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OBJECTIVE@#To analyze the proliferation potential of bone marrow-derived mesenchymal stem cells (MSC) in patients with myelodysplastic syndrome (MDS).@*METHODS@#The MSC derived from the 24 patients with newly diagnosed MDS (MDS-MSC group) and MSC derived from 15 patients with nutritional anemia (control group) in the Affiliated Hospital of Hebei University were used as the research objects. The proliferation potential of MSC was analyzed by colony-forming unit assay, doubling time, cumulative passaging, cell number after 10 days of culture with equal amount of MSC and MTT experiment. The mechanism of abnormal proliferation was analyzed by cell cycle experiment, apoptosis experiment and p21 gene expression assay.@*RESULTS@#In the colony forming unit assay, the number of MDS-MSC colonies was 4.44±2.51, which was significantly lower than that of the control group (12.44±2.55)(P<0.01); the doubling time of MDS-MSC group was significantly longer than that of the control group (7.80±3.26 vs 3.63±0.85) (P<0.01); the number of MDS-MSC in 5×10@*CONCLUSION@#The proliferative capability of MDS-MSC is significantly reduced, which relates with the arrest of cell cycle in G
Subject(s)
Humans , Apoptosis , Bone Marrow Cells , Cell Proliferation , Mesenchymal Stem Cells , Myelodysplastic SyndromesABSTRACT
Emerging data have demonstrated that bone marrow mesenchymal stem cells (MSCs) play important roles in the progression of myelodysplastic syndrome (MDS). Experiments in vitro have showed that MSCs derived from MDS patients (MDS-MSC) exhibit the biological characteristics of cell senescence. Although the underlying mechanisms that regulate cell senescence need to be further elucidated, existing researches indicate that the mechanisms of MDS-MSC senescence have significant heterogeneity. Depth understanding of the underlying mechanisms involved in cell senescence of MDS-MSC are crucial to explore the potential therapeutic target of MDS. Therefore, this review summarizes research advances related with MSC senescence, such as MDS-MSC intrinsic changes in telomere shortening, DNA methylation status, oxidative stress and signal pathways regulating cell senescence in recent years.
Subject(s)
Humans , Bone Marrow , Bone Marrow Cells , Cellular Senescence , Mesenchymal Stem Cells , Myelodysplastic SyndromesABSTRACT
Myelodysplastic syndrome (MDS) is definded as a group of clonal hematological malignancies characterized by bone marrow (BM) ineffective.hematopoiesis and increases risk for progression to acute myeloid leukemia. The altered BM mesenchymal stem cells (MSCs) play a pivotal role in the evolution and propagation of MDS. Com-pared to normal MSCs, MSCs in MDS often exhibit altered Cytogenetic, epigenetic, differentiation and functional properties, moreover, high MSCs density is associated with poor prognostic factors, which translated into a signifi-cantly diminished ability to support normal hematopoiesis, facilitates survival of malignant hematopoietic cells, ulti-mately promote disease progression and transform to acute myeloid leukemia.Therefore, characterization of key steps in the pathogenesis of MDS will lead to new approaches to treat patients with this disease.
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Hypomethylating agents(HMA) currently are widely used in the treatment of myelodysplastic syndromes (MDS), provide a significant improvement in the treatment of MDS. However, resistance to HMA is an almost universal phenomenon. This review was focused on immune effects related to DNA methylation, and to explore the mechanism underlying HMA resistance involved in immune checkpoint pathways. However, the optimal role of checkpoint blockade therapy (CBT) and immune checkpoint pathways remain in HMA failure questionable. The better understanding of immune checkpoint pathways in resistance of HMA offers a compelling rationale to introduce CBT in patients as a novel treatment option. CBT is an established strategy in solid tumors with potential as an adjunctive therapy in hematologic malignancies, therefore, may alter the treatment landscape in MDS. The suitability and effectiveness of combining HMA with CBT need to be confirmed by the results of ongoing clinical trials, so as to find novel strategies to improve outcome after failure of HMA.
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<p><b>OBJECTIVE</b>To investigate the effects of absolute lymphocyte count(ALC) before start of the first cycle of consolidation chemotherapy(CC) on the relapse free survival in the patients with acute myeloid leukemia(AML), so as to explore a simple and easy method for predicting AML relapse.</p><p><b>METHODS</b>The clinical data of 132 patients with newly diagnosed AML (all non-acute promyelotic leukemia) from 2011 to 2017 were analyzed retrospectively. The 132 AML patients were treated with standard induction chemotherapy (IC) and consolidation chemotherapy (CC). According to lymphocyte count of patients before start of the first cycle of CC, the AML patients were divided into 2 group: high lymphocyte count group (H-Lym≥1.2×10/L) and low lymphocyte count group (L-Lym<1.2×10/L). The differences in ralapse rate and relapse-free survival between 2 groups were analyzed.</p><p><b>RESULTS</b>Among 132 patients with AML, patients who could be valuated and were elicible for the study accounted for 65 (49.24%). The absolute leukocyte count, age, chromosome karyotypes before IC of patients did not show statistical difference between H-Lym group (40 cases) and L-Lym group (25 cases). Unvarvate analysis showed that the Low lymphocyte count and unfavorable chromosome karyotypes were poor prognostic factors for the relapse-free survival time, and there was significant difference between 2 groups (P<0.01). The relapse risk in patients of L-Lym group increased, the hazard ratio (HR)=3.01 (95% CI=1.55-4.98) (P<0.01). In multivariate analysis containing unfavorable prognostic karyotypes, this trend still existed (HR=2.52, 95% CI 1.28-9.98)(P<0.01).</p><p><b>CONCLUSION</b>The AML patients with high lymphocyte count before the first CC have more long relapse free survival time suggesting that the lymphocyte count before the first CC may be prognostic factor for relapse free survival of AML patients.</p>
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Humans , Consolidation Chemotherapy , Leukemia, Myeloid, Acute , Lymphocyte Count , Prognosis , Recurrence , Retrospective StudiesABSTRACT
Objective To investigate the relations of absolute lymphocyte counts (ALC) to the therapeutic responses in patients with myelodysplastic syndrome (MDS) after the first course of decitabine (DAC) treatment.Methods Clinical data of 35 patients with MDS and MDS-derived secondary acute myeloid leukemia (AML) who were admitted in the Affiliated Hospital of Hebei University from Jan.2014 to Dec.2016 and treated with DAC were included in the present study.The patients were grouped into high lymphocyte group (H-Lym,ALC ≥ 1.2 × 109/L) and low lymphocyte group (L-Lym,ALC＜1.2 × 109/L) based on the ALC in days 28-35 after the first course of DAC treatment.The baseline data of both groups were compared with Pearson x2 analysis,while t test was used to analyze the changes of lymphocyte number before and after the first course of DAC treatment.Progressionfree survival (PFS) was estimated with Kaplan-Meier method,and the cumulative survival (CS) was compared between the two groups using log-rank test.Results Of the 35 patients,15 were in H-Lym group and 20 in L-Lym group.No significant difference existed in the baseline lymphocyte levels between the two groups (P＞0.05).The statistically significant differences (P＜0.05) existed only in the patients of the two groups who were with the proportion of bone marrow blasts ≥ 10％.The ALC in H-Lym group were slightly higher after the first course of DAC treatment than that at the time of diagnosis,but with no statistically significant (P＞0.05).However,the ALC in L-Lym group were significantly lower after the first course of DAC treatment than that at the time of diagnosis (P＜0.05).Patients had higher overall response rate (ORR) in H-Lym group than in L-Lym group (80％ vs.40％,P＜0.05).The median PFS was 10 months in H-Lym group and 7.6 months in L-Lym group (P＜0.05).Univariate analysis showed that the low ALC was a poor prognostic factor for the progression ofMDS (P＜0.05).Conclusion Patients with ALC ≥ 1.2 × 109/L after the first course of DAC treatment will have better ORR and longer PFS.
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OBJECTIVE@#To investigate a reliable clinical indication for predicting the therapeutic response of decitabine therapy in the patients with myelodysplastic syndromes (MDS).@*METHODS@#The clinical efficacy of decitabine for 55 cases of MDS was analyzed retrospectively. According to the lymphocyte level at d28 after the first time treatment with decitabine, the patients were divided into high lymphocyte level group (H-Lym≥1.2×10/L) and low lymphocyte level group (L-Lym<1.2×10/L), and the overall response rate (ORR) and the progression-free survival (PFS) time in 2 groups were compared.@*RESULTS@#As compared with L-Lym group, the ORR and PFS time in H-Lym group were significantly enhanced ［(76.0% vs 50.0%) (P<0.05) and median time (15.7 months vs 8.5 months)(P<0.05), respectively］;the ratio of platelet level ≥100×10/L in H-Lym group was very significantly higher than that in L-Lym group (72.0% vs 20.0%)(P<0.01). Multivariat analysis showed that the risk of disease progression in L-Lym group was 4.45-fold of H-Lym group (95% CI:1.58-12.59)(P<0.05).@*CONCLUSION@#The patients with lymphocyte level ≥1.2×10/L at day 28 after the first time treatment with decitabine show the higher ORR and longer PFS time, therefore. the lymphocyte level at day 28 after first time treatment with decitabine can be used as an early clinical indicator for predecting the response to decitabine treatment.
Subject(s)
Humans , Antimetabolites, Antineoplastic , Decitabine , Lymphocytes , Myelodysplastic Syndromes , Retrospective Studies , Treatment OutcomeABSTRACT
Objective To study the influence from load strength on solute transport rate in lacunar-canalicular system (LCS) of loaded tibia using finite element method.Methods Based on micro-CT scan images of adult mice tibia, the finite element model of the tibia, which was regarded as being homogeneous biphasic-solute, was established by software of Mimics, Hypermesh and FEBio. The relationship between transport rate and solute diffusivity/load strength was obtained by setting 3 groups of different solute diffusivity (3, 15, 30 μm2/s) and load strength (0.2, 2.0, 5.0 N), respectively. By comparing the results from both fluorescence recovery after photobleaching (FRAP) experiment and finite element method, the effect of load stimulation on transport enhancement was analyzed. Results The transport rate increased with the increase of diffusion rate and load strength. The results from finite element method were basically consistent with the solute transport rules by comparing data from FRAP experiment. Conclusions The research findings can provide some basis for load response and liquidity in deep area of cortical bone, and for further revealing the mechanism of bone regeneration.
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<p><b>OBJECTIVE</b>To carry out the molecular epidemiological study of the wild-type measles virus isolated in Qinghai Province during 2000-2011, and provide a scientific basis for the measles elimination.</p><p><b>METHODS</b>Measles viruses were isolated using B95a cell line or Vero/SLAM cell line from throat swabs collected from suspected measles cases during measles outbreak and sporadic in 6 prefectures during 2000-2011. The fragment of 696 nucleotides of N gene carboxy terminal was amplified by using RT-PCR methods. The PCR products were sequenced and analyzed. The phylogenetic tree was conducted with the viruses isolated in viruses from other province.</p><p><b>RESULTS</b>Total 19 measles viruses were isolated during 2000-2011 in Qinghai province and all belong to genotype H1a. The results of phylogenetic tree showed that viruses in 2000-2005 and in 2009-2011 were distributed in two different lineages, and it revealed that these strains belonged to at least 2 viral transmission chains and the viruses circulated during 2000-2005 were not detected after 2005.</p><p><b>CONCLUSION</b>Genotype H1a was the predominant genotype circulated in Qinghai province during 2000-2011. Qinghai measles virus strains had not evolved independently, but coevolved with the measles virus strains in other provinces in mainland China. The variation of important amino acid sites of measles virus should be continuous monitored and provide the scientific strategy for the measles elimination.</p>
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Humans , China , Epidemiology , Disease Outbreaks , Genotype , Measles , Epidemiology , Virology , Measles virus , Classification , Genetics , Molecular Epidemiology , Molecular Sequence Data , PhylogenyABSTRACT
Objective To discuss the method for defining personalized materials properties of the fresh human long bone with alcohol treatment and the effect from the number of bone materials on finite element results. Methods Based on images from CT scans, a three dimensional solid model of the long bone was established in Mimics, which was then classified into the cortical bone, cancellous bone and marrow in Hypermesh. Based on relevant empirical formulas, material parameters of the cortical bone and cancellous bone were given, respectively, and 5 finite element analysis (FEA) models with different numbers of materials were set up. The simulation for linear elasticity of the compression was carried out in Abaqus and the results were validated by in vitro verification test. Results Under the end displacement ranging from 0 to 1 mm, the average relative error between the simulation results and the experimental data for holistic force-displacement was about 10%, when the materials number was defined as 1 kind of the cancellous bone and over 10 kinds of the cortical bone. And the average relative error between the simulation results and the experimental data for the deformation of the measurement points was 14.6%. The error of holistic force displacement for 1 kind of the cortical bone was 2.83% when the end displacement ranged from 0 to 0.5 mm. Conclusions (1) Using the gray value of CT scans, materials properties of the main component of the bone could be defined accurately. (2) The simulation result was greatly affected by the material number of the cortical bone, and defining 10 kinds of the cortical bone could satisfy the FEA need. (3) The FEA model with 1 kind of the cortical bone also could satisfy the need of analysis under small deformation.