Neutralization of Interleukin-9 Decreasing Mast Cells Infiltration in Experimental Autoimmune Encephalomyelitis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Th9 cells are a newly discovered CD4+ T helper cell subtype, characterized by high interleukin (IL)-9 secretion. Growing evidences suggest that Th9 cells are involved in the pathogenic mechanism of multiple sclerosis (MS). Mast cells are multifunctional innate immune cells, which are perhaps best known for their role as dominant effector cells in allergies and asthma. Several lines of evidence point to an important role for mast cells in MS and its animal models. Simultaneously, there is dynamic "cross-talk" between Th9 and mast cells. The aim of the present study was to examine the IL-9-mast cell axis in experimental autoimmune encephalomyelitis (EAE) and determine its interaction after neutralizing anti-IL-9 antibody treatment.</p><p><b>METHODS</b>Female C57BL/6 mice were randomly divided into three groups (n = 5 in each group): mice with myelin oligodendrocyte glycoprotein (MOG)-induced EAE (EAE group), EAE mice treated with anti-IL-9 antibody (anti-IL-9 Abs group), and EAE mice treated with IgG isotype control (IgG group). EAE clinical score was evaluated. Mast cells from central nervous system (CNS) were detected by flow cytometry. The production of chemokine recruiting mast cells in the CNS was explored by reverse transcription-polymerase chain reaction (RT-PCR). In mice with MOG-induced EAE, the expression of IL-9 receptor (IL-9R) complexes in CNS and spleen mast cells was also explored by RT-PCR, and then was repeating validated by immunocytochemistry. In vitro, spleen cells from EAE mice were cultured with anti-IL-9 antibody, and quantity of mast cells was counted by flow cytometry after co-culture.</p><p><b>RESULTS</b>Compared with IgG group, IL-9 blockade delayed clinical disease onset and ameliorated EAE severity (t = -2.217, P = 0.031), accompany with mast cells infiltration decreases (day 5: t = -8.005, P < 0.001; day 15: t = -11.857, P < 0.001; day 20: t = -5.243, P = 0.001) in anti-IL-9 Abs group. The messenger RNA expressions of C-C motif chemokine ligand 5 (t = -5.932, P = 0.003) and vascular cell adhesion molecule-1 (t = -4.029, P = 0.004) were significantly decreased after IL-9 neutralization in anti-IL-9 Abs group, compared with IgG group. In MOG-induced EAE, the IL-9R complexes were expressed in CNS and spleen mast cells. In vitro, splenocytes cultured with anti-IL-9 antibody showed significantly lower levels of mast cells in a dose-dependent manner, compared with splenocytes cultured with anti-mouse IgG (5 μg/ml: t = -0.894, P = 0.397; 10 μg/ml: t = -3.348, P = 0.019; 20 μg/ml: t = -7.639, P < 0.001).</p><p><b>CONCLUSIONS</b>This study revealed that IL-9 neutralization reduced mast cell infiltration in CNS and ameliorated EAE, which might be relate to the interaction between IL-9 and mast cells.</p>

Clinical Comparative Study of Two Kind Doses of Bortezomib Combinated with Bisphosphonates for Treating Patients with Multiple Myeloma Ostespathy / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical efficacy and safety of conventional dose and reduction dose of bortezomib in combination with bisphosphonates for treating patients with multiple myeloma ostespathy.</p><p><b>METHODS</b>A total of 150 patients with multiple myeloma ostespathy were chosen in the period from March 2011 to July 2015 and randomly were divided into 2 groups: A group (75 cases) and B group (75 cases). The patients in A and B groups were treated with conventional dose of bortezomib and reduction dose of bortezomib on the basis of bisphosphonates respectively and the clinical efficacy, the improvement rate of life quality, NRS score, levels of IL-6 and CRP before and after treatment, and the adverse effects of 2 groups were compared.</p><p><b>RESULTS</b>There was no significant difference in the clinical efficacy between 2 groups (P<0.05). The improvement rate of patients life quality in B group was significantly better than that in A group (P>0.05). There was no significant difference in the NRS score, levels of IL-6 and CRP after treatment between 2 groups (P>0.05). There was no significant difference in the incidence of neutrophil reduction and thrombocytopenia between 2 groups (P<0.05). The incidence of BiPN, nausea and vomiting, herpes zoster and fatigue of B group was significantly lower than that in A group (P<0.05).</p><p><b>CONCLUSION</b>Conventional dose and reduction dose of bortezomib in combination with bisphosphonates for treating patients with multiple myeloma ostespathy possess the same effects, including pain relief and disease progression control; but the reduction dose of bortezomib application can efficiently improve the life quality of patients and reduce the risk of adverse reactions.</p>

Infection Status and Prognosis Analysis of Epstein-Barr Virus in Patients with Newly Diagnosed Hodgkin's Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the Epstein Barr virus(EBV) positive rate in newly diagnosed Hodgkin's lymphoma(HL) and the prognostic significance of EBV status.</p><p><b>METHODS</b>A total of 120 previously untreated patients with histologically confirmed Hodgkin's lymphoma were enrolled in this study. The EBV infection status was confirmed through examining EBV-RNA(EBER) or EBV latent membrane protein-1, and these patients were divided into EBV positive group and EBV negative group. The correlation of clinical features and EBV infection status was analyzed. For analysis of prognostic significance of EBV infection, the patients were divided into dead and survival groups, and the factors affecting the living conditions were analyzed.</p><p><b>RESULTS</b>Among 120 patients with HL, 36 patients(30.0%) were found with EBV infection. In EBVHL group patients were male, aged 6-15 and 61-74, the proportion of patients with mixed cellular sybtype was significantly higher than that in EBVHL group(P<0.05). The 1 year and 2 year total survival rate of patients in EBVgroup were 88.9% and 83.3%, and significantly lower than 97.6% and 95.2% in EBVgroup. Out of the 120 patients with HL, 10 patients died(8.3%). In death group, patients aged 61-74 and did not received radiotherapy, their proportion of EBVinfection was significantly hyher than that in survival group (P<0.05). Multiriabl analysis showed that the age 61-74 and EBVinfection were the risk factors for survival coditions of patients (P<0.05).</p><p><b>CONCLUSION</b>The EBV infection relates with HL, the clinical featuses of HL patients with EBVor EBVare different, the total survival time of patients in EBVgroup is shorter than that of patients in EBVgroup, the EBVinfection is a risk factor for total survival time of patients with HL.</p>

Effect of G Protein-coupled Receptor Kinase 6 on Proliferation and Apoptosis of Multiple Myeloma Cells and Its Mechanisms / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the effect of G protein-coupled receptor kinase 6(GRK6) on proliferation and apoptosis of multiple myeloma(MM) cells and its mechanisms.</p><p><b>METHODS</b>The samples were collected from MM patients and healthy people for study in vivo. The plasma cells isolated from multiple myeloma patients, as well as U266 and NCI H929 myeloma cell lines were used for study in vitro. Western blot and quantitative real-time PCR were used to evaluate the protein and mRNA of expression of GRK6 in multiple myeloma, cell proliferation and apoptosis were tested by BrdU and Annexin V-FITC/PI assays.</p><p><b>RESULTS</b>The protein and mRNA expression of GRK6 in multiple myeloma was higher than those in control group, and the expression level of GRK6 in stage I of MM was higher than that in control group, while the expression level of GRK6 in stage II was higher than that in stage I, but lower than that in stage III (P<0.05). U266 and MM cells showed high-sensitivity to CX-4945, except NCI H929. GRK6 expression level in U266, NCI H929 and MM cells treated with siRNA and CX-4945, significantly decreased as compared with those cells treated by CX-4945 alone. Cell proliferations of U266, NCI H92 and MM groups treated with CX-4945 were (58.25±18.24)%, (64.32±20.03)% and (45.42±25.01)% respectively, moreover, their apoptotic rates were (62.82±53.21)%, (43.25±47.05)% and (85.67±40.32)% respectively.</p><p><b>CONCLUSION</b>The expression level of GRK6 in multiple myeloma increases, and GRK6 inhibitor CX-4945 inhibits proliferation and promotes apoptosis of myeloma cells; GRK6 regulates Rac1 and involves in the proliferation and apoptosis pathway of multiple myeloma cells.</p>