Clinical features of SF3B1 mutation in patients with myelodysplastic syndrome with excess blasts / 中华内科杂志

Objective: To exploring the clinical features of SF3B1-mutated myelodysplastic syndrome with excess blasts (MDS-EB) and analyzing the association between SF3B1 mutation, and efficacy and prognostic significance for patients with MDS-EB. Methods: This was a retrospective case series study. The clinical data of 266 patients with MDS-EB diagnosed in the First Affiliated Hospital of Zhengzhou University between April 2016 and November 2021 were analyzed. The observed indicators included blood routine counts, mutated genes, overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and leukemia-free survival (LFS). The Kaplan-Meier method was used to depict the survival curves. The Log-rank test method was equally used to compare survival across groups and performed the Cox proportional hazard regression model for prognostic analysis. Results: In 266 patients with MDS-EB, 166 (62.4%) were men, and the median age was 57 (17-81) years. Moreover, there were included 26 and 240 patients in the SF3B1-mutated and SF3B1 wild-type groups. Patients in the SF3B1-mutated group were older [median age 65 (51, 69) years vs. 56 (46, 66) years, P=0.033], had higher white blood cell (WBC) counts [3.08 (2.35, 4.78) × 109/L vs. 2.13 (1.40, 3.77) × 109/L], platelet (PLT) counts [122.5 (50.5, 215.0) ×109/L vs. 49.0 (24.3, 100.8) × 109/L], absolute neutrophil counts (ANC) [1.83 (1.01, 2.88) × 109/L vs. 0.80 (0.41, 1.99) × 109/L]and occurrence of DNMT3A mutation [23.1% (6/26) vs. 6.7% (16/240)] (all P<0.05). The ORR were similar in both groups after 2 and 4 cycles of therapy (P=0.348, P=1.000). Moreover, the LFS (P=0.218), PFS (P=0.179) and OS (P=0.188) were similar across the groups. Univariate Cox analysis revealed that SF3B1 mutation did not affect the prognosis of patients with MDS-EB (OS: P=0.193; PFS: P=0.184). Conclusions: Patients with SF3B1 mutation were older, with greater WBC, PLT, and ANC, and SF3B1 mutation easily co-occurred with DNMT3A mutation. From this model, there were no significant differences in efficacy and survival of MDS-EB with or without SF3B1 mutation.

Effect of Metformin on Proliferation Capacity, Apoptosis and Glycolysis in K562 Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of metformin on the proliferation, apoptosis and energy metabolism of acute myeloid leukemia (AML) K562 cells and the possible mechanism.@*METHODS@#Different doses (0, 5, 10, 20 and 30 mmol/L) of metformin was added into the K562 cells, which were cultivated for 24 h, 48 h and 72 h. The inverted optical microscope was used to observe the cell growth, CCK 8 was used to detect the cell vitality. The appropriate metformin doses (0, 10, 20 and 30 mmol/L) and the best time (48 h) were selected for subsequent experiments. The flow cytometer with Annexin V-FITC /PI doulde staining was used to detect apoptosis; the glucose detection kit and lactate detection kit were used to detect glucose consumption and lactate production; fluorescence quantitative PCR was used to detect glycolysis-related gene expression, and Western blot was used to detect protein expression.@*RESULTS@#Metformin inhibited the proliferation of K562 cells in a dose-dependent manner (r=0.92), and the relative survival in the 30 mmol/L group was as low as 19.84% at 72 h. When treated with metformin for 48 h, the apoptosis rates of 0, 10, 20 and 30 mmol/L groups were 5.14%, 12.19%, 26.29% and 35.5%, respectively. Compared with the control group, the glucose consumption and lactate secretion of K562 cells treated with metformin were significantly reduced (P<0.05), and showed a dose-dependent effect(r=0.94,r=0.93,respectively). Metformin inhibited the expression of GLUT1, LDHA, ALDOA, PDK1, and PGK1 genes of K562 cells (P<0.05) showing a dose-dependent manner(r=0.83，r=0.80，r=0.72，r=0.76，r=0.73,respectively). Metformin inhibited the expression of P-Akt, P-S6, GLUT1, LDHA proteins of K562 cells(P<0.05), showing a dose-dependent relationship(r=0.80，r=0.92，r=0.83，r=0.92,respectively).@*CONCLUSION@#Metformin can inhibit the growth and proliferation of K562 cells and promote the apoptosis of K562 cells by inhibiting glycolysis energy metabolism. PI3K/Akt/mTOR signaling pathway may be one of the molecular mechanisms of metformin on k562 cells.

Application of heart rate and rating of perceived exertion scale in monitoring physical fatigue in divers during heliox saturation diving / 第二军医大学学报

Objective To study the application of heart rate(HR) and rating of perceived exertion(RPE) scale in monitoring the physical fatigue in the divers during the 100 msw heliox saturation diving. Methods The 100 msw pressure environment was simulated by a 500 msw saturation diving system: pressure was 1.1 MPa; oxygen partial pressure was 35-52 kPa; carbon dioxide partial pressure was <0.5 kPa;the temperature during exposure to high pressure was (31.0±1.7)℃;and the relative humidity was (76.8±3.5)%. Respiratory gas was heliox. The 18 divers' HR and the scores of RPE scale were recorded at 6 time points, including (1)the day before the subjects entered the chamber; (2) the first day that the subjects were exposed to 100 msw pressure environment; (3) the peak of the subject physical exercise load test under 100 msw pressure environment; (4) the second day under 100 msw pressure environment; (5) the first day that the subjects were out of the chamber; and (6) the seventh day that the subjects were out of the chamber. All the data were analyzed with paired-samples t-test. The correlation was analyzed with Pearson correlation. Results From the day before the subjects entered the chamber to the first day that the subjects were exposed to 100 msw pressure environment, the resting HR of subjects was significantly decreased (P<0.05); From the first day that the subjects were out of the chamber to the seventh day that the subjects were out of the chamber, the resting HR was significantly increased (P<0.05). Significant differences were also found in the basic RPE score of the subjectes between before entering the chamber and after entering the chamber(P<0.05). During the 100 msw heliox saturation, with the variable physical work loads, the trend of of heart rate changes was still in accordance with the score of RPE scale, with that measured at the peak of the subject physical exercise load test under 100 msw pressure being significantly different from that measured at the first day the subjects were exposed to 100msw pressure (P<0.05).The RPE score was significantly related with the HR of divers (r=0.734, P<0.01). Conclusion The combined application of HR and RPE scale can monitor the physical fatigue of the divers during 100msw heliox saturation diving.

Benign Multiple Sclerosis is Associated with Reduced Thinning of the Retinal Nerve Fiber and Ganglion Cell Layers in Non-Optic-Neuritis Eyes

BACKGROUND AND PURPOSE: It is exceedingly difficult to differentiate benign multiple sclerosis (BMS) from relapsing-remitting multiple sclerosis (RRMS) based on clinical characteristics, neuroimaging, and cerebrospinal fluid tests. Optical coherence tomography (OCT) allows quantification of retinal structures, such as the retinal nerve fiber layer (RNFL) thickness, at the optic disc and the ganglion cell layer (GCL) at the macula, on a micrometer scale. It can also be used to trace minor alterations and the progression of neurodegeneration, help predict BMS, and influence the choice of therapy. To utilize OCT to detect the extent of changes of the optic disk and macular microstructure in patients with BMS and RRMS compared to healthy controls (HCs), with special focus on changes related to the presence/absence of optic neuritis (ON). METHODS: Spectral-domain OCT was applied to examine eyes from 36 patients with multiple sclerosis (MS), comprising 11 with BMS and 25 with RRMS, and 34 HCs. RESULTS: The RNFL and GCL were significantly thinner in eyes previously affected by ON, irrespective of the type of MS (i.e., BMS or RRMS), than in HCs. Significant thinning of the GCL was also observed in non-ON RRMS (and not non-ON BMS) compared to HCs. Correspondingly, a significant association between disease duration and thinning rates of the RNFL and GCL was observed only in non-ON RRMS (-0.54+/-0.24 and -0.43+/-0.21 microm/year, mean+/-SE; p<0.05 for both), and not in non-ON BMS (-0.11+/-0.27 and -0.24+/-0.24 microm/year). CONCLUSIONS: The RNFL and GCL were thinner in both ON- and non-ON MS, but the change was more pronounced in ON MS, irrespective of the MS subtype studied herein. GCL thinning and the thinning rate of both the GCL and RNFL were less pronounced in non-ON BMS than in non-ON RRMS. These findings may help to predict the course of BMS.

Effects of novel human chemokine-like factor superfamily 8 on proliferation and EGFR expression of HL-60 cells / 中国实验血液学杂志

This study was aimed to investigate the effect of chemokine-like factor superfamily 8 (CKLFSF8) on proliferation and expression of epidermal growth factor receptor (EGFR) of HL-60 cells. Expression of CKLFSF8 mRNA on HL-60 cell line was assayed by RT-PCR; the target gene was transfected into the cells by lipid vector, cell proliferation was determined by MTT assay, while expression of EGFR in HL-60 was determined by immunocytochemical technique. The results indicated that expression of CKLFSF8 existed in HL-60 cells. After transfection, cell proliferation was inhibited (P < 0.05) and the expression of EGFR in HL-60 cells was also discovered to be inhibited (P < 0.05). It is concluded that the proliferation and expression of EGFR in HL-60 cells can be inhibited by transfection of CKLFSF8. The novel chemokine may provide a new approach in the treatment of leukemia.

Production of specific CTL induced by exosomes derived from K562 cells / 中国实验血液学杂志

The aim of this study was to investigate whether exosomes derived from K562 cells and human monocyte-derived dendritic cells (DCs) transfected with total RNA of K562 cells are capable of inducing antigen-specific cytotoxic T lymphocytes (CTL) responses in vitro. DCs were generated from peripheral blood mononuclear cells (PBMNC) of healthy volunteers in the presence of GM-CSF and IL-4, and then were transfected with K562 RNA by using DOTAP lipofection. Exosomes was extracted from the supernatant of DCs and K562 cells. The T cell were activated to be tumor specific CTL after DCs and exosomes were co-cultured with autologous T cells derived from healthy volunteers' PBMNC. The effect of CTL on K562 cells was detected by MTT assay. The results showed that treatment of T cells with exosomes derived from K562 cells or DCs transfected with total RNA of K562 cells could significantly promote their killing ability on K562 cells as compared with untreated T cells (P < 0.05). The killing ability of T cells treated with exosomes on K562 cells was stronger than on HL-60 cells (P < 0.05). It is concluded that the specific CTL immune response to leukemia cells can be induced by exosomes derived from K562 cells.