Tyrosine kinase inhibitors discontinuation for chronic myeloid leukemia: a multicenter retrospective analysis in China / 中华血液学杂志

Objective: The clinical characteristics and outcomes of patients with chronic myeloid leukemia (CML) who had discontinued tyrosine kinase inhibitors (TKI) therapy were analyzed retrospectively. Methods: Clinical data of 109 cases of chronic CML patients who had discontinued TKI therapy in seven centers were retrospectively analyzed from June 1, 2005 to March 1, 2018. 91 cases with complete clinical data were enrolled in this study. We aimed to observe the status of patients with treatment free remission (TFR) after TKI therapy discontinuation and its prognostic factors. Results: 38 of 91 patients lost MMR after a median follow-up of 9 months and the estimated TFR was 52.6%. 31 of 38 patients who met the definition of molecular relapse resumed TKI treatment immediately and regained the major molecular response (MMR) with a median time of 3 months (range, 1-12 months). No significant difference was found in median course of imatinib therapy between the TFR group and the relapse. Similarly, duration to MMR, age and gender also showed no difference between the two groups. The longer duration of MMR maintenance (more than 24 months), the lower relapse rate was observed (P=0.027). Conclusion: TKI might be safely discontinued in part of CML patients.

Detection of cytokine expression patterns in the peripheral blood of patients with acute leukemia by antibody microarray analysis / 华中科技大学学报（医学）（英德文版）

The cytokines of acute leukemia (AL) patients have certain expression patterns, forming a complex network involved in diagnosis, progression, and prognosis. We collected the serum of different AL patients before and after complete remission (CR) for detection of cytokines by using an antibody chip. The expression patterns of cytokines were determined by using bioinformatics computational analysis. The results showed that there were significant differences in the cytokine expression patterns between AL patients and normal controls, as well as between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). In confirmatory test, ELISA revealed the expression of uPAR in AL. Moreover, the bioinformatic analysis showed that the differentially expressed cytokines among the AL groups were involved in different biological behaviors and were closely related with the development of the disease. It was concluded that the cytokine expression pattern of AL patients is significantly different from that of healthy volunteers. Also, differences of cytokine expression patterns exist between AML and ALL, and between before and after CR in the same subtype of AL, which holds important clinical significance for revealing disease progression.

Detection of cytokine expression patterns in the peripheral blood of patients with acute leukemia by antibody microarray analysis / 华中科技大学学报（医学）（英德文版）

The cytokines of acute leukemia (AL) patients have certain expression patterns, forming a complex network involved in diagnosis, progression, and prognosis. We collected the serum of different AL patients before and after complete remission (CR) for detection of cytokines by using an antibody chip. The expression patterns of cytokines were determined by using bioinformatics computational analysis. The results showed that there were significant differences in the cytokine expression patterns between AL patients and normal controls, as well as between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). In confirmatory test, ELISA revealed the expression of uPAR in AL. Moreover, the bioinformatic analysis showed that the differentially expressed cytokines among the AL groups were involved in different biological behaviors and were closely related with the development of the disease. It was concluded that the cytokine expression pattern of AL patients is significantly different from that of healthy volunteers. Also, differences of cytokine expression patterns exist between AML and ALL, and between before and after CR in the same subtype of AL, which holds important clinical significance for revealing disease progression.

Exogenous VEGF promotes hematopoietic stem cell mobilization / 中国实验血液学杂志

This study was aimed to investigate the effect of exogenous VEGF on hematopoietic stem cell mobilization and immune system. The C57BL/6J mice were randomly divided into the normal control group, VEGF short-term group (5 d) and VEGF long-term group (27 d). Mice in the experimental group were injected ip with VEGF (100 ng/d); mice in control group were injected ip with PBS. The white blood cell (WBC) count and the ratio of lymphocyte in the peripheral blood at different time point were assayed by hemacytometer. The percentage of hematopoietic stem cell (HSC), lymphocyte subgroup, regulatory T cell (Treg), myeloid-derived suppressor cells (MDSC) in the peripheral blood and spleen of different groups were detected by flow cytometry. The morphological changes of spleen and spleen index of mice in the control and long-term group were observed by microscopy. The results showed that the absolute number of WBC in the peripheral blood of mice significantly increased after injection of VEGF, and the peak value was at day 3. The percentage of Lin(-)Sca-1(+)CD117(+) cells in the peripheral blood and spleen of the long-term group were significantly higher than that in the normal control group (P < 0.05). The spleen of the mice in VEGF long-term group was larger than that of the control group, the spleen index also increased (P < 0.05), and remarkable extramedullary hematopoietic signs were found in the HE stained sections. There was no significant change in the total ratio of lymphocytes in the peripheral blood after injection, but the percentage of CD3(+) cells and the CD3(+)/B220(+) ratio in the long-term group deceased; the percentages of Treg and Gr-1(+)CD11b(+) MDSC in the experimental groups increased (P < 0.05), which more significantly increased in the long-term group than that in the short-term group (P < 0.05). It is concluded that the exogenous VEGF promotes hematopoietic stem cell mobilization, and at same time up-regulates the many kinds of suppressive immune cell levels which leads to changes of immuno-function.

Accurate rebuilding of sagittal plane radian measure for treatment of thoracolumbar vertebrate fracture: A comparative study / 第二军医大学学报

Objective To conduct a comparative study on the middle- and long-term efficacies of individualized titanium stick angular designs for treating thoracolumbar vertebrate fractures. Methods A total of 96 patients were divided into two groups,with 50 in the treatment group and 46 in the control group. The titanium stick in the treatment group was folded based on the numerical value which had been obtained by measuring and calculating the standard lateral projection of thoracolumbar vertebrate before the operation; the numerical value on sagittal plane was the sum of the average angle of its upper and subtus athletic segment, the angulation of subtus athletic segment and the angle of subtus vertebral body. The titanium stick in the control group was folded based on experience during the operation, with other treatments being the same. The patients were followed-up for at least 6 months, with an average of (18±5) months. All the patients received radiography examination pre- and post-operatively. And 42 patients received CT examination before and at the last follow-up; another 30 patients received MRI examination at last follow-up. Results At the final follow-up, the anterior, posterior vertebral heights were (1.06±0.46) mm and (0.42±0.26) mm for the treatment group and (2.37±0.86) mm (P<0.05) and (0.79±0.46) mm for the control group, respectively. The average loss of Cobb angle was (1.57±0.51)° in the treatment group and (2.49±0.89)° in the control group at final follow-up (P<0.05). The treatment group had 21 cases with fish tail and the control group had 25. The failure rate of internal fixation was 6% in the treatment group and 13% in the control group. The eggshell phenomenon on CT findings was found in 10 of the 22 patients in the treatment group and in 9 of the 20 cases in the control group at final follow-up. The neurological status was improved at least by 1 Frankel grade in the patients who had preoperative incomplete paraplegia. The scores of Oswestry Disability Questionnaire for the treatment group were: 0 in 17 cases, 2 in 15 cases, 4 in 11 cases, 6 in 2 cases, 8 in 2 cases, 56 in 1 case,80 in 1 case, and 88 in 1 case; for the control group were 0 in 10 cases, 4 in 15 cases, 6 in 11 cases, 8 in 2 cases, 10 in 2 cases,18 in 2 cases, 50 in 2 cases, and 80 in 2 cases. There were significant differente between the two groups (34% vs 21.74%, P<0.05). Conclusion When transpedicle vertebral arch internal fixation system is used for treatment of thoracolumbar vertebrae fractures via posterior approach, individualized titanium stick angular design can accurately regain the physiologic curve of the fixed thoracolumbar segment,reducing operational time,loss of vertebral height correction, failure rate of internal fixation, incidence of backache, and degeneration of adjacent segment.

Amplification of functional myeloid-derived suppressor cells during stem cell mobilization induced by granulocyte colony-stimulation-factor / 华中科技大学学报（医学）（英德文版）

The effects of granulocyte colony-stimulation-factor (G-CSF) on stem cell mobilization and its impact on the amplification of myeloid-derived suppressor cells (MDSCs) of donor mice were examined. A mouse model of stem cell mobilization was established by consecutive subcutaneous injection of 100 μg/kg G-CSF for 5 days. The blood from the donor mice was routinely examined during mobilization. Stem cells and MDSCs were analyzed by flow cytometry. The immunosuppressive molecules derived from MDSCs in serum and spleen, including hydrogen dioxide (H2O2) and nitric oxide (NO), and the activity of nitric oxide synthase (NOS) were determined during the mobilization. Apoptosis of T lymphocytes was assessed by using Annexin-V/PI. During stem cell mobilization, the number of lymphocytes and white blood cells in the peripheral blood was increased, and peaked on the 4th day. The number of stem cells in G-CSF-treated mice was significantly greater than that in controls (P<0.01). The expansions of MSDCs were also observed after G-CSF mobilization, with a more notable rate of growth in the peripheral blood than in the spleen. The activity of NOS and the production of NO were increased in the donor mice, and the serum H2O2 levels were approximately 4-fold greater than the controls. Consequently, apoptosis of T lymphocytes was increased and showed a positive correlation with the elevated percentage of MDSCs. It was concluded that G-CSF could provide sufficient peripheral blood stem cells for transplantation. Exogenous administration of G-CSF caused the accumulation of MDSCs in the peripheral blood and the spleen, which could lead to apoptosis of T lymphocytes and may offer a new strategy for the prevention and treatment of graft versus host disease.

Research progress of mesenchymal stem cell-derived microvesicle / 中国实验血液学杂志

Mesenchymal stem cell-derived microvesicle (MSC-MV) is a membrane secretory system which includes microparticle and exosome, and MSC-MV is released by MSC in resting or activated state. MSC-MV selectively package the biological active substances such as lipids, proteins, mRNA and miRNA but not loads them randomly. It has definitive effect of reducing tissue injury, promoting morphological and functional recovery of the injured tissue, and this effect is probably mediated by miRNA. What is more, the MSC-MV may also possess the biological function of immunological regulation, modulation of cell growth and differentiation. The generation, constitution, and function of MSC-MV are reviewed in this article.

Amplification of functional myeloid-derived suppressor cells during stem cell mobilization induced by granulocyte colony-stimulation-factor / 华中科技大学学报（医学）（英德文版）

The effects of granulocyte colony-stimulation-factor (G-CSF) on stem cell mobilization and its impact on the amplification of myeloid-derived suppressor cells (MDSCs) of donor mice were examined. A mouse model of stem cell mobilization was established by consecutive subcutaneous injection of 100 μg/kg G-CSF for 5 days. The blood from the donor mice was routinely examined during mobilization. Stem cells and MDSCs were analyzed by flow cytometry. The immunosuppressive molecules derived from MDSCs in serum and spleen, including hydrogen dioxide (H2O2) and nitric oxide (NO), and the activity of nitric oxide synthase (NOS) were determined during the mobilization. Apoptosis of T lymphocytes was assessed by using Annexin-V/PI. During stem cell mobilization, the number of lymphocytes and white blood cells in the peripheral blood was increased, and peaked on the 4th day. The number of stem cells in G-CSF-treated mice was significantly greater than that in controls (P<0.01). The expansions of MSDCs were also observed after G-CSF mobilization, with a more notable rate of growth in the peripheral blood than in the spleen. The activity of NOS and the production of NO were increased in the donor mice, and the serum H2O2 levels were approximately 4-fold greater than the controls. Consequently, apoptosis of T lymphocytes was increased and showed a positive correlation with the elevated percentage of MDSCs. It was concluded that G-CSF could provide sufficient peripheral blood stem cells for transplantation. Exogenous administration of G-CSF caused the accumulation of MDSCs in the peripheral blood and the spleen, which could lead to apoptosis of T lymphocytes and may offer a new strategy for the prevention and treatment of graft versus host disease.