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Objective:To evaluate the short-term efficacy and the improvement of quality of life of enzyme replacement therapy (ERT) with Imiglucerase on children with Gaucher disease(GD) through the same time monitoring.Methods:Six children diagnosed as GD who were treated by ERT with Imiglucerase in the Department of Hematology of the Children′s Hospital of Shanxi Province from May 2019 to May 2020 were recruited.Every 3 months, the sizes of the liver and spleen was palpated, the change of bone pain was recorded, and the haematological index was examed.The volumes of the liver and spleen at 1-year treatment were measured by CT.Bone involvement was examined by magnetic resonance imaging (MRI). In addition, the body weight, height, and the 36-Item Short Form Survey (SF-36) were measured and compared with pre-treatment levels.These data were analyzed statistically by SPSS 25.0 and the difference between pretherapy and post-treatment was compared by paired t test. Results:Six children diagnosed as GD received ERT with Imiglucerase.No adverse events were reported.Decreased volumes of the liver and spleen, and increased hemoglobin level and platelet count were detected after 3-6 months of ERT.After 1 year of ERT, hemoglobin level significantly increased compared with pre-treatment level ( t=4.200, P=0.008). Although the platelet count increased at 1-year ERT, it was comparable with pre-treatment level ( t=2.260, P=0.073). The volumes of liver and spleen decreased by (22.10±15.28)% ( t=2.725, P=0.042) and (47.10±18.42)% ( t=3.162, P=0.034) after 1 year of ERT, respectively.During the first year of ERT, the height and weight increased (6.17±2.86) cm ( t=5.286, P=0.003) and (4.08±2.01) kg ( t=4.975, P=0.004), respectively.SF-36 score increased significantly from (489.35±103.99) points to (632.75±73.34) points ( t=5.740, P=0.002). After 1 year of ERT, 1 patient still had bone pain, and 2 cases were worse in bone MRI, which may be attributed to the short period of follow-up and insufficient dose, and another 3 had no change in bone MRI. Conclusions:ERT ameliorates GD-associated anemia, organomegaly and growth retardation, and improves the growth rate of body mass and height and the quality of life in the short period.However, short-term ERT does not improve the bone disease.
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Objective:To investigate the relationship between NUDT15 gene polymorphism and tolerance to treatment with 6-mercaptopurine (6-MP) in children with acute lymphoblastic leukemia (ALL).Methods:Fifty-eight children diagnosed with ALL in Shanxi Children's Hospital from January 2019 to December 2020 were recruited. All of them were treated with CCLG-ALL2018 chemotherapy regimen and the bone marrow showed complete remission. They received 6-MP oral treatment during maintenance treatment. Single nucleotide polymorphism of NUDT15 gene was detected by real-time fluorescence quantitative polymerase chain reaction. The bone marrow suppression after 6-MP treatment and 6-MP tolerance dose in patients with different NUDT15 genotypes were analyzed.Results:Among 58 patients, 3 patients had NUDT15 TT genotype, 46 patients had CC genotype and 9 patients had TC genotype. During maintenance treatment with 6-MP, the differences in leukocyte count, hemoglobin and platelet count among the three groups of patients with different NUDT15 genotypes were statistically significant (all P < 0.05). Among 58 patients, 23 (39.66%) patients had varying degrees of neutropenia after medication, including 16 cases of NUDT15 CC genotype, 5 cases of TC genotype and 2 cases of TT genotype. There was a statistically significant difference in bone marrow suppression among the three groups ( H = 29.10, P < 0.05). The dosages of 6-MP used in patients with TT, CC and TC genotypes were (10.4±8.8) mg·m -2·d -1, (41.5±1.3) mg·m -2·d -1 and (36.7±2.4) mg·m -2·d -1, respectively, and the difference was statistically significant ( F = 16.95, P < 0.05). Conclusions:Children with different NUDT15 genotypes have different tolerance to 6-MP, and NUDT15 gene polymorphism is associated with 6-MP intolerance during maintenance treatment in children with ALL, which may affect the treatment of the disease.
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Objective:To explore the clinical characteristics and prognostic factors of children with relapsed acute lymphoblastic leukemia (ALL).Methods:The clinical data of 52 children with relapsed ALL in Children's Hospital of Shanxi Province from January 2010 to April 2019 were retrospectively analyzed. The clinical characteristics of the children were summarized and the prognostic factors after recurrence were analyzed.Results:Till May 1, 2019, 5 out of 52 children gave up treatment after diagnosis and were lost to follow-up. For the remaining 47 children with successful follow-up, the median age at initial diagnosis was 60 months (11-168 months), the median time from initial diagnosis to relapse was 21 months (2-112 months), the median follow-up time was 5.5 months (1.0-69.0 months), and the 2-year overall survival (OS) rate after relapse was 31%. Nine patients accepted allogeneic hematopoietic stem cell transplantation after the second time complete remission, the median time from diagnosis to transplantation was 4.5 months (3.0-7.0 months), and the median follow-up time was 22 months (4-69 months). The 2-year OS rates in relapsed children with white blood cell count < 50×10 9/L and ≥ 50×10 9/L at initial diagnosis were 39% and 13%, respectively (χ 2=5.623, P=0.018). The 2-year OS rate after relapse in standard-risk, intermediate-risk and high-risk groups were 72%, 31% and 8%, respectively (χ 2=10.068, P=0.007). The 2-year OS rate after relapse in very early relapse, early relapse and late relapse groups were 0, 33% and 79%, respectively (χ 2=30.066, P < 0.01). The 2-year OS rate after relapse in chemotherapy with or without radiotherapy group, transplantation group and irregular treatment group were 57%, 89% and 0, respectively (χ 2=26.885, P < 0.01). Cox multivariate analysis showed that relapse time was the independent risk factor affecting the prognosis of children with relapsed ALL ( HR=0.340, 95% CI 0.146-0.789, P=0.012). Compared with the transplantation group, the risk of death in the chemotherapy with or without radiotherapy group and the irregular treatment group was significantly higher ( HR=12.313, 95% CI 1.266-119.758, P=0.031; HR=20.699, 95% CI 2.230-192.129, P=0.008), suggesting that hematopoietic stem cell transplantation is a protective factor for the prognosis of children with relapsed ALL. Conclusions:The relapse of ALL in children mainly happens in very early and early time. The main part of relapse is bone marrow, and there are many high-risk patients at initial diagnosis. The risk group at initial diagnosis, white blood cell count at initial diagnosis, relapse time, and treatment after relapse are the risk factors affecting the prognosis, and the relapse time and hematopoietic stem cell transplantation are the independent prognostic factors.
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Objective@#To investigate the current status of family hardiness and its influencing factors in children with leukemia.@*Methods@#The children with leukemia and their caregivers in the Children's Hospital of Shanxi from August to November 2017 were enrolled. A questionnaire survey was conducted using a convenient sampling method, and 100 questionnaires were distributed. The questionnaire included the General Status Questionnaire, the Family Hardiness Index (FHI), the Coping Health Inventory for Parents (CHIP) and the Positive and Negative Affect Scale (PANAS).@*Results@#A total of 92 valid questionnaires were collected. Among the scores of family hardiness in children with leukemia [(3.29±0.43) points], the responsibility score [(3.32±0.45) points] was higher than the control score [(3.31±0.46) points] and the challenge score [(3.23±0.53) points], and the challenge score was the lowest. The score of frequency of coping styles used by the caregiver of the child with leukemia was (3.64±0.70) points, the most frequent coping style used by the caregiver was "family unity, optimism, cooperative attitude" [(3.73±0.89) points], and the positive [(3.28±0.84) points] and negative [(2.51±0.80) points] emotions were in a moderate state. The child's sex, age, stage of chemotherapy and medical insurance status, the caregiver of the child, the age of the caregiver, the family's place of residence, and the education level were the related factors affecting the family hardiness score (all P < 0.01). The age of child, CHIP-1, CHIP-2, positive emotion and negative emotion were independent factors affecting the family hardiness (all P < 0.05). The CHIP, CHIP-1, CHIP-2 and positive emotion were positively correlated with the family hardiness (r values were 0.827, 0.883, 0.707 and 0.846, all P < 0.01); the negative emotion was negatively correlated with the family hardiness (r=-0.832, P < 0.01).@*Conclusion@#The family hardiness of children with leukemia is in the middle and upper level, the children's age, caregiver's coping style, positive emotion and negative emotion are factors affecting the family hardiness.
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Objective:To design and construct the replication-deficient recombinant adenovirus Ad-siCTGF which can silence the expression of connective tissue growth factor (CTGF) by RNA interference and verified its function. Methods:A specific sequence, which was verified to be able to silence CTGF gene with high efficiency, was cloned into pSES-HUS vector to produce the shuttle plasmid pSES-siCTGF. The plasmid after Pme Ⅰ linearization was cotransduced with pAdEasy into BJ5183 E.coli strains to construct recombinant vector Ad-siCTGF. After linearization treatment with Pac Ⅰ enzyme digestion Ad-siCTGF was transfected into HEK293 cells via liposome mediation. The recombinant adenovirus was packaged. The titer of the Ad-siCTGF was increased after three times of cross-infection. 4T1 cells were infected with the adenovirus. The silencing efficiency was tested by real-time fluorescence quantitative (RFQ)-PCR and Western blotting.Results:Pac Ⅰ enzyme digestion electrophoresis indentified that recombinant adenovirus was successfully constructed. The titer of the recombinant adenovirus Ad-siCTGF was 2.6×10~(10) pfu/mL after amplification and purification. The CTGF mRNA and protein expression in 4T1 cells were decreased by 36.27% and 31.56%, respectively, compared with the control groups.Conclusion:The recombinant adenovirus which can silence the expression of CTGF was successfully constructed. It laid a good foundation for further investigation of the action mechanism of CTGF in tumor cells.