Objective To investigate the effects of curcumin on proliferation and apoptosis of CD34+CD38-KG1a cells and its synergetic effect with busulfan on CD34+CD38-KG1a cells.Methods The expressions of CD34 and CD38 on the surface of KG1a cells and the effect of curcumin on the cell cycle and apoptosis in CD34+CD38-KG1a cells were detected by flow cytometry.MTT assay was used to analyze curcumin’s inhibitory effects on proliferation and synergistic effect with busulfan on CD34+CD38-KG1a.Clone formation rate was measured by methylcellulose colony-formation assay.Morphological changes of apoptotic cells were observed with the inverted optical microscope.The expression of Bcl-2 at the protein level was detected by Western blot.Results The percentage of CD34+CD38-KG1a was (98.2±3.2)% in KG1a cells.Curcumin could inhibit the proliferation in time-and dose-dependent manners and reduce the colony-formation ability of CD34+CD38-KG1a.The coefficient of drug interaction between curcumin and busulfan was less than 1.CD34+CD38-KG1a cells were arrested in the G0/G1 phase by decreasing S phase cells.Meanwhile,curcumin induced the apoptosis of CD34+CD38-KG1a cells. Apoptotic cells became bigger than normal ones,with unclear cell structure and rough edge of cell membrane.The expression of Bcl-2 at the protein level was down-regulated by curcumin.Conclusion Curcumin inhibited the proliferation of CD34+CD38-KG1a cells by reducing colony-formation ability,arresting cells in the G0/G1 phase and inducing apoptosis.Besides,there was a synergistic effect between curcumin and busulfan in CD34+CD38-KG1a cells.The down-regulated expression of Bcl-2 at the protein level may be associated with curcumin-induced apoptosis of CD34+CD38-KG1a cells.

Objective:To investigate the therapeutic effect of venetoclax combined with azacitidine in treatment of myelodysplastic syndromes (MDS) complicated with monoclonal globulinemia of unknown significance (MGUS).Methods:The clinical data of a patient with MDS complicated with MGUS in the Second People's Hospital of Shenzhen in December 2020 were retrospectively analyzed, and the literatures were reviewed.Results:According to results of bone marrow smear, cytogenetics, and next-generation sequencing, the patient was diagnosed as MDS and MGUS complicated with ASXL1, RUNX1, EZH2, STAG2 mutations as well as t(11;14). No response was observed after 2 courses of azacitidine and 1 course of azacitidine plus HAG. Later the patient achieved complete remission and negative RUNX1 and STAG2 mutations after a course of venetoclax combined with azacitidine. Meanwhile, M protein exhibited a decrease more than 50%. To date, the patient was still in complete remission.Conclusions:The regimen of venetoclax combined with azacitidine shows a significant efficacy and good tolerance to patient with co-occurrence of MDS and MGUS with t(11; 14).

Objective:To explore the efficacy and safety of in-class transition from proteasome inhibitor bortezomib to ixazomib in the treatment of newly-treated patients with multiple myeloma (MM).Methods:The clinical data of 63 newly-treated MM patients in Shenzhen Second People's Hospital from January 2018 to December 2020 were retrospectively analyzed. They were divided into transition group (23 cases) and bortezomib group (40 cases). Both groups were treated with bortezomib-containing regimen as the first-line treatment regimen. In case of intolerable adverse reactions, patients in the transition group were treated with ixazomib instead of bortezomib, while the patients in the bortezomib group did not undergo drug transition. The curative effect and progression-free survival (PFS) were compared between the two groups.Results:In the transition group, the overall response rate (ORR) before in-class transition was 95.7% (22/23), the rate of ≥ very good partial remission (VGPR) was 52.2% (12/23); the ORR after transition was 95.7% (22/23), and the rate of ≥ VGPR was 82.6% (19/23). In the bortezomib group, ORR was 90.0% (36/40), and the rate of ≥ VGPR was 72.5% (29/40). There was no significant difference in ORR and the rate of ≥VGPR between the two groups ( χ2 = 0.64, P=0.424; χ2 = 0.82, P = 0.364). The median number of cycles of PI therapy in the transition group was 9, and the median PFS time was not reached. The median number of cycles of PI therapy in the bortezomib group was 7.5, and the median PFS time was 30.0 months (95% CI 19.1-40.9 months), there was no significant difference in PFS between the two groups ( P = 0.275). In the bortezomib group, 12 patients discontinued bortezomib due to adverse reactions, the median PFS time was 20.0 months (95% CI 12.6-27.4 months), and the PFS of patients who discontinued PI in the transition group and the bortezomib group was compared, the difference was statistically significant ( P = 0.043). In the transition group, 21 patients (21/23, 91.3%) developed peripheral neuropathy, and the incidence of ≥grade 3 adverse reactions was 13.0% (3/23); in the bortezomib group, 22 patients (22/40, 55.0%) developed peripheral neuropathy, and the incidence of ≥grade 3 adverse reactions was 12.5% (5/40). Conclusions:For newly-treated MM patients, the transition from bortezomib to ixazomib can improve the depth of remission and reduce the recurrence caused by the discontinuation of PI.

AIM: To predict the core targets and related signaling pathways of Yi-xin-yin oral liquid for the treatment of arrhythmia, heart failure and myocarditis based on UHPLC-Q-TOF/MS, network pharmacology, molecular docking methods, cell experiments, according to the“homotherapy for heteropathy”theory in traditional Chinese medicine. METHODS: UHPLC-Q-TOF / MS was used to analyze and identify the chemical composition of Yi-xin-yin oral liquid Extract and the blood-absorbing components of rats oral administrated with Yi-xin-yin oral liquid extract, which compounds were applied in the databases searching for the potential targets (TCMSP, SwissTargetPrediction) and disease targets (OMIM, Genecard). Venn diagram was used for target intersection, and the subsequent protein-protein interaction network obtained core targets by STRING11.5 database, and then construct a "disease-component-target" network by cytoscape3.9.0. Finally, DAVID database was used to analysis GO function and KEGG enrichment analysis of core targets, and molecular docking validation was performed using Autodock vina software. And, validated with H9c2 cells for potential active ingredients and targets. RESULTS: A total of 156 compounds were identified from Yi - xin-yin Oral Liquid extract; 34 compounds were identified from rat serum, including 6-gin-gerol, isoliquiritigenin, glycyrrhizic acid and other compounds, and 139 intersecting targets were obtained. The KEGG pathway enrichment analysis mainly involved the TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway and so on. The TNF and IL-6 targets were selected for molecular docking with the main compounds, and the docking results were good (less than -5 kcal/mol). In vitro cellular experiments have shown that Yi-xin-yin oral liquid can exert therapeutic effects by regulating TNF and IL-6. CONCLUSION: The main potential active ingredients of Yi-xin-yin oral liquid may be isoliquiritigenin, glycyrrhetinic acid, calycosin-7-glucoside, salvianolic acid B, and 6-gingerol, which mainly act on TNF, IL-6 and other targets to regulate specific signaling pathways and exert therapeutic effects.