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Objective:To analyze the relationship between FAB morphological classification and World Health Organization (WHO) 2016 classification in children with acute erythroid leukemia(AEL), and to summarize the clinical features and prognosis.Methods:Clinical data of de nova childhood AEL patients from January 1, 2002 to December 31, 2019, in Pediatric Blood Disease Center, Institute of Hematology & Blood Disease Hospital were retrospectively analyzed.All of them were re-evaluated according to the WHO 2016 classification.Results:(1) A total of 20 patients were diagnosed as AEL by FAB classification.According to the criteria of WHO 2016, they were re-diagnosed as myelodysplastic syndromes (MDS)- refractory anemia with excess of blasts (11 cases), acute myeloid leukemia with MDS-related changes (3 cases), acute monocytic leukemia (1 case), and pure red leukemia (PEL, 5 cases). (2) Pathological hematopoiesis was frequently detected in bone marrow smears.Auer bodies were seen occasionally in some blasts.The most common antigen expressing were CD 117, CD 13, CD 33, CD 34, CD7, and CD 38.Karyotype analysis was performed in 18 cases successfully, involving 6 cases with abnormal karyotypes, including + 8, -7, 22p+ , t (3; 5: ? ), + 3q-, 15q-, and del (9)(q13). (3) Thirteen cases were treated by chemotherapy, and the one-course complete remission rate was 38.5%.By July 1, 2020, only 2 cases were alive without disease.The overall survival was 49 months and 11 months, respectively. Conclusions:Childhood AEL is susceptible to pathological hematopoiesis, poor response to early chemotherapy and poor prognosis.After re-evaluation according to WHO 2016 classification, most of them were diagnosed as MDS-related.Therefore, adjusting the suitable induction regimen with allogeneic hematopoietic stem cell transplantation may improve the prognosis.
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Objective:To investigate the effect of SKF96365, store-operated calcium entry (SOCE) inhibitor, on liver and kidney injury induced by paraquat (PQ).Methods:A549 cells were cultured in vitro and divided into the control group (DMSO group, SKF 2 μmol/L group, and SKF 10 μmol/L group) and PQ group (PQ+DMSO group, PQ+SKF 2 μmol/L group, and PQ+SKF 10 μmol/L group). The nuclear factor of activated T cells (NFAT) in A549 cells was detected by luciferase reporter gene technique. The mouse model of PQ poisoning was constructed and divided into the control group, SKF group, PQ group and PQ+SKF group. In the PQ group, mice were injected with 50 mg/kg PQ intraperitoneally; in the SKF group, mice were injected intraperitoneally with 10 mg/kg SKF96365 for 3 days. Mice in the PQ+SKF group received 50 mg/kg intraperitoneal injection of PQ once and 10 mg/kg intraperitoneal injection of SKF96365 daily for 3 days. On the fourth day, the mice were sacrificed, and the liver and kidney tissues were taken. The histopathological changes of liver and kidney tissues were observed by hematoxylin-eosin (H&E) staining, and the apoptosis of liver and kidney tissues was observed by TUNEL staining. One-way analysis of variance was used to compare the mean values of normally distributed measurement data between groups. Comparisons between groups were performed using the least significant difference t-test. Results:The luciferase reporter gene technology showed that NFAT was significantly activated in the PQ group. After pretreatment with SKF96365, NFAT activation decreased sharply in a dose-dependent manner. HE staining showed that the outline structure of liver and kidney tissues in the PQ groups were unclear, cells swelled and a large number of inflammatory cells infiltrated; in the PQ+SKF group, liver cell swelling and inflammatory cell infiltration decreased significantly. TUNEL staining showed that the apoptotic cells in liver and kidney tissues increased in the PQ groups, and the apoptosis decreased remarkably in the PQ+SKF group.Conclusions:SOCE inhibitor SKF96365 can significantly reduce the liver and kidney injury caused by PQ.
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Objective:To investigate the clinical characteristics, diagnosis and treatment methods of children with gene mutation-negative essential thrombocytosis (ET).Methods:The clinical data of a child with gene mutation-negative ET in the Blood Diseases Hospital of Chinese Academy of Medical Sciences were collected, and the related literature was reviewed.Results:The epistaxis was the main clinical symptom of this child. He was diagnosed as ET (gene mutation-negative) by bone marrow aspiration and gene detection. After hydroxyurea treatment, the platelet count increased and the clinical symptoms were improved.Conclusions:The incidence rate of ET in children is low, and the frequency of gene mutation-negative ET in children reported in the literature is different. The large number of samples and long-term follow-up studies are needed.
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Objective:To investigate the clinical features and prognosis of children with positive flow cytometry of cerebrospinal fluid(CNSI + )in maintained acute lymphoblastic leukemia(ALL). Methods:Clinical data including clinical characteristics, diagnosis, treatment and prognosis of 12 patients with ALL CNSI diagnosis in maintenance period were analyzed to explore the prognostic factors.Results:The 12 children with CNSI + in maintenance were mainly male, and all of them were B-ALL.High leukemia cell count at first diagnosis( χ2=6.374, P=0.012), insensitivity to glucocorticoid pretherapy( χ2=5.048, P=0.025), increased rate of abnormal CSF cells(≥60%, χ2=7.024, P=0.008), course of CNSI + ≤14 months( χ2=4.873, P=0.027)and complex karyotype( χ2=9.356, P=0.002)are the adverse prognostic factors.Karyotype is an independent factor( P=0.017). Conclusion:The prognosis of children with CNSI + is unfavourable.Intrathecal injection and chemotherapy are the important treatment for children with CNSI + in maintenance period.Hematopoietic stem cell transplantation is an important choice for children with relapse.
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Objective:To explore the effect of KCa3.1 activating NLRP3 inflammasome in paraquat PQ treated-alveolar epithelial cells.Methods:The A549 cells were cultured in vitro and divided into the control group, TRAM-34 (specific inhibitor of KCa3.1) group, PQ group and PQ+TRAM-34 group. The expression of KCa3.1 was detected by immunofluorescence in A549 cells. Western blot was used to detect the level of the proteins related with the NLRP3 infammasome and NEK7 protein. And the level of cell potassium was detected by cell potassium concentration kit.Results:The level of KCa3.1 was significantly increased in A549 cells after PQ treatment by immunofluorescence. The expressions of NLRP3 infammasome-related proteins (NLRP3, ASC and Caspase-1) and NEK7 protein were increased after PQ treatment, and the expressions of NLRP3 infammasome-related proteins and NEK7 protein were decreased after inhibition of KCa3.1, and the difference was statistically significant [NLRP3/β-actin (control group vs TRAM-34 group vs PQ group vs PQ+TRAM-34 group): [ (0.02±0.00) vs (0.03±0.00) vs (0.74±0.00) vs (0.32±0.01) , ASC/β-actin (control group vs TRAM-34 group vs PQ group vs PQ+TRAM-34 group): [ (0.12±0.01) vs (0.11±0.03) vs (0.46±0.02) vs (0.17±0.03) ];Caspase-1/ β-actin (control group vs TRAM-34 group vs PQ group vs PQ+TRAM-34 group): [ (0.05±0.00) vs (0.04±0.00) vs (0.34±0.03) vs (0.15±0.01) ]; NEK7/ β-actin (control group vs PQ group vs PQ+TRAM-34 group);[ (0.38±0.03) vs (0.83±0.02) vs (0.51±0.01) , P<0.01]. The potassium level was decreased after PQ treatment and the degree could be declined by the KCa3.1 inhibitor by colorimetric detection with statistically significant difference (control group vs PQ group vs PQ+TRAM-34 group:[ (1.00±0.00) vs (0.60±0.05) vs (0.86±0.02) , P<0.01]. Conclusions:The KCa3.1 could promote the outflow of intracellular potassium and up-regulate the expression of NEK7, thereby activate the NLRP3 inflammatory in PQ-induced pulmonary fibrosis.
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Objective@#To clarify the prevalence, clinical features and molecular characteristics of germline GATA2 mutations in pediatric primary myelodysplastic syndromes (MDS) .@*Methods@#Next-generation sequencing technology was used to detect mutations in GATA2 and other myeloid malignancy genes in 129 children with primary MDS from Jan. 2007 to Jan. 2018. The relationship between genotypes and phenotypes was analyzed.@*Results@#Germline GATA2 mutations accounted for 8.5% (11/129) of all primary MDS cases, and 14.0% (11/50) of MDS with excess blasts (MDS-EB) and acute myeloid leukaemia with myelodysplasia-related changes (AML-MRC) . Compared with GATA2 wild-type patients, GATA2 mutated patients were older at diagnosis[8 (1-16) years old vs 6 years old (range: 1 month old-18 years old) , P=0.035]and higher risk of monosomy 7 (72.7%vs 5.2%, P<0.001) and classified into MDS-EB and AML-MRC compared with refractory cytopenia of childhood (RCC) (63.6%vs 36.4%, P=0.111) . The multivariate analysis showed SETBP1 mutation (P=0.041, OR=9.003, 95%CI 1.098-73.787) and isolated monosomy 7 (P=0.002, OR=24.835, 95%CI 3.305-186.620) were significantly associated with germline mutated GATA2. Overall survival (OS) and outcomes of hematopoietic stem cell transplantation (HSCT) were not influenced by GATA2 mutational status.@*Conclusions@#Our data identify germline GATA2 mutations have a high prevalence in older pediatric patients with monosomy 7, and high risk of progression into advanced MDS subtypes. GATA2 mutation status does not affect OS in pediatric primary MDS.
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Objective@#To evaluate the efficacy of the Chinese Children′s Leukemia Group (CCLG) acute lymphoblastic leukemia (ALL) 2008 protocol (CCLG-ALL 2008) in the treatment of children′s T-cell acute lymphoblastic leukemia (T-ALL).@*Methods@#Clinical characteristics and outcomes of 84 newly diagnosed T-ALL children (63 males and 21 females) treated with CCLG-ALL 2008 protocol from April 2008 to April 2015 in the Department of Pediatric Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences were analyzed retrospectively. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and event free survival (EFS), and COX regression was used to evaluate the influencing factors of OS and EFS.@*Results@#(1) Baseline data: 84 children were included, 56 cases (67%) of children were younger than 10 years old. Patients whose white blood cell count≥50×109/L ranked 70% (59/84). Karyotype: 58% (49/84) with normal karyotype, 10% (8/84) with abnormality of chromosome 11, 8%(7/84) with abnormality of chromosome 9, 2%(2/84) with abnormality in both chromosome 11 and chromosome 9, 8% (7/84) with other complex karyotypes. Fusion gene: 33%(28/84) were SIL-TAL1 positive. The patients were grouped by CCLG-ALL 2008 risk score, 40% (34/84) were in the intermediate risk group and 60% (50/84) in the high risk group. (2) Treatment efficacy: 84 cases were followed up until May 30, 2018. The follow-up time was 42.0 (0.3-120.0) months. The sensitivity rate of prednisone treatment was 56% (47/84); the complete response (CR) rate after the induction therapy of vincristine+daunoblastina+L-asparaginase+dexamethasone (VDLD)(d 33) was 88% (74/84); the total CR rate after VDLD induction combined with cyclophosphamide+cytarabine+6-mercaptopurine (CAM) treatment (d80) was 94% (79/84); the recurrence rate was 24% (20/84). Among the 20 recurrent cases, there were 13 cases (65%) with ultra-early recurrence (within 18 months after diagnosis), 6 cases (30%) with early recurrence (18 to 36 months after diagnosis); 1 patient (5%) with late recurrence (over 36 months after diagnosis). During the follow-up period, twenty-eight children (33%) died (22 cases with recurrence or suspending treatment without remission, 2 cases with infection, 1 case of sudden death in chemotherapy, 1 patient failed in transplantation, 1 patient with severe cirrhosis, and 1 patient with unknown cause). (3) Kaplan-Meier analysis: the 5-year OS and EFS of the 84 children were (63±6)% and (60±6)% respectively. (4) Efficacy in different risk groups: prednisone sensitivity rates in the two different risk groups were 100% (34/34) and 26% (13/50), respectively (χ2=3.237, P<0.05). The CR rates at the end of VDLD induction therapy (d 33) were 100% (34/34) and 80% (40/50), respectively (χ2=2.767, P<0.05). The recurrence rate of children in the two groups was 12% (4/34) and 32% (16/50), respectively (χ2=4.245, P<0.05).The mortality rates of the two groups were 21% (7/34) and 42% (21/50), respectively (χ2=3.198, P<0.05). Kaplan-Meier analysis showed that the 5-year OS of the two groups were (77±7)% and (53±8)%; and the 5-year EFS of the two groups were (75±8)% and (49±8)% (χ2=4.235, 3.875, both P<0.05) . (5) COX multivariate regression analysis showed that the classification of risk according to CCLG-ALL 2008 was an important factor influencing the prognosis of children with T-ALL (OR=3.313, 95% CI 1.165-9.422, P=0.025).@*Conclusions@#The results of the risk group treatment according to the CCLG-ALL 2008 protocol showed that the long-term survival of children with middle risk was significantly better than that of children at high risk.
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Objective@#To investigate the efficacy and the prognostic factors of Chinese Academy of Medical Sciences 2005 (CAMS-2005) regimen in the treatment of pediatric acute myeloid leukemia (AML).@*Methods@#Eighty-eight cases of newly-diagnosed AML patients, who were treated with the CAMS-2005 regimen from April 2005 to July 2009, were enrolled in this case observational study. Clinical characteristics, long-term prognosis and prognostic factors were analyzed retrospectively. Overall survival (OS) and event free survival (EFS) rates were estimated by the Kaplan-Meier method. Rates of survival between the groups were compared by the Log-rank test. Prognostic factors were evaluated by COX regression analysis.@*Results@#A total of 82 cases were enrolled in this study, including 34 core binding factor(CBF)-AML patients and 48 non-CBF-AML patients. There were 45 males and 37 females. The median age at diagnosis was 8.0 (0.7-16.0) years. During the induction therapy, 3 patients (4%) developed treatment-related early-death, while 63 patients (77%) achieved complete remission (CR) and 53 patients (65%) achieved CR after 1 course. Twenty-one patients (33%) had relapsed disease. The CR rates of CBF-AML patients and non-CBF-AML patients were 91% (31/34) and 67% (32/48) (χ2=5.410, P=0.020) , while the relapse rates were 29% (9/31) and 38% (12/32) (χ2=0.508, P=0.476) . The 8-year OS and EFS rates of all 82 patients were 59%(48/82) and 51%(42/82). The 8-year OS rates of CBF-AML patients and non-CBF-AML patients were 74% (25/34) and 48%(23/48) (χ2=5.812, P=0.016), while the 8-year EFS rates of CBF-AML patients and non-CBF-AML patients were 71%(24/34) and 38%(18/48) (χ2=8.682, P=0.003). There were statistically significant differences between groups. The 8-year OS rates of patients who achieved CR after 1 course and other patients were 68% (36/53) and 46% (12/26) (χ2=9.606, P=0.002), while the 8-year EFS rates were 66% (35/53) and 27% (7/26) (χ2=19.471, P=0.000), the differences were all statistically significant. COX multivariate analysis showed that CBF-AML or non-CBF-AML and whether achieved CR after 1 course were independent prognostic factors of OS rates (relative risk: 2.538, 2.561) and EFS rates (relative risk: 3.050, 3.686) (P <0.05).@*Conclusions@#The efficacy of the CAMS-2005 regimen in the treatment of AML patients was well. CBF-AML or non-CBF-AML and whether achieved CR after 1 course were independent prognostic factors for pediatric AML patients.
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With the transformation of the ＂patient－centered＂medical model,patient education has become an important part of the holistic nursing care .As an implementation medium of patient education , patient education materials are the premise for the development of patient education .The quality of patient education materials plays a positive role in improving the quality of care .This article summarizes the domestic and international research progress of patient education materials assessment tools ;it also summarizes the currently used international patient education materials assessment tool ;it explores the existing problems in the domestic research .In addition,this article discusses the different characteristics of commonly used international assessment tools , and identifies an applicable patient education materials assessment tool that can be introduced into China so as to guide the domestic research direction in the future.
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Objective To study the effects of fibroblast growth factor 2 (FGF2) on the proliferation and gene expression profiles of rabbit articular chondrocytes in vitro after different time periods of stimulation.Methods The chondrocytes were isolated and cultured in vitro,and the 3rd generation cells were harvested.Cells were divided into three groups.In the group 1 (FGF2 short-time action group),chondrocytes were cultured in medium with FGF2 for one day,and then transferred to fresh culture medium without FGF2 and cultured for another 6 days.In the group 2 (FGF2 long-time action group),chondrocytes were cultured in medium with FGF2 for 7 days.In the Group 3 (control group),chondrocytes were cultured in culture medium without FGF2 for 7 days.After culture for 1,3,and 7 days,the proliferation of chondrocytes in the all groups was detected respectively.Following extraction of mRNA,the gene expressions of BMP2,BMP4,SOX9 and COL2A1 of the chondrocytes in the all groups were determined by quantitative real-time polymerase chain reaction (qRT-PCR).The content of type Ⅱ collagen was measured via immunofluorescence staining.Results Compared with the control group,FGF2 promoted the proliferation of chondrocytes in the short-and long-time action groups and there was no significant difference between the two FGF2-treated groups.The results of qRT-PCR indicated that different treatment induced different gene expression profile.Particularly,compared with the control group and the FGF2 long-time action group,the expression of BMP2,BMP4,SOX9 and COL2A1 in the short-time action group were significantly upregulated at the 7th day.Immunofluorescence intensity of type Ⅱ collagen in the group 1 was stronger than that in the control group and group 2.Conclusions Different administration of FGF2 for different time periods induced different responses of chondrocytes.Short-term FGF2 stimulation was more beneficial to maintain the phenotype of chondrocytes and the synthesis of extracellular matrix.
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Objective@#To evaluate heterogeneity and clonal evolution in pediatric ETV6-RUNX1+ acute lymphoblastic leukemia (ALL) in China.@*Methods@#Totally 48 children (<14 years) with newly diagnosed ETV6-RUNX1+ ALL in Institute of Hematology and Blood Disease Hospital, CAMS and PUMC, from February 2006 to June 2011 were included. The copy number variations were analyzed by quantitative multigene fluorescence in situ hybridization (QM-FISH) in 48 patients. Non-normal distribution of measurement data were shown with Median (range) , count data were shown with percent (%) . Overall survival and event-free survival were estimated by the Kaplan-Meier method and compared with the log-rank test.@*Results@#Forty-eight patients were tested by QM-FISH. Of 48 patients, 70.8% harbored one clone, 18.8% two subclones, and 10.4% three or more subclones. The clone heterogeneity was detected by two different models: the linear succession model and the branching evolution model. ETV6-RUNX1+ ALL relapse evolved from an ancestral clone or a new clone. The patients relapsed from a new clone got the worse outcome.@*Conclusion@#The clone evolution was detected in pediatric ETV6-RUNX1+ ALL in China. QM-FISH might be helpful to evaluate the outcome of relapsed patients. A new clone was associated with a poorer outcome.
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Objective To observe the effect of variable frequency vibration therapy while sitting in an anti-spasmodic posture on spasticity and the motor function of the upper limbs among stroke survivors.Methods Thirty stroke survivors with upper limb spasticity were randomly divided into a treatment group and a control group,each of 15.Both groups were given routine rehabilitation training for 4 weeks while the treatment group was additionally provided with variable frequency vibration training while sitting in anti-spasmodic postures.Before and after the treatment,the modified Ashworth scale (MAS) was used to assess spasticity.The root mean square (RMS) value of the surface electromyogram amplitude of the affected biceps when extended passively and those of the triceps,obliques and multifidus in maximum isometric contraction was measured and recorded.The motor function of the affected upper limbs was evaluated using the active range of motion (A-ROM) of the shoulder,elbow and wrist,as well as a Fugl-Meyer assessment (FMA).Moreover,ability in the activities of daily living (ADL) was assessed using the modified Barthel index (MBI).Results After the treatment,significant improvement was observed in the average MAS,A-ROM,RMS,FMA and MBI results in both groups compared to those before the treatment.Moreover,the results in the treatment group were significantly better than those of the control group,on average.Conclusions Variable frequency vibration therapy while sitting in an anti-spasmodic posture combined with traditional rehabilitation is more effective than the latter alone in relieving spasticity as well as improving motor function and ability in the activities of daily living among stroke survivors with the upper limb spasticity.
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The joint is an important athletic organ,and has special structure,i.e.no blood supply in the mature articular cartilage.Hence,once articular cartilage is damaged and is difficult to self-repair.Nowadays,there are several clinical methods for articular cartilage injury,such as micro-fracture,transplant of articular cartilage,replacement of articular cartilage and cartilage tissue engineering.But the repairing effects of these methods are unsatisfactory.Growth factors are biologically active substances that are synthesized by cells in vivo and can accelerate cell growth,promote cell proliferation and induce cell migration etc.There are many growth factors participate in the development of cartilage,such as fibroblast growth factor (FGF),bone morphogenetic protein(BMP),insulin-like growth factor (IGF) and so on.Some research showed that the addition of exogenous growth factor in articular cartilage repair can effectively promote the repair of articular cartilage injury.In this paper,the main growth factors used for articular cartilage injury repair were reviewed,and the functions of these factors in the development and the repair of articular cartilage were discussed.The problems of growth factors in the application of articular cartilage repair were analyzed.
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OBJECTIVE:To improve teaching quality of the course of Medicinal Chemistry.METHODS:On the basis of understanding the nature,characteristics and main existing teaching problems of the course of Medicinal Chemistry,concept map method was used to reveal the regularities of the course contents in order to organize classroom teaching.RESULTS:The regularities of the intricate abstract course contents of Medicinal Chemistry,including regularities of some specific drugs and interrelationships among drugs,were intuitively reflected by concept map method.In daily teaching activities,under teacher's guidance,students autonomously discovered course knowledge by drawing concept map.Different students had different learning results,but on the whole,autonomous learning ability and learning efficiency of the students were improved.CONCLUSIONS:The concept map method is effective method for improving the teaching quality of Medicinal Chemistry.
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The joint is an important athletic organ,and has special structure,i.e.no blood supply in the mature articular cartilage.Hence,once articular cartilage is damaged and is difficult to self-repair.Nowadays,there are several clinical methods for articular cartilage injury,such as micro-fracture,transplant of articular cartilage,replacement of articular cartilage and cartilage tissue engineering.But the repairing effects of these methods are unsatisfactory.Growth factors are biologically active substances that are synthesized by cells in vivo and can accelerate cell growth,promote cell proliferation and induce cell migration etc.There are many growth factors participate in the development of cartilage,such as fibroblast growth factor (FGF),bone morphogenetic protein(BMP),insulin-like growth factor (IGF) and so on.Some research showed that the addition of exogenous growth factor in articular cartilage repair can effectively promote the repair of articular cartilage injury.In this paper,the main growth factors used for articular cartilage injury repair were reviewed,and the functions of these factors in the development and the repair of articular cartilage were discussed.The problems of growth factors in the application of articular cartilage repair were analyzed.
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OBJECTIVE:To improve teaching quality of the course of Medicinal Chemistry.METHODS:On the basis of understanding the nature,characteristics and main existing teaching problems of the course of Medicinal Chemistry,concept map method was used to reveal the regularities of the course contents in order to organize classroom teaching.RESULTS:The regularities of the intricate abstract course contents of Medicinal Chemistry,including regularities of some specific drugs and interrelationships among drugs,were intuitively reflected by concept map method.In daily teaching activities,under teacher's guidance,students autonomously discovered course knowledge by drawing concept map.Different students had different learning results,but on the whole,autonomous learning ability and learning efficiency of the students were improved.CONCLUSIONS:The concept map method is effective method for improving the teaching quality of Medicinal Chemistry.
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To study the biological function of DNAH2 (Homo sapiens dynein, axonemal, heavy chain 2) gene, we constructed human stable U2OS cell line of DNAH2 gene knockout through CRISPR/Cas9n double nick system. The A, B sgRNAs (Single guide RNA) and complementary strands were designed and synthesized. The double-stranded structures were formed during annealing, and connected with BbsⅠ cohesive ends-containing pX462 linear vector to construct the recombinant eukaryotic expression plasmids, including pX462-DNAH2-A and pX462-DNAH2-B. After the co-transfection of the two plasmids into U2OS cells, the addition of puromycin and limiting dilution method were used to obtain positive monoclonal cell line. Western blotting assay was then performed to detect the expression of DNAH2 protein, and PCR-sequencing technology was finally utilized to analyze the mutation feature. The results showed that A, B sgRNAs duplex was successfully inserted into pX462 vector, and DNAH2 protein was not expressed and DNAH2 gene suffered from the frame-shift mutation in U2OS-DNAH2-KO monoclonal cell line. These demonstrated that DNAH2 knockout U2OS stable cell line was successfully constructed through CRISPR/Cas9n double nick system, which providing a useful tool for the study of DNAH2 gene.
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<p><b>OBJECTIVE</b>To identify ikaros family zinc finger1 (IKZF1) deletion in patients with pediatric B cells-acute lymphoblastic leukemia (B-ALL) without reproducible chromosomal abnomalities and further investigate its value in this part of patients' pathogenesis and prognosis.</p><p><b>METHOD</b>The study was approved by the institutional review board of the authors' hospital and informed consent was obtained from the patients and/or their legal guardians. Data of 96 children with B-ALL patients without reproducible cytogenetic abnormalities whose bone marrows specimens were enough for DNA extraction for the detection were retrospectively selected. All the patients were diagnosed and systematically treated according to CCLG-ALL2008 in our hospital from April 2008 to April 2013. The 96 patients were divided into two groups according to the result of IKZF1's detection by multiplex ligation-dependent probe amplification (MLPA): The cases that with any of eight exons of IKZF1 deleted were entered into"Group with IKZF1 deletion"otherwise entered"Group without IKZF1 deletion". Disease free survival (DFS), event-free survival (EFS) and overall survival (OS) were compared between the two groups.</p><p><b>RESULT</b>Nineteen out of 96 B-ALL patients without reproducible cytogenetic abnormalities had IKZF1 deletion (20%). Three of 19 patients with IKZF1 deletions of the whole gene; ten of 19 patients with IKZF1 deletions of exon 1; 4 of 19 patients with IKZF1 deletions of exons 4-7; one of 19 patients with IKZF1 deletions of exons 2-7 and one of 19 patients with IKZF1 deletions of exons 1-6. Whose white blood cell (WBC) ≥ 50 × 10(9)/L inIKZF1 diletion group was more than whthout IKZF1 deletion group(42% vs. 13%, P=0.004). Patients with IKZF1 deletions had a lower 3-year DFS (0.67 ± 0.13 vs. 0.93 ± 0.04, P=0.001); EFS (0.67 ± 0.13 vs. 0.90 ± 0.04, P = 0.012) and OS(0.79 ± 0.09 vs. 0.96 ± 0.02, P=0.010) compared to those without IKZF1 deletions. Excluding the influence of sex, age, WBC count at diagnosis, cerebrospinal fluid state and prednisone response IKZF1 deletion still affected the patients' DFS, EFS and OS ( P<0.05 for all comparisons).</p><p><b>CONCLUSION</b>Some of pediatric B-cell precursor ALL without reproducible cytogenetic abnormalities had been detected to have IKZF1 deletion; IKZF1 deletion is an independent poor prognostic factor in these patients.</p>
Subject(s)
Child , Humans , Chromosome Aberrations , Disease-Free Survival , Exons , Gene Deletion , Ikaros Transcription Factor , Genetics , Multiplex Polymerase Chain Reaction , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Genetics , Prognosis , Zinc FingersABSTRACT
<p><b>OBJECTIVE</b>To evaluate the copy number variations (CNVs) in pediatric ETV6/RUNX1 gene positive acute lymphoblastic leukemia(ALL) and its correlation with clinical features and prognosis.</p><p><b>METHOD</b>Totally 141 children (<14 years of age) with newly diagnosed ETV6/RUNX1 positive ALL in Institute of Hematology and Blood Diseases Hospital, were included from January 2006 to November 2012. The CNVs were analyzed by multiplex ligation-dependent probe amplification (MLPA). The survival rate between the patients with CNVs were explored. Overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier method and compared with the log-rank test.</p><p><b>RESULT</b>Among the 141 cases, 55.3% (n=78) were boys and 44.7% (n=63) were girls and the median age was 4 (1-13) years. The estimated 5-year DFS rate for the patients was (84±4)%. The estimated 5-year OS rate for the patients was (85±4)%. Ninety-five patients were tested MLPA. CNVs were detected in 73 cases (76.8%). CNVs of genes EBF1(15.8%), CDKN2A/2B(18.9%), PAX5(21.1%), ETV6(54.8%), BTG1(10.5%) were detected in more than 10% of the patients. Among the 95 patients, EBF1 deletions were found in 9 patients and EBF1 amplifications were found in 6 patients; 5-year recurrence-free survival (RFS) was statistically significant among 3 groups (χ(2)=9.809, P=0.007) . PAX5 deletions were found in 13 patients and PAX5 amplifications were found in 7 patients; the difference in 5-year RFS was statistically significant between 3 groups(χ(2)=7.622, P=0.022). ETV6 deletions were found in 39 patients and ETV6 amplifications were found in 13 patients; the difference in 5-year RFS was statistically significant among the 3 groups (χ(2)=11.045, P=0.004).</p><p><b>CONCLUSION</b>The CNVs had prognostic relevance in ETV6/RUNX1 positive ALL.</p>
Subject(s)
Adolescent , Child , Humans , Core Binding Factor Alpha 2 Subunit , DNA Copy Number Variations , Disease-Free Survival , Multiplex Polymerase Chain Reaction , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Prognosis , Proto-Oncogene Proteins c-ets , Repressor Proteins , Survival RateABSTRACT
Objective To observe the movement patterns of the geniohyoid muscle in swallowing of healthy subjects by using the real-time B/M-mode ultrasound imaging.Methods Thirty healthy subjects were recruited and the movement patterns of their geniohyoid muscles in swallowing of 5 ml juice-like,thin liquid,honey-like and budding-like bolus.The parameters included the range and the duration of geniohyoid muscle movement.Each subject was measured for 3 times to get the average.Results The range of geniohyoid muscle movement in swallowing of the above bolus was (6.993 ± 1.776)mm,(7.463 ± 1.947)mm,(8.446 ±2.293)mm and (8.905 ±2.057)mm,respectively,with significant differences among them except that between juice-like and thin liquid bolus swallowing,as well as between honey-like and budding-like bolus swallowing.The duration of geniohyoid muscle movement was (0.899 ±0.129)s,(1.019 ±0.149)s,(1.119 ±0.111)s and (1.211 ±0.141)s in juice-like,thin liquid,honey-like and budding-like bolus swallowing,with significant differences among them.When swallowing the same bolus,the range and duration of geniohyoid muscle movement of males were significantly longer than those of females.Conclusions B/M-mode imaging provides a useful technique for assessment the movement of the geniohyoid muscle.The bolus viscosity has an impact on the movement of the geniohyoid muscle.Compared with the range of movement,the duration of geniohyoid muscle movement is a better index for evaluating the effect of bolus viscosity on the geniohyoid muscle movement.