Multiple myeloma (MM) is a heterogeneous disease with certain cytogenetic abnormalities [1q21 gains,t(4;14),del 17p] associated with worse outcome.The extensive use of thalidomide,lenalidomide and bortezomib has dramatically improved the outcome for patients with MM and some cytogenetic abnormalities.It is also widely proved that bortezomib can partly overcome the harmful affects of t (4;14).However,till now,there are many controversies about the effects of some novel agents worked on certain cytogenetic abnormalities.In this review,the effects of novel agents in cytogenetic abnormalities were summaried to provide new information on clinical treatment of this disease.

With the recent success of B-cell receptor (BCR) signaling pathway inhibitor in the treatment of patients with relapsed or refractory non-Hodgkin lymphoma (NHL), a number of new agents targeting the BCR signaling pathway are in a clinical research stage. In addition, multiple trials combining these agents with conventional cytotoxic chemotherapy, immunomodulatory agents, monoclonal antibodies, or other kinase inhibitors are underway. Studies have also found the drug resistance of BCR signaling pathway inhibitors, drawing attention of the mechanism and the way to overcome the drug resistance. Combined with the research progress reported in 57th American Society of Hematology (ASH) annual meeting, this article summarized the recent progress of BCR signaling pathway inhibitors and their resistance mechanism to provide new information on clinical therapy.

Objective To investigate the efficacy,safety of allogeneic hematopoietic stem cell transplantation(Allo-HSCT)in lupus mice.Methods22BXSB was pre-treated with myleran and cyclophosphamide,12BXSB were treated with CTX and prednisone as the control group.Peripheral blood stem cells of doner mouse(C57BL/6)after mobilizing with G-CSF were infused into recipients after pretreatment.Hematopoietic and immune reconstitution after transplantation were measured by blood cell analysis and flowcytometry.Recipients' renal pathological changes were measured with direct immunofluorescence after transplantation,proteinuria and anti-dsDNA antibody were also determined.Complications and mortality were compared between the two groups.Recipients'genetic map was analysed with PCR.Results Recipients'complete chimerism was observed after60days of transplantation.The lowest value of WBC declined to0.2?0.1?10 9 /L in Allo-HSCT group.The duration of WBC increased from the lowest value up to1.0?10 9 /L was47.5?12.8d in Allo-HSCT group.Early immune reconstitution could not be found in Allo-HSCT group.After transplantation reduction of proteinuria occurred in95.5%BXSB,anti-ds-DNA antibody turned to negative in54.5%BXSB,decrease of kindey immunofluorescence in90.9%BXSB,there was a significant difference between the two groups.There was no significant difference in the incidences of complication of bleeding,pneumonia and mortality between the Allo-HSCT group and the control group.Conclusions Allo-HSCT is an effective treatment method for lupus mice.It may be helpful in improving proteinuria and anti-dsDNA antibody and renal pathological changes of lupus mice.But the incidences of complication and mortality related to transplantation in Allo-HSCT group are higher than those in control group,so the value of Allo-HSCT in the treatment lupu mice has to be further studied.

Objective:To investigate influence of Fludarabine to lupus activity of lupus mice and the effectiveness and safety of Fludarabine on the treatment of BXSB lupus mice and their possible methanism Methods:Fludarabine of 30 mg/(m 2?d) was injected into BXSB by tail vein,3 days continuously Results of treatment was observed through counting number of peripheral blood WBC Anti ds DNA and anti nuclear antibody in BXSB serum was measured by ELISA Pathologic transformation of kidney or urine protein was measured by immunofluorescence or urine protein test paper after treated by Fludarabine Expression of CD4 +Fas +?CD8 +Fas +?CD45RO + Fas + on T lymphocyte were measured by flowcytometry Results:The number of peripheral blood WBC of BXSB mice began to decline from the third day after treated by Fludarabine The lowest value 〔0 5?0 2)?10 9 L -1 〕of the number of peripheral blood WBC appeared on the seventh day and on the nineteenth day the number of peripheral blood WBC was up to 1 0?10 9 L -1 after treated by Fludarabine The falling of anti ds DNA and anti nuclear antibody in BXSB serum appeared on the fourteenth and twentieth one day after treated by Fludarabine, respectively Reduction of from +～++ turning?kindey immunofluorescence were 72 7% in group of Fludarabine Reduction of protein urine from ++～+++ turning ?～ - appeared on the twentieth one and twentieth eight days Reduction of expression of CD4 +Fas +?CD8 +Fas +?CD45RO + Fas + on T lymphocyte was obvious after treated by Fludarabine Conclusion:Fludarabine can evidently reduce the serum level of anti ds DNA and anti nuclear antibody of BXSB and reduce injury of kidney and formation of protein urine So Fludarabine may have good curative effect to severe SLE Fludarabine can reduce expression of CD4 +Fas +?CD8 +Fas +?CD45RO + Fas + on T lymphocyte,which may be one of methanism of Fludarabine to SLE

Objective To observe the anti-tumor effect on human multiple myeloma cell lines U266 and KM3 with a combination of varinostat and melphalan in vitro.Methods The cell proliferation of U266 and KM3 was datected with MTT assay when treated them with vorinostat alone and melphalan alone,then calculate their IC50 values respectively.Fixed the concentrations of vorinostator melphalan,the cell proliferation was datected in combination with melphalan/vorinostat in seriesly concentrations by MTr assay.Then to calculate drug combination index(CI).Results The IC50 value of U266 was 5.0-7.5 μmol/L and that of KM3 was 2.5-5.0 μmol/L when treated by vorinostat alone,the IC50 value of U266 was 40-60 μmol/L and that of KM3 was 60-80 μmol/L treated by melphalan alone.When fixed the concentration of vorinostat(in U266 the concentration was 1.25 μmol/L,in KM3 the concentration was 1.0 μ mol/L),Synergism(CI＜0.9)was observed when the concentrations of melphalan were 20 μmol/L,40 μmol/L,60 μ mol/L and 80 μ mol/L in U266,40 μmol/L,60 μmol/L,80 μmol/L and 100 μmol/L in KM3;When fixed the concertration of melphalan (in U266,was 10 μmol/L,in KM3 was 20 μmol/L),synergism(CI＜0.9)was observed when the concentrations of vorinostat were 1.0 μmol/L,2.5 μmol/L,5.0 μmol/L and 7.5 μmol/L in U266,and 1.0 μmol/L,2.5μmol/L,5.0 μmol/L in KM3.An additive effect was observed with the czombination of vorinostat 7.5 μmol/L plus melphalan 20 μmol/L in KM3(CI=0.93).Conclusion Vorinostat had potential anti-myeloma effect alone,and had synergistic anti-tumor effect with melphalan in vitro.

Objective To detect specific cell killing effect of radiation combined with horseradish peroxidase (HRP)/indole-3-acetic (IAA) suicide gene therapy controlled by a novel radio-inducible and cancer-specific chimeric gene promoter in lung cancer. Methods We constructed a plasmid expressing HRP enzyme under the control of chimeric human telomerase reverse transcriptase (hTERT) promoter carrying 6 CArG elements, a plasmid expressing HRP enzyme under the control of hTERT promoter carrying single CArG element, and two control plasmids, which named pE6-hTERT-HRP, phTERT-HRP, pControl-HRP, and pControl-luc, respectively. After radiation, the proliferation inhibition and apoptosis induction effect of each type of plasmid in lung cancer cells (A549, SPC-A1) and normal lung cells (hEL) was detected by cell counting and Annexin V-FITC staining. The change of radiosensitivity of lung cancer cells with plasmid system was also detected by clonogenic assays. Results After a single dose radiation of 6 Gy,the average proliferation inhibition rates of pE6-hTERT-HRP, phTERT-HRP, pControl-HRP, and pControl-luc systems were 72. 92% ,40.60% , 51.00% and 25.19% (F= 67.31 , P< 0.01) in A549 cells ,64.63%,30.02%,48.23% and 23.16% (F=64.94, P< 0.01) in SPC-A1 cells, and 20.81%,18.05%, 44.20% and 18.32% (F=52. 19,P<0.01) in normal hEL cells, respectively. The average early apoptosis rates of these four plasmid systems were 36. 63%, 22. 30%, 24. 33% and 12. 53% (F =50. 99,P <0. 01) in A549 cells, 33.73%, 17. 37%, 22. 43% and 11.20% (F = 20. 76, P < 0. 01) in SPC-A1 cells, and 13.53 %, 12. 5%, 21.93% and 12. 16% (F = 15. 08, P < 0. 01) in normal hEL cells,respectively. The sensitizing enhancement ratios of the four plasmid systems were 3.45, 2. 29, 3.05 and 1.21 in A549 cells, while 2. 68, 2. 15, 3.05 and 1.21 in SPC-A1 cells, respectively. Conclusions The new suicide gene system controlled by chimeric promoter may provide a novel therapeutic modality for lung cancer.

BACKGROUND: Continuous blood purification can remove cytokines and inflammatory mediators, maintain homeostasis and prevent the occurrence of multiple organ dysfunction syndrome in patients with severe pancreatitis, which has become the main therapy for severe pancreatitis. Since the hemodialysis technology began to be applied clinical y, the biological and physicochemical properties of hemodialysis membrane materials have been studied. A variety of hemodialysis membranes have been developed in order to improve the biocompatibility and anticoagulant effect in vitro. OBJECTIVE: To investigate the application effect of hemodialysis membranes on severe pancreatitis. METHODS: Ten Wistar rats were selected to make rat models of severe pancreatitis and then were randomized into two groups (n=5 per group): homophone membrane group and polysulfone membrane group. Hemodialysis- related biochemical parameters were detected in the two groups. RESULTS AND CONCLUSION: Compared with the homophone membrane, ultrafiltration coefficient, creatinine clearance, blood urea nitrogen clearance, phosphorus clearance, number of circulating endothelial cel s, and levels of plasma nitric oxide and asymmetric dimethylarginine were significantly lower in the polysulfone membrane group (P < 0.05). Vitamin B12 clearance and amount of pre-congestion increased significantly in the polysulfone membrane group as compared with the homophone membrane (P < 0.05). These findings indicate that the polysulfone membrane for hemodialysis has good biocompatibility, and keeps a stable environment in vivo for severe pancreatitis patients.

Objective To detect the selective inhibitory effects of irradiation plus adenovirusmediated horseradish peroxidase ( HRP)/indole-3-acetic acid (IAA) suicide gene system using tumorspecific and radio-inducible chimeric promoter on human hepatocellular carcinoma subcutaneously xenografted in nude mouse.MethodsRecombinant replicated-deficient adenovirus vector containing HRP gene and chimeric human telomerase reverse transcriptase (hTERT) promoter carrying 6 radioinducible CArG elements was constructed.A human subcutaneous transplanting hepatocellular carcinoma (MHCC97 cell line) model was treated with -γ-ray irradiation plus intra-tumor injections of adenoviral vector and intra-peritoneal injections of prodrug IAA.The change of tumor volume and tumor growth inhibiting rate,the survival time of nude mice,as well as histopathology of xenograft tumor and normal tissues were evaluated.Results Thirty one days after the treatment,the relative tumor volumes in the negative,adenovirus therapy,irradiation,and combination groups were 49.23 ± 4.55,27.71 :± 7.74,28.53 + 10.48 and 11.58 ± 3.23,respectively.There was a significantly statistical difference among them (F = 16.288,P ＜0.01 ).The inhibition effect in the combination group was strongest as compared with that in other groups,and its inhibition ratio was 76.5%.The survival period extended to 43 d in the combination group,which showed a significantly difference with that in the control group(x2 = 18.307 ,P ＜0.01 ).The area of tumors necrosis in the combination group was larger than that in the other groups,and the normal tissues showed no treatment-related toxic effect in all groups.However,multiple hepatocellular carcinoma metastases were observed in the liver in the control group,there were a few metastases in the monotherapy groups and no metastasis in the combination group.Conclusions Adenovirus-mediated suicide gene therapy plus radiotherapy dramatically could inhibit tumor growth and prolong median survival time.It might provide a promising therapeutic modality for hepatocellular carcinoma therapy.

Objective:To differentiate hepatitis B virus (HBV) infection from hepatitis C virus (HCV) infection among different indolent B-cell non-Hodgkin lymphoma (B-NHL) subtypes. The correlation between indolent B-NHL and hepatitis viral infection was also investi-gated. Methods:A total of 733 indolent B-NHL patients from January 1994 to January 2014 with integrated clinical information were retrospectively investigated. We compared the hepatitis viral infection between the general population and indolent B-NHL patients. We analyzed the infection rate of hepatitis virus in the different indolent B-NHL subtypes and examined their correlations. Results:The HBs-Ag positive rate of the indolent B-NHL was 7.9%, which was not significantly different with that of the general population (7.9%vs. 7.2%, P=0.548). Among the different indolent B-NHL subtypes, the 48 splenic marginal zone lymphoma (SMZL) patients exhibited the highest HBs-Ag positive rate, which was significantly higher than those of the general population (18.8%vs. 7.2%, P=0.002), other indo-lent B-NHL subtypes (18.8%vs. 7.2%, P=0.004), and other marginal zone B-cell lymphoma (MZL) patients (18.8%vs. 7.1%, P=0.005). The HBs-Ag positive rates between other B-NHL subtypes and the general population were not significantly different. The coexpression of HBs-Ag, HBe-Ag, and anti-HBc-Ab exhibited no significant difference among the various B-NHL subtypes. However, the co-expres-sion of HBs-Ag, HBe-Ab, and anti-HBc-Ab was significantly higher in the SMZL group than the other B-NHL subtypes (16.7%vs. 4.7%, P<0.001).The positive rate of the anti-hepatitis C virus antibody (HCV-Ab) was 1.9%in 733 indolent B-NHL patients, which was significant-ly higher than in the general population (1.9%vs. 0.4%, P<0.001). The HCV-Ab positive rates in the chronic lymphocytic leukemia, lym-phoplasmacytic lymphoma/Waldenstr?m macroglobulinemia, SMZL, hairy cell leukemia, nodal marginal zone B-cell lymphoma group were 2.2%, 2.5%, 4.2%, 3%, and 3.7%, respectively. These values were significantly higher than those of the general population. Preva-lence rates of HCV in B-cell lymphoproliferative disorders, unclassified, extranodal marginal zone B-cell lymphoma of mucosa-associat-ed tissue lymphoma, B-cell prolymphocytic leukemia, and follicular lymphoma groups were not significantly different compared with the general population. Conclusion:Prevalence rate of HBV was higher in the SMZL group than other indolent B-NHL groups, which suggests that HBV infection may play an etiologic role in SMZL.

Objective To compare three dimensional arterial spin labeling(3D-ASL) and dynamic susceptibility contrast-perfusion weighted imaging(DSC-PWI) in evaluating the cerebral hemodynamic of Moyamoya disease. Methods Approved by the institutional review board, 26 cases of Moyamoya patients who were diagnosed by DSA were enrolled. Diffusion weighted image, 3D-TOF-MRA, 3D-ASL, DSC-WPI, and T1WI were performed in 3.0 T MR scanner. ROI were positioned in the abnormal perfusion areas and the control area according to the arterial dominant territory to obtain quantitative parameters of perfusion. Perfusion parameters including cerebral blood flow(CBF) of ASL, cerebral blood flow(CBF), cerebral blood volume(CBV), mean transit time(MTT), and time to peak(TTP)of DSC-PWI , and relative parameters (ASL-rCBF, DSC-rCBF, DSC-rCBV, DSC-rMTT, DSC-rTTP) that the ratio of abnormal perfusion area and the control area were calculated. Meanwhile, the areas of the lower perfusion region of ASL and TTP images in the same slice were measured. Difference of the above-mentioned parameters and areas was processed by paired Student′ t test. Furthermore, correlation of relative values of perfusion parameters(ASL-rCBF, DSC-rCBF, DSC-rCBV, DSC-rMTT, and DSC-rTTP) was processed by Pearson correlation test. Results There were significant statistics differences between values of ASL-CBF, DSC-MTT, and DSC-TTP in abnormal perfusion [(28.18 ± 10.19)ml · 100 g-1 · min-1,(7.98 ± 2.22)s,(29.93 ± 3.95)s] and the control areas [(49.50 ± 11.37)ml · 100 g-1 · min-1,(6.07 ± 1.11)s,(27.34 ± 2.58)s] (t=-12.818, 4.193, 6.163, all P<0.01). There was no significant statistics difference in the lower perfusion area between ASL-CBF [(5 729.63 ± 4 563.79) mm2]and DSC-TTP[(5 875.33 ± 4 723.08)mm2](t=-1.774,P>0.05). Furthermore, the Pearson correlation test showed significant linear dependence between ASL-rCBF(0.56±0.14)and DSC-rMTT(1.34± 0.42), and DSC-rTTP(1.09 ± 0.69)(r=-0.630,-0.748, P<0.01). Conclusions There is a correlation between 3D-ASL and DSC-PWI in assessing the magnitude and areas of the reduction of blood perfusion of Moyamoya patients. Moreover, the ASL technique possesses advantages of non-invasion use of the gadolinium contrast.