Chronic myelogenous leukemia (CML) has a high proportion in hematologic malignancy.Past decade,the appearance and development of tyrosine kinase inhibitors (TKIs) is the milestone of the treatment of CML.TKIs have antitumor effect with inhibition of the phosphorylation of kinases and the downstream signal transduction.In recent years,many large medical institutions at home and abroad worked on clinical experiment researches to investigate the mechanism of TKIs and how to choose TKIs in CML patients.This work is of great significance to the clinic.

Objective To study the immunomodulatory functions of adult human bone marrow-derived mesenchymal stem cells in vitro.Methods Adult human BMMSCs were separated with Percoll((1.073) g/ml) and cultured in Dulbecco's Modified Eagle's Medium with low glucose containing 10% fetal calf serum.The purity of BMMSCs was identified with the spindle-fibroblastic morphology by microphotograph and the phenotypes were tested by fluorescence-activated cell sorter(FACS).BMMSCs were plated in 96-well plates.After treated with mitomycin,BMMSCs were co-cultured for 72 h with allogeneic lymphocytes isolated from peripheral blood.Effects of MSCs on PHA induced lymphocytes transformation were investigated.The proliferation of lymphocytes was measured by MTT method.Results Peripheral blood lymphocytes proliferation was suppressed by BMMSCs and the inhibition ratio was (60.68%)(P

Acute Kidney Injury ; chemically induced ; enzymology ; Animals ; Disease Models, Animal ; Gentamicins ; Peptidyl-Dipeptidase A ; metabolism ; Rats

It provides a new approach to treat myelodysplastic syndromes when decitabine comes out.In order to improve the understanding of the role of decitabine and to provide a reference for the clinical treatment of middle-risk and high-risk myelodysplastic syndromes,this article mianly summarized drug combination,prognostic molecular markers,and reviewed the mechanism of action,main medication regimen in recent 5 years for the treatment of middle-risk and high-risk myelodysplastic syndromes with decitabine.

Objective To explore the effects and the molecular mechanism of synergistic hepatocarcinogenesis of HBV and AFB1 in the development of HCC by studying the difference in protein expression profiles in hepatocellular carcinoma exposed to hepatitis B virus and Aflatoxin B1.Method 32 HCC specimens were labeled under four categories based on their biomarkers of HBV and AFB1 exposure:group A:HBV(+)/AFB1 (+),10 cases,group B:HBV(+)/AFB1 (-),10 cases,group C:HBV(-)/AFB1(+),6 cases,groupD:HBV(-)/AFB1(-),6 cases.Normal hepatic tissues from 10 cases of hepatic hemangioma,liver resection and liver transplant donor were chosen as the normal control group.Isobaric Tagging Reagent Quantitative (iTRAQ) Proteomics together with 2DLC MS/MS were applied to analyze the differentially expressed proteins among the 4 groups.Result (1) A total of 117 unique differentially expressed proteins including 53 up-regulated proteins and 64 down-regulated proteins were identified in the four groups.The number of unique differentially expressed proteins,including up-regulated and down-regulated proteins,in group A,group B,group C and group D were 106,97,104 and 74 respectively.(2) Among the 117 differentially expressed proteins,9 proteins were heat shock proteins or chaperones,and they were up regulated in group A,B and C.Besides,15 proteins were detoxification and drug metabolism pathway related proteins,12 of them were down-regulated in group A,and more than half of them were also down-regulated in group B and C.(3) The Reverse Transcriptase PCR result showed the mean expression level of AKR1B10 mRNA in group A was significantly higher than group B,C and D (all P＜0.05,respectively).Group C also showed significantly a higher expression level of AKR1B10 mRNA than group D (P＜0.05).The Western-blot results showed the mean expression level of AKR1B10 protein in group A was significantly higher than group B and D (all P＜0.05,respectively).Conclusions The up-regulated expression of heat shock protein and the down-regulated expression of most protein enzymes related to detoxification and drug metabolism were the common molecular biological events of HCC associated with exposure to HBV and AFB1.This suggested the synergistic hepatocarcinogenesis effects of HBV and AFB1 may be related to dysregulation of protein enzymes related to detoxification and drug metabolism.The overexpression of AKR1B10 may be involved in the AFB1-related hepatocarcinogenesis process.

Objective To explore the feasibility and safety of cotransplantation of autologous bone marrow-derived mesenehymal stem cells (MSCs) and peripheral blood stem cells in hematological malignant diseases and to observe its effect on hematopoietic reconstruction after cotransplantation. Methods Adult human MSCs were isolated from the healthy bone marrow of the patient himself with Percoll (1. 073 g/ml) and cultured in Dulbecco's modified Eagle's medium with low glucose containing 10% AB type human serum. After conditioning regimen of high-dose chemotherapy and radiotherapy, cotransplantation of autologous bone marrow-derived MSCs and peripheral blood stem cells was done in five patients with hematological malignant diseases. Results The process of the infusion was safe and there were no adverse reactions or other toxicities related to the infustion of MSCs. The median time to achieve neutrophil counts greater than 0. 5 × 109/L was 9.4 days ( ranging from 8 to 11 days) after cotransplantation and platelet counts greater than 20 × 109/L 12. 2 days (ranging from 10 to 14 days). Conclusion Cotransplantation of autologous bone marrow-derived MSCs and peripheral blood stem cells in hematological malignant diseases is feasible and safe. The rapid hematopoietic reconstruction after cotransplantation shows that MSCs have an effect on hematopeiesis, but the mechanism is still to be investigated.

BACKGROUND: Preliminary study has proven that adult human bone marrow-derived mesenchymal stem cells (MSCs) suppress peripheral blood lymphocytes proliferation.But the mechanism was still to be investigated.OBJECTIVE: To study the negatively regulatory effect of adult human MSCs on allogeneic lymphocyte proliferation by cell-free condition.DESIGN,TIME AND SETTING: Cytological observation in vitro,which was performed in the Lanzhou General Hospital,Lanzhou Military Area Command of Chinese PLA between October 2005 and December 2007.MATERIALS: The bone marrow sample was provided by the allo-transplantation donor.The peripheral blood lymphocytes were provided by the healthy volunteer.METHODS: Adult human MSCs were separated with Percoll + adherence method.Allogeneic peripheral blood lymphocytes were obtained from healthy donors with Ficoll solution and the cell concentration was adjusted as 2×109/L for use.100μ L MSCs culture supernatant was taken out in 96-well plates.The groups were following: A superuatant + 3-day MSCs culture media (100 μ L/well); B superuatant + phytohemagglutini (PHA; 1 g/L,5 μ L); C medium + LG-DMEM culture media containing 10% fetal bovine serum (100 μ L); D medium + PHA (1 g/L,5 μ L).The cells were incubated at 37 ℃ with 5% CO2 in a fully humidified atmosphere for three days.MAIN OUTCOME MEASURES: Effect of MSCs supematant on proliferation and transformation of variant lymphocytes.RESULTS: Peripheral blood lymphocytes proliferation was suppressed as compared with the blank control group and PHA group after MSCs culture,and the inhibition ratio was 9.00% (P ＜ 0.05).When lymphocytes were stimulated by PHA,the suppression effects were even stronger and the inhibition ratio was 20.91% (P ＜ 0.01).CONCLUSION: Adult human MSCs supernatant can suppress peripheral blood lymphocytes proliferation and transformation; furthermore,PHA can enhance the inhibitory effect,suggesting the negative regulation is at least in part due to indirectly inhibiting lymphocytes via soluble cytokines.

Folic Acid ; administration & dosage ; therapeutic use ; Humans ; Neural Tube Defects ; prevention & control

Objective To construct the objective system of 5+3 integrated clinical medicine personnel training mode.Methods For the attitude,knowledge and ability clinical medical students should have,who received 5+3 integrated training,we adopted literature research,expert interviews intending to make a preliminary questionnaire items,and invited experts and graduates to modify the expressions of the items a number of times,and eventually formed the final questionnaire that met the study objective.We asked 500 teachers in basic medicine,clinical medicine,and medical humanities and so on,to evaluate the importance of the questionnaire.406 valid questionnaires were recovered and the effective recovery rate was 81.2％.Epidata 3.1 and SPSS 19.0 were used for survey data summary statistics,exploratory factor analysis and factor weighting method were used to get the goal of talent training base,and on these basis target system was constructed.Results In 5+3 integrated medical education model,clinical medical personnel training target system included knowledge,attitude and ability of the part,a total of 9 target groups.Each group contained elements in the training target system for different weights,among which attitude included a common factor,proportion of 27.51％;knowledge consisted of three factors,the proportion of 29.34％;and the ability contained five common factors,accounting for highest proportion of 43.15％.Conclusion 5+3 integrated clinical medical talents training target system established in this study highlights the ability requirements,emphasizes the comprehensive quality training,which accords with the principles of talent training goal and the requirements of 5+3 medical education model,has certain guiding significance for the curriculum reform,and can be used for reference in the development of talents training program for medical colleges and universities.

Objective To explore the abilities and personal qualities that medical undergraduates need for their future clinical work, and develop their competency model. Methods The self-made ques-tionnaire survey on medical undergraduates' competencies was conducted among the 1326 medical under-graduates in a medical university by using the cluster sampling method, and the 1099 effective question-naires were collected with effective rates of 82.88%. The exploratory factor analysis was used to analyze the internal structure of competency item and to build the competency model. The rating method was used to calculate the weight of each competency item. Results The overall Cronbach's alpha coefficient of the competency questionnaire was 0.965, and the coefficient of each dimension was above 0.832. The KMO statistic value was 0.970, and the probability associated with Bartlett test statistic was P=0.000, showing that the questionnaire has high reliability and validity. The competency model of medical undergraduates covers six aspects, namely, craftsmanship, personal qualities, professional learning, interpersonal communication, psychological adaptation and the pursuit of excellence, which contain 49 factors. The cumulative variance contribution rate was 54.729%. The weights of these six aspects in the model were 0.204 4, 0.202 1, 0.175 3, 0.158 8, 0.137 6 and 0.121 8 respectively. Conclusion The competency model of undergraduate medi-cal students has a certain scientific and practical value, which can provide new evaluation methods and ideas for medical education objectives, quality assurance, teaching evaluation, medical personnel selection and training.