查看“CRS”的源代码

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        <strong>细胞因子释放综合征</strong>（Cytokine Release Syndrome, CRS）是一种由于免疫效应细胞（如 [[CAR-T]]、[[TCR-T]] 或双特异性抗体）激活而引发的全身性急性炎症反应。其核心特征是促炎细胞因子（如 [[IL-6]]、[[IFN-γ]]、[[TNF-α]]）在血液中爆发式升高。CRS 是[[细胞免疫治疗]]中最常见的剂量限制性毒性，临床表现涵盖从轻度发热到致死性的[[低血压]]、缺氧及多器官功能衰竭。
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        <div style="font-size: 1.25em; font-weight: bold; letter-spacing: 1px; text-decoration: none !important;">CRS · 临床毒性图谱</div>
        <div style="font-size: 0.75em; opacity: 0.8; margin-top: 4px; white-space: nowrap; text-decoration: none !important;">Cytokine Release Syndrome (点击展开)</div>
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                [[文件:CRS_Cascade_Mechanism_Icon.png|130px|CRS 细胞因子瀑布机制示意]]
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            <div style="font-size: 0.85em; color: #64748b; margin-top: 15px; font-weight: 600;">T 细胞-巨噬细胞级联激活模型</div>
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                <th style="text-align: left; padding: 12px 18px; border-bottom: 1px solid #f1f5f9; color: #64748b; font-weight: 600; width: 40%; background-color: #fcfdfe;">关键驱动因子</th>
                <td style="padding: 12px 18px; border-bottom: 1px solid #f1f5f9; color: #1e293b;">[[IL-6]], IL-1, IFN-γ</td>
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                <th style="text-align: left; padding: 12px 18px; border-bottom: 1px solid #f1f5f9; color: #64748b; font-weight: 600; background-color: #fcfdfe;">主要一线靶药</th>
                <td style="padding: 12px 18px; border-bottom: 1px solid #f1f5f9; color: #1e293b;">[[托珠单抗]] (Tocilizumab)</td>
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                <th style="text-align: left; padding: 12px 18px; color: #64748b; font-weight: 600; background-color: #fcfdfe;">管理指南</th>
                <td style="padding: 12px 18px; color: #1e3a8a; font-weight: bold;">[[ASTCT 分级系统]]</td>
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    CRS 的发生并非单一细胞的行为，而是效应细胞与宿主免疫系统之间的有害“共振”：
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    <li style="margin-bottom: 10px;"><strong>原发性触发：</strong> CAR-T 细胞识别肿瘤抗原后释放 IFN-γ，激活周围的[[单核细胞]]及[[巨噬细胞]]（TAM）。</li>
    <li style="margin-bottom: 10px;"><strong>次级放大：</strong> 活化的巨噬细胞通过 [[NF-κB 通路]] 暴发式释放核心促炎因子 **[[IL-6]]** 和 IL-1。</li>
    <li style="margin-bottom: 10px;"><strong>内皮受损：</strong> 超生理浓度的细胞因子诱导[[内皮细胞]]活化，引发[[毛细血管渗漏]]、低血压以及弥散性血管内凝血（DIC）。</li>
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    目前临床多采用 ASTCT 共识指南，将 CRS 的严重程度与升压药使用及氧合需求对齐：
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            <th style="padding: 12px; border: 1px solid #e2e8f0; color: #1e3a8a;">CRS 分级</th>
            <th style="padding: 12px; border: 1px solid #e2e8f0; color: #1e3a8a;">临床指征</th>
            <th style="padding: 12px; border: 1px solid #e2e8f0; color: #1e3a8a;">标准干预策略</th>
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            <td style="padding: 10px; border: 1px solid #e2e8f0; background: #fcfdfe; font-weight: bold;">1 级 (Grade 1)</td>
            <td style="padding: 10px; border: 1px solid #e2e8f0;">发热 (≥38°C)，无低血压或缺氧。</td>
            <td style="padding: 10px; border: 1px solid #e2e8f0;">抗感染、退热、密切观察。</td>
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            <td style="padding: 10px; border: 1px solid #e2e8f0; background: #fcfdfe; font-weight: bold;">2 级 (Grade 2)</td>
            <td style="padding: 10px; border: 1px solid #e2e8f0;">低血压 (补液有效) 或 需鼻导管吸氧。</td>
            <td style="padding: 10px; border: 1px solid #e2e8f0;">**托珠单抗** ± 地塞米松。</td>
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            <td style="padding: 10px; border: 1px solid #e2e8f0; background: #fcfdfe; font-weight: bold;">3/4 级 (Severe)</td>
            <td style="padding: 10px; border: 1px solid #e2e8f0;">需升压药、高流量吸氧或机械通气。</td>
            <td style="padding: 10px; border: 1px solid #e2e8f0;">大剂量激素 + 联合[[阿那白滞素]]。</td>
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    在下一代细胞治疗的研发中，CRS 的管理重心正从“救治”转向“预判”：
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    <li style="margin-bottom: 10px;"><strong>生物标志物监控：</strong> 回输后早期 **[[CRP]]**（C反应蛋白）和**铁蛋白**的动力学曲线是预测重症 CRS 的金标准。</li>
    <li style="margin-bottom: 10px;"><strong>内皮保护：</strong> 监测 Ang-2/Ang-1 比例，评估血管损伤程度，预防由于 CRS 演变而来的 [[ICANS]]。</li>
    <li style="margin-bottom: 10px;"><strong>工程化优化：</strong> 引入“安全开关”（如 [[iCaspase-9]]）或开发可控激活的 CAR-T 细胞，旨在降低细胞因子释放的峰值。</li>
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        [1] Lee DW, et al. "ASTCT Consensus Grading for Cytokine Release Syndrome and Immune Effector Cell-Associated Neurotoxicity Syndrome." <em>BBMT</em>. 2019. 
        <span style="color: #64748b;">(点评：全球临床管理的标准化共识，确立了 CRS 与神经毒性分级的统一语言。)</span>
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        [2] Neelapu SS, et al. "Chimeric antigen receptor T-cell therapy — assessment and management of toxicities." <em>Nature Reviews Clinical Oncology</em>. 2018. 
        <span style="color: #64748b;">(点评：详述了 CRS 的细胞动力学基础，为早期使用 IL-6R 拮抗剂提供了理论支持。)</span>
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        [3] Norelli M, et al. "Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity." <em>Nature Medicine</em>. 2018. 
        <span style="color: #64748b;">(点评：里程碑式发现，揭示了巨噬细胞在 CRS 发病中的主导作用，并将 IL-1 确定为潜在的高级靶点。)</span>
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    <div style="background-color: #1e3a8a; color: #ffffff; text-align: center; font-weight: bold; padding: 12px; text-decoration: none !important;">CRS 相关领域导航</div>
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        [[细胞因子风暴]] • [[ICANS]] • [[托珠单抗]] • [[IL-6 信号轴]] • [[ASTCT 分级指南]]
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