ABSTRACT
AIM:To investigate the effect of bromodomain-containing protein 4(BRD4)inhibitors on the via-bility and apoptosis of activated B cell-like diffuse large B-cell lymphoma(ABC-DLBCL)cells and the molecular mecha-nism. METHODS:The ABC-DLBCL cells were treated with BRD4 inhibitors JQ1 and I-BET-762,and Bruton tyrosine kinase(BTK)inhibitor ibrutinib. The viability and death of the cells were determined by CCK-8 assay and PI staining,re-spectively. The mRNA levels of BTK,phospholipase Cγ(PLCγ),LYN,SYK,interleukin-6(IL-6),MYC,protein ki-nase Cβ(PKCβ),mucosa-associated lymphoid tissue lymphoma translocation protein 1(MALT1),MYC and RELA were detected by real-time PCR. The protein levels of BTK,PLCγ,MYC and RELA were determined by Western blot. Super-enhancer around BTK gene was revealed by bioinformatics analysis. RESULTS:The ABC-DLBCL cells were sensitive to BRD4/super-enhancer inhibitors such as JQ1 and I-BET-762. Both JQ1 and I-BET-762 inhibited the chronic active B-cell receptor(BCR)/nuclear factorκB(NFκB)signaling through reducing the transcription of BTK,but they had minimal ef-fect on other components in BCR/NFκB signaling. Interestingly,there was no super-enhancer around BTK gene,and the inhibitory effect of JQ1 was likely due to disruption of BRD4 binding within BTK gene. Inhibition of BRD4 had synergic ef-fect with BTK inhibitor ibrutinib. Moreover,inhibition of BRD4 induced significant cell death in ibrutinib-resistant ABC-DLBCL cells. CONCLUSION:Inhibitors of BRD4 induce ABC-DLBCL cell death via blocking BCR/NFκB signaling and has synergic effect with BTK inhibitor. Inhibition of BRD4 might be a promising strategy for treatment of ABC-DLBCL,es-pecially ibrutinib-resistant ABC-DLBCL.
ABSTRACT
Objective To study effects of fluid resuscitation on thoracoabdominal injury combined with hemorrhagic traumatic shock.Method A total of 98 patients,who were treated in Affiliated Zhongshan Hospital of Dalian University from November 2004 to December 2006,were retrospectively analyzed.The patients were diagnozed according to Surgery(fifth edition).Patients were divided into delayed fluid resuscitation group(n= 51)and immediate fluid resuscitation group(n=47).Patients in delayed fluid resuscitation group were given with balanced salt solution for the body to maintain basic requirements.Patients in immediate fluid resuscitation group were rapidly administered with a lot of isotonic crystaUoid and(or)colloid solution after admission. Hemoglobin,platelet count,hematocrit,blood lactic acid,basedeficit,preoperative resuscitation time and mortality were compared between the two groups.Paired t test and variance analysis or x~2 test were used.Results The transfusion fluid volume of delayed group and immediate group was(1586?346)ml,(3520?575)ml, respectively,with P value