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鐞嗚В绱�(x矛)鑳炲寲瀛�(xu茅)銆佸厤鐤啋鍏夌窗(x矛)鑳炲寲瀛�(xu茅)銆佺窗(x矛)鑳炲厜搴﹀拰娴佸紡绱�(x矛)鑳炲垎闆㈡妧琛�(sh霉) 浜嗚В闆婚彙绱�(x矛)鑳炲寲瀛�(xu茅)鍜岄浕閺″厤鐤窗(x矛)鑳炲寲瀛�(xu茅)鎶€琛�(sh霉) 浜嗚В椤井鏀惧皠鑷’褰�銆佸垎瀛愬師浣嶉洔浜� 3.3. 浜嗚В绱�(x矛)鑳炲煿椁�(y菐ng)銆佺窗(x矛)鑳炲伐绋�銆侀’寰搷浣�銆佹椿楂旀煋鑹茬瓑鎶€琛�(sh霉)鏂规硶 4锛� 绱�(x矛)鑳炲櫒鐨勭祼(ji茅)妲�(g貌u)鑸囧姛鑳� 4.1. 鍏�(n猫i)鑶滅郴绲�(t菕ng)鐨勬蹇靛強鍏剁祫鎴愭垚鍝� 4.2. 鍏�(n猫i)璩�(zh矛)缍�(w菐ng) 4.2.1.鎺屾彙鍏�(n猫i)璩�(zh矛)缍�(w菐ng)鐨勫舰鎱�(t脿i)绲�(ji茅)妲�(g貌u)鐗瑰緛鍜岄鍒�(绮楅潰鍏�(n猫i)璩�(zh矛)缍�(w菐ng)鍜屽厜闈㈠収(n猫i)璩�(zh矛)缍�(w菐ng)) 4.2.2.鐞嗚В鎺屾彙绮楅潰鍏�(n猫i)璩�(zh矛)缍�(w菐ng)鐨勪富瑕佸姛鑳� 鎺屾彙鎸変俊铏熻偨鍋囪鍙冭垏鍒嗘硨铔嬬櫧鍜屾憾閰堕珨閰剁瓑铔嬬櫧鍚堟垚. 鎺屾彙铔嬬櫧璩�(zh矛)鐨勪慨椋�(鍖呮嫭 N-閫f帴绯栧熀鍖�銆侀叞鍩哄寲绛�)鍜屾纰烘姌鐤� 4.2.3.鎺屾彙鍏夐潰鍏�(n猫i)璩�(zh矛)缍�(w菐ng)鐨勫姛鑳斤細鑶滆剛椤炲拰鐢鹃婵€绱犲悎鎴�銆佽優璩�(zh矛)婧惰啝 Ca2+姘村钩瑾�(di脿o)绡€(ji茅)銆佽В姣� 鍜屽弮鑸囩硸鍏冨悎鎴愯垏鍒嗚В绛� 4.3. 楂樼埦鍩洪珨 4.3.1.鎺屾彙楂樼埦鍩洪珨鐨勫舰鎱�(t脿i)绲�(ji茅)妲�(g貌u)鐗归粸锛岀祼(ji茅)妲�(g貌u)鍒嗗崁(q奴)锛屽強鍚勫崁(q奴)鐨勬(bi膩o)蹇楁€ч叾 4.3.2.鎺屾彙楂樼埦鍩洪珨鐨勫姛鑳� 铔嬬櫧璩�(zh矛)鐨勪慨椋惧拰鍔犲伐锛歄-閫f帴绯栧熀鍖栬垏纾烽吀鍖栧拰纭吀鍖�锛汵-閫f帴绯栧熀鍖栫殑鏀� 4.4. 婧堕叾楂� 4.4.1.鎺屾彙婧堕叾楂旂殑褰㈡厠(t脿i)绲�(ji茅)妲�(g貌u)鍙婂寲瀛�(xu茅)绲勬垚鐗归粸 4.4.2.鎺屾彙婧堕叾楂旂殑鍔熻兘 婧堕叾楂旂殑鍩烘湰鍔熻兘锛嶆秷鍖栦綔鐢ㄥ強婧堕叾楂旂殑浜為鍔冨垎 婧堕叾楂斿湪鑷櫖涓殑浣滅敤 婧堕叾楂旂殑鍏朵粬鍔熻兘 , 4.4.3. 浜嗚В婧堕叾楂旂殑鐧�(f膩)鐢� 4.5. 寰珨 4.5.1.鎺屾彙寰珨鐨勫叐绋鍨嬪強鍏跺叡鍚岀殑褰㈡厠(t脿i)绲�(ji茅)妲�(g貌u)鍜岄叾鐗瑰緛 4.5.2.鐞嗚В閬庢哀鐗╅叾楂旂殑閰剁壒榛炲拰鍔熻兘锛嶈В姣掍綔鐢紝妞嶇墿鍏夊懠鍚镐腑鐨勪箼閱囬吀 浠h瑵 4.5.3.鎺屾彙涔欓啗閰稿惊鐠�(hu谩n)楂旂殑閰剁壒榛炲拰鍔熻兘锛嶅弮鑸囩ó瀛愯悓鐧�(f膩)涓殑绯栫暟鐢熶綔鐢� 4.5.4.浜嗚В闂�(gu膩n)浜庡井楂旂殑鐧�(f膩)鐢熷晱椤� 4.6. 绶氱矑楂� 4.6.1.鎺屾彙椤井褰㈡厠(t脿i)鐗瑰緛鍜屼富瑕佸姛鑳芥瑕� 4.6.2.鎺屾彙瓒呭井绲�(ji茅)妲�(g貌u)鑸囧姛鑳藉畾浣嶅強鍚勯儴鐨勭祼(ji茅)妲�(g貌u)鍜屽寲瀛�(xu茅)鐨勭祫鎴愮壒榛� 4.6.3.鐞嗚В鍏�(n猫i)鑶滈€�(j矛n)琛岃兘閲忚綁(zhu菐n)鍖�(姘у寲纾烽吀鍖�)鐨勫垎瀛愬拰瓒呭垎瀛愮祼(ji茅)妲�(g貌u)鍩虹(ch菙)鑸囪綁(zhu菐n)鍖栨(j墨)鍒� 4.7.钁夌稜楂� 4.7.1.鎺屾彙钁夌稜楂旂殑椤井褰㈡厠(t脿i)鐗瑰緛鍜岃秴寰祼(ji茅)妲�(g貌u) 4.7.1.1.椤井褰㈡厠(t脿i)鐗瑰緛 4.7.1.2.瓒呭井绲�(ji茅)妲�(g貌u)锛� 椤炲泭楂�(鐗囧堡绯荤当(t菕ng))锛氬熀绮掗鍥婇珨(闄勫熀绮掓蹇�)銆佸熀璩�(zh矛)椤炲泭楂斻€佸熀璩�(zh矛)(鍏�(n猫i)鑵�) 4.7.2.鐞嗚В鎺屾彙钁夌稜楂旂殑涓昏鍔熻兘锛嶅厜鍚堜綔鐢ㄦ瑕侊細 绺藉弽鎳�(y墨ng)锛涢殠娈靛強浜為殠娈靛妰鍒�(鍏夊弽鎳�(y墨ng)锛氬師鍒濆弽鎳�(y墨ng)鈫掗浕瀛愬偝閬炩啋ATP 鍚堟垚锛涙殫鍙嶆噳(y墨ng)锛氬崱鐖� 鏂囧惊鐠�(hu谩n))锛涘弽鎳�(y墨ng)瀹氫綅 4.7.3. 鐞嗚В鎺屾彙椤炲泭楂旇啘閫�(j矛n)琛屽厜鍙嶆噳(y墨ng)(鍏夊悎纾烽吀鍖�)鐨勫垎瀛愬拰瓒呭垎瀛愮祼(ji茅)妲�(g貌u)鍩虹(ch菙)鍜屽弽鎳�(y墨ng)閬庣▼ 4.8. 绶氱矑楂斿拰钁夌稜楂旂殑鍗婅嚜涓绘€� 4.8.1.鎺屾彙鍗婅嚜涓绘€х殑涓昏琛ㄧ従(xi脿n) 4.8.2.鐞嗚В绱�(x矛)鑳炶唱(zh矛)鍚堟垚鐨勭窔绮掗珨钁夌稜楂旇泲鐧戒箣杞�(zhu菐n)閬�(y霉n)姗�(j墨)鍒�銆傞檮锛氬垎瀛愪即濞樻蹇� 4.8.3.浜嗚В绶氱矑楂斿拰钁夌稜楂旂殑绻佹畺鏂瑰紡 4.9.浜嗚В寤g京鍜岀嫻缇╃殑绱�(x矛)鑳為鏋舵蹇� 4.10.寰挡 4.10.1.鎺屾彙寰挡鐨勫舰鎱�(t脿i)绲�(ji茅)妲�(g貌u)鍙婃(g貌u)鎴愬井绲茬殑鍒嗗瓙--鑲屽嫊铔嬬櫧 4.10.2.鎺屾彙寰挡鐨勭祫瑁濆拰瑙h仛銆佹案涔呮€у井绲茶垏鏆檪鎬у井绲� 4.10.3.鎺屾彙寰挡绲�(ji茅)鍚堣泲鐧� 4.10.4.鐞嗚В姗磱鑲岀簴缍�(绱�(x矛)鑳�)涓殑寰挡绯荤当(t菕ng)鑸囪倢鑲夋敹绺(j墨)鍒� 4.10.5.鎺屾彙闈炶倢鑲夌窗(x矛)鑳炰腑寰挡鐨勭壒榛炲拰鍔熻兘锛氬井绲ㄦ瘺涓殑鏀灦浣滅敤銆佽優璩�(zh矛)娴佸嫊鍜岀窗(x矛)鑳炵Щ 鍕曚腑鐨勪綔鐢�銆佽優璩�(zh矛)鍒嗚涓殑鏀剁府鐠�(hu谩n)浣滅敤銆佺窗(x矛)鑳為€f帴涓殑浣滅敤(闄勮憲甯�銆佹噳(y墨ng)鍔涚簴缍�) 4.10.6.鎺屾彙寰挡鐨勭壒鐣版€х牬澹炶棩鐗╁拰绌�(w臎n)瀹氳棩鐗� 4.11.寰 4.11.1 鎺屾彙寰鐨勫舰鎱�(t脿i)绲�(ji茅)妲�(g貌u)鍜屽井绠$殑绋鍙婂垎甯� 4.11.2 鎺屾彙寰铔嬬櫧鍜屽井绠$祼(ji茅)鍚堣泲鐧� 4.11.3 鎺屾彙寰鐨勭祫瑁�銆佸幓绲勮鑸囧井绠$祫绻斾腑蹇�锛屽井绠$殑鈥滄粦杌娾€濈従(xi脿n)璞�锛屾案涔呮€у井绠″拰 鏆檪鎬у井绠� 4.11.4 鐞嗚В寰鐨勫姛鑳� 4.11.5 鎺屾彙寰鐨勭壒鐣版€ц棩鐗╁拰寰绲勬垚鐨勭窗(x矛)鑳炲櫒 4.12.涓枔绾栫董 4.12.1. 鎺屾彙涓枔绾栫董鐨勪竴鑸舰鎱�(t脿i)鍜岄鍨嬪強椤炲瀷鐨勭窗(x矛)鑳炵壒鐣版€� 4.12.2. 鐞嗚В涓枔绾栫董铔嬬櫧鍒嗗瓙鐨勪竴鑸祼(ji茅)妲�(g貌u)妯″紡鍙婁腑闁撶簴缍殑绲勮 4.12.3. 浜嗚В涓枔绾栫董绲�(ji茅)鍚堣泲鐧� 4.12.4. 鐞嗚В涓枔绾栫董鐨勫姛鑳斤細鏀灦鍜岄€f帴浣滅敤锛涗俊铏熷偝閬炲拰鍩哄洜琛ㄩ仈(d谩)绛夋柟闈㈢殑鍙兘浣� 鐢�銆� 4.13. 鏍哥硸楂� 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鐞嗚В瑾�(di脿o)鎺х窗(x矛)鑳炲娈栧拰绱�(x矛)鑳炲懆鏈熺殑鍏朵粬涓昏鍥犵礌 10锛庣窗(x矛)鑳炲垎鍖�銆佽“鑰佽垏鍑嬩骸 10.1. 绱�(x矛)鑳炵殑鍒嗗寲 10.1.1.鎺屾彙绱�(x矛)鑳炲垎鍖栫殑姒傚康鍙婅垏鍏剁浉闂�(gu膩n)鐨勫咕鍊嬫蹇碉紙绱�(x矛)鑳炵殑鐧�(f膩)鑲叉經鑳�銆佸共绱�(x矛)鑳烇級 10.1.2.浜嗚В绱�(x矛)鑳炶唱(zh矛)鍦ㄦ棭鏈熻儦鑳庣窗(x矛)鑳炲垎鍖栦腑鐨勬焙瀹氫綔鐢ㄥ拰浣滅敤鐨勭墿璩�(zh矛)鍩虹(ch菙)--寰炲舰鎱�(t脿i)鐧�(f膩)鐢熸焙 瀹氬瓙鍒版瘝楂� mRNA 10.1.3.鎺屾彙鏍稿熀鍥犵殑琛ㄩ仈(d谩)鑸囩窗(x矛)鑳炲垎鍖栵紙绱�(x矛)鑳炴牳鍦ㄧ窗(x矛)鑳炲垎鍖栦腑鐨勪綔鐢級 10.1.4.鎺屾彙绱�(x矛)鑳為枔鐩镐簰浣滅敤灏嶇窗(x矛)鑳炲垎鍖栫殑褰遍熆鍙婄浉浜掍綔鐢ㄩ鍨嬶細瑾樺皫(d菐o)浣滅敤銆佺窗(x矛)鑳炲弽鏁堟噳(y墨ng)銆� 婵€绱犱綔鐢� 10.1.5.鎺屾彙鐠�(hu谩n)澧冨皪绱�(x矛)鑳炲垎鍖栫殑褰遍熆 10.2. 绱�(x矛)鑳炵殑琛拌€佸拰姝讳骸 10.2.1.鎺屾彙绱�(x矛)鑳炶“鑰佸拰姝讳骸鐨勫瑙€鎬ц垏 Hayflick 鐣岄檺 10.2.3 鎺屾彙.绱�(x矛)鑳炶“鑰佺殑鐗瑰緛鎬ц〃鐝�(xi脿n) 10.2.3.鎺屾彙绱�(x矛)鑳炶“鑰佺殑鍘熷洜鍜屽亣瑾� 10.2.3.1.鑷敱鍩虹悊璜� 10.2.3.2.绱�(x矛)鑳炵殑绶ㄧ▼鎬ф浜¤垏绶ㄧ▼鎬ф浜$浉闂�(gu膩n)鍩哄洜 10.2.3.3. 绱�(x矛)鑳炲噵浜$殑閫斿緫 11锛庣窗(x矛)鑳炶捣婧愯垏閫�(j矛n)鍖� 11.1. 浜嗚В鏈夐棞(gu膩n)绱�(x矛)鑳炶捣婧愮殑鐮旂┒锛屽亣瑾拰灏氬瓨鍟忛 11.2. 浜嗚В寰炲師鏍哥窗(x矛)鑳炲埌鐪熸牳绱�(x矛)鑳炵殑閫�(j矛n)鍖� 11.2.1.鐪熸牳绱�(x矛)鑳炴簮浜庡師鏍哥窗(x矛)鑳炵殑璀夋摎(j霉)锛氬彜鐢熺墿瀛�(xu茅)锛堝寲鐭筹級鐨勮瓑鎿�(j霉)锛涘垎瀛愮敓鐗╁(xu茅)鐨勮瓑鎿�(j霉)锛� 娲诲寲鐭崇殑璀夋摎(j霉) 11.2.2.鐪熸牳绱�(x矛)鑳炵殑绁栧厛鍙兘鏄彜浠e師绱�(x矛)鑿岀殑鐮旂┒璀夋摎(j霉)锛氱窗(x矛)鑳炲鎴愪唤鐨勭爺绌�锛孌NA 搴忓垪 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