簡介：中文中文5400字出處出處MIZUUCHIH,COLWELLCW,MATSUDAS,ETALEFFECTOFTOTALKNEEARTHROPLASTYIMPLANTPOSITIONONFLEXIONANGLEBEFOREIMPLANTBONEIMPINGEMENTJTHEJOURNALOFARTHROPLASTY,2011,265721727全膝關(guān)節(jié)置換術(shù)中假體位置對于假體全膝關(guān)節(jié)置換術(shù)中假體位置對于假體骨撞擊前的最大屈膝角度的影響骨撞擊前的最大屈膝角度的影響MIZUUCHIH,COLWELLCW,MATSUDAS,ETAL全膝關(guān)節(jié)置換術(shù)（TOTALKNEEARTHROPLASTY，TKA）已成為最成功的骨科手術(shù)之一，文獻報道的假體存活率在15年后仍可高于90。隨著TKA術(shù)后長期結(jié)果的不斷改善，如何達到術(shù)后關(guān)節(jié)活動度最大化的問題又重新引起了人們的關(guān)注。對于亞洲國家以及經(jīng)常需要屈膝而坐的患者而言，術(shù)后屈膝活動的范圍尤為重要。即使在北美，高達75的患者認為在TKA術(shù)后進行諸如蹲坐、跪和園藝勞動等需要較大膝屈曲度的活動時困難增大。已有許多臨床研究探討了影響TKA術(shù)后關(guān)節(jié)活動度的相關(guān)因素。其中患者相關(guān)因素（如術(shù)前活動度、BMI、合并疾病、年齡、性別）可極大地影響術(shù)后關(guān)節(jié)活動度（RANGEOFMOTION，ROM）。同樣地，包括關(guān)節(jié)線高度、髕骨軌跡、恰當(dāng)?shù)那扉g隙平衡、后關(guān)節(jié)囊松解、骨贅切除等在內(nèi)的手術(shù)技巧均可影響術(shù)后ROM。另外，經(jīng)體內(nèi)透視分析證實，股骨后髁偏心距（POSTERIORCONDYLAROFFSET，PCO）也是一個重要因素。既往研究已經(jīng)分析過假體力線及相對位置對術(shù)后ROM的影響。WALKER等報道，向后方和近端調(diào)整股骨假體位置及增加脛骨假體后傾角度可增大股骨與脛骨塑料模型之間的屈曲角度。MASSIN和GOURNAY通過對膝關(guān)節(jié)側(cè)位片上假體元件的二維投影模板進行分析，認為更大的PCO可增加脛骨假體的后傾角度，而偏后的股脛接觸點可以增加膝關(guān)節(jié)屈曲度。然而，對患者三維解剖形態(tài)與假體位置的聯(lián)合效應(yīng)的研究目前尚未見報道。因此，我們建立了病例相關(guān)的假體骨撞擊解剖模型，以評估假體位置和解剖變異對屈曲角度的影響。研究的主要假設(shè)是假體位置將顯著影響發(fā)生假體骨撞擊前的膝關(guān)節(jié)最大屈曲角度。次要假設(shè)是PCO與膝關(guān)節(jié)最大屈曲角度有顯著關(guān)系。材料和方法假體位置經(jīng)倫理審查委員會批準(zhǔn)后，對60位行TKA的患者進行術(shù)前CT掃描，并選取其中10個膝關(guān)節(jié)來匹配實踐中常用的大、中、小型號的膝關(guān)節(jié)假體。每位患者的CT掃描均包含100MM厚的股骨頭部分，200MM厚以膝關(guān)節(jié)為中心的部分及100MM厚的踝關(guān)節(jié)部分，掃描層厚度為2MM。利用MIMICS軟件（MATERIALISE，LEUVEN，BELGIUM）讀取每個病例的斷層影像數(shù)據(jù)并創(chuàng)建患者的三維股骨、脛骨幾何結(jié)構(gòu)。然后，在MAGICS軟件（MATERIALISE）輔助下應(yīng)用三角網(wǎng)格模型進行表面重建。骨幾何結(jié)構(gòu)以STL格式（STEREOLITHOGRAPHYFORMAT）導(dǎo)入計算機輔助設(shè)計程序（RHINOCEROS；ROBERTMCNEELANDASSOCIATES，SEATTLE，WASH（圖1A）。用一個與股骨頭大小相匹配的球體定義出髖關(guān)節(jié)中心。臨床股骨髁上軸定義為內(nèi)、外上髁中心的連線，取臨結(jié)果應(yīng)用重復(fù)測量方差分析對不同假體位置時的最大屈曲角度進行分析。應(yīng)用BONFERRONI校正的事后比較檢驗分析相對于假體標(biāo)準(zhǔn)位置的不同位置下，最大屈曲角度之間差異的顯著性。應(yīng)用SPEARMAN等級相關(guān)分析檢測PCO與最大屈曲角度之間線性相關(guān)的強度。效應(yīng)分析證實，如假定標(biāo)準(zhǔn)差為25°，樣本量為10的試驗足以檢測最大屈曲角度為3°或以上的差異，把握度為090。試驗測定的尸膝最大屈曲角度為1420°±36°（均值±標(biāo)準(zhǔn)差；范圍1380°1460°）。從尸膝CT掃描生成的模型最大屈曲度為1472°±49°（范圍1428°1518°），這與模擬試驗測量結(jié)果相近，兩者間的平均絕對誤差為52°±16°（31°68°）。在所有10例膝關(guān)節(jié)中，2例股骨假體必須向前方位移超過1MM（分別為23和49MM），以避免出現(xiàn)股骨前皮質(zhì)切跡。機械軸和解剖軸間的屈曲角度差異為31°±11°（12°45°）。因此我們在評估前后位移的影響時，將股骨假體軸線與股骨的解剖軸對齊。利用此方法放置股骨假體與將股骨假體軸線與股骨的機械軸對齊時測量所得的前后位移值相差小于1MM。當(dāng)假體處于標(biāo)準(zhǔn)位置時，10個膝關(guān)節(jié)的平均最大屈曲角度為1363°±47°（13070°1437°）。10個膝關(guān)節(jié)之間屈伸活動度的差異為130°，這反映了本組病例之間的解剖變異。當(dāng)脛骨假體后傾角度為0°時，越向近端放置股骨假體，最大關(guān)節(jié)屈曲角度越大，而向遠端放置股骨假體則會減小最大屈曲角度（圖3，相對于假體標(biāo)準(zhǔn)位置的各個位置P均001。股骨假體前移會減小最大屈曲角度，而后移會使之增大（圖3，相對于假體標(biāo)準(zhǔn)位置的各個位置P均001）。但是，脛骨假體的水平位移卻有相反的效果假體前移使最大屈曲角度增大，而后移使之減小（圖3，襯墊前移時P001，襯墊后移時P002）。另外，增加脛骨假體后傾角度同樣可以增加最大屈曲角度（表2，P001）。脛骨假體后傾角0°7°間的平均屈曲角度差異為50°（46°57°）。股骨假體位置、脛骨假體位置以及后傾角度對術(shù)后最大屈曲度有不同的影響（圖4）。對增大屈曲角度影響最大的因素是股骨假體后移（平均15°/MM）和脛骨假體前移（平均09°/MM）。當(dāng)膝關(guān)節(jié)假體放置處于股骨假體后移2MM、脛骨假體前移10MM及后傾7°的位置時，其屈曲角度較標(biāo)準(zhǔn)位置放置假體增加14°。10例膝關(guān)節(jié)的平均PCO值為246±27MM（207283MM）。最大屈曲角度與PCO有顯著相關(guān)性（圖5A，SPEARMAN等級相關(guān)分析，P001；R2072）。由于PCO隨股骨直徑的增大而增大，所以我們根據(jù)假體的前后徑大小對PCO進行了標(biāo)準(zhǔn)化處理。標(biāo)準(zhǔn)化后最大屈曲角度與PCO之間依然有較強的相關(guān)性（R2073，圖5B）。隨著PCO的增大，最大屈曲角度平均增加15°/MM。這個結(jié)果與上文提及的股骨假體后移導(dǎo)致最大屈曲角度的增長（15°/MM）關(guān)系相一致，其原因在于股骨假體的后移可直接增加PCO。討論由于許多因素可以影響術(shù)后關(guān)節(jié)活動度，有必要確定其中哪些因素相對更重要。既往研究報道了假體對線和相對位置對術(shù)后關(guān)節(jié)活動度的影響。然而，既往使用的塑料骨骼模型和

簡介：中文中文3400字出處出處PUNUKOLLUG,KHANIA,GOWDARM,ETALCARDIACTROPONINIRELEASEINACUTEPULMONARYEMBOLISMINRELATIONTOTHEDURATIONOFSYMPTOMSJINTERNATIONALJOURNALOFCARDIOLOGY,2005,99220711急性肺動脈栓塞心肌肌鈣蛋白急性肺動脈栓塞心肌肌鈣蛋白I釋放與癥狀的持續(xù)時間的相關(guān)性研究釋放與癥狀的持續(xù)時間的相關(guān)性研究GOPIKRISHNAPUNUKOLLU,IJAZAKHAN,RAMESHMGOWDA,GAURAVLAKHANPAL,BALENDUCVASAVADA,TERRENCEJSACCHI【摘要】目的探討血壓正常的急性肺栓塞患者肌鈣蛋白I釋放持續(xù)時間與癥狀。方法57名血壓正常的急性肺栓塞患者被納入研究范圍。將患者分為兩組，癥狀持續(xù)時間≤72H后被分為A組，癥狀持續(xù)時間72H者為B組，血清心肌肌鈣蛋白I水平測定入院時。結(jié)果平均年齡為68±18歲和23例（40％）為男性。33例（58％）患者癥狀持續(xù)時間≤72H（A組）和24（42％）例癥狀持續(xù)時間72小時（B組）。兩組有類似的超聲心動圖右心室功能障礙患病率（A組55％N18與B組42％N10，PNS）。16例患者血清心肌肌鈣蛋白I升高（33±23NG/ML，范圍0683NG/ML）。血清肌鈣蛋白I水平與右心室功能不全相關(guān)（P0015）。所有患者血清肌鈣蛋白I升高患者（N16）都為A組患者（P30MM或右心室/左心室舒張末徑比1），（2）矛盾間隔收縮運動（3）肺動脈高壓（肺加速時間30毫米汞柱）存在。右心室功能不全不考慮急性右心室壁肥厚的存在。23實驗室數(shù)據(jù)中，急性肺栓塞的窗口期癥狀持續(xù)可以延長至14天1921。43心肌肌鈣蛋白I釋放動力學(xué)肌鈣蛋白的大部分與肌原纖維結(jié)合，其余的是在細胞質(zhì)。在急性心肌梗死癥狀出現(xiàn)后46H后時釋放，24小時后達峰，峰值達到參考值上限約2050倍。這些亞基的濃度在血中持續(xù)升高許多天，肌鈣蛋白I為47天和肌鈣蛋白T為1014天。據(jù)估計，34％的心肌肌鈣蛋白I和68％的肌鈣蛋白T在游離的細胞質(zhì)成分中被發(fā)現(xiàn)24,25。在心肌損傷的初始階段，細胞質(zhì)肌鈣蛋白的釋放發(fā)生與外周血中肌鈣蛋白可被檢測出22，此外，已被證明，心肌梗死后其他形式的心臟肌鈣蛋白I和T被釋放到血液中26。因此，心肌肌鈣蛋白I和T的釋放和清除機制仍未完全理解。沒有研究評價急性肺栓塞的發(fā)病癥狀與肌鈣蛋白釋放的關(guān)系，盡管有研究評估有關(guān)這些標(biāo)記物持續(xù)的時間11,12。KONSTANTINIDES等12研究126例患者，其中51％的患者癥狀的持續(xù)時間的不到24小時，肌鈣蛋白水平升高與患者出現(xiàn)癥狀的關(guān)系沒有被評估。進行觀察內(nèi)43例臨床懷疑急性肺栓塞肌鈣蛋白水平升高的患者中41例肌鈣蛋白水平峰值出現(xiàn)在4小時。揚尼齊斯等11研究了56例肺栓塞患者癥狀持續(xù)中位時間為3天，范圍為112天，并上報心臟肌鈣蛋白T水平，32％的患者與心肌肌鈣蛋白T的釋放有關(guān)，癥狀的持續(xù)時間沒有數(shù)據(jù)報道。44本研究的發(fā)現(xiàn)本研究中，心肌肌鈣蛋白I水平升高與肺栓塞伴有右心功能不全相關(guān)，與其他的研究相似，但有趣的是，沒有癥狀持續(xù)時間超過72小時的患者心肌肌鈣蛋白I的水平升高，盡管有右心功能不全。這可能代表在經(jīng)過初期的水平輕度升高后患者的心肌肌鈣蛋白I水平正?；?。肺栓塞是否升高心肌肌鈣蛋白I代表細胞質(zhì)肌鈣蛋白的泄漏，需要研究與肌鈣蛋白I與有關(guān)癥狀的持續(xù)時間的關(guān)系，而不是頻繁的采樣。血壓正常的肺栓塞患者被納入研究范圍，因為肌鈣蛋白風(fēng)險分層是非常有用的，特別是在血壓正常的肺栓塞患者28，低血壓和休克，肺栓塞本身有較強的預(yù)測預(yù)后更差，在這些患者心臟肌鈣蛋白I可能沒有攜帶多少額外的預(yù)后價值。5結(jié)論癥狀持續(xù)小于等于72小時的急性肺栓塞患者心肌肌鈣蛋白I的動態(tài)釋放可能與癥狀持續(xù)時間較長的患者不同。因此，使用心肌肌鈣蛋白I在急性肺栓塞危險分層可能會受到限制。需要頻繁取樣進行的一項研究來了解心肌肌鈣蛋白I與急性肺栓塞的癥狀的持續(xù)時間，可以給更深入地了解這個概念。

簡介：中文中文3200字出處出處WANGLL,HUANGY,WANGG,ETALTHEPOTENTIALROLEOFMICRORNA146INALZHEIMER’SDISEASEBIOMARKERORTHERAPEUTICTARGETJMEDICALHYPOTHESES,2012,783398401MIRNA146在阿爾茨海默氏病中潛在的作用或治療目標(biāo)在阿爾茨海默氏病中潛在的作用或治療目標(biāo)LILINGWANG,YUEHUANG,GANGWANG,SHENGDICHEN摘要最近，有越來越多的證據(jù)表明MIRNA146與免疫和炎癥信號的上調(diào)有關(guān)通過研究它的目標(biāo)基因發(fā)現(xiàn)，如IRAK1和TRAF6基因。此外，大量的數(shù)據(jù)支持炎癥基因與炎癥信號的上調(diào)會促進AD的發(fā)生和發(fā)展。這篇綜述主要寫了最近關(guān)于MIR146在AD的發(fā)病機制修飾免疫應(yīng)答及其后續(xù)影響。介紹AD是一種進行性的神經(jīng)病變，最常見癡呆形式是存在于老齡化人口之間。AD的神經(jīng)病理改變特征主要是以神經(jīng)纖維突出和神經(jīng)元的損失及胞內(nèi)神經(jīng)纖維錯亂和胞外淀粉樣蛋白斑的形成為主。AD經(jīng)典的發(fā)病機制是異常的淀粉樣前體蛋白AΒ42的沉積，導(dǎo)致了異常的淀粉樣前體蛋白（APP）的處理。最近，關(guān)于神經(jīng)內(nèi)分泌網(wǎng)絡(luò)系統(tǒng)失調(diào)也會導(dǎo)致AD的研究越來越多。生理上，先天免疫和炎癥信號對大腦穩(wěn)態(tài)、神經(jīng)保護和修護是非常重要的。一旦過度活化，它們將產(chǎn)生過多的氧自由基，促炎癥細胞因子導(dǎo)致神經(jīng)退行性病變。因此，炎癥反應(yīng)是一個通過復(fù)雜的胞內(nèi)和胞外網(wǎng)絡(luò)系統(tǒng)被高度調(diào)節(jié)的。最近，一系列的研究證明MIRNA可以影響哺乳動物的免疫細胞分化，隨后引起的免疫應(yīng)答已經(jīng)證明與各種人類腦功能的紊亂有關(guān)，包括SD。MIRNAMIRNA146在小鼠和人腦中大量存在，它首次被確定為免疫調(diào)節(jié)劑是通過研究將人單核細胞暴露于各種細菌中的成分時200MIRNA的表達譜。另外，以往的研究指出MIR146參與炎癥信號上調(diào)，這種炎癥信號與朊病毒誘導(dǎo)的神經(jīng)退行性疾病、類風(fēng)濕性關(guān)節(jié)炎和顳葉癲癇有關(guān)。特別是，在AD患者的腦中，已經(jīng)證明MIR146是上調(diào)的，這說明MIR146的失調(diào)控將會導(dǎo)致在AD炎癥老年斑。本文中，我們將討論MIR146和它在AD中的潛在作用，這不僅可能提供AD發(fā)病機制的新視覺，還可能提供治療AD潛在的治療靶點。MIR146和它的目標(biāo)分子和它的目標(biāo)分子用表達分析的方法發(fā)現(xiàn)MIR146在氣管、肺、胸腺、結(jié)腸癌、腎癌、前列腺癌、皮膚、腦和大部分的免疫及炎癥反應(yīng)中的水平很高。這種廣泛的表達說明了MIR146可能起著重要的生理作用。這也很好地證明MIRNA及可以阻斷MRNA的轉(zhuǎn)導(dǎo)也可以通過結(jié)合目標(biāo)分子的3‘URT降低其穩(wěn)定性。MIR146家族有兩個成員構(gòu)成，MIR146A和MIR146B，它們編碼不同的基因（染色體5Q33和10Q24,，分別地）。這兩個MIRNA主要靠它們在3’區(qū)域的兩個核苷酸成熟序列來區(qū)分。TAGANOV和他的同事們首先證明了MIR146A和MIR146B與免疫反應(yīng)有關(guān)。兩種MIRNA的轉(zhuǎn)錄水平在脂多糖的刺激后上調(diào)，但是只有成熟的MIR146A被生成了。啟動子分析表明NFKB與MIR146A的上調(diào)有關(guān)，但是與MIR146B的上調(diào)無關(guān)。還發(fā)現(xiàn)MIR146A和MIR146B都可以抑制白細胞介素1受體相關(guān)激酶1（IRAK1）和TNF受體相關(guān)因子6（TRAF6）。但是，關(guān)于MIR146B的轉(zhuǎn)錄調(diào)控因子卻知道的很少。隨后，PERRY和他的同事們用IL1Β處理的人肺A549上皮細胞報道了MIR146A和MIR146B的轉(zhuǎn)錄是通過有絲分裂原活化蛋白（MAP）激酶通路來調(diào)節(jié)的。除了NFKB，IL1Β誘導(dǎo)，MIR146A的表達還通過N末端激酶（JNK）1/2依賴機制來調(diào)控，同時MIR146B的表達通過JNK1/2和有絲分裂原活化蛋白激酶（MEK）1/2依賴機制來介導(dǎo)。綜上所述，我們提出了兩種MIR146的異構(gòu)體可能調(diào)控相同的MRNA目標(biāo)群，可能作用于復(fù)雜網(wǎng)絡(luò)的一部分調(diào)節(jié)免疫反應(yīng)。胞中發(fā)現(xiàn)MIR146A上調(diào)，這提出了來自人血液中的MIR146A的測量可以用于評估沒有收到感染的患者炎癥的情況和程度。LEDERHUBER和他的同事們報道了MIR146在來自外周靜脈的人單核細胞中可以被檢測到用實時PCR的方法。它們發(fā)現(xiàn)在LPS的刺激24小時之后MIR146家族的成員會上調(diào)。這個有趣的發(fā)現(xiàn)說明AD患者可以用想實時PCR的方法預(yù)先篩選，進一步檢測MIR146升高的水平?？墒?，有幾個問題仍然沒有被解決（1）到什么程度，外周改變會反映在中樞神經(jīng)系統(tǒng)的變化；（2）MIR146的改變與AD病理進程之間的機制關(guān)系。相似的問題也存在于MIR在卒中和其他神經(jīng)系統(tǒng)疾病。結(jié)論和觀點結(jié)論和觀點為了確定MIR146A和B的生理功能，有必要認識他們潛在的目標(biāo)。MIR146抑制一組基因，包括IRAK1，TRAF6，CFH,和TSPAN12。我們預(yù)測MIR146A和B參與AD的發(fā)病機制通過抑制上述基因并改變他們下游的信號通路。最初，MIR146作為負調(diào)控調(diào)節(jié)劑被確定的在控制TOLL樣受體和細胞因子信號中，然后，IRAK1NFKB信號通過MIR146A的抑制最終引起了IRAK2NVKB信號通路的活化，這導(dǎo)致炎癥反應(yīng)通過不清楚的機制增強了。此外，MIR146的目標(biāo)基因，如ROCK1，EGFR和NOTCH1，在癌癥中有重要的作用。MIR146是否在AD的發(fā)生機制介導(dǎo)抑制這些基因仍然有待進一步研究。為了拓展關(guān)于MIR146在AD中的功能，用敲除MIR146A或者MIR146B的方法分析小鼠的表型是非常有必要的。綜上所述，MIR146的功能表明，它至少在兩方面有應(yīng)用的潛力。第一個是作為AD早期臨床檢測，因為它可以作為AD早期的臨床標(biāo)志物，而且在成人血液循環(huán)中的單核細胞中以最小創(chuàng)傷形式輕松獲得。這種情況下，臨床確診AD應(yīng)當(dāng)用足夠的病例數(shù)量，以評估其潛力。另一個是治療的潛力，因為MIR146A在AD治療方面的應(yīng)用。AD和應(yīng)激性腦細胞與顯著下調(diào)的MIR146A目標(biāo)有關(guān)，這些目標(biāo)基因編碼IRAK1，CFH和TSPAN12。使用抗MIR146A可以抑制影響MIR146A上調(diào)的因素，或者這可以成為潛在的治療方法。應(yīng)用抗MIR146A在AD轉(zhuǎn)基因小鼠模型上是下一步即將進行的臨床試驗。

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簡介：中文中文6000字出處出處LIJY,YONGTY,MICHAELMZ,ETALREVIEWTHEROLEOFMICRORNASINKIDNEYDISEASEJNEPHROLOGY,2010,156599–608泛素樣蛋白泛素樣蛋白FAT10介導(dǎo)介導(dǎo)NFΚB激活激活JYLI，TYYONG，MZMICHAEL，JMGLEADLE摘要NFΚB是一種先天免疫的中心介質(zhì)，與幾種腎病的發(fā)病機制都有關(guān)。FAT10是一種TNFΑ誘導(dǎo)的泛素樣蛋白質(zhì)，被公認為在免疫反應(yīng)中發(fā)揮作用，但是FAT10是否參與TNFΑ誘導(dǎo)的NFΚB活化過程仍然是未知的。在這里，使用FAT10/和FAT10/的小鼠體內(nèi)的腎小管上皮細胞（RTEC），我們觀察到FAT10的缺乏阻止了TNFΑ誘導(dǎo)的NFΚB的活化，也降低了NFΚB調(diào)節(jié)基因的誘導(dǎo)。除去正常的IKBΑ的退化和多次泛素化，F(xiàn)AT10的缺乏會降低TNFΑ誘導(dǎo)的IKBΑ的退化和P65在RTECS（腎小管上皮細胞）中的核易位，表明IKBΑ多重泛素化的有缺陷的蛋白酶體的降解。此外，F(xiàn)AT10的缺乏降低了蛋白酶亞基低分子多肽2（LMP2）的表達。用FAT10使FAT10/的腎小管上皮細胞的轉(zhuǎn)導(dǎo)恢復(fù)了LMP2的表達，TNFΑ誘導(dǎo)的IKBΑ的降解，P65的核易位和NFΚB的活化。而且LMP2的轉(zhuǎn)染恢復(fù)了在FAT10/的腎小管上皮細胞中IKBΑ的退化。人類的慢性腎臟疾病常見類型與FAT10在腎小管間質(zhì)的上調(diào)有關(guān)。這些數(shù)據(jù)說明了FAT10介導(dǎo)NFΚB活化，而且可能在慢性腎臟疾病中促進腎小管間質(zhì)炎癥。關(guān)鍵詞生物標(biāo)志物,糖尿病腎病,上皮細胞間充質(zhì)細胞轉(zhuǎn)換,腎疾病,MICRORNANFKB是一種泛素樣的轉(zhuǎn)錄因子，它在免疫反應(yīng)，細胞凋亡和細胞周期調(diào)控中控制基因的表達。NFKB異常的調(diào)節(jié)可能導(dǎo)致炎癥和自身免疫疾病，損害抗病毒免疫反應(yīng)，并促進細胞的惡性轉(zhuǎn)化13。激活的NFKB，后續(xù)反應(yīng)產(chǎn)生的細胞因子、趨化因子和粘附因子在一些腎臟疾病中是重要因素，這些疾病包括糖尿病腎病4,5，高血壓性腎硬化6,7，IGA腎病8，膜性腎病9和艾滋病病毒相關(guān)腎病1012。經(jīng)典的NFKB活化通路可能被各種刺激誘發(fā)，如TNFΑ。TNFΑ誘導(dǎo)的NFΚB的活化是通過在質(zhì)膜上的腫瘤壞死因子受體I來銜接參與的，隨后的信號傳導(dǎo)最后激活了IKB激酶復(fù)合體，同時又反過來使IKBΑ磷酸化。磷酸化的IKBΑ迅速地多次泛素化，導(dǎo)致了IKBΑ通過26S蛋白酶復(fù)合體的降解，NFKB的釋放，NFKB隨后又轉(zhuǎn)移到細胞核并激活靶位基因的轉(zhuǎn)錄1316。26S蛋白酶體，一種真核細胞中主要的蛋白酶，識別并降解多重泛素化蛋白（17,18）。26S蛋白酶體的蛋白水解核心復(fù)合體是20S核心顆粒，這種顆粒有幾個亞基構(gòu)成。低分子多肽2（LMP2）是一種IFNΓ誘導(dǎo)的亞基，它可以取代亞基Y（又稱DELTA或者Β1）在20S核心顆粒中（19）。LMP2在20S核心顆粒中的存在導(dǎo)致了糜蛋白酶和胰蛋白酶在體外的活化，調(diào)整蛋白酶的切割位點（20,21）。一些研究已經(jīng)證明了LMP2在IKBΑ的降解和NFKB隨后的活化過程中扮演著重要的角色。我們先前報道了FAT10在體外艾滋病病毒感染的腎小管上皮細胞和來自艾滋病病毒攜帶者的腎病患者和常染色體顯性遺傳的多囊腎的腎臟樣本中上調(diào)，而且增加的FAT10誘導(dǎo)腎小管上皮細胞的凋亡（25）在非應(yīng)激狀態(tài)下的小鼠，F(xiàn)AT10的敲除引起最小的表型改變，可是這些小鼠在注射了LPS之后表現(xiàn)出死亡敏感性的增加（26）。FAT10在成熟的樹突狀細胞和B細胞中表達（27,28），并且可以在各種組織中被前炎癥細胞因子IFNΓ和TNFΑ誘導(dǎo)（29，30）。不過FAT10在免疫反應(yīng)中的作用還沒有被研究。我們發(fā)現(xiàn)FAT10在HIV1感染的腎小管上皮細胞中上調(diào)，而且這種上調(diào)類似于NFKB調(diào)節(jié)基因活化的方式（31），加上我們知道NFKB的活化是在多個水平上通過泛素蛋白激酶系統(tǒng)被控制的，這可以提示我們假設(shè)FAT10參與調(diào)控NFKB的活化。IRESEGFP的共轉(zhuǎn)染并沒有被誘導(dǎo)。這些結(jié)果表明在FAT10/小鼠RTECS中FAT10的表達恢復(fù)了TNFΑ和LPS誘導(dǎo)了構(gòu)成PGL2/NFKB的NFKB報道基因的活化。在RTECS中FAT10對于對于TNFΑ誘導(dǎo)的核轉(zhuǎn)位是必要的Α誘導(dǎo)的核轉(zhuǎn)位是必要的在用TNFΑ處理之前，P65主要位于FAT10/和FAT10/的RTECS的細胞質(zhì)中（圖4A）。用TNF?。?0NG/ML）處理15和60分鐘后，大部分P65在FAT10/RTECS的核中被檢測到,但是在FAT10/RTECS中卻是在細胞質(zhì)中檢測到，這表明TNFΑ誘導(dǎo)NFKB的核易位在FAT10/RTECS中是有缺陷的。在來自于FAT10/和FAT10/小鼠中使用分離出的新鮮原始非永生的RTECS也觀察到相似的結(jié)果（如圖4B），這表明了在P65易位中觀察到的缺陷并不是T抗原永生化的結(jié)果。我們也研究了是否TNFΑ誘導(dǎo)的P65易位在從小鼠腹腔分離出來的巨噬細胞中被破壞。這些在FAT10/巨噬細胞TNFΑ誘導(dǎo)的P65核易位與在FAT10/巨噬細胞中沒有區(qū)別（參考圖1）。FAT10/RTECS用HRFAT10IRESEGFP或者HRIRESEGFP慢病毒感染。3天后，將細胞與TNF?。?0NG/ML）或運載體一起培養(yǎng)15和60分。如圖5所示，在與TNFΑ培養(yǎng)前，在用病毒感染的FAT10/RTECS中定位P65蛋白質(zhì)；然而，用TNFΑ處理后（15和60分），P65主要在用慢病毒感染的FAT10/RTECS的細胞質(zhì)中檢測出，而P65主要在用HRFAT10IRESEGFP感染的FAT10/RTECS的細胞核中檢測出。這些結(jié)果表明用FAT10表達運載體的FAT10/RTECS轉(zhuǎn)導(dǎo)是足以恢復(fù)TNFΑ誘導(dǎo)NFKB核易位的。在RTECS中FAT10對于對于TNFΑ誘導(dǎo)Α誘導(dǎo)IKBΑ降解是必要的Α降解是必要的在FAT10/RTECS總的IKBΑ通過WESTERNBLOTTING方法分析證明了通過5分鐘的TNFΑ處理厚蛋白水平是降低的,在10分鐘時達到了一個最低點，這個水平持續(xù)從基線降低了60分鐘（圖6A,B）。與此相反，在TNFΑ暴露后總的IKBΑ蛋白質(zhì)在FAT10/RTECS中并沒有降低，這說明TNFΑ誘導(dǎo)IKBΑ降解在FAT10/RTECS中是缺乏的（圖6A和B）。在TNFΑ暴露前后IKBΑ的MRNA的表達在FAT10/和FAT10/RTECS中并沒有顯著差異（圖6C）。用FAT10表達的慢病毒（HRFAT10IRESEGFP）或空控慢病毒HRIRESEGFP轉(zhuǎn)導(dǎo)FAT10/RTECS。經(jīng)過三天的轉(zhuǎn)導(dǎo)，將細胞與TNFΑ或運載體一起培養(yǎng)10分鐘。用TNFΑ處理后，在用HRFAT10IRESEGFP感染的FAT10/RTECS中而不是用控制病毒感染的細胞中IKBΑ蛋白質(zhì)水平顯著地降低了（圖6D）。因此，F(xiàn)AT10在FAT10/RTECS中的表達足以恢復(fù)TNFΑ誘導(dǎo)的IKBΑ降解。在FAT10/RTECS中TNFΑ誘導(dǎo)Α誘導(dǎo)IKBΑ磷酸化是不受影響的Α磷酸化是不受影響的在FAT10/和FAT10/RTECS中，PIKBΑ的水平在用TNFΑ處理后快速地增加了，在5分鐘達到了最高水平。在FAT10/RTECS中TNFΑ誘導(dǎo)IKBΑ磷酸化是不會受損的，與FAT10/RTECS相比似乎還有些增加（圖7）。有趣的是，在FAT10/RTECS中用TNFΑ處理后20分鐘，PIKBΑ的水平返回到了處理前的水平，但是用TNFΑ處理20分鐘后在FAT10/RTECS中PIKBΑ的水平比處理前仍有62倍的增加。這些結(jié)果表明PIKBΑ的降解在FAT10/RTECS中是受損的。FAT10并不影響泛素化和磷酸化并不影響泛素化和磷酸化IKBΑ也與Α也與PIKBΑ相互沒有影響Α相互沒有影響在用TNFΑ和MG132（為了阻斷多重泛素化的蛋白質(zhì)的蛋白酶體降解）處理后，PIKBΑ被免疫沉淀，用WESTERNBLOTTING方法將泛素化PIKBΑ用抗泛素化被檢測出。泛素化PIKBΑ的水平在FAT10/和FAT10/TRECS中是相似的（圖8A），這表明在FAT10/RTECS中NFKB的不能激活并不是PIKBΑ泛素化不全的結(jié)果。因為FAT10的共軛底物蛋白能通過26S蛋白酶定位目標(biāo)進行降解（33），我們研究了是否FAT10形成了IKBΑ的結(jié)合物，因此帶動其蛋白酶體解體；但是當(dāng)我們在用TNFΑ處理后，用抗PIKBΑ免疫沉淀來自FAT10/細胞的蛋白質(zhì)，我們不能無法檢測到免疫沉

簡介：中文中文5200字出處出處DUANYY,ZHANGHB,LIULW,ETALEFFECTSOFDISTALPROTECTIONONLEFTVENTRICULARFUNCTIONINACUTEANTERIORMYOCARDIALINFARCTIONADOPPLERECHOCARDIOGRAPHICSTUDYJINTERNATIONALJOURNALOFCARDIOVASCULARIMAGING,2010,262125133在急性前壁心肌梗死中遠端保護對左室功能的影響多普勒超聲心在急性前壁心肌梗死中遠端保護對左室功能的影響多普勒超聲心動圖的研究動圖的研究摘要摘要對于急性心肌梗死的病人，遠端保護裝置在經(jīng)皮冠狀動脈介入治療中是否能改善心肌功能仍然在爭論當(dāng)中。運用組織多普勒成像，我們評估在使用遠端保護裝置（DPDS）的急性前壁心肌梗死的病人和使用傳統(tǒng)PCI術(shù)相比，左室整體和局部的收縮和舒張功能。96名急性前壁心肌梗死的病人被隨機分配到DPDS組（DPD的，N46例）或傳統(tǒng)PCI組（對照組，N50例）。在36個月的隨訪，DPD組的左室射血分數(shù)高于對照組516±36VS493±53；530±37VS508±52,P005。此外，在DPD組通過組織多普勒成像獲得的收縮高峰SA和舒張早期EA的二尖瓣環(huán)速度顯著高于對照組SA757±053VS712±062CM/SAND771±063VS732±059CM/SEA723±078VS689±086CM/SAND749±069VS704±085CM/S,RESPECTIVELYALLP\005然而，從一個月隨訪的DPD組相較于對照組，收縮期和舒張期局部心肌的速度得到顯著改善ALLP\005。接受DPD組治療的患者體驗到心臟功能加速改善。因此，急性前壁心肌梗死的病人能夠從在PCI術(shù)中使用遠端保護裝置（DPDS）中受益。關(guān)鍵詞關(guān)鍵詞超聲心動圖，組織多普勒成像，遠端保護裝置。簡介簡介重建心肌灌注在急性心肌梗死的微創(chuàng)治療中是至關(guān)重要的。然而，在經(jīng)皮冠狀動脈介入治療中“漫流”和“無復(fù)流”現(xiàn)象普遍發(fā)生。這些現(xiàn)象通過減少外周血流而沒有明顯的血管阻塞而具有特征1–4。微血管阻塞經(jīng)常被當(dāng)作根本的原因，越來越多的證據(jù)表明斑塊負荷和血小板血栓在微血管血栓形成中發(fā)揮關(guān)鍵作用2,3。“漫流”和“無流”的治療可能很困難，治療遠端栓塞的最好方法就是防止其形成。在急性心肌梗死的背景下遠端保護裝置因此成為一個有吸引力的概念4。在血管成形術(shù)或支架植入術(shù)中遠端保護裝置用于臨時遠端球囊栓塞，并允許在順流血流恢復(fù)前通過吸氣改善任何游離的斑塊。遠端保護裝置最初的研究一致地表明改善斑塊（膽固醇結(jié)晶，泡沫細胞，纖維斑塊），否則將會導(dǎo)致心肌床的栓塞2–8。然而，遠端保護裝置研究的結(jié)果顯示不一致。在急性心肌梗死病人的遠端保護裝置的早期研究當(dāng)中，報告與常規(guī)的PCI技術(shù)相比心肌灌注和ST段解析度均得到改善2,3,6–8。后來的某些研究得到不確定的結(jié)果9–11。與傳統(tǒng)的PCI術(shù)相比，在急性心肌梗死的病人中遠端保護裝置是否能使心肌功能得到改善仍在爭論當(dāng)中3,7–9。在遠端保護裝置的研究中有有限的超聲心動圖數(shù)據(jù)描述心臟功能的改變，但是沒有數(shù)據(jù)描述局部心肌功能的改變。只有左室攝血分數(shù)和室壁運動積分指數(shù)在一些研究中被用來評估左室整體的收縮功能。組織多普勒成像使一種能夠?qū)φw以及局部功能進行定量、客觀評估的有效的超聲心動圖工具12–14。在本研究中，我們試圖通過組織多普勒成像在急性前壁心肌梗死的病人中，評估遠端保護裝置對左室整體和局部收縮及舒張功能的影響。方法方法研究人數(shù)研究人數(shù)患者包括在研究中首次提到的，急性前壁心肌梗死以及按傳統(tǒng)PCI術(shù)進行的病人。急性心肌梗死定義為胸痛持續(xù)超過30分鐘但少于6小時，伴有前胸導(dǎo)聯(lián)ST段持續(xù)抬高。在所冠狀動脈介入治療冠狀動脈介入治療冠狀動脈造影顯示在所有病人的冠狀動脈左前降支有明顯的狹窄。每個組的大部分患者804比上800,P094在最初冠脈造影冠狀動脈左前降支是完全阻塞。在兩組所有目標(biāo)病灶均成功植入支架。在血管成形術(shù)和支架植入術(shù)遠端保護裝置閉塞球囊使得遠端保護裝置組的所有患者得到完全的保護。在遠端保護裝置組沒有相關(guān)手術(shù)并發(fā)癥記錄。支架植入術(shù)后，遠端保護裝置組96的患者和對照組78的患者在冠狀動脈左前降支的TIMI血流分級3級P0003。兩研究組沒有關(guān)鍵的程序特征差異TABLE2，在兩研究組的隨訪中沒有重大的不利臨床事件發(fā)生。左心室整體功能左心室整體功能在經(jīng)皮冠狀動脈介入術(shù)前遠端保護裝置組和對照組在整體收縮和舒張功能沒有顯著差異。所有超聲心動圖參數(shù)，如左室舒張末期容積基線和E/A比值，在兩組之間沒有明顯差異。與對照組相比，在第3個月和6個月的隨訪中，遠端保護裝置組有較高的左室射血分數(shù)，較高的收縮高峰二尖瓣速度（SA），和一較小的左室舒張末期容積，盡管在1個月的時候他們之間只有輕微但不明顯的差異。在干預(yù)后的任何一個時間點，兩組之間在E/A比值上沒有統(tǒng)計差異。與二尖瓣反流速度相比，在3個月和6個月的隨訪中相較于對照組，遠端保護裝置組的二尖瓣舒張早期峰值（EA）得到明顯改善FIG2。局部心肌功能局部心肌功能在經(jīng)皮冠狀動脈介入術(shù)前，左室前壁局部室壁運動積分指數(shù)（RWMSI）和心肌組織多普勒成像速度，遠端保護裝置組和對照組沒有差異。開始治療一個月后，在各個隨訪時間點，遠端保護裝置組的收縮高峰心肌速度（SM）值明顯高于對照組。在一個月的隨訪中，兩組的局部室壁運動積分指數(shù)（RWMSI）相似。遠端保護裝置組的局部室壁運動積分指數(shù)（RWMSI），在經(jīng)皮冠脈介入術(shù)后3個月，才開始顯著低于對照組。在隨訪的所有時間點，遠端保護裝置組的舒張早期峰值心肌速度（EM）值顯著高于對照組FIG3。討論討論應(yīng)用組織多普勒成像，我們發(fā)現(xiàn)接受遠端保護裝置的經(jīng)皮冠脈介入的急性前壁心肌梗死的病人，相較于傳統(tǒng)經(jīng)皮冠脈介入的病人，在干預(yù)后的3個月和6個月整體收縮和舒張功能得到改善。通過組織多普勒成像，在1個月、3個月、6個月，遠端保護裝置組得到的收縮期和舒張期局部心肌功能，相較于對照組有顯著改善。遠端保護裝置的功效遠端保護裝置的功效醫(yī)源性和自發(fā)下游微栓塞的動脈粥樣硬化，越來越多的被認為是心血管疾病發(fā)生率和死亡率的來源。為了減少這種遠端栓塞，遠端保護裝置機械方法吸收栓塞物質(zhì)普遍的在自體冠脈干預(yù)和其他領(lǐng)域運用。隨著栓塞物質(zhì)的吸收，研究報告表明使用遠端保護裝置相較于傳統(tǒng)的經(jīng)皮冠脈介入（PCI）技術(shù)，TIMI3級血流速度得到改善，ST段下降，梗死面積減少1–8。最近，通過在最初和營救血管成形術(shù)試驗中吸收栓子（REMEDIA），隨機評估機械減少遠端栓塞的效用，顯示在心肌保護手臂中相較于那些在標(biāo)準(zhǔn)的經(jīng)皮冠脈介入（PCI）術(shù)中，能得到更好的血管造影和心電圖心肌灌注率7。隨著遠端保護裝置有前景的結(jié)果，在急性心肌梗死介入治療中一些不確定和矛盾的數(shù)據(jù)成為爭論的主題9–11。大量隨機增強心肌功效和恢復(fù)吸收游離殘渣EMERALD試驗顯示，在大部分接受急診PCI術(shù)的急性心肌梗死的病人中，遠端保護裝置能有效的取回栓塞物質(zhì)。然而，遠端栓塞保護在改善微血管流，更好地成功灌注，減少梗死面積和提高無事件生存率上沒有作用9。

簡介：中文中文12萬字萬字出處出處REITSMAS,SLAAFDW,VINKH,ETALTHEENDOTHELIALGLYCOCALYXCOMPOSITION,FUNCTIONS,ANDVISUALIZATIONJPFLüGERSARCHIVEUROPEANJOURNALOFPHYSIOLOGY,2007,4543345359內(nèi)皮細胞糖萼組成，功能及可視性內(nèi)皮細胞糖萼組成，功能及可視性REITSMAS,SLAAFDW,VINKH,ETAL摘要本文旨在提出關(guān)于內(nèi)皮細胞糖萼構(gòu)成與功能的最新知識。內(nèi)皮糖萼是一個覆蓋于管腔內(nèi)皮、與細胞膜連接，由蛋白多糖及糖蛋白等構(gòu)成的網(wǎng)絡(luò)。其中包含內(nèi)皮源性及血源性的可溶性分子。近十年來,人們對血管內(nèi)皮糖萼在各種生理、病理過程中作用的認識在不斷增加,其中包括細胞膜的機械運輸、止血、信號傳導(dǎo)以及血細胞與血管壁的相互作用。本文就內(nèi)皮細胞糖萼在糖尿病、缺血/再灌注組織損傷、動脈粥樣硬化中的起到的作用進行綜述。從微觀和宏觀的實驗數(shù)據(jù)揭示內(nèi)皮細胞糖萼對心血管系統(tǒng)的保護作用。為評估內(nèi)皮細胞糖萼的確切作用，將這一細微結(jié)構(gòu)可視化，是一個巨大的挑戰(zhàn)。已有綜述列舉目前為止將內(nèi)皮細胞糖萼可視化的不同方法，其中包括通過雙光子顯微鏡成像技術(shù)，及通過該項技術(shù)獲得的第一數(shù)據(jù)。關(guān)鍵詞內(nèi)皮細胞糖萼。內(nèi)皮細胞表面層。硫酸乙酰肝素。透明質(zhì)酸。血管疾病。光學(xué)成像。雙光子顯微成像。簡介40年前，LUFT通過電子顯微鏡成像技術(shù)使得內(nèi)皮細胞糖萼可視化成為可能。至今，我們對內(nèi)皮細胞糖萼層組成和功能了解仍然較少。在過去的幾十年里，人們高度認可內(nèi)皮細胞糖萼在血管生理、病理過程中的重要作用。在2000年P(guān)RIES等人的綜述以及其他最近的評論中都有描述。人們對內(nèi)皮細胞糖萼在病、生理中作用的關(guān)注始于人們發(fā)現(xiàn)血管系統(tǒng)的代謝水平和藥理活性水平的不同決定了毛細血管內(nèi)血細胞比容的不同。一方面代謝水平與激動劑誘作用，提高紅細胞流動速率。另一方面，管內(nèi)紅細胞比容的關(guān)系可部分由FAHRAEUS效應(yīng)的延伸血漿撇清原理解釋。然而,由于肝素酶可分解內(nèi)皮細胞糖萼上硫酸乙酰肝素，應(yīng)用肝素酶進行的微血管的局部治療可破壞這種關(guān)系。這一發(fā)現(xiàn)與用理論估計預(yù)測的蛋白多糖（粘蛋白）蛋白多糖被普遍認為是內(nèi)皮細胞糖萼中最重要的“支柱”分子，由一個核心蛋白組成，有一條或多條糖胺聚糖鏈與之相連。蛋白多糖核心蛋白之間有著明顯的不同，區(qū)別于分子量大小、連接糖胺聚糖鏈的數(shù)量以及是否與細胞膜相連。多配體（蛋白）聚糖及磷脂酰肌醇（蛋白）聚糖的核心蛋白組通過跨膜區(qū)域（多配體（蛋白）聚糖）或糖基化磷脂酰肌醇錨（磷脂酰肌醇（蛋白）聚糖）與細胞膜緊密連接。其他蛋白多糖，例如MIMECAN、基底膜蛋白多糖、二聚糖，在他們聚集、糖胺聚糖鏈被修改之后被分泌。這領(lǐng)導(dǎo)了存在于內(nèi)皮細胞糖萼及血流中的可溶性蛋白多糖的生成。蛋白多糖與糖胺聚糖鏈的連接非?；祀s，這說明了，一種核心蛋白可包含不同種類型的糖胺聚糖鏈。不同糖胺聚糖鏈之間的組成比例因周圍環(huán)境及刺激的不同而變化。因此，不能根據(jù)一種糖胺聚糖鏈而命名這種蛋白多糖。例如，多配體（蛋白）聚糖1蛋白多糖通常被稱為硫酸乙酰肝素蛋白多糖。實際上，他包含的硫酸乙酰肝素的數(shù)量與硫酸軟骨素鏈的數(shù)量很相近。有五種類型的糖胺聚糖鏈硫酸乙酰肝素、硫酸軟骨素、硫酸皮膚素、硫酸角質(zhì)素及透明質(zhì)酸。他們是線性聚合物，由于硫酸化、（去）乙?；潭鹊牟煌?，具有長度可變的二聚糖。每一個二聚糖都由一個質(zhì)酸和氨基己糖組成。糖胺聚糖分類取決于包含何種質(zhì)酸或是氨基己糖，以及是否被硫酸化。五種糖胺聚糖中每一種都已被仔細的調(diào)查與廣泛的研究過。硫酸皮膚素常常被認為是單獨一類糖胺聚糖，盡管它是B型硫酸軟骨素。兩者之間的差異可能是由于硫酸皮膚素中，GLUCURONIC葡糖醛酸通過差向異構(gòu)轉(zhuǎn)變成艾杜糖醛酸。這對最終的功能有著重要的影響。只要有可能，我們會盡可能的區(qū)分兩者，或者以下，我們將以硫酸軟骨素|硫酸皮膚素命名。在血管系統(tǒng)中，硫酸乙酰肝素蛋白多糖大約占目前已發(fā)現(xiàn)的內(nèi)皮細胞糖萼中蛋白多糖的5090。然而，這個數(shù)字是可變的，內(nèi)皮細胞表達蛋白多糖取決于不同的刺激。例如，多配體（蛋白）聚糖的表達程度與內(nèi)皮細胞激活及化學(xué)因子刺激的不同而不同。在內(nèi)皮細胞糖萼中，第二常見的糖胺聚糖是硫酸軟骨素|硫酸皮膚素。據(jù)報道，在血管內(nèi)皮，硫酸乙酰肝素與硫酸軟骨素的表達有一個經(jīng)典的比例41。在血管系統(tǒng)中，硫酸角質(zhì)素糖胺聚糖的表達和其在（?。┥碇械闹匾赃€不明確。在內(nèi)皮細胞糖萼中另一個重要的糖胺聚糖是透明質(zhì)酸。這種長的聚合物分子（可長達104KDA）與其他糖胺聚糖不同，他不與核心蛋白

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簡介：中文中文1萬字萬字出處出處MEDAF,FOLCIM,BACCARELLIA,ETALTHEEPIGENETICSOFAUTOIMMUNITYJCELLULARMOLECULARIMMUNOLOGY,2011,83226236自身免疫表觀遺傳學(xué)自身免疫表觀遺傳學(xué)摘要摘要自身免疫性疾病的病因始終不為人們所知。同卵雙生子的疾病共顯率低于50，然而全基因組關(guān)聯(lián)研究只在一小部分病人發(fā)現(xiàn)了顯著關(guān)聯(lián)性。這個證據(jù)強烈支持了還有其他的補充機制涉及到了基因表達的調(diào)節(jié)過程最終導(dǎo)致了顯著的自身免疫病。組蛋白翻譯后修飾以及DNA甲基化是兩個主要的表觀遺傳學(xué)機制可能導(dǎo)致免疫耐受的下降以及自身免疫疾病的持續(xù)。在最近幾年對臨床以及實驗的研究中提出了表觀遺傳學(xué)可能使我們更容易理解自身免疫病的起病和疾病的持續(xù)。更特殊的是，數(shù)據(jù)顯示表觀遺傳學(xué)的改變在系統(tǒng)性紅斑狼瘡，風(fēng)濕性關(guān)節(jié)炎，多發(fā)性硬化以及其他自身免疫病的影響，在某些病例是基于機械的觀察。在這篇文章，我們討論一下目前所知道的以及我們對未來的展望。最后，表觀遺傳學(xué)的治療已經(jīng)被用于腫瘤學(xué)，也可能在自身免疫病的治療中有良好的作用。為何研究表觀遺傳學(xué)為何研究表觀遺傳學(xué)自身免疫病通常被認為是一種復(fù)雜的疾病。遺傳背景使得人們對疾病有一定的易感性或抵抗性，但是它并不能成為疾病發(fā)展的使動原因。許多發(fā)病時環(huán)境的相似性已經(jīng)證實了，但是自身免疫性疾病的病因還不為人們所知。全基因組關(guān)聯(lián)研究已經(jīng)證實了強烈的遺傳背景的存在，但是這個研究并沒有證實免疫耐受下降的單基因機制，并且強烈的基因關(guān)聯(lián)性也只在一小部分人中被證實。在同卵雙生子自身免疫性疾病的不完全共顯率強烈的支持其他補充機制可能涉及到基因表達的調(diào)節(jié)，最終導(dǎo)致自身免疫疾病。基于這些觀察，用一些新的方法來分析組蛋白修飾和DNA甲基化支持了表觀遺傳學(xué)可能在引起自身免疫性疾病中起了重要的作用這一概念。表觀遺傳學(xué)研究的機制即決定和維持基因組的功能，不伴有DNA序列的改變。表觀遺傳基因組和表觀遺傳基因型被認為是細胞通過表觀遺傳學(xué)機制誘導(dǎo)基因表大的特異的和穩(wěn)定的模式。在功能上，表觀遺傳學(xué)機制，確實在細胞分化過程中占重要的角色，它能夠誘導(dǎo)基因穩(wěn)定的表達和抑制。表觀遺傳學(xué)也能夠干預(yù)細胞的代謝，以此使細胞適應(yīng)周圍環(huán)境的改變。表觀遺傳學(xué)對環(huán)境和基因相互作用中扮演的角色，已經(jīng)在一些有趣的實驗中證實，當(dāng)環(huán)境改變，會對基因表達產(chǎn)生修飾。首先，一項生殖的研究調(diào)查食物成分的改變對其影響，食物中富含甲基供體，為了改變懷孕刺鼠到的毛色，與喂養(yǎng)普通食物組對比，這些特殊食物所謂養(yǎng)出來的刺鼠后代毛色有特殊的改變。這個現(xiàn)象被證實有很明顯的DNA甲基化的改變，這就是非常徹底的表觀遺傳學(xué)的研究機制。這個過程是IAP逆轉(zhuǎn)錄病毒插入元件靜息，最終限制了刺鼠等位基因的表現(xiàn)。另一個典型的例子就是荷蘭人在二戰(zhàn)期間在子宮內(nèi)和兒童時期挨餓，對于胰島素樣生長因子表達調(diào)節(jié)區(qū)DNA甲基化分析，證明暴露組與非暴露組相比存在一個高度保守的低甲基化狀態(tài)。最近的觀察研究已經(jīng)證實，DNA甲基化與一些遺傳因素有關(guān)，包括懷孕前吸煙，酒精攝入，環(huán)境污染物?；谶@些觀察，表觀遺傳學(xué)機制應(yīng)該被視為是環(huán)境和基因組作用的先驅(qū)。這樣就結(jié)合了那句老話“壞基因，壞運氣”。這個被實驗證據(jù)所支持，DRFRAGA和其同事證明了表觀遺傳學(xué)也許能夠解釋同卵雙生子自生免疫疾病非共顯率的問題。隨著年齡的增長，表型的異常顯著的增加，被稱為“表觀遺傳學(xué)流”，它是基于不同環(huán)境暴露所產(chǎn)生的。500個堿基對組成，CG的含量超過過55，CPG島有一個關(guān)鍵的調(diào)節(jié)功能，它存在于啟動子區(qū)域并占了大部分的區(qū)域。改變CPG島的甲基化狀態(tài)，也許能改變?nèi)旧|(zhì)結(jié)構(gòu)，最終能調(diào)節(jié)啟動轉(zhuǎn)錄因子與轉(zhuǎn)錄機制的相互作用。作為結(jié)果，在大多數(shù)的例子中，這種獲得性的和遺傳性的的甲基化狀態(tài)能夠?qū)е禄虮磉_的抑制，另外，CPG島甲基化狀態(tài)能與一種叫甲基CPG結(jié)合域的蛋白相互作用，盡管他們在不同細胞，不同位點的不同作用還不為大家所知，MBP蛋白被認為通過結(jié)合甲基化的DNA來抑制基因的表達，這個過程將會導(dǎo)致染色質(zhì)的修飾和重塑。DNA甲基化在基因表達中的重要性，通過性染色體的平衡呈現(xiàn)出來，女性X染色體的轉(zhuǎn)錄被部分抑制，這個事實通過對特異性的序列甲基化來實現(xiàn)的。哺乳動物的基因包含分散的基因簇，他從親代繼承的甲基化狀態(tài)決定了他某些特異性基因的表達機體繼承了這些表達了的或為表達的富含CPG的基因序列，被稱為基因印跡。因此，這些基因印跡甲基化過程的錯誤能夠使這些基因表達被繼承下來。從臨床的角度，DNA甲基化的重要性，尤其是甲基化損傷，是體現(xiàn)在兩個疾病，SILVERRUSSEL不對稱身材矮小性發(fā)育異常綜合征和BECKWITHWIEDEMANN。這兩種狀況都來自于11號染色體上基因印跡甲基化的錯誤，這種錯誤發(fā)生在編碼IGFF2以及母源基因表達（H19）。在生理情況系這些基因只在父源等位基因發(fā)生甲基化。BECKWITHWIEDEMANN綜合征由于父源母源的等位基因都發(fā)生甲基化而過多表達IGF2，然而，如果是這兩個印跡中心甲基化消失會導(dǎo)致IGF2位點的抑制以及H19表達增加最終導(dǎo)致SILVERRUSSEL綜合征。MICRORNAMICRORNA是翻譯后的調(diào)節(jié)因子，它涉及很多生理的過程，包括生長，分化，增殖、凋亡。MIRNA是一個22NT長非編碼RNA，他通過結(jié)合互補MRNA來抑制翻譯，并導(dǎo)致特定的RNA的降解。MIRNAS是基因編碼MRNA并且通過RNA聚合酶Ⅱ翻譯，與普通的編碼蛋白質(zhì)的RNA一樣，最近在自身免疫疾病和慢性炎癥中發(fā)現(xiàn)了他們。最著名的表觀遺傳學(xué)調(diào)節(jié)就是MIRNADNA相互作用，其代表就是女性X染色體的靜息。事實，兩條X染色體有一條在女性通過表觀遺傳學(xué)調(diào)節(jié)而處于靜息，導(dǎo)致X染色體的會存在劑量補償。這種平衡是通過X染色體靜息中心的X染色體靜息基因的轉(zhuǎn)錄來調(diào)節(jié)，這就使女性的基因表達與男性相適應(yīng)。XIST編碼一個非編碼MRNA包裝X染色體以此過程使得一大群在X染色體上的基因序列靜息。組蛋白抑制性標(biāo)記物和DNA甲基化是這種靜息變得很穩(wěn)定，因為這些發(fā)生在X染色體上表觀遺傳學(xué)的錯誤能夠涉及到某些疾病的發(fā)病機制，包括自身免疫疾病。這確實是富有吸引人的假說，這就能夠解釋某些自身免疫病女性占優(yōu)勢的原因。自身免疫疾病和表觀遺傳修飾自身免疫疾病和表觀遺傳修飾表觀遺傳學(xué)對在所有復(fù)雜疾病中的影響里在快速的提高，并很快會在我們對醫(yī)學(xué)的理解中占重要的地位，我們也許可以假想表觀遺傳學(xué)將填補在特定情況下疾病發(fā)病機制中關(guān)于基因和環(huán)境因素的之間關(guān)系的空白。在某些自身免疫性疾病，免疫細胞的表觀遺傳學(xué)調(diào)節(jié)過程中出現(xiàn)的特異性損害可能會導(dǎo)致免疫耐受下降，這個過程涉及到基因低甲基化和轉(zhuǎn)錄抑制。在自身免疫性疾病中，表觀遺傳學(xué)主要是通過人類外周血單核細胞核或用動物模型來研究。在體和體外研究模型已經(jīng)證實，表觀基因組的變異也許可以導(dǎo)致自身反應(yīng)性T細胞克隆的發(fā)生，特異性的表觀遺傳學(xué)缺陷與某些自身免疫性疾病是有關(guān)的。例如，通過表觀遺傳學(xué)的調(diào)控，輔助性T細胞分化成TH1細胞亞群并產(chǎn)生IFN?并能夠?qū)辜毦琓H2細胞產(chǎn)生IL4和IL13。TH1細胞有的IFNΓ啟動子區(qū)域去甲基化，

簡介：中文中文4000字出處出處KACZY?SKAA,KOSTRUBIECM,CIURZY?SKIM,ETALBTYPENATRIURETICPEPTIDEINACUTEPULMONARYEMBOLISMJCLINICACHIMICAACTA,2008,398214BNP在急性肺動脈栓塞預(yù)后中的意義在急性肺動脈栓塞預(yù)后中的意義ANNAKACZY?SKA,MACIEJKOSTRUBIEC,MICHA?CIURZY?SKI,PIOTRPRUSZCZYK【摘要】急性或慢性左心室功能不全時心肌擴張會導(dǎo)致心房利鈉肽的釋放。然而，有證據(jù)表明，B型利鈉肽（BNP）和N端片段（NTPROBNP）可能來源于右心室，當(dāng)急性肺栓塞尤其存在右心功能不全（RVD）時它們的濃度會升高。近來，急性肺栓塞（APE）嚴重程度評估以及危險分層受到關(guān)注，治療方案的選擇是基于對患者的血流動力學(xué)狀態(tài)、心肌損傷標(biāo)志物以及右心功能不全。BNP的和NTPROBNP是有助于識別存在右心功能不全的APE患者，在新興的超聲心動圖作為輔助工具的前提下，BNP或NTPROBNP水平升高也顯著的預(yù)測APE死亡和/或復(fù)雜的臨床過程?！娟P(guān)鍵字】急性肺栓塞，BNP，NTPROBNP水平，右心室功能不全，預(yù)后眾所周知，急性或慢性左心室功能不全時心肌擴張會導(dǎo)致心房利鈉肽的釋放。然而，有證據(jù)表明，B型利鈉肽（BNP）和N端片段（NTPROBNP）可能來源于右心室，當(dāng)急性肺栓塞尤其存在右心功能不全（RVD）時它們的濃度會升高。最近強調(diào)指出，急性肺栓塞（APE）以及嚴重程度評估的風(fēng)險分層和治療方案的選擇是基于對患者的血流動力學(xué)狀態(tài)、心肌損傷標(biāo)志物和右心功能不全（RVD）。右心室功能，可直接由超聲心動圖和/或增強螺旋CT評估。由于血漿腦利鈉肽濃度反映右心功能不全的嚴重程度，因此，它的作用在APE危險分層中也被探討。針對B型利鈉肽，尤其是對于右心功能不全的檢測和臨床過程的嚴重程度預(yù)測。筆者進行了探討。1文獻選擇通過檢索“肺栓塞”，“BNP”和“NTPROBNP”，從1997年至2008年3月，共檢索到49篇文章。32兩篇文獻被排除，因為它們是病例報告、評論文章、社論或信件。他們沒有結(jié)束點，或沒有提供的生物標(biāo)志物的濃度值。最終，17個有關(guān)BNP和NTPROBNP濃度升高影響短期死亡率，結(jié)果不良事件（死亡，心源性休克，需要溶栓，導(dǎo)管或外科手術(shù)取栓術(shù)，使用升壓藥，需要氣管插管和機械通氣，心肺復(fù)蘇），右心室功能不全的研究被選擇（表1）。2BNP和NTPROBNP含量測定B型利鈉肽前肽（PROBNP）可裂解為相同分子量的B型利鈉肽（BNP）和N末端片段（NTPROBNP）。BNP具有生理活性。BNP可由幾種放射免疫學(xué)或熒光免疫方法來測定濃度，而對于NTPROBNP，只有電化學(xué)發(fā)光免疫分析（ECLIA）測定。因此，BNP和NTPROBNP水平評估的結(jié)果是很難進行比較。3BNP和NTPROBNP水平在右心室功能不全檢測中的意義第一份關(guān)于APE中B型利鈉肽意義的報告來自2001年1。雖然患者數(shù)量較少，但是該研究證明，APE患者血漿BNP水平急性期較對照組顯著升高，在年齡和性別匹配的情況下。右室擴大的患者中最高的BNP濃度為（235（341628）PMOL/L），放射免疫學(xué)方法測定，APE相關(guān)死亡只發(fā)生在本組。相同的結(jié)果在庫徹等人研究的73例患者中被證實在2。懇求主要作者在分析截止90皮克/毫升作為BNP值用于排除充血性心臟衰竭。在大多數(shù)BNP升高的患者中，不同程度的RVD是由經(jīng)胸超聲心動圖觀察到的。此外，在克魯格等3的研究中，BNP90CUTOFF值皮克/毫升這個時候，作為ROC分析時計算所用，這是一個有意義的預(yù)測值，在不伴左心室功能障礙的亞組分析中（AUC07895％CI064092，敏感性64％，特異性94％）。在一項67例患者的研究中，200皮克/毫升被報道可預(yù)究中，分析評估預(yù)測致命的結(jié)果和/或后靜脈血栓栓塞在3個月內(nèi)復(fù)發(fā)的BNP濃度15。其計算截止點為125PMOL/L，靈敏度為60％，特異性為60％，陽性預(yù)測值為57％（AUC06395％CI為056070）。下面觀察老年患者（65歲），有臨床并發(fā)癥的患者BNP濃度顯著高于無并發(fā)癥的患者（274（142581）VS78（33230）PG/ML，P100皮克/毫升4。在TULEVSKI等的研究中，一半的患者入院時BNP濃度升高（10PMOL/L）。2例死亡患者的BNP濃度10PMOL/L17。從庫徹等人的關(guān)于NTPROBNP對于APE意義的的首份報73例患者中，發(fā)生并發(fā)癥的患者NTPROBNP水平顯著高于未發(fā)生不良結(jié)果（4250（8049,607）VS121（1634,802）PG/ML，P1000PG/ML為發(fā)生復(fù)雜臨床事件的陰性預(yù)測值為95％，死亡率為100。1相同的值，在另一個研究中被證實（AUC0809）20。NTPROBNP1000的PG/ML被用于預(yù)測不利的結(jié)果（OR117995％CI為16527，P0007）。NTPROBNP1000PG/ML的患者比7500PG/ML和24小時內(nèi)濃度下降小于50％的患者30天亡率為61％（95％CI39％84％）18。正如之前提到的，無LV充血性心力衰竭的右心功能不全患者，沒有已經(jīng)確定的分界點。ROC分析BNP濃度范圍從90到200PG/ML5,14,3,4。對于NTPROBNP，一個分析報告得出500PG/ML為分界點6（表2）。較低的閾值90100皮克/毫升有較高的靈敏度和中度的特異性，而采取更高的閾值科提高檢查出RVD的特異性。也有幾個分界點預(yù)測APE的不利結(jié)果。RIA法BNP提出了3個值125PMOL/L，25PMOL/L和10PMOL/L15,17,12。后兩個有類似的敏感性，但特異性較高的為10PMOL/L（表3）。對于由免疫方法測定的BNP的閾值范圍為50PG/ML和487PG/ML14,3,16,4,2。建議預(yù)測不良預(yù)后的分界值有高靈敏性及中度的特異性。只有一個研究3沒有確定BNP在預(yù)測APE不良預(yù)后中的作用。NTPROBNP閾值介于500至1000PG/M，他們有很高的陰性預(yù)測值20,7,6,19一項研究顯示7600PG/ML預(yù)測APE發(fā)生死亡有較高的特異性8。5結(jié)論根據(jù)研究，B型鈉尿肽可起源于右心室，對APE患者進行危險分層有重要的意義。BNP和NTPROBNP作為超聲心動圖的輔助工具也有助于確定患者是否發(fā)生右心功能不全。然而，仍需要包括大樣本患者、建立標(biāo)準(zhǔn)化的閾值，排除急性右心功能不全的患者研

簡介：ORIGINALPAPEREFFECTSOFDISTALPROTECTIONONLEFTVENTRICULARFUNCTIONINACUTEANTERIORMYOCARDIALINFARCTIONADOPPLERECHOCARDIOGRAPHICSTUDYYUNYANDUAN?HAIBINZHANG?LIWENLIU?XIAODONGZHOU?CHENGXIANGLI?JUNLI?TINGZHU?HAILISU?YONGSHENGZHU?HONGLINGLI?JUNZHANGRECEIVED14JANUARY2009/ACCEPTED16SEPTEMBER2009/PUBLISHEDONLINE4OCTOBER2009?SPRINGERSCIENCEBUSINESSMEDIA,BV2009ABSTRACTWHETHERDISTALPROTECTIONDEVICESDPDSDURINGPERCUTANEOUSCORONARYINTERVENTIONPCICANIMPROVEMYOCARDIALFUNCTIONINPATIENTSWITHACUTEMYOCARDIALINFARCTIONAMIISSTILLUNDERDEBATEUSINGTISSUEDOPPLERIMAGINGTDI,WEEVALUATETHEGLOBALANDREGIONALLEFTVENTRICULARSYSTOLICANDDIASTOLICFUNCTIONSINPATIENTSWITHANTERIORAMIUSINGDPDSCOMPAREDWITHCONVENTIONALPCININETYSIXPATIENTSWITHANTERIORAMIWERERANDOMLYASSIGNEDTOEITHERPCIWITHDPDSDPD,N46ORTRADITIONALPCICONTROL,N50GROUPSATTHE3AND6MONTHFOLLOWUPS,THEDPDGROUPHADAHIGHERLEFTVENTRICULAREJECTIONFRACTIONTHANTHECONTROLGROUP516±36VS493±53AND530±37VS508±52,RESPECTIVELYBOTHP\005MOREOVER,PEAKSYSTOLICSAANDEARLYDIASTOLICEAMITRALANNULARVELOCITIESOBTAINEDBYTDIWERESIGNIFICANTLYHIGHERINTHEDPDGROUPTHANINTHECONTROLGROUPSA757±053VS712±062CM/SAND771±063VS732±059CM/SEA723±078VS689±086CM/SAND749±069VS704±085CM/S,RESPECTIVELYALLP\005HOWEVER,SYSTOLICANDDIASTOLICREGIONALMYOCARDIALVELOCITIESSIGNIFICANTLYIMPROVEDINTHEDPDGROUPFROMTHE1MONTHFOLLOWUPCOMPAREDWITHTHOSEINTHECONTROLGROUPALLP\005PATIENTSWHORECEIVEDTREATMENTWITHDPDSEXPERIENCEDENHANCEDIMPROVEMENTOFCARDIACFUNCTIONTHUS,ANTERIORAMIPATIENTSCANBENEFITFROMDPDSDURINGPCIKEYWORDSECHOCARDIOGRAPHY?TISSUEDOPPLERIMAGING?DISTALPROTECTIONDEVICESABBREVIATIONSAPEAKFLOWVELOCITYDURINGLATEDIASTOLEAMIACUTEMYOCARDIALINFARCTIONDPDSDISTALPROTECTIONDEVICESEPEAKFLOWVELOCITYDURINGEARLYDIASTOLEEAPEAKEARLYDIASTOLICMITRALANNULARVELOCITIESEMPEAKEARLYDIASTOLICMYOCARDIALVELOCITIESLADLEFTANTERIORDESCENDINGCORONARYARTERYLVLEFTVENTRICLE/VENTRICULARPCIPERCUTANEOUSCORONARYINTERVENTIONRWMSIREGIONALWALLMOTIONSCOREINDEXSAPEAKSYSTOLICMITRALANNULARVELOCITIESYUNYANDUANANDHAIBINZHANGCONTRIBUTEDEQUALLYTOTHISSTUDYYYDUAN?HBZHANG?LWLIU?XDZHOU?JLI?TZHU?HLSU?YSZHU?HLLI?JZHANGFLOWGRADE3WITHINTHEVESSELWASCONSIDEREDTOBENORMALTHEPOSTINTERVENTIONANDFOLLOWUPTHERAPYSTRATEGIESWERESIMILARINTHETWOGROUPSECHOCARDIOGRAPHICEXAMINATIONECHOCARDIOGRAPHYWASPERFORMEDBEFOREPCIANDAT1,3,AND6MONTHSAFTERPCITHEOBSERVERWASBLINDTOALLCLINICALANDANGIOGRAPHICDATAALLECHOCARDIOGRAMSWEREPERFORMEDWITHANULTRASOUNDSYSTEMHDI5000ATL,PHILIPSMEDICALSYSTEM,USATHELVVOLUMESANDEJECTIONFRACTIONSWERECALCULATEDUSINGTHEMODIFIEDBIPLANESIMPSON’SFORMULAWITHIMAGESOBTAINEDFROMTHEAPICALFOURANDTWOCHAMBERVIEWSASRECOMMENDEDBYTHEAMERICANSOCIETYOFECHOCARDIOGRAPHY16PULSEDDOPPLERMEASUREMENTSOFLVFILLINGWEREOBTAINEDINTHEAPICALFOURCHAMBERVIEW,WITHTHESAMPLEVOLUMEPLACEDATTHELEVELOFTHEMITRALTIPSWEOBTAINEDPEAKFLOWVELOCITIESDURINGEARLYEANDLATEADIASTOLICFILLING,ANDTHEDIASTOLICTRANSMITRALE/AVELOCITYRATIOTHEPULSEDWAVETDIWASACQUIREDFROMAPICALFOURCHAMBER,TWOCHAMBER,ANDLONGAXISVIEWSA5MMSAMPLEVOLUMEOFTDIWASPOSITIONEDINSIXPOINTSOFTHEMITRALANNULUS,ANDTHEPEAKSYSTOLICSAANDPEAKEARLYDIASTOLICEAVELOCITIESWEREMEASUREDTOASSESSGLOBALLVSYSTOLICANDDIASTOLICFUNCTIONSTHERESULTSAREREPORTEDASAMEANOFTHESIXSAMPLESOFTHEMITRALANNULUSMEASUREMENTSOFTHEREGIONALMYOCARDIALVELOCITIESWERESAMPLEDINBASAL,MIDLEVEL,ANDAPICALSEGMENTSOFTHELVANTERIORWALLSFROMAPICALTWOCHAMBERVIEWSPEAKSYSTOLICMYOCARDIALVELOCITIESSMANDEARLYDIASTOLICMYOCARDIALVELOCITIESEMWEREOBTAINEDTHELVANTERIORWALLMOTIONWASSEMIQUANTITATIVELYGRADEDFROM1TO4ASFOLLOWS1NORMAL,2HYPOKINESIS,3AKINESIS,AND4DYSKINESISTHEREGIONALWALLMOTIONSCOREINDEXRWMSIOFTHEANTERIORWALLWASDERIVEDFROMTHEMEANOFTHETHREESEGMENTSCORES16WEPREVIOUSLYREPORTEDTHEMETHODSANDREPRODUCIBILITYOFTDIINDICESINOURLABORATORY17,18INTRAOBSERVERVARIABILITYWAS42±22FORSA,44±22FOREA,38±18FORSM,AND40±23FOREMTHECORRESPONDINGVALUESFORINTEROBSERVERVARIABILITYWERE49±27,55±29,46±25,AND52±24,RESPECTIVELYSTATISTICALANALYSISVALUESAREEXPRESSEDASTHEMEANS±STANDARDDEVIATIONS,WHENAPPROPRIATEGROUPDIFFERENCESWEREDETECTEDBYTHESTUDENT’STTESTORANALYSISOFVARIANCEANOVAFORCONTINUOUSVARIABLESANDV2TESTFORDISCRETEVARIABLESAPVALUE\005WASCONSIDEREDSTATISTICALLYSIGNIFICANTALLSTATISTICALANALYSESWEREPERFORMEDUSINGSTANDARDSTATISTICSSOFTWARESPSSVERSION100RESULTSGENERALCLINICALCHARACTERISTICSDURINGTHEENROLLMENTPERIOD,178PATIENTSWITHTHEIRFIRST,ANTERIORAMIWERESCREENEDOFTHESEPATIENTS,96WEREELIGIBLEFORRANDOMIZATIONFIFTYPATIENTSWERERANDOMLYASSIGNEDTOTHECONTROLGROUPAND46TOTHEDPDGROUPFIG1THEAGESOFTHESEPATIENTS81MALESWEREBETWEEN31AND75YEARSWITHAMEANAGEOF56±7YEARSBASELINECLINICALANDANGIOGRAPHICFEATURESWEREWELLMATCHEDBETWEENTHETWOSTUDYGROUPSTABLE1INTJCARDIOVASCIMAGING201026125–133127123

簡介：ULTRASOUNDSCREENINGOFPERIARTICULARSOFTTISSUEABNORMALITYAROUNDMETALONMETALBEARINGSTAKASHINISHII,MD,PHD,TAKASHISAKAI,MD,PHD,YMASAKITAKAO,MD,PHD,YHIDEKIYOSHIKAWA,MD,PHD,YANDNOBUHIKOSUGANO,MD,PHDABSTRACTALTHOUGHMETALHYPERSENSITIVITYORPSEUDOTUMORSARECONCERNSFORMETALONMETALMOMBEARINGS,DETAILEDPATHOLOGIESOFPATTERNS,SEVERITY,ANDINCIDENCEOFPERIPROSTHETICSOFTTISSUELESIONSAREINCOMPLETELYUNDERSTOODWEEXAMINEDTHEPOTENTIALOFULTRASOUNDFORSCREENINGOFPERIARTICULARSOFTTISSUELESIONSAROUNDMOMBEARINGSULTRASOUNDEXAMINATIONSWERECONDUCTEDIN88HIPS79PATIENTSWITHMOMHIPRESURFACINGSORMOMTOTALHIPARTHROPLASTIESWITHALARGEFEMORALHEADFOURQUALITATIVEULTRASOUNDPATTERNSWERESHOWN,INCLUDINGNORMALPATTERNIN69HIPS,JOINTEXPANSIONPATTERNIN11HIPS,CYSTICPATTERNIN5HIPS,ANDMASSPATTERNIN3HIPSHIPSWITHTHELATTER3ABNORMALPATTERNSSHOWEDSIGNIFICANTLYHIGHERFREQUENCYOFCLINICALSYMPTOMS,WITHOUTSIGNIFICANTDIFFERENCESOFSEX,DURATIONOFIMPLANTATION,HEADSIZES,ANDCUPABDUCTION/ANTEVERSIONANGLES,COMPAREDWITHHIPSWITHNORMALPATTERNULTRASOUNDEXAMINATIONPROVIDESSENSITIVESCREENINGOFSOFTTISSUEREACTIONSAROUNDMOMBEARINGSANDMAYBEUSEFULINMONITORINGPROGRESSIONANDDEFININGTREATMENTFORPERIARTICULARSOFTTISSUEABNORMALITIESKEYWORDSMETALONMETAL,ULTRASOUND,MRIMAGING,SOFTTISSUEREACTION,BEARINGS?2012ELSEVIERINCALLRIGHTSRESERVEDINTHE2000S,RENEWEDMETALONMETALMOMHIPRESURFACINGANDTOTALHIPARTHROPLASTYTHAWITHALARGEFEMORALHEADGAINEDGREATPOPULARITYWITHTHEEXPECTATIONOFLOWBEARINGWEAR,HIGHFUNCTIONANDACTIVITYOFPATIENTS,ANDLOWINCIDENCEOFPOSTOPERATIVEDISLOCATION13ASMOMHIPARTHROPLASTIESHAVEBECOMEMOREWIDESPREAD,INCREASINGABNORMALREACTIONSINPERIARTICULARSOFTTISSUEREACTIONSTHATPRESENTASCYSTS,FLUIDCOLLECTION,ENHANCEDBURSAE,SOLIDMASS,ANDINFLAMMATORYMASSESHAVEBEENREPORTED410SOMEOFTHESECASESWERERELATEDTOSEVEREPAININTHEHIPORGROIN,PALPABLEHUGEMASSES,OREXTENSIVEPERIPROSTHETICBONELOSSLEADINGTOREVISIONSURGERYWITHRESECTIONOFSOFTTISSUELESIONS,ANDALTERATIONINBEARINGSWITHOTHERMATERIALS9FROMANALYSESOFRETRIEVEDTISSUEANDCOMPONENTS,ADELAYEDTYPEHYPERSENSITIVEREACTIONSPECIFICALLYTERMEDASEPTICLYMPHOCYTICVASCULITIS–ASSOCIATEDLESIONSORRESPONSETOEXCESSIVEWEARPARTICLESOFMOMBEARINGSWASSUSPECTEDASTHEMAINCAUSEOFTHESOFTTISSUEREACTIONS5,1113HOWEVER,THEDETAILEDPATHOLOGIESOFPATTERNS,SEVERITY,INCIDENCE,ANDNATURALCOURSEOFPERIPROSTHETICSOFTTISSUELESIONSHAVENOTYETBEENELUCIDATEDONEOFTHEDIFFICULTIESENCOUNTEREDININVESTIGATIONOFPERIARTICULARSOFTTISSUEREACTIONSAROUNDARTIFICIALJOINTSISTHEABSENCEOFSENSITIVEIMAGINGMODALITIESPLAINRADIOGRAPHYANDCOMPUTEDTOMOGRAPHYARELESSSENSITIVEFORTHEEVALUATIONOFSOFTTISSUEDISORDERSBECAUSEOFPOORIMAGINGCONTRASTBETWEENNORMALANDABNORMALSTRUCTURESMAGNETICRESONANCEIMAGINGMRIHASTHEADVANTAGESOFSUPERIORIMAGINGCONTRASTFORSOFTTISSUEABNORMALITIESANDTHEREADYAVAILABILITYOF3DIMENSIONALASSESSMENTOFABNORMALLESIONSHOWEVER,THEASSESSMENTOFSOFTTISSUEREACTIONSADJACENTTOTHEIMPLANTWASDIFFICULTBECAUSEOFMETALSUSCEPTIBILITYARTIFACTSEVENWHILEUSINGSOPHISTICATEDMETALARTIFACTREDUCTIONTECHNIQUES9,14,15ULTRASOUNDASSESSMENTAROUNDTHEHIPARTHROPLASTYHASSEVERALADVANTAGESOVEROTHERIMAGINGMODALITIESTHESEINCLUDETHEABSENCEOFIONIZINGRADIATION,ABSENCEOFMETALARTIFACTSINTRODUCEDBYIMPLANTS,ANDRELATIVELYLOWCOST16THEREFORE,ULTRASOUNDASSESSMENTMAYBESUITABLEFORTHESCREENINGOFPERIARTICULARSOFTTISSUEREACTIONSAFTERHIPARTHROPLASTYSOMEREPORTSDEMONSTRATEDTHEUSEOFULTRASOUNDFORTHEEVALUATIONOFPERIARTICULARSOFTTISSUEREACTIONSINMOMBEARINGS6,17,18FROMTHEDEPARTMENTOFORTHOPAEDICMEDICALENGINEERING,OSAKAUNIVERSITYGRADUATESCHOOLOFMEDICINE,22YAMADAOKA,SUITA,OSAKA,JAPANANDYDEPARTMENTOFORTHOPAEDICSURGERY,OSAKAUNIVERSITYGRADUATESCHOOLOFMEDICINE,22YAMADAOKA,SUITA,OSAKA,JAPANSUBMITTEDAPRIL4,2011ACCEPTEDSEPTEMBER16,2011THECONFLICTOFINTERESTSTATEMENTASSOCIATEDWITHTHISARTICLECANBEFOUNDATDOI101016/JARTH201109015REPRINTREQUESTSTAKASHINISHII,MD,DEPARTMENTOFORTHOPAEDICMEDICALENGINEERING,OSAKAUNIVERSITYGRADUATESCHOOLOFMEDICINE,22YAMADAOKA,SUITA,OSAKA5650871,JAPAN?2012ELSEVIERINCALLRIGHTSRESERVED08835403/270600123600/0DOI101016/JARTH201109015895THEJOURNALOFARTHROPLASTYVOL27NO62012COMPONENTAND4“MASSPATTERN”WITHALARGEMASSEXTENDINGANTERIORTOTHEFEMORALCOMPONENTTHEREWERE69HIPSWITHTHENORMALPATTERN,11HIPSWITHTHEJOINTEXPANSIONPATTERN,5HIPSWITHTHECYSTICPATTERN,AND3HIPSWITHTHEMASSPATTERNWHENTHEJOINTEXPANSION,CYSTIC,ANDMASSPATTERNSWERECLASSIFIEDINTOTHEABNORMALPATTERNONULTRASOUND,THEFREQUENCYOFCLINICALSYMPTOMSWASSIGNIFICANTLYHIGHERINHIPSWITHTHEABNORMALPATTERN63THANINHIPSWITHTHENORMALPATTERN25TABLE1THEREWASNOSIGNIFICANTLYDIFFERENCEREGARDINGOTHERPATIENTSPROFILES,DURATIONOFIMPLANTINSITU,TYPESOFOPERATIONANDBEARINGS,CUPANDHEADSIZES,RADIOLOGICPARAMETERSOFTHEIMPLANTPLACEMENT,ANDPRESENCEOFOSTEOLYSIS,BETWEENTHEHIPWITHNORMALANDABNORMALPATTERNSALLOFTHE3PATIENTSSHOWINGMASSPATTERNONULTRASOUNDWEREWOMENWITHMTHAOPERATIONSANDHADONLYSLIGHTPAINORDISCOMFORTINTHEHIPTABLE2FIG1CLASSIFICATIONOFPERIARTICULARSOFTTISSUEREACTIONSONANTERIORLONGITUDINALORTRANSVERSEULTRASOUNDIMAGESNORMALPATTERNA,JOINTEXPANSIONPATTERNB,CYSTICPATTERNC,ANDMASSPATTERNDARROWSINDICATEANTERIORCAPSULEANDARROWHEADSINDICATEMASSLESIONULTRASOUNDSCREENINGOFPERIARTICULARABNORMA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簡介：INVITEDCRITICALREVIEWBTYPENATRIURETICPEPTIDEINACUTEPULMONARYEMBOLISMANNAKACZY?SKA,MACIEJKOSTRUBIEC,MICHA?CIURZY?SKI,PIOTRPRUSZCZYK?DEPARTMENTOFINTERNALMEDICINEANDCARDIOLOGY,MEDICALUNIVERSITYOFWARSAW,POLANDABSTRACTARTICLEINFOARTICLEHISTORYRECEIVED14MAY2008RECEIVEDINREVISEDFORM25JUNE2008ACCEPTED19JULY2008AVAILABLEONLINE24JULY2008KEYWORDSACUTEPULMONARYEMBOLISMBNPNTPROBNPRIGHTVENTRICLEDYSFUNCTIONPROGNOSISMYOCARDIALSTRETCHLEADSTOTHENATRIURETICPEPTIDESRELEASEINACUTEORCHRONICLEFTVENTRICULARDYSFUNCTIONHOWEVER,THEREISANACCUMULATINGEVIDENCETHATBTYPENATRIURETICPEPTIDEBNPANDITSNTERMINALFRAGMENTNTPROBNPMAYORIGINATEFROMRIGHTVENTRICLEANDTHEIRCONCENTRATIONSAREELEVATEDINPATIENTSWITHACUTEPULMONARYEMBOLISMAPEESPECIALLYWHENRESULTINGINRIGHTVENTRICULARDYSFUNCTIONRVDRECENTLYITISUNDERLINEDTHATSEVERITYASSESSMENTOFAPEASWELLASTHERISKSTRATIFICATIONANDTHERAPYSELECTIONISBASEDBOTHONPATIENTSHEMODYNAMICSTATUSANDMARKERSOFMYOCARDIALINJURYANDRVDBNPANDNTPROBNPAREHELPFULINIDENTIFYINGPATIENTSWITHRVDINAPE,EMERGINGASANADJUNCTIVETOOLTOECHOCARDIOGRAPHYELEVATEDBNPORNTPROBNPLEVELSAREALSOSIGNIFICANTPREDICTORSOFDEATHAND/ORCOMPLICATEDCLINICALCOURSEINAPE?2008ELSEVIERBVALLRIGHTSRESERVEDCONTENTS1STUDIESSELECTION12BNPANDNTPROBNPASSAYS13BNPANDNTPROBNPINTHEDETECTIONOFRVD24PROGNOSTICVALUEOFBNPANDNTPROBNPINAPE25CONCLUSIONS4REFERENCES4ITISWELLKNOWNTHATMYOCARDIALSTRETCHLEADSTOTHENATRIURETICPEPTIDESRELEASEINACUTEORCHRONICLEFTVENTRICULARDYSFUNCTIONHOWEVER,THEREISANACCUMULATINGEVIDENCETHATCONCENTRATIONSOFBTYPENATRIURETICPEPTIDEBNPANDITSNTERMINALFRAGMENTNTPROBNPAREELEVATEDINPATIENTSWITHACUTEPULMONARYEMBOLISMAPEESPECIALLYWHENRESULTINGINRIGHTVENTRICULARDYSFUNCTIONRECENTLYITISUNDERLINEDTHATSEVERITYASSESSMENTOFACUTEPULMONARYEMBOLISMAPEASWELLASTHERISKSTRATIFICATIONANDTHERAPYSELECTIONISBASEDBOTHONPATIENTSHEMODYNAMICSTATUSANDMARKERSOFMYOCARDIALINJURYANDRIGHTVENTRICULARDYSFUNCTIONRVDRIGHTVENTRICULARFUNCTIONCANBEDIRECTLYASSESSEDATECHOCARDIOGRAPHYAND/ORCONTRASTENHANCEDSPIRALCOMPUTEDTOMOGRAPHYSINCEPLASMACONCENTRATIONOFBRAINNATRIURETICPEPTIDEREFLECTSTHESEVERITYOFRVDITSASSESSMENTWASIMPLOREDINAPERISKSTRATIFICATIONASWELLWEPERFORMEDASYSTEMATICREVIEWAIMEDONBTYPENATRIURETICPEPTIDESINAPEESPECIALLYFORTHERVDDETECTIONANDCLINICALCOURSEPREDICTION1STUDIESSELECTIONOVERALL49ARTICLESWEREFOUNDSEARCHINGPUBMEDBYTERMS‘PULMONARYEMBOLISM’,‘BNP’AND‘NTPROBNP’FROM1997TOMARCH2008THIRTYTWOPAPERSWEREEXCLUDEDFROMCURRENTREVIEWBECAUSETHEYWERECASEREPORTS,REVIEWPAPERS,EDITORIALSORLETTERSTHEYDIDNOTREPORTONENDPOINTSORDIDNOTPROVIDEVALUESOFBIOMARKERSCONCENTRATIONEVENTUALLY,17STUDIESCONCERNINGTHEINFLUENCEOFELEVATEDBNPANDNTPROBNPONSHORTTERMMORTALITY,ADVERSEOUTCOMEEVENTSDEATH,CARDIOGENICSHOCK,NEEDFORTHROMBOLYSIS,CATHETERORSURGICALEMBOLECTOMY,USEOFVASOPRESSORS,NEEDFORENDOTRACHEALINTUBATIONANDMECHANICALVENTILATION,CARDIOPULMONARYRESUSCITATIONANDRVDWERESELECTEDTABLE12BNPANDNTPROBNPASSAYSPROPEPTIDEFORBTYPENATRIURETICPEPTIDEPROBNPISCLEAVEDTOEQUIMOLARAMOUNTSOFBTYPENATRIURETICPEPTIDEBNPANDNTERMINALFRAGMENTNTPROBNPBNPISPHYSIOLOGICALLYACTIVEBNPCONCENTRATIONISASSESSEDUSINGSEVERALRADIOIMMUNOLOGICASSAYSORIMMUNOFLUOROMETRICASSAYS,WHILEFORNTPROBNPONETESTISCLINICACHIMICAACTA39820081–4?CORRESPONDINGAUTHORDEPARTMENTOFINTERNALMEDICINEANDCARDIOLOGY,MEDICALUNIVERSITYOFWARSAW,ULLINDLEYA402005WARSAW,POLANDTEL48225021144FAX48225022142EMAILADDRESSPIOTRPRUSZCZYKAMWAWEDUPLPPRUSZCZYK00098981/–SEEFRONTMATTER?2008ELSEVIERBVALLRIGHTSRESERVEDDOI101016/JCCA200807020CONTENTSLISTSAVAILABLEATSCIENCEDIRECTCLINICACHIMICAACTAJOURNALHOMEPAGEWWWELSEVIERCOM/LOCATE/CLINCHIMCOMPLICATEDCLINICALCOURSEWITHOR8095CI13–501,P0026INTERESTINGLYAUTHORSALSOATTEMPTEDTOIDENTIFYTHEMOSTSENSITIVEBNPCUTOFFLEVELFORIDENTIFYINGLOWRISKAPEPATIENTSITTURNEDTOBEB50PG/MLWITHITSNEGATIVEPREDICTIVEVALUEOF972ELEVATEDBNPWASALSOFOUNDTOBEAPREDICTOROFALLCAUSEASWELLASAPERELATEDMORTALITYINGROUPOF110PATIENTS12THREEMONTHMORTALITYWAS10INTERESTINGLYALLDEATHSOCCURREDINPATIENTSWITHBNPCONCENTRATIONINSECONDANDTHIRDTERTILEIEEXCEEDING25PMOL/LAND217PMOL/L,RESPECTIVELYINTHESTUDYBYKRüGERETAL3,HOWEVER,BNPCUTOFFVALUEOFN90PG/ML,ASCALCULATEDFROMROCANALYSIS,WASNOTDIRECTLYASSOCIATEDNEITHERWITHINHOSPITALCOMPLICATEDCOURSENORWITHSHORTTERMMORTALITYHOWEVER,ASMENTIONEDEARLIERITWASREPORTEDTOBEUSEFULINRVDPREDICTIONIMPORTANTLY,ASEXPECTED,HIGHERINCIDENCEOFCOMPLICATIONSASWELLASTRENDTOWARDHIGHERMORTALITYWASOBSERVEDINPATIENTSWITHRVDCONVERSELY,ASMALLSTUDYONUNSELECTEDGROUPOF17PATIENTSWITHAPE,INCLUDINGPATIENTSBOTHWITHANDWITHOUTRVDREPORTEDSIGNIFICANTLYHIGHERCONCENTRATIONOFBNPINPATIENTSWHODIEDOFPETHANINTHOSEWHOSURVIVED916775–3362VS144119–274PMOL/L,P00213THEFOLLOWINGSTUDYCOMPRISING61INITIALLYHEMODYNAMICALLYSTABLEPATIENTSREPORTEDHIGHERBNPCONCENTRATIONONADMISSIONINPATIENTSWITHSUBSEQUENTCOMPLICATEDCLINICALCOURSETHANWITHFAVORABLEOUTCOME950±314VS296±353PG/ML,PB0000114IMPORTANTLYALL4INHOSPITALDEATHSAND11COMPLICATIONSOBSERVEDINTHISSTUDYOCCURREDINPATIENTSWITHBNPINTHEHIGHESTTERTILE,NAMELY527–1300PG/MLROCANALYSISCONFIRMEDCUTOFFPOINTOF487PG/MLASINDICATINGPATIENTSWITHHIGHERRISKOFCOMPLICATIONSAUC09895CI096–099,SENSITIVITY86,SPECIFICITY100INTHE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簡介：EFFECTOFTOTALKNEEARTHROPLASTYIMPLANTPOSITIONONFLEXIONANGLEBEFOREIMPLANTBONEIMPINGEMENTHIDEKIMIZUUCHI,MD,PHD,YCLIFFORDWCOLWELLJR,MD,SHUICHIMATSUDA,MD,PHD,YCESARFLORESHERNANDEZ,BS,YUKIHIDEIWAMOTO,MD,PHD,YANDDARRYLDDLIMA,MD,PHDABSTRACTWEGENERATEDPATIENTSPECIFICCOMPUTERMODELSOFTOTALKNEEARTHROPLASTYFROM10PATIENTSTOCOMPUTEMAXIMUMFLEXIONANGLEBEFOREIMPLANTBONEIMPINGEMENTMOTIONWASSIMULATEDFOR5DIFFERENTFEMORALIMPLANTPOSITIONSAND11DIFFERENTTIBIALINSERTPOSITIONSAT4DIFFERENTTIBIALPOSTERIORSLOPESINTHENEUTRALPOSITION,THEMEANMAXIMUMFLEXIONANGLEWAS1363°THERANGEBECAUSEOFANATOMICALVARIATIONAMONGPATIENTSWAS130°ACOMBINATIONOF2MMPOSTERIORTRANSLATIONOFTHEFEMORALCOMPONENTWITHA10MMANTERIORTRANSLATIONOFTHEINSERTANDA7°POSTERIORSLOPEINCREASEDFLEXIONBYAMEANOF14°RELATIVETOTHENEUTRALPOSITIONTHERATEOFCHANGEINFLEXIONANGLEWAS04°/MMTO15°/MMWITHRESPECTTOIMPLANTPOSITIONAND15°/MMINCREASEINTHEPOSTERIORCONDYLAROFFSETKEYWORDSTOTALKNEEARTHROPLASTY,KNEEFLEXIONANGLE,COMPUTERSIMULATION,COMPONENTPOSITION,ANATOMICALVARIATION?2011ELSEVIERINCALLRIGHTSRESERVEDTOTALKNEEARTHROPLASTYTKAHASBECOMEONEOFTHEMOSTSUCCESSFULORTHOPEDICPROCEDURESWITHREPORTEDSURVIVALRATESOFGREATERTHAN90AFTER15YEARS1,2WITHTHEIMPROVEMENTOFLONGTERMOUTCOMES,THEREISRENEWEDINTERESTINMAXIMIZINGRANGEOFMOTIONAFTERTKA310THERANGEOFMOTIONINFLEXIONISEXTREMELYIMPORTANTINASIANCOUNTRIESANDFORPATIENTSWITHLIFESTYLESTHATINVOLVESITTINGONTHEFLOORINDEEPFLEXION3EVENINNORTHAMERICANPATIENTS,UPTO75IDENTIFIEDTHATACTIVITIESREQUIRINGDEEPERKNEEFLEXIONANGLESUCHASSQUATTING,KNEELING,ANDGARDENINGWEREPERFORMEDWITHGREATERDIFFICULTYAFTERTKA4MANYCLINICALSTUDIESHAVEINVESTIGATEDFACTORSAFFECTINGPOSTOPERATIVERANGEOFMOTION5,6,10,11PATIENTRELATEDFACTORSSUCHASPREOPERATIVERANGEOFMOTION,BODYMASSINDEX,DISEASE,AGE,ANDSEXGREATLYINFLUENCETHEPOSTOPERATIVERANGEOFMOTIONSIMILARLY,SURGICALTECHNIQUESCANALSOAFFECTTHEPOSTOPERATIVERANGEOFMOTIONEXAMPLESINCLUDETHEHEIGHTOFJOINTLINE,PATELLARTRACKING,APPROPRIATEGAPBALANCING,RELEASEOFPOSTERIORCAPSULE,ANDREMOVALOFTHEOSTEOPHYTESANOTHERIMPORTANTFACTORISTHEPOSTERIORCONDYLAROFFSETPCO,WHICHHASBEENASSOCIATEDWITHPOSTOPERATIVERANGEOFMOTIONINFLUOROSCOPICANALYSISINVIVO5PREVIOUSSTUDIESHAVEANALYZEDTHEEFFECTOFIMPLANTALIGNMENTANDRELATIVEPOSITIONONPOSTOPERATIVERANGEOFMOTION1215WALKERETAL12REPORTEDTHATPOSTERIORANDPROXIMALFEMORALPLACEMENTANDAGREATERPOSTERIORTIBIALSLOPEINCREASEDMAXIMUMFLEXIONANGLEINPLASTICMODELSOFTHEFEMURANDTIBIAMASSINANDGOURNAY13DEMONSTRATEDTHATGREATERPCOINCREASEDTIBIALPOSTERIORSLOPE,ANDAMOREPOSTERIORFEMOROTIBIALCONTACTPOINTCANINCREASEFLEXIONINASTUDYTHATUSED2DIMENSIONALTEMPLATESOFPROSTHETICCOMPONENTSONLATERALKNEERADIOGRAPHSHOWEVER,THECOMBINEDEFFECTOFTHE3DIMENSIONALANATOMYOFTHEPATIENTANDTHEIMPLANTPOSITIONHASNOTBEENSTUDIEDWEGENERATEDPATIENTSPECIFICANATOMICALMODELSOFIMPLANTBONEIMPINGEMENTTOEVALUATETHEEFFECTOFIMPLANTPOSITIONANDANATOMICALVARIATIONONFLEXIONANGLEOURPRIMARYHYPOTHESISWASTHATIMPLANTPOSITIONWOULDSIGNIFICANTLYAFFECTMAXIMUMKNEEFLEXIONANGLEBEFOREBONEPROSTHESISIMPINGEMENTOURSECONDARYHYPOTHESISWASTHATTHEPCOWOULDCORRELATESIGNIFICANTLYWITHMAXIMUMFLEXIONANGLEFROMTHESHILEYCENTERFORORTHOPAEDICRESEARCHANDEDUCATIONATSCRIPPSCLINIC,LAJOLLA,CAANDYDEPARTMENTOFORTHOPAEDICSURGERY,GRADUATESCHOOLOFMEDICALSCIENCES,KYUSHUUNIVERSITY,FUKUOKA,JAPANSUBMITTEDAPRIL19,2010ACCEPTEDAUGUST1,2010NOBENEFITSORFUNDSWERERECEIVEDINSUPPORTOFTHESTUDYREPRINTREQUESTSDARRYLDDLIMA,MD,PHD,SHILEYCENTERFORORTHOPAEDICRESEARCHANDEDUCATIONATSCRIPPSCLINIC,11025NTORREYPINESROAD,SUITE140,LAJOLLA,CA92037?2011ELSEVIERINCALLRIGHTSRESERVED08835403/260500113600/0DOI101016/JARTH201008002721THEJOURNALOFARTHROPLASTYVOL26NO52011INSERTACONSTANTMASSWASAPPLIEDATAFIXEDDISTANCE300MMFROMTHECLINICALEPICONDYLARAXISOFTHEFEMURTOGENERATEAFLEXIONMOMENTBECAUSEOFGRAVITYTHEFEMURWASTHENALLOWEDTOFLEX,ANDTHEMAXIMUMFLEXIONWASRECORDEDBEFOREIMPINGEMENTBETWEENTHEPOSTERIORCORTEXOFTHEFEMURANDTHETIBIALINSERTFIG2PEAKFLEXIONANGLESWERERECORDEDASTHEINSERTWASMOVEDAT2MMINTERVALSRANGINGFROM10MMANTERIORTO10MMPOSTERIORFOREACHOFTHE5FEMORALIMPLANTPOSITIONSNEUTRAL,2MMANTERIOR/POSTERIOR,AND2MMPROXIMAL/DISTALFROMTHENEUTRALTHISPROCESSWASTHENREPEATEDFOREACHOF4TIBIALPOSTERIORSLOPEANGLES0°,3°,5°,AND7°TOTHEMECHANICALAXISOFTHETIBIAWEALSOMEASUREDTHEPCOFOREACHOFTHEDIFFERENTFEMORALIMPLANTPOSITIONSASDEPICTEDINFIG1BPOSTERIORCONDYLAROFFSETWASMEASUREDASTHEMAXIMUMDISTANCEBETWEENTHEPOSTERIORSURFACEOFTHEDISTALFEMURANDTHEPOSTERIORCONDYLE5VALIDATIONOFTHECOMPUTERMODELFOURFRESHFROZENHUMANCADAVERKNEESWERETESTEDTOVALIDATETHECOMPUTERMODELCOMPUTEDTOMOGRAPHICSCANSWEREOBTAINEDAFTERIMPLANTINGFIDUCIALMARKERSINEACHTIBIAANDFEMUR3TITANIUMSCREWSINEACHBONEKNEEARTHROPLASTYWASPERFORMEDUSINGASURGICALNAVIGATIONSYSTEMSTRYKERNAVIGATION,FREIBURG,GERMANYCOMPONENTALIGNMENTWASSIMILARTOTHATDESCRIBEDFORTHECOMPUTATIONALMODELSCORPIOCRSTRYKERORTHOPAEDICSTIBIALANDFEMORALCOMPONENTSWEREUSEDTHEPATELLAWASNOTRESURFACEDALLSOFTTISSUESAROUNDTHEKNEEJOINTWEREREMOVEDASMUCHASPOSSIBLEEXCEPTTHEPOSTERIORCRUCIATELIGAMENT,THEMEDIALANDLATERALCOLLATERALLIGAMENTS,ANDTHEEXTENSORMECHANISMAFTERARTHROPLASTYTHETIBIAWASMOUNTEDVERTICALLYONACUSTOMRIG,ANDTHEFEMURWASALL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