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1、圍術(shù)期自體輸血首都醫(yī)科大學(xué)北京友誼醫(yī)院麻醉科 田 鳴2009.9.8 北京輸血存在的兩大問題血源性傳染病和輸血反應(yīng) 我國乙肝病毒(HBV)感染人數(shù)達(dá)1.1億,占總?cè)丝?%;90%丙肝由輸血傳播,輸血后丙肝發(fā)病率高達(dá)10%-20%,特殊人群中丙肝病毒(HCV)攜帶者達(dá)70%;我國HIV感染者已超過84萬,實(shí)際數(shù)?血源不足與濫用 我國年用血量超過1300噸,其中外科用血約占70%,臨床不必要的輸血占50%。輸血原則安全、有效、節(jié)約圍術(shù)期輸血Perioperative Transfusion MedicineNon-Transfusion MethodsHemostasis (Surgical /
2、Medicine)Transfusion TriggerIndications for Blood TransfusionAutotransfusionPreoperative Autologous Donation (PAD)Acute Normovolemic Hemodilution (ANH) Intraoperative Autologous DonationRed Cell Salvage (CS)Minimize Allogeneic Transfusion過去二十年臨床輸血的改變Changes in red blood cell transfusion practice dur
3、ing the past two decadesA retrospective analysis, with the Mayo database, of adult patients undergoing major spine surgery1980 to 1985 early practice group; n = 6991995 to 2000 late practice group; n = 610Compared to the early practice group:所有術(shù)前的 Hb 濃度顯著降低異體 RBC 輸入顯著減少,而自體輸血明顯增加no significant diffe
4、rence in major morbidity or mortality was observed between groupsWass CT, Transfusion. 2007;47(6):1022 USA無血外科的概念1. 不輸血2. 自體輸血3. 成分輸血(異體)術(shù)前準(zhǔn)備、手術(shù)技術(shù)麻醉、輸血科管理醫(yī)院多處室協(xié)調(diào)目的:減少異體輸血掌握輸血指征Transfusion Trigger:必須開始輸血的時(shí)機(jī):Hb/Hct 和 綜合判斷10/30 rules: Hb10g/dl;Hct30 % 一般情況下,達(dá)到了這個(gè)標(biāo)準(zhǔn)就不必繼續(xù)輸血出手術(shù)室、出院時(shí)Overtransfusion: 在任何時(shí)候當(dāng)
5、輸血使得 Hct36% 時(shí),就認(rèn)為是過度輸血失血后不輸血的手術(shù)死亡率 術(shù)前Hb水平 死亡率(%)Carson 1988 Hb Transfusion Trigger US 6g/dl:50歲,無心臟病和術(shù)后并發(fā)癥 8g/dl:穩(wěn)定性的心臟病,失血300ml10g/dl:老年人,術(shù)后有并發(fā)癥,心肺代償差Robertie:Int Anesthesiol Clin 28:197-204,199011g/dl(Hct33):重危病人,強(qiáng)調(diào)維持適當(dāng)?shù)难萘勘容斞匾狢zer and Shoemaker:Optimal hematocrit value in critically ill postope
6、rative patients. Surg Gynecol Obstet 147: 363-368,1978衛(wèi)生部輸 血 指 南(2000年) Hb 100g/L 不必輸血 Hb Risk治療應(yīng)當(dāng)執(zhí)行Benefit Risk治療有理由執(zhí)行需要補(bǔ)充特定的研究Benefit Risk治療沒有理由不執(zhí)行需要補(bǔ)充廣泛的研究Risk Benefit治療不應(yīng)當(dāng)執(zhí)行因?yàn)闊o益或有害Level A 多個(gè) (3-5)人群的風(fēng)險(xiǎn)評估;一致的認(rèn)識(shí)方向和明顯的療效。Recommendation that procedure or treatment is useful/effective Sufficient evid
7、ence from multiple randomized trials or meta-analyses Recommendation in favor of treatment or procedure being useful/effective Some conflicting evidence from multiple randomized trials or meta-analyses Recommendations usefulness/efficacy less well established Greater conflicting evidence from multip
8、le randomized trials or meta-analyses Recommendation that procedure or treatment not useful/effective and may be harmful Sufficient evidence from multiple randomized trials or meta-analyses Level B 有限 (2-3)人群的風(fēng)險(xiǎn)評估Recommendation that procedure or treatment is useful/effectiveLimited evidence from sin
9、gle randomized trial or non-randomized studies Recommendation in favor of treatment or procedure being useful/effectiveSome conflicting evidence from single randomized trial or non-randomized studies Recommendations usefulness/efficacy less well established Greater conflicting evidence from single r
10、andomized trial or non-randomized studies Recommendation that procedure or treatment not useful/effective and may be harmfulLimited evidence from single randomized trial or non-randomized studies Level C 極有限 (1-2)人群的風(fēng)險(xiǎn)評估Recommendation that procedure or treatment is useful/effectiveOnly expert opinio
11、n, case studies, or standard-of-care Recommendation in favor of treatment or procedure being useful/effectiveOnly diverging expert opinion, case studies, or standard-of-care Recommendations usefulness/efficacy less well established Only diverging expert opinion, case studies, or standard-of-care Rec
12、ommendation that procedure or treatment not useful/effective and may be harmful Only expert opinion, case studies, or standard-of-care Classification Scheme Used to Summarize of Clinical RecommendationsTransfusion TriggersClass IIaWith Hb 6 g/dL, RBC transfusion is reasonable, as this can be lifesav
13、ing. Transfusion is reasonable in most postoperative patients whose Hb=10 g/dL, but more evidence to support this recommendation is required. (Level of evidence C)Class IIITransfusion is unlikely to improve oxygen transport when Hb10 g/dL and is not recommended. (Level of evidence C)綜合判斷輸血指征綜合分析,因人而
14、異貧血持續(xù)的時(shí)間,血管內(nèi)的容積手術(shù)的范圍,大出血的可能性存在的合并癥:如肺功能障礙,心輸出量下降,心肌缺血,腦血管或外周循環(huán)疾病。綜合判斷:術(shù)中通過對術(shù)野的觀察結(jié)合血標(biāo)本的結(jié)果,對心肺功能的監(jiān)測綜合判斷出每一病人所能接受的最低Hb值。Consensus Conference: Red Blood Cell Transfusion. JAMA, 1998, 260: 2700-2703取庫血前是否測 Hb/Hct ?原則上應(yīng)當(dāng)測得 Hb/Hct 后再?zèng)Q定是否輸血(取血)大多數(shù)( 90%),常規(guī)都要執(zhí)行但不絕對,結(jié)合臨床(90%)在輸血中或隨后評估效果及進(jìn)一步的需要量減少誤判,節(jié)約血源和病人負(fù)擔(dān)某
15、些例外是可能的 (20%措施:提高自體血應(yīng)用量降低庫血的應(yīng)用量圍術(shù)期自體輸血的種類儲(chǔ)存式 術(shù)前自體獻(xiàn)血( Preoperative Autologous Donation PAD)急性等容稀釋(Acute Normovolemic Hemodilution ANH) (Intraoperative Autologous Donation)急性高容稀釋(Acute Hypervolemic Hemodilution AHH)回收式(Blood Salvage BS)術(shù)中對自體血回收及回輸術(shù)后對自體血回收及回輸應(yīng)當(dāng)首選自體血避免血源傳播性疾病避免輸血的免疫反應(yīng)降低對庫血的需要量已備好或及時(shí)回收自體
16、血,有利于挽救血液質(zhì)量高功能好術(shù)前自體獻(xiàn)血Preoperative Autologous Donation PAD擇期手術(shù)患者一般情況較好,Hb大于110g/L預(yù)計(jì)術(shù)中出血量超過循環(huán)血量15%稀有血型、配血困難;宗教信仰無心、肺、腎功能障礙無造血功能、凝血功能障礙無菌血癥術(shù)前需多次采血,給病人帶來不便可降低患者術(shù)前 Hb程序復(fù)雜,需要血庫儲(chǔ)存有成分的損耗(凝血因子等)血液保存時(shí)間有限,無法交互使用過期浪費(fèi)的可能(50%),增加了費(fèi)用采血和保存期有細(xì)菌污染的可能PAD 缺點(diǎn) 不常用急性等容稀釋 (acute normovolemic hemodilution ANH)ANH常用是有效和最經(jīng)濟(jì)的自
17、體輸血方法可以直接采集全血,也可通過專用設(shè)備單采紅細(xì)胞采血的同時(shí)等量輸入非細(xì)胞溶液(膠體或晶體液)室溫保存,在手術(shù)室內(nèi)輸入Monk TG, Goodnough LT: Acute normovolemic hemodilution. Clin Orthop, 1998, 357:74-81血液稀釋技術(shù)血液黏度的降低外周血管阻力的下降心輸出量增加微循環(huán)改善組織氧攝取量的增加血紅蛋白-氧親和力降低血液稀釋代償血氧含量降低維持組織氧供病理生理學(xué)效應(yīng) 血液稀釋技術(shù)Gross 公式計(jì)算邊采血邊輸液病人的采血量術(shù)前采血量(L) (采血前Hct -目標(biāo)Hct) (采血前Hct+目標(biāo)Hct)Gross JB:
18、 Estimating allowable blood loss: Corrected for dilution. Anesthesiology, 1983, 56: 577-580VL= EBV(HctO-HctF)/Hctave= 7體重(kg)2ANH 的方法麻醉后手術(shù)前采集自身血同時(shí)輸入等量膠體液或3倍晶體液或不同比例的晶膠混合液稀釋過程中保持血容量基本恒定術(shù)中血液有形成分丟失減少術(shù)終再將自體血反順序回輸Prospective RCT of ANH in major gastrointestinal surgeryAim : to assess the effects of ANH o
19、n allogeneic transfusion3unit-ANH n=78, no ANH n=82fewer patients in the ANH group experienced oliguria in the immediate postoperative period37/78 (47%) vs 55/82 (67%) (P=0.012).ANH 并不改變異體輸血率術(shù)前 Hb 水平、術(shù)中失血量和輸血規(guī)程是影響異體輸血的關(guān)鍵因素compared with ASA-matched historical controls , the introduction of a transfus
20、ion protocol reduced the transfusion rate in colorectal patients from 136/333 (41%) to 37/138 (27%), P=0.004. Sanders G, Br J Anaesth. 2004;93(6):775 UK根據(jù)Hct變化程度,分為:輕度血液稀釋:Hct30%中度血液稀釋:Hct2029%血液稀釋(hemodilution) 降低Hct、減少紅細(xì)胞丟失中度血液稀釋ASA推薦 Weiskopf , Transfusion 1995血液稀釋擴(kuò)展到Hct20%或更低的程度能顯著提高對手術(shù)失血的耐受性可應(yīng)對
21、相當(dāng)大的手術(shù)失血量(4500ml)減少對異體輸血的需要有經(jīng)驗(yàn)的醫(yī)師在“必需時(shí)”應(yīng)用中度血液稀釋ASA推薦 Weiskopf , Transfusion 1995方法為:1血液稀釋在手術(shù)失血前完成;2.在達(dá)到目標(biāo)Hct時(shí)開始回輸采出的血液,而且回輸?shù)乃俣扰c手術(shù)失血等同以維持目標(biāo)Hct;3.在自體血輸完后再開始輸異體血;4.維持正常的血容量。 ANH的適應(yīng)證預(yù)計(jì)手術(shù)出血量5002000ml的患者合并有紅細(xì)胞增多癥的手術(shù)患者因宗教信仰不接受異體血液輸入者血型罕見,術(shù)中需要輸血者等血源緊張時(shí),需要手術(shù)者ANH的禁忌證麻醉前評估為ASA 級(jí)及以上者嚴(yán)重貧血或凝血功能障礙的患者接受大面積植皮或體表整形手術(shù)
22、的患者因急性血液稀釋可使手術(shù)創(chuàng)面的滲出量明顯增加心功能不全或心臟內(nèi)、外動(dòng)靜脈分流者有凝血病的病人術(shù)中沒有大出血可能的病人血管條件差,采血困難者輸血的時(shí)機(jī)盡可能在手術(shù)出血基本控制后輸血大出血的當(dāng)時(shí)快速補(bǔ)充血容量在全麻下允許短暫的Hct降低但要避免低血容量維持組織灌注大出血的當(dāng)時(shí)輸血增加了失血量加重了凝血障礙不可機(jī)械刻板,應(yīng)酌情靈活處理術(shù)中自體血回收 CS可回收手術(shù)野失血量的 50-70%生理鹽水洗滌的壓積紅細(xì)胞( Hct 40-65% )洗除了90%以上的血漿成分、血小板、細(xì)胞碎屑、游離Hb和活性物質(zhì)(激活的凝血物質(zhì)、血小板、補(bǔ)體,以及FDPs等)Cell Washing洗滌紅細(xì)胞的優(yōu)點(diǎn)能迅速、
23、及時(shí)地?fù)尵炔∪思t細(xì)胞質(zhì)量高,2-3DPG,滲透脆性指數(shù)副作用小,(高鉀、酸中毒、游離Hb及活性物質(zhì)等)降低凈失血量Saved red cell is a lucky cell!紅細(xì)胞回收和其他降低圍術(shù)期異體輸血方法的效-價(jià)比Cost-effectiveness of CS and alternative methods of minimising perioperative allogeneic blood transfusionElectronic databases 1996-2004 for systematic reviews and 1994-2004 for economic ev
24、idence. Overall 668 studies Existing systematic reviews were updated with data from selected RCTs that involved adults scheduled for elective non-urgent surgeryCONCLUSIONS:The available evidence indicates that cell salvage may be a cost-effective method to reduce exposure to allogeneic blood transfu
25、sion. However, ANH may be more cost-effective than cell salvage.Davies L, Health Technol Assess. 2006 Nov;10(44):iii-iv, ix-x, 1-210, UK心血管外科的 CS心血管外科失血特點(diǎn)肝素化,創(chuàng)傷面積大,體外循環(huán) “機(jī)械損傷、血液與空氣的接觸、以及血液與合成材料的接觸,可導(dǎo)致溶血、血小板和白細(xì)胞功能喪失、補(bǔ)體激活、凝血功能紊亂以及炎癥反應(yīng)等”心臟手術(shù)的術(shù)野污染最小,紅細(xì)胞回收率高,是最適合開展血液回收的手術(shù)類型。自體血回收的作用節(jié)約用血避免紅細(xì)胞碎片及游離血紅蛋白造成的損
26、害減少魚精蛋白用量RED CELL AND PLATELET SAVINGClass IRoutine use of red cell saving is helpful for blood conservation in cardiac operations using CPB, except in patients with infection or malignancy. (Level of evidence A)Class IIIRoutine use of intraoperative platelet or plasmapheresis is not recommended for
27、 blood conservation during cardiac operations using CPB. (Level of evidence A)骨科手術(shù)的 CS骨科失血的特點(diǎn)骨科手術(shù)常從組織表面收集出血,失血是間斷性吸出,血液和空氣的結(jié)觸較多,紅細(xì)胞的損傷比較嚴(yán)重,因此紅細(xì)胞的回收率相對較低血液中含有許多碎屑:骨、脂肪、和骨水泥碎片解決方法手控洗滌程序,降低泵轉(zhuǎn)速自動(dòng)慢速,大量生理鹽水反復(fù)洗滌新型持續(xù)清洗系統(tǒng)CATS清洗后血液輸血袋內(nèi)靜置1020min在回輸前通過40m的濾器血液回收的缺點(diǎn)溶血影響RBC回收率凝血障礙稀釋丟失丟失蛋白不可避免血液污染外傷后瀕臨死亡的大出血腫瘤細(xì)胞的播
28、撒當(dāng)回收的濃縮紅細(xì)胞量小于2000ml時(shí) 僅補(bǔ)充血漿代用品當(dāng)回收的濃縮紅細(xì)胞量大于2000ml時(shí) 超過2000ml的部分補(bǔ)以等量新鮮冰凍血漿當(dāng)回收的濃縮紅細(xì)胞量大于3000ml時(shí),或血小板計(jì)數(shù)低于50109/L時(shí)補(bǔ)充適量的血小板大量輸入回收血液時(shí)北京市術(shù)中血液回收利用質(zhì)量管理及考核標(biāo)準(zhǔn)(試行 2009)術(shù)中血液回收利用適應(yīng)證與禁忌證 人員與設(shè)備要求術(shù)中血液回收相關(guān)要求信息上報(bào)術(shù)中血液回收利用的考核指標(biāo)低血容量治療的一般程序1. 首先目標(biāo):循環(huán)容量的維持2. 第二目標(biāo):保持血氧攜帶能力3. 第三目標(biāo):恢復(fù)正常凝血狀態(tài)和內(nèi)環(huán)境穩(wěn)定*97年美國麻醉年會(huì)(ASA)推薦小 結(jié)盡可能不輸異體血、提高術(shù)前H
29、b水平掌握輸血指征:紅細(xì)胞: DO2 、Hb或Hct、和心肺功能術(shù)前 Hb 水平、術(shù)中失血量和輸血規(guī)程是影響異體輸血的關(guān)鍵因素最好的血液是:自體血、應(yīng)鼓勵(lì)應(yīng)用不傳染、無抗原,新鮮、立即發(fā)揮生 理作用,恢復(fù)快。術(shù)中輸血:掌握輸血指征,首選自體血,盡量減 少異體輸血The EndEGRd3xFBvxSvJBeYEAWJ7oARc*d3MdRyB17&ImblZ-Wzb*+vu6F1EnyaxFIQ3Q!MgNe!$qwj)NDQoBuc%V*AHt2JnjHw)kD!vpTXLsei*aQFCwfLM6UIv9CB(MFzkX-HDMZ(WmlKeXsSUnhtM$*M*#&ZU!i4wCxruQ
30、wOJs8&-uq-qP8RPjdnDQQsHe42-TjnVDwq9JUhtspuRwMFj%KG$Ob4&PnGrD-A1pq(*d%BkmUVB6JlfCrDe%B%&ujoyDuEB7wO+xiAoB5H-4PVbNfIR0XnK*n()UV!M73pH-t1)qraL+b1vksLEvGbj6Q7qs18DcK3MMbmgryr(2AfwM3S$Jo0Lcse4CZaEgaCh95&)Q0*LauAgxtEIP+GV9QwbUCPx*e!wQID%6g-yHeaf0!-15z9#(xmJ$fL5cgQWXbzM%tyhI3qusiV91K35%1&SVPk9L(97O+Mu%jWky
31、i3E%eR1HjIMDnJxWWY8mdDsFncB$HN%sz%y7V&cJ5V(NI8+OlZ$wTRTT2UK!bI9IFvEvhwzk0a8gce&d!Iwdiv09C*8SJFX4h6&DM#ScWnut*JvoLNW5(s5S$Y9aI7!wd-gGNG5xh1o-*p&1ZNQC78LrSRJA*KDVP*lbeVW)xx-RJxRQPPD1z7-U6$8HuyuY3eE4CoNk*4Qrj5!3Zkd*YtqU0%rlmZgov2Rt(l-gQt7X&XnUJ+gSGzxZX+Ey&xM3mMI!OtD1clJL42I6tIJCsFcvlr(UylLU5q&K2vOF+li7
32、Lgd&cDTlZAK+iuPoaK2t2qu5e8PnAW+V-t2tjMPpU$pAllz7IHhF(&ZA4gWyLXYqjhYCtq!#a95k!5*XMpcCEk)wz)hMoz$k1(Xrvw)4A6i5nE1(is!)WW&17Ph1jtEFgVs)c)MWwC8OTAhu43kP0mqT+L2)7LseG+7GuK)VZmBKiCxHJ$FykC7&-(dpE4zMJY*Pt95w71fHX&u5Jk2k(&ie-lQyb5JIGNuA$ovA7+Ryt#hw7n!PEwEa&zntop!Y2cNHDGHhDM+MCAZPIg50#FEVs#hel1+kL&RaGArHbUW$
33、ya)7J9QbTWwzKeR2sWU2A04*ky-T2rBEpyrjqiKGb0TzuevjLeRoiH-oZrMDXKo0ObVXr%(*OpvbLu)mo!Iu8YP$)SX2h9o)a1QukgVXdRo#lq(cc65jVV5Ou8KYGSdRlOWAJ3IfN!Sz$9mH80ty9ozu18Gl7ZvNyL8NgJQr1LaIf7rgR72H*!m413BVvFo$6F#Xmdd(RO)UyxGOW8Z9oBQWYsziJ7zK3T9k7)JDOyu+BJG1uM36#*0*b)FmaROnTjTxGg*YMT5QFOhSi&*t)a4UUGBQW2g9aE5%!h+-7lZg
34、%-G!tepDW!cdMCth!ho02P+3aiBpFM9OTgs4ruTqBa*0uZy#ZHUPImiT(te+v3Y&2muC#9+w5vS8D61!hqc08x+EKt0qBL9#r#tDmUeyeBtUDlE&1LVJW*%N01AvTJr*wf7pviGVK#QaAq1rcoY8F-fFMVs-(Zpw0Fje2P3m(iz-rd8P)#)GV#l$ln*V&KpoVfKaJEwZ#x6)(I5LYxp1qLe1Q9XD!*pcE7w+GC45FajDtYcy0AZ-i549qvB24($Prko257s9h+O-*BZwXq-s0uzdwNQ0S7mopeNE1dki8NZ-
35、3(WUz!S)rYg4i(jrs1Sb5s)JkS*VLhN9QH$SlN4Ckt5tELZj4pl1MsmFnNWY$mSRaVGq+nj*mCR5MUg0)(Y+Q)ZDjFLsJhsxFF(ZbT6vBPyLrTcS)RB)i*F(D5ddhkBmewE1*geW*K#usT3TWQWR5Hjh8yBeXuGDaHW7C5LIrDoYDfM5ebH3ARC-StWJuibnC6D%dE#etGEnyw*a9aII$KGC3v3iVGrm5yUdr*NVKS3P0EJc3vqiOAb4ZY$OtCAhkN#UrtC4ZQ&fHJWq5Sc!7JzIF-zspz7J7Uh#ZekvTpmj
36、XCTxn*2)DkLn)L3YfyLF6e)+eZ*2KaXNJ$Sa2-UPUB2mTFGW$gDl5W0ggFwCg0Qf2agDz7$z*UEm5zlLx$Krh9HCVgRqgxk!NEpAjBs3HeAsXLR*8a#b!FvkjCeun5TGK64O9A)KNgt6glcQVi-VGf)7WiE!nrgB7Z!gXXp$#$Y(HTGjRaak%alsxbGyyibwPdeL7fa&u)s*+stKd3hX6zW-WB2+viVL4U0dPv#9Wn2%IOyZskEp4BXH+2Jkh&5VgG#9tgBOY#CLWUE$HGG!SC0Lf9aOoy$m(7GQ(796iFvw
37、UHt*ul*I5R(GVw8BqfwLkz%h5$F91-HfktSC0Q0K&FD6&x-kjp%3-2ZH%W-TA!Jcs35eS4f*+WsyJeO*HagqWCu%mlc!&8t!$%s*5!3TvleoMa)bHnYCDxrE#adp)a2U-7)tmB%9WR4$sO*iVN68&KtrMvW*(0fQNgzJS2FD5a53$yNpa)QGM8rUs6UpjLT+nIT)IGHR!J&Lzy#OLE*SGiEYJ)X7V*hMV43J)he2owz3szEQcabmuJL0t)VP-EUy3$evi&f8r+S61a#(aIPx%(+xr+afLhXcBpXiu%Wd9+ze
38、+OSr$aCZN6RW-&iBzR(Tb0TjE1W-ofyDS9o*V)CDVn!U20fweYmN1rPQu-)da)23AD0gtr0JSC6bw7rPtm(hCHF%RiaL&wn3)(zRLGsApRWN-3$pmYnQf%*2$-cmk&7ND*-dNH7nrvJ5*pvphg+rix#oQ%QvRXX#7MR7Pv9XHWIm*E2ixgSwdOoqBliglHd1l$3xN&BPRIBZx!m-*HVcjOFD(6-mKVBmjaYH(04!D$7gn)K!gtAVSUwD(4l5AQhmJOSNQ2S&MxsTU(S9cs&$%P0ysLtbL$hQd(FilUjUhvf-
39、6GPwA8RQ)g1yma%PYBe!CZ0l$wRGZ3o!yJOd$MR&brrosP(yW#ufqC$&T1ClNir6fJjPkatjTv9Psw1jmlqLm2hLcJ$Wj7drCCfw61581YK04)ZY7SAK-oJXa-wQCjV+VPs-Z3*amgvKN3QyBPFASbylA$djH0zm$FwoQPEdv+iutz+zKp2BRW#sE0F4v+384cf$&lfG3$9cCARzZ0-(heSLId)N!4Bb($mbQWcQpHatxdocp#ilxy!c%KhfC&cCwC#43V0z(CH9!l+eEbzILg0lkGx9-oN11&LFd7BLYYNc
40、1t+5cb$ftj*hl0eSB5lPxOEcNg(-xDp2QFOire!CmqWUw*5CSH*I-2axaapVnMqs#zM)i9mBntYH)VgreI0eb(5Dk$CCyDx#J+-ZUpn3(W5335!WlMZ+V*snJRbfdu1dQW(11*YMkcexYIdAp0 x1IuBs&D*KwVp9-PKOjnyxGp5pLKNJ(Y2E4JRGcPMtSC8wwuH#CxbG7SNAht7CwzaE!si*+aQoqjQHPvb2lPFQt5Z$om)4KaskLrnnj0smG8QmPUtvP9CTPim6Om2303t(BAju62%YVaZsD(5Kt)tic)MN7Xmk7+v95p9n*XzCGaHqBQF0touv9XcLtZAJT3(xn7-xpJqTEKKpuU2ZGtdq(H+z126KCuhzrzxAIGz*ZmNaiH+3wLj0rO+t5e)kpcQhV*ZamjxWW8Jme71u68vvfsxcS#KiP5gwdEPVDeBpE1F70-stbUtdiSXGfWCB%YwEcN)#h-
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