Screening of serum susceptibility biomarkers in patients with mild liver function abnormalities based on non-targeted metabolomics / 中国中药杂志

In the present study,non-targeted metabolomics technique was used to screen potentially susceptibility biomarkers in patients with mild liver function abnormalities during long-term use of Chinese herbal compound. According to the inclusion and exclusion criteria,we collected 7 cases of patients with abnormal liver function during the period of complete taking Chinese herbal medicine( 60 days),and 18 cases of patients with normal liver function in re-examination from the reproductive medicine center in our hospital. Ultra performance liquid chromatography coupled with time-of-flight mass spectrometry( UPLC-Q-TOF/MS~E) technique combined with Progenesis QI software was used to analyze the differential biomarkers in serum of patients with wild liver function abnormalities and normal liver function. 11 potential biomarkers such as bilirubin,pantothenic acid,hippuric acid,sphingomyelin,palmitic acid,and oleic acid were tentatively identified. Metabolic disorders in patients with herbal-induced mild liver abnormality were mainly related to two pathways: pantothenic acid and coenzyme A biosynthesis and linoleic acid metabolism. It could provide a reference for the early warning of mild liver function abnormalities of patients that may be caused by long-term use of Chinese medicine compound in clinical application,and will lay a foundation for further understanding the endogenous substance changes in different levels of liver injury.

LAP+CD4+ T cells are elevated among the peripheral blood mononuclear cells and tumor tissue of patients with hepatocellular carcinoma.

The purpose of the present study was to investigate the role of latency-associated peptide (LAP)+CD4+T cells in hepatocellular carcinoma (HCC) immunity. Flow cytometric analysis was performed to detect the proportion of LAP+CD4+ T cells among the peripheral blood mononuclear cells (PBMCs) of 30 HBV-infected HCC patients at the pre-operative and post-operative stages, as well as 30 hepatitis B virus (HBV)-infected volunteers as a control group. Furthermore, tumor tissues and peri-tumor tissues from 28 patients with HCC, as well as hepatic tissues from 28 HBV-infected patients with benign lesions were subjected to immunohistochemical analysis with double staining for LAP and CD4, and the average number of the LAP+CD4+T cells in each visual field was quantified. The results indicated that the proportion of LAP+CD4+ T cells in the PBMCs of patients with HCC was significantly higher than that in the control group (1.84±0.85 vs. 0.73±0.39%, P=0.019), while it was significantly reduced after the operation (1.07±0.35, P=0.021), but still slightly, if not significantly, higher compared with that in the control group (P=0.342). Furthermore, the number of LAP+CD4+ T cells per high-magnification microscopic field (magnification, ×400) in the HCC tissues was 11.25±3.00, which was significantly higher than that in the peri-cancer tissues (5.75±1.00) and that in the HBV-infected hepatic tissues around benign lesions (2.61±0.83). In peri-cancer tissues, LAP+CD4+ T cells were also significantly more abundant than in control tissues. Furthermore, in the HCC tissues, LAP+CD4+ T cells were present as clusters in the tumor stroma and closely associated with CD4+ T lymphocytes. By contrast, in the peri-cancer liver tissues and HBV-infected hepatic tissues around benign lesions, LAP+CD4+ T cells were sparsely distributed. LAP+CD4+ T cells have marked inhibitory effects, and in the peripheral blood and tumor tissues of patients with HCC, they have an important role in the suppression of anti-tumor immunity and in the immune evasion of tumor cells.