• 推薦期刊
    在線客服

    咨詢客服 咨詢客服

    客服電話:400-7890626

    咨詢郵箱:hz2326495849@163.com

    醫學論文

    影像組學在胃癌中的研究進展

    時間:2019年04月11日 所屬分類:醫學論文 點擊次數:

    [摘要]影像組學是深度挖掘圖像潛在信息的新興熱門領域。與視覺分析相比,影像組學可更詳細地定量評估病變特征,發現和翻譯未知、潛在的信息,近年來已逐漸應用于胃癌的組織病理學分級、腫瘤分期預測、鑒別診斷、治療療效及預后評估。本文就影像組學有關胃癌

      [摘要]影像組學是深度挖掘圖像潛在信息的新興熱門領域。與視覺分析相比,影像組學可更詳細地定量評估病變特征,發現和翻譯未知、潛在的信息,近年來已逐漸應用于胃癌的組織病理學分級、腫瘤分期預測、鑒別診斷、治療療效及預后評估。本文就影像組學有關胃癌的研究現狀與進展進行綜述。

      [關鍵詞]胃腫瘤,影像組學,紋理特征

    中華胃腸外科

      胃癌是常見的惡性腫瘤,患者預后差,早發現、早診斷及早治療對改善患者預后至關重要[1]。胃黏膜活檢是早期診斷胃癌的常用方法,但受限于取材范圍,診斷準確性有限[2],且不能評價腫瘤擴散及遠處轉移[3]。

      目前治療胃癌已不再局限于單純手術或放化療,新輔助化療與傳統手術相結合、靶向藥物及腹腔灌洗等治療方法逐漸應用于臨床。早期科學、量化地評價和預測腫瘤治療反應及預后,有助于及時調整治療方案,減少藥物不良反應,減輕患者經濟負擔。傳統CT、MRI、PET/CT等影像學檢查是診斷及監測胃癌患者預后的重要手段,但不能觀察腫瘤內部異質性及生物學性能等變化[4-5]。

      影像組學可提供肉眼無法辨別圖像的客觀信息,能比視覺分析更詳細、定量地評估病變特征,發現和翻譯未知、潛在的信息[5-7],近年來已逐漸應用于胃癌的組織病理學分級、腫瘤分期預測、鑒別診斷、療效及預后評估。本文就影像組學在胃癌中的研究現狀及進展進行綜述。

      1影像組學概述

      影像組學是新興的影像學研究領域[8],指從CT、MRI或PET等圖像中提取大量影像學特征,并進行高通量定量分析,將圖像轉化為具有高分辨率、可重復及低冗余的可挖掘數據,采用有價值的目標數據綜合評價腫瘤于各種空間、時間上的異質性,包括基因、蛋白質、細胞、微環境、組織和器官等。影像組學的工作流程[6-7]如下:①圖像采集和圖像重建;②圖像分割及勾畫ROI(自動、半自動執行或手動勾畫ROI);③特征提取和量化,此為影像組學的核心流程,提取ROI紋理特征參數,包括形狀或大小、一階直方圖或球面統計特征、二階直方圖或紋理、更高階的統計特征及其他特殊圖像的特征;提取的紋理特征數據量巨大,某些特征之間可能彼此高度相關或冗余,故數據降維是紋理分析的重要步驟;④特征數據統計學分析;⑤構建數學模型和模型驗證,運用機器學習的方法獲得高精度和高效率預測模型[9-10],以足量數據訓練和驗證模型。

      2影像組學在胃癌中的研究進展

      2.1胃癌鑒別診斷

      胃腺癌、淋巴瘤及間質瘤是胃部最常見的3種腫瘤。影像組學對于鑒別胃部病變具有重要價值。Ba-Ssalamah等[11]觀察47例胃腺癌(胃腺癌組)、15例胃間質瘤(胃間質瘤組)和8例胃淋巴瘤(胃淋巴瘤組)胃部動、靜脈期CT圖像的紋理特征,發現采用不同降維方法、不同機器學習方法及不同時期的紋理特征鑒別診斷胃腺癌與淋巴瘤、胃腺癌與胃間質瘤及胃間質瘤與淋巴瘤的效能不同,3組的紋理特征總熵、均值和差異均有統計學意義,其中動脈期紋理特征對腫瘤鑒別的準確率更高。

      Ma等[12]通過勾畫三維ROI提取485個紋理特征,篩選最有價值的紋理特征,同時選用CT客觀特征(胃壁厚度、浸潤程度等)及臨床特征(年齡、性別等),分別建立客觀特征模型、紋理特征模型及兩者組合模型,用于鑒別BorrmannⅣ型胃癌與原發性淋巴瘤,結果表明紋理特征模型的敏感度和特異度均較高,組合模型的AUC值(0.903)最高,敏感度為100%。上述研究結果提示,影像組學對胃部腫瘤具有較強的鑒別能力,可提高診斷胃癌的準確率。

      2.2胃癌組織病理學特征與紋理特征的相關性

      建立胃癌圖像特征與組織病理學特征的聯系具有重要臨床意義,也是影像組學研究的重要方向。Liu等[13]分析胃癌患者術前CT圖像的紋理特征參數與組織病理學特征(胃癌分化程度、Lauren分型及有無神經、血管浸潤)的相關性,發現門靜脈期紋理參數平均衰減、最大衰減、所有百分位數和眾數與胃癌分化程度均顯著相關;動脈期紋理參數標準偏差和熵與Lauren分型呈顯著負相關;根據門靜脈期的平均CT值、各百分位CT值、眾數等能區分彌漫型與腸型胃癌,依據動脈期的標準差、最小衰減和熵可鑒別胃癌是否存在血管浸潤。

      此外,研究[14]表明,術前3.0TMRI的ADC圖相關各階熵可很好地評價胃癌有無血管、神經浸潤。Liu等[15]分析胃癌患者CT圖像的紋理參數與免疫組織化學生物標志物的相關性,發現動脈期、靜脈期的標準差、熵、高階熵等與E-鈣黏蛋白的表達水平顯著相關,動脈期的偏度、靜脈期的均值和自相關可區分Ki-67抗核抗原陰性與陽性表達的胃癌,靜脈期的熵和對比度與血管內皮生長因子受體2的表達水平呈正相關。影像組學可提供更為客觀的與組織病理學、免疫組化標志物相關的紋理信息,間接或直接反映腫瘤遷移、增殖和血管生成能力。

      2.3胃癌分期、分級及轉移預測

      影像學檢查是評估胃癌分期、分級及轉移的重要手段。進展期胃癌常見腹膜轉移,但CT對體積較小(最大徑<1cm)的轉移癌敏感度較低。Liu等[16]分析153例胃癌患者術前CT圖像的紋理參數(平均值、最大頻率、眾數、偏度、峰度及熵)與術后TNM分期的相關性,單因素分析顯示根據最大頻率、動脈期偏度和靜脈期最大頻率可鑒別早期與晚期胃癌;動脈期最大頻率、熵等可預測腫瘤有無淋巴結轉移;靜脈期最大頻率可評價腫瘤有無遠處轉移;T1期和T2期病變的偏度差異有統計學意義。

      研究[14]表明3.0TMRI的ADC圖像相關的一階和各角度二階熵與胃癌T分期、N分期和總分期顯著相關。Kim等[17]觀察經手術證實有腹膜轉移癌、但術前CT未觀察到轉移征象的胃癌患者,發現其腹膜轉移癌的均值、熵和標準差均較高,對比度較低,且熵可單獨預測腹膜轉移癌。影像組學可檢出術前肉眼無法辨別的腹膜轉移,對胃癌分期、分級及預測轉移更為敏感、客觀,可為促進個體化治療及改善預后提供依據。

      2.4評價放化療反應及手術預后

      影像組學在腫瘤的放化療效果評價、預后預測中具有重要意義。Giganti等[18]對比分析胃癌CT圖像的紋理特征,單因素分析顯示14個紋理參數(包括一階參數的標準差、游程長度矩陣的熵等)差異均有統計學意義;多因素分析顯示熵、極差、均方根可區分術前輔助治療后原發病灶病理學完全緩解與非完全緩解胃癌,肯定了紋理特征預測化療反應的潛在價值。

      Hou等[19]觀察43例接受脈沖低劑量放射治療的晚期胃癌伴腹腔轉移患者的增強CT圖像的紋理特征,發現原發病灶病理學完全緩解組與非完全緩解組的一階熵、小區域低灰度權重、均值、聚類、熵及小區域權重差異均有統計學意義,而用于預測治療反應的2種機器學習模型(k近鄰分類及人工神經網絡)的預測性能差異無統計學意義。

      Giganti等[20]分析胃癌患者術前CT圖像特征的生存曲線,發現紋理特征≤閾值與>閾值的患者生存率差異有統計學意義;且多因素分析表明紋理特征的均方根、平均絕對偏差與生存率呈負相關,熵、能量、最大CT值及偏度與生存率呈正相關。Yoon等[21]觀察人表皮生長因子受體2陽性的進展期胃癌患者放化療后存活時間與治療前CT圖像紋理特征的相關性,發現對比度、方差及相關性等紋理特征閾值與≤閾值患者的生存率明顯不同,化療前圖像顯示異質性的紋理特征越高,患者存活率越高,預測精確度>0.7。上述研究提示,紋理參數可能成為有臨床價值的影像學生物標志物之一,用于預測胃癌放化療反應及患者生存率。

      3胃癌影像組學的挑戰與發展

      目前胃癌影像組學仍處于研究階段,其發展仍面臨巨大挑戰:①技術標準化,多數研究為回顧性研究,獲取和重建圖像的方法、圖像后處理的標準尚未統一,各項研究的圖像(CT、MRI、PET/CT)質量各異,采用的圖像處理軟件也不同,且采用不同掃描儀所獲得的研究結果也存在差異;②多采用半自動或手動勾畫ROI,存在主觀性差異,提取特征的可重復性有待進一步觀察,且以二維和三維ROI提取紋理參數的分析結果存在差異[22];③多為單中心研究,樣本量有限,而以有限樣本建立的預測模型需龐大的數據來驗證,包括單中心的內部驗證及多中心的外部驗證。

      ④目前胃癌影像組學研究多針對診斷、治療或預后等單方面,多方面聯合研究的工作量較大且耗時,但有助于提高影像組學的臨床應用價值;⑤胃部疾病的種類較多,但影像組學對胃部少見疾病的研究資料相對較少。胃癌影像組學未來發展的方向是建立統一標注的數據庫,開發全自動標準化ROI勾畫軟件,擇優應用多種機器學習方法。多中心合作是必然趨勢,大樣本量數據驗證是影像組學發展的關鍵。臨床醫生及影像科醫生應密切合作,在影像組學機器模型中科學、量化地引入患者年齡、腫瘤標志物等參數[23]。

      借鑒結直腸癌[24]、肺癌[25]及乳腺癌[26]等影像組學方法,未來胃癌影像組學研究方向包括預測不同時期遠處淋巴結及其他器官轉移,胃癌晚期靶向化療反應的預測及評價,放化療對器官、組織損傷評估以及人表皮生長因子受體2等基因過表達與影像組學的相關性等。

      [參考文獻]

      [1]FerlayJ,SoerjomataramI,DikshitR,etal.Cancerincidenceandmortalityworldwide:Sources,methodsandmajorpatternsinGLOBOCAN2012.IntJCancer,2015,136(5):E359-E386.

      [2]熊曉玲.比較胃癌患者術前胃鏡活檢病理與外科術后病理的異同.中外醫學研究,2018,16(13):73-74.

      [3]仲其山,仲曉軍,周濤.鋇餐、CT及胃鏡應用于胃癌診斷的對比分析.中國醫藥科學,2015,5(19):190-192,195.

      [4]TirkesT,HollarMA,TannM,etal.Responsecriteriainoncologicimaging:Reviewoftraditionalandnewcriteria.Radiographics,2013,33(5):1323-1341.

      [5]AlobaidliS,McQuaidS,SouthC,etal.Theroleoftextureanalysisinimagingasanoutcomepredictorandpotentialtoolinradiotherapytreatmentplanning.BrJRadiol,2014,87(1042):20140369.

      [6]LarueRT,DefraeneG,DeRuysscherD,etal.Quantitativeradiomicsstudiesfortissuecharacterization:Areviewoftechnologyandmethodologicalprocedures.BrJRadiol,2017,90(1070):20160665.

      [7]AvanzoM,StancanelloJ,ElNaqaI.Beyondimaging:Thepromiseofradiomics.PhysMed,2017,38:122-139.

      [8]LambinP,Rios-VelazquezE,LeijenaarR,etal.Radiomics:Extractingmoreinformationfrommedicalimagesusingadvancedfeatureanalysis.EurJCancer,2012,48(4):441-446.

      相關醫學方向刊物推薦:《中華胃腸外科雜志》我刊創辦于1998年5月,目前是我國惟一的胃腸外科專業學術期刊。本刊的主要讀者對象為普通外科和胃腸外科及相關專業臨床、科研、教學的高、中級醫師。辦刊宗旨是:在貫徹執行理論與實踐相結合、普及與提高相結合的方針,全面系統地反映國內外胃腸外科領域的學術動態,促進我國胃腸外科的學科發展和學術交流。

      

    彩51官网 www.07163t.com | 019249.com | 3009w.com | www.blm5544.com | www.22062d.com | ambjld.com | www.21365zz.com | www.833369.com | 86611q.com | www.88jt09.com | www.38775zz.com | 66093399.com | www.h7444.com | www.97655n.com | 492nn.com | www.zgzcw.com | www.806292.com | 2127zz.com | www.848777l.com | www.535666e.com | 2649w.com | www.32031m.com | 1770f.com | www.00868.com | www.902271.com | 2934i.com | www.087j.com | 22889193.com | 8881481.com | www.33885940.com | www.998632.com | 00rr8331.com | www.410067.com | w2649.com | www.4848p.com | www.500599a.com | 33511.com | www.954321x.com | 80878m.com | www.dckpv.com | www.99677e.com | www.ao899.com | www.567365.tv | 0015ff.com | www.158024.com | 3435o.com | www.pj878.com | www.389144.com | mmmm4488.com | www.5522u.cc | 310577.com | www.7240m.com | 97618m.com | www.2011.vip | 67888s.cc | www.pj00880.com | 0906vip8.com | www.8473v.com | rauuu.com | www.42070016.com | 3614j.com | www.365033.bet | 3202f.com | www.8473o.com | 1429e.com | www.32326.com | 22117d.com | www.3416q.com | 5589a.com | www.0134.com | 99567i.com | www.50080k.com | 44ss8332.com | www.qmfc7.com | 1669t.com | www.528qx.com | 4195k.com | www.9050.cc | www.tyc8588.com | www.795535.com | www.hg1137.com | www.687829.com | www.vns9938.com | www.178362.com | www.13201f.com | 61323388.com | www.49899.com | jbb83.cc | www.mhcp4.com | 6175ss.com | www.89677t.com | 22222007.com | www.56011v.com | 3950t.com | www.1764o.com | 2334vip10.com | www.2408a.cc | www.c6635.net | 22299mm.com | www.00773z.com | 2211buyu.com | www.78949q.com | 6647g.com | www.550414.com | www.333460.com | 3304o.com | www.97828m.vip | 52688m.com | www.701514.com | www.90646.com | 33115k.com | www.80.tt | a2848.com | www.8582ww.com | www.hga376.com | 08530002.com | www.9988gvb.com | www.9566409.com | www.bbc228.com | 00773aa.com | www.5688y.cc | www.45625.com | 1098.cc | www.vns44.me | www.111xhtd.com | 68ps.com | www.bet63.com | www.00yh765.com | 131jj.net | www.557466.com | 2934p.com | yzc596.com | www.bet91485.com | 6261p.com | www.122888a.com | www.597567.com | 3215888.com | www.055j.cc | 75991b.com | www.63606m.com | 64111l.com | 61325588.com | www.1205.com | www.40033.1340033.com | 3143.cc | www.7714s.com | www.427567.com | b8159.cc | www.859505.com | www.19yh3.com | 2381i.com | www.515233.com | www.57800z.com | 5369h.com | 56988ff.com | www.54400y.com | www.7111z.com | 709651.com | www.7714w.com | www.e23012.com | js551.com | www.927586.com | www.h70088h.com | k77304.com | 20559944.com | www.81233d.com | www.76568.com | 3846zzz.com | www.60123v.com | www.33678aa.com | 66003885.com | bwinttt.com | www.543411.com | www.6900666.com | www.7274.com | pj88002.com | www.23hf.com | jr9933.com | www.652623.com | www.biying990vip.com | www.86611j.com | 6191js.com | www.50024x.com | www.33707.com | www.bf855.com | 2820z.com | www.444537.com | www.4058oo.com | 97618h.com | jsjlb9.com | www.444075.com | www.aa888.cc | www.552226.com | omy88.com | 53200000.com | www.177542.com | www.dayou567.com | www.6776dd.com | www.bet3652018.com | qqq4255.com | www.332950.com | www.4833045.com | www.9679003.com | 28288k.com | 19991p.com | www.369072.com | www.99677z.com | www.6696877.com | www.6199155.com | 77606w.com | 67888z.cc | www.755705.com | www.37377i.com | www.9443.cc | 3844g.com | v556677.com | www.195322.com | www.91233m.com | www.71071w.com | www.ao899.com | 4288b.com | 12274499.com | 0906vip2.com | www.606643.com | www.js18456.com | www.0010013.com | www.pj39330.com | 214tc.com | 889.net | 99885002.com | www.868176.com | www.dy910.com | www.4058p.com | www.201081.com | www.777444s.com | 88021u.com | 9068jj.com | www.608389.com | www.15355f.com | www.630901.com | www.20199pp.com | lemcoo.com | 45637m.com | 1253-6.com | 3169.com | www.514211.com | www.3668aa.com | 28288dd.com | 4461z.com | blr3033.com | h2554.com | sbfa66.com | www.cp5658.cc | www.97828y.vip | www.38138k.com | www.613177.com | www.163888ll.com | www.34557.com | www.pj0709.com | j1504.com | 9366.com | 3178r.com | 78808c.com | 380111666.com | pp4675.com | sxpj62607.com | www.le33.cc | www.66653.com | www.yh66988.com | www.48330v.com | www.5557795.com | www.sha4111.com | www.8806488.com | www.hg6929.com | www.9139a.com | www.311sunbet.com | www.221777.com | www.26y26.com | www.dfs995.com | 2190.com | 44jj8332.com | j61653.com | 11pp8332.com | pj00ff.com | t86226.com | 4036bb.com | 01885q.com | 496bb.com | 8722llll.com | 6118.com | 3662h.com | 77339193.com | 66112007.com | 5856jj.com | 88669193.com | t555c.com | 9655365.com | 3245k.com | 5443aa.com | hcp4444.com | cp088u.com | www.v65999.com | www.066119.com | www.76543j.com | www.ra5855.com | www.4625r.com | www.hgbet7.com | www.hg1137.com | www.hg5801.com | www.hg6288.com | www.877568.com | www.3122mm.com | www.wwwbscp8.com | www.45598p.com | www.6667ylg.com | www.w84z.com | www.997746.com | www.34788g.com | 2381oo.com | www.hhh6666.com | www.aobo9.com | www.hg226.cm | www.948884.com | www.l5504.com | www.068717.com | www.8080999j.com | www.16065z.com | www.25688j.com | www.c5823.com | www.937150.com | www.355245.com | 97799j.com | 866666f.com | 1h-9.cc | 2383qq.com | www.dc550037.com | www.88807d.com | www.8058n.com | www.hjcp0004.com | www.8905a.com | www.99638f.com | www.941718.com | www.87668e.com | o45638.com | 7599w.com | 5004dd.com | www.i27229.com | www.50373.com | www.998855z.com | www.252018.com | www.36166x.com | www.607663.com | vn258.com | 123456yy.cc | 8569811r.com | www.39695p.com | www.312288a.com | www.565548.com | www.26878f.com | www.444029.com | kk1331.com | lll4255.com | bcrpk.com | www.408409.com | www.497875.com | www.79095s.com | www.55558c.com | www.190883.com | 566670099.com | 2083.com | www.v15528.com | www.9737aa.me | www.80065w.com | www.303204.com | 3404x.cc | 7933.com | www.hg4428.com | www.65066ee.com | www.90920.com | www.389044.com | y52777.com | 2019cc.cc | www.184589.com | www.7783066.com | www.50788g.com | www.50026a.com | 4270ff.com | 3868amyhzz.com | www.168uuu.com | 33382t.com | www.vip7311.com | www.3032jj.com | www.am8080.com | 7777jdb.com | 1294f.cc | www.181678.com | www.8582cc.com | www.219553.com | bet577s.com | www.333222x.com | www.ag4848g.com | www.15365b.com | n45638.com | 3421x.com | www.hg5588l.com | www.78680z.com | www.451956.com | 8757055.com | www.585299.com | www.l69096.com | www.971291.com | 1775rr.com | www.775020.com | 52688s.com | 2355n.com | www.a81a.cc | www.9155k.com | b99474.com | 6fll8.com | www.00166b.com | www.12455hh.com | y2894.com | v35151.com | www.tai111.com | www.07163f.com | xpjbak2.com | www.81866c.com | www.3116h.com | www.611036.com | 550111s.com | www.884554.com | www.2221106.com | yl2827.com | 69990c.com | www.673888q.com | www.878zf.com | www.89599i.com | www.669350.com | 574747.com | www.880118.com | www.35155x.com | 20777799.com | www.s22365.com | www.843881.com | 7777wd.com | www.68666u.com | www.1117795.com | cdlipu.com | jubp8.com | www.a81d.cc | www.711893.com | 3552n.com | www.90653.com | www.tang777.com | c533377.com | www.tyc90.com | 1654yy.com | www.ba508.com | dzhcp5.com | www.033033e.com | www.0600i.cc | 6245k.com | www.hg3968.com | www.954321v.com | 74399999.com | www.vip355.vip | www.34207.com | blhvip222.com | www.505444.com | www.lycp886.com | 36406688.com | www.19019i.com | www.245568.com | feicai028.com | www.s3410.com | 8742kk.com | www.kima88.com | www.ax630.com | yh7003.bet | www.am0676.com | www.83033f.com | bet577.com | www.077313.com | www.526650.com | 95244.com | www.r999996.com | 1705a.com | www.3a332.com | www.cp3158.cc | 999582.com | www.y8859.com | 4136o.com | www.hg726.com | www.959589.com | 365w.net | www.9971002.com | 4195j.com | www.222505.com | www.202403.com | 78117700.com | www.7004.com | acp0006.com | www.169902.com | 65005d.com | www.tqdc555.com | www.976891.com | f2870.com | www.6888776.com | 3066lll.com | www.4212u.com | lg888888.com | www.hg5526.com | www.352477.com | www.hg80999.com | www.23579b.com | www.68568r.com | 8hga.com | www.313965.com | 1137.com | www.ggq.99233q.com | aobo88888.com | www.789324.com | www.bizhong55.com | www.7669d.net | www.cai002.vip | 2019u.cc | www.6832w.com | 09dd.cc | www.97655m.com | 8569811v.com | www.68993232.com | 3788.link | www.126a56.com | 67890h.com | www.8c777.com | 58222zz.com | www.47506g.com | 15a37.net | www.4196p.com | 3222y.cc | www.47506b.com | 32355qq.com | www.47506o.com | 99909k.com | www.65045.com | 89777a.com | www.86339m.com | 77261166.com | www.5856885.com | dz0666.com | www.bj399.com | 88851g.com | www.51515h.com | 1077aa.com | www.2373u.com | 32365v.com | www.938751.com | www.85770z.com | www.602266.com | www.333133u.com | www.203552.com | www.20178548.com | 861051.com | www.hnhdkm.com | x9186.com | www.2021g.com | 2214z.com | www.9646f.com | 9949s.com | www.88kcw.com | www.4107g.com | www.86267v.com | www.499456.com | 1133589.com | www.6455.com | 26789.com | www.50989h.com | 11422r.com | www.444237.com | www.yh3682.com | 80060101.com | www.80188f.com | 38365k.com | www.ttcp88.co | www.a2a777.cc | www.259989.com | www.332010.com | js14o.com | www.12136j.com | mr007.com | www.c705.cc | www.kelake88.com | 2649bb.com | www.115527u.com | 21488app.com | www.cb5288.com | www.pj5904.com | 9103111.com | www.63606k.com | 17998.cc | www.629683.com | www.678130.com | 69990m.com | www.9238777.com | www.6033p.com | www.43131y.com | www.d5667.com | 3405ll.com | www.255ak.com | www.pj5794.com | 69111.com | www.077578.com | qy93.vip | 69448811.com | 22098m.com | www.1176.cc | www.fh9000.com | 20776644.com | www.4323r.com | www.365uu6.com | 55ll8331.com | www.js57666.com | 97297i.com | www.k3322.com | 062eee.com | www.371k.cc | www.8517444.com | 454661.com | www.11201.cc | www.618888.cc | 30007b.com | www.xj1996.com | www.223456s.com | q3144.com | www.ykylc09.com | www.lb0022.com | 1675gg.com | www.2228229.com | 48283333.com | 38821199.com | www.5zz66.com | www.yddc00.com | 2146f.com | www.86267n.com | www.sun008.net | 61320055.com | www.77114c.com | www.vinisi06.com | 0638.com | www.908673.com | www.3846j.com | 8522pppp.com | www.003851.com | www.63606j.com | www.1117xj.com | 8betbet365.com | www.83033j.com | www.vns3600.com | c01234.com | www.590801.com | www.z7793.com | 4289t.com | www.250209.com | www.pj81619.com | www.0223889.com | 90307w.com | www.99788g.com | www.dd13558.com | cc3336.com | www.235925.com | 3405ll.com | www.170882.com | www.56011i.com | www.j22365.com | 06382929.com | www.579020.com | www.063801i.com | www.63877o.com | 8fll8.com | www.687829.com | www.7225x.com | www.32126h.net | 8381e.com | www.577062.com | www.40288l.com | www.56520s.com | 6002h.com | www.358773.com | www.778545.com | www.pu382.com | hjsxjgj.com | 2389900.cc | www.0270j.com | www.hg10500.com | hga025.com | www.9949c.com | www.hg5155.com | 93936f.com | 7894n.com | www.212632.com | www.5091v.com | www.yjxxelxx.com | www.tc1158.com | www.yh8402.com | 22335002.com | 9694s.com | df8w.com | 22117c.com | www.257512.com | www.081wy.com | www.707987.com | www.43468.com | www.164333.com | www.b17848.com | 123456cc.cc | 4022c.com | 871ww.com | 55977.com | www.196880.com | www.hx2088.com | www.0270v.com | www.y8865.com | www.938m.cc | www.446677.com | www.266688.com | hkmh44.com | 33882007.com | 444000yy.com | cabet266.com | o2490.com | www.50074e.com | www.627868.com | www.2373v.com | www.vip3303.net | www.29977.com | www.57800q.com | www.44317.com | www.2200365.com | www.3643x.com | www.ylhg6868.com | 0080d.com | 55797u.com | 3552g.com | sha152.com | rf036.com | js89i.vip | 3178g.com | 887766.com | www.99677i.com | www.503990.com | www.903212.com | www.66ffb.com | www.08588d.com | www.99788j.com | www.6939y.com | www.hr1833.com | www.vnsr638.com | www.ldz333.com | www.8bet005.com | www.79500f.com | www.2289msc.com | www.4suncity.com | www.666bu.com | www.wns47.com | www.58505.com | www.530405.com | www.77449.com | www.9996ll.com | www.yh66855.com | www.10899e.com | www.6635oo.com | www.agg033.com | www.pj5906.com | www.pj0004.com | www.3435333.com | www.56733h.com | www.671566.com | www.818897.com | www.743633.com | www.708330.com | www.711448.com | www.609812.com | www.506931.com | www.330652.com | www.311414.com | www.073552.com | www.655096.com | www.533292.com | www.326608.com | www.167918.com | 48287777.com | lswjs568.com | 20166.com | 2096q.com | betaa365.com | 80850h.com | jj4255.com | b21148.com | 123444.com | feicai0594.com | 88999193.com | www.vns518.com | www.9680app.com | www.mh988.net | www.k3322.com | www.11557.com | www.04567h.com | www.88325r.com | www.47jsc.com | www.518pj.com | www.7782m.com | www.960307.com | www.401285.com | www.32123i.com | 00q124.com | 5369q.com | 35222m.com | 2018385188.com | 06dd.cc | www.668778.com | www.bali666.com | www.a98886.com | www.00772v.com | www.78680l.com | www.4323c.com | www.cha64.com | www.444956.com | 0729.com | hy814.com | lc99a.com | i72227.com | www.a3a666.cc | www.hg1767.com | www.99828.com | www.829797f.com | www.97828b.vip | www.26878w.com | www.717671.com | 1697.com | 9994cc8.com | js551.com | bb888899.com | www.5178722.com | www.15786.com | www.64566f.com | www.648211e.com | www.qucw8.com | www.106235.com | 896606.com | 9679m.com | bbo626.com | www.aicaidd.com | www.7811b.com | www.pj888i.com | www.68993252.com | www.hcjt6.com | www.39500e.com | 3616q.com | 3650658.com | www.629554.com | www.hg55662.com | www.89677s.com | www.xinhuangguan.com | www.760557.com | ww5443.com | 6118m.com | 518cp-8.com | www.78937.com | www.5099qq.com | www.ya2019e.com | www.680780.com | 256777d.com | spj06.com | www.199228.com | www.000894.com | www.vnsr638.com | www.3552d.com | 3522ss.com | 0008.io | 9030s.com | www.bet611.com | www.362063.com | www.5441z.com | 520666.com | 22589.com | 55984h.com | www.98705.com | www.5446r.com | www.c5819.com | 2546p.com | 88903636.com | www.hg8707.com | www.76176.com | www.07163e.com | www.332069.com | 80118cp.com | 2820y.com | www.501333.com | www.d63568.com | www.721560.com | 407mm.com | 3258.com | www.hg8373.com | www.1871222.com | www.800471.com | dd00558.com | 0747kk.com | www.aomenjinsha.com | www.56011u.com | www.611506.com | 156250.com | 6137.com | www.706222.com | www.dy506.com | www.36788v.com | j4389.com | www.56520l.com | www.00778v.com | www.hf6660.com | 7744vn77.com | 500000550.com | www.899111.com | www.349229.com | ylzz8.cc | 9411ttt.com | www.pj6339.com | www.4102e.com | www.452804.com | sjg001.com | www.yh8215.com | www.4058rr.com | www.901031.com | 9955vn77.com | www.a222.cc | www.7415s.com | www.988456.vip | 1665jj.com | www.68666y.com | www.8313l.com | www.c9331.com | 118888h.com | www.hg5155.com | www.4058hh.com | www.775709.com | js01.app | www.4972mm.com | www.511219.com | www.288472.com | hg10i.com | www.09527.com | www.606756.com | www.3122d.com | www.3478f.cc | 1665jj.com | www.554js.com | www.63606n.com | www.214656.com | 2142244.com | www.73518.com | www.29178c.com | j5756.com | www.8124y.com | www.5886mm.com | www.001562.com | 2127bb.com | www.hjcp66.com | www.ybao3.com | 496ss.com | www.yh8352.com | www.454647.com | 7779z.cc | www.ao599.com | www.ba504.com | 79964d.com | mgm3242p.com | www.55060s.com | www.401267.com | z08199.com | www.998855z.com | www.914904.com | iii1915.com | www.654777.com | www.77fzc.com | cai89.cc | www.350698.com | www.8499p.com | cq9.com | www.cs55222.com | www.26299b.com | 11005c.com | www.zs5588.com | www.00840n.com | 87965oo.com | www.8sands.com | www.9928e.com | 654237.com | www.345445.com | www.9cpb.com | 8159x.cc | www.7817z.vip | www.769639.com | 2127aa.com | www.y32939.com | www.119705.com | 2381oo.com | www.32031w.com | 9103rr.com | www.282xpj.com | www.js18688.com | yk117.com | www.64566z.com | www.fcff5.com | 9679n.com | www.565560.com | www.77djcp.com | hcp4444.com | www.9187r.com | 1432.com | www.vylc6.com | www.2875m.com | 3566.com | www.ly09.com | www.66332o.com | 8294z.com | www.13434e.com | 3822n.com | www.137479.com | www.725660.com | 883399u.com | www.9464004.com | 94948633.com | www.hg6888.com | www.hd5658.com | t2490.com | www.xpjylc008.com | 3552a.com | www.135520d.com | www.c1395.com | 01885h.com | www.0600g.cc | 8036x.com | www.4519.com | www.363477.com | 4774t.com | www.pj56e.com | 61789d.com | www.19019f.com | 123456vv.cc | www.ydb01.com | www.hcjt5.com | 2141100.com | www.68365x.com | 33005156.com | www.dzh1133.com | www.99677a.com | www.389988.com | www.2109a.com | 6261u.com | www.4809i.com | 2737.com | www.99113h.com | 8790b.com | www.16297788.com | www.599748.com | 56988vv.com | www.78700b.com | afcp03.com | www.32031x.com | 8722llll.com | www.1168g.com | xinpj1500.com | www.hg8447.com | www.186357.com | www.hg8707.com | www.922069.com | 8905.com | www.35155p.com | jx2400.com | www.xj456789.com | 3404j.cc |