OBJECTIVE To systematically analyze the serum metabolomic profile of phlegm-dampness retention syndrome (PD) in girls with central precocious puberty (CPP) and screen differential metabolites distinguishing it from yin-deficiency fire-hyperactivity syndrome (YD), providing evidence for objective diagnosis of traditional Chinese medicine (TCM) syndromes.

METHODS Participants included CPP girls with PD (PD group, n=20), CPP girls with YD (YD group, n=24), and healthy girls (NC group, n=22). Serum metabolites were detected by gas chromatography-mass spectrometry (GC-MS). Differential metabolites were screened via orthogonal partial least squares-discriminant analysis (OPLS-DA) and one-way ANOVA. Metabolic pathway enrichment was performed using MetaboAnalyst 6.0, and diagnostic models were constructed via random forest algorithm.

RESULTS Comparative metabolomic analysis revealed 47 differential metabolites between the PD and NC groups, and 56 differential metabolites between YD and PD groups, encompassing carbohydrates, lipids, amino acids and their derivatives, steroid hormone metabolites, and neurotransmitter-related compounds. Pathway enrichment analysis identified three key dysregulated metabolic pathways, including the pentose phosphate pathway, β-alanine metabolism, and glutathione metabolism. Venn diagram analysis further pinpointed four overlapping differential metabolites across all three groups, which included enkephalin, 2-monopalmitin, adipic acid, and 1-indanol. Further random forest analysis was employed to plot receiver operating characteristic (ROC) curves for the combination of these four metabolites. The calculated area under the curve (AUC) values were 0.832 between PD and NC groups, and 0.881 between YD and PD groups, suggesting promising diagnostic potential.

CONCLUSION This study identifies four potential serum biomarkers for phlegm-dampness syndrome in girls with CPP. These metabolites participate in the disease pathogenesis by modulating glucose-lipid metabolic imbalance, providing metabolomic evidence for the characterization of phlegm-dampness syndrome in CPP.