We report the large-scale use of compositional data analysis to establish a baseline microbiota composition in an extremely healthy cohort of the Chinese population. This baseline will serve for comparison for future cohorts with chronic or acute disease. In addition to the expected difference in the microbiota of children and adults, we found that the microbiota of the elderly in this population was similar in almost all respects to that of healthy people in the same population who are scores of years younger. We speculate that this similarity is a consequence of an active healthy lifestyle and diet, although cause and effect cannot be ascribed in this (or any other) cross-sectional design. One surprising result was that the gut microbiota of persons in their 20s was distinct from those of other age cohorts, and this result was replicated, suggesting that it is a reproducible finding and distinct from those of other populations.

Background: The inner association of inflammation with voriconazole (VCZ) metabolism has not been fully investigated. We intend to investigate the effects of inflammation on liver function, VCZ trough concentration (C0), C0/dose ratio and the ratio of VCZ to VCZ-N-oxide concentration (C0/CN) in adult and elderly patients.Methods: A single-center retrospective study was conducted among patients who were treated in our hospital between January 2018 and December 2021. For each eligible patient, demographic details, medical history, laboratory parameters, procalcitonin (PCT), C reactive protein (CRP), and interleukin-6 (IL-6) were collected from the medical chart. VCZ CN, TNF-α, IL-1β, IL-8, and IL-10 concentrations were detected in blood samples.Results: A total of 356 patients were included in our study, with 195 patients in the adult cohort (<60 years) and 161 patients in the elderly cohort (≥60 years). In adult patients, CRP and IL-8 levels showed moderate association with VCZ C0/CN ratio (CRP: r = 0.512, p < 0.001; IL-8: r = 0.476, p = 0.002). IL-6 level shallowly associated with VCZ C0/CN ratio both in adult and elderly patients (r = 0.355, p = 0.003; r = 0.386, p = 0.001). A significantly higher VCZ C0, C0/dose ratio and C0/CN ratio was observed in adult patients with severe inflammation compared with patients with moderate inflammation and no to mild inflammation, as reflected by PCT levels (p < 0.05). However, there was no significant difference observed among different inflammation degrees in elderly patients. Lower albumin (AL) and higher total bilirubin (TBIL) were observed along with the degree of inflammation in both adult and elderly patients, as reflected by CRP and PCT levels (p < 0.05).Conclusion: Inflammation may affect the metabolism of VCZ to VCZ-N-oxide both in adult and elderly patients, and decreased plasma AL levels and increased TBIL levels under inflammatory conditions may also alter VCZ metabolism.

No abstract

Background: The efferocytosis-related molecules have been considered to be correlated with the resistance to cancer chemotherapy. The aim of this study was to investigate the expression and significance of efferocytosis-related molecules in cancers and the correlation of their expression with anticancer drug sensitivity, and provide new potential targets and treatment options for cancers.Methods: We investigated the differential expression of 15 efferocytosis-related molecules (Axl, Tyro3, MerTK, CX3CL1, Tim-4, BAI1, Stab2, Gas6, IDO1, Rac1, MFGE8, ICAM-1, CD47, CD31, and PD-L1) and other 12 common immune checkpoint-related molecules in tumor and normal tissues, the correlation between their expression and various clinicopathological features in 16 types of cancers using publicly available pancancer datasets in The Cancer Genome Atlas. We also analyzed the correlation of the expression of efferocytosis and immune checkpoint related molecules with 126 types of anticancer drugs sensitivity using drug-RNA-seq data.Results: There is a panel of circulating molecules among the 27 molecules. Based on the results of differential expression and correlation with various clinicopathological features of efferocytosis-related molecules in cancers, we identified new potential therapeutic targets for anticancer therapy, such as Axl for kidney renal clear cell carcinoma, Tyro3 for liver hepatocellular carcinoma, and IDO1 for renal papillary cell carcinoma. Except for BAI1, CD31, and MerTK, the enhanced expressions of Axl, Tyro3, Gas6, MFGE8, Stab2, Tim-4, CX3CL1, IDO1, Rac1, and PD-L1 were associated with decreased sensitivity of the cancer cells to many anti-cancer drugs; however, for other common immune checkpoint-related molecules, only enhanced expressions of PD-1, CD28, CTLA4, and HVEM were associated with decreased sensitivity of the cancer cells to a few drugs.Conclusion: The efferocytosis-related molecules were significantly associated with clinical outcomes in many types of cancers and played important roles in resistance to chemotherapy. Combination therapy targeting efferocytosis-related molecules and other immune checkpoint-related molecules is necessary to reduce resistance to chemotherapy.