Objective:To clarify the changes in the bone marrow vascular system in the early stage of sepsis in animal model.Methods:A sepsis mouse model was established by cecal ligation and puncture (CLP), and HE staining, immunofluorescence staining, flow cytometry and real-time quantitative PCR were used to comprehensively analyze the varieties of bone marrow vascular system in structure, the relative proportion of vascular endothelial cells and the expressions of damage-related genes at mRNA level.Results:A series of adaptive changes occurred in the bone marrow vascular system in the early stage of sepsis.Histological analysis showed that the bone marrow vascular structure was significantly remodeled.The average density of bone marrow sinusoids in the CLP group was (410.43±72.63)counts/mm 2, which was significantly higher than that in the sham group[(294.43±68.94)counts /mm 2, P<0.01]. The area of luminal pixels accounted for (43.46±3.21)%, which was significantly higher than that in the sham group[(30.28±4.44)%, P<0.001]. The exudation amount of evans blue in the bone marrow tissue of the CLP group was (0.42±0.12)ng/mg tissue, which was significantly higher than that in the sham group[(0.24±0.09)ng/mg tissue, P<0.05], suggesting increased vascular permeability.The results of flow cytometry analysis showed that the EC in bone marrow of the CLP group mice was in a proliferative state, with the proportion of Ki67 + endothelial cell increasing[(1.91±0.65)% vs.(5.06±1.10)%, P<0.01]. The mRNA levels of some genes related to the activation of vascular endothelial cells were up-regulated. Conclusion:Sepsis changes the structure and function of the bone marrow vascular system, and has a significant impact on the bone marrow microenvironment.

Acute B-lymphoblastic leukemia (B-ALL) is the most common type of acute lymphoblastic leukemia. Chemotherapy is the main treatment for most patients, but there are serious side effects. CD19 is generally highly expressed in B-lineage malignancies and plays a key role in B cell signal transduction, activation and development. Therefore, it has become one of the effective targets for treatment of B-cell malignancies. At present, a variety of therapies targeting CD19 have been developed, including antibody drug conjugates, monoclonal antibodies, bispecific antibodies and chimeric antigen receptors cell therapies. This paper reviews the clinical trial progress of CD19-targeted therapy for B-ALL.