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BackgroundHome-based intervention occupies a prominent place in the treatment of autism spectrum disorder （ASD） in children， whereas previous studies on the effect of home-based early intensive behavioral intervention on verbal ability of children with ASD are somewhat inadequate. ObjectiveTo study the effects of intensive family behavioral of intervention based on Verbal Behavior Milestones Assessment and Placement Program （VB-MAPP） on the language ability of children with ASD， so as to provide references for the development of family intervention strategies for children with ASD. MethodsChildren aged 2 to 3 years old who attended the Children's Rehabilitation Department of the Second Affiliated Hospital of Shantou University Medical College from September 2020 to December 2021 and met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria for ASD were selected as the study objects. A non-randomized concurrent control trial was conducted to compare a study group （n=24） receiving home-based early intensive behavioral intervention using VB-MAPP with a control group （n=14） receiving training from other special institutions or early childhood education institutions. The intervention lasted for 6 months in both groups. Before and after the intervention， the VB-MAPP milestone assessment was performed in the two groups， and the VB-MAPP milestone score， mand， trac and listener responds were selected as the study indicators. Then the intervention effect was compared between two groups， and the multiple linear regression was performed to screen the related influencing factors. ResultsAfter intervention， the total milestone assessment score， mand， tact and listener responds scores of study group were higher than those of control group， with statistical difference （Z=-4.339~-2.195， P<0.05 or 0.01）. Multiple linear regression analysis denoted that the average weekly hours of home-based intervention in the first three months had certain effect on listener responds （β=1.029， P<0.05）. ConclusionApplication of home-based early intensive behavior intervention using VB-MAPP may contribute to the improvement of verbal abilities such as mand， tact and listener responds in children with ASD. ［Funded by 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund （number， 20200601）］
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Objective To determine the effect of rapamycin(Rapa) on JAK2, ABCA3, and the immune checkpoint PD-1/PD-L1 in exosomes derived from JAK2 V617F positive HEL cells. Methods Human erythroleukemia HEL cells (JAK2 V617F mutation-positive) were cultured in vitro, and rapamycin was added at concentrations of 10, 50, and 100 nmol/L. The control group was established and cell proliferation inhibition rate was detected by CCK-8. Based on the inhibition rate of cell proliferation, cells intervened with 10 and 50 nmol/L Rapa were selected. Exosomes were extracted using a kit and identified by Western blot and flow cytometry. JAK2, ABCA3, and PD-1/PD-L1 mRNA changes in exosomes were detected by fluorescent quantitative PCR. The expression of exosome PD-1/PD-L1 protein was determined by flow cytometry. Results The exosomes extracted with the exosome kit all expressed characteristic CD9, CD63, and CD81 proteins, which were consistent with the general characteristics of exosomes. JAK2 mRNA can be detected in exosomes from HEL cells; Rapa reduced exosome production by HEL cells, and dose-dependently decreased gene expression of JAK2, ABCA3, and PD-L1 in exosomes. In addition, Rapa inhibited exosomal PD-L1 protein expression and had no significant effect on PD-1 protein expression. Conclusion HEL cells may transmit JAK2 mutant gene signals via exosomes. Rapa can reduce the production of exosomes and inhibits JAK2 mutated signals delivered by exosomes and suppresses PD-L1 protein expression.
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Objective@#To explore the relationship between prepregnancy body mass index, weight gain during pregnancy with preschool obesity and body composition in offspring, so as to provide evidence for gestational weight gain and childhood obesity prevention.@*Methods@#A total of 1 333 preschool children were recruited from 3 kindergartens in Tianjin from September to December 2020. Structured questionnaire was used to collect children s lifestyle information. Height, weight and body fat mass of children were assessed, and body fat percentage (FM%), fat mass index (FMI) and non fat mass index (FFMI) were calculated. Maternal medical records were collected and the mothers were grouped according to their prepregnancy weight status and weight gain during pregnancy. χ 2 test, t test, linear regression model and Logistic regression were used to analyze the differences of obesity and body composition among different groups.@*Results@#The prevalence of overweight and obesity in preschoolers was 12.7% and 7.7%. After adjusting maternal age and delivery, gestational age, gender, age and lifestyle of children, the correlation between maternal pre pregnancy BMI,gestational weight gain with obesity and body composition indexes of children in preschool age was statistically significant ( P <0.05). For mothers with normal weight before pregnancy, excessive weight gain during pregnancy increased risk of high FM% and high FMI in offspring ( OR=1.81, 1.68, P <0.05). There was no significant correlation between maternal weight gain during pregnancy with offspring obesity and body composition among mothers with prepregnant overweight or obesity.@*Conclusion@#Maternal weight status before pregnancy and weight gain during pregnancy are correlated with obesity and body composition in the preschool age of offspring. It is suggested that mothers should maintain appropriate weight status before and during pregnancy.
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Objective:To investigate the safety, efficacy and survival of brentuximab vedotin (BV) monotherapy and BV combined with chemotherapy for relapsed or refractory lymphoma.Methods:A total of 47 patients with relapsed or refractory Hodgkin's lymphoma (HL) in First Medical Center of PLA general Hospital and Fourth Medical Center of PLA General Hospital from October 2011 to December 2018 were admitted, including 35 cases (BV monotherapy group) and 12 cases (BV combined with chemotherapy group); there were 8 cases of relapsed or refractory anaplastic large cell lymphoma (ALCL), 4 cases in BV monotherapy group and 4 cases in BV combined with chemotherapy group. The safety, clinical efficacy and survival of two neoplasms in different groups were compared.Results:For relapsed or refractory HL, the objective remission rate (ORR) and complete remission rate (CRR) was 67.7% (21/31) and 16.1% (5/31), and the median progressive-free survival (PFS) time was 3.5 months (1.5-24.0 months) in BV monotherapy group; ORR and CRR was 81.8% (9/11) and 27.3% (3/11), and median PFS time was 5.5 months (2.0 - 24.0 months) in BV combined with chemotherapy group; there was no statistical difference in ORR and CRR between the both groups (χ 2 = 0.788, P = 0.375; χ 2 = 0.654, P = 0.419). There were 4 cases in BV monotherapy group for ALCL, of which 3 could be evaluated for efficacy, including 1 case of complete remission (CR) and 1 case of partial remission (PR); there were 4 cases in BV combined with chemotherapy group for ALCL, of which 4 could be evaluated for efficacy, including 2 cases of CR and 2 cases of PR. The common adverse events in BV monotherapy group were anemia, leukopenia, thrombocytopenia, fever, elevated transaminase, fatigue, nausea, peripheral neuritis and cough. Grade ≥3 adverse events were mainly anemia, thrombocytopenia and leukopenia. The common adverse events of BV combined with chemotherapy group were similar to those of BV monotherapy group, and there were significant differences in bone marrow suppression (thrombocytopenia, leukopenia) between the two groups (all P < 0.05). Conclusions:The clinical efficacy of BV combined with chemotherapy is better than that of BV monotherapy in treatment of relapsed or refractory lymphoma, and the survival time is prolonged. The adverse reaction of BV combined with chemotherapy is mainly manifested in bone marrow suppression, and the safety and tolerability of patients are acceptable.
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Objective@#To investigate the regulation of JAK2 tyrosine kinase inhibitor ruxolitinib on extracellular matrix metalloproteinase (MMP in JAK2V617F positive myeloproliferative neoplasms (MPN) cells.@*Methods@#①Forty cases of newly diagnosed JAK2V617F positive MPN patients and 15 healthy volunteers as control in Baoding No.1 Hospital between January 2012 and December 2015 were enrolled in this study. JAK2V617F/JAK2 ratio was detected by real-time-PCR; the expression levels of phosphorylation protein tyrosine kinase 2 (p-JAK2) , MMP-2 and MMP-9 in pathological tissues of bone marrow were detected by immunohistochemistry. The bone marrow cells of JAK2V617F positive MPN patients were treated with ruxolitinib, then the migration ability and MMP-2, MMP-9 gene and protein expression levels were detected. ②The human erythroleukemia cell line HEL cells were treated with different concentrations of ruxolitinib (0, 50, 100, 250, 500, 1 000 nmol/L) . The cell viability was detected by CCK-8 test; cell migration ability was tested by transwell chambers. The mRNA expression levels of JAK2, MMP-2 and MMP-9 were detected by real-time-PCR. The protein expression levels of p-JAK2, MMP-2 and MMP-9 were detected by Western blot.@*Results@#①The expression levels of p-JAK2, MMP-2 and MMP-9 in the newly diagnosed group were significantly higher than control group respectively [ (78.56±24.55) % vs (41.59±17.29) %, P<0.05; (48.25±18.74) % vs (22.79±13.89) %, P<0.05; (53.29±19.28) % vs (15.56±14.96) %, P<0.05]. Spearman correlation analysis showed the positive correlation of MMP-2 and MMP-9 protein expression levels with JAK2V617F mutation (r=0.526, P=0.001; r=0.543, P=0.001) . ②The proliferation of HEL cells was inhibited by different concentrations of ruxolitinib in time and dose dependent manner. ③Cell migration test showed the number of cells leaked to the low chamber in MPN patients bone marrow cells and HEL cells treated with 5 nmol/L of ruxolitinib group were significantly lower than that without ruxolitinib treatment after 24 h [ (154.7±27.5) vs (320.3±67.3) , t=13.47, P<0.05; (70.7±10.5) vs (135.3±16.7) , t=13.89, P<0.05]. The mRNA and protein expression levels of JAK2, MMP-2 and MMP-9 decreased with the increased concentration of ruxolitinib.@*Conclusion@#Ruxolitinib inhibits MPN cell migration and expression of MMP-2 and MMP-9 via JAK2 signal pathway.
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AIM:To investigate the effect of AG 490 on the expression of VEGF and HIF-1α, and the capacity of invasion in human erythroleukemia (HEL) cells.METHODS:The HEL cells were treated with AG490 at different con-centrations .The cell viability was detected by CCK-8 assay.The apoptosis was detected by Hoechst staining .The apoptosis and the cell cycle were analyzed by flow cytometry .The capacity of migration was evaluated by Transwell assay .The mRNA expression level of JAK2 was measured by RT-PCR.The protein levels of p-JAK2, VEGF and HIF-1αwere determined by Western blot.RESULTS:The HEL cell viabilities were 88%, 75%, 48%, 10%and 0.12%after treated with AG490 at 20, 40, 60, 80 and 100 μmol/L for 48 h, respectively.The results of Hoechst staining showed that brilliant blue cells in 80 μmol/L AG490 group was significantly increased compared with control group for 48 h.The apoptosis rate of 80μmol/L AG490 group was significantly increased compared with control group at 48 h after AG490 treatment.The number of membrane-permeating HEL cells in 20μmol/L AG490 group at 24 h after AG490 treatment was significantly lower than that in control group (P<0.05).The mRNA level of JAK2 decreased in a concentration-dependent manner after the HEL cells were treated with different concentrations of AG 490 for 48 h.The protein levels of p-JAK2, VEGF and HIF-1αwere lower in AG490 treatment groups than those in control group (P<0.05).CONCLUSION: AG490 inhibits the expression of VEGF and HIF-1αin HEL cells by inhibiting JAK2 pathway.