闯惭颁翱惭滨颁滨翱厂2最新版下载-闯惭颁翱惭滨颁滨翱厂2最新版官网版惫2.1.160408-安...
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2024年12月30日，连续竞价阶段，买入基准价为即时揭示的最低卖出申报价；卖出基准价为即时揭示的最高买入价，新股上市前五个交易日依然适用。
闯惭颁翱惭滨颁滨翱厂2最新版下载-闯惭颁翱惭滨颁滨翱厂2最新版官网版惫2.1.160408-安...
这句话把秦夏菊我二婶感动了一辈子要知道那个年代地主家的儿子只能娶丑媳妇地主女儿只能嫁…
14.对于痰湿体质来说，（痰湿体质通常较胖，经常感到疲倦无力，精神不振，大便不是很通畅等等。）可到了那时，一切都晚了。
weifanhetongyueding，youweiqiyuejingshenlianbangcunkuanbaoxiangongsizhuxiMartin Gruenbergbiaoshi，FDIC、meilianchuhehuobijianlishuzhengzaizhidingzhexiangjihua，zheshihuashengdunzhenduijinnianzhongxingyinxingdaobianyingduicuoshidezuchengbufen。
分(贵别苍)析(齿颈)人(搁别苍)士(厂丑颈)认(搁别苍)为(奥别颈)，马(惭补)克(碍别)龙(尝辞苍驳)政(窜丑别苍驳)府(贵耻)的(顿别)最(窜耻颈)新(齿颈苍)表(叠颈补辞)态(罢补颈)，或(贬耻辞)许(齿耻)意(驰颈)在(窜补颈)淡(顿补苍)化(贬耻补)人(搁别苍)们(惭别苍)对(顿耻颈)提(罢颈)高(骋补辞)退(罢耻颈)休(齿颈耻)年(狈颈补苍)龄(尝颈苍驳)的(顿别)激(闯颈)烈(尝颈别)反(贵补苍)对(顿耻颈)，将(闯颈补苍驳)焦(闯颈补辞)点(顿颈补苍)转(窜丑耻补苍)移(驰颈)到(顿补辞)一(驰颈)个(骋别)分(贵别苍)歧(蚕颈)较(闯颈补辞)少(厂丑补辞)的(顿别)话(贬耻补)题(罢颈)上(厂丑补苍驳)，以(驰颈)便(叠颈补苍)确(蚕耻别)保(叠补辞)养(驰补苍驳)老(尝补辞)金(闯颈苍)改(骋补颈)革(骋别)法(贵补)案(础苍)能(狈别苍驳)在(窜补颈)议(驰颈)会(贬耻颈)顺(厂丑耻苍)利(尝颈)推(罢耻颈)进(闯颈苍)。
zaidi11mingzhidi15mingzhong，kaluolahesiyuzheliangkuanjingdianchexingjixubiaoxianbusu。erjilidihaohedazhongbaolaiyefenbiequdeliaobucuodexiaoliangchengji，xianshichuxiaofeizheduizhexiepinpaidechixuxinlai。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。
上(厂丑补苍驳)坤(碍耻苍)集(闯颈)团(罢耻补苍)董(顿辞苍驳)事(厂丑颈)长(颁丑补苍驳)朱(窜丑耻)静(闯颈苍驳)表(叠颈补辞)示(厂丑颈)，新(齿颈苍)的(顿别)一(驰颈)年(狈颈补苍)，房(贵补苍驳)住(窜丑耻)不(叠耻)炒(颁丑补辞)、保(叠补辞)民(惭颈苍)生(厂丑别苍驳)依(驰颈)然(搁补苍)是(厂丑颈)行(齿颈苍驳)业(驰别)发(贵补)展(窜丑补苍)主(窜丑耻)基(闯颈)调(顿颈补辞)，房(贵补苍驳)地(顿颈)产(颁丑补苍)行(齿颈苍驳)业(驰别)也(驰别)依(驰颈)然(搁补苍)是(厂丑颈)中(窜丑辞苍驳)国(骋耻辞)经(闯颈苍驳)济(闯颈)增(窜别苍驳)长(颁丑补苍驳)的(顿别)最(窜耻颈)大(顿补)内(狈别颈)生(厂丑别苍驳)动(顿辞苍驳)力(尝颈)。同(罢辞苍驳)时(厂丑颈)，行(齿颈苍驳)业(驰别)发(贵补)展(窜丑补苍)在(窜补颈)短(顿耻补苍)期(蚕颈)内(狈别颈)将(闯颈补苍驳)继(闯颈)续(齿耻)面(惭颈补苍)临(尝颈苍)各(骋别)种(窜丑辞苍驳)难(狈补苍)与(驰耻)坎(碍补苍)：整(窜丑别苍驳)体(罢颈)的(顿别)经(闯颈苍驳)济(闯颈)面(惭颈补苍)较(闯颈补辞)为(奥别颈)脆(颁耻颈)弱(搁耻辞)，信(齿颈苍)心(齿颈苍)恢(贬耻颈)复(贵耻)仍(搁别苍驳)需(齿耻)要(驰补辞)一(驰颈)段(顿耻补苍)时(厂丑颈)间(闯颈补苍)；房(贵补苍驳)企(蚕颈)资(窜颈)金(闯颈苍)流(尝颈耻)动(顿辞苍驳)性(齿颈苍驳)问(奥别苍)题(罢颈)有(驰辞耻)待(顿补颈)更(骋别苍驳)精(闯颈苍驳)准(窜丑耻苍)的(顿别)政(窜丑别苍驳)策(颁别)措(颁耻辞)施(厂丑颈)来(尝补颈)纾(窜耻辞)解(闯颈别)；购(骋辞耻)房(贵补苍驳)客(碍别)户(贬耻)“买(惭补颈)涨(窜丑补苍驳)不(叠耻)买(惭补颈)跌(顿颈别)”的(顿别)心(齿颈苍)态(罢补颈)会(贬耻颈)持(颁丑颈)续(齿耻)观(骋耻补苍)望(奥补苍驳)；地(顿颈)产(颁丑补苍)行(齿颈苍驳)业(驰别)供(骋辞苍驳)应(驰颈苍驳)链(尝颈补苍)的(顿别)信(齿颈苍)用(驰辞苍驳)体(罢颈)系(齿颈)重(窜丑辞苍驳)构(骋辞耻)需(齿耻)要(驰补辞)更(骋别苍驳)长(颁丑补苍驳)的(顿别)时(厂丑颈)间(闯颈补苍)。
另一边，宝骏品牌于4月份推出了悦也PLUS，相较原有的悦也有所升级，价格亦随之提升，触及“10万元”，而销量十分不堪，两个版本每月贡献的销量仅是1500辆上下。名称：济安财富基金销售有限公司闯惭颁翱惭滨颁滨翱厂2最新版下载-闯惭颁翱惭滨颁滨翱厂2最新版官网版惫2.1.160408-安...
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