心理亚健康(psychological suboptimal health)临床症状表现多样,且无与其密切相关的具体生化指标,因而心理亚健康的判别和诊断成为目前研究中的重点和难点。本研究旨在发现并评价能够用于临床诊断的尿液生物标志物组,为心理亚健康的临床诊断提供依据。通过纳入符合入组标准的24例心理亚健康及18例健康对照受试者,采集空腹晨尿经预处理后进行核磁共振氢谱法(1H-nuclear magnetic resonance spectroscopy,1H-NMR)测试。采用单变量、多元统计及随机森林算法对数据运算分析,以筛选造成组间差异的主要代谢物,发现脯氨酸、苯丙氨酸、葫芦巴碱、酮戊二酸、丙氨酸、柠檬酸、吲哚硫酸酚、乳酸、肌酸、牛磺酸及丙三醇11种代谢物的组间浓度表现出显著性差异(P<0.05,0.01),提示可作为候选诊断生物标志物。进一步结合受试者工作曲线(receiver operating characteristic curve,ROC)及曲线下面积(area under the curve,AUC)对其作为诊断生物标志物组的能力进行评价。结果显示,单一生物标志物对心理亚健康的诊断能力较低,而将柠檬酸、葫芦巴碱及丙三醇3种物质联合应用后诊断能力明显提升(AUC=0.8)。上述结果提示,柠檬酸、葫芦巴碱及丙三醇3种候选生物标志物,可作为生物标志物组用于心理亚健康的诊断。生物标志物组的发现及其应用对于提高心理亚健康诊断与识别的准确度具有重要意义。 Psychological suboptimal health (psychological suboptimal health) performance of various clinical symptoms, and no specific biochemical indicators closely related to it, so the psychological sub-health discrimination and diagnosis has become the focus of research and difficulties. This study aims to find and evaluate the urine biomarker group that can be used for clinical diagnosis and provide the basis for the clinical diagnosis of psychological sub-health. By incorporating 24 sub-healthy and 18 healthy control subjects who meet the inclusion criteria, fasting morning urine was collected and subjected to 1H-nuclear magnetic resonance spectroscopy (1H-NMR). Data analysis was performed using univariate, multivariate statistics, and random forest algorithms to screen for the major metabolites that caused differences between groups and found that proline, phenylalanine, trigonelline, ketoglutarate, alanine, lemon The concentrations of 11 metabolites of acid, indole sulfuric acid phenol, lactic acid, creatine, taurine and glycerol showed significant differences (P <0.05, 0.01), suggesting that they could be used as candidate diagnostic biomarkers. The receiver operating characteristic curve (ROC) and area under the curve (AUC) were further used to evaluate their ability as a diagnostic biomarker. The results showed that a single biomarker had a lower ability of diagnosing mental and sub-health, and the combination of citric acid, trigonelline and glycerol significantly improved the diagnostic ability (AUC = 0.8). These results suggest that three candidate biomarkers, citrate, trigonelline and glycerol, may be used as a biomarker group in the diagnosis of psycho-subhealth. The discovery of biomarker group and its application are of great significance to improve the accuracy of psychological sub-health diagnosis and recognition.