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Original research
Thrombosis origin identification of cardioembolism and large artery atherosclerosis by distinct metabolites
  1. Wei Li1,2,3,
  2. Xuesong Bai1,3,
  3. Jiheng Hao2,
  4. Xin Xu1,3,
  5. Feng Lin4,
  6. Qunlong Jiang2,
  7. Chunguang Ding5,
  8. Gaolei Dai2,
  9. Fangda Peng5,
  10. Meng Zhang2,
  11. Yao Feng1,
  12. Jiyue Wang2,
  13. Xianyang Chen6,7,
  14. Teng Xue7,8,
  15. Xiaofan Guo9,
  16. Zhaolin Fu1,3,
  17. Wen-huo Chen10,
  18. Liyong Zhang2,
  19. Chaodong Wang11,12,
  20. Liqun Jiao1,3,13
  1. 1Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
  2. 2Department of Neurosurgery, Liaocheng People’s Hospital, Liaocheng City, Shandong Province, China
  3. 3China International Neuroscience Institute (China-INI), Beijing, China
  4. 4Department of Neurology, Sanming First Hospital and First Hospital of Sanming Affiliated to Fujian Medical University, Sanming City, Fujian Province, China
  5. 5National Center for Occupational Safety and Health, NHC, Beijing, China
  6. 6Zhongguancun Biological and Medical Big Data Center, Beijing, China
  7. 7Bao Feng Key Laboratory of Genetics and Metabolism, Beijing, China
  8. 8Zhongyuanborui Key Laborotory of Genetics and Metabolism, Guangdong-Macao In-depth Cooperation Zone in Hengqin, Zhuhai City, Guangdong Province, China
  9. 9Department of Neurology, Loma Linda University Health, Loma Linda, California, USA
  10. 10Department of Neurology, Zhangzhou Affiliated Hospital, Fujian Medical University, Zhangzhou City, Fujian Province, China
  11. 11Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
  12. 12National Clinical Research Center for Geriatric Diseases, Beijing, China
  13. 13Department of Interventional Neuroradiology, Xuanwu Hospital, Capital Medical University, Beijing, China
  1. Correspondence to Dr Liqun Jiao, Department of Neurosurgery, Xuanwu Hospital, Beijing 100053, China; liqunjiao{at}; Dr Liyong Zhang, Department of Neurosurgery, Liaocheng people’s hospital, Liaocheng City, Shandong Province, People's Republic of China; 13346256936{at}


Background The diagnosis of cerebral thrombosis origin is challenging and remains unclear. This study aims to identify thrombosis due to cardioembolism (CE) and large artery atherosclerosis (LAA) from a new perspective of distinct metabolites.

Methods Distinct metabolites between 26 CE and 22 LAA origin thrombi, which were extracted after successful mechanical thrombectomy in patients with acute ischemic stroke in the anterior circulation, were analyzed with a ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) system. Enriched metabolic pathways related to the metabolites were identified. Least absolute shrinkage selection operator regression analyses and a filtering method were used to select potential predictors. Furthermore, four machine learning classifiers, including decision tree, logistic regression, random forest (RF), and k means unsupervised classification model, were used to evaluate the predictive ability of the selected metabolites.

Results UPLC-QTOF-MS analysis revealed that levels of 88 and 55 metabolites were elevated in LAA and CE thrombi, respectively. Kyoto Encyclopedia of Genes and Genomes analysis revealed a significant difference between the pathways enriched in the two types of thrombi. Six metabolites (diglyceride (DG, 18:3/24:0), DG (22:0/24:0), phytosphingosine, galabiosylceramide (18:1/24:1), triglyceride (15:0/16:1/o–18:0), and glucosylceramide (18:1/24:0)) were finally selected to build a predictive model. The predictive RF model was confirmed to be the best, with a satisfactory stability and prediction capacity (area under the curve=0.889).

Conclusions Six metabolites as potential predictors for distinguishing between cerebral thrombi of CE and LAA origin were identified. The results are useful for understanding the pathogenesis and for secondary stroke prevention.

  • Embolic
  • Stroke
  • Thrombectomy
  • Thrombolysis

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable.

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  • WL, XB and JH are joint first authors.

  • WL, XB and JH contributed equally.

  • Contributors WL, XB, CW, and LJ conceived and designed the study. JH, XX, CD, FP, YF, and XC conducted the assays and contributed to data acquisition. ZF, FL, QJ, GD, MZ, and JW provided the study materials or patients. TX, XG, WC, LZ, CW, and LJ analyzed the data, made the figures, and wrote and revised the manuscript. All authors approved the final manuscript. LJ take overall responsibility for the manuscript.

  • Funding This work was supported by the National Natural Science Foundation (82171303, 82171412).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.