邢唷>? ?欹g 餜bjbjVV46r<r<hO `````ttt8lt膉`V$飅駃駃駃駃駃駃$恗Bpzji```j``l~j???``飅?飅??Eh桬鸷楩^w?"wE踚攋0膉嘐紁7紁 桬桬紁`獷0$?jj?膉紁 , &: D桍N2ba'`YN媁潃巔€8h鱾x {|o僫rg梑舥襨籰梪剉塠hQ'`^Nwo僨[O2015t^4g15錯pS裇 Xd亯'YYpe譙8h鱾x nucleos(t)ide analogues NAs {|o僫r籰梪剉ba'`YN媁潃巔chronic hepatitis B CHB €梺g籰梪 钀R€u髞梺壢~珟籰梪  €N€*NSO魰?^X[(Wf>f剉頬_ 郪dk(W4N奮擽(u菑 z-N梺壠[R裿KmNAs{|o僫rg籰梪剉塠hQ'`0,g噀鑕(W鵞NAs{|o僫rg梑舥襨籰梪剉塠hQ'`penc蹚L堔V~楙`觺 燫:_^'Y4N奮;S^鵞鴙sQ塠hQ'`顣槝剉茓 v^:N4N奮瀃鯈衏汷c黐0 sQ.曂ba'`YN媁潃巔8h鱾x {|o僫r塠hQ'`Safety of Long-Term Anti-Viral Treatment with Nucleos(t)ide Analogues for Patients with Chronic Hepatitis BAbstract Most chronic hepatitis B (CHB) patients need long-term treatment with nucleos(t)ide analogues (NAs), whereas part of them even need life-long treatment. However, due to heterogeneity of human beings, it is great important to monitor the long-term safety of NAs in the management of patients with chronic hepatitis B in clinical practice. This article aimed to review the safety data of long-term anti-viral treatment with NAs with the expectation to enhance the awareness of clinicians to these issues and support clinical practice. Key words: chronic hepatitis B; nucleos(t)ide analogues; safety顅MR 8h鱾x {|o僫rnucleos(t)ide analogues NAs /fba'`YN媁潃巔chronic hepatitis B CHB €梑舥襨籰梪剉;N亯 愰b wQ g梪He:_0;`SO塠hQ'`孴€譙'`o倉Y0g(u筫縊I{O縍[1]06q € 'YYpe譙NAs{|o僫r籰梪剉CHB€梺g籰梪 钀R€u髞梺壢~珟籰梪  €N€*NSO魰?^X[(Wf>f剉頬_ 颯齹X[(WN T剉Tv^莡bT€T(uo僆{臽礠 郪dk(W4N奮擽(u菑 z-N梺壠[R裿KmNAs{|o僫rg籰梪剉塠hQ'`0FO皊 gsQ嶯NAs{|o僫r塠hQ'`筫b梽vpenc'YYeg陙4N奮鑜孮諎寶 vQ硚eQ剉€?^龕 g%Nf:y NLAM籰梪€鴙詋 LdT籰梪€鶴皊3/4CKGS貧剉詋婳儚貧[4]12.9% vs 4.1% P<0.001  vQ-N2婳鶴皊寑舥0鍿Nyxvz硚eQ655婳O(uLdT剉CHB€彇繈4t^ 觺済裇皊71%剉€鶴皊1/21^7ULN CKGS貧  €16%剉€鶴皊3/4>7ULN CKGS貧0dkY 6.1%剉€鶴皊寑墍No倠N鯪 vQ-N4婳€鶴皊寑舥[5-7]04N奮瀃鯈-N CKGS貧鬴8^翂 42%^77%剉€X[(WCK4ls^GS貧 vQ-NNJS剉€4O g莡秗[8]0'k2mo兞Tt@\European Medicines Agency, EMEA lQ^剉塠hQ'`penc>f:y2008-03-01^2008-08-31g魰 qQ裇u6婳*j箏寑秐銐舥婳 vQ-N3婳憉f:y蛻寑OW{k[12-13]02.2 線_c$O CHB€線_c$O剉詋婳儚貧 Tv^藛}v?\Q兀?\Q?\謡蔛^a觛'`}v苸迉?\剉CHB€詋婳颯R+R貧緩38.1%Q?0.6%Q?.9%孴9.0% vQ-N64.6%剉€4O g線舥[14]0dkY 俌€Tv^X[(WvQ諲\o(W剉線襨'`螛i栢V } S靊€t^0≧ 仴|7hlxSQ?Y鉔P'`潃lxSQ欯垕SQ|?\舥Q?m≧'`線\t線巔Q€襨'`o僫r籰梪Q[SOhV榌鹹iI{[1] R^\嶯線_c砙剉貧qS篘08h鱾{|f:y ADV/f裇u>fW劸€烺齹譙_c [eGFR d"50 mL/min]剉靣藌剺Km郪P[[18]0dkY 貜 gxvz衏:yADVT€TLAM籰梪颯鵞LAM€o儯`€剉線烺齹 bNo俼_蚑 vQ-N鶺縹寑Pnd枃screatinine clearance CrCl 50^89 mL/min€剉線烺齹譙_c5t^/}裇u噑貧緩45% >fW勜殠N鶺縹CrCl>89 mL/min剉€17% [19]0ADV b線_c$O剉钀MOMO嶯褟飠\ 颯齹鵞線\ N畍苸迉wQ g魐剉襨'`\O(u0xvzhfADV線襨'`wQ gBR蠎漁V?`ADV 30 mgQ?0 mg孴120 mg籰梪48hT鰁剉線襨'`裇u噑R+R:N13%Q?7%孴50%[20]0TDF T7h颯黐魜線_c$O =\Ny槼~eQ3*NhQt彇:g鵞gqxvz剉Gl;`R恎衏:yTDFNO>fW?e豐線烺齹[21]0FO(WNy槼~eQ61婳CHB€剉xvz-N 39%剉€(WTDFs^GW籰梪29*NgT鶴皊\o(W剉線\譙_c鶑a vQ-N線\鱴蛻8T6e噑tubular resorption of phosphate rate TRP <82%剉€詋婳:N9.8%  €蟸GFR!hckT線\g'Y鱴x懶v蛻8T6e噑tubular maximum phosphate reabsorption rate TmPO4/GFR  NM杽v€詋婳:N29.5%[22]0Ny?W齎謡?\舥N坢S線舥xvz@b潃舥褃蹚L垊vgxvzqQ硚eQ51婳譙ADVbTDF籰梪剉CHB€ xvz觺済>f:yADVbTDF籰梪2^9t^剉線\烺齹湒峹/}裇u噑貧緩15% [23]0 gxvz衏:yLdT颯齹wQ g9e刄eGFR剉\O(u[24-26] FOvQ:g6RNf0Anna S. LokI{:NLdT颯齹wQ g線烺齹軴\O(u FONnx歔購N軴'`\O(u/fLdT靣 g剉  €N購N\o(W穬蕍v^*g厤菑vQ貧€o冄Su噑孴^y蟸寑墍筫b梽vNo偼S擽[15]02014t^裇h垊vNy榚g陙餝~n剉M戼[鵞gqxvz>f:yETV 0.5 mg孴LdT 600 mg籰梪GW颯9e刄CHB線烺齹 yr+R/f鵞嶯{彟^線烺齹NhQ剉€[27]02.3 細舥豐(WCHB NAs{|o僫r鵞細剉\O(u蚇*g齹穬梍EQR翄f0颯齹剉:g6R/f1u嶯NAs{|o僫r鵞線\剉_c砙_w峃O鱴@埱u (?wSN硩蹚 €裇U\b:No彣毰u[8]0NAs{|o僫r_w崉v細舥豐颯鶴皊uSchQ_螾f[蔛舥tf[剉9e豐0wR€颯h埌s:N@堶xM朜OQ€P慓S貧Qx'`鱴x憊慓S貧蔛?\鱴GS貧0彇@wgo凍e魰剉鯺 q_螾f[纇錱颯鶴皊%_+o'`鉔"_8^  iQ氳惃?崗u~g蔛Y裇'`榖I{0線;m纇颯>f:y線\%_+o'`棙抾豐4OYvp'`?I{[28]02010t^Hepatology N裇h垊vNyxvzqQ硚eQ319婳蟸NAs{|o僫r籰梪剉CHB€ s^GWt^劅63乗 vQ-N7u'`€詋婳:N76% 57%:N潃lxS€ 鍕xvz觺済>f:y19%剉€鶴皊(崗u~g莡 49%剉€鶴皊蠎"N1Y 68%剉€芠BMD 鶴皊M朜O0t^劅Q?`+R孴8h鱾x憑|o僫rADV/TDF 籰梪NBMD剉M朜O靣藌鴙sQ[29]0vQ颯齹:g6R:N8h鱾x憑|o僫r籰梪黐魜線\譙_c KNT鐍裇剉NO鱴@埱u颯O鶺(?wSN硩0sSONOBR蠎剉8h鱾x憑|o僫r俌ADV 籰梪 蚇颯黐魜>fW剟vNO鱴@埱u  boS[8]04N奮 N gSO(uADVbTDF籰梪CHB€颯齹黐魜鶴皊冿S<\鼅T乢Fanconi s Syndrome)[30-31] 2014t^ 0癳駛f:y20%譙TDF籰梪剉€鶴皊哊線\烺齹_8^[31]0鍕Bg譥 Tt^裇h垊v鍿Ny橓[齎褳篘W O'`冿S<\鼅T乢剉xvz衏:yvQ\o(W:g6R颯齹N菑'lSirv慐HHADHvT湒峹_w崉v縹抾SO鉔" }qN gsQ[32]0'YYpeTDF_w崉v冿S<\鼅T乢€\PoTvQ褟飠\烺齹颯b`Yck8^[33]02.4 hT鬡^y蟸舥豐NAs{|o僫r鵞^y蟸鹼邁剉q_蚑N8^翂0Ny橓[詋LdTUSoNLdTT€TPEG-IFN籰梪CHB剉轛~?`R恎xvz觺済>f:yLdTUSo兓l梪膥€ 剉PN裇u噑:N4%2/53   €LdTT€TPEG-IFN alfa-2a籰梪膥€剉購N裇u噑:N19%9/48 [34]0LdT/PEG-IFNT€T籰梪黐魜剉PN鬴:N%N蛻 莡秗裇\O輱粂w嵥Y籰梪剉鰁魰颯齹鬴韜-NMO鰁魰4.5*Ng [35]02008t^EMEA亯BlLdT剉魦ffN-N燫eQ癳剉f婮T f婜yCHB€O(uLdTX[(WPN螛i0顅MRLdTNr^pb }interferon IFN T€T騗bCHB籰梪剉亂蘝翄0vQ諲NAs{|o僫r剉PN舥婳JTU翂  g3婳潃lxS€vQ-N2婳:N1Y鉔Pg 1婳:N鉔Pg 蟸ETVR+R籰梪7*Ng04*Ng蔛27*NgT鶴皊PN (W\P(uETV 9e(uvQ諲NAsv^鵞莡YtT €莡秗孾hQ坢1Y[36]02.5 sNx憍?N襨齎邩罷o兞T裿cwt@\Food and Drug Administration FDA 亯Bl@b g剉NAs{|o僫r龕錘褳Fhf婮T剉b__ JT鍂郪wQ g縹抾SO襨'`颯齹黐魜sNx憍?N襨剉\o(W螛i朳8]0NAs{|o僫r_w崉vsNx憍?N襨?^N仾€豐'`Q~抾SOb_`烺齹_8^Q€z亷pQy蟸舥豐蔛寑舥 gsQ0sNx憍?N襨颯亃6q裇\O bHT悥?S'`裇\O w嵥Y鰁?^4O gv`胈QTT孴y佦u0KNT颯蹚U\:N|T8T%`肙Ql韜孴:'l[37]0YpeLAM孴TDF剉sNx憍?N襨JT龕/f篘{|MQ玼:w柵u襨human immunodeficiency virus HIV 籰梪-NNvQ諲o僫rT€T擽(u鰁裇u剉[38]02009t^ LangeI{穇齎f[€轛~?`聣遊0R16婳CHB潃lxS€-N5婳€(W譙ETV籰梪T4^240 d鶴皊sNx憍?N襨 JT T鰁c鶴購汵鶴皊sNx憍?N襨剉€GWX[(W%N蛻剉潃_c$OMELDe"20  vQYO11婳MELD膵RNO嶯18剉€*g鶴皊@nsNx?ls^瀀燫 R恎裇皊MELD膵RN€sNx憍?N襨剉裇u>fW匄vsQ[39]0:NfNAso僫rNsNx憍?N襨剉sQ鹼 購汵穇齎f[€T韣蹚L垎NMR粀'`聣遊  T7h(W1Y鉔Pg€-N鵞詋ETV0TDF0LAMNADV剉梪HeN塠hQ'` 裇皊sNx?`x?N襨螛iY翂嶯潃線烺齹_c$O孴葉+gg潃舥€ vQ裇u颯齹N緐舥,g珟秗`剉sQT€'`鬴'Y  €No僫r,g珟鄀sQ[40]03 8h鱾x {|o僫r4N奮塠hQ'`剉裿KmNt1u嶯N TNAs{|o僫r(WCHBg籰梪菑 z-N颯齹X[(WT蛓塠hQ'`顣槝 郪dk籰梪MR臺{槚橦QN€蹚L圗QR焞 JT鍂籰梪菑 z-N颯齹鶴皊剉No偼S擽  T鰁(W4N奮擽(u菑 z-N鵞vQ塠hQ'`蹚L埰[R剉裿Km孴t03.1 8^翂No偼S擽剉裿KmNt3.1.1 寑x懤ov慓S貧N寑舥剉裿KmNt(W4N奮擽(uNAs菑 z-N 梺夰[CK歔g裿Km $\vQ/fO(uLdT籰梪剉€0N鎒裇皊CKGS貧 4N奮;S^梺壽廘坱?R蕥璭 /f&TNNAs鴙sQ0ck8^臽礠 N gR萷袕≧b€曵e魰袕≧TCK颯GS貧 7u'`鬴:N8^翂0俌済鶴皊vQ諲烻郪鄀誰銐蕬剉 NCKGS貧鴙sQ剉c韣'`寑墍紆踰孴b 寑鄀汻 颯$R璭:NNNAs鴙sQ剉寑舥01/2CKGS貧俌鄀莡秗鄀梱r+RYt 3/4CKGS貧€梺墵R:_裿Km孴彇繈0@b gNAs{|o僫ryr+R/fLdTNLAM 籰梪€GW擽裿Km細寑莡秗0LdT籰梪MR椑hKm@n寑x慞憣TCK4ls^ 籰梪g魰蟢3*Ngb6*Ng纇Km1!k[41]0寑舥歔IN:Nc韣剉烻郪*gf剉寑墍紆踰孴/b寑鄀汻4O彇CK65乗 N璭瀀燫01u嶯€t^CHB€8^4O g線烺齹螿 郪dk鵞嶯購{|€g籰梪菑 z-N梺夢f燫芠R裿Kmo僫r剉塠hQ'`顣槝 v^9hnc€t^€剉線烺齹臽礠宼eNAs{|o僫r剉O(uBR蠎翂h? 0 4\卂銐砆剉顣槝 4.1 顅MRhQt凈V匭a觛HBVv^N梺墺c譙NAs{|o僫r籰梪剉篘pe'Y R^^0T蛓NAs(W4N奮 N擽(u剉鰁魰NN vQ塠hQ'`筫b\*g梍0REQR茓0ag鯪AQ笅鰁擽鷁藌孾刄剉彇繈SO鹼孴o僫r塠hQ'`裿KmQ 錘縊蔛鰁裇皊顣槝 塠hQ(uo04.2 梑舥襨T€T籰梪CHB€剉g塠hQ'` S靊NAs{|o僫rKN魰剉T€T錘蔛NAs{|o僫rNIFNKN魰剉T€T GW梺壽Nekxvz蔛膵鱊04.3 (W gTv^緐舥臽礠 N NAs{|o僫rNvQ諲o僫r俌諲@l{|o僫r KN魰剉鴙扤\O(u蔛塠hQ'`_N g卂嶯蹚Nekxvz0耂€噀.s[1] Eur  BDlnptv2 4   " . 磙毯酞順弡gUCU/{U&h/mGh璝5丆JOJPJQJaJo(#h/mGh攁CJOJPJQJaJo(#h/mGh=!3CJOJPJQJaJo(&h/mGhl5丆JOJPJQJaJo(&h/mGh=!35丆JOJPJQJaJo(h筁Y5丱JQJ#h筁Yh璝CJOJPJQJaJo(h趡h璝5丆J OJQJaJ #h趡h*{CJ OJPJQJaJ o(#h趡h=!3CJ OJPJQJaJ o(h筁Y5丆J OJQJaJ o(#h筁Yh筁YCJOJPJQJaJo(  Dnp J L $ & $dp^a$gdrj$勦dpWD`勦a$gdrj $dpa$gdrj $dpa$gd筁Y $dpa$gdrj dpgd筁Y $dpa$gd筁Y. 0 @ B H J L ` b j l t v ~ €  " $ & 6 8 碹碹晒﹨s棭棭筪㏑"h/mGhl5丆JOJQJaJo(h/mGh璝CJOJQJaJ"h/mGh羀j5丆JOJQJaJo("h/mGh縧5丆JOJQJaJo("h/mGh沖S5丆JOJQJaJo(h/mGh=!35丆JOJQJaJh/mGh璝5丆JOJQJaJ#h/mGh璝CJOJPJQJaJo(#h/mGh=!3CJOJPJQJaJo(#h/mGhwCJOJPJQJaJo(8    7 g w z F_0襻裱裱裱裱裱裱裱裱裱窳瘪●●憗o[o&h/mGh=!3CJH*OJPJQJaJo(#h/mGh=!3CJOJPJQJaJo(h/mGh趡CJOJQJaJo(h/mGhlCJOJQJaJo(h/mGh秝hCJOJQJaJo(h/mGh=!35丆JOJQJaJh/mGh璝5丆JOJQJaJh/mGh=!3CJOJQJaJo(h/mGhwCJOJQJaJo(h/mGh=!3CJOJQJaJ!02JLVlnvx@碹思〝█踤Z跦踤Z踤Z踤#h/mGh1KCJOJPJQJaJo('h/mGh=!3CJOJPJQJ^JaJo(#h/mGh=!3CJOJQJ^JaJo(&h/mGhF5丆JOJPJQJaJo(&h/mGhl5丆JOJPJQJaJo(&h/mGh=!35丆JOJPJQJaJo(h/mGh璝CJOJQJaJh/mGh璝CJOJQJaJo(#h/mGh=!3CJOJPJQJaJo(#h/mGh攁CJOJPJQJaJo(B>f|zk$dpa$gdrj$勦dpWD`勦a$gdrj$勦dp@&WD`勦a$gdrj$dp@&a$gdrj$勦dpWD^`勦a$gdrj$dp^a$gdrj$勦dpWD`勦a$gdrj$勚dpWD^`勚a$gdrj @B.02<>@Bbdf熠屎授ㄚ斱靲l€X熠F2'h/mGh=!3CJOJPJQJ^JaJo(#h/mGh=!3CJOJQJ^JaJo(&h/mGh趡5丆JOJPJQJaJo(&h/mGhl5丆JOJPJQJaJo(&h/mGh=!35丆JOJPJQJaJo(&h/mGh=!3CJH*OJPJQJaJo(#h/mGh攁CJOJPJQJaJo(h/mGh磑CJOJPJaJo(h/mGh=!3CJOJPJaJo(#h/mGh=!3CJOJPJQJaJo(&h/mGh璝5丆JOJPJQJaJo(TVf|&碣堑|莏荹荊?琼偾&h/mGh璝5丆JOJPJQJaJo(&h/mGh=!3CJH*OJPJQJaJo(h/mGCJOJPJQJaJo(#h/mGh趡CJOJPJQJaJo( h/mG5丆JOJPJQJaJo(&h/mGh=!35丆JOJPJQJaJo(&h/mGhl5丆JOJPJQJaJo(#h/mGh璝CJOJPJQJaJo(#h/mGh=!3CJOJPJQJaJo('h/mGh=!3CJOJPJQJ^JaJo(#h/mGh=!3CJOJQJ^JaJo(2468:@jnpv &熠期期瘶瘉瘉熠o陟赸o赸陟#h/mGh{XCJOJPJQJaJo(#h/mGh趡CJOJPJQJaJo(,h/mGh=!3B*CJOJPJQJaJo(ph,h/mGh趡B*CJOJPJQJaJo(ph,h/mGh=!3B*CJOJPJQJaJo(ph&h/mGh=!36丆JOJPJQJaJo(#h/mGh=!3CJOJPJQJaJo(&h/mGh=!3CJH*OJPJQJaJo("x碹芹帝≯≯芹弣矍鄣iUi鄣跜#h/mGh=!3CJOJQJ^JaJo(&h/mGhl5丆JOJPJQJaJo(&h/mGh=!35丆JOJPJQJaJo(#h/mGhwuCJOJPJQJaJo(#h/mGh坋€CJOJPJQJaJo(&h/mGh=!36丆JOJPJQJaJo(#h/mGh璝CJOJPJQJaJo(&h/mGh=!3CJH*OJPJQJaJo(#h/mGh=!3CJOJPJQJaJo(#h/mGhHACJOJPJQJaJo( RZ  ! !!!!!L!胭肭偾偾城匐匐匐匐匐匐城∏城徢}nZ&h/mGh=!35丆JOJPJQJaJo(h/mGh璝CJOJQJaJ#h/mGh?lCJOJPJQJaJo(#h/mGh秝hCJOJPJQJaJo(#h/mGh璝CJOJPJQJaJo(&h/mGh=!3CJH*OJPJQJaJo(#h/mGh=!3CJOJPJQJaJo(#h/mGh=!3CJOJQJ^JaJo('h/mGh=!3CJOJPJQJ^JaJo(! !N!R!Z!b!j!r!z!$d$Ifa$ $dha$$勦dpWD`勦a$gdrj L!N!P!R!X!Z!`!b!h!j!p!r!x!z!|!??????????????"""","."0"P"R"T"V"X"Z"\"燔痰灥灥灥灥灇僱僱僱僱僱僱僱僱僱僱殐l僱僱,h?,h璝B*CJOJPJQJaJo(ph,h?,h=!3B*CJOJPJQJaJo(phh璝,h?,h璝B*CJOJPJQJaJo(ph,h?,h=!3B*CJOJPJQJaJo(phh璝B*CJOJQJaJphh=!3B*CJOJQJaJph&h/mGh璝5丆JOJPJQJaJo(*z!|!???????aSHHHHHH d$If$d$Ifa$kd$$If杔斶謭?/ +? 3 t?44 la]?""."0"R"V"Z"^"VHHH$d$Ifa$kd$$If杔敍謭?/ +? 3 t?44 la] d$If\"^"`"b"d"f"h"v"x"|"~"??????????????????????????#$#&#*#,#4#6#@#B#N#P#Z#\#`#b#n#p#r#t#橐橐槲议议议议议议我橐橐橐阂橐橐橐槲遥橐橐阂橐阂橐橐槲h璝OJQJ,h?,hIB*CJOJPJQJaJo(ph&h?lB*CJOJPJQJaJo(phh璝,h?,h=!3B*CJOJPJQJaJo(ph,h?,h璝B*CJOJPJQJaJo(ph7^"b"f"h"x"~"???SH d$IfkdT$$If杔斞謭?/ +? 3 t?44 la]$d$Ifa$???????SHH7$d$Ifa$gd?l d$Ifkd$$If杔?謭?/ +? 3 t?44 la]$d$Ifa$?????&#,#SH d$Ifkd$$If杔?謭?/ +? €3€€€€ t?44 la]$d$Ifa$,#B#\#b#p#r#t#B8 $dha$kd<$$If杔敳謭?/ +? €3€€€€ t?44 la]$d$Ifa$$d$Ifa$gd?lt#€#????????B$F$^$f$??%% %%\%`%x%€%??&&F&H&P&V&^&`&b&??f(n(?? )*)碹砩淀身身m淀身戫mm淀韒韒響淀淼淼響淼#h/mGh=!3CJOJQJ^JaJo(#h/mGh璝CJOJPJQJaJo(#h/mGh?lCJOJPJQJaJo(#h/mGh?CJOJPJQJaJo(&h/mGh=!3CJH*OJPJQJaJo(#h/mGh秝hCJOJPJQJaJo(#h/mGh?vCJOJPJQJaJo(#h/mGh=!3CJOJPJQJaJo(*t#?b&.)??f+t,r.l1?x4???*9$dp^a$gdrj $dpa$gdrj$勦dpWD^`勦a$gdrj$dp@&^a$gdrj $dpa$gdrj$勦dpWD`勦a$gdrj$勦dpWD`勦a$gdrj*),).)X)f)**??????\+b+d+f+?碹傻傻傻{gS?S-#h/mGhCJOJPJQJaJo(&h/mGhCJH*OJPJQJaJo(&h/mGhCJOJPJQJ\乤Jo(&h/mGh璝5丆JOJPJQJaJo(&h/mGh=!35丆JOJPJQJaJo(&h/mGhl5丆JOJPJQJaJo(#h/mGhlCJOJPJQJaJo(&h/mGh=!3CJH*OJPJQJaJo(#h/mGh=!3CJOJPJQJaJo(#h/mGh璝CJOJPJQJaJo(#h/mGh?lCJOJPJQJaJo(??????, ,h,p,r,t,~,?~-€-???.(...h.n.p.r.???碣碣碣碣懦煁硧wa婰嫵嫵L碂撑)h/mGh=!3CJH*OJPJQJ\乤Jo(*h/mGh=!3CJOJPJQJ\乛JaJo(&h/mGh=!3CJOJQJ\乛JaJo(&h/mGh=!3CJOJPJQJ\乤Jo(&h/mGh璝CJOJPJQJ\乤Jo(#h/mGh=!3CJOJPJQJaJo(&h/mGh=!3CJH*OJPJQJaJo('h/mGh=!3CJOJPJQJ^JaJo(#h/mGh=!3CJOJQJ^JaJo(?? / ///0/8/V0X0??11`1h1j1l1t1€1?€2???l4t4v4x4€4??@5F5r5碹碹碹芹帝芹芹芹{g矍矍矍郏弡g矍&h/mGh璝5丆JOJPJQJaJo(&h/mGh=!35丆JOJPJQJaJo(&h/mGhl5丆JOJPJQJaJo(#h/mGh璝CJOJPJQJaJo(#h/mGh+6CJOJPJQJaJo(&h/mGh=!3CJH*OJPJQJaJo(#h/mGh=!3CJOJPJQJaJo(#h/mGhCJOJPJQJaJo("r5t5???????6 66??77 7$7???????9碣碣碣碣碣懦懦〕彸懦懦}iU&h/mGh=!35丆JOJPJQJaJo(&h/mGh璝5丆JOJPJQJaJo(#h/mGh璝CJOJPJQJaJo(#h/mGhCJOJPJQJaJo(#h/mGh7CJOJPJQJaJo(#h/mGh=!3CJOJPJQJaJo(&h/mGh=!3CJH*OJPJQJaJo('h/mGh=!3CJOJPJQJ^JaJo(#h/mGh=!3CJOJQJ^JaJo(99(9*9???? ::::8:::侜凓f;h;孄嶜雏<<><@<熵堑Φ捸捸秦挼€祤祅礧@W,h/mGh{wB*CJOJPJQJaJo(ph,h/mGh=!3B*CJOJPJQJaJo(ph#h/mGh?CJOJPJQJaJo(#h/mGh璝CJOJPJQJaJo(&h/mGh璝5丆JOJPJQJaJo(h/mGCJOJPJQJaJo(#h/mGh=!3CJOJPJQJaJo( h/mG5丆JOJPJQJaJo(&h/mGh=!35丆JOJPJQJaJo(&h/mGh?5丆JOJPJQJaJo(*9??:::凓h;L<它F=妄楚唼?6BxD艱 $dha$$勦dpWD`勦a$gdrj $dpa$gdrj$dp@&a$gdrj$dp^a$gdrj$勚dpWD^`勚a$gdrj@<H<J<L<牲它4=8=D=F=r=z=她妄??炳楚蔺缧恭恭暓儳oD&h/mGh=!35丆JOJPJQJaJo(,h/mGh璝B*CJOJPJQJaJo(ph&h/mGh=!3CJH*OJPJQJaJo(#h/mGh璝CJOJPJQJaJo(#h/mGh?CJOJPJQJaJo(#h/mGh=!3CJOJPJQJaJo(,h/mGh璝B*CJOJPJQJaJo(ph,h/mGh=!3B*CJOJPJQJaJo(ph/h/mGh=!3B*CJH*OJPJQJaJo(ph蔺唼????????R@T@\@^@f@轆郃B2B4B6B咮圔淏濨禕築郆釨鬊鶥淐癈vDxD熠融融蹿②恷恷谌诖冖趈趈谌趈诖诖冖#h/mGh?CJOJPJQJaJo('h/mGh=!3CJOJPJQJ^JaJo(#h/mGh=!3CJOJQJ^JaJo(#h/mGh璝CJOJPJQJaJo(&h/mGh=!3CJH*OJPJQJaJo(#h/mGh?CJOJPJQJaJo(#h/mGh=!3CJOJPJQJaJo(&h/mGh璝5丆JOJPJQJaJo("xD禗腄艱褼訢釪銬鍰鐳鶧﨑EEEE&E(E:E>EPERETEZE\EbEdE熵莫惇悓惇r獝猺獝猺獝尓怺D,h?,hr_B*CJOJPJQJaJo(ph,h?,h=!3B*CJOJPJQJaJo(ph2h?,h?5丅*CJOJPJQJ\乤Jo(phh璝2h?,h璝5丅*CJOJPJQJ\乤Jo(ph2h?,h=!35丅*CJOJPJQJ\乤Jo(ph&h/mGh璝5丆JOJPJQJaJo(&h/mGh=!3CJH*OJPJQJaJo(&h/mGh=!35丆JOJPJQJaJo(艱訢銬鍰鐳E(EREd$Ifgdl" d$IfSkd$$If杔4旕???19! tj$44 la$d$Ifa$RETE\ErE圗濫xmgm$If d$If$d$Ifa$ykd$$If杔4攦謀?J?1  .  tj$44 ladEpErExEzE咵圗嶦怑淓濫燛‥狤癊睧窫綞翬腅蔈橐榫楫闂橐搚耶覔_y镠橐,h?,hr_B*CJOJPJQJaJo(ph2h?,h=!35丅*CJOJPJQJ\乤Jo(ph2h?,h璝5丅*CJOJPJQJ\乤Jo(phh璝,h?,h竬=B*CJOJPJQJaJo(phh?,h璝CJOJPJaJo(&hl"B*CJOJPJQJaJo(ph,h?,h璝B*CJOJPJQJaJo(ph,h?,h=!3B*CJOJPJQJaJo(ph濫燛‥{{u{$If d$IfykdR$$If杔4?謀?J?1 ` .  tj$44 la‥狤睧腅諩鐴xmmm d$If$d$Ifa$ykd,$$If杔4?謀?J?1   .  tj$44 la蔈蠩訣諩蹺釫鍱鐴闑霦麰﨓FF,F.F0F6F8F:FFFHFJFLFXFZF\F`F橐灰ひ粻喴灰灰粻l喴U一议一,h?,hr_B*CJOJPJQJaJo(ph2h?,h=!35丅*CJOJPJQJ\乤Jo(ph2h?,h璝5丅*CJOJPJQJ\乤Jo(phh璝,h?,h竬=B*CJOJPJQJaJo(ph,h?,h璝B*CJOJPJQJaJo(ph,h?,h=!3B*CJOJPJQJaJo(ph,h?,h!AB*CJOJPJQJaJo(ph鐴闑霦﨓F.F{{{{ d$Ifykd$$If杔4?謀?J?1  .  tj$44 la.F0F8FJF\FpFxmm_d$Ifgdl" d$If$d$Ifa$ykd$$If杔4?謀?J?1  .  tj$44 la`FbFdFjFnFpFrFtF凢咶朏楩癋睩碏篎糉綟蔉蘁蜦蠪蹻轋郌銯煺菊В壵ддВo壵X乍誂乍,h?,h!AB*CJOJPJQJaJo(ph,h?,hr_B*CJOJPJQJaJo(ph2h?,h=!35丅*CJOJPJQJ\乤Jo(ph2h?,h璝5丅*CJOJPJQJ\乤Jo(phh璝,h?,h璝B*CJOJPJQJaJo(ph,h?,h竬=B*CJOJPJQJaJo(ph,h?,h=!3B*CJOJPJQJaJo(ph&hl"B*CJOJPJQJaJo(phpFrFtF咶楩睩{{{{ d$Ifykd&$$If杔4?謀?J?1  .  tj$44 la睩碏糉蜦郌餏xmmm d$If$d$Ifa$ykd$$If杔4?謀?J?1  .  tj$44 la銯闒頕餏騀鬎GGGGG G*G,G:GTHTpTxT燭猅琓甌繲耇蜹蠺黅UU頤餟鳸鶸黆碣碣碣碣碣砼睗媦媦媏婼婣#h/mGh璝CJOJPJQJaJo(#h/mGhZZCJOJPJQJaJo(&h/mGh=!3CJH*OJPJQJaJo(#h/mGh?CJOJPJQJaJo(#h/mGh=!3CJOJPJQJaJo(&h/mGh璝5丆JOJPJQJaJo(&h/mGh=!35丆JOJPJQJaJo(&h/mGha,5丆JOJPJQJaJo(&h/mGha,CJH*OJPJQJaJo(#h/mGha,CJOJPJQJaJo(黆VV頥餠鯲鳹tWvW釽鋀鎃鑇餡騑鶺X$&,.4@BFHN⒛碣砬砬登砬慝牀巭omo]N]No]N]Noh/mGh潸VCJOJQJaJh/mGh潸VCJOJQJaJo(Uh/mGh=!3CJOJQJaJh/mGh?CJOJQJaJo(h璝5丱JQJh=!35丱JQJh璝5丆JOJQJh璝CJOJQJ#h/mGha,CJOJPJQJaJo(#h/mGh=!3CJOJPJQJaJo(&h/mGh=!35丆JOJPJQJaJo(#h/mGh璝CJOJPJQJaJo(V餠vW鋀鎃鑇騑P娖r⑹v 形盅枰幵收$dpとWD`a$gdrjm$$dp^a$gdrj dpgdrj $dpa$gdrjdpgdrjopean Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection [J]. J Hepatol, 2012, 57(1):167-185.[2] Kakuda TN. Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced mitochondrial toxicity [J]. Clin Ther, 2000, 22(6):685-708.[3] jl. 寑x懤ov慓S貧剉4N奮aINNyr裇'`貧寑x懤ov慇埱u[J]. -N齎瀃(u?Q褃Bg譥, 2009, 6:494-496.[4] Liaw YF, Gane E, Leung N, et al. 2-Year GLOBE trial results: telbivudine is superior to lamivudine in patients with chronic hepatitis B [J]. Gastroenterology, 2009, 136:486-495.[5] Jung M, Uddin A, Dong Y, et al. Creatine kinase elevations during 4 years telbivudine anti-hepatitis B virus (HBV) treatment are not predictive of muscle events [J]. Hepatol Int, 2011, 5:117.[6] 褢n櫉, 媠-N餦, 霑R? I{. f詋+Y歔孴蒪s|+Y歔籰梪ba'`YN媁潃巔鵞寑x懤ov憚vq_蚑 [J]. 4N奮潃苺舥Bg譥, 2011, 27(02):143-145.[7] Wang Y, Thongsawat S, Gane EJ, et al. Efficacy and safety of continuous 4-year telbivudine treatment in patients with chronic hepatitis B [J]. J Viral Hepat, 2013, 20(4):e37-46.[8] Fung J, Seto WK, Lai CL, et al. Extrahepatic effects of nucleoside and nucleotide analogues in chronic hepatitis B treatment [J]. J Gastroenterol Hepatol, 2014, 29(3):428-434.[9]'k2mo兞Tt@\Q賨http://www.ema.europa.eu/docs/en_GB/document_library/EPAR__Procedural_steps_taken_and_scientific_information_after_authorisation/human/000372/WC500054476.pdf.[10] 齎禰邩罷o兞T裿cwt@\. f嬚`籰梪YN媁潃巔剉8h鱾{|梑舥襨o?f詋+Y歔孴蒪s|+Y歔剉*j箏寑秐銐莡[EB/OL]. o兞TNo偼S擽酧o`惀b, 2010-07-22[2015-01-30]. http://www.cdr.gov.cn/xxtb_255/ypblfyxxtb/201007/t20100722_2839.html.[11] Lin GL, Wu YK, Li XY, et al. The effect on creatine phosphokinase of the patients with chronic hepatitis B were treated with telbivudine, entecavir, adefovir dipivoxil and lamivudine [J]. Hepatology, 2011, 54:1044A. [12] Kim BK, Oh J, Kwon SY, et al. Clevudine myopathy in patients with chronic hepatitis B [J]. Journal of hepatology, 2009, 51:829-834.[13] Seok JI, Lee DK, Lee CH, et al. Long-term therapy with clevudine for chronic hepatitis B can be associated with myopathy characterized by depletion of mitochondrial DNA [J]. Hepatology, 2009, 49:2080-2086.[14] Amet S, Bronowicki JP, Thabut D, et al. Prevalence of renal abnormalities in chronic HBV infection: The HARPE study [J]. Liver Int, 2015, 35(1):148-55. [15] Yapali S, Lok AS. Potential benefit of telbivudine on renal function does not outweigh its high rate of antiviral drug resistance and other adverse effects [J]. Gastroenterology, 2014, 146(1):15-19.[16] Qi XP, Xiong S, Yang H, et al. In vitro susceptibility of adefovir-associated hepatitis B virus polymerase mutations to other antiviral agents [J]. Antivir Ther, 2007, 12(3):355-362.[17] Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years [J]. Gastroenterology, 2006, 131(6):1743-1751.[18] Ha NB, Garcia RT, Trinh HN, et al. Renal dysfunction in chronic hepatitis B patients treated with adefovir dipivoxil [J]. Hepatology, 2009, 50(3):727-734.[19] Vigano M, Lampertico P, Iavarone M, et al. High risk of renal impairment during long-term adefovir and lamivudine combination therapy in patients with lamivudine-resistasnt chronic hepatitis B [J]. Journal of hepatology, 2009, 50:S338-S339.[20] Izzedine H, Hulot JS, Launay-Vacher V, et al. Renal safety of adefovir dipivoxil in patients with chronic hepatitis B: two double-blind, randomized, placebo-controlled studies [J]. Kidney Int, 2004, 66(3):1153-1158.[21] Marcellin P, Heathcote EJ, Berg T, et al. Effects of tenofovir disoproxil fumarate on renal function in chronic HBV patients in three global randomized studies [J]. Journal of hepatology, 2011, 54:S296-S297.[22] Brodzinski A, Fueloep B, Schlosser B, et al. Prevalence of renal alterations indicative for proximal tubular damage (PTD) in patients with chronic hepatitis B virus (HBV) infection during long-term treatment with tenofovir disoproxil fumarate (TDF) [J]. Hepatology, 2010, 52:515A-516A.[23] Gara N, Zhao X, Collins MT, et al. Renal tubular dysfunction during long-term adefovir or tenofovir therapy in chronic hepatitis B [J]. Aliment Pharmacol Ther, 2012, 35(11):1317-1325.[24] Chan HL, Chen YC, Gane EJ, et al. Randomized clinical trial: efficacy and safety of telbivudine and lamivudine in treatment-nave patients with HBV-related decompensated cirrhosis [J]. J Viral Hepat, 2012, 19(10):732-743.[25] Gane EJ, Deray G, Liaw YF, et al. Telbivudine improves renal function in patients with chronic hepatitis B [J]. Gastroenterology, 2014, 146(1):138-146.[26] Lee M, Oh S, Lee HJ, et al. Telbivudine protects renal function in patients with chronic hepatitis B infection in conjunction with adefovir-based combination therapy [J]. J Viral Hepat, 2014, 21(12):873-881. [27] Tsai MC, Chen CH, Hung CH, et al. A comparison of efficacy and safety of 2-year telbivudine and entecavir treatment in patients with chronic hepatitis B: a match-control study [J]. Clin Microbiol Infect, 2014, 20(2):O90-O100.[28] 0ugm, 媠褢駛, "宖_決, I{. ?柗_弝鏃o懟l梪YN潃魜NO@堶x'`oS莡剉皊秗R恎[J]. -N齎o僫rfb, 2013,10(5):294-298.[29] Vigano M, Lampertico P, Eller-Vainicher C, et al. High prevalence of reduced bone mineral density in patients with chronic hepatitis B under nucleos(t)ides anlogues treatment [J]. Hepatology, 2010, 52:526A.[30] Wong T, Girgis CM, Ngu MC, et al. Hypophosphatemic osteomalacia after low-dose adefovir dipivoxil therapy for hepatitis B [J]. J Clin Endo Metabol, 2010, 95:479-480.[31] Hamnvik OP, Becker CB, Levy BD, et al. Clinical problem-solving. Wasting away [J]. N Engl J Med, 2014, 370(10):959-966.[32] Klootwijk ED, Reichold M, Helip-Wooley A, et al. Mistargeting of peroxisomal EHHADH and inherited renal Fanconi's syndrome [J]. N Engl J Med 2014, 370(2), 129-138.[33] Woodward CL, Hall AM, Williams IG, et al. Tenofovir-associated renal and bone toxicity [J]. HIV Med 2009, 10:482-487.[34] Goncalves J, Laeufle R, Avila C. Increased risk with combination of telbivudine and pegylated-interferon alfa-2a in study CLDT600A2406, compared to uncommon rate with telbivudine monotherapy from the Novartis global database [J]. Journal of hepatology, 2009, 50:S329-S330.[35] Marcellin P, Avila C, Wursthorn K, et al. Telbivudine (LDT) plus peg-interferon (PegIFN) in HBeAg-positive chronic hepatitis B - very potent antiviral efficacy but risk of peripheral neuropathy (PN) [J]. Journal of hepatology, 2010, 52:S6-S7.[36] Zhang XH, Wu YK, Cao H, et al. Clinical characterization of peripheral neuropathy associaterd with entecavir in patients with HBV-induced cirrhosis [J]. Zhonghua Gan Zang Bing Za Zhi, 2012, 20(9), 707-708.[37] Jin JL, Hu P, Lu JH, et al. Lactic acidosis during telbivudine treatment for HBV: A case report and literature review [J]. World J Gastroenterol, 2013, 19:5575-5580.[38] Cohen SM, Levy RM, Jovanovich JF, et al. Fatal lactic acidosis associated with the use of combination oral medications to treat reactivation of hepatitis B [J]. J Clin Gastroenterol, 2009, 43:1008-1010.[39] Lange CM, Bojunga J, Hofmann WP, et al. Severe lactic acidosis during treatment of chronic hepatitis B with entecavir in patients with impaired liver function [J]. Hepatology, 2009, 50:2001-2006.[40] Lange CM, Sprinzl K, Vermehren J, et al. Prospective observation of lactate values during treatment of chronic hepatitis B with nucleos(t)ide analogues in patients with decompensated liver disease [C]. 116th Congress of the German Society of Internal Medicine; 2010 Apr 9-14; Wiesbaden.[41] Fontana RJ. Side effects of long-term oral antiviral therapy for hepatitis B [J]. Hepatology, 2009, 49(5 Suppl):S185-S195.[42] Thompson PD, Clarkson P, Karas RH, et al. Statin-associated myopathy [J]. JAMA, 2003, 289(13):1681-1690.[43] Assy N, Djibre A, Tzuker M, et al. Vitamin D supplement prevents myalgia and elevation of CPK in chronic hepatitis B patients treated with telbivudine [J]. J Hepatol, 2011, 54:S283.[44] 蒪s|+Y歔Gr魦ffN(:峮fN),2012t^7g23錯. [45] f詋+Y歔Gr魦ffN( }詋O), 2013t^4g15錯. [46] 蘙l歺?f鷭弝鏃孨!TKTo慓r魦ffN(鏃^t穇), 2013t^10g9錯.[47] ?柗_弝鏃o慓r魦ffN(:嶔~汻), 2009t^7g17錯.[48] i`faS鏃Gr魦ffN(ZS飴歔), 2013t^9g7錯. [49] Lin J, Denker BM. Azotemia and urinary abnormalities. Harrison's Principles of Internal Medicine [M], 18th ed. New York: McGraw-Hill Professional, 2011.[50] Labarga P, Barreiro P, Martin-Carbonero L, et al. Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir [J]. AIDS, 2009, 23(6):689-696.[51] Marcellin P, Chang TT, Lim SG, et al. Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B [J]. Hepatology, 2008, 48(3):750-758. [52] Pol S, Lampertico P. First-line treatment of chronic hepatitis B with entecavir or tenofovir in 'real-life' settings: from clinical trials to clinical practice [J]. J Viral Hepat, 2012, 19(6):377-386.[53] Liaw YF, Kao JH, Piratvisuth T, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update [J]. Hepatol Int, 2012, 6:531-561.[54]!単fN. f詋+Y歔Nr^pb }T€(u_w崉vhT鬡^y蟸舥剉4N奮yr筽蔛2柣l[J]. o僫rNo偼S擽Bg譥, 2009, 11(5): 346-350.[55] Anonymous. FDA pregnancy class definitions. <http://en.wikipedia.org/ wiki/Pregnancy_c-ategory/>; 2010 [accessed 08.10].[56] Hepatitis B (chronic): Diagnosis and management of chronic hepatitis B in children, young people and adults. June 2013. NICE clinical guideline 165. guidance.nice.org.uk/cg165.[57] Jonas MM, Block JM, Haber BA, et al. Treatment of children with chronic hepatitis B virus infection in the United States: patient selection and therapeutic options [J]. Hepatology, 2010, 52:2192-2205.[58]-NNS;Sf[O潃舥f[RO, -NNS;Sf[Oa觛舥f[RO. ba'`YN媁潃巔2柣lcWS2010t^Hr [J]. -NNS4N奮a觛舥Bg譥, 2011, 4(1):1-13.gb{N禰 c覻l黚髼抍廭 H\鶄 m_糝 "孏Y餦 笅Oe 鯯SfIQ N禰膥bXT c覻l黚髼抍廭 }v矁 H\鶄 H?lO bi_T€ 臑f[ R郹沍 R譥NS Rh篘 NgQR m_糝 ?k 蟼 媠\‐ 媠荝 "孏Y餦 笅Oe 恄沴o 鯯SfIQ 鯯N淨 褠譥NS⒛つ"&FHNPX\`hl埰娖捚樒毱纹衅BLHLprz度荷镟袜镟井囡囡嗑湂z妟奾X囡嗑Xh/mGh=!36丆JOJQJaJ#h/mGh璝CJOJPJQJaJo(h/mGh=!3CJOJPJaJo(#h/mGh=!3CJOJPJQJaJo(#h/mGh?CJOJPJQJaJo(h/mGh?CJOJQJaJo(h/mGh璝CJOJQJaJ%h/mGh=!3B* CJOJQJaJph3fh/mGh=!3CJOJQJaJh/mGh=!3CJOJQJaJo( 荷忌 Xdr偸埵屖炇犑⑹枋蚴 HRtv|幫愅镟芽瓫瓑瓑瓑瓑wg郬嘌g郬囡嘌繅h/mGh=!36丆JOJQJaJh/mGh?CJOJQJaJo(#h/mGh璝CJOJPJQJaJo(#h/mGh=!3CJOJPJQJaJo(#h/mGh&v7CJOJPJQJaJo(#h/mGh宱CJOJPJQJaJo(#h/mGh?CJOJPJQJaJo(h/mGh璝CJOJQJaJh/mGh=!3CJOJQJaJh/mGh$zCJOJQJaJo(愅 涛挝形谖粑6@F^f娤屜幭$皲掌阀棁w噖j\j\O\B2h/mGh?CJOJQJaJo(h/mGh璝OJQJ^Jh/mGhHAOJQJ^Jh/mGhHAOJQJ^Jo(h/mGh=!3OJQJ^Jh/mGhHAOJPJQJ^Jo(h/mGh=!3OJPJQJ^Jo(h/mGh[NOJPJQJ^Jo(h/mGh?OJPJQJ^Jo(h/mGh璝CJOJQJaJh/mGh=!3CJOJQJaJh/mGhr+ CJOJQJaJh淸CJOJQJaJo(h淸h淸CJOJQJaJ$PZ愌捬匝盅嘌娨屢嬉枰蛞$.屧幵樤谠湓娬溦炚ㄕ恼日收哉`bl溩ψ鹤刎谪湄@JTZpr|蹿沮襻裱衤柴狁疡虏襻衤柴狁q虏衤柴狁狁虏襻裱駜衤柴h/mGh柄CJOJQJaJo(h/mGh肸$CJOJQJaJo(h/mGh肸$CJOJQJaJh/mGh?CJOJQJaJo(h/mGh璝CJOJQJaJh/mGh$zCJOJQJaJo(h/mGh=!36丆JOJQJaJh/mGh=!3CJOJQJaJ3收b谪r槽炤XH落堟络n<陔傢陬燥&H8搠4扎f?$dp^a$gdrj沮df樭炢佰槽价<>溳炤ㄝ鲚:@VXbㄟ策 XbFHR娿斻VX冷落啼 嗘堟掓孺益犁络嚏鲧襻裱衤柴Ⅰ狁虏瘼襻駫衤柴Ⅰ虏瘼衤傫Ⅰ狁聜瘼衤傫Ⅰ聜h/mGh羬CJOJQJaJo(h/mGh?CJOJQJaJo(h/mGh=!36丆JOJQJaJh/mGh?CJOJQJaJo(h/mGh璝CJOJQJaJh/mGh柄CJOJQJaJo(h/mGh$zCJOJQJaJo(h/mGh=!3CJOJQJaJ3鲧Fhlnx搁株仃:<FLPVZ`dfhj齐仉陔潆:D@B€傢岉马雾~€仡陬漕$.绎燥镟朽帘囡唷嗔睉傂傂r戉朽辛编镟∴帘囡唷嗔编镟h/mGh&v7CJOJQJaJo(h/mGh鷅&CJOJQJaJh/mGh=!3CJOJQJaJo(h/mGh$zCJOJQJaJo(h/mGh羬CJOJQJaJo(h/mGh璝CJOJQJaJh/mGh鷅&CJOJQJaJo(h/mGh=!3CJOJQJaJh/mGh=!36丆JOJQJaJ,燥揎2<茵责$&0tv€蜀恬荞揆漶&骟梵FHR橍Ⅳ68Br|hj镟朽类憋唷朽∴憘鄏c唷啾镟戉憋嘈啾镟朽h/mGh蒵CJOJQJaJh/mGh蒵CJOJQJaJo(h/mGh$zCJOJQJaJh/mGhHzCJOJQJaJo(h/mGh=!3CJOJQJaJo(h/mGh璝CJOJQJaJh/mGh$zCJOJQJaJo(h/mGh=!36丆JOJQJaJh/mGh=!3CJOJQJaJh/mGh羬CJOJQJaJo(&j谗瑚诀洒眺憎伧荀搠梓24>債岡tv寅扎搡 *dfp袋军廅慆襻襻襻襻褚埋柴衣癫瘼褚埋柴Ⅰ衣搩搒揷h/mGhDdLCJOJQJaJo(h/mGh*qCJOJQJaJo(h/mGhDdL6丆JOJQJaJh/mGhDdLCJOJQJaJh/mGhHzCJOJQJaJo(h/mGh=!36丆JOJQJaJh/mGh羬CJOJQJaJo(h/mGh璝CJOJQJaJh/mGh=!3CJOJQJaJo(h/mGh=!3CJOJQJaJ%羹??????@Bdf镟辛嘈帘羵拎辛sc罶罶罜h/mGh$CJOJQJaJo(h/mGh=!3CJOJQJaJo(h/mGhr_6丆JOJQJaJh/mGhr_CJOJQJaJh/mGhHzCJOJQJaJo(h/mGh=!36丆JOJQJaJh/mGh>]sCJOJQJaJh/mGh>]sCJOJQJaJo(h/mGh=!3CJOJQJaJh/mGh羬CJOJQJaJo(h/mGh璝CJOJQJaJh/mGhKR4CJOJQJaJo(?B\,d  F  D L2 dhgd'3 $dha$$dp^a$gdrj$dp^a$gdrj $@BL^dvxz~疋意意鲁猡拃n€n\抧JnJnJn\扟\#h/mGhV CJOJPJQJaJo(#h/mGh璝CJOJPJQJaJo(#h/mGh?CJOJPJQJaJo(#h/mGh闟CJOJPJQJaJo(#h/mGh羬CJOJPJQJaJo(h/mGh璝CJOJQJaJh/mGh蒵CJOJQJaJh/mGh蒵CJOJQJaJo(h/mGh=!3CJOJQJaJo(h/mGh=!3CJOJQJaJh/mGhHzCJOJQJaJ$Z\ft&(.26<@B碹煞恁窌卾gWGvGgv7h/mGhgCJOJQJaJo(h/mGh/CJOJQJaJo(h/mGh$CJOJQJaJo(h/mGh/CJOJQJaJh/mGh=!3CJOJQJaJh/mGh?VCJOJQJaJo(h/mGh羬CJOJQJaJo(#h/mGh?CJOJPJQJaJo(#h/mGh璝CJOJPJQJaJo(#h/mGh=!3CJOJPJQJaJo(#h/mGhV CJOJPJQJaJo(#h/mGh羬CJOJPJQJaJo(BDVX*,6t~b d n   n p    襻颐页窑斠勔t窑斠勔窑d覄襱窑R#h/mGh CJOJPJQJaJo(h/mGh CJOJQJaJo(h/mGh$CJOJQJaJo(h/mGh=!36丆JOJQJaJh/mGh羬CJOJQJaJo(h/mGh璝CJOJQJaJh/mGh/CJOJQJaJo(h/mGh/CJOJQJaJh/mGh=!3CJOJQJaJh/mGh萅CJOJQJaJo(h/mGhgCJOJQJaJ          $ & 0 2 4 D F P   B 碹琼淀mmm憗憃_PCPhCJOJQJaJo(h/mGh=!3CJOJQJaJh/mGh CJOJQJaJo(#h/mGh璝CJOJPJQJaJo(h/mGhHCJOJPJaJo(#h/mGhHCJOJPJQJaJo(#h/mGhaFCJOJPJQJaJo(#h/mGh餈OCJOJPJQJaJo('h/mGh=!3CJOJPJQJ^JaJo(#h/mGh=!3CJOJQJ^JaJo(#h/mGh=!3CJOJPJQJaJo(B D N >@JLT襻荫嵋乱惨⒁駩~lZH#h/mGhHCJOJPJQJaJo(#h/mGhr_CJOJPJQJaJo(#h/mGh=!3CJOJPJQJaJo(#h/mGh篈CJOJPJQJaJo(#h/mGh CJOJPJQJaJo(h/mGh=!3CJOJQJaJo(h/mGh$CJOJQJaJo(h/mGh=!36丆JOJQJaJh/mGh=!3CJOJQJaJh/mGh CJOJQJaJo(h/mGh璝CJOJQJaJ02獒陨陨径捕捕捕簿h蟦Cjh蟦CUh'3h'3OJQJh'35丆JOJQJh'35丆JOJQJo(h璝OJQJ,h/mGh璝B*CJOJPJQJaJo(ph $dha$ dgd璝 21恏:p 靶/ 班=!皧"皧#悹$悹%芭芭 愋$$If朷!vh#v #v3#v#v#v#v:V 杔斶 t?,5 535555/ /  a]$$If朷!vh#v #v3#v#v#v#v:V 杔敍 t?,5 535555/  / a]$$If朷!vh#v #v3#v#v#v#v:V 杔斞 t?,5 535555/ a]$$If朷!vh#v #v3#v#v#v#v:V 杔? t?,5 535555/ a]$$If朷!vh#v #v3#v#v#v#v:V 杔? t?,,5 535555/  / a]$$If朷!vh#v #v3#v#v#v#v:V 杔敳 t?,,5 535555/  / a]$$If!vh#v1#v9!:V 杔4旕 tj$+,,5159!/ / / /  $$If!vh#v1#v #v #v. :V 杔4攦 tj$+,,515 5 5. / / /  / / / $$If!vh#v1#v #v #v. :V 杔4? tj$++,,,515 5 5. / / / / / / $$If!vh#v1#v #v #v. :V 杔4? tj$++,,,515 5 5. /  /  / / / $$If!vh#v1#v #v #v. :V 杔4? tj$+,,515 5 5. / / $$If!vh#v1#v #v #v. :V 杔4? tj$+,,515 5 5. /  / $$If!vh#v1#v #v #v. :V 杔4? tj$+,,515 5 5. / / $$If!vh#v1#v #v #v. :V 杔4? tj$+,,515 5 5. / /  / $$If!vh#v1#v #v #v. :V 杔4? tj$+,,515 5 5. / / / $$If!vh#v1#v #v #v. :V 杔4  tj$+,,,515 5 5. / /  / $$If!vh#v1#v #v #v. :V 杔? tj$,515 5 5. /  / / /  b) vvvvvvvvv444>4hH664>4666666666666666666666666666666666666666666666646666 0@P`p€6666 0@P`p€ 0@P`p€ 0@P`p€ 0@P`p€ 0@P`p€ 0@P`p€8XV~PJ_HmH nHsH tHN`?N 璝ck噀 dと$CJOJQJ_HaJmH nHsH tH$A ?$ 貫祂=刉[SOBi@?B 0nf恏圏h4 l4a k ? 0鄀Rh *j@* %璝0yb鑜;N槝5乗?@$ $璝0yb鑜噀W[2Y@2 &璝噀ch觺刧 CJOJaJD橜"D "璝0yb鑜Fh噀,g dCJOJ QJ ^J aJ6 26 !璝0ud?6B6  璝0u wd?0@R0 '璝佽l噀,gG$CJaJP^@bP 璝0nf?Q賨)d[$\$CJOJPJQJaJZ>@Z #璝h槝d?PO伣m$!@B* CJ4KHOJ QJ aJ4ph6\"X`?" 璝@:_6乚?'`?( 璝0yb鑜_(uCJaJ$&`?$ 璝佽l_(uH*.﨩. 璝 R鶴祂=? ^勑m$6?6璝0頞1_HmH nHsH tHP﨩P 璝 R鶴祂=?dWD`勅`劋CJOJQJ^JaJP﨩P 璝 R鶴祂=?dWD`勅`劋CJOJQJ^JaJ"" 璝nobr1&& 璝0u w Char&& 璝0u Char@?!@ 璝0 yb鑜Fh噀,g CharCJOJ QJ ^J aJL?1L 璝h槝 Char%@B* CJ4KHOJ PJQJ aJ4ph6\*A* 璝0 yb鑜噀W[ Char0?Q0 璝0 yb鑜;N槝 Char5乗??a< 璝 噀ch觺刧 CharCJOJQJaJ:?q: 璝 佽l噀,g CharCJOJQJaJ*U`?* HA厤 >*B*phPK!檗?[Content_Types].xml瑧薔?E鱄鼉?J湶@%閭菐洽|廊?韶钵UL襎B l,?鳛;鉹得槣B+$G]ミ7O侪V墎}J灢0礊E鞝m祁h钤=踉剳艘 螢a酤s??, 酧萆犂汖Hp Ua/ 鞺O d*:?.媐筎镀绵U钞/!?$V[|h棗魊v兹s⊥-i荱秚. 窘幉?曦讵?C妿盾ebs)噽绠羈Mj孊錯跟k誴倭 u躮幉礃,渇奷垏$蛻鰗6GU摛琕f褈豣?兄衎這踧扵TW洠.宿沝)i朄卺vdq?Y岞沕>X鲪彄?倇2%恥╃Hx玟+a塔萬6]>蚮#s蘭?贱皅焣蒯丏H祦ehK曼JK€臵摰a=-J罔xV,瑻1黭V@菰捬堷獦炻妿濤楻)+"z醦豖靈H?U餲H%碱0尃?阑9m笕%绱閵o 萎c杽8茛Y'[?ぼ螬`鳹j籷钿畼?%W奺?sE?瘀ai?嗝b亼顢η 9癙R?`p0飛?姬6儆縨蟉Ν﹙h€咉H厒恗?S}Gg蒖AΒ 媸臍= {匁5.氤軨!敽a摂 頿熡z?鰶胐k{鄊O>稒?棁虭撆?71Ηo秅go齚:f詹e叄爲洱k歱拢?謱菋跆8肉皹D 糃B?81e誉nE疱eU}H类dm1iQ6撮瑜支<殒z[[v渱?伫p妾sz?儩F貕礭j褥叆Qv??邧可鈨洂`虜4逽 3t萧4空h懂PK!褠煻'theme/theme/_rels/themeManager.xml.rels剰M ?匃倃oo雍?輬协勪56?$Q祉?.嘺緳i粭澤c2?h:闀q毩m胳嶡RN壻;d癭値o7g慘(M&$R(.1榬'J摐袏T鶂?V?&A然蠬鱱}狇|?絙{朠?除8塯/]As賲(⑵锑#洩L蔥汉倪PK-!檗?[Content_Types].xmlPK-!ブх6 0_rels/.relsPK-!kytheme/theme/themeManager.xmlPK-!閘N嵈theme/theme/theme1.xmlPK-!褠煻' theme/theme/_rels/themeManager.xml.relsPK] vO 6 . 8 0@L!\"t#*)??r59@<蔺xDdE蔈`F銯擥jHJJP黂黆⒛荷愅$沮鲧燥jB B ,./0234568;@BCDEFHIJMPSVY[\^_`z!?^"??,#t#*9艱RE濫‥鐴.FpF睩餏圙VH0JV收?-179:<=>?AGKLNOQRTUWXZ]a饃  ?€溇徽喠s溍帕>@€€€餒 ??  饞??  養 S  ? OLE_LINK1 OLE_LINK2 OLE_LINK3 OLE_LINK4::wOIIwO !#)-./08:CFMT[ *+./5>?CJRSW^ghlorsvwz*:B    & ' / 1 2 8 S W Y _ b j t z   W ^ ` f  % & + / 1 < G J K f h { |  €   0 7 8 = @ L \ rz{~VW'1469=@Ycmnr(7+IKNQRUX[ehilnopq&'*17:MQRW[\]23=A-589<>ACPWX  +89<DKwx|~49:FTV[fhilrsy|u ",/56:,Zd"#&)HLMdj/Z]hnx~" # $ % ) + w | ~  !!-!+Q+Y+????????+,,,, ,Q,[,_,c,??- --+-??????a.l.1/9/??????????0 0J0T0m0q0??1%1@1D1H1R1W1]1??????????>3E3F3J3f3q3v3?????????????????????,545t5~5????????6666????????????U7_7z7???O8X8Y8c8d8l8x8??????9-96979;9l9p9: :=:A:F:K:O:S:];e;岥扄e<i<j<s<桙欬淈烖狘|???奎妩朦稂?==s=z=価夶欭}笼驱听淆埤臊忑? >>>><>@>F>M>f>m>湖峻恂膻瘙?? ?? ?$?/?K?T?e?i???@@@@K@V@[@d@鳣AA&A3AGBGFGLGPGVG蒅訥蹽鉍鵊礼HH HHHHHHH"H#H&H.H/H0H1H3H4H3a3e<扅KF\F薋笻I@I桳鬖MhOjOkOmOnOpOqOsOwO薟0畡置))畂?叭l?>D?>D%a菵靉n?勓?勓`?(勑?齘勑`?齩(.勑?齘勑`?齩(..?勅鸮?`勅鹢(... 劆刞鷁劆`刞鷒( .... 匄鴁`匄鴒( ..... 刾剱鱚刾`剱鱫(...... 刾剱鱚刾`剱鱫(....... 勜 ?鯺勜 `?鰋(........€刪剺刪`剺(刪剺刪`剺(.€勑?齘勑`?齩(..€?勅鸮?`勅鹢(...€ ?勅鸮?`勅鹢( ....€ 劆刞鷁劆`刞鷒( .....€ 劆刞鷁劆`刞鷒(......€ 匄鴁`匄鴒(.......€ 刾剱鱚刾`剱鱫(........劼凗劼`凗?o(勑?齘勑`??o(.勑?齘勑`??o(..?勅鸮?`勅?o(... 劆刞鷁劆`刞?o( .... 匄鴁`匄?o( ..... 刾剱鱚刾`剱?o(...... 刾剱鱚刾`剱?o(....... 勜 ?鯺勜 `??o(........刪剺刪`剺﨩JQJ^Jo(.€凥刓凥`刓)勳刓勳`刓.€剱刓剱`刓.€?刓?`刓)勜 刓勜 `刓.€剕 刓剕 `刓.€ 刓 `刓)勀刓勀`刓. 勓?勓`??QJo( 勑?齘勑`??QJo(. 勑?齘勑`??QJo(.. ?勅鸮?`勅?QJo(... 劆刞鷁劆`刞?QJo( .... 匄鴁`匄?QJo( ..... 刾剱鱚刾`剱?QJo(......  刾剱鱚刾`剱?QJo(.......  勜 ?鯺勜 `??QJo(........)?>D%a菵畂?薟0N0酳  0 ?烃縑Z馺d磎+}]": H*qCz4}`7&;ゞ磑wN`:?AVT爊{?抂鎗渧?q.XA7P鶵躩鎪t `R{`dCo|t:1`歵0}9贱荌鐹協瓄 z  5 hA J  ? :@ 蘓 蔥 /^ 秠 ? ? ? 駻 橳 V] |f Nl 鵸 Gv 纕 Tw      ? @5 ? ~W Fx  \$?CD蔔僣g鑛媤倊/N1?V?YH烵籤僩榽/!?h2躋搑ZzQ{寍 /??鼲朌mJzP/^瀆aa *攁 m6s舲~l\??宻u?R*"Q頥fY纗???6臝蒛`x緘m]a'S=轔Alcr{  ???6%7T8 ;M>鳯腪絔yk \3!p#(:-092?U@ B鉑[芵4g萾bv ?楜g@臜扞>~ w wve|??(?}O訶*\l噖:霡薉>L鯫=y~?扄峂阥yn閠Nb+餎jHLI峑﹊畃??扊YA揮駊ww 9aB霯哰s*  r+ ? 4 A 瓵 鐵 cH xN lO 蕁 (!*!D3!ND!繣!哫! ]!醖!de!(y!種"鏤"Wj"妋"br"I#R(#?#?#X>#騑#q#$$?$?$L6$@$楨$≦$肸$ac$ %R%?%?%#A%YD%鑂%=Z%%&&€"&_&a&鷅&o&$'*%'?'BS'孼'嶾'^']c'6(?(?(]W(Pl(粇())))x")UB) I)*N)1S))渁)***?*?*咠*n]*區*恏*瀟*5%+?+隓+^+b,I,^,?,E=,~H,Nj,峹,p-?-jd-Qq- w-粅-..铤.齥.坢.e}./!>/uH/#T/~[/4p/0?090轛0EZ0yy0q{0瘂0P 11o 1)!1?1萀1%]1:2%2%2@220-2?2C32鯣2ug2畇2€w2d3>33=!3?3?3J3絈3V3"{37|34>44?4?4?4:34矹4KR4攙4+555?5:5袮5*G5禜5S5\5馷5\d5鑙56W6 66?6t66f6}m677}7y&7?7?7綪7蚏7zZ7}d7蝔7萺7&v7剘7888烡8/I8 W8{]8Me8阤8c|8]9$9?9?9a:9c=9滯9c9+f9{9:a:|,:迭:哅:O:TR:n:f;;P;;;;; ;8M;稺;;h;$v;<<<J<?<?<蠪<{_<o=/&=瘊=?=A={O=諿=刧=@x=竬=?>6R>m[>Vf>s>鯲?絏?軿?#k??@=@扜@礜@\g@;AA?A?A!PAaUA乑A梍AqxA衺ABEB8!B?B?B%7B貸B轣B}eB韟B漿BC C0C帔CP;C蟦COuCD~XDMbD恇DEE?E腁E骴E間E靝EFNFeFF'F?F?F僛F:]FaFGGGG'G?G狖G餑G/mGHlHN+H?H\>H嘍H禭HasH鎤H皘Hh~H&/I砱I県I搚I瀪IJ?J{.J?JR4JQQJ踕JSrJH{JK?K?K%K?K1K臔K郞KXPK{UK絚K辒K蘵K L[:L酐L馎LdZL蒨LDdL%M?MD;M瑻M汵M`M!`M蚦M |MCNN,N/NZN弝NO[O9*O?O餈OM}O77P袺PHOP^uP=~PQQvQQ#CQ睭Q鉗Q酭QWQRRRR[-R?R8>R旽R閇R.SSS!S~&S岯S哱S沖S黣SFpS靪STATT_Tp,T?T\NTF\T塩TLfTgT8sTUU#U?U{2U(EU隣U閌U\eU鵮UV~V#V?V**VU*V潸V郍V砐V歛VsbVedV顃V}WWiWNW_WxW,W?W"5WPEW維WidWnWOX?X?X?X睑Xr=X選XX} Y?Y覤Y筁YafYZZZZ()Z4Zt8Z褾ZdZ>gZ籯Z,Ze[z[q [?[-)[?[?[?[璆[蔩[蕕[\! \ \?\N,\1\淴\賎\琧\d\d\6|\p|\/]3R]蒖]}W]Z]鏮]xb]?^?^?^笯^#Y^褄^_#_J)_?_慫_礶_択_6`c ```?`苀`媜`眜``aasaaD^p硃pAqU q"qfqq?q0Lq蘒q5cq*lqcoq<r`!rt-r朆reQrr8xrsss!s>]s耟s7os[us泇stt/!t! C"&??]B/N硁K藊t> m!d+?@訞`B C頧鯾韉KnXs1E?Z-oBZrj*?楛銪菶郖跶鋔k鷙Z{, aG%-鱅環FiA~鈤=x0???:;鉕{Z骳蔱甼鱶 筑??TA"B贐WX蟏鎥 A 擣R\靎~xY" JQS塖JY阧8sV?艱tEK_齜7z晑菿hS@t(.橯TiN ???珿1H2W纀噅乿w S:TLdY璴mm`px檤"10贔 H奌圥6Tur~ 薾m 冫Y?uNO_PMUWSa糽[obt=yMX%??Eai3t蓒o],U23K揫渀沜唊烖橮hMzW}#qgf  ?\N焗眡7 %x)馴Vc厁C c%??欽W攇辢唙觱舲:}W4 ?蔺pG嘷Jaf鹙usu4vwV ?楜昌塏8Y檂b軂 ???p4釧dHuU僔_o'?S7慗oXZ{0IB鉌峉awuAwSy?8)='A駻H鵷黺歽瓇W?8.uI K7^e&|9 ?="~'??柄w<CD濳玨髃Qux/xe<&烰扻h.r< 4l"_踗@k|r{{np X[?$/o/親郬臽^} \??H甃颫jI"?鴐鵴cz絈ee纗ke?PF鱅nK絈[玚4c韊niB%>} | 1e4==昗爍ss皚??疘韃 d|gz2/"?I鮆T╞X6^3?泣釧岯xL~f?$?]@/FG鱄]jT ?V0?'Vo> ZO&?w;JVW抧St謜漿$?螱糒﹜Sc%J)??痝 )")2禘鳺Sa乻 O????[N0T觠€{]mIIE霯)d齤Sk硏*{? !_#???ZC鶫獿睶< QwT蒵P6?X@贏乥 ?'3軩`W砶pWq];昋閕饃 x(HAD縁dQT禱禼! -NZ*{觚蒫沝謉km\"??腍軰dQ[蝅hsBv09?+6??篈=N筧鴙 A?13[@v@mZ淸x?釹^Aj67??躷黽<?躊鱚oa馼靏kp --t1絀塳  1恸塁"I硏2)?睩_QxW籛攃緌F7"'?C7?碨Mb苪(??q+?虳*Em?稔?H篨琙m^鉳僴,s?5跶凾QeVuw-//??lH5KhQ凲kT踀XY裛Ea趡p'?鷝=)[6匧璝蟚 La,ZG%KdmY_*?MC8DezPr 縄bhzl??+<py??n; C朻IU FV*D-q5.H萅 ?f5〣螪廏kO鱒Ua醟HsqxQo [?襂XX奺総!v8xe#罝S_v_5e7k!m銁C6#s3?;<?rD鏳#o u#?)妩EJ{X奭籧j ?y(?!8桞pEfSY`羏焗X ??vh鴋鮱< u)婝/JS餪靑Hz晑6)?薝羬 鳊隩遜縧宱顂u*4(\6SZk?cH*N籓琷鹟/vr顳﨧酧BY oWv:蘇穛鵴鷕9w?/3&;*CbL馧訲覺璟€n|uz&.?pM!h磇琸it鵻  &?踙瀖n?键@鵑 .螸EY莈huv踸.}y.%?氟CmDs~XF Gy"%??贎{E頵葂@F g{?0E狥廡Na錼?滻琞梎紀p$ ? &[&?Y/?vE|RDinmq| +齊蝃9mRB y閥 ??EA獶^W卂€a萯?1??頏糋僋蔦鉵蟭0y亇??蘓 ?S-2?)Cqs?6 $籃EKPvb"kL h*?E郞奭蚼w蛚, ??PA荕鑧6|CCW瞗簅?!AfP:R鈇唓蘶{x=Tnrk?硘hOjO@€7777d  ??vO``@```&`H`J`Unknown G? €Times New Roman5€Symbol3. ? €Arial;5 N媅_GB23123Rz個{h媅;媅SOSimSun;褳SOSimHeiE. Century Gothic7.?@ Calibri5. ?a€Tahoma7?@CambriaA?$BCambria Math q€ha"2gZ|4g蓏4g 嶤(悙 嶤(€?!%),.:;>?]}    & 0 2 3 : !6"000 0 00000006??兀﨑  =@\]^?$([{  0 0 000000Y;[??亖2@O@OC僎€HX ?$P?2! xx baYN潃8h鱾x {|o僫rg梑舥襨籰梪剉塠hQ'` Reed ElsevierUser      ?鄥燆鵒h珣+'迟0 $0 P \ ht€0慢乙肝核苷(酸)类药物长期抗病毒治疗的安全性 Reed Elsevier Normal.dotmUser14Microsoft Office Word@d?@.趧)w@n祩@@Dl/^w 嶤?胀諟.摋+,D胀諟.摋+,d  hp  Reed Elsevier(@O .慢乙肝核苷(酸)类药物长期抗病毒治疗的安全性 Title(_gKSOProductBuildVer_NewReviewCycle2052-9.1.0.4866  !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~€??????????Root Entry F鄒滷^w€Data 1Table躳WordDocument46SummaryInformation(DocumentSummaryInformation8MsoDataStore0|~F^w鸷楩^w5XXVUCRPDUHV5==2 0|~F^w廎^wItem  PropertiesF14LENRQ==2 0|~F^w鸷楩^wItem   PropertiesUCompObjn? ? ??? ?  FMicrosoft Word 97-2003 文档 MSWordDocWord.Document.8?瞦