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筋委縮性側索硬化症(ALS)を対象とした 乳歯幹細胞を用いた培養上清治療の有効性を確認


2022年1月12日
株式会社再生医学研究所
(協力:スマート・クリニック東京)

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報道機関 各位
                                          
 株式会社再生医学研究所(代表:上田実・名古屋大学名誉教授・東京都中央区)の上田実・名古屋大学名誉教授と研究グループは乳歯幹細胞由来培養上清(SHED-CMと略す)の投与によって、脳や脊髄の炎症が強力に抑えられ、神経細胞の喪失と運動能力の低下を改善することにより、アルツハイマー病、慢性期脳梗塞などに著明な効果があることを明らかにしてきました(1-4)。これらの結果から、SHED-CMは筋萎縮性側索硬化症(Amyotrophic Lateral Sclerosis:ALSと略す)の神経細胞を活性化し運動能力を回復させる新たな治療法になる可能性が高いと考えられます。
 このたびSHED-CMを用いてALSの治療を行い、急速に悪化しつつあった呼吸機能を安定化させ、四肢および頸部の痙縮の解除および運動可動域の改善をみとめたことをご報告します。
なお本症例の詳細は、米国科学誌、Neurology and Neuro Rehabilitation(筆頭著者;上田実)に投稿中です。

 培養上清治療は幹細胞治療にかわる新しい再生医療として注目を集めています(図1)。なかでも乳歯歯髄由来の幹細胞を原材料とするSHED-CMには神経保護、軸索伸長、神経伝達を促進する作用や免疫抑制効果を持つ多彩な神経栄養因子が含まれています(図2)。

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【本発表のポイント】

1・乳歯幹細胞由来の培養上清を用いて世界ではじめてALSの治療を行った。
2・呼吸機能の安定維持と痙縮による全身硬直を改善し関節の自動運動を回復した。
3・培養上清治療は幹細胞治療に代わる新しい再生医療になる可能性が示された。
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【背景】
 ALSは原因不明の神経の難病で主として中年以降の男性に発病し、運動神経(上位運動ニューロン、下位運動ニューロン)の変性によって嚥下、発声、呼吸などの機能が失われ、発症後は進行が止まることはなく、3〜5年で死に至る深刻な病気です(図3)。
 日本には約9000人、世界では約40万人の患者がいると推定されていますが、ALSに対する有効な治療法はなく、国の指定する最も重要な「アン・メット・メディカル・ニーズ」の代表例といわれています。
 進行性の症状のなかで患者と看護者を最も苦しめる症状として痙縮(Spasticity Contracture:全身の関節が固まり動かなくなること)があります。痙縮はALSに特徴的な症状のひとつで、患者の生活の質(QOL)および日常生活動作(ADL)を著しく障害します。痙縮を、薬剤や細胞移植で改善したという報告は過去になく、本症例は世界初の成功例と考えられます。

【症例報告】
 患者(68歳、男性)は2019年2月ころに手足の筋肉の萎縮と運動障害を自覚して、近くの病院を受診しました。担当医は精密検査の必要性を感じ、地域の基幹病院である横浜市立大学病院脳神経内科に紹介をしました。同病院で、筋電図検査、MRI、呼吸機能検査など多方面からの検査を実施した結果、2020年6月にALSと診断されたのです。その後、患者はALSの拠点病院である北里大学病院神経内科に転院し、慎重に経過が観察されていましたが症状の進行は止まらず、家族が新しい治療法としてSHED-CMによる治療を希望したため、2021年1月、上田名誉教授および連携病院であるスマート・クリニック・東京(東京都千代田区)を紹介されました。
 患者には呼吸機能の急速な低下{%肺活量(基準値80%以上)は66・5%(2020年6月)から46.1%(同8月)に低下}と痙縮による全身硬直がみられ、病状が急速に進行していることを確認しました。そのため患者および家族のインフォームド・コンセントのもとSHED-CMによる治療を開始しました。
 2021年1月よりSHED-CMの点鼻投与および同年9月より点滴治療が実施された結果、呼吸機能の低下などの病状の進行が停止し、点滴治療開始後1週で、四肢と頸部に痙縮の緩和と関節可動域の拡大がみられ、その後も改善が続いています(図4)。2022年1月現在、呼吸機能の安定 (室内気、SpO2, 95%以上)と痙縮の改善・可動域の拡大が維持されています(表1)今後は針筋電図、EMGなどで神経再生の経過をフォローする予定です。

 進行性の痙縮は運動神経の炎症と変性によって生じるALSに特徴的な症状です。発症後は進行を遅らせることはできても進行を停止・改善に成功した例は過去にみられません。特に本例のようなALS重症度が4〜5の高齢者の予後は悲観的と考えられてきました。
 しかし今回の治療結果のように、急速に悪化しつつある呼吸機能を安定化させ、自動的・他動的な運動可動域の向上がみられたことは、SHED-CMの抗炎症および神経再生効果が高いことを意味しています。
 本例治療結果はALSのような治療法のない難治性の運動障害をともなう神経変性疾患に対して、SHED-CMの投与は有望な治療法になりえることを明確に示しており、今後は発症後早期の例や壮年者に対象を拡大し、完治を目指したいと考えています。

【文参考献】
1. Mita,T. (2015) Conditioned medium from the stem cells of human dental pulp improve cognitive function in a mouse model of Alzheimer’s disease. Behav. Brain. Res. 293: 189-197.
2. Inoue,T et al.(2013) Stem cells from human exfoliated deciduous tooth derived conditioned medium enhance recovery of focal cerebral ischemia in rats. Tissue Eng.Part A 19:24-29.
3. Shimojima,C. et al .(2016) Conditioned medium from the stem cells of human exfoliated deciduous teeth ameliorates experimental autoimmune encephalomyelitis. J.Immuno.196-8
4. 上田実著「驚異の再生医療~培養上清とはなにか」扶桑社新書 2021年11月第5刷

【添付図表】
図1・培養上清治療の概念図
図2・乳歯歯髄幹細胞由来の培養上清の作成法
図3・筋萎縮性側索硬化症(ALS)
図4・運動可動域の測定法
表1・運動可動域の改善結果

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【用語解説】
1・乳歯幹細胞由来培養上清 
 (Stem cells from human exfoliated deciduous teeth derived conditioned medium ;SHED-CM)
乳歯歯髄に存在する幹細胞の産生する数千種類におよぶ生理活性物質の複合物。
神経保護、軸索伸長、神経伝達を促進する作用をもつ。

2・培養上清治療
 幹細胞由来の培養上清のもつ抗炎症・神経細胞保護・血管新生・免疫抑制作用などを応用して脳梗塞、アルツハイマー病、脊髄損傷、心不全、糖尿病、肝硬変、間質性肺炎などの再生医療を行うこと。幹細胞治療と治療効果は同じで、安全性が高く、用量用法の選択肢が多く、投与が簡便であることが特徴優とされている。また幹細胞治療に比べて費用対効果が高いことも長所である。

3・アン・メット・メディカル・ニーズ
 まだ治療法が確立されておらず、強く望まれているが、医薬品などの開発が進んでいない治療分野における医療ニーズ。ALSはその代表的疾患のひとつである。

4・点鼻投与
鼻腔内に培養上清を噴出して中枢神経に直接投与する方法。培養上清は分子量の小さなサイトカインが主体なので、臭球、三叉神経、鼻粘膜などを介して脳内に浸潤することができる。一方、幹細胞は血液脳関門に阻まれ中枢に到達できない。この点が脳の幹細胞治療を遅らせた原因のひとつといえる。

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    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
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    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
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    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
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    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
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    Function: instanceBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
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    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 116
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
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    Function: endChild

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    Line: 123
    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

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    Line Number: 41

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 416
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
    Line: 88
    Function: instanceBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 116
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 71
    Function: endChild

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

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    Severity: Notice

    Message: Trying to access array offset on value of type null

    Filename: smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php

    Line Number: 24

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
    Line: 24
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d136f97_11902452

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 384
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 416
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
    Line: 88
    Function: instanceBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 116
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 71
    Function: endChild

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

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    Severity: Notice

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    Filename: smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php

    Line Number: 29

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
    Line: 29
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d136f97_11902452

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 384
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 416
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
    Line: 88
    Function: instanceBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 116
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 71
    Function: endChild

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

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    Severity: Notice

    Message: Undefined offset: 2

    Filename: smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php

    Line Number: 41

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
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