Chinese Journal of Tissue Engineering Research ›› 2025, Vol. 29 ›› Issue (24): 5116-5126.doi: 10.12307/2025.734

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Biomarkers affecting the progression of mild to moderate cognitive impairment after stroke: #br# a non-targeted metabolomics analysis

Wang Zhifeng1, Yang Jiao2, Xi Yujiang1, Xu Shuangfeng1, Shi Ting1, Lan Junfeng1, Hao Zhihui1, He Pengfen1, Yang Aiming3, Pan Pan2, #br# Wang Jian1#br#   

  1. 1The First Clinical Medical College of Yunnan University of Chinese Medicine, Kunming 650000, Yunnan Province, China; 2The Second Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming 650000, Yunnan Province, China; 3Yunnan Hospital of Traditional Chinese Medicine, Kunming 650021, Yunnan Province, China
  • Received:2024-08-08 Accepted:2024-10-22 Online:2025-08-28 Published:2025-01-24
  • Contact: Wang Jian, MD, Associate professor, The First Clinical Medical College of Yunnan University of Chinese Medicine, Kunming 650000, Yunnan Province, China Co-corresponding author: Pan Pan, MD, Lecturer, The Second Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming 650000, Yunnan Province, China
  • About author:Wang Zhifeng, Master candidate, The First Clinical Medical College of Yunnan University of Chinese Medicine, Kunming 650000, Yunnan Province, China
  • Supported by:
    General Project of Applied Basic Research Program of Yunnan Province, No. 202201AT070214 (to WJ); Joint Special Funds for Applied Basic Research in Traditional Chinese Medicine of Yunnan Provincial Department of Science and Technology, Nos. 202001AZ070001-020 and 202301AZ070001-016 (to WJ); Two-type Talents Project of Yunnan Province, No. 202205AD160024 (to WJ); Scientific Research Fund Project of Yunnan Provincial Department of Education, Nos. 2024Y398 (to WZF) and 2024Y391 (to HPF); Department of Science and Technology of Yunnan Province - Basic Research Program, No. 202201AU070176 (to PP)

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Abstract: BACKGROUND: Cognitive impairment is the most common complication after stroke, and its severity is closely related to the patient’s prognosis. The prognosis of patients can be significantly improved if the severity of their cognitive impairment is recognized and targeted early. 
OBJECTIVE: To initially explore potential biomarkers affecting the progression of post-stroke cognitive impairment, thereby providing a richer and unique reference for the study of their pathophysiological mechanisms.
METHODS: Using ultra performance liquid chromatography-mass spectrometry, non-targeted metabolomics analysis was conducted on serum samples from patients with mild and moderate post-stroke cognitive impairment to identify differential metabolites between the two groups. To further validate the diagnostic efficacy of the differential metabolites, the receiver operating characteristic curve analysis was used to evaluate their accuracy and sensitivity in distinguishing disease severity. In addition, pathway analysis was conducted on the differential metabolites.
RESULTS AND CONCLUSION: (1) There were significant differences in metabolic profiles between patients with mild and moderate post-stroke cognitive impairment, and 9 differential metabolites were screened by the receiver operating characteristic curve. (2) Differential metabolite pathway analysis revealed that the metabolic pathways affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment included tryptophan metabolism, D-amino acid metabolism, biotin metabolism, retinol metabolism, aminoacyl-tRNA biosynthesis, lysine degradation, protein digestion and uptake, pyrimidine metabolism, cysteine and methionine metabolism, ABC transporter proteins, amino acid biosynthesis, and 2-oxocarboxylic acid metabolism. To conclude, 9 potential biomarkers affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment have been identified, involving 12 metabolic pathways including tryptophan metabolism, D-amino acid metabolism and retinol metabolism.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: post-stroke cognitive impairment, non-targeted metabolomics, ultra performance liquid chromatography-mass spectrometry, biomarker, differential metabolites, area under the curve, variable importance in projection

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