The aim of this study was to investigate the effect of human bone marrow mesenchymal stem cells on human T-cell proliferation resulted from stimulation with PHA and possible immunomodulating mechanism. T cells were positively selected by CD3(+) magnetic beads, and were then co-cultured with irradiated MSCs overnight before the addition of PHA. T-cell proliferation was measured by BrdU assay and the degree of apoptosis was assessed by flow cytometry with Annexin V/PI. T cells co-cultured with or without MSCs were treated with PHA for 72 hours, then harvested. They were labeled with anti-CD4, anti-CD8, anti-CD25 antibodies and analyzed by flow cytometry. The results showed that MSCs inhibited T-cell proliferation, but did not induce T cell apoptosis. There were no significant changes in the ratio of CD4(+) and CD8(+) T cells of MSC-treated group, as compared with the control group. After stimulation with PHA, there was an increase in CD4(+) T cells and decrease of CD4(+)CD25(+) cells in MSC co-cultured group. It is concluded that the MSCs inhibit T-cell proliferation after stimulation with PHA, and show more inhibitive effects on CD8(+) and CD4(+) T cells, but CD25(+) regulatory T cells may not be involved in this process.
Bone Marrow Cells ; cytology ; CD4-CD8 Ratio ; Cell Proliferation ; Cells, Cultured ; Coculture Techniques ; Humans ; Mesenchymal Stromal Cells ; cytology ; physiology ; T-Lymphocyte Subsets ; cytology

OBJECTIVES: To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma. METHODS: A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021. RESULTS: The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years. CONCLUSIONS Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child ; Child, Preschool ; Combined Modality Therapy ; Humans ; Infant ; Neuroblastoma/drug therapy* ; Positron-Emission Tomography ; Radionuclide Imaging ; Retrospective Studies ; Treatment Outcome

Background/Aims: Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics, and antiviral activity of three doses of EDP-514 in treatment-naive viremic patients with HBeAgpositive or -negative chronic HBV infection. Methods: Patients with HBsAg detectable at screening and at least 6 months previously were eligible. HBeAg-positive and -negative patients had a serum/plasma HBV DNA level ≥20,000 and ≥2,000 IU/mL, respectively. Twenty-five patients were randomized to EDP-514 200 (n=6), 400 (n=6) or 800 mg (n=7) or placebo (n=6) once daily for 28 days. Results: A dose-related increase in EDP-514 exposure (AUClast and Cmax) was observed across doses. At Day 28, mean reductions in HBV DNA were –2.9, –3.3, –3.5 and –0.2 log10 IU/mL with EDP-514 200 mg, 400 mg, 800 mg, and placebo groups, respectively. The corresponding mean change from baseline for HBV RNA levels was –2.9, –2.4, –2.0, and –0.02 log10 U/mL. No virologic failures were observed. No clinically meaningful changes from baseline were observed for HBsAg, HBeAg or HBcrAg. Nine patients reported treatment emergent adverse events of mild or moderate severity with no discontinuations, serious AEs or deaths. Conclusions In treatment-naïve viremic patients, oral EDP-514 was generally safe and well-tolerated, displayed PK profile supportive of once-daily dosing, and markedly reduced HBV DNA and HBV RNA.