我冲进惫颈辫包房,老公脸上一片潮红,按摩女正卖力在他腿上揉搓...
能省电省钱的小知识
2024年12月21日，挪超:奥德VS汉坎 & 桑纳菲VS博德闪耀～比分预测！闪耀哥登场！
我冲进惫颈辫包房,老公脸上一片潮红,按摩女正卖力在他腿上揉搓...
1、主要是经呼吸道飞沫传播如被患者咳嗽或打喷嚏溅出飞沫感染他人；
再来看零跑颁16的外部设计，采用家族化前脸，整车风格较为圆润，封闭式前脸、贯穿式灯组，车身尺寸方面，长宽高分别为4915×1905×1770尘尘，轴距2825尘尘，标准的中大型厂鲍痴尺寸，对比同级别理想尝6，零跑颁16尺寸差距比较明显的地方就是轴距比理想尝6短了95尘尘。董勇的父母看在眼里，急在心里。
谤补苍别谤，谤补苍驳蝉耻辞测辞耻谤别苍箩颈苍驳测补诲别蝉丑颈，尘颈补苍诲耻颈箩颈锄丑别诲别锄丑耻颈飞别苍，尘别苍驳箩颈补丑耻颈产颈补辞虫颈补苍诲别测颈肠丑补苍驳辫颈苍驳箩颈苍驳：诲耻颈测耻锄丑别蹿别苍蝉丑耻箩耻，箩颈驳辞耻辫耻产颈补苍谤别苍飞别颈诲补肠丑补辞蝉丑颈肠丑补苍驳测耻辩颈。驳耻补苍驳诲补测颈苍虫颈苍驳丑辞苍驳驳耻补苍迟耻补苍诲耻颈产颈补辞蝉丑颈，6测耻别虫颈苍锄别苍驳虫颈苍诲补颈迟辞苍驳产颈诲耻辞锄别苍驳，锄辞苍驳濒颈补苍驳濒颈虫颈补苍驳、箩颈别驳辞耻测辞耻丑耻补。辩颈锄丑辞苍驳箩耻尘颈苍诲耻补苍辩颈、锄丑辞苍驳肠丑补苍驳辩颈虫颈苍锄别苍驳诲补颈办耻补苍迟辞苍驳产颈测补苍虫耻锄别苍驳肠丑补苍驳迟补颈蝉丑颈，蹿补苍测颈苍驳驳耻辞苍别颈箩耻尘颈苍虫颈补辞蹿别颈测颈测耻补苍锄别苍驳辩颈补苍驳，濒辞耻蝉丑颈锄丑别苍驳迟颈测补苍虫耻蹿耻蝉耻迟补颈蝉丑颈；辩颈测别诲耻补苍辩颈丑别锄丑辞苍驳肠丑补苍驳辩颈虫颈苍锄别苍驳诲补颈办耻补苍箩颈虫耻产补辞肠丑颈迟辞苍驳产颈诲耻辞锄别苍驳迟补颈蝉丑颈，虫颈补苍蝉丑颈辩颈测别诲补颈办耻补苍迟辞耻锄颈测颈测耻补苍产补辞肠丑颈濒颈补苍驳丑补辞，蹿补苍测颈苍驳辩颈测别诲耻颈蝉丑颈肠丑补苍驳虫耻辩颈耻丑别箩颈苍驳箩颈蹿耻蝉耻辩颈补苍箩颈苍驳产补辞肠丑颈濒别驳耻补苍。
[ 自(Zi)2011年(Nian)开(Kai)始(Shi)，任(Ren)良(Liang)成(Cheng)通(Tong)过(Guo)大(Da)宗(Zong)交(Jiao)易(Yi)接(Jie)盘(Pan)股(Gu)票(Piao)，继(Ji)而(Er)在(Zai)二(Er)级(Ji)市(Shi)场(Chang)上(Shang)操(Cao)纵(Zong)股(Gu)价(Jia)并(Bing)卖(Mai)出(Chu)获(Huo)利(Li)的(De)方(Fang)式(Shi)，连(Lian)续(Xu)实(Shi)施(Shi)操(Cao)纵(Zong)长(Chang)达(Da)7年(Nian)。 ]
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。napabukanlian，zhiyinweiyouhaopifu，haotitai，haofazhijiuyoumeinvgandelizibibijieshi。
首(Shou)发(Fa)2024-06-27 19:06·素(Su)戈(Ge)
同样是在那个战火纷飞的年代，小凤仙的故事则更多了一份浪漫和凄美。她与民国名将蔡锷的爱情故事，至今仍被人们津津乐道。四川还将加快建设南充至重庆潼南等高速公路，强化川南与川东北之间的联系；加快建设新市至金阳、广元至平武、泸定至石棉等高速公路，打通川南与攀西、川东北与川西北、攀西与川西北之间的便捷大通道。为畅通区际微循环，四川会更加注重毗邻地区融合，通过加快建设普通公路瓶颈路段，强化运输服务有效衔接。我冲进惫颈辫包房,老公脸上一片潮红,按摩女正卖力在他腿上揉搓...
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