ABSTRACT
Erdheim-Chester disease (ECD) is a rare histiocytosis that tends to co-exist with other myeloid malignancies. Here, we use genetic and transcriptomic sequencing to delineate a case of co-occurring BRAFV600E-mutated ECD and acute myeloid leukemia (AML), followed by AML remission and relapse. The AML relapse involved the extinction of clones with KMT2A-AFDN and FLT3-ITD, and the predominance of PTPN11-mutated subclones with distinct transcriptomic features. This case report has highlighted the screening for other myeloid malignancies at the diagnosis of ECD and the clinical significance of PTPN11-mutated AML subclones that require meticulous monitoring.
ABSTRACT
Waldenström's macroglobulinemia (WM) is an uncommon lymphoproliferative disorder, and the precise cellular landscape and the mechanisms of progression from IgM monoclonal gammopathy of undetermined significance (MGUS) to WM remain unclear. We performed single-cell RNA sequencing of CD19 + and CD19-CD38 + cells from healthy donors, IgM MGUS and WM patients. We found that samples from IgM MGUS and WM patients were composed of fewer early B-cell subsets and more T cells and NK cells than those from healthy controls. Compared with those of IgM MGUS patients, mature B cells of WM patients showed upregulation of HES1, GADD45B, NEAT1, DUSP22, RGS1, RGS16, and PIM1. We also identified a subpopulation of CD3 + CD19 + cells in IgM MGUS and WM patients, and trajectory analysis suggested that this subpopulation might be a stem cell-like subset. Further targeted gene sequencing of CD3 + CD19 + and CD3-CD19 + cells proved that MYD88 might be the early events in tumorigenesis according to variant allele fraction analysis. Additional subclonal hits such as CXCR4 and MAP2K1 mutations could be acquired during tumor progression. CXCL signaling, CCL signaling, IL2 signaling and TGFß signaling pathways were involved in communication between CD3 + CD19 + cells and other immune cells. Our findings reveal the composition of CD38 + immune microenvironment together with B cells and plasma cells in IgM MGUS and WM patients, and provide comprehensive insights into mechanisms of progression from IgM MGUS to WM. The rare CD3 + CD19 + cells might be cells with "stemness" feature.
ABSTRACT
Methane is an important greenhouse gas and whether reservoirs act as a source or sink of methane has attracted great attention worldwide. However, unrepresentative sampling periods and a lack of consideration of unfavorable weather conditions have limited the accurate estimation of CH4 emission from reservoirs. This study focused on the middle reach of Xiangxi Bay in the Three Gorges Reservoir to track an entire rainfall-runoff event via on-site measurements in the summer of 2019, and initiatively investigated the impact of rainfall and inflow processes on methane concentration and emission. Results showed that from before to after the rainfall event, methane flux at the air-water interface ranged between 0.011 and 0.326 mg·(m2·h)-1, indicating a net source of methane to the atmosphere. Both wind velocity and rainfall affected methane evasion from the surface by altering the gas transfer velocity, with the effect of wind being more prominent. Methane concentrations at the bottom layer significantly increased when rainfall-induced density flow from the watershed arrived at the sampling section. This was likely due to methane export from upstream and along the flow path. During this event, discharge was too small to destratify the water column, and methane was strongly oxidized as it diffused upwards, having little impact on surface methane concentrations and air-water methane flux.
ABSTRACT
Investigate the effect of mild hypothermia on serum inflammatory factor HMGB1 of brain-dead donors, and its significance for renal transplantation recipients.In our hospital between January 2018 and January 2019 up to the standard of brain death donor (aged 18 to 65 years old) prospective cohort study, brain death donor were randomly divided into mild hypothermia group and the non-mild hypothermia group. Serum were collected from donor at different periods, and enzyme-linked immunoassay (ELISA) was used to determine the serum HMGB1 concentration to compare the difference between the 2 donor groups. The early recovery of renal function after renal transplantation was followed up, and the incidence of delayed graft function (DGF) and early recovery of renal function were compared between the 2 groups. The correlation between donor HMGB1 and recipient DGF was analyzed.Between 17 donors in the mild hypothermia group and 17 in the non-mild hypothermia group, there were no statistically significant differences in the age, perioperative urine volume and ICU stay between the 2 groups. After mild hypothermia treatment, serum HMGB1 levels of brain death donors were significantly decreased. While in non-mild hypothermia brain death donor group without treatment, serum HMGB1 was significantly increased. There were no statistically significant differences in age and preoperative creatinine between the 2 recipient groups, including 33 patients in the mild hypothermia group and 34 patients in the non-mild hypothermia group. DGF incidence was lower in mild hypothermia group comparing with non-mild hypothermia group with statistical significance. The levels of HMGB1 from donor before procurement is correlated with the occurrence of DGF of the recipient.Mild hypothermia therapy can reduce the levels of serum HMGB1, improve the function of donor organs. The levels of HMGB1 before donor procurement can be used to predict the occurrence of DGF in kidney transplant recipients. Our study shows that HMGB1 can be potentially used as therapeutic target of early intervention for brain death donors. Furthermore, mild hypothermia therapy can be applied in the maintenance of brain death donors for kidney transplant recipient to improve the successful rate of transplantation.
