Clinical features and prognosis of core binding factor acute myeloid leukemia children in South China: a multicenter study / 中华儿科杂志

Objective: To analyze the clinical features, efficacy and prognosis factors of core binding factor (CBF) acute myeloid leukemia (AML) children in South China. Methods: This was a retrospective cohort study. Clinical data of 584 AML patients from 9 hospitals between January 2015 to December 2020 was collected. According to fusion gene results, all patients were divided into two groups: CBF-AML group (189 cases) and non-CBF-AML group (395 cases). CBF-AML group were divided into AML1-ETO subgroup (154 cases) and CBFβ-MYH11 subgroup (35 cases). Patients in CBF-AML group chosen different induction scheme were divided into group A (fludarabine, cytarabine, granulocyte colony stimulating factor and idarubicin (FLAG-IDA) scheme, 134 cases) and group B (daunorubicin, cytarabine and etoposide (DAE) scheme, 55 cases). Age, gender, response rate, recurrence rate, mortality, molecular genetic characteristics and other clinical data were compared between groups. Kaplan-Meier method was used for survival analysis and survival curve was drawn. Cox regression model was used to analyze prognostic factors. Results: A total of 584 AML children were diagnosed, including 346 males and 238 females. And a total of 189 children with CBF-AML were included, including 117 males and 72 females. The age of diagnosis was 7.3 (4.5,10.0)years, and the white blood cell count at initial diagnosis was 21.4 (9.7, 47.7)×109/L.The complete remission rate of the first course (CR1) of induction therapy, relapse rate, and mortality of children with CBF-AML were significantly different from those in the non-CBF-AML group (91.0% (172/189) vs. 78.0% (308/395); 10.1% (19/189) vs. 18.7% (74/395); 13.2% (25/189) vs. 25.6% (101/395), all P<0.05). In children with CBF-AML, the CBFβ-MYH11 subgroup had higher initial white blood cells and lower proportion of extramedullary invasion than the AML1-ETO subgroup, with statistical significance (65.7% (23/35) vs. 14.9% (23/154), 2.9% (1/35) vs. 16.9% (26/154), both P<0.05). AML1-ETO subgroup had more additional chromosome abnormalities (75/154), especially sex chromosome loss (53/154). Compared with group B, group A had more additional chromosome abnormalities and a higher proportion of tumor reduction regimen, with statistical significance (50.0% (67/134) vs. 29.1% (16/55), 34.3% (46/134) vs. 18.2% (10/55), both P<0.05). Significant differences were found in 5-years event free survival (EFS) rate and 5-year overall survival (OS) rate between CBF-AML group and non-CBF-AML group ((77.0±6.4)%vs. (61.9±6.7)%,(83.7±9.0)%vs. (67.3±7.2)%, both P<0.05).EFS and OS rates of AML1-ETO subgroup and CBFβ-MYH11 subgroup in children with CBF-AML were not significantly different (both P>0.05). Multivariate analysis showed in the AML1-ETO subgroup, CR1 rate and high white blood cell count (≥50×109/L) were independent risk factors for EFS (HR=0.24, 95%CI 0.07-0.85,HR=1.01, 95%CI 1.00-1.02, both P<0.05) and OS (HR=0.24, 95%CI 0.06-0.87; HR=1.01, 95%CI 1.00-1.02; both P<0.05). Conclusions: In CBF-AML, AML1-ETO is more common which has a higher extramedullary involvement and additional chromosome abnormalities, especially sex chromosome loss. The prognosis of AML1-ETO was similar to that of CBFβ-MYH11. The selection of induction regimen group FLAG-IDA for high white blood cell count and additional chromosome abnormality can improve the prognosis.

Public KAP for COVID-19 and its influencing factors / 上海预防医学

Objective To understand the current status and influencing factors of public cognition, attitude, and behavior (KAP) for COVID-19, and to help the development of strategies for COVID-19 prevention and treatment. Methods Snowballing-based online questionnaire was used to conduct an anonymous survey. Results A total of 1 576 questionnaires were received, and 1 553 were effective (recovery rate 98.5%).The awareness rate for epidemiological knowledge was 87.3%, 93.1% for etiology knowledge and 85.9% for prevention and treatment knowledge.The average score for attitude towards COVID-19 fear was 15.47±3.15, agreement with relevant government regulations and policies was 11.28±1.58, and for preventive behavior was 24.47±2.61.Men′s knowledge scores in epidemiology and etiology were higher than women′s (P < 0.05).Women′s attitude towards epidemic fear and government identification were scored higher than men′s (P < 0.05).The public health prevention knowledge score was higher in subjects with urban household registration than in those with rural household registration (P < 0.05).Regression analysis showed that gender, age, occupation, level of attention on pandemic, epidemiological knowledge, and etiology knowledge were the influencing factors for the fear attitude to the epidemic (P < 0.05);the attention level and prevention knowledge were the influencing factors for prevention behavior (P < 0.05). Conclusion The public awareness rate of COVID-19 and attitude towards government identification are relatively high.The degree of pandemic fear and preventive behavior are above average.More targeted public education on COVID-19 is highly recommended.

Clinical and genetic analyses of juvenile myelomonocytic leukemia / 中国当代儿科杂志

OBJECTIVE@#To study the clinical and genetic features of juvenile myelomonocytic leukemia (JMML) and the association between genotype and prognosis. Methods The clinical data of 15 children who were diagnosed with JMML were collected. Next-generation sequencing was used to detect common gene mutations of JMML.@*RESULTS@#The male/female ratio was 6.5:1, and the age of onset was 19 months (range 2-67 months). Of the 15 children, 11 (73%) experienced disease onset before the age of 4 years, with abdominal distension and pyrexia as initial symptoms. All children had hepatosplenomegaly and superficial lymphadenectasis, with a number of peripheral blood mononuclear cells of >1.0×10/L and a percentage of juvenile cells of 1%-7% in peripheral blood smear. The percentage of bone marrow blasts + juvenile cells was <20%, and the percentage of monoblasts + promonocytes was 1%-10%. Of the 15 children, 10 (67%) had a higher level of hemoglobin F than the normal level at the corresponding age, with the highest level of 62.5%. All 15 children had the absence of Philadelphia chromosome, and one child had chromosome 7 deletion. All 15 children had a negative result of BCR/ABL fusion gene detection. PTPN11 gene mutation was found in 5 children (33%), NF1 mutation in 4 children (27%), CBL mutation in 3 children (20%), and RAS mutation in 3 children (20%). No children received regular chemotherapy, and one child underwent hematopoietic stem cell transplantation. The median follow-up time of 15 children was 18 months (range 1-48 months). Among the 15 children, 8 died (among whom 4 had PTPN11 gene mutation, 3 had NF1 mutation, and 1 had RAS mutation) and 7 survived. The children with PTPN11 mutation had the worst prognosis and the highest mortality rate, and those with CBL or NRAS mutation had a relatively good prognosis. The level of hemoglobin F was negatively correlated with survival time (r=-7.21, P=0.002).@*CONCLUSIONS@#In children with JMML, the type of gene mutation is associated with prognosis. The children with PTPN11 mutation often have a poor prognosis, and those with CBL or NRAS mutation have a relatively good prognosis.

Clinical Significance of CRLF2 High Expression in Bone Marrow Mononuclear Cells from Children with Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To detect the expression of CRLF2 in bone marrow mononuclear cells from children with newly diagnosed acute lymphoblastic leukemia(ALL) and to explore its clinical significance in pediatric ALL.@*METHODS@#A total of 218 children with newly diagnosed ALL who achieveal the complete remission and had the complete follow-up information were selected, and the expression level of CRLF2 in bone marrow mononuclear cells of these children was detected by real-time fluorescent quantitative PCR, and the significance of CRLF2 expression level in clinical prognosis of ALL children was analyzed by using statistical method.@*RESULTS@#28 cases in 218 children with complete data showed high expression of CRLF2. The cumulative recurrence rate in the CRLF2 high expression group was significantly higher than that in the low expression group (53.6% vs 12.6%) (P＜0.01). The predicted 5-year recurrence-free survival rate (RFS) of ALL children with CRLF2 high expression was significantly higher than that of low expression group (P＜0.01). There was no significant difference in the predicted 5-year RFS between ALL children with CRLF2 low and high expression in the standard-risk(SR) group (P＞0.05). The predicted 5-year RFS of ALL children with CRLF2 low expression was higher than that of ALL children with CRLF2 high expression in the intermediate-risk (IR) and high-risk (HR) groups. (P＜0.05). Cox analysis showed that CRLF2 high expression is an independent risk factor for the relapse of children with ALL.@*CONCLUSION@#The recurrence rate of pediatric ALL with CRLF2 high expression is high, and CRLF2 high expression is an important prognostic factor for high risk of relapse in ALL children with IR and HR. It is necessary to use CRLF2 expression as an indicator of risk stratification in pediatric ALL.

Effects of minimal residual disease level on day 33 of remission induction and IKZF1 genotype on the survival of children with B-lineage acute lymphoblastic leukemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of minimal residual disease (MRD) level on day 33 of remission induction and IKZF1 genotype on the survival of children with B-lineage acute lymphoblastic leukemia (B-ALL).</p><p><b>METHODS</b>A total of 152 children with newly-diagnosed B-ALL who had complete remission after the first cycle of the chemotherapy and had complete follow-up information were enrolled in this study. According to the MRD detection by flow cytometry on day 33 of remission induction, they were divided into three groups: standard-risk (SR) group (MRD <10; n=60), intermediate-risk (IR) group (10≤ MRD <10; n=55), and high-risk (HR) group (MRD ≥10; n=37). Nested RT-PCR was used to determine the IKZF1 genotype of all children before chemotherapy. The effects of MRD level on day 33 of remission induction and IKZF1 genotype on the recurrence-free survival (RFS) of children with B-ALL were analyzed.</p><p><b>RESULTS</b>There were 7 common IKZF1 subtypes in all the 152 children with B-ALL: IK1, IK2/3, IK4, IK6, IK8, IK9, and IK10. Of the 152 children, 130 had functional subtypes of IKZF1 and 22 had non-functional subtypes of IKZF1. During the follow-up period, relapse occurred in 26 (17%) children, and the recurrence rate was highest in the HR group (P<0.05). However, there was no significant difference in the recurrence rate between the SR group and the IR group (P>0.05). The cumulative recurrence rate of the children with non-functional subtypes of IKZF1 was significantly higher than that of those with functional types of IKZF1 (P<0.01). The predicted 5-year RFS rates in the SR, IR, and HR groups were (94.2±2.9)%, (86.7±3.8)%, and (56.2±4.5)% respectively (P<0.05). The 5-year RFS rate of the children with functional subtypes of IKZF1 was significantly higher than that of those with non-functional subtypes of IKZF1 (P<0.01). There was no significant difference in the predicted 5-year RFS rate between the children with functional subtypes of IKZF1 and those with non-functional subtypes of IKZF1 in the SR group (P>0.05). However, the predicted 5-year RFS rate of the children with functional subtypes of IKZF1 was significantly higher than that of those with non-functional subtypes of IKZF1 in the IR group and the HR group (P<0.05).</p><p><b>CONCLUSIONS</b>B-ALL children with non-functional subtypes of IKZF1 have a high recurrence rate, and the recurrence rate will be even higher in B-ALL children with non-functional subtypes of IKZF1 and MRD ≥10 on day 33 of chemotherapy.</p>

Establishment of rat models of fever and shivering in different degrees / 中国比较医学杂志

Objective To explore the body temperature thresholds of shivering in febrile rats during therapeutic hypothermia, and establish rat models of shivering in different degrees. Methods A randomized controlled trial was adopted. Rats weighted 200 ± 20 g and basal body temperature of 36. 8-38. 3℃ were induced with fever using 20% dry yeast solution through dorsal subcutaneous injection. 40 rats were randomly divided into 4 groups:10 mL ice pack group, 20 mL ice pack group, 40 mL ice pack group and control group, 10 rats in each group. Physical cooling was implemented for 30 minutes in the neck and armpits. No cooling measures was given to the control group. The shivering of rats were observed, and the threshold of anal temperature was monitored. Results In the rats with hyperthermia, shivering was not observed in any part of the rats in the control group and in the therapeutic hypothermia group of 10 mL ice pack. The rats in the therapeutic hypothermia group of 20 mL ice pack developed mild shivering, which manifested as piloerection, head and neck trembling, with or without upper limbs trembling. The threshold of the average rectal temperature of mild shivering was 37. 25℃, The incidence of mild shivering was 100%. The rats in the therapeutic hypothermia group of 40 mL ice pack developed severe shivering, which manifested as piloercetion, head, neck, limbs and trunk were trembling, and tail muscle tension increased. The threshold of the average rectal temperature of severe shivering was 37. 07℃, severe shivering occurred in 90% of the rats. Conclusions No shivering, mild shivering, and severe shivering models can be established by intervention with ice pack in rats with high fever during therapeutic hypothermia.

Establishment of rat models of fever and shivering in different degrees / 中国比较医学杂志

Objective To explore the body temperature thresholds of shivering in febrile rats during therapeutic hypothermia, and establish rat models of shivering in different degrees. Methods A randomized controlled trial was adopted. Rats weighted 200 ± 20 g and basal body temperature of 36. 8-38. 3℃ were induced with fever using 20% dry yeast solution through dorsal subcutaneous injection. 40 rats were randomly divided into 4 groups:10 mL ice pack group, 20 mL ice pack group, 40 mL ice pack group and control group, 10 rats in each group. Physical cooling was implemented for 30 minutes in the neck and armpits. No cooling measures was given to the control group. The shivering of rats were observed, and the threshold of anal temperature was monitored. Results In the rats with hyperthermia, shivering was not observed in any part of the rats in the control group and in the therapeutic hypothermia group of 10 mL ice pack. The rats in the therapeutic hypothermia group of 20 mL ice pack developed mild shivering, which manifested as piloerection, head and neck trembling, with or without upper limbs trembling. The threshold of the average rectal temperature of mild shivering was 37. 25℃, The incidence of mild shivering was 100%. The rats in the therapeutic hypothermia group of 40 mL ice pack developed severe shivering, which manifested as piloercetion, head, neck, limbs and trunk were trembling, and tail muscle tension increased. The threshold of the average rectal temperature of severe shivering was 37. 07℃, severe shivering occurred in 90% of the rats. Conclusions No shivering, mild shivering, and severe shivering models can be established by intervention with ice pack in rats with high fever during therapeutic hypothermia.

Effect of Icaritin on Proliferation and Apoptosis of THP-1 Cell and Its Mechanism / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of icaritin on the proliferation and apoptosis of THP-1 cells and its mechanism.</p><p><b>METHODS</b>After treated with various concentrations of icaritin, cell proliferation was detected by MTS method, and apoptosis was measured with flow cytometry and Hoechst 33258 staining. Expression of BCL-2, BAX and Caspase-3 protein in THP-1 cell was detected by Western blot.</p><p><b>RESULTS</b>After treatment with various concentrations (4-32 µmol/L) of icaritin for 24, 48, 72 h, the inhibition rate of cell growth significantly increased (P<0.05) in time-dose dependent manner(r=0.946); and the apoptotic rate of cells significantly increased (P<0.05) in time-dose dependent manner(r= 0.924). The expression of BCL-2 protein at 48 h decreased significantly in icaritin-treated group, compared with that in control group (P<0.05), while the expression of BAX and Caspase3 protein at 48 h increased significantly in icaritin-treated group, compared with that in control group (P<0.05).</p><p><b>CONCLUSION</b>Icaritin can inhibit proliferation and induce apoptosis of THP-1 in vitro, Icaritin may induce apoptosis in THP-1 cells through the mitochondrial pathway.</p>

Effect of glucocorticoid on dendritic cells in children with chronic immune thrombocytopenia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the change in dendritic cells (DCs) in children with chronic immune thrombocytopenia (cITP) and the effect of glucocorticoid on DCs in children with cITP.</p><p><b>METHODS</b>Fifteen children with cITP and 20 healthy controls were included in the study. Flow cytometry was used to measure the DC subsets count in the 15 children with cITP before and after glucocorticoid treatment as well as the corresponding values in the 20 healthy controls. The DCs derived from peripheral blood monocytes in children with cITP were cultured in vitro and collected, and their immunophenotypes were determined by flow cytometry.</p><p><b>RESULTS</b>Before glucocorticoid treatment, the children with cITP showed no notable change in the absolute count of myeloid DCs (mDCs) but showed decreased absolute count of plasmacytoid DCs (pDCs) and increased mDC/pDC ratio compared with the healthy controls (P<0.05). After glucocorticoid treatment, the children with cITP demonstrated increased absolute count of pDCs and decreased absolute count of mDCs and mDC/pDC ratio compared with before treatment (P<0.05). Before glucocorticoid treatment, the children with cITP had significantly higher positive rates of HLA-DR, CD80, CD83 and CD86 on peripheral blood DCs than the healthy controls (P<0.01). All the positive rates were significantly decreased after glucocorticoid treatment (P<0.01), so that there was no significant difference from the healthy controls (P>0.05).</p><p><b>CONCLUSIONS</b>Disproportion and functional disturbance of DC subsets is associated with the pathogenesis of cITP in children. Glucocorticoid can strengthen the immunosuppression of DCs in children with cITP, which may contribute to the effectiveness of glucocorticoid as a treatment.</p>

Effects of zearalenone on the proliferation of SK-N-SH human neuroblastoma cells / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate effects of zearalenone (ZEA) on the proliferation of SK-N-SH human neuroblastoma cells in vitro and its possible mechanism.</p><p><b>METHODS</b>SK-N-SH cells were cultured in estrogen-free improved minimum essential medium and divided into 5 groups based on different treatments: group 1, without treatment; group 2, treated with 17beta-estradiol (E(2)); group 3, treated with ZEA; group 4, treated with both E(2) and ICI 182780; group 5, treated with both ZEA and ICI 182780. Absorbance value (AV) was determined at the time point of 0, 24, 48 and 72 hours, and DNA proliferation index (PI) at 72 hours. Flow cytometer, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) were employed to monitor cell apoptosis.</p><p><b>RESULTS</b>At 24, 48 and 72 hours, the AV of group 3 were 1.39, 1.32, and 1.22 times to those of group 1, respectively. PI in group 3 was 1.43 times of that in group 1 at 72 hours. The results of group 2 were similar to those in group 3. At the same time, the growth of cells was inhibited by ICI 182780 despite the presence of E(2) and ZEA. Apoptosis cells were abundant in group 1 and ICI 182780 groups, but little in E(2) and ZEA groups.</p><p><b>CONCLUSION</b>ZEA might promote the proliferation of SK-N-SH cells to a level similar to that of E(2), which might probably be brought about via estrogen receptor pathways and depressing apoptosis.</p>

Utilization Analysis of Hypoglycemics in 36 Hospitals of Guangzhou in 2003～2005 / 中国药房

1.CONCLUS-ION:The use of hypoglycemics in Guangzhou is basically in line with the rational level,except for few cases in improper use of combination therapies.