ABSTRACT
Background: Hepatoblastoma (HB) is the most common liver malignancy in childhood with poor prognosis and lack of effective therapeutic targets. Single-cell transcriptome sequencing technology has been widely used in the study of malignant tumors, which can understand the tumor microenvironment and tumor heterogeneity. Materials and methods: Two children with HB and a healthy child were selected as the research subjects. Peripheral blood and tumor tissue were collected for single-cell transcriptome sequencing, and the sequencing data were compared and analyzed to describe the differences in the immune microenvironment between children with HB and normal children. Results: There were significant differences in the number and gene expression levels of natural killer cells (NK cells) between children with HB and normal children. More natural killer cells were seen in children with HB compared to normal control. KIR2DL were highly expressed in children with HB. Conclusion: Single-cell transcriptome sequencing of peripheral blood mononuclear cells (PBMC) and tumor tissue from children with HB revealed that KIR2DL was significantly up-regulated in NK cells from children with HB. HLA-C molecules on the surface of tumor cells interact with inhibitory receptor KIR2DL on the surface of NK cells, inhibiting the cytotoxicity of NK cells, resulting in immune escape of tumors. Inhibitors of related immune checkpoints to block the interaction between HLA-C and KIR2DL and enhance the cytotoxicity of NK cells, which may be a new strategy for HB treatment.
ABSTRACT
OBJECTIVE: Progressive weakness of respiratory muscles remains one of the leading causes of death among patients with Duchenne muscular dystrophy (DMD). Currently, there are few pulmonary function data among Chinese DMD patients. This study was carried out to evaluate the sniff nasal inspiratory pressure (SNIP) change among a group of Chinese DMD patients, and compare it with the SNIP value of patients with neuromuscular disorders in other countries. METHODS: SNIP data were collected in three research groups that consists of 581 subjects: 125 DMD boys who have taken steroid (Age 5.0-13.3, DMD-steroid group), 145 DMD steroid-naive boys (Age 5.0-13.9, DMD-nonsteroid group), and 311 healthy controls (Age 5.0-14.0, Control group). RESULTS: The SNIP for DMD-nonsteroid group, DMD-steroid group and Control group were: 56.5 (±14.3)â¯cm H2O,66.4 (±15.5)â¯cm H2O and 78.9 (±21.5) respectively. The SNIP in the DMD-nonsteroid group became significantly different from that of the healthy controls since age 7.0-8.9. The significant difference of SNIP between DMD-steroid group and DMD-nonsteroid group at age 7.0-10.9. The peak value of SNIP in the DMD-nonsteroid group appeared at age 8.7, and decreased dramatically thereafter, while in DMD-steroid group and the Control group peaked at 10.2â¯years and 12.2â¯years respectively. There was a bit difference between SNIP in this group and that in previous researches which may be due to geographical distribution and ethnic backgrounds. CONCLUSION: This study strengthens the previous findings that SNIP can be used to evaluate respiratory dysfunction during the early stage of young patients with neuromuscular disorders, and demonstrates that steroid is effective in slowing the decrease of SNIP in this group of Chinese DMD boys.