Basic research and clinical research on multiple myeloma (MM) have extensively progressed, as proven by the change in the definition of complete response (CR). With improvements in laboratory technology and introduction of novel agents, CR particu-larly emphasized both micro-and macro-models. The development of CR yielded therapeutic advances in MM and vice versa. The defi-nitions of response and treatment strategies were closely connected and improved. A need exists for further detailed studies on long-term disease control, such as optimal combination of agents. Given the shortage of new drugs and the distinctiveness of health in-surance, Chinese doctors should select the best treatment projects based on real-life situation in China.

Immune thrombocytopenia (ITP), the most common hemorrhagic disease, is an organ-specific autoimmune disease characterized by decreased platelets count due to auto-antibodies mediating platelets destruction and insufficient platelets production. The etiology of ITP is still not completely known. Regulatory T cells, also called Tregs, are character-ized by CD4+CD25+, and positive of transcription factor forkhead box P3. They belong to a subpopulation of T cells special-ized for immune regulation and play an important role in maintaining the immune balance. Decreased production and defect-ed function of CD4+CD25+Treg was found not only in the ITP animal model but also in the ITP patients. It indicates that the Treg was involved in the pathology of ITP. This review focus on the characteristic and function of Tregs and their relationship with pathogenesis of ITP.

Objective To explore the difference of immunosuppresive effect between the expanded Stro-1+ and Stro-1-subgroups of human mesenchymal stem cells in vitro. Methods Mononuclear cells (MNCs) were isolated from bone marrow (BM) samples and seeded in a T-75 cm2 tissue culture flask contained with Dexter medium. When 50% confluence was obtained, adherent cells were collected and incubated with anti-stro-1 antibody, and the Stro-1+ and Stro-1-MSCs were further seeded for expansion. The total culture time (median) was 15 days. Cells were then analyzed by flow cytometry. One-way mix lymphocyte reaction (MLR) (1?105 responding cells and an equal number of stimulating cells/well were co-cultured in 96-well plates) and nonspecific mitogenic stimuli phytohemagglutinin (PHA) plus interleukin-2 (IL-2) induced lymphocytes proliferation (PBL 1?105/well were mixed with PHA 10?g/ml and IL-2 500U/ml in 96-well culture plates) were established in vitro. 1?103-3?104 irradiated Stro-1+ MSCs and Stro-1-MSCs were added into the two systems at the beginning of reaction. Immunosuppressive actions of both Stro-1+ or Stro-1-MSCs were compared. Results Adherent cells contained a median of 9% (range 5%-26%) Stro-1+ cells, which expressed higher immunophenotype of MSCs. In both reaction systems, suppressive actions occurred in a dose-dependent fashion when whatever Stro-1+ MSC or Stro-1-MSC were added. However, that the addition of 1?103 Stro-1-cells enhanced rather than inhibited the lymphocyte proliferation in one-way MLR. In the presence of various concentrations of MSCs, Stro-1+ MSCs always showed a significantly increased inhibitory effects in comparison to Stro-1-MSCs (P

35), while the expression level of TGF-?1 in Stro-1-MSC was significant higher than that detected in Stro-1+MSC (2-??Ct=0.39, P

PCI-32765,an oral selective and irreversible inhibitor of Bruton tyrosine kinase (BTK),inhibits survival,activation,proliferation and migration of malignant B cells by blocking B cell receptor signaling pathway.PCI-32765 not only acts on malignant B cell,but also prevents resistance to chemical drugs.Therefore,PCI-32765 has broad prospects in the treatment of B cell malignancies.

Objective:To study the role of FDCs-miR-548m-CDK6 axis on clonogenicity in mantle cell lymphoma. Methods:RT-qPCR and Western blot were used respectively to test the expression of miR-548m and CDK6. Bioinformatics assay was applied to predict the targets of miR-548m, and Western Blot was used to test the expression level of CDK6 after miR-548m overexpression or in-hibition. Luciferase report assay was performed to test whether CDK6 was a direct target of miR-548m. Colony forming assay was used to test the colony forming activity in MCL after overexpression of miR-548m or knockdown of CDK6. Results:Cell adhesion to FDCs induced downregulation of miR-548m and CDK6 expression in MCL. Bioinformatics assay revealed that miR-548m could target the 3'-UTR of CDK6 and that a negative correlation exists between the level of miR-548m and the CDK6 expression. Luciferase report as-say confirmed that miR-548m directly targeted 3'-UTR of CDK6. Colony forming assay showed that overexpression of miR-548m or knockdown of CDK6 significantly suppressed MCL colony formation. Conclusion:This study reveals that FDC-enhanced mantle cell lymphoma clonogenicity is mediated by the miR-548m/CDK6 axis.

Objective To study ischemic effects on reentrant activities and cardiac arrhythmias using a computational approach. Method The Noble 98 mathematical model of ventricular cell was used in the study. The operator splitting and adaptive time step methods were utilized to integrate the partial differential equations in cardiac conduction models. The ischemic cells were simulated by decreasing the intracellular ATP concentration, reducing the Na+ conductance, and increasing the extracellular K+ concentration in a two-dimensional tissue. Spiral waves were initiated by the cross field technique. Result The results showed that spiral waves in local severe ischemia displayed three different morphologies,whereas in moderate ischemia only two kinds of wave forms exhibited. When the degree of ischemia reached a critical value, the reentrant wave could break. But for larger areas of ischemia spiral wave formed a typical functional reentry around the obstacle. Conclusion The study demonstrates that size and level of ischemia have effects on VTs and VFs. Large ischemic area is beneficial for maintenance of spiral wave and can provide a high probability in the genesis of VTs. Spiral waves can easily break up and degenerate into VFs under critical area or level of ischemia.

Objective To study the difference in immunomodulatory effects among non-Hodgkin lymphoma (NHL)-, Hodgkin lymphoma (HL)- and normal adult bone marrow-derived mesenthymal stem cells (MSCs). Methods MSCs were obtained from HL, NHL and normal adult bone marrow and cultured in expanded medium. Immunophenotype was investigated by FACS. The levels of cytokines were evaluated by enzyme linked immunosorbent assay (ELISA). T-cell suppression ability was evaluated by Transwell. Moreover, the immunoregulatory ability of HL-, NHL- and normal adult bone marrow-derived MSCs was detected by mixed lymphocyte culture assay. Results HL-, NHLand normal adult bone marrow-derived MSCs were similar in morphology and immunophenotype, and they did not express HLA-DR and co-stirnulatory molecules (CD40, CD80 and CD86). All HL-,NHL- and normal adult bone marrow-derived MSCs could significantly suppress T lymphocytes'proliferation in a dose-dependent manner and such an effect could be reversed by anti-TGF-β1 antibody.MSCs differentiated into various mesenchymal lineages did not alter their immunosuppressive effects on T-cell proliferation. Conclusion The similar immunomodulatory effects were found among HL-,NHL- and normal adult bone marrow-derived MSCs, which was not changed by differentiation.

Objective:To determine the effect of Hes1 on bone marrow CD34+cells in acute myeloid leukemia (AML). Meth-ods:Bone marrow mononuclear cells were isolated by using Ficoll. Then, the proportion and cell cycle of CD34+cells were analyzed by using fluorescence-activated cell sorting (FACS). CD34+cells were cultured in vitro for colony-forming cells (CFC). The expression of Hes1 in CD34+cells was evaluated by using real-time polymerase chain reaction. After upregulating the expression of Hes1 in CD34+cells, the cell cycle was analyzed through FACS, and the colony formation of CD34+Hes1+cells was analyzed by CFC. Results:The ra-tio of CD34+cells in the bone marrow was lower in the AML group than in the control group. In addition, more CD34+cells underwent quiescence in the AML group than in the control group. In vitro assay showed that the colony formation of CD34+cells was lower in the AML group than in the control group. The expression of Hes1 was higher in the CD34+cells from the AML patients than that in the CD34+ cells from normal donors. After Hes1 transduction, more CD34+ cells underwent quiescence and showed weak proliferation. Conclusion:The proportion of CD34+cells in the bone marrow was lower in AML patients than in normal donors. A large proportion of CD34+cells underwent quiescence, which was related to Hes1, in AML patients.

Antineoplastic Agents ; therapeutic use ; Enhancer of Zeste Homolog 2 Protein ; Epigenesis, Genetic ; Histone Deacetylase Inhibitors ; therapeutic use ; Humans ; Hydroxamic Acids ; therapeutic use ; Indoles ; therapeutic use ; Lymphoma ; classification ; drug therapy ; genetics ; metabolism ; MicroRNAs ; metabolism ; Phenotype ; Polycomb Repressive Complex 2 ; metabolism ; Polycomb-Group Proteins ; metabolism