目的 建立古今分层的慢性疲劳综合征（chronic fatigue syndrome，CFS）食药物质方剂库，挖掘用药规律。方法 检索《中华医典》（第5版）及中国知网、万方数据知识服务平台、维普中文科技期刊全文数据库及中国生物医学文献服务系统4个数据库从建库至2026年3月收录的CFS相关方剂，从边际频率、共现结构和整体组方空间3个层次对古代和现代（2组）用药规律进行稳健比较。各层次均报告效应量并施加多重比较校正，另以32个分析规格与5 000次来源聚类重抽样核验稳健性。结果 最终纳入391首方剂（古代264首、现代127首），以2组合并出现频次≥10的39味食药物质为统一特征集。边际频率层次，甘草、当归、茯苓的偏好指数（preference index，PI）绝对值均＜0.10且95%置信区间跨0，为2组共有的核心药群；党参、黄精呈现代偏好（PI分别为1.67、1.85）；四气呈平温偏移，五味与归经差异有限。共现结构层次，现代组741个药对经多重比较校正后仅3对显著，2组共现网络模块度分别为0.258、0.249，均呈核心-外围拓扑。整体组方空间层次，置换多元方差分析（permutational multivariate analysis of variance，PERMANOVA）显示组方结构差异显著而效应量甚小（F＝8.67，R²＝0.022，P＜0.001）。结论 古今CFS相关方剂在食药物质的选择上同大于异，组间结构差异可检出而效应量甚小；甘草、茯苓、当归构成2组共有的核心药群，该判定在多项敏感性分析下方向未变，可作为后续药理与临床评价的优先候选。

Objective To establish a chronologically stratified corpus of medicine-food homology (MFH) formulae for chronic fatigue syndrome (CFS), and to conduct a robust comparison of classical and contemporary prescribing structure at three levels: marginal frequency, co-occurrence structure and overall formula space. Methods CFS-related formulae were retrieved from the Encyclopedia of Traditional Chinese Medicine (Zhonghua Yidian, 5th edition) and four databases including China National Knowledge Infrastructure (CNKI) Wanfang Data, the China Science and Technology Journal Database, and the SinoMed database, from inception to March 2026. A total of 391 formulae (264 classical and 127 contemporary) were included. The 39 MFH substances with a pooled frequency ≥10 formed a unified feature set; effect sizes and multiple-comparison correction were reported at each level, and robustness was examined across 32 analytical specifications and by 5 000 source-cluster resamplings. Results At the marginal-frequency level, Gancao (Glycyrrhizae Radix et Rhizoma), Danggui (Angelicae Sinensis Radix) and Fuling (Poria) had absolute preference index (PI) values < 0.10 with 95% confidence interval (CI) spanning zero, forming a core group shared by both corpora, whereas Dangshen (Codonopsis Radix) and Huangjing (Polygonati Rhizoma) showed contemporary preference (PI 1.67 and 1.85). The four qi shifted towards neutral and warm, while differences in flavour and meridian tropism were limited. At the co-occurrence level, only three of the 741 herb pairs in the contemporary corpus remained significant after correction; network modularity was 0.258 and 0.249, indicating a core-periphery topology in both corpora. At the level of the overall formula space, permutational multivariate analysis of variance (PERMANOVA) showed a significant but very small structural difference (F = 8.67, R² = 0.022, P < 0.001). Conclusion The two corpora were more alike than different in their selection of MFH substances, structural differences being detectable but small. A shared core group was identified whose composition was unchanged in direction across sensitivity analyses, making these substances priority candidates for subsequent pharmacological and clinical evaluation. Historical change and publication bias remain indistinguishable, and the findings serve only as literature-level clues for candidate MFH combinations for CFS.

R285

高水平科研标志性成果“揭榜挂帅”（721100E010）；浙江省卫生健康行业科技计划项目（2025HY0516）