BACKGROUND: At present, bone remodeling biological model study usually applys finite element method combing with computer technique to simulate and predict bone quantity or bone structure. In this study the author integrate inversion method with animal experiment to establish a quantification bone remodeling biological model of in vivo bone tissue in real stress environment.OBJECTIVE: To set up a quantification biological model of bone growth and remodeling adaptation, which integrates animal experiments, parameter inversion identification of mathematical functions, and technique of computer simulation. DESIGN, TIME AND SETTING: The experiment was accomplished in Animal Experiment Center of Dalian Medical University in October 2002.MATERIALS: 60 female Sprague Dawley mice of 6-week old were used in this study. Challenger double-energy X ray bone density device was provided from DMS Company, France. Sensation l6 CT machine was provided from Germany Siemens Company.METHODS: 60 mice were randomly divided into two groups: i 5 animals were in normal control groups. 45 in experiment groups. By designing a new animal experiment, we investigate the effects of stress environments on bone growth and remodeling of rapid growing rats and gather the bone mineral density (BMD) of proximal femur in the same interval for the unknown parameters (B and K) inversion of bone growth and remodeling equation to create the femur three-dimension geometrical model based on CT images. MAIN OUTCOMING MEASURES: Body weight of animal, bone density and CT imagine of proximal femur. RESULTS: Body mass in the experiment group and control group was increased with the rat growing; BMD in the control group and overloading group was also increased with the rat growing; but BMD in the unloading group was decreased in the fifth week. Inversion and experimental data showed that parameter B was rapidly decreased as compared to time, and it was closed to zero in the 10th week. Parameter K was rapidly increased as compared to time. and it was gradually increased from the 5th to the 10th weeks, moreover, it was closed to the horizontal line after 10 weeks. This predicted that rapid growth was over, and bone reconstitution and absorption came into another balance cycle. CONCLUSION: The thought and method used in the model creating in.this paper provide clue and reference to establish human model of bone growth and remodeling.

Objectives To compare the efficacy and adverse effects of combining all-trans retinoic acid and arsenic triox-ide with or without anthracyclines on the treatment of childhood acute promyelocytic leukemia (APL) patients. Methods The retrospective study included 46 children as newly diagnosed APL from January 1st, 2001 to December 31st , 2012. Efficacy and adverse effects for different induction therapies and in high and low white blood cell (WBC) count subgroups were studied. Results In the non antharcycline containing group, 2 patients died during remission induction, and in the antharcycline containing group none of the patients died. No statistical difference was observed between the antharcycline containing group and the non antharcycline containing group in complete remission, the length of time to achieve molecular complete remission and minimal residual disease quantitative analysis at the end of the induction. The mean duration of high WBC count subgroup in the anthar-cycline containing group was shortened than that of the non antharcycline containing group (P<0.05). The recovery time of the abnormal coagulation was found similar between these two groups. Conclusions The use of antharcycline in induction therapy could shorten the duration of high WBC count and reduced the WBC count peak , thus reduces the risk of early death.

Objectives To investigate the inlfuence of polymorphisms of SLC19A1 80G>A, MDR1 exon26C>T and MDR1 exon21G>T/A on curative effect and adverse reaction of high-dose methotrexate in patients with acute lymphoblastic leukemia. Methods MALDI-TOF-MS technique was used to detect the polymorphisms of SLC19A1 80G>A, MDR1 exon 26C>T and MDR1 exon21G>T/A in 108 patients with acute lymphoblastic leukemia (ALL). The relationship of genetic polymorphism, survival rate and toxicity was analyzed. Results The 36-month event-free survival was not related to any polymorphisms of MDR1 and SLC19A1. Patients with mutant types of MDR1 exon26C>T and MDR1 exon21G>T/A showed a much higher MTX plasma levels at 24 hours and higher incidence of hepatic injury (P<0.05). Conclusions The genetic polymorphism of MDR1 exon26>T, MDR1 exon21G>T/A has a large inlfuence on hepatic toxicity and plasma concentra-tions of MTX.

Objective: To analyze the clinical outcome and the prognostic factor in pediatric patients with core binding factor-acute myeloid leukemia (CBF-AML). Methods: A total of 121 newly diagnosed pediatric CBF-AML patients enrolled from Aug. 2005 to Sep. 2017 were retrospectively reviewed. Cumulative incidence of relapse (CIR), event-free survival (EFS) and overall survival (OS) rates were estimated by Kaplan-Meier method and prognostic factors were evaluated by Cox regression with SPSS. Results: Of the 121 patients, 120 patients were assessed for bone marrow remission after induction chemotherapy. 100 cases (83.3%) achieved complete remission (CR) after the first course of chemotherapy. 119 cases (99.2%) achieved CR after the second course of chemotherapy. Of the 121 patients, 13 patients (10.7%) had recurrence with the median interval of recurrence as 13.8 months (3.7 to 58.8 months). 17 patients (14.0%) died. The CIR, EFS and OS at 3 years were 12.7%, 77.5% and 82.8%, respectively. The factors including age at diagnosis, sex, initial WBC count, presence of extramedullary leukemia, C-KIT expression, additional chromosomal abnormalities, and CR after the first course of chemotherapy were analyzed by multivariate regression analysis of Cox. Multivariate analysis identified that additional chromosomal abnormalities was the only independent risk factor affecting OS (HR=4.289, 95%CI 1.070-17.183, P=0.040). Conclusions Pediatric CBF-AML was a unique setting of prognostic subtypes. Chemotherapy produced good responses. Additional chromosomal abnormalities was the only independent risk factor for OS in pediatric CBF-AML.

Objective: To explore the clinical features and prognostic factors of Ph-positive and/or BCR-ABL positive acute lymphoblastic leukemia (Ph⁺ ALL) in children. Methods: The clinical data of 68 Ph⁺ ALL children who were treated at Peking University People's Hospital from December 2006 to December 2016 was retrospectively reviewed. Survival analysis were estimated by Kaplan-Meier method. Univariate analysis was estimated by Log-rank test and Chi-square, and multivariate analysis was estimated by Cox proportional hazards regression model. Results: In the 68 cases, the proportion of male to female was 2.1∶1, with a median age of 8 (1-16) years, and the median overall survival (OS) and disease free survival (DFS) were 16.8 months and 13.5 months, respectively. The early response rate to treatment was 43.9%, with myeloid-antigens-expression group lower than the non-expression group (29.6% vs 61.3%, χ²=5.814, P=0.020); The complete remission (CR) rate after one-course induction therapy was 86.2% (56/65), with good-response group higher than the poor-response group (100.0% vs 74.2%, χ²=6.680, P=0.003);The CR rate after induction in patients receiving imatinib plus chemotherapy was higher than the patients receiving chemotherapy only (94.9% vs 73.1%, χ²=5.185, P=0.024). The 2-and 5-year OS were (61.4±7.0)% and (50.8±8.1)%, respectively. The 2-and 5-year DFS were (54.6±6.8)% and (48.6±7.3)%, respectively. Univariate analysis showed that the initial WBC, LDH, spleen size, liver size, with-myeloid-antigens-expression, early response to treatment, MRD (BCR-ABL) after one-course induction, application of imatinib and different treatment options affected 2-year OS rate (all P<0.05). LDH, spleen size, liver size, with-myeloid-antigens-expression, early response to treatment, MRD (BCR-ABL) after one-course induction, application of imatinib and different treatment options affected 2-year DFS rate (all P<0.05). Multivariate prognostic analysis for OS (RR=45.7, 95% CI 1.4-1 528.2, P=0.033) and DFS (RR=52.3, 95% CI 1.6-1 725.9, P=0.026) showed that the spleen ≥ 3 cm was the independent risk factor. Conclusions Pediatric Ph⁺ ALL is a special condition with unique clinical and biological features. The early response to treatment was poor in patients with myeloid-antigens-expression, which resulted in a low CR rate after one-course induction and the administration of imatinib can remarkably improve the CR rate. Initial spleen ≥ 3 cm is an independent prognostic factor. The efficacy of chemotherapy alone is poor, and imatinib combined with chemotherapy is applauded in the aim of improving outcomes.

Objective To explore the clinical characteristics and relevant factors affecting treatment and prognosis of TCF3-PBX1 positive acute lymphoblastic leukemia (ALL). Methods The clinical data of 29 children with newly diagnosed TCF3-PBX1 positive ALL from August 2006 to August 2015 were analyzed retrospectively. The expression level of TCF3-PXB1 fusion gene was monitored by regular quantitative reverse transcription polymerase chain reaction. The factors influencing prognosis in children with TCF3-PBX1 positive ALL were analyzed. Results There were 29 children (16 males and 13 females) with a median age of 8 years (9 months to 16 years). The most common immunophenotype was pre-B cell type (pre-B) (58.6％). The karyotype analysis showed that unbalanced translocation was more common (41.4％). The complete remission rate was 100％ on thirty-third day in 29 children, but the minimal residual disease (MRD) was not completely negative. Three cases were relapsed, all of whom were MRD positive. Cox multivariate regression analysis showed that age was an independent risk factor for 5 year overall survival (P<0.05). The 5 year overall survival rate and disease-free survival rate were (82±8)％ and (81±7)％respectively. Conclusions Childhood TCF3-PBX1 positive ALL is a highly heterogeneous disease with high rate of complete remission and good long-term efficacy. The risk stratification and individualized treatment is the key to improve the cure rate.

Objective To explore the prognostic value of quantitative monitoring of RUNX1-RUNX1T1 fusion gene in pediatric t(8;21)/RUNX1-RUNX1T1 positive acute myeloid leukemia(AML).Methods A total of 81 new-ly diagnosed AML children with t(8;21)/RUNX1-RUNX1T1 positive were enrolled in the People′s Hospital,Peking University,between August 2005 and January 2016.RUNX1-RUNX1T1 gene copy number of all the patients was analyzed by real-time quantitative PCR(qPCR)technology at diagnosis and after therapy in all patients.Cumulative incidence of relapse rate(CIR),event-free survival(EFS)rate and overall survival(OS)rate were estimated by Ka-plan-Meier method and prognostic factors were evaluated by COX regression. Results The level of RUNX1-RUNX1T1 gene on diagnosis was used as the baseline to determine whether the level of gene after treatment had a more than 3 logarithmic(3 log)reduction.After 2 courses of induction therapy,the patients with a more than 3 log reduction of RUNX1-RUNX1T1 transcript levels(≥3 log)had better EFS rate(82.4% vs.57.6%,χ2=7.454,P<0.01),and better OS(93.6% vs.59.3%,χ2=9.703,P<0.01),compared to the patients with a less than 3 log reduction(<3 log).Multivariate analysis showed that 3 log reduction in RUNX1-RUNX1T1 transcript levels after 2 courses of in-duction therapy was an independent prognostic factor for EFS rate[hazard ratio(HR)=4.223,95% confidence interval (CI):1.507-11.836,P<0.01]and OS rate(HR=5.002,95%CI:1.282-19.516,P<0.05).When periodically monitoring the RUNX1-RUNX1T1 gene,63 out of the 81 children patients were monitored for more than 6 times.The patients who had a more than 3 log reduction of gene before,but then those whose gene transcript level rose more than 1 log level were divided into group A,and the remaining patients were divided group B,and the difference of CIR was statistically significant between group A and group B(46. 7% vs. 4. 7%,P <0. 01). Conclusions RUNX1-RUNX1T1 gene copy number was detected with qPCR method in pediatric t(8;21)/RUNX1-RUNX1T1 positive AML,which can determine the treatment effect,predict the recurrence of patients and assess long-term prognosis.Thus it has great clinical application value.

Objective:To explore the molecular response and prognostic factors of pediatric patients with Ph-positive acute lymphoblastic leukemia (Ph + ALL) treated by tyrosine kinase inhibitors (TKI) with chemotherapy in TKI era. Methods:The clinical data of children newly diagnosed with Ph + ALL admitted at Department of Pediatrics, Peking University People′s Hospital from August 2006 to February 2017 were retrospectively reviewed.The molecular biological characteristics and survival prognosis of the 30 patients who received continuous TKI with chemotherapy from early induction combined and no subsequent transplantation were analyzed. Results:The 30 patients with Ph + ALL had 19 males and 11 females with a median age of 8-year-old (ranging from 2 to 16 years). The complete remission (CR) rate after the first cycle of induction chemotherapy was 96.7% (29/30 cases), with overall CR rate of 100.0%; Before treatment, the mean level of BCR/ ABL mRNA in the 30 patients was 73.2% (0.12%-160.60%) and the level declined significantly with the progression of chemotherapy courses, reaching the plateau stage at the 6 th month of chemotherapy ( Z=-1.922, P>0.05); nine patients had recurrence, with a median recurrence time of 7 months (3.7-58.8 months). Univariate analysis showed that age ( P<0.05), the lever of minimal residual disease (MRD) after induction chemotherapy ( P<0.01) and the MRD level at the 3 th month of induction chemotherapy ( P<0.01) affected the recurrence rate.The median follow-up time of 30 patients was 42.6 months (6.4-96.5 months), and the 3-year overall survival (OS) rate and event-free survival (EFS) rate were (78.6±7.8)% and (72.4±8.4)%, respectively; Cox multivariate analysis showed that the initial white blood cell count ≥34.0×10 9/L ( OR=11.955, 95% CI: 1.075-132.899, P<0.05) and BCR/ ABL mRNA reduction less than 3 log from baseline [major molecular response (MMR)] at the 3 th month of induction chemotherapy ( OR=8.563, 95% CI: 1.254-58.478, P<0.05) were independent risk factors affecting the 3-year EFS rate.In addition, the initial white blood cell count ≥34.0×10 9/L ( OR=14.327, 95% CI: 1.843-243.592, P<0.05) was also an independent risk factor affecting the 3-year OS rate. Conclusions:The application of TKI can significantly deepen the molecular response of Ph + ALL in children.In the TKI era, the initial white blood cell count ≥ 34.0×10 9/L and BCR/ ABL mRNA reduction less than 3 log from baseline (MMR) at the 3 th month of induction chemotherapy are independent risk factors for the long-term survival of pediatric Ph + ALL.

OBJECTIVETo evaluate the safety and efficacy of chimeric antigen receptors T cells (CAR-T) in childhood acute B lymphoblastic leukemia (B-ALL).

METHODSA relapsed B-ALL child after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was treated with CAR-T, and the related literatures were reviewed.

RESULTAn 11-year-old girl with TEL-AML1 fusion gene positive BALL who suffered a bone marrow relapse 28 months after remission from conventional chemotherapy. During the second remission, the patient received haploidentical allo-HSCT. She relapsed with detectable TEL-AML1 fusion gene even after chemotherapy and donor leukocyte infusions. She received an experimental donor-derived fourth generation CD19 CAR-T therapy. After infusion of 1 × 10(6)/kg CAR-T cells, she experienced only mild or moderate cytokine-release syndrome and the minimal residual disease turned negative. Then three maintenance of CAR-T cell infusions [(0.83-1.65)×10(6)/kg] was administered, and the disease-free survival had lasted for 10 months. However, the TEL-AML1 copies in her blood still increased and she died with leukemia relapse after additional CAR-T cell infusion.

CONCLUSIONTreatment of relapsed B-ALL with the fourth generation CAR-T cells directed against CD19 was effective and safe. CAR-T therapy is a novel therapeutic approach that could be useful for patients with relapsed and refractory B-ALL who have failed all other treatment options.

Bone Marrow ; Child ; Core Binding Factor Alpha 2 Subunit ; genetics ; Disease-Free Survival ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Neoplasm, Residual ; Oncogene Proteins, Fusion ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; therapy ; Receptors, Antigen, T-Cell ; genetics ; Recurrence ; Remission Induction ; T-Lymphocytes ; cytology ; Transplantation, Homologous

To solve the problems of small one-time ablation range and easy charring of the tissue around the electrode associated with the tumor radiofrequency ablation needle, based on the multiphysical field coupling analysis software COMSOL, the effects of needle material, the number of sub needles and the bending angle of sub needles on the ablation effect of radiofrequency ablation electrode needle were studied. The results show that compared with titanium alloy and stainless steel, nickel titanium alloy has better radiofrequency energy transmission efficiency and it is the best material for electrode needle. The number of sub needles has a great influence on the average necrosis depth and the maximum necrosis diameter. Under the same conditions, the more the number of sub needles, the larger the volume of coagulation necrosis area. The bending angle of the needle has a great effect on the maximum diameter of the coagulated necrotic area, but has little effect on the average necrotic depth. Under the same other conditions, the coagulation necrosis area formed by ablation increased with the increase of the bending angle of the sub needle. For the three needles with bending angles of 60 °, 90 ° and 120 ° analyzed in this paper, the one with bending angle of 120 ° can obtain the largest coagulation necrosis area. In general, the design of nickel titanium alloy with 120 ° bending 8-pin is the optimal. The average depth of radiofrequency ablation necrosis area is 32.40 mm, and the maximum necrosis diameter is 52.65 mm. The above optimized design parameters can provide guidance for the structure and material design of tumor radiofrequency ablation needle.
Humans ; Needles ; Temperature ; Catheter Ablation/methods* ; Necrosis ; Neoplasms/surgery* ; Alloys