixiangguan（buchongbiao S5 he S6 ）。3.taolunzaizhexiangyanjiuzhong，womencaiyongliaofeiqinruxingrutouzhuangniaolushangpizhongliudeduocanshufenlei，baokuotubianzhuangtai、mianyibiaoxinghezuzhibinglixue，yishitugaijindanduzuzhixuefenjidefengxianpinggu。zaizhiqianhewomenmuqiandefenxizhong，rutouzhuangniaolushangpizhongliudefenjijuyouchadaozhongdudeguanchazhejiankezhongfuxing。raner，zhongliudejingquefenjiduiyuzhiliaojuecehejiangdifufaheqinxidefengxianzhiguanzhongyao [ 2 , 17 ]。fenjidechayikenengshiyouyuduifenjidexingtaixuetezheng（jiegou、xibaoxue、yousifenliedeng）fuyubutongdequanzhong，jinguanduocichangshimingquedingyifenjibiaozhun [18 ]]. raner，zhongsuozhouzhi，fenjixitongzongshishejiyidingchengdudezhuguanxing，yingxiangguanchazhejiandezaixianxing。zairutouzhuangniaolushangpizhongliuzhong，zuikunnandetiaozhanshi PUN-LMP yu LG-PUC dequbie，yinweizheliangzhongshitidujuyoudianxingderutouzhuangjiegou，jibeiniaolushangpifugaiderutouquefadingduanyousifenliehuodong，weiyidedingyitezhengshicunzaiheshangpiyixinghewenluandeshuliang，keyizhuguanpinggu。zai PUN-LMP deqingkuangxia，niaolushangpikanqilaigenghou，danshijishangyinggaipaichufeidianxingxing，erzai LG-PUC deqingkuangxia，rutouzaidifangdabeishuxiaxianshichuyouxudewaiguan，bingqiecunzaifeidianxingxingdanqingwei [ 19 , 20]. zaiwomendeyanjiuzhong，yuwenxianyizhi，PUN-LMP biaoxianchuzuidichengdudeguanchazhejianyizhixinghekezhongfuxing，bingqiezhenduan LG-PUC erbushi PUN-LMP dequshizengjia。ciwai，zaibijiao PUN-LMP he LG-PUC shi，fufalvdechayixiangduixiangsi。PUN-LMP binglidefufalvyinwenxianzhongdeyanjiueryi，kenengshiyizhongshoufenleibiaozhunyingxiangdejieguo。PUN-LMP defufalvwei 17% zhi 35%，LG-PUC wei 48-71%，HG-PUC binglidefufalvwei 78%。xiangbizhixia，PUN-LMP deqinxifengxianwei 1-3%，LG-PUC wei 5%，HG-PUC bingligaoda 45% [ 21 ]。youyuzuzhixuetezhengbiaoxianchumingxiandejuxianxing，yinciyanjiuliaoqitagongju，ruyousifenliejishu、zengzhilvheteyixingmianyizuzhihuaxuebiaojiwudebiaoda，zuoweiduiniaolushangpizhongliujinxingfenjidefuzhufangfa。shiyongtongguobandingliangfangfapinggudeyousifenliehuoxingdeyanjiubiaoming，fenjidekezhongfuxingdi，bingqieyuyuhoudexiangguanxingcha [ 18 ]。raner，duiruxianaideyanjiubiaoming，keyitongguodingliangfangfagaishanyousifenliejishu [ 22]]. zaiwomendeyanjiuzhong，shiyong p-HH3 mianyiransejinxingyousifenliejishuyijianshaozhuguanxing，jinguanbixutidao p-HH3 ransebunengzhijieyu H&E qiepianshangdeyousifenliejishujinxingbijiao。zaisuoyou HG-PUC binglizhongjunguanchadaogaoyousifenliezhishu（10 HPF zhong > 20 ciyousifenlie），biaoming p-HH3 deyousifenliejishushifenjideyouyongcanshu。tongguo MIB-1 ransepinggudezengzhilvyeshiyigeyouyongdetezheng，dan PUN-LMP he LG-PUC zhijiandezengzhilvchayixiweiqiezhongdie，yinciwufajiangqiyongzuofenjideweiyicanshu [23 ]。yixiezuozhebaodaoliao CK 20 he p53 ransezuoweiniaolushangpifayubuliangdekeguanbiaozhi [ 24]. CK20 tongchangjinzaizhengchangniaolushangpidesanzhuangxibaozhongbiaoda，ermimanxingquanceng CK20 ranseshi HG-PUC detezheng [ 25 ]。raner，zai PUN-LMP he LG-PUC binglizhongbaodaoliaobuyizhide CK20 biaoda；yinci，buyingdandushiyongcicanshu [ 26 ]。jinnianlai，qiangdadegaotongliangcexujishudechuxianshiwomenduiniaolushangpiaitubianqingkuanghetedinggaibiandeyuhouyingxiangdelijiequdeliaozhongdajinzhan，congerdaozhiliaobangzuoaidejizhongfenzifenlei。jubaodao，NMIBC shijiyinzuwendingdezhongliu，qitezhengshiFGFR3tubianhuoransetiyiwei（zaidayue 70%dedijibiezhongliuzhong）[ 27、28 ]，zhekenengdaozhizaoqiniaolushangpizengsheng [ 29 ]。yuzhexieshujuyizhi，FGFR3tubianshiwomenxiliezhongzuichangjiandeyichuangaibian（64.1% debingli）。zhengruyuqidenayang，FGFR3tubianyufeigaojibiaoxingxiangguan。PIK3CAzhongdejihuotubianhezhanliandanbaifuhewuzhongliuyizhijiyinSTAG2zhongdeshihuotubiansihuzaifabingjizhizhongqiciyaozuoyong，yinweidaduoshuzhexietubianyuFGFR3gaibiantongshifasheng[ 30、31、32 ]，zhengruzaidaduoshubenyanjiuzhongdeanli。zhebiaomingPIK3CAheSTAG2gaibianbenshenyudijinzhanfengxianxiangguan [ 33 , 34 ]。xiangfan，gaojirutouzhuangaihejinrunxingzhongliujingchangxianshiTP53degaibian、ERCC2hePTENjiyinhetonglu [ 35、36 ]。henshaofaxianzhibingxingTP53tubian，danruguocunzai，tamenjinzai LG- he HG-PUC zhongbeishibie，yuqitaaizhengyiyang，daibiaoexingzhongliudeyichuantezheng [ 37、38 ]。DNA jiexuanmeiERCC2，zhiqianbeimiaoshuwei MIBC zhongshunbozhiliaominganxingdeshengwubiaozhiwu，tongyangsihuzaibangzuoaidefashengzhongfahuizuoyong [ 39 , 40 ]。raner，zhengrubenxiliezhongsuoguanchadaode，tayekeyizaisuoyouleibiede NMIBC zhongshibiechulai。yiaijiyinPTENyu NMIBC (40%) xiangbi，zai MIBC (90%) zhongdabufenjiyinshihuo [ 41 ]。raner，zaigaixiliezhong，zai PUN-LMP binglizhongyefaxianliaoshihuodePTEN （2/4 binglifashengtubian）。juyouPTENhuoTP53tubiandehanjian PUN-LMP he LG-PUC bingli（tongchangyugaojibiezhongliuxiangguan）shifouxianshichugenggaodejinzhanfengxianhuanyoudaiguancha。zaiwomendezhuchengfenfenxizhongduimianyizuzhihuaxuehefenzibiaozhiwudelianhepinggushiwomennenggoushibiechujuyouxianzhuobutongjinzhanfengxiandeliangzu，jinguanbinglishulianghenshao。ciwai，zhezhongshiyongduogecanshudejuleifenxibiaoming PUN-LMP he LG-PUC miqiexiangguan，kenengdaibiaoliaoyixilieshengwuxuexingwei。jianyu PUN-LMP he LG-PUC shiyongxiangtongdelinchuanghezhiliaofangfa，muqianjiyuzuzhixuetezhengbingzaiqijieshizhongjuyouxiangdangdadezhuguanxingdequfendejibenyuanlishangbuqingchu，xuyaoduigengduobinglijinxingjinyibufenxi[ 19 , 21 , 42 , 43]. caiyongewaidedanbaizhiheyichuanbiaojideduocanshufenxikeyongyu NMIBC fenji，bingkenenggaishanlinchuangxingweideyuceyijifufahejinzhandefengxian。yinggaijinshenjieshizhexiangyanjiudejieguo，yinweizhexiangyanjiuzhidaibiaoliaoyouxianshuliangdehuanzhe，qizhongzhifenxiliaoyouxianshuliangdedanbaizhibiaozhiwuhetubian。zhexianggongzuozhuyaobiaoshiyuanliyanjiudezhengming，qizhongdezhuyaomubiaoshibiaomingduocanshufangfajuyouyixieyouxiwangdejieguo，yinggaizaigengdadeduiliezhongjinxingceshi。zaigexinghuayiliaoshidai，jiancetubianhuoqimianyizuzhihuaxuetidaiwudefenzizuduiyuxuanzezuijialiaofaheyucebangzuoaihuanzhedeyuhouzhiguanzhongyao。youyu PUN-LMP he UPC daibiaobangzuoaihuanzhelinchuangguochengzhongdezaoqizhenduan，yincitamendeduocanshufenxi（baokuodanbaizhishengwubiaozhiwuhetubianpufenxi）henyouxiwang，yinggaizaigengdadeduiliezhongjinxing。si、cailiaoyufangfa4.1. zhongliuyangbenzaizhexiangyanjiuzhong，womennaruliaotubingendaxueyiyuanbinglixueheshenjingbinglixueyanjiusuozai 2013 nianzhi 2020 nianjianzhenduanweifeijinrunxingrutouzhuangniaolushangpizhongliudesuoyouyangben，zhexieyangbenfuhewomendexuanzebiaozhun：rutouzhuangfeijiroujinrunxingbangzuoaihuanzhedehuojianfenjizuowei PUN-LMP、LG-PUC huo HG-PUC。xuanzedaibiaoxingkuaijinxingfenxi。ciwai，19 gemeiyouzhongliuhuofayuyichangdebangzuohuojianyangbenyongzuoyinxingduizhao。benyanjiujingtubingendaxueyixueyuanlunliweiyuanhuipizhun (547/2021BO2)。4.2. genju 2016 nian WHO fenleidezuzhixuefenleiweiliaogenju WHO 2016 nianfenleijinxingzhongxinfenlei，sanweibinglixuejiamangmupingguliaoyongsumujingheshuhong (HE) ransede 3 ?m houqiepian。binglibeifenleiwei PUN-LMP、feiqinruxing LG-PUC huo HG-PUC。zaidi、zhonghegaofangdabeishu（100×、200× he 400×）xiajinxingxibaoxuehejiegoutezhengdepinggu[ 8、44]. PUN-LMP beizhenduanweijuyoulisanderutou、xichangqieweironghedebingli，dabufenbeizhengchangdeniaolushangpixibaofugai，xibaoxueyixingxing、yousifenliehehuaisijishaohuobucunzai。feiqinruxing LG-PUC huojianxianshiniaolushangpixiabanbufenpailieyouxuderutou，juyouqingduxibaoxueyixinghehanjiandeyousifenlie。feiqinruxing HG-PUC binglizaidibeijingxiabiaoxianchuwanquanwuxudewaiguan，zheshiyouyuzhenggeshangpigaodudejiegouwenluan、zhongduzhigaoduyixingheyousifenliehuodong [44 ]。4.3. linchuangshujushenchaliaoyiliaojilu，baokuonianling、xingbie、jibingbiaoxian、weizhi、fanwei、TNM fenqi、zhiliaohesuifang。wufufashengcunqi (RFS) shicongzhenduanriqidao 5 nianhuozuihouyicisuifangjisuande。4.4. mianyizuzhihuaxuegenjuzhizaoshangdefangan，shiyongzidongranseji（Ventana Medical Systems，Tucson，AZ，USA）jinxingmianyiranse。daidianzaibopianyong CK20 (M7019, Dako Cytomation, Glostrup, Denmark), p16 (06594441001, CINtech, Roche, Manheim, Germany) p21 (556431, BD Pharmigen, San Jose, CA, USA), p53 (DO-7 , Novocastra, Leica Biosystems, Wetzlar, Germany), MIB-1 (M7240, Dako Cytomation, Glostrup, Denmark), p-HH3 (117C826, IMGENEX, San Diego, CA, USA) he FGFR3 (sc-13121, Santa Cruz Biotechnology ，deguohaidebao）。mianyizuzhihuaxueshiyongzuzhipingfenjinxinglianghua，ruxiasuoshu。genjuqiangduhexibaobaifenbiduiransejinxingpingfen。zaimohexibaozhizhongpingguqiangdubingpingfenwei 0：yinxing，+：ruo，++：zhongdeng，+++：qiang。ranhoutongguojiangranseqiangduchengyiyangxingransexibaodebaifenbilaijisuanzuzhipingfen。ciwai，p-HH3 mianyizuzhihuaxueyongyujiandingzhengzaijingliyousifenliedexibao。tongguojisuan 2 mm zhongransexibaodeshulianglaipingguransetu 2，shiyong Zeiss Axioskop xianweijing（Zeiss，Oberkochen，Deutschland）duiniaolushangpideshangcengjinxingdayue 10 gelianxudegaobeishiye [HPF]。4.5. DNAtiqugenjuzhizaoshangdeshuoming，shiyong Maxwell ? RSC DNA FFPE shijihehe Maxwell ? RSC yiqi（Promega，meiguoweisikangxingzhoumaidixunshi）congshengyudehuojiancailiaozhongtiqujiyinzu DNA 。genjuzhizaoshangdefangan，shiyong Qubit dsDNA HS jianceshijihe（Thermo Fisher Scientific，Waltham，MA，USA）de Qubit yingguangjidui DNA jinxingdingliang。ruxianqianbaodaodenayang，jinxingzhiliangkongzhijuhemeilianfanying (PCR) yiquedingkekuozengde DNA changdu [ 45]。xuanzejuyouzhishao 200 bp kekuozeng DNA debinglijinxing NGS baxiangfenxi。4.6. baxiangxiayidaicexubaxiangtubianfenxiyouxiayidaicexu (NGS)（Ion GeneStudio S5 prime，Thermo Fisher Scientific，Waltham，MA，USA）shiyong AmpliSeq Custom Panel jinxing，hangairutouzhuangfeijiroujinrunxingniaolushangpibangzuoaizhongzuichangjiandefufatubianjiyin（wanzhengdebianmaxulie：ERCC2、FGFR3、PIK3CA、PTEN、STAG2heTP53（buchongbiao S1). genjuzhizaoshangdeshouceshiyong Ion AmpliSeq Library Kit v2.0、Ion Library TaqMan Quantitation Kit、Ion 510、Ion 520 he Ion 530 Kit—Chef he Ion 520 Chip Kit jinxingkuozengziwenkuzhibeihebandaoticexu（Thermo Fisher Scientific，meiguomasazhusaizhouwoersemu）。wulishilabaomaiderutouzhuangfeijiroujinrunxingniaolushangpibangzuoyongyuyanzheng NGS mianban。yurenleicankaoxuliexiangbi，feitongyitixibaobianyidebianyidiaoyongshishiyong Ion Reporter ruanjian（Thermo Fisher Scientific，Waltham，MA，USA）jinxingde。4.7. juleifenxijinxingjuleifenxiyiquedingjuyouxiangsixingdehuanzhezu。jindui 37 lijinxingliaofenxi，yinwei 8 lihuanzhedeshujuqueshi。zhixingbianliangbiaozhunhua (Versi) yihuodelingjunzhiheyibiaozhuncha。juleifenxijiyuyixiabianti：zuzhixuefenlei（PUN-LMP、LG-PUC he HG-PUC）、mianyizuzhihuaxue（CK20、p53、MIB-1、p16、p21、FGFR3 he p-HH-3）hetubianERCC2 , FGFR3 , PIK3CA , PTEN , STAG2 , TP53zhuangtai（tubianyufeitubian）。K-Medoids jiqunde Partitioning around Medoids (PAM) suanfayongyugenjuhuanzhedexiangsixingduihuanzhejinxingfenzu，yinweigaisuanfaduizaoshengheyichangzhibutaimingan。zaizhezhongfangfazhong，meigejiqunduyoujiqunzhongdeyigeshujudianbiaoshi。zhexiedianbeimingmingweicuzhongxindian（cuzhongdeduixiang，qiyucuzhongsuoyouqitachengyuanzhijiandepingjunchayizuixiao）。[ 46 , 47 ]。shiyongoushijulijisuanlianggeshizhixiangliangzhijiandejuli，qidingyiruxia：4.8. tongjifenxishiyong R ruanjianbanben 4.0（R tongjijisuanjijinhui，weiyena，aodili）jinxingtongjifenxi。shiyongpinlvhebilimiaoshufenleibianliang；shuzhibianliangbaogaoweijunzhihebiaozhuncha (±SD) huozhongweishuhesifenweiju (IQR)，jutiqujueyushujudefenbu。tongguoyanjiufengdu、pianduhe QQ tulaipinggufenbudezhengtaixing。shiyongkafangjianyanpinggufenleibianliang。zhixing Fleiss de Kappa ceshiyiceliangguanchazhejiandebianyixing。tongguo Kaplan-Meier fangfafenxiwufufashengcun (RFS)，bingshiyongduishuzhijianyanlaijianyanzujianchayi。suifangdingyiweicong 24 geyuedaojieguofashenghuoyiqitafangshishanshideshijian。shiyongdanbianliangheduobianliang Cox bilifengxianhuiguilaipinggujiqunhewufufashengcunzhijiandeguanlian。duobianliangmoxingdehouxuanfengxianyinsushigenjulinchuangkaolvheshuangbianliangfenxidetongjixuexianzhuojieguoxuanzede。zhixingxianghouxuanzeyicongmoxingzhongshunxushanchubianliang。tongguojuzhenxiangguanjianchaduozhonggongxianxing。jieguobaogaoweifengxianbihe 95% zhixinqujian。shiyong Schoenfeld canchapinggubilifengxianjiashe。suoyoutongjijianyandushishuangcede，bingqie duobianliangmoxingdehouxuanfengxianyinsushigenjulinchuangkaolvheshuangbianliangfenxidetongjixuexianzhuojieguoxuanzede。zhixingxianghouxuanzeyicongmoxingzhongshunxushanchubianliang。tongguojuzhenxiangguanjianchaduozhonggongxianxing。jieguobaogaoweifengxianbihe 95% zhixinqujian。shiyong Schoenfeld canchapinggubilifengxianjiashe。suoyoutongjijianyandushishuangcede，bingqie duobianliangmoxingdehouxuanfengxianyinsushigenjulinchuangkaolvheshuangbianliangfenxidetongjixuexianzhuojieguoxuanzede。zhixingxianghouxuanzeyicongmoxingzhongshunxushanchubianliang。tongguojuzhenxiangguanjianchaduozhonggongxianxing。jieguobaogaoweifengxianbihe 95% zhixinqujian。shiyong Schoenfeld canchapinggubilifengxianjiashe。suoyoutongjijianyandushishuangcede，bingqiep < 0.05 beirenweibiaomingjuyoutongjixueyiyi。5。jielunzaiguoqudejishinianzhong，jieheaizhengzhenduanzhongbutongfuzachengdudefenleiyichengweizhongliujiancehefencengdezhongyaogongju。tamenyulinchuangxingweiyouhenqiangdexiangguanxing，bingtigongshengwuxuedongchaliheduizhongliudelijie，zhexiezhongliuzaikezhongfufenlei（ru PUN-LMP）zhongxianshichukunnan。zaizhexianggongzuozhong，womenqueren PUN-LMP he LG-PUC zhijiandejigezuzhixue、mianyibiaoxingheyichuantezhengxianshizhongdie，yefanyingzaikekaodifenlizhelianggeshitidekunnanshang。zhezuizhongdaozhiliao PUN-LMP he LG-PUC shifoudaibiaoshengwulianxutidewenti，zuzhixuefenjiweinengchongfenbozhuodaozheyidian，xuyaotianjiafenzihebiaoxingtezhengzuoweifuzhugongjuyigenghaodijinxingfengxianfenceng。
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