Background and purpose:Despite the high remission rate in patients with multiple myeloma (MM) after the standard regimen, but often relapsed and resistant. It has been shown that modulation of cAMP can induce cell cycle arrest and apoptosis in a variety of tumor cells, which has become an interesting approach to cancer therapy. This study aimed to investigate possible effects of cyclic adenosine monophosphate (cAMP) analogue 8-(4-chlorophenylthio) adenosine 3’, 5’-cyclic monophosphate (8-CPT-cAMP) on multiple myeloma cells, provide direction to develop new drugs for the treatment of MM. Methods:The myeloma cell line U266 cells were treated with 8-CPT-cAMP of different concentrations. The proliferation of U266 cells was evaluated through cell counting kit (CCK-8) assay, lfow cytometry was used to analyze the changes of cell were distribution, apoptosis rate as well as mitochondrial transmem-brane potential (ΔΨm) in U266 cells before and after the treatment. Meanwhile, real-time quantitative polymerase chain reaction (RT-PCR) and Western blot assay were used to detect expression levels of apoptosis regulators including caspase-8, caspase-9, Bcl-2 and Bax genes in U266 cells before and after the treatment. Results:The U266 cells were treated 5 days with 8-CPT-cAMP of different concentration, it was shown that 8-CPT-cAMP could signiifcantly inhibit cell growth of U266 cells in a concentration and time dependent manner, the IC50 of 8-CPT-cAMP was reduced obvious prolonged reaction time, and reached to 58.52μmol/L in the iffth day. The cell cycle of U266 cells was stopped in G0/G1 stage as the progress of concentration. It was showed statistical signiifcant difference associated with the cellular proliferation inhibition rate and apoptosis rate in different concentration and control (P<0.05). Meanwhile, 8-CPT-cAMP could induce mitochondrial transmembrane potential collapse in U266 cells. Compared with control groups, the levels of Bcl-2 mRNA transcripts and protein in U266 cells were reduced in 8-CPT-cAMP treated groups (P<0.05), while the levels of caspase-9, Bax mRNA transcription and the expression of Bax protein were increased in treatment groups, but the caspase-8 mRNA had no statistical signiifcant difference with controls. Conclusion:8-CPT-cAMP can inhibit the proliferation and promote apoptosis of myeloma cells, which might be mediated by caspase via mitochondrial pathway.

Background and purpose:Although bortezomib has become one of the major therapeutic agents against newly diagnosed or relapsed multiple myeloma (MM), there are some patients who become resistant to bor-tezomib and then relapse, emerging as a major obstacle to long-term survival of MM patients. It has been found that elevation of intracellular cyclic adenosine monophosphate (cAMP) levels could induce cell cycle arrest and apoptosis in MM cells,which has become an interesting approach to MM therapy. This study aimed to investigate possible effects of forskolin combined with bortezomib on bortezomib-resistant myeloma cells and further explore its mechanisms. Methods:The bortezomib-resistant MM cell lines H929-R and primary cells from patients who do not respond to bortezomib were used asin vitro models. The inlfuences of bortezomib and/or forskolin on MM cells were evaluated through cellular morphology, changes of cell distribution and apoptotic rate. Meanwhile, lfow cytometry analysis was used to detect mitochondrial transmembrane potential (ΔΨm) and the expression levels of apoptosis regulators in these cells before and after the treatment were detected by Western blot.Results:Bortezomib (20 nmol/L) synergized with forskolin (50nmol/L) to induce apoptosis of H929-R cells and bortezomib-resistant primary cells. In addition, borte-zomib synergized with forskolin to induce collapse of mitochondrial transmembrane and facilitate the degradation of anti-apoptosis proteins including Bcl-2 and Mcl-1.Conclusion:Bortezomib could synergize with forskolin to induce apoptosis in bortezomib-resistant MM cells.

Objective To investigate the application value of case-based learning (CBL) combined with teaching rounds in the standardized training of residents in department of hematology. Methods A total of 124 residents who received standardized training in department of hematology from August 2015 to July 2018 were selected and randomly divided into experimental group and control group. The residents in the experimental group received the teaching method of CBL combined with teaching rounds, while those in the control group received traditional teaching rounds. The two groups were compared in terms of department examination scores and teaching quality. Results Compared with the control group, the experimental group had significantly higher scores of the department examinations of hematological theoretical knowledge and case analysis (P<0.05). The residents in the experimental group thought that the new teaching method of CBL combined with teaching rounds could stimulate their interest in learning hematological diseases, improve self-study abilities , help them to combine theoretical knowledge with clinical practice , enhance their knowledge of hematological diseases, and cultivate their clinical thinking ability. Conclusion CBL combined with teaching rounds has achieved good results in standardized training of residents in department of hematology, and thus it holds promise for application in standardized training of other specialties in internal medicine.