Prognostic value of pre-and post-transplantation 18F-fluorodeoxyglucose positron emission tomography results in non-Hodgkin lymphoma patients receiving autologous stem cell transplantation

Objective： High-dose chemotherapy （HDC） followed by autologous stem cell transplantation （ASCT） is the standard of care in the upfront or relapsed/refractory setting in some patients with non-Hodgkin lymphoma （NHL）. However, a proportion of patients do not respond to ASCT. lSF-fluorodeoxyglueose （FDG） positron emission tomography （PET）/computed tomography （CT） has been widely used for staging, response evaluation, and prognosis prediction. Here, we investigated the prognostic role of PET/CT in NHL patients before and after ASCT. Methods： A retrospective study was conducted at Peking University Cancer Hospital. All NHL patients who underwent ASCT between March 2010 and July 2016 were identified. Patients who had PET/CT scan before and after ASCT were included. Deauville criteria （5-point scale） were used to interpret PET scans. Univariate and multivariate survival analyses were performed using Cox regression. The predictive value of PET scanning was estimated by comparing the area under the receiver operating characteristic （ROC） curve. Results： In total, 79 patients were enrolled in this study. In univariate analysis, pre- and post-ASCT PET result was identified as prognostic factors for 3-year progression-free survival （PFS） and overall survival （OS）. Patients with negative pre-ASCT PET result demonstrated significantly better PFS （84.2% vs. 54.2%） and OS （89.2% vs. 63.6%） than patients with positive pre-ASCT PET result. PFS （91.6% vs. 25.3%） and OS （96.5% vs. 36.8%） were also significantly different between patients with negative and positive post-ASCT PET result. Multivariate analysis also showed a significant association between survival and post-ASCT PET result. ROC analysis revealed that the predictive value of post-ASCT PET result was superior to that of pre-ASCT PET result alone. Combined pre- and post-ASCT PET result is better for predicting outcomes in patients with NHL receiving transplantation. Deauville criteria score 〉3 was identified as the best cutoffvalue for post-ASCT PET. Conclusions： Post-ASCT PET result was more important than pre-ASCT PET result in predicting outcomes for NHL patients who underwent ASCT. The prognostic significance can be improved when combining pre- ASCT PET result with post-ASCT PET result. Deauville criteria can be used for interpreting PET scans in this scenario.

Restoration and protection of brachial plexus injury: hot topics in the last decade

Brachial plexus injury is frequently induced by injuries, accidents or birth trauma. Upper limb function may be partially or totally lost after injury, or left permanently disabled. With the de- velopment of various medical technologies, different types of interventions are used, but their effectiveness is wide ranging. Many repair methods have phasic characteristics, i.e., repairs are done in different phases. This study explored research progress and hot topic methods for pro- tection after brachial plexus injury, by analyzing 1,797 articles concerning the repair of brachial plexus injuries, published between 2004 and 2013 and indexed by the Science Citation Index database. Results revealed that there are many methods used to repair brachial plexus injury, and their effects are varied. Intervention methods include nerve transfer surgery, electrical stimula- tion, cell transplantation, neurotrophic factor therapy and drug treatment. Therapeutic methods in this field change according to the hot topic of research.

Schwann cells originating from skin-derived precursors promote peripheral nerve regeneration in rats

Artificial guidance channels containing Schwann cells can promote the regeneration of injured peripheral nerve over long distances. However, primary Schwann cells are not suitable for autotransplantation. Under specific conditions, skin-derived progenitors can be induced to dif- ferentiate into Schwann cells. Therefore, adult rat dorsal skin （dermis）-derived progenitors were isolated and induced to differentiate with DMEM/F12 containing B27, neuregulin 1, and for- skolin. Immunofluorescence staining and reverse transcription polymerase chain reaction （RT- PCR） confirmed that the resultant cells were indeed Schwann cells. Artificial guidance channels containing skin-derived progenitors, Schwann cells originating from skin-derived progenitors, or primary Schwann cells were used to bridge 5 mm sciatic nerve defects. Schwann cells originating from skin-derived progenitors significantly promoted sciatic nerve axonal regeneration. The sig- nificant recovery of injured rat sciatic nerve function after the transplantation of Schwann cells originating from skin-derived progenitors was confirmed by electromyogram. The therapeutic effect of Schwann cells originating from skin-derived progenitors was better than that of skin-de- rived progenitors. These findings indicate that Schwann cells originating from skin-derived precursors can promote peripheral nerve regeneration in rats.

Human CD34loCD133lo fetal liver cells support the expansion of human CD34hiCD133hi hematopoietic stem cells

We have recently discovered a unique CD34loCD133lo cell population in the human fetal liver （FL） that gives rise to cells in the hepatic lineage. In this study, we further characterized the biological functions of FL CD341~CD133~~ cells. Our findings show that these CD341~CD133I~ cells express markers of both endodermal and mesodermal lineages and have the capability to differentiate into hepatocyte and mesenchymal lineage cells by ex vivo differentiation assays. Furthermore, we show that CD34~~CD 133I~ cel Is express growth factors that are important for human hematopoietic stem cell （HSC） expansion： stem cell factor （SCF）, insulin-like growth factor 2 （IGF2）, C-X-C motif chemokine 12 （CXCL12）, and factors in the angiopoietin-like protein family. Co-culture of autologous FL HSCs and allogenic HSCs derived from cord blood with CD34loCD133lo cells supports and expands both types of HSCs.These findings are not only essential for extending our understanding of the HSC niche during the development of embryonic and fetal hematopoiesis but will also potentially benefit adult stem cell transplantations in clinics because expanded HSCs demonstrate the same capacity as primary cells to reconstitute the human immune system and mediate long-term hematopoiesis in vivo. Together,CD34loCD133lo cells not only serve as stem/progenitor cells for liver development but are also an essential component of the HSC niche in the human FL.

MATHEMATICAL MODELING OF CELL DYNAMICS AFTER ALLOGENEIC BONE MARROW TRANSPLANTATION

In this paper a basic mathematical model is introduced to describe the dynamics of three ceil lines after allogeneic stem cell transplantation： normal host cells, leukemic host cells and donor cells. Their evolution is one of competitive type and depends upon kinetic and cell-cell interaction parameters. Numerical simulations prove that the evolution can ultimately lead either to the normal hematopoietic state achieved by the expansion of the donor cells and the elimination of the host cells, or to the leukemic hematopoietic state characterized by the proliferation of the cancer line and the suppression of the other cell lines. One state or the other is reached depending on cell-cell interactions （anti-host, anti-leukemia and anti-graft effects） and initial cell concentrations at transplantation.The model also provides a theoretical basis for the control of post-transplant evolution aimed at the achievement of normal hematopoiesis.