蔡思逸李書(shū)綱邱貴興
(中國(guó)醫(yī)學(xué)科學(xué)院北京協(xié)和醫(yī)學(xué)院北京協(xié)和醫(yī)院骨科,北京100730)
20世紀(jì)70年代,Nash和Engler先后報(bào)道將體感誘發(fā)誘發(fā)電位監(jiān)測(cè)(SEPs)應(yīng)用于脊柱側(cè)彎矯形手術(shù)中。隨著SEPs在脊柱手術(shù)中的廣泛開(kāi)展,脊柱手術(shù)的安全性大幅提高[1,2]。然而,不到10年,單一SEPs監(jiān)護(hù)的問(wèn)題很快暴露,Lesser和Ginsburg分別報(bào)道了一例病例,患者術(shù)中SEPs信號(hào)在正常范圍,但術(shù)后均出現(xiàn)了嚴(yán)重的運(yùn)動(dòng)功能障礙,甚至癱瘓[3,4]。此后,類(lèi)似的報(bào)道相繼出現(xiàn)[5-7],SEPs對(duì)脊髓運(yùn)動(dòng)傳導(dǎo)束的監(jiān)護(hù)能力從此受到質(zhì)疑。從神經(jīng)解剖學(xué)的角度來(lái)看,脊柱傳導(dǎo)SEPs的主要途徑為脊髓的背側(cè)結(jié)構(gòu),而自主的運(yùn)動(dòng)電位的傳導(dǎo)途徑主要來(lái)源于錐體系,在脊髓主要為位于椎體前索和前外側(cè)索的皮質(zhì)脊髓束。皮質(zhì)脊髓束損害或脊髓背側(cè)受損可以分別發(fā)生。針對(duì)脊髓運(yùn)動(dòng)傳導(dǎo)束傳導(dǎo)的運(yùn)動(dòng)電位的監(jiān)測(cè)手段呼之欲出。1980年Merton通過(guò)單脈沖經(jīng)顱電刺激在清醒患者身體誘發(fā)出一個(gè)運(yùn)動(dòng)電位,1984年Merton、1985年Baker分別通過(guò)經(jīng)顱磁刺激(TMS)和經(jīng)顱電刺激(TES)誘發(fā)出動(dòng)作電位(MEP),并在脊髓硬膜表面、肌肉上記錄。脊柱手術(shù)中關(guān)于運(yùn)動(dòng)傳導(dǎo)束的神經(jīng)電生理監(jiān)測(cè)的特異性的監(jiān)測(cè)手段MEP,對(duì)MEP的認(rèn)識(shí)幫助我們理解了這些所謂的術(shù)中SEPs信號(hào)保留缺出現(xiàn)運(yùn)動(dòng)功能損害的SEPs“假陰性病例”,也進(jìn)一步的認(rèn)識(shí)了脊髓的損傷機(jī)制,提高了手術(shù)的安全性,這一手段目前得到了廣泛應(yīng)用和深入研究。
當(dāng)大腦皮層或脊髓受到電刺激后,一旦電流超過(guò)神經(jīng)組織的興奮閾值,錐體細(xì)胞軸突會(huì)產(chǎn)生去極化的動(dòng)作電位,隨皮質(zhì)脊髓束向下行傳導(dǎo)到位于脊髓前角的α運(yùn)動(dòng)神經(jīng)元、靶肌肉,可以在傳導(dǎo)途徑上和相應(yīng)的靶肌群上收集記錄。根據(jù)收集部位的不同MEP主要有三類(lèi),包括肌肉MEPs,脊髓MEPs和神經(jīng)元MEPs。目前主要監(jiān)測(cè)的對(duì)象為肌肉MEPs和脊髓MEPs。經(jīng)顱刺激產(chǎn)生的D波(直接波)可在脊髓上直接收集,被認(rèn)為是脊髓MEPs。在肌肉上收集的MEPs由D波(直接波)和I波(間接波)共同組成。D波起源于快傳導(dǎo)錐體束神經(jīng)元的近端軸索,I波起源在興奮性中間神經(jīng)元,是電刺激的間接作用結(jié)果。
Penfield and Boldrey等人早在1937年就發(fā)現(xiàn),直接對(duì)暴露的大腦運(yùn)動(dòng)皮層進(jìn)行頻率在50~60 Hz間的一串電刺激可以觸發(fā)面部肌肉及肢體的活動(dòng)。這一技術(shù)在過(guò)去被廣泛應(yīng)用于神經(jīng)外科手術(shù)中,因?yàn)樾枰_(kāi)顱刺激,并且應(yīng)用這種方法癲癇的發(fā)生率高達(dá)30%,這一方法沒(méi)有在脊髓的運(yùn)動(dòng)傳導(dǎo)束監(jiān)測(cè)中廣泛開(kāi)展[11]。1984年,Levy等[12]描述將一個(gè)面積為3 cm×5 cm的電極板置于運(yùn)動(dòng)區(qū)頭皮上作陽(yáng)極,硬顎為陰極,施加時(shí)程為50 μs~10 ms,頻率為5~25 Hz,強(qiáng)度為20~40 mA的雙相恒流脈沖電流,在麻醉狀態(tài)下可以誘發(fā)出動(dòng)作電位。
目前常見(jiàn)的刺激電極有三種類(lèi)型:①表面電極,通過(guò)火棉膠將腦電圖用地杯狀電極黏合在頭皮上;②腦電圖針樣電極;③形似拔塞螺鉆的針形電極(CSelectrode, NicoletBiomedical, Madison,WI),拔塞螺鉆針樣電極因?yàn)殡娮杩馆^低,是TES的理想選擇。但是嬰兒由于前囟未閉,有可能穿透前囟,所以對(duì)于嬰兒,推薦使用EEG杯形表面電極。
關(guān)于電極放置的位置存在爭(zhēng)議。對(duì)于經(jīng)顱電刺激的電極位置也存在爭(zhēng)議。Szelenyi等對(duì)TES電極位置對(duì)電位誘發(fā)的影響進(jìn)行了研究[13]。根據(jù)國(guó)際EEG10-20系統(tǒng),電極通常選擇的位置有六個(gè)(C1,C2,Cz[或Cz后方1 cm],C3,C4,和Cz前方6 cm)。合理的位置選擇和組合可以提高效率。例如,當(dāng)電極的組合為Cz(+)和Cz前6 cm點(diǎn)(-)時(shí),通??梢栽谛g(shù)中僅僅誘發(fā)下肢的活動(dòng),避免其他部位肌肉運(yùn)動(dòng)影響手術(shù)[14]。當(dāng)然也有學(xué)者選擇C3(C4)對(duì)Cz或者C3對(duì)應(yīng)C4的組合[15,16]。對(duì)于TES,正極電極是活動(dòng)電極,放置的位置決定特定部位肌肉的運(yùn)動(dòng)電位。Burke等學(xué)者傾向應(yīng)用C3(+)或C4(+)對(duì)應(yīng)Cz(-)來(lái)誘發(fā)上肢運(yùn)動(dòng)電位,Cz(+)對(duì)應(yīng)C3(-)或C4(-)來(lái)進(jìn)行下肢的刺激。這種選擇性的誘發(fā)只需要低強(qiáng)度的刺激就夠了。當(dāng)經(jīng)顱刺激達(dá)到一定強(qiáng)度時(shí),負(fù)極和正極同時(shí)都可以成為刺激電極,他們之間的電流便刺激大腦內(nèi)的皮質(zhì)脊髓通路活化了下行纖維[17]。Ubags等還提出應(yīng)用圓周樣結(jié)構(gòu)的陰極可以引起MEPs波幅的明顯升高[18]。
刺激參數(shù):①單脈沖技術(shù):20世紀(jì)80年代,Merton在清醒的患者顱骨上應(yīng)用單個(gè)電刺激獲得了運(yùn)動(dòng)電位[9],后來(lái)他對(duì)麻醉后的患者采用這種單脈沖電刺激,未能成功獲得MEPs,這可能是由于麻醉抑制了整個(gè)脊髓包括α運(yùn)動(dòng)神經(jīng)元池的活性,由大腦皮質(zhì)產(chǎn)生下行復(fù)合波的過(guò)程因此受到破壞。由于單個(gè)脈沖刺激技術(shù)僅僅在部分患者處于淺麻醉或全靜脈麻醉時(shí)可以引出MEPs,這一技術(shù)被逐漸棄用[19,20]。②多脈沖刺激技術(shù):在顱外應(yīng)用5~7個(gè)連續(xù)脈沖,α運(yùn)動(dòng)神經(jīng)元可以接受到多個(gè)下行傳導(dǎo)電位,獲得足夠的能量達(dá)到閾值,產(chǎn)生肌肉MEPs[20,21]。更進(jìn)一步的研究是,對(duì)于麻醉后的患者,頭皮應(yīng)用3個(gè)或以上的串刺激(連續(xù)脈沖刺激)才能誘發(fā)出I波[23]。推測(cè)多脈沖連續(xù)刺激提高M(jìn)EPs引出的作用機(jī)制有:波數(shù)量增加,全部激活的神經(jīng)元數(shù)量增加,臨時(shí)的募集效應(yīng),空間募集效應(yīng);產(chǎn)生了疊加效應(yīng),提高了引出率[18]。串刺激被推薦應(yīng)用于麻醉患者,可是關(guān)于串刺激的具體參數(shù)(串刺激個(gè)數(shù),單個(gè)刺激的時(shí)長(zhǎng),單個(gè)刺激間的間隔,串刺激間的重復(fù)頻率)也未達(dá)成統(tǒng)一。Bartley[24]、Novak[25]、Deletis[26]等分別對(duì)這些參數(shù)進(jìn)行相關(guān)研究,目前的研究認(rèn)為有效的刺激持續(xù)時(shí)間為0.5ms,因?yàn)檫@種較長(zhǎng)持續(xù)時(shí)間的刺激可以促進(jìn)這些連續(xù)的D波波幅恢復(fù)的更快;刺激間隔根據(jù)刺激強(qiáng)度而定,強(qiáng)度越強(qiáng),間隔越短;推薦的刺激間隔為4 ms。串刺激的重復(fù)率是一個(gè)很重要的變量,目前的發(fā)現(xiàn)是重復(fù)率越高,MEP波幅越大。大多數(shù)MEP相關(guān)研究采用的脈沖誘發(fā)電壓儀器均為恒壓刺激儀[15,16,19]。
MEPs信號(hào)的接收:通過(guò)放置在被監(jiān)測(cè)脊髓節(jié)段遠(yuǎn)端的脊髓硬膜上或硬膜下的針樣電極可以取得D波,肌肉MEPs則可以通過(guò)將腦電圖針樣電極埋入相應(yīng)的肌肉進(jìn)行采集。拇短展肌和第一跖骨肌可以做為采集上肢信號(hào)的靶肌肉[27],對(duì)于下肢有人采用拇展?。?8],也有人應(yīng)用脛前肌。但是,增加肌肉監(jiān)測(cè)的數(shù)量并不能帶來(lái)更多的益處。
理論上在脊硬膜外或硬膜下可以收集D波和I波,單一D波反映皮質(zhì)脊髓束快傳導(dǎo)纖維的同步化活動(dòng),是皮質(zhì)錐體細(xì)胞軸突的近端部分的直接受到刺激的結(jié)果,其波幅反映了每一個(gè)纖維傳導(dǎo)沖動(dòng)的幅度、傳導(dǎo)纖維的數(shù)量以及它們放電的同步化程度[6],I波部分反映了皮質(zhì)脊髓束的神經(jīng)元總體的反應(yīng)程度,常容易受到抑制,不易測(cè)出。D波的正常波動(dòng)范圍通常在10%之內(nèi)[29]。D波變化超過(guò)20%的曾被認(rèn)為是一個(gè)警示[30]。近年的研究認(rèn)為,在脊柱脊髓手術(shù)中,D波降幅超過(guò)50%有意義[31]。D波在應(yīng)用上也有其局限性,由于D波極端的非同步性,可能在手術(shù)一開(kāi)始無(wú)法獲取;術(shù)前癱瘓的患者,無(wú)法在癱瘓節(jié)段以遠(yuǎn)處收集到D波;D波不適合用于T10-11尾端,因?yàn)檫@一區(qū)域皮質(zhì)脊髓束(corticalspinal tract,CT)快軸突數(shù)量不足,無(wú)法產(chǎn)生足夠大的D波波幅達(dá)到監(jiān)測(cè)目的;收集D波需要暴露硬膜,對(duì)于部分脊柱矯形手術(shù),增加了風(fēng)險(xiǎn)。Tamaki等[32]術(shù)前在硬膜下放置細(xì)針樣電極,根據(jù)他們的報(bào)道,并無(wú)感染或是出血等并發(fā)癥;當(dāng)然如果遇到脊髓腔內(nèi)內(nèi)的粘連,收集電極放置難度則更大。此外,近期的一項(xiàng)研究認(rèn)為,D波監(jiān)測(cè)應(yīng)用在脊柱矯形手術(shù)中假陽(yáng)性率和假陰性率均很高。研究中發(fā)現(xiàn)93例患者中4例D波下降,21例D波上升,然而,MEPs和SEPs并未出現(xiàn)并行的改變。因此,研究者認(rèn)為,應(yīng)用D波雙極記錄作為評(píng)價(jià)CT功能完整性的手段值得商榷[33]。
肌肉MEP信號(hào)又稱復(fù)合MEPs(compound MEP,CMEPs),在靶肌肉上收集。CMEPs較D波成分復(fù)雜,D波盡管反映了皮質(zhì)脊髓束的功能,但不能監(jiān)測(cè)脊髓前角灰質(zhì)的信號(hào)傳播,因此有學(xué)者認(rèn)為,肌源性記錄可以較好的預(yù)測(cè)脊髓損傷[15]。CMEPs作為一種復(fù)合波,波形的改變一度被認(rèn)為是術(shù)中脊髓情況變化的一項(xiàng)指標(biāo),2005年Quinones-Hinojosa等[34]的研究報(bào)道,參與研究的8名患者,術(shù)中波形由多重波變?yōu)殡p重波,但是術(shù)后肌力均為正常。這一研究支持了很多之前的推測(cè)[35,36]。目前CMEPs的監(jiān)測(cè)指標(biāo)是其波幅的變化、潛伏期或僅僅是有或無(wú)。CMEPs因?yàn)椴僮鬏^為簡(jiǎn)單,廣泛開(kāi)展。但是單純的CMEPs也不能完全反應(yīng)脊髓的運(yùn)動(dòng)情況。在 Deletis[37]和 Sala[40]的研究中,在近 100例的髓內(nèi)手術(shù)患者,術(shù)畢D波降至50%,CMEPs完全喪失時(shí),也僅僅出現(xiàn)一過(guò)性的癱瘓。有學(xué)者認(rèn)為手術(shù)過(guò)程中,CMEPs的下降可能緣于誘發(fā)電閾值的提高。尤其在進(jìn)行髓內(nèi)手術(shù)時(shí),精細(xì)操作,如果不損傷皮質(zhì)脊髓束(CT)的快速軸突則不會(huì)導(dǎo)致D波的明顯喪失。術(shù)后D波保留,至少是原波幅的50%是CT快運(yùn)動(dòng)神經(jīng)元未損害的保證,關(guān)系到患者自主運(yùn)動(dòng)是否保留[38]。患者在脊柱手術(shù)中D波喪失,可能預(yù)示永久性癱瘓[39]。
在臨床應(yīng)用中常常需要將兩種記錄方式聯(lián)合起來(lái)。沒(méi)有或無(wú)法D波監(jiān)測(cè),需要極為小心的進(jìn)行MEP監(jiān)測(cè),50%以上的降幅就需要報(bào)警。
手術(shù)中對(duì)脊髓的物理或化學(xué)損傷是影響術(shù)中運(yùn)動(dòng)誘發(fā)電位變化的根本原因,這些損傷可以具體表現(xiàn)為對(duì)脊髓的牽拉、觸碰、扭轉(zhuǎn)或是對(duì)脊髓血供的影響,這種損傷可以是一過(guò)性的,也可能是毀滅性的。
手術(shù)終止不是運(yùn)動(dòng)誘發(fā)電位在術(shù)中發(fā)生變化后唯一的選擇,除了懷疑脊髓已經(jīng)發(fā)生不可逆的損傷,還可以做很多調(diào)整的措施。很多研究報(bào)道,暫時(shí)停止手術(shù)一段時(shí)間MEP信號(hào)可能恢復(fù),局部組織短暫缺氧后耐受可能是原因之一[40]。用溫水沖洗手術(shù)區(qū)域也可以促進(jìn)信號(hào)的恢復(fù),低體溫和由于局部細(xì)胞膜創(chuàng)傷引起K+離子堆積都可能是對(duì)這一現(xiàn)象的原因[41,42]。Seyal、Sloan 等均報(bào)道低血壓和MEP信號(hào)降低有相關(guān)性,使用少量的血管升壓藥可以促進(jìn)MEP信號(hào)的恢復(fù),這一現(xiàn)象也許和脊髓局部的灌注相關(guān)[43,44]。
關(guān)于TES運(yùn)動(dòng)誘發(fā)電位的安全性,報(bào)道過(guò)的副反應(yīng)主要有唇舌咬傷、下頜骨骨折、癲癇、心律失常、頭皮燒傷。所以術(shù)前通常需要在舌、唇間放上墊片保護(hù)。
是否可以對(duì)曾經(jīng)出現(xiàn)過(guò)癲癇的患者應(yīng)用TES技術(shù)目前還在爭(zhēng)論。需要根據(jù)利弊權(quán)衡,因人而異[45]。目前相關(guān)的研究提示,至少對(duì)于神經(jīng)外科的幕上手術(shù),術(shù)前有無(wú)癲癇的患者采用TES后癲癇發(fā)生率無(wú)差異。
TES相對(duì)禁忌包括癲癇、顱骨缺損、顱內(nèi)壓升高、心臟病、體內(nèi)有起搏器或者其他生物內(nèi)植入物[46]。之前認(rèn)為,當(dāng)患者有嚴(yán)重運(yùn)動(dòng)神經(jīng)系統(tǒng)病變時(shí),不適合采用肌肉MEPs,因?yàn)檫@類(lèi)肌肉MEPS可能無(wú)法誘發(fā)。DiCindio等[47]報(bào)道,甚至當(dāng)出現(xiàn)腦癱時(shí),肌肉MEPs可以引出。
經(jīng)顱磁刺激(transcranial magnetic stimulation,TMS),是通過(guò)時(shí)變磁場(chǎng)作用于大腦皮質(zhì)產(chǎn)生感應(yīng)電流改變皮質(zhì)神經(jīng)細(xì)胞的動(dòng)作電位,從而影響腦代謝和神經(jīng)電活動(dòng)。TMS刺激皮質(zhì)運(yùn)動(dòng)區(qū)或傳出通路,在刺激點(diǎn)遠(yuǎn)端的傳出途徑或靶肌肉可以記錄到動(dòng)作誘發(fā)電位[48]。TMS刺激脈沖電流有單相、雙相及減弱的正弦波脈沖3種。磁刺激通過(guò)感應(yīng)電流作用于大腦皮層運(yùn)動(dòng)區(qū),通過(guò)突觸間的連接間接興奮白質(zhì)內(nèi)的皮質(zhì)脊髓神經(jīng)元軸索,引起I波下傳[49,50]。
因?yàn)槎ㄎ痪€圈所產(chǎn)生的電流方向與錐體細(xì)胞起源部分不相垂直,TMS硬脊膜外記錄的MEP以I波主導(dǎo),TMS不太適合記錄D波。同時(shí)I波的差異及I波對(duì)揮發(fā)性麻醉藥物的高度敏感使TMS不適合用于術(shù)中監(jiān)測(cè)。
但是由于TMS無(wú)痛、無(wú)創(chuàng)方面的優(yōu)勢(shì),仍然有學(xué)者致力于將TMS應(yīng)用于脊柱手術(shù)的術(shù)中監(jiān)測(cè)中。2010年謝紅雯等使用依托咪酯+芬太尼技術(shù)麻醉的26例患者,MEP均記錄良好,成功記錄MEP的患者中有6例(23%)因?yàn)樾g(shù)中MEP波幅下降超過(guò)50%而向術(shù)者發(fā)出報(bào)警[51]。
TES與TMS相比較,儀器體積小、價(jià)格便宜,由于刺激通過(guò)固定在頭皮上的電極來(lái)施行,可以產(chǎn)生穩(wěn)定的刺激。TCE-MEPs對(duì)麻醉藥不敏感,在術(shù)中監(jiān)測(cè)時(shí)反應(yīng)波波幅大、潛伏期短、引出率高、重復(fù)性好、參量變異小,更適合應(yīng)用在手術(shù)中對(duì)運(yùn)動(dòng)通路系統(tǒng)進(jìn)行監(jiān)測(cè)。
通過(guò)頭皮或脊髓獲取SEP是用來(lái)監(jiān)測(cè)脊髓背側(cè)柱功能的經(jīng)典方法。在MEP前,SEPs是術(shù)中脊髓監(jiān)護(hù)的常規(guī)手段。對(duì)于彌漫的脊髓損傷,SEPs監(jiān)護(hù)可以間接提示脊髓外側(cè)束的損害。以脊柱矯形為例,由于矯形中對(duì)神經(jīng)和血管的牽拉,可能同時(shí)影響運(yùn)動(dòng)和感覺(jué)通路。Nuwer等的大宗報(bào)告發(fā)現(xiàn)僅有0.063%患者在保留術(shù)后SEPs情況下出現(xiàn)了永久的脊髓損害(假陰性),假陽(yáng)性率為0.983%。這提示,SEPs對(duì)監(jiān)測(cè)患者脊髓的運(yùn)動(dòng)傳導(dǎo)通路也是有價(jià)值的。但是不足以監(jiān)測(cè)所有脊髓長(zhǎng)傳導(dǎo)通路[52]。
H反射是路經(jīng)單一突觸的脊椎反射,涉及一個(gè)傳入感覺(jué)神經(jīng)和一個(gè)傳出α運(yùn)動(dòng)神經(jīng)元。通過(guò)記錄H反射弧波幅可以間接了解運(yùn)動(dòng)傳導(dǎo)通路。在動(dòng)物試驗(yàn)中已經(jīng)發(fā)現(xiàn)脊髓的急性橫斷或冷卻,會(huì)導(dǎo)致α運(yùn)動(dòng)神經(jīng)元超極化[53]。當(dāng)運(yùn)動(dòng)通路損傷后,超極化的運(yùn)動(dòng)神經(jīng)元會(huì)導(dǎo)致反射振幅明顯下降。
在一項(xiàng)31例患者的研究中發(fā)現(xiàn),當(dāng)麻醉?xiàng)l件為70%的NO,和1.37%的異氟烷,通過(guò)在膝后脛神經(jīng)上進(jìn)行刺激可以在比目魚(yú)肌上獲得H反射波。研究中發(fā)現(xiàn)4例患者在術(shù)中出現(xiàn)波幅中度或一過(guò)性下降,沒(méi)有出現(xiàn)術(shù)后神經(jīng)系統(tǒng)損害,2例患者在整個(gè)手術(shù)過(guò)程中H反射波幅下降超過(guò)90%,術(shù)后患者出現(xiàn)癱瘓[53]。相反,在另一項(xiàng)更大樣本量的研究中(n=129),3.9%的患者術(shù)后出現(xiàn)運(yùn)動(dòng)功能損傷,術(shù)中H反射波卻無(wú)改變。因?yàn)镠波反映的是節(jié)段脊髓反射弧上的結(jié)構(gòu)完整性,通過(guò)監(jiān)測(cè)H反射波來(lái)預(yù)測(cè)運(yùn)動(dòng)傳導(dǎo)束損害的可靠性值得懷疑[54]。
利用MEP進(jìn)行術(shù)中脊髓功能區(qū)識(shí)別、繪圖在近年已經(jīng)被報(bào)道、應(yīng)用。神經(jīng)外科手術(shù)應(yīng)用較多,通過(guò)在脊髓中對(duì)脊髓皮質(zhì)脊髓束的識(shí)別、定位可以避開(kāi)皮質(zhì)脊髓束進(jìn)行脊髓內(nèi)腫瘤的切除[55]。也有研究者應(yīng)用自由肌電圖在脊髓內(nèi)腫瘤手術(shù)中監(jiān)測(cè)皮質(zhì)脊髓束的傳導(dǎo)功能,但是由于病例數(shù)太少,這一應(yīng)用還有待進(jìn)一步研究[56]。
總之,術(shù)中運(yùn)動(dòng)傳導(dǎo)束的電生理監(jiān)測(cè)應(yīng)用已有20余年,可以提示患者目前的脊髓運(yùn)動(dòng)功能情況,影響手術(shù)的進(jìn)程,預(yù)測(cè)術(shù)后效果,在脊柱脊髓手術(shù)中已經(jīng)成為外科醫(yī)生的重要輔助工具。
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