Affiliated Hospital of Medical School, Jinling Hospital, Nanjing University, Nanjing, China.
Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China.
Mikrochim Acta. 2024 Apr 3;191(5):231. doi: 10.1007/s00604-024-06312-5.
Blood stasis syndrome (BSS) has persistent health risks; however, its pathogenesis remains elusive. This obscurity may result in missed opportunities for early intervention, increased susceptibility to chronic diseases, and reduced accuracy and efficacy of treatments. Metabolomics, employing the matrix-assisted laser desorption/ionization (MALDI) strategy, presents distinct advantages in biomarker discovery and unraveling molecular mechanisms. Nonetheless, the challenge is to develop efficient matrices for high-sensitivity and high-throughput analysis of diverse potential biomarkers in complex biosamples. This work utilized nitrogen-doped porous transition metal carbides and nitrides (NP-MXene) as a MALDI matrix to delve into the molecular mechanisms underlying BSS pathogenesis. Structural optimization yielded heightened peak sensitivity (by 1.49-fold) and increased peak numbers (by 1.16-fold) in clinical biosamples. Validation with animal models and clinical serum biosamples revealed significant differences in metabolic fingerprints between BSS and control groups, achieving an overall diagnostic efficacy of 0.905 (95% CI, 0.76-0.979). Prostaglandin F2α was identified as a potential biomarker (diagnostics efficiency of 0.711, specificity = 0.7, sensitivity = 0.6), and pathway enrichment analysis disclosed disruptions in arachidonic acid metabolism in BSS. This innovative approach not only advances comprehension of BSS pathogenesis, but also provides valuable insights for personalized treatment and diagnostic precision.
血瘀证（BSS）存在持续的健康风险；然而，其发病机制仍不清楚。这种模糊性可能导致错失早期干预的机会，增加患慢性病的易感性，以及降低治疗的准确性和疗效。代谢组学采用基质辅助激光解吸/电离（MALDI）策略，在生物标志物发现和揭示分子机制方面具有明显的优势。然而，挑战在于开发有效的基质，以实现对复杂生物样本中多种潜在生物标志物进行高灵敏度和高通量分析。本工作利用氮掺杂多孔过渡金属碳化物和氮化物（NP-MXene）作为 MALDI 基质，深入研究 BSS 发病机制的分子机制。结构优化使临床生物样本的峰灵敏度提高了 1.49 倍，峰数量增加了 1.16 倍。通过动物模型和临床血清生物样本的验证，发现 BSS 和对照组之间的代谢指纹存在显著差异，总体诊断效能为 0.905（95%置信区间，0.76-0.979）。前列腺素 F2α被鉴定为一种潜在的生物标志物（诊断效率为 0.711，特异性=0.7，灵敏度=0.6），途径富集分析显示 BSS 中花生四烯酸代谢紊乱。这种创新方法不仅推进了对 BSS 发病机制的理解，还为个性化治疗和诊断精度提供了有价值的见解。
