Objective To investigate the mechanism of microRNA-214-3p(miR-214-3p)targe-ting CHUK to regulate the nuclear factor(NF)-κB pathway in modulating the chemosensitivity of lym-phoma cells to ibrutinib.Methods The half-maximal inhibitory concentration(IC50)was used to verify the ibrutinib-resistant cell model.The expression levels of miR-214-3p and CHUK mRNA in tissues and cells were detected by quantitative real-time polymerase chain reaction(qRT-PCR).Western blotting(WB)was employed to assess CHUK protein levels.A dual-luciferase reporter assay was performed to confirm the direct targeting relationship between miR-214-3p and CHUK.Cell viability was measured using CCK-8 assay.Flow cytometry was used to evaluate cell apoptosis.The expression of the NF-κB p65 signaling pathway was detected by WB.Results The CHUK mRNA and CHUK protein expression levels were higher in ibrutinib-resistant cells than in control cells(P＜0.05).The qRT-PCR results showed that miR-214-3p was downregulated in ibrutinib-resistant cells.The dual-luciferase reporter assay confirmed that miR-214-3p directly targeted CHUK.Transfection of miR-214-3p mimics and knockdown of CHUK(si-CHUK)reduced the number of colony-forming cells,whereas transfection of miR-214-3p inhibitor increased the number of colony-forming cells(P＜0.05).Transfection of miR-214-3p mimics and knockdown of CHUK(si-CHUK)can promote apoptosis,while transfection of miR-214-3p inhibitor can inhibit apoptosis(P＜0.05).Inhibition of the NF-κB p65 pathway was observed in cells transfected with miR-214-3p mimics(P＜0.05).Conclusion MiR-214-3p may regulate the NF-κB p65 pathway by targeting the expression of CHUK,thereby enhancing the chemosensitivity of ibrutinib to lymphoma.

Objective:To explore the clinical short-term efficacy of venetoclax (Ven) combined with azacitidine (AZA) in treatment of newly treated and relapsed/refractory patients with acute myeloid leukemia (AML).Methods:The data of 18 newly treated and relapsed/refractory patients with AML who received Ven+AZA treatment in Suzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine from April 2020 to June 2022 were retrospectively analyzed. The complete remission or complete remission with incomplete recovery of blood cell count (CR/CRi) and objective remission rate (ORR) [calculated as CR/CRi+partial remission (PR)] were analyzed in newly treated and relapsed/refractory patients or patients with different gene mutations. The patients were followed up until June 30, 2022, and the overall survival (OS) of relapsed/refractory patients was analyzed. The occurrence of adverse reactions was summarized.Results:The median age of the 18 patients was 58 years old (23-81 years old), 8 were males and 10 were females; 6 were newly treated and 12 were relapsed/refractory; the median follow-up time was 3 months (1-15 months). In 6 newly treated patients, after the first cycle of Ven+AZA, 5 cases achieved CR/CRi, and the ORR was 83.3% (5/6). In 12 relapsed/refractory patients, after the first cycle of Ven+AZA, 5 cases achieved CR/CRi, 3 achieved PR, and the ORR was 66.7% (8/12). Among the 18 patients, 7 cases had FLT3-ITD/TKD mutation, after the first cycle of Ven+AZA, 1 case achieved CR/CRi, 1 case achieved PR, and the ORR was 28.6% (2/7); 3 cases had NPM1 mutation combined with FLT3-ITD/TKD mutation, 1 case achieved CR/CRi, and the ORR was 33.3% (1/3); 4 cases had IDH1/2 mutation, and 3 cases of them combined with FLT3-ITD/TKD mutation, all of which were non-remission, and the other 1 relapsed/refractory patient combined with K/NRAS mutation achieved CR/CRi; among the 4 cases with K/NRAS mutation, 2 cases combined with FLT3-ITD/TKD mutation, including 1 case of NR and 1 case of PR, and the other 2 cases achieved CR/CRi, the ORR was 75.0% (3/4). Of the 12 relapsed/refractory patients, 6 died by the end of follow-up, with a median OS time of 2.6 months (1- 8 months), including 4 cases of disease progression and 2 cases of disease relapse; the 6 surviving patients had stable disease. All the 18 patients had ≥grade 3 hematologic adverse reactions, and non-hematologic adverse reactions included lung infection, nausea, vomiting and diarrhea.Conclusions:Ven+AZA treatment for newly treated and relapsed/refractory AML patients results in a high response rate with tolerable adverse reactions, but it is not effective in AML patients with FLT3-ITD/TKD mutation.

Objective To investigate the effects on proliferation of multiple myeloma cell lines U266 and RPMI 8226 induced by puerariae radix flavones (PRF) in vitro and its possible mechanism.Methods Exposed to 0,10,30,50,100 μg/ml PRF for 48 h and 72 h,the U266 and RPMI 8226 cells proliferation inhibitory rates were detected by MTT assay,cell cycles by flow cytometry (FCM),morphologic changes of U266 cells by Wright' s staining,and early-stage apoptotic rates of U266 cells by FITC-Annexin V/PI staining with FCM.Analysis of DNA fragment was made to test characteristic apoptosis DNA ladder in U266 cells.Results 0,10,30,50,100 μg/ml PRF could inhibit the proliferation of U266 and RPMI 8226 cells in a dose-dependent manner (U266 ＞ RPMI 8226).Cell cycle analyses in U266 and RPMI 8226 cells showed that sub-diploid peaks,but cell cycles changed minor.Wright's staining of U266 cells showed hardly any apoptostic character istic.Annexin V/PI double staining indicated that early-stage apoptotic rates of U266 cells exposed to 0,10,30,50,100 μg/ml PRF for 48 h were mildly increased in a dose-dependent manner.They were (3.20±0.36) ％,(5.20±0.92) ％,(7.30±1.22) ％,(8.10±0.53) ％ and (10.80±0.90) ％,respectively.The group differences had statistical significance (P ＜ 0.05).Analysis of DNA fragment barely exhibited the characteristic DNA ladder in U266 cells.Conclusion A certain concentrations of PRF could inhibit the proliferation of U266 and RPMI 8226 cells significantly.It is suggested that apoptosis related to the proliferative inhibition mechanism induced by PRF in U266 cell line,but not main.Other pathways such as necrosis and autophagy whether or not involved need further investigation.

As important regulators of apoptosis,bcl-2-family proteins regulate all major types of cell death,including apoptosis,necrosis,and autophagy.It's known that impaired apoptosis is a critical step in tumor development.Overexpression of antiapoptotic proteins of bcl-2 family is associated with the development and prognoses of malignant lymphoproliferative disorders.