基于核磁共振氢谱筛选隐性梅毒患者血清代谢组学生物标志物的研究

目的　基于核磁共振氢谱（proton nuclear magnetic resonance spectroscopy，1 H NMR）筛选隐性梅毒患者血清中的特征代谢产物，从血清代谢组学角度探索隐性梅毒对机体代谢的影响及其可能的机制。方法　取2018 年12月～ 2020年6 月在河北燕达医院就诊的24例隐性梅毒患者、24例健康对照者血清样本，应用1 H NMR分析技术进行非靶向代谢组学分析，将两组共计48个血清样本的代谢物浓度数据集，并转换为标准格式上传到Metaboanalyst 4.0统计分析平台，通过贝叶斯核磁信号在线处理系统进行特征代谢产物受试者工作特征曲线（receiver operating characteristic curve，ROC）分析，根据化合物匹配得分（score≥6）确定化合物种类。结果　48个样品经贝叶斯核磁信号在线处理系统分析，根据score≥6归属得到43种化合物，ROC分析表明，隐性梅毒患者组的左旋肉碱和甲醇强度平均值显著高于健康对照组（1 069±132 vs 483±65，1 778±315 vs 279±94），差异均有统计学意义（t=3.98，4.56，均P＜0.000 1），两个特征代谢物的ROC曲线下面积（area under curve，AUC）分别为0.883和0.877。结论　左旋肉碱和甲醇可作为隐性梅毒患者的潜在生物标志物，这些发现可能为隐性梅毒相关的代谢物未来研究提供重要的信息和思路。

Study on Screening of Metabolomic Biomarkers in Recessive SyphilisPatients Based on 1H NMR

Objective　To screen the characteristic metabolites in the serum of patients with latent syphilis based on protonnuclear magnetic resonance spectroscopy（1H NMR）, and to explore the effect of latent syphilis on metabolism and its possiblemechanism from the perspective of serum metabolites. Methods　24 patients with latent syphilis and 24 healthy controls whowere treated in Hebei Yanda Hospital from December 2018 to June 2020 were selected. The non target metabolomics analysiswas carried out by 1H NMR spectroscopy. The concentration data set of metabolites in 48 serum samples in two groups wereuploaded to Metaboanalyst 4.0 statistical analysis platform, through Bayesian nuclear magnetic signal online processing systemto analyze the receiver operating characteristic (ROC) curve of metabolites, and the types of compounds according to the score ofcompound matching (score ≥ 6) were determined. Results　48 samples were analyzed by Bayesian nuclear magnetic signal onlineprocessing system. 43 compounds were obtained according to score ≥ 6. ROC curve analysis showed that the concentrationsof L-carnitine and methanol in the recessive syphilis group were significantly higher than those in the control group（1 069±132vs 483±65，1 778±315 vs 279±94）,the differences were statistically significant（t=3.98, 4.56, all P ＜ 0.000 1）,and areaunder curve(AUC) of ROC of the two characteristic metabolites was 0.883 and 0.877, respectively. Conclusion　L-carnitine andmethanol can be used as potential biomarkers in patients with latent syphilis. These findings may provide important informationand ideas for the future study of metabolites related to latent syphilis.