ABSTRACT
BACKGROUND@#Anterior thalamic nuclei (ATN) deep brain stimulation (DBS) is an effective method of controlling epilepsy, especially temporal lobe epilepsy. Mossy fiber sprouting (MFS) plays an indispensable role in the pathogenesis and progression of epilepsy, but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown. This study aimed to investigate the effect of ATN-DBS on MFS, as well as potential signaling pathways by a kainic acid (KA)-induced epileptic model.@*METHODS@#Twenty-four rhesus monkeys were randomly assigned to control, epilepsy (EP), EP-sham-DBS, and EP-DBS groups. KA was injected to establish the chronic epileptic model. The left ATN was implanted with a DBS lead and stimulated for 8 weeks. Enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus. One-way analysis of variance, followed by the Tukey post hoc correction, was used to analyze the statistical significance of differences among multiple groups.@*RESULTS@#ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy. The number of ectopic granule cells was reduced in monkeys that received ATN stimulation (P < 0.0001). Levels of 3',5'-cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the hippocampus, together with Akt phosphorylation, were noticeably reduced in monkeys that received ATN stimulation (P = 0.0030 and P = 0.0001, respectively). ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions (all P < 0.0001).@*CONCLUSION@#ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells, which may be associated with the reduced MFS in chronic epilepsy. The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.
Subject(s)
Humans , Adenosine Monophosphate , Anterior Thalamic Nuclei , Cyclic AMP-Dependent Protein Kinases , Deep Brain Stimulation , Epilepsy/therapy , Epilepsy, Temporal Lobe/therapy , Hippocampus , Mossy Fibers, Hippocampal , Signal TransductionABSTRACT
BACKGROUND: Recurrence of acute leukemia after hematopoietic stem cell transplantation is one of the major problems affecting the long-term survival of patients. Early intervention to prevent ALL recurrence after transplantation can improve disease-free survival, overall survival and reduce post-transplant mortality. Monitoring of minimal residual disease (MRD) by flow cytometry and PCR-based molecular biology techniques is a widely reliable and practicable method. OBJECTIVE: To dynamically monitor the MRD level of acute lymphoblastic leukemia after peripheral blood haploidentical hematopoietic stem cell transplantation and to explore its implications for predicting early relapse. METHODS: A retrospective study was conducted in 53 patients with acute lymphoblastic leukemia who had underwgone peripheral blood haploidentical hematopoietic stem cell transplantation at the First Affiliated Hospital of Zhengzhou University from June 2011 to June 2017. The patients were followed up for postoperative 1, 3, 6, 12 months to observe the relation between MRD levels and relapse after transplantation. RESULTS AND CONCLUSION: (1) The disease-free survival rate of MRD positive group and MRD negative group were 20.0% and 65.8%, respectively; and the overall survival rates were 50.8% and 68.9% in the two groups, respectively. There were significant differences between two groups. (2) Among 16 MRD positive patients accepting clinical intervention after transplantation, 4 patients presented with MRD negative and had no recurrence. (3) Eleven hematologic recurrence patients were given tyrosine kinase inhibitor-targeted therapy, chemotherapy, donor lymphocytes Infusion and secondary transplantation, but they eventually died. The median time from the discovery of MRD positive to hematologic recurrence was 100 (7-190) days, and during this period. Clinical intervention was confirmed to extend the recurrence time. In this study, one case refused clinical intervention, and eventually died of recurrence. Our findings indicate that dynamic monitoring of the MRD level in acute lymphoblastic leukemia patients after peripheral blood haploidentical transplantation can predict recurrence, by which the patients can be given early intervention to reduce the risk of recurrence and improve disease-free survival and overall survival.
ABSTRACT
BACKGROUND: In recent years, genetic haploidentical peripheral blood stem cell transplantation has been gradually improved, and haploid allogeneic hematopoietic stem cell transplantation has become an important treatment choice for malignant hematopoietic disease. OBJECTIVE: To observe the clinical efficacy of genetic haploidentical peripheral blood stem cell transplantation for myelodysplastic syndrome. METHODS: The clinical data of 21 myelodysplastic syndrome cases undergoing genetic haploidentical peripheral blood stem cell transplantation were retrospectively analyzed. Modified BU/CY+ATG administration was performed as a pretreatment strategy for haploidentical peripheral blood stem cell transplantation, and the combined use of cyclosporine A+mycophenolate mofetil+short-range methotrexate±basiliximab was adopted to prevent graft-versus-host disease (GVHD). RESULTS AND CONCLUSION: (1) The 21 cases were followed for an median of 333 days (22-1 222 days), with 76% (16/21) infection of granulocyte lack period, 100% (21/21) neutrophil reconstruction, the median implantation time of 12 days (7-17 days), 81% (17/21) platelet engraftment, and the median implantation time of 14 days (7-68 days). (2) The accumulative incidence of GVHD was 52.4% (11/21), including 29% (6/21) of acute GVHD and 24% (5/21) of chronic GVHD. The incidence of hemorrhagic cystitis was 38.1% (8/21). The recurrence rate after transplantation was 4.8% (1/21). (3) The 2-year non-relapse mortality was 48% (10/21), and the 2-year disease-free survival rate was 46.8%. These results show that in the absence of HLA-identical related donors and unrelated donor, genetic haploidentical peripheral blood stem cell transplantation is a safe, effective, feasible and alternative treatment option for myelodysplastic syndrome.