A validated liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of D- and L-amino acids in human serum. Under the optimum conditions, except for DL-proline, L-glutamine, and D-lysine, the enantioseparation of the other 19 enantiomeric pairs of proteinogenic amino acids and nonchiral glycine was achieved with a CROWNPAK CR-I(+) chiral column within 13 min. The lower limits of quantitation for L-amino acids (including glycine) and D-amino acids were 5-56.25 μM and 0.625-500 nM, respectively, in human serum. The intraday precision and interday precision for all the analytes were less than 15%, and the accuracy ranged from -12.84% to 12.37% at three quality control levels. The proposed method, exhibiting high rapidity, enantioresolution, and sensitivity, was successfully applied to the quantification of D- and L-amino acid levels in serum from hepatocellular carcinoma patients and healthy individuals. The serum concentrations of L-arginine, L-isoleucine, L-aspartate, L-tryptophan, L-alanine, L-methionine, L-serine, glycine, L-valine, L-leucine, L-phenylalanine, L-threonine, D-isoleucine, D-alanine, D-glutamate, D-glutamine, D-methionine, and D-threonine were significantly reduced in the hepatocellular carcinoma patients compared with the healthy individuals (P < 0.01). D-Glutamate and D-glutamine were identified as the most downregulated serum markers (fold change greater than 1.5), which deserves further attention in hepatocellular carcinoma research. Graphical abstract Simultaneous determination of D- and L-amino acids in human serum from hepatocellular carcinoma patients and healthy individuals. AA amino acid, HCC hepatocellular carcinoma, LC liquid chromatography, MS/MS tandem mass spectrometry, NC normal control, TIC total ion chromatogram.

More than two‐thirds of patients with hepatocellular carcinoma (HCC) cannot receive curative therapy and have poor survival due to late diagnosis and few prognostic directions. In our study, nontargeted and targeted metabolomics analyses were conducted by liquid chromatography–mass spectrometry to characterize metabolic features of HCC and identify diagnostic and prognostic biomarker candidate incorporating liver tissue and serum metabolites. A total of 552 subjects, including 432 with liver tissue and 120 with serum specimens, were recruited in China. In the discovery cohort, a series of 138 metabolites were identified to discriminate HCC tissues from matched nontumor tissues. Retinol presented with the highest area under the curve (AUC) of 0.991 and associated with Edmondson grade. In the validation cohort, all metabolites in retinol metabolism pathway were examined and the levels of retinol and retinal in tumor tissue and serum decreased in the order of normal to cirrhosis to HCC of Edmondson Grades I to IV. Retinol and retinal levels could also differentiate between HCC and cirrhosis, with AUCs of 0.996 and 0.994, respectively, in tissue and 0.812 and 0.744, respectively, in serum. The AUC of the combined retinol and retinal panel in serum was 0.852. Univariate and multivariate Cox regression identified this panel as an independent predictor for HCC and showed that low expression of retinol and retinal correlated with decreased survival time. In conclusion, the retinol metabolic signature had considerable diagnostic and prognostic value for identifying HCC patients who would benefit from prompt therapy and optimal prognostic direction.

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Identification of distinct metabolic characteristics of pneumonia in type 2 diabetes mellitusDear Editor, Pneumonia is the leading infectious cause of death worldwide, with approximately 3 million annual casualties based on the World Health Organization data. 1 The incidence and short-or long-term mortality of lower respiratory tract infections in patients with type 2 diabetes mellitus (T2DM) are much higher than those of non-diabetic patients. [2][3][4] To our knowledge, the number of patients in China with T2DM was 88.5 million in the year 2017. The elderly have the highest prevalence of T2DM in China and are also more susceptible to pneumonia. 5,6 Early detection and intervention in pneumonia patients with T2DM are crucial; however, few specific targets for this purpose have been identified.In this study, we conducted ultraperformance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) metabolome profiling of serum samples and a transcriptomic validation of peripheral blood mononuclear cells (PBMCs) to determine the metabolic characteristics of pneumonia in T2DM patients (Figure 1A, study scheme). All methods are detailed in Materials and Methods section of the Supporting Information.Thirty-six pneumonia patients with T2DM, 31 nondiabetic pneumonia patients, 31 T2DM patients without pneumonia, and 31 healthy controls without pneumonia or T2DM were enrolled between March 2018 and December 2018 in the discovery set. Twenty-five pneumonia patients with T2DM, 31 non-diabetic pneumonia patients, 27 T2DM patients without pneumonia, and 27 healthy controls were enrolled between January 2019 and December 2019 in the validation set. The ages and sexes of the subjects in each group of the discovery and validation sets were balanced as closely as possible. Except for serum glucose level, there were no significant differences in the parameters between pneumonia patients with or without T2DM (Table 1). However, pneumonia patients with T2DM required longer hospital stays to achieve clinical stability compared with nondiabetic pneumonia patients in both the discovery setThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.