Background: HLA matched sibling donor HSCT (SDT) had been proved as first selection for thalassemia major (TM) and results of alternative donor (AD) HSCT (ADT) including unrelated donor HSCT (UDT), cord blood transplantation (CBT) and parent donor HSCT (PDT) continuously improved in practice of leukemia HSCT in the last decade, but outcome of ADT in TM were not both the idea or in small-size study. Aims: to fine out a protocol to improve outcomes of ADT for TM patients. Methods: Total 586 consecutive (2008-12-1 to 2016-6-30)TM patients from four pediatric HSCT centers in China were analyzed with median follow-up of 57 (21–116) months. Ratio of male to female was 378 to 208, Median age was 6 (range, 1–23) years old. 10/10 and 9/10 HLA mismatch were defined as full-match (FM) and well-match (WM), respectively. 224 patients underwent SDT (221 FM, 3 WM), 47 FM-CBT, 315 ADT including 275 UDTs (214 FM, 61 WM) and 40 PDTs (21 FM, 19 WM). G-CSF mobilized peripheral blood stem cells was adopted as stem cell source in almost HSCTs but CBTs. All patients received a uniform conditioning with Cyclophosphamide (Cy), Fludarabine, Thiotepa and intravenous Busulfan (Bu). Prophylaxis of GVHD included ATG and Sirolimus or Tacrolimus or Cyclosporine A. Particularity of the protocol was Bu following Cy, a constant target dose (8.0 x108/kg) and multi-drugs combining. Results: 9-year OS, TFS, GR and TRM were 94.4%, 91.6%, 3.9% and 5.6%, respectively, in total 586 HSCTs (Fig.1); 95.9%, 95.5%, 1.4% and 4.1%, respectively, in 224 SDTs, 92.7%, 88.9%, 5.3% and 7.3%, respectively, in 315 ADTs; 92.4%, 88.1%, 6% and 7.6%, respectively, in 275 UDTs (Fig.2); 97.9%, 95.4%, 2.6% and 2.1%, respectively, in 47 sibling CBTs; and 95%, 95%, 0 % and 5%,respectively, in 40 PDTs. ADT had more III-IV aGVHD than MST (7% vs. 1.5%). Likewise, To compare matched HSCT, well-matched HSCT had more ≥ II cGVHD (5.1% vs. 0.8%). Incidence of VOD and cytopenia after engraftment were 2.7%. was 14.5 in total, respectively.Summary/Conclusion: A Bu following Cy, constant target dose and multi-drug combining protocol improved markedly the results in ADT although ADT had more III-IV aGVHD than SDT. When compared with FM-ADT, WM-ADT had more ≥II cGVHD in spite of similar OS, TFS, TRM and GR. We don’t suggest, therefor, to use well matched ADT in TM HSCT.
Recent studies have suggested that brain-derived neurotrophic factor (BNDF) and its receptor, trkB, may provide neuroprotection following injury to the central nervous system. Conversely, other studies have implicated BDNF as a contributing factor to neurodegenerative events that occur following injury. In order to further investigate the role of BDNF in neuroprotection, we subjected adult rats to a lateral fluid percussion (FP) injury of moderate severity (2.0–2.1 atm) or sham injury. After survival periods of 1, 3, 6, 24, or 72 h, the brains were processed for the in situ hybridization localization of BDNF and trkB mRNAs using 35S-labeled cRNA probes. Hybridization levels were compared between injured and sham animals for regions of the cortex that were located within, adjacent to, and remote from the site of the cortical contusion. BDNF mRNA levels were significantly decreased in the injured cortex at 72 h, increased in adjacent cortical areas at 3 h, and increased bilaterally in the piriform cortex from 3 to 24 h post-FP injury. Expression of trkB mRNA was significantly decreased at all postinjury time-points in the injured cortex and at 24 h in the adjacent cortex. These results demonstrate that, following lateral FP injury, BDNF and trkB mRNA levels are decreased in cortical regions that contain degenerating neurons, generally unchanged in adjacent regions, and increased in remote areas. Thus, injury-induced decreases in the expression of BDNF and trkB may confer vulnerability to neurons within the cortical contusion.
We present recent developments of Yb-fiber laser front-ends tailored for a variety of special needs for high repetition rate accelerator driven FEL and UED facilities.
SUMMARY To determine whether HHV-6 infection induces expression and production of IL-10 and IL-12 in monocytes/macrophages, and to explore the influence of IFN-γ on cytokine production in HHV-6-infected cells, expression and production of IL-10 and IL-12 were evaluated through reverse transcription-polymerase chain reaction (RT-PCR) and sandwich ELISA. HHV-6 infection induced the expression and the production of IL-10 and IL-12 in monocytes and THP-1 cells. Kinetic study showed that the expression of IL-12 mRNA decreased with accumulation of IL-10 mRNA. Expression and production of IL-12 were markedly increased when anti-human IL-10 MoAbs were added to the cultures, implying that endogenous IL-10 induced by HHV-6 inhibited IL-12 production. Addition of increasing concentrations of IFN-γ to the cultures of HHV-6-infected cells enhanced the expression of IL-12 gene, while the accumulation of IL-10 mRNA was down-regulated. Determination of protein levels of IL-10 and IL-12 by ELISA also showed that IFN-γ increased IL-12 and decreased IL-10 production. These results suggest that IFN-γ regulates the production of IL-10 and IL-12 at transcriptional level mainly through inhibiting endogenous IL-10 production in HHV-6-infected monocyte/macrophage lineage.
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