The immunomodulatory drugs (IMiD) thalidomide and lenalidomide,and the proteasome inhibitor (PI) bortezomib have dramatically improved clinical outcomes for patients with relapsed/refractory multiple myeloma(MM).But a part of patients become refractory or intolerant to these agents.Numerous agents are currently in clinical development,including new IMiD (pomalidomide),new PI (eg,carfilzomib,MLN9708,and marizomib),histone deacetylase inhibitors (eg,panobinostat and vorinostat) and signal transduction modulators (eg,perifosine),and have demonstrated promising anti-myeloma activity in patients with relapsed/refractory MM,particularly in those who are refractory to approved novel agents.This article describes antimyeloma agents currently available or in clinical development for relapsed/refractory patients.

Autologous stem cell transplantation (ASCT) has been considered as frontline therapy for patients with multiple myeloma (MM) based on the increased rate of response and prolonged progression-free survival compared with conventional chemotherapy.In the recent years,the favorable results shown by newdrug-based multidrug inductions,consolidations,and long-term maintenance approaches have challenged the role of ASCT.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has shown to be a potentially curative treatment for MM.However,the effectiveness of high-dose conditioning with conventional allo-HSCT is compromised by transplant-related mortality (TRM).Nonmyeloablative transplantation has showed reduced TRM and promising graft-versus-myeloma effects,but rates of acute and chronic graft-versus-host disease remain high.This article provides an overview of clinical trials and aims to define the role of stem cell transplantation in the era of novel agents.

Objective To investigate the applying comparative values of anticoagulant and thrombolytic Sak-hirudin fusion protein used in cardiopulmonary bypass.Methods From february 2013 to July 2014,selected nitinol sheet into uncoated group (group A),base coated group (chitosan,group B),chitosan/ Sak group (group C),chitosan/hirudin group (group D),chitosan/Sak-hirudin fusion protein group (group E),there were included in the fresh round of blood hemolysis,the blood cell hemolysis rates were calculated.Meanwhile used the healthy newborns umbilical vein endothelial cells were added into various categories nitinol sheet for cell compatibility testing.Results The samples hemolysis rates in the 5 groups were around 1.5% and the RBC,WBC and PLT counts compared in the 5 groups were showed no differences (P <0.05).The ex-tent of proliferation and adhesion in the group E were significantly lower than the other four groups,compared to significant differences (P <0.05).There were no differences to compare group A and group B (P >0.05).Randomized double-blind cell count result shows that the group C,D and E compared to the group A,B were more significant differences (P <0.05), at the same time,the group E compared to the group C,D differences were statistically significant (P <0.05).Conclusion Compared to Staphylokinase and hirudin alone,Sak-hirudin fusion protein used in cardiopulmonary bypass can play stronger anticoagulant and antithrombotic effects,its safety and ensures the effectiveness that interventional treatment of cardiovascu-lar disease.

0.05],but significant difference existed in children with HSPN compared with HSP and control group[(3.01?1.52) g/d vs (0.05?0.02) g/d or (0.04?0.02) g/d Pa

Objective To explore the effect of endothelin-1(ET-1) and C-reactive protein(CPR) on vascular endothelial cell dysfunction in simple obese children.Methods Thirty-nine simple obese children in the First Hospital of Huangshi City were chosen from Jan.2006 to Jun.2008 as experimental group (obese group) and 21 healthy children as healthy control group with the same age and gender were enrolled in the study.The levels of plasma ET-1 and serum CRP were tested by radioimmunoassay.Data were analyzed with t test and linear correlation analysis.Results Compared with plasma ET-1 level in healthy control group[(43.5?10.2) ng?L-1],the level in obese group[(57.8?19.7) ng?L-1] had significant difference(t=3.704,P

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive, fibrosing interstitial pneumonia of unknown etiology , a median survival time of which is 2 to 3 years.The diagnosis and treatment are important for IPF in time.Krebs von den lungen-6(KL-6), Surfactant protein-A(SP-A) and Surfactant protein-D(SP-D) are acceptable biomarkers in clinical for idiopathic pulmonary fibrosis in Japan,which have shown good sensitivity at diagnosis IPF and predict the prognoses for patients with IPF . However , the differential diagnosis of IPF from other interstitial lung diseases is still challenging .Other biomarkers are being developed , one of which would have the best specificity and sensitivity at diagnosis IPF.Those biomarkers about pathogenesis of IPF includes alveolar epithelial cell dysfunction , fibrogenesis and immune dysregulation are shown .They are potential to account for underlying disease mechanisms , accelerated drug development and advance clinical management.

K. There was no significant difference in the yield among the treatments of N+K, CK, P, N+P, and N, but the results of these five treatments were significantly higher than that of P+K and K. In addition, cichoric acid content did not considerably changed after treatment of various fertilizer combinations. For the second harvest date the yield of N, N+K, P, and N+P were 47.7%, 35.4%, 33.8%, and 12.3% higher respectively than that of CK, the yield of N+P+K, P+K, and K were 7.7%, 10.8%, and 28.5% lower respectively than that of CK. There was significant difference in the yield between the treatment of N and CK, the yield of K was significantly lower than that of CK. Conclusion The results indicate that cichoric acid content is not significantly affected by the treatment of various fertilizer combinations and the yield is strongly influenced by N fertilizer, weakly by P fertilizer, on the contrary the application of potassium chloride results in a decrease in yield.

Objective To analyze the differential expressions of miR-146a,miR-206,miR-223 and let-7c-1,such as cell differentiation-related miRNAs,in CXCR4-positive and CXCR4-negative subsets of the Lewis lung cancer cell lines(LLC).Methods CXCR4-positive and CXCR4-negative subsets were isolated from LLC by immunomagnetic beads sorting,and then their total cellular RNA were extracted by Trizol,expression of 4 miRNAs were detected by real-time fluorescence quantitative PCR(TaqMan probe),and potential target genes of miRNA whose differential expression was the most significant were predicted.Immunohistochemistry was carried out to confirm differential expression of the key molecule of certain research value within CXCR4-positive and CXCR4-negative subsets growing tumor tissue,and a BLAST search was performed to identify homologies of its 3′UTR.Results Compared to CXCR4-negative subsets,the expression of 4 miRNAs were lower in CXCR4-positive subsets,and expression of miR-223 had the most significant difference(Fold change=8.26).By softwares forecasting,miR-223 had potential target sites of IGF1R,IGFBP5,Pik3cb,ELK-1 and E2F1 mRNA,such as key molecular of IGF1R signaling pathway.The expression of IGF1R of CXCR4-positive subsets growing tumor tissue was significantly higher than that of CXCR4-negative subsets.Conclusion miR-223 is lowly expressed in CXCR4 positive cells from Lewis lung carcinoma cell lines.Position 238～244 nt and 688～695 nt in target sequences of 3′UTR of IGF1R mRNA was highly homologous by screening.Close correlation is found between miR-223 and IGF1R signaling pathway.The mechanisms underlying this biologically important finding need to be further explored.

0.05).Tumor formation was found in subgroups of positive CXCR4 cells(7 ? 103 ).Negative and positive CXCR cells were inoculated into 3 mice respectively at the concentration of 5 ? 105 and 2 ? 104 cells.No metastasis occurred in the former group.However,lung metastasis was found in 2 mice and ear metastasis was observed in 1mouse of the latter group.Conclusion Subgroups of positive CXCR4 cells in LLC are characterized by certain properties of cancer metastatic stem cells and have the ability to renew themselves and metabolize.