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Background Acute megakaryoblastic leukemia (AMKL) is a biologically heterogeneous subtype of acute myeloid leukemia that originates from megakaryocytes. Patients with AMKL with non-Down syndrome (DS) had a poorer prognosis. However, clear prognostic indicators and treatment recommendations for this subgroup remain controversial. Patients and Methods Herein, we performed a retrospective study on 40 patients (age ≤ 18 years) with non-Down syndrome AMKL at our institution. We assessed the effect of different prognostic factors, such as their cytogenetic abnormalities, early treatment response, and the role of hematopoietic stem cell transplantation (HSCT) as post-remission treatment on the outcomes. Results The complete remission (CR) rate of the patients was 57.9% and 81.1%, respectively, at the end of induction therapy 1 and 2. The overall survival (OS) and event-free survival rates at 2 years were 41% ± 13% and 41% ± 10%, respectively. An analysis of the cytogenetic features showed that patients with +21 or hyperdiploid (> 50 chromosomes) had significantly better OS than those in other cytogenetic subgroups (Plog-rank = .048 and Plog-rank = .040, respectively). Besides cytogenetics, an excellent early treatment response (CR and minimal residual disease Conclusion AMKL in patients with non-Down syndrome has a poor outcome. With poor OS but CR rates comparable with other acute myeloid leukemia subtypes, allogenic HSCT may be a better option for post-remission therapy than conventional chemotherapy, especially for those having a poor response to induction therapy.

The presence of minimal residual disease (MRD) is a risk factor for relapse among children with acute myeloid leukemia (AML), and eliminating MRD can usually improve survival rates. To investigate the effect of expanded activated autologous lymphocytes (EAALs) combined with chemotherapy on eliminating MRD and improving survival rates of children with AML, we retrospectively analyzed the results of 115 children with low- or intermediate-risk AML with MRD treated at the Pediatric Hematological Center, Peking University People's Hospital, between January 2010 and January 2016. The patients were assigned to the chemotherapy plus EAAL (combined therapy) group (n = 61) and chemotherapy group (n = 54). The MRD-negativity rates were 95.1% (58/61) in the combined therapy group and 63.0% (34/54) in the chemotherapy group (P 0.0001) during consolidation treatment. The 5-year event-free survival rate was higher in the combined therapy group than in the chemotherapy group (86.3 ± 4.6% vs. 72.1 ± 6.1%, P = 0.025). No severe adverse event was observed after EAAL infusion. The present study showed that EAAL combined with chemotherapy could improve the MRD-negativity rate and event-free survival rate among children with AML with low level MRD-positive status.

Background The impact of extramedullary infiltration (EMI) on the clinical outcomes of pediatric patients with acute myeloid leukemia (AML) are controversial. Patients and Methods A total of 214 pediatric patients with low-risk AML were classified as having EMI (central nervous leukemia [CNSL] and/or myeloid sarcoma [MS]) and not having EMI. Patients with isolated MS before AML diagnosis by bone marrow examination were confirmed with histopathologic examination. For patients diagnosed with AML by bone marrow examination, a thorough physical examination and radiologic imaging were used to confirm MS. Results Male gender, a high white blood cell count, the FAB-M5 subtype, t(8;21) and t(1;11) abnormalities, and c-KIT mutations were associated with EMI. The presence of MS was associated with a low complete remission rate (63.6% vs. 79.4%; P = .000) and poor 3-year relapse-free survival (RFS) (62.6% ± 7.5% vs. 87.0% ± 2.8%; P = .000) and 3-year overall survival (73.5% ± 7% vs. 88.8% ± 2.6%; P = .011). Multivariate analysis revealed that MS was a poor prognostic factor for RFS and overall survival. Bone infiltration was an independent risk factor for inferior RFS with MS. Patients with CNSL had a low complete remission rate (58.3% vs. 77.2%; P = .045); however, CNSL did not significantly affect the survival of low-risk patients with AML. Conclusion MS should be considered an independent risk factor to guide stratified treatment.

The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly haploidentical (haplo)-HSCT, in pediatric patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) in the tyrosine kinase inhibitor (TKI) era is unclear. This study aimed to identify prognostic factors and explore the role of haplo-HSCT in the treatment of Ph+ ALL in the TKI era. We analyzed clinical data of Ph+ ALL patients aged 1 to 18 years who received imatinib added to intensive chemotherapy at the start of induction therapy. Among the 68 patients who completed at least 2 consolidation cycles, 44 underwent transplantation (transplant arm) and 24 received continuous TKI with chemotherapy (nontransplant arm). At the 3-year follow-up the cumulative incidence of relapse (CIR), event-free survival (EFS), and overall survival (OS) were 23.5%, 73.4%, and 80.3%, respectively. Multivariate analysis showed that hematologic response (whether complete remission [CR] was achieved) at the induction end, BCR-ABL levels (whether major molecular response [MMR] was achieved) at 3 months, and transplantation were independent affecting factors for CIR, EFS, and OS. In the risk stratification analysis based on the first 2 prognostic factors mentioned above, no significant difference existed between the transplant and nontransplant arms for the probabilities of 3-year OS, EFS, and CIR in the standard-risk group (no poor prognostic factors). Meanwhile, OS, EFS, and CIR rates were significantly better in the transplant arm in the high-risk group (≥1 poor prognostic factor). Among the 44 patients in the transplant arm, 37 underwent haplo-HSCT. Achieving CR at the induction end, MMR at 3 months, and haplo-transplant were also independent favorable factors of CIR, EFS, and OS in the nontransplant and haplo-HSCT arms. Haplo-HSCT showed a significant survival advantage in the high-risk group only. Hematologic response at the induction end and BCR-ABL levels at 3 months are likely to be useful for identifying pediatric Ph+ ALL patients at a high risk of relapse in the TKI era. Children with Ph+ ALL in first CR may benefit from allo-HSCT, particularly those at high risk. Haplo-HSCT could achieve good long-term survival for pediatric Ph+ ALL. Thus, haplo-HSCT can be an alternative approach for high-risk Ph+ ALL patients.

This study was performed to evaluate the cortical bone resorption of fibular bone after maxillary reconstruction with a fibula free flap. A total of 35 patients with maxillary defects that were repaired using a fibula flap (62 fibula segments) between January 2011 and January 2016 were enrolled. Computed tomography (CT) images taken 1 week and 1 year postoperative were used to evaluate cortical bone resorption. The 62 fibula segments were measured on four different surfaces in the CT images. At 1 week, the thickness of the cortical bone was 2.57 ± 0.58 mm, 2.72 ± 0.46 mm, 3.84 ± 0.98 mm, and 4.36 ± 0.90 mm for the exterior, interior, superior, and inferior sides, respectively. At approximately 1 year, the cortical bone thickness was significantly reduced to 2.00 ± 0.65 mm (P 0.01), 2.25 ± 0.60 mm (P 0.01), 3.37 ± 0.90 mm (P 0.01), and 2.96 ± 0.84 mm (P 0.01) for the exterior, interior, superior, and inferior sides, respectively. The cortical bone thickness of fibular bone is significantly reduced 1 year after the restoration of maxillary defects with a fibula free flap, most significantly on the inferior side.

In this data article, we provide five datasets of mantis mitochondrial genomes: (1) PCG123: nucleotide sequences of 13 protein-coding genes including all codon positions; (2) PCG123R: nucleotide sequences of two rRNAs and 13 protein-coding genes including all codon positions; (3) PCG12: nucleotide sequences of 13 protein-coding genes without third codon positions; (4) PCG12R: nucleotide sequences of two rRNAs and 13 protein-coding genes without third codon positions, and (5) PCGAA: amino acid sequences of 13 protein-coding genes. These were used to construct phylogenetic relationships within Mantodea and the phylogenetic trees inferred from Bayesian analysis using two data sets (PCG12R, PCGAA) and Maximum Likelihood analysis using four data sets (PCG123, PCG12, PCG12R and PCGAA). We also provide initiation codon, termination codon, amino acid length and nucleotide diversity (Pi) of protein-coding genes among 27 mantises. The whole mitochondrial genomes of 27 praying mantises were submitted to GenBank with the accession numbers KY689112–KY689138.

After reconstruction of a segmental mandibular defect with a fibular free flap, a vascular crisis can be detected clinically and a "no-flow" phenomenon found during re-exploration. Traditional methods used to solve this include removal of the failed flap and delayed mandibular reconstruction, or restoration of the defect with a functional reconstruction plate or contralateral fibular free flap. Our aim therefore was to investigate under what circumstances it is feasible to use a non-vascularised fibular bone graft (NVFB) as a free bone graft after the failure of a vascularised fibular free flap. From 1 January 2010-31 December 2014, 10 patients who had NVFB after failure of a fibular free flap were included in the study. All patients were treated at the Peking University School and Hospital of Stomatology. NVFB were preserved successfully without infection in all 10 cases, and follow-up imaging showed that it had incorporated well with the residual mandible, the basic function and facial aesthetics of which were maintained. In conclusion we have identified that by precise selection of patients, detailed preoperative planning, and meticulous postoperative care, NVFB can be used as a "rescue" technique after failure of a fibular free flap, and can successfully restore the segmental mandibular defect and facial contour.

A seven-color panel was used to detect minimal residual disease (MRD) in T cell acute lymphoblastic leukemia (T-ALL) via flow cytometry (FCM). Its availability and clinical significance were studied in T-ALL patients with newly diagnosed (n = 64), relapsed (n = 48) and morphologically complete remission (n = 103). The following four features were used to identify immature cCD3+ T cells: CD34+, TdT+, but mCD3-/dim+, and CD45dim+. Among these features, either TdT or CD34 expression was the most useful and were found in 93.8% of patients at diagnosis and 86.7% of patients who relapsed. Although some of the immature markers had disappeared in 23 of 59 cases after therapy, only one case presented with a false negative MRD. Of the 74 consecutive patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), MRD-positive patients showed a higher relapse rate, a higher cumulative incidence of relapse at 4 years and a shorter median relapse-free survival than MRD-negative patients at post-HSCT(72.7% vs 17.3%, P = 0.000; 100% vs 19.9%, P 0.0001; and 16 months vs undefined, P 0.0001). We demonstrated that this panel could be applied to97% of T-ALL patients to detect MRD and predict relapse after allo-HSCT even in the absence of the initial immunophenotype.

We acquired 21 complete mitogenomes and 6 nearly complete mitogenomes of mantises belonging to 8 families (Hymenopodidae, Iridopterygidae, Mantidae, Metallyticidae, Sibyllidae, Tarachodidae, Thespidae, Toxoderidae) using 14 pairs of mantid specific primer sets and found that 5 species of mantises have duplicate copies (2-4) of trnR: Ambivia undata, Creobroter jiangxiensis, Creobroter urbanus, Phyllothelys sp1. and Theopropus elegans while two novel gene arrangements CR-I-NCR-I-NCR-I-NCR-I-NCR-I-NCR*-Q-M and COII-K*-D*-K-D*-K-D*-K-D were found in Schizocephala bicornis and Stenotoxodera porioni, respectively. The multiple copies of trnR are caused by independent duplications. The gene arrangements in Stenotoxodera porioni with three identical copies of trnK can be explained as mid-way through the TDRL process while the form of gene arrangement in Schizocephala bicornis is unclear. In the phylogeny at the family level, the monophyly of Liturgusidae and Iridopterygidae was supported, whereas the monophyly of Hymenopodidae, Mantidae and Tarachodidae wasn't. The features of mantis mitochondrial genomes including high duplication rates of trnR, trnK and trnI indicate that Mantodea mitochondrial genomes maybe a useful model system for studying gene duplication. However, derived gene arrangements may not be appropriate for phylogenetic inference in Mantodea as they aren't synapomorphy and aren't shared by close relatives.

Objectives To examine treatment outcomes and factors associated with poor outcome of multidrug-resistant (MDR) tuberculosis (TB) in China. Methods We conducted a prospective observational cohort study including consecutive patients with MDR-TB between 2009 and 2013 in six regions of Zhejiang province. Patients were prescribed treatments by infectious disease specialists, and treatment outcomes were recorded. Sociodemographic characteristics were obtained through a structured questionnaire. The primary endpoint was poor treatment outcomes, defined as treatment failure based on microbiologic persistence, default (lost to follow-up) or death at 24 months. We assessed risk factors for poor treatment outcomes using a Cox proportional hazards model. Results A total of 820 MDR-TB patients were observed, and 537 with known treatment outcomes were included in our study. Overall, the treatment success rate was 40.2 per 100 years (374/537 participants, 69.6%), while treatment failure, death and default rates were 10.0 per 100 years (101 participants, 18.8%), 3.4 per 100 years (36 participants, 6.7%) and 2.7 per 100 years (26 participants, 4.8%) respectively. Independent predictors of poor treatment outcomes included age >60 years (hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.2–4.2), patients registered as experiencing relapse (HR 2.2, 95% CI 1.1–4.4), patients registered as receiving treatment after failure (HR 2.4, 95% CI 1.2–4.9), use of standardized MDR-TB regimens (HR 0.6, 95% CI 0.4–1.0), cavitary disease (HR 4.9, 95% CI 2.8–8.6) and adverse events (HR 2.5, 95% CI 1.2–5.5). Conclusions Under well-designed treatment and management scheme, high treatment success rates were achieved in a high-MDR-TB-burden country. Antimicrobial susceptibility testing for all second-line drugs should be conducted to further assist in the treatment of MDR-TB.

To investigate the prognostic value of PRAME expression in pediatric acute lymphoblastic leukemia(ALL), we measured PRAME transcript levels at diagnosis in 191 patients(146 B-ALL; 45T-ALL)receiving chemotherapy only. PRAME overexpression was defined as transcript levels higher than 0.30%, which is the upper limit of normal bone marrow and the optimal cutoff value derived from ROC curve analysis. PRAME overexpression was identified in 45.5% of patients. In B-ALL, PRAME overexpression was significantly associated with lower CIR(cumulative incidence of relapse), higher DFS (disease-freesurvival), and OS(overall survival) rates at 3 years, respectively (5.8% vs. 14.9%, P = 0.014; 94.2% vs. 85.1%, P = 0.014; 96.0% vs. 87.4%, P = 0.039). PRAME overexpression had no impact on outcome in T-ALL patients. Among B-ALL patients with non-poor cytogenetic risk, those with PRAME overexpression showed significantly lower CIR, higher DFS and OS rates at 3 years, respectively (8.47% vs. 14.5%, P = 0.009; 96.5% vs. 85.5%, P = 0.009; 98.4% vs. 88.0%, P = 0.023). Furthermore, PRAME overexpression was an independent good prognostic factor for relapse in all B-ALL patients and B-ALL patients with non-poor cytogenetic risk. Therefore, the prognostic significance of PRAME overexpression differed by ALL subtype; It predicted good outcome in pediatric B-ALL receiving chemotherapy.

Three complete mitochondrial genomes of Blaberidae (Insecta: Blattodea) (Gromphadorhina portentosa, Panchlora nivea, Blaptica dubia) and one complete mt genome of Blattidae (Insecta: Blattodea) (Shelfordella lateralis) were sequenced to further understand the characteristics of cockroach mitogenomes and reconstruct the phylogenetic relationship of Blattodea. The gene order and orientation of these four cockroach genomes were similar to known cockroach mt genomes, and contained 13 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes and one control region. The mt genomes of Blattodea exhibited a characteristics of a high A+T composition (70.7%-74.3%) and dominant usage of the TAA stop codon. The AT content of the whole mt genome, PCGs and total tRNAs in G. portentosa was the lowest in known cockroaches. The presence of a 71-bp intergenic spacer region between trnQ and trnM was a unique feature in B. dubia, but absent in other cockroaches, which can be explained by the duplication/random loss model. Based on the nucleotide and amino acid datasets of the 13 PCGs genes, neighbor-joining (NJ), maximum parsimony (MP), maximum likelihood (ML) and bayesian inference (BI) analyses were used to rebuild the phylogenetic relationship of cockroaches. All phylogenetic analyses consistently placed Isoptera as the sister cluster to Cryptocercidae of Blattodea. Ectobiidae and Blaberidae (Blaberoidea) formed a sister clade to Blattidae. Corydiidae is a sister clade of all the remaining cockroach species with a high value in NJ and MP analyses of nucleotide and amino acid datasets, and ML and BI analyses of the amino acid dataset.

To explore new risk predictors for a high risk of relapse in Philadelphia chromosome negative (Ph-) B cell acute lymphoblastic leukaemia (B-ALL) patients, 196 paediatric Ph- B-ALL patients (≤ 18 years) were retrospectively analysed. We mainly focus on investigating the prognostic value of CD38 and CD58 expression in leukemic blasts in these patients by four colour flow cytometry. The CD38+ CD58- group (n=16) had a higher relapse rate, a shorter 3-year event-free survival (EFS) and overall survival (OS) than the CD38+ CD58+ group (n=157; 31.3% vs 10.2%, P=0.04; 52.4% vs 92.3%, P

The mandible has an important role in appearance and function. The aim of this study was to describe and evaluate surgical navigation-assisted mandibular reconstruction with the fibula flap. Patients recruited into the study had a custom dental splint fabricated to maintain the mandible in a fixed position. Later, the computed tomography (CT) scan, preoperative design, and operation on the mandible were done in the same position. At 1 week after surgery, a CT scan was done to evaluate the repeatability between the preoperative design and the postoperative result. Twenty patients were enrolled in this study. Good repeatability between the postoperative CT and the preoperative design was found. The repeatability between the preoperative plan and postoperative outcome was 79.1 ± 8.6% at within 1mm, 87.1 ± 6.7% at within 2mm, and 91.9 ± 5.4% at within 3mm. From this study, it can be concluded that surgical navigation techniques can precisely transfer the preoperative design to the operation in mandible reconstruction with a fibula flap. This will assist the surgeon in achieving good cosmetic and functional outcomes.

To investigate the effect of tyrosine kinase inhibitors (TKIs) on the statural growth in children with acute lymphoblastic leukemia (ALL).We retrospectively collected data from 344 children with ALL younger than 17 years old at diagnosis identified in pediatric department of Peking University People's Hospital. The children were divided into three groups: conventional chemotherapy group, imatinib group and dasatinib group. Height was expressed as standard deviation score(HtSDS). In the three groups, we compared the HtSDS and △HtSDS at the start of treatment and during follow-up period and also compared the adult height and median parental height(MPH). We further compared the HtSDS classified by age and gender in imatinib group. At last, univariate analysis was used to analyze the influencing factors on the deceleration of height growth by imatinib.There were 298 children in conventional chemotherapy group, 39 in imatinib group and 7 in dasatinib group. In imatinib group, the mean HtSDS of children at follow-up time was significantly lower than that at the start of treatment (P0.05), regardless of age and gender. In imatinib group, the decrease of HtSDS in girls was more obvious than in boys(P = 0.031). The HtSDS gradually decreased in the first and the second year in imatinib group. After discontinuation of imatinib, the HtSDS had no obvious change. Multivariate analysis showed that the HtSDS at the start of imatinib was negatively correlated with severe growth impairment on imatinib therapy. The HtSDS in dasatinib group and conventional chemotherapy group maintained a high degree of consistency.Imatinib can affect growth velocity in children with ALL, regardless of age and gender. With the discontinuation of imatinib, the inhibitory effect will not continue. The lower HtSDS at the start of imatinib therapy, the more obvious effect of imatinib on growth impairment will be, and the effect will be more obvious in girls than boys.

B-cell acute lymphoblastic leukemia (B-ALL) with MLL-rearrangements (MLL-r) is rare in pediatric patients (aged1 year), and optimal treatment strategies remain unclear. This study aimed to retrospectively evaluate the clinical characteristics, outcomes, and effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) of 37 non-infant children with t(v;11q23)/MLL-r B-ALL. Their 4-year overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR) were 69.8 %, 58.2 %, and 39.1 %, respectively, and differed significantly between patients receiving allo-HSCT (18/19 cases received haploidentical [haplo]-HSCT) at the first complete remission (HSCT at CR1, n = 19; 87.4 %, 89.5 % and 5.3 %) and those continuing consolidation therapy (Non-HSCT at CR1, n = 18; 52.2 %, 25.9 %, and 74.1 %, respectively), and the p values were 0.022,0.001 and0.001, respectively. Of the 13 patients experiencing relapse during consolidation chemotherapy, the five continuing with chemotherapy only died within 44 months, and the eight patients opting for allo-HSCT after CR2 had a 4-year OS of 57.1 %. Multivariate analysis revealed HSCT at CR1 as the only independent protective factor for OS, EFS, and CIR. The present results indicate that allo-HSCT (especially haplo-HSCT) at CR1 may decrease the relapse rate and improve the prognosis of non-infant children with t(v;11q23)/MLL-r B-ALL.

This retrospective single-center study assessed the incidence and clinical features of immune manifestations of refractory cytopenia of childhood (RCC) and childhood aplastic anemia (AA). We evaluated 72 children with RCC and 123 with AA between February 2008 and March 2013. RCC was associated with autoimmune disease in 4 children, including 1 case each with autoimmune hemolytic anemia, rheumatoid arthritis, systemic lupus erythematosus, and anaphylactoid purpura. No children with AA were diagnosed with autoimmune diseases. Immune abnormalities were common in both RCC and AA; the most significant reductions were in the relative numbers of CD3-CD56+ subsets found in RCC. Despite the many similar immunologic abnormalities in AA and RCC, the rate of autoimmune disease was significantly lower in childhood AA than RCC (p=0.008, χ2=6.976). The relative numbers of natural killer cells were significantly lower in RCC patients than AA patients. By month 6, there was no significant difference in autoimmune manifestations between RCC and AA in relation to the response to immunosuppressive therapy (p=0.907, χ2=0.014). The large overlap of analogous immunologic abnormalities indicates that RCC and childhood AA may share the same pathogenesis.