Exploring the Occurrence Mechanism and Early-Warning Model of Phlebitis Induced by Aescinate Based on Metabolomics in Cerebral Infarction Patients

Abstract

Objective

This study aims to explore the mechanism underlying the induction of phlebitis by aescinate and create an early-warning model of phlebitis based on metabolomics.

Methods

Patients with cerebral infarction enrolled had been treated with aescinate. Plasma samples were collected either before administration of aescinate, upon the occurrence of phlebitis, or at the end of treatment. Non-targeted metabolomics and targeted amino acid metabolomics were carried out to analyze metabolic profiles and quantify the metabolites.

Results

Untargeted metabolomics revealed six differential metabolites in baseline samples versus post-treatment samples and four differential metabolites in baseline samples from patients with or without phlebitis. Pathways of these differential metabolites were mainly enriched in amino acid metabolism. Ten differential amino acids with a VIP value of >1 were identified in the baseline samples, enabling us to distinguish between patients with or without phlebitis. A logistic regression model was constructed (AUC 0.825) for early warning of phlebitis of grade 2 or higher.

Conclusion

The occurrence of aescinate-induced phlebitis, which can be predicted early during onset, may be associated with perturbations of the endogenous metabolic profile, especially the metabolism of amino acids.

Graphical Abstract

Keywords:

• aescinate
• diagnostic model
• mechanism
• metabolomics
• phlebitis

CRediT Authorship Contribution Statement

All authors made significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Data Sharing Statement

The data generated in this study are available from the corresponding author on reasonable request.

Ethics Approval and Consent to Participate

The study protocol was approved by the ethics committee of Shanghai Changzheng Hospital and performed in accordance with the ethics standards for studies involving human subjects according to the Declaration of Helsinki and its amendments. All patients who took part in the study signed the informed consent form.

Disclosure

The authors declare no conflicts.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (82274173, 82204819), Shanghai Municipal Health Commission (20214Y319), Shanghai Natural Science Foundation(22ZR147750), Innovative Clinical Research Project of Shanghai Changzheng Hospital (2020YLCYJ-Y02), and Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission (23Y11906600).