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Background The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been unified. Purpose: In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored. Methods On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine. Results A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% and 92.3%, respectively. The 3-year EFS rates of R1, R2, and R3 patients were 100%, 89.5%, and 67.9%, respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3%, 65.7%, 55.7%, and 67.9%, respectively. Conclusions This study established a new risk stratification system for the precise treatment of pediatric ALCL that is convenient and feasible in clinical practice. Among high-risk patients, patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment.

Acute myeloid leukemia (AML) is a severe hematologic malignancy that threatens human health. Long non-coding RNA (lncRNA) is emerged as a key player in human cancer. Herein, we explored the role of LINC00998 in human AML. LINC00998 was significantly decreased in human AML, which was linked to relapse and poor prognosis. Stable overexpression of LINC00998 inhibited AML cell viability, colony ability, DNA synthesis rate and increased apoptosis. LINC00998 was mainly located in the cytoplasm, in which interacted with ZFP36 ring finger protein (ZFP36), a mRNA destabilizing factor, resulting in increased decay of mammalian target of rapamycin complex 2 (mTORC2), a well-known proto-oncogene in AML. Overexpression of mTORC2 partly blocked the tumor suppressive effects of LINC00998. Importantly, LINC00998 shortened in vivo AML cell survival in xenograft tumor model. Taken together, we found that LINC00998 is a novel tumor-inhibiting lncRNA in human AML. The dysregulation of LINC00998/ZFP36/mTORC2 axis is linked to leukemogenesis and progression.

Here, we report a rare case of a 12-year-old boy who was initially diagnosed with B cell lymphoblastic lymphoma (BLBL) and developed myeloid sarcoma (MS) eight months after chemotherapy. Next-generation sequencing (NGS) showed mutations of KRAS and NRAS genes in both the bone marrow and lymph node. He presented an abnormal karyotype of 46, XY, −9, der (16) t (9; 16) (q13; q12), +mar. He received chemotherapy according to the South China Children’s Leukemia Group 2016 protocol. Complete remission was achieved by the 15th day post-treatment. Eight months later and immediately prior to the start of maintenance therapy, the patient developed fever, skin nodules in both upper arms, and enlargement of bilateral testes. Pathological analysis of skin and testicular biopsies suggested the diagnosis of myeloid sarcoma (MS). Again, NGS examination showed mutations of KRAS and NRAS genes. The patient underwent haploidentical hematopoietic stem cell transplantation but unfortunately did not survive. The interval of eight-month interval between the initial disease onset and MS brings into question whether MS developed as part of the initial onset of disease or as a secondary tumor in association with chemotherapy. Thus, understanding the pathogenesis of MS involving abnormalities of lymphoid progenitors may assist in the prediction of prognosis and development of novel target therapies.

Bloodstream infection (BSI) is a serious complication in pediatric hematology-oncology patients. To evaluate the clinical significance of C-reactive protein (CRP), procalcitonin (PCT), albumin, fibrinogen, and D-dimer as potential biomarkers to differentiate among various subtypes of BSIs in pediatric patients with hematological and oncological diseases, we retrieved and analyzed the medical records of pediatric hematology-oncology patients diagnosed with BSI at our hospital between January 2016 and December 2017. The demographic (sex and age) and clinical (primary diseases) characteristics, and laboratory test results (white blood cell and absolute neutrophil counts, and serum CRP, PCT, albumin, fibrinogen, and D-dimer levels) were compared between nosocomial and non-nosocomial; neutropenic and non-neutropenic; and gram-positive and gram-negative BSI episodes. A total of 125 BSI episodes were included, including 69 (55.2%) nosocomial cases, 94 (75.2%) neutropenic cases, and 49 (39.2%) gram-positive episodes. Of the 5 potential biomarkers evaluated (CRP, PCT, albumin, fibrinogen, and D-dimer), PCT levels were significantly lower in neutropenic episodes and gram-positive BSIs (P=0.008 and P=0.001, respectively). At a cutoff value of 0.67 ng/mL, the diagnostic sensitivity, specificity, and positive/negative predictive values of PCT for the differentiation of gram-positive and gram-negative bacterial sepsis were 74.2%, 64.6%, 70.8%, and 65.2%, respectively. We concluded that PCT might potentially serve as a biomarker to differentiate between gram-positive and gram-negative BSIs in pediatric hematology-oncology patients.

Background: Postoperative nausea and vomiting (PONV) refers to a problem commonly occurring after surgery. Acupuncture is considered a critical complementary alternative therapy for PONV. The acupoints selection critically determines the efficacy of acupuncture, whereas the selection rules remain unclear. The objective of the present study was to delve into the principles of acupoints selection for PONV using data mining technology. Methods: The clinical trials assessing the acupuncture effect for PONV were searched with the use of computer in PubMed, China National Knowledge Infrastructure, and Chinese Biomedical Database; the time span was confined as 2009-2019. The database of acupuncture prescriptions for PONV was built using Excel 2016; the description and association were analyzed by IBM SPSS modeler 18. Result: Eighty-three relevant literatures were screened out. The number of specific acupoints took up 72.5% of all acupoints; specific acupoints exhibited the frequency taking up 91.30% of the total frequency. As revealed from the result, Neiguan (PC 6), Zusanli (ST 36), Hegu (LI 4), and Zhongwan (CV 12) were most frequently applied, suggesting the tightest associations. Most acupoints were taken from the stomach meridian and pericardium meridian. The common acupoints were concentrated in the lower limbs, chest, as well as abdomen. Conclusion: Data mining acts as a feasible method to identify acupoints selection and compatibility characteristics. As suggested from our study, the acupoints selection for PONV prioritizes specific acupoints and related meridians. The selection and combination of acupoints comply with the theory of traditional Chinese medicine.

Circular RNAs (circRNAs) are a type of non‑coding RNA with important roles in the regulation of various biological processes involved in malignant progression. However, the potential molecular mechanisms and roles of circRNAs in kidney cancer have remained to be fully elucidated. In a previous study by our group, high‑throughput microarray sequencing data were analyzed to determine the differentially expressed circRNAs in kidney cancer. In this analysis, a novel circRNA (hsa_circ_0100312, named circKL) was identified as a frequently downregulated circRNA in kidney cancer cells and tissues by reverse transcription‑quantitative PCR. In the present study, Cell Counting Kit‑8, colony formation, Transwell, wound‑healing and mouse xenograft assays as well as a lung metastasis experiment were performed to confirm the functions of circKL. The experiments confirmed that circKL overexpression significantly inhibited the proliferation, migration, tumor growth and metastasis of kidney cancer both

Bloodstream infections (BSI) represent one of the most serious complications in patients in the hematology-oncology unit. In this study, the prevalence, distribution, drug sensitivity profiles, and clinical outcome of BSI were analyzed in pediatric patients with hematological malignancies. Patients admitted to the pediatric hematology-oncology unit at Shenzhen Children's Hospital (Shenzen, China) between January 2016 and December 2017 were enrolled. Their medical records, including gender, age, primary diseases, and microbiology results of all clinical specimens, were reviewed. The incidence of BSI, microbiology characteristics, and effectiveness of antimicrobial therapy were analyzed. A total of 125 BSI cases in 108 patients (mean age, 5.5 years) were recorded, of which 69 (55.2%) were nosocomial BSI cases. The overall rate of BSI was 18.8% in the hematology-oncology unit, of which 75 (75.2%) episodes were neutropenic patients. Patients with nosocomial BSIs and the neutropenic group were older (p#.02, p#.03). HSCTs and AML were more often observed in nosocomial BSIs, while solid tumors were more found in nonnosocomial and non-neutropenic BSIs. BSIs were dominated by Gram-negative pathogens (49.6%) in the hematology-oncology unit compared with Gram-positive pathogens (39.2%). The most common pathogens were coagulase-negative Staphylococcus (24.2%) followed by Klebsiella pneumonia (15.2%), Escherichia coli (12.5%), viridans streptococci (8.2%), and Candida species (7.8%). The antibiotic therapy success rate in patients was 93.5%. Based on our center's experience, Gram-negative pathogens were commonly observed among pediatric hematology-oncology patients with BSI. Coagulase-negative Staphylococcus and K. pneumoniae predominated and antibiotic therapy was effective in these patients.

Our previous study revealed altered resting-stated brain function in children with acute lymphoblastic leukemia (ALL) on new-onset stage. To investigate the effects after induction chemotherapy, a pilot self-contrast study was conducted to compare the difference in resting-stated brain function between pre- and post-induction chemotherapy of ALL. Fractional amplitude of low-frequency fluctuation (fALFF) was employed for fMRI data analysis. Clinical and resting state functional magnetic resonance imaging (RS-fMRI) data of 14 new-onset pediatric ALL patients were collected before and after 3 months of induction chemotherapy. Fourteen age- and gender-matched healthy controls (HCs) were recruited for comparison. Before induction chemotherapy, fALFF values of ALL patients decreased globally, especially in the default mode network (DMN), left frontal lobe, left occipital lobe, and bilateral postcentral gyri as compared to HCs. After induction chemotherapy, fALFF values of ALL patients decreased significantly in the bilateral cuneus, left lingual and calcarine gyri, and left mid frontal gyrus. Paired-sample t-tests and self-contrast analysis showed fALFF increased in the left precuneus, bilateral cuneus, left occipital lobe, bilateral frontal gyri, and bilateral temporal lobes, whereas fALFF in the bilateral precuneus decreased in the ALL patients after induction, which suggests potential side-effects of the treatment. The alteration of fALFF values suggested that resting brain function was impaired before induction chemotherapy and mostly recovered after treatment. This study suggested that fALFF is a reliable and feasible tool in detecting spontaneous brain activity to monitor early neurocognitive impairments in pediatric ALL to better understand the underlying neurobiological mechanisms of chemotherapy on the brain.

Introduction Previous studies have shown that miR-373 functions as either a tumor suppressor or an oncogene depending on which type of cancer it's operating in. However, the functional role of miR-373 in neuroblastoma (NB) remains largely unclear. Methods Expression of miR-373 and SRC kinase signaling inhibitor 1 (SRCIN1) in 20 metastatic and 20 primary NB tissues was detected by quantitative real-time PCR (qRT-PCR) and Western blotting. MTT assay, flow cytometry analysis and transwell migration and invasion assays were performed to evaluate the influence of miR-373 inhibition on the growth, migration and invasion of NB cells, respectively. In vivo experiment was applied to determine the effect of miR-373 inhibition on tumor growth. Dual-luciferase reporter assay was used to confirm the interaction between miR-373 and SRCIN1. Results We observed a significant increase in the expression of miR-373 in metastatic NB samples compared with primary NB samples, and this was inversely correlated with SRCIN1 expression. Functional studies revealed that depletion of miR-373 inhibited in vitro NB cell growth, migration and invasion, and also suppressed tumor growth in an in vivo mouse model. Moreover, we identified that SRCIN1 was a direct and functional target gene of miR-373. Silencing of SRCIN1 partially rescued the antimiR-373-mediated inhibition of cell growth, migration and invasion. Conclusion The data from our study verified a potential oncogenic role of miR-373 in NB cells that occurs through direct targeting SRCIN1. The newly identified miR-373/SRCIN1 axis represents a new potential candidate for therapeutic intervention of malignant NB.

Technological Pedagogical Content Knowledge (TPACK) is a new type of teacher knowledge framework, a new definition of the structure of teachers' professional knowledge in the information age, and an important indicator for evaluating teachers' information teaching ability in the information age. This paper first introduces the design of the TPACK questionnaire; then conducts a statistical analysis of the data after the survey (the basic situation of the primary school mathematics teacher in Inner Mongolia and the analysis of the status quo of the teacher TPACK). Based on the existing problems of primary school mathematics teachers TPACK in Inner Mongolia, this article puts forward the countermeasures to promote the development of teachers’ TPACK by improving teachers’ “subject education technology ability” and practicing multiple action paths systematically.

BACKGROUND Upregulation of the Wnt/ß-catenin pathway has been demonstrated to promote tumor proliferation and chemoresistance in lymphoma. Our objective was to evaluate the effect of the Wnt/ß-catenin pathway inhibitor WNT974 in lymphoma cells. MATERIAL AND METHODS Human lymphoma cell lines HUT-78 and BJAB were treated with or without 1 μM WNT974±0.15 μg/L doxorubicin (Dox). Cell viability and proliferation were evaluated by CCK-8 and colony formation assay. Expression of proliferating cell nuclear antigen (PCNA), KI67, and apoptotic-related proteins including Bcl-2, Bax, cleaved-caspase3, and cleaved-caspase9, together with Wnt pathway proteins Wnt, ß-catenin, Axin2, and c-Myc, were detected by Western blot analysis. Flow cytometry was used to calculate the ratio of apoptotic cells. RESULTS In HUT-78 and BJAB cells, 1 μM WNT974 significantly reduced viability and colony formation. The expression of 2 markers of tumor cell proliferation, protein PCNA and KI67, was also reduced by WNT974. Treatment with 1 μM WNT974 for 48 h increased the rate of cell apoptosis, inhibited the expression of anti-apoptotic protein Bcl-2, and enhanced pro-apoptotic proteins Bax, cleaved-caspase3, and cleaved-caspase9 expression in both cell lines. After treatment with WNT974 plus Dox, cell viability was markedly decreased compared with Dox treatment alone. Mechanistically, WNT974 prevented the expression of Wnt, Axin2, ß-catenin, and its target gene c-Myc. CONCLUSIONS WNT974 effectively treats lymphoma by inhibiting cell proliferation, inducing cell apoptosis, and enhancing chemosensitivity to Dox, and these effects are dependent on blocking Wnt/ß-catenin signaling.

The aim of the present study was to investigate the association between methylation of cyclin-dependent kinase inhibitor 2B (CDKN2B) CpG islands and telomerase activity in children with acute lymphoblastic leukemia (ALL). A total of 72 children with ALL and 12 children with immune thrombocytopenia (ITP) were subjected to bone marrow aspiration and methylation-specific polymerase chain reaction analysis, and modified telomeric repeat amplification protocol assay analyses, to evaluate CDKN2B methylation and telomerase activity, respectively. The results of the present study demonstrated that, of these 72 children with ALL, 31 exhibited CDKN2B methylation at diagnosis (43.1%), whereas 41 exhibited no CDKN2B methylation (36.9%). However, no CDKN2B methylation was detected in the ITP controls. Furthermore, the mean level of telomerase activity was 39.52±39.33 total product generated (TPG) units in children with ALL, which was significantly increased compared with 2.49±2.27 TPG units in the ITP controls (P=0.002). The mean levels of telomerase were 49.09±44.43 and 29.99±32.43 TPG units in children with ALL with and without CDKN2B methylation, respectively (P=0.041), therefore children with ALL exhibited significantly increased levels of telomerase. The increased telomerase activity was significantly associated with increased risk of childhood ALL (P=0.023). A total of 22/31 children with ALL with methylated CDKN2B (71.0%) and 17/41 children with ALL with unmethylated CDKN2B (41.46%) exhibited increased telomerase activity (>15 TPG units). The results of the present study suggest that hypermethylation of CDKN2B CpG islands and hyperactivity of telomerase are common events in childhood ALL, and hypermethylation of CDKN2B CpG islands was significantly associated with upregulated telomerase activity (P=0.013).

Hydatids may persist for years if left undiagnosed. Early identification is challenging, especially in patients from nonendemic regions. It is crucial for clinicians to be aware of the presence of the disease to avoid devastating outcomes.

e22005 Background: To uncover the genomic characteristics as well as to, within the scope of pediatric soft tissue sarcoma (psts), assess the clinical value of Next Generation Sequencing (NGS), we present the first report of genomic profiles in Chinese psts. Methods: Tumor tissue, as well as peripheral blood from 41 psts patients, were collected in Sun Yat-Sen University Cancer Center, Shenzhen Children's Hospital and Nanfang Hospital. Samples were sequenced in a CLIA/CAP-accredited laboratory with a targeted NGS panel (Onco PanScan plus; GenetronHealth.inc) consisted of all exons of 831 cancer-related genes and mRNA of 395 genes. Bioinformatics analysis was conducted using a build-in computational pipeline. Results: A total of 41 samples consisted of five major histology types including rhabdomyosarcoma (RMS) (n = 11), fibrosarcoma (n = 4), Ewing's sarcoma (n = 4), INI1-deficient mesenchymal tumor (n = 4), and other mesenchymal tumors (n = 18). All patients were with doubtful diagnosis,advanced, relapsed, or refractory sarcoma, of which 85% samples were from initial diagnoses. In totally, we identified 116 somatic aberrations and 4 pathogenic or likely pathogenic germline mutations, with a median tumor mutational burden of 0.47/Mb (0–6.57). Genomic analysis revealed frequent alterations in TP53 (10%), NTRK fusion (10%), PAX3/7 fusion (8%), and ARID1A (7%). ARID1A (18% vs. 0%) and TP53 (18% vs. 3%) mutations were found with higher frequency compared with pediatric RMS data in a previous study (Jack et al 2014). ARID1A mutation was only reported in a RMS case report (Cramer et al 2017). Furthermore, the mutation of ARID1A potentially match PARP inhibitors, which may provide more therapeutic options. In addition, NGS aided pathologic diagnosis in 63% (26/41) patients. The proportion of confirmed diagnosis, differential diagnosis, and the excluded diagnosis was 41.5%, 12.2%, and 9.7%, respectively. Druggable alterations were detected in 39% patients (Table). Four patients received the treatment recommended by genetic testing, three of them with NTRK fusion were recruited in a matched clinical trial could be evaluated and showed partial remission upon Larotrectinib. Conclusions: We discovered ARID1A mutations, which potentially sensitive to PARP-inhibition, were at a higher incidence in Chinese RMS. This study demonstrated the value of NGS test in guiding the clinical practice of psts in Chinese population. [Table: see text]

BACKGROUND:γ-Glutamyl hydrolase (GGH) regulates intracellular folates and antifolates such as methotrexate (MTX) for proper nucleotide biosynthesis and antifolate-induced cytotoxicity, respectively. In addition to genetic polymorphism and karyotypic abnormalities, methylation of CpG island 1 (CpG1) in the promoter region is found to modulate GGH activity by reducing GGH mRNA expression in acute lymphoblastic leukemia (ALL) cells. We aim to investigate methylation status of two CpG islands (CpG1 and CpG2) in the GGH promoter region in pediatric patients with ALL and acute myelogenous leukemia (AML). METHODS:70B-ALL, 29 AML, 10 ITP (idiopathic thrombocytopenic purpura) and 40 healthy children are recruited in the present study. MS-HRM (methylation-sensitive high-resolution melting) and bisulfite sequencing PCR (BSP) are used to detect methylation change and its level in CpG1 and CpG2 in the GGH promoter region. GGH mRNA expression is quantified by real-time PCR. Correlation between CpG island methylation and GGH mRNA expression is assessed by statistical software. RESULTS:Methylations of CpG1 are detected in leukemia cells samples obtained from 30.9% (21/68) of patients with ALL and 20.7% (6/29) of patients with AML. These methylations are not detected in the controls. Methylations of CpG2 are detected in leukemia cell samples obtained from 44.1% (30/68) of the ALL patients and 37.9% (11/29) of the AML patients. These percentages are significantly higher than that observed in the control cell samples: 6.0% (3/50) (Fisher's exact test, P = 0.000). The abundance of CpG1 methylation in all leukemia cell samples is classified as Grade I (methylation level is less than 10%) and the abundance of CpG2 methylation in leukemia cell samples is classified in separate grades. Our results indicate that methylation of CpG1 or hypermethylation (the methylation level is greater than 10%) of CpG2 could significantly reduce GGH mRNA expression in leukemia cells from the ALL and AML patients (ALL-CpG1: t = 4.632, P = 0.000; ALL-CpG2: t = 3.250, P = 0.006; AML-CpG1: t = -2.254, P = 0.037; AML-CpG2: t = 1.328, P = 0.202). CONCLUSION:Either methylation of CpG1 or hypermethylation of CpG2 in GGH promoter region can significantly reduce GGH mRNA expression in pediatric patients with acute leukemia, which can improve the response to treatment.

Objective Cognitive impairments had been reported in childhood acute lymphoblastic leukemia, what caused the impairments needed to be demonstrated, chemotherapy-related or the disease itself. The primary aim of this exploratory investigation was to determine if there were changes in brain function of children with acute lymphoblastic leukemia before chemotherapy. Methods In this study, we advanced a measure named regional homogeneity to evaluate the resting-state brain activities, intelligence quotient test was performed at same time. Using regional homogeneity, we first investigated the resting state brain function in patients with new onset childhood acute lymphoblastic leukemia before chemotherapy, healthy children as control. Results The decreased ReHo values were mainly founded in the default mode network and left frontal lobe, bilateral inferior parietal lobule, bilateral temporal lobe, bilateral occipital lobe, precentral gyrus, bilateral cerebellum in the newly diagnosed acute lymphoblastic leukemia patients compared with the healthy control. While in contrast, increased ReHo values were mainly shown in the right frontal lobe (language area), superior frontal gyrus-R, middle frontal gyrus-R and inferior parietal lobule-R for acute lymphoblastic leukemia patients group. There were no significant differences for intelligence quotient measurements between the acute lymphoblastic leukemia patient group and the healthy control in performance intelligence quotient, verbal intelligence quotient, total intelligence quotient. Conclusion The altered brain functions are associated with cognitive change and language, it is suggested that there may be cognition impairment before the chemotherapy. Regional homogeneity by functional magnetic resonance image is a sensitive way for early detection on brain damage in childhood acute lymphoblastic leukemia.

Among mining algorithms based on association rules, Apriori technique, mining frequent itermsets and interesting associations in transaction database, is not only the first used association rule mining technique but also the most popular one. After studying, it is found out that the traditional Apriori algorithms have two major bottlenecks: scanning the database frequently; generating a large number of candidate sets. Based on the inherent defects of Apriori algorithm, some related improvements are carried out: 1) using new database mapping way to avoid scanning the database repeatedly; 2) further pruning frequent itemsets and candidate itemsets in order to improve joining efficiency; 3) using overlap strategy to count support to achieve high efficiency. Under the same conditions, the results illustrate that the proposed improved Apriori algorithm improves the operating efficiency compared with other improved algorithms.

Trichloromethane was detected by gas chromatography-mass spectrum- selected ion monitoring system during killing algae with chlorine dioxide. After oxidized by chlorine dioxide, the algal solution was filtered to removed algae, the filtrate was cultured with chlorine, and the trichloromethane was also analyzed. The results showed thattrichloromethane did not form during killing algae with chlorine dioxide, but the solution which was oxidized bychlorine dioxide and filtered to removed algae generated trichloromethane after cultured with chlorine. The concentration of trichloromethane formed was influenced by the dose of chlorine dioxide used to killing algae, initial algal number and chlorine concentration. When chlorine dioxide was below 3 mg L-1, the trichloromethane concentration fast increased with the dose of chlorine dioxide increasing, while chlorine dioxide was above 3 mg L-1, the trichloromethane concentration reached to a steady value. The trichloromethane concentration also increased with the increase of initial algal number and chlorine concentration. But even chlorine concentration was as high as 10 mg L-1, the trichloromethane concentration was not over 28μg L-1, which was lower than the requirement for 0.06 mg L-1 trichloromethane in China Standards for Drinking Water Quality (GB5749-2006).

Acute B lymphoblastic leukemia (B-ALL) is one of the most common types of childhood cancer worldwide and chemotherapy is the main treatment approach. Despite good response rates to chemotherapy regiments, many patients eventually relapse and minimal residual disease (MRD) is the leading risk factor for relapse. The evolution of leukemic clones during disease development and treatment may have clinical significance. In this study, we performed immunoglobulin heavy chain (IGH) repertoire high throughput sequencing (HTS) on the diagnostic and post-treatment samples of 51 pediatric B-ALL patients. We identified leukemic IGH clones in 92.2% of the diagnostic samples and nearly half of the patients were polyclonal. About one-third of the leukemic clones have correct open reading frame in the complementarity determining region 3 (CDR3) of IGH, which demonstrates that the leukemic B cells were in the early developmental stage. We also demonstrated the higher sensitivity of HTS in MRD detection and investigated the clinical value of using peripheral blood in MRD detection and monitoring the clonal IGH evolution. In addition, we found leukemic clones were extensively undergoing continuous clonal IGH evolution by variable gene replacement. Dynamic frequency change and newly emerged evolved IGH clones were identified upon the pressure of chemotherapy. In summary, we confirmed the high sensitivity and universal applicability of HTS in MRD detection. We also reported the ubiquitous evolved IGH clones in B-ALL samples and their response to chemotherapy during treatment.

Objective s: To exam the outcomes of children with acute lymphoblastic leukemia (ALL) treated on Berlin-Frankfürt-Münster (BFM) International ALL- based protocol, GD 2008ALL protocol. Method s : In total, 274 patients with newly diagnosed ALL age 1 to 16 years were enrolled onto GD2008ALL protocol from July 1, 2008 to June 30, 2016. Five-year overall survival (OS) rates and even-free survival (EFS) rates were examined with additional analyses of causes of relapse and death. Results:The 5-year probabilities of OS and EFS were 90.8% and 86.9%. The 5-year EFS were 91.7% in SR group, 86.5% in IR group and 82.6% in HR group, respectively. Twenty-five patients were died. Reasons for mortality included 8 cases due to relapse of leukemia, seven cases due to severe infection, one case due to hepatic failure, one case due to intracranial hemorrhage from accident, eight cases abandoned after relapse. There were 29 cases relapsed, including 22 cases (75%) relapsed of the bone marrow alone, 1 case (3.6%) CNS relapsed alone, 2 cases (7.1%) testicular relapsed and 4 cases (14.3%) relapsed of bone marrow and extramedullary. Eleven patients survived after therapy for relapse, of which 7 had received HSCT, two out of the 7 had relapsed after HSCT, and continued on CART therapy. Four out of the 11 relapsed patients received relapsed ALLR3 protocol for treatment. All 11 patients remained in remission status. Conclusion:Our single institutional review of pediatric ALL treated on GD 2008ALL Protocol was tolerated and has good long term outcomes. Although relapse is a major factor affecting long term survival, there are still have options such as HSCT or immunotherapy available for these patients. Disclosures No relevant conflicts of interest to declare.

Using statistical parametric mapping (SPM), we evaluate the feasibility and accuracy of (18) F -2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET) for clinical diagnosis with characteristic hypo-metabolic regions, and examine the consistency of cerebral hypo-metabolism in Alzheimer's disease (AD) cross multicenters at both the group and the individual levels. Four groups of scan data including 39 AD patients and 52 healthy control subjects derived from three centers were analyzed and comparisons between patient subgroups or individual patient and relevant control population were performed using Two Sample T-test. In the group analysis, the hypo-metabolic regions of AD patients obtained from different PET centers were similar and consistent. The common hypo-metabolic cerebral areas were located bilaterally in the posterior cingulate and medial parietal cortex, temporo-parietal cortex, prefrontal cortex, and the middle and inferior temporal gyrus (uncorrected, p

The aim of the present study was to investigate the association between methylation of cyclin-dependent kinase inhibitor 2B (CDKN2B) CpG islands and telomerase activity in children with acute lymphoblastic leukemia (ALL). A total of 72 children with ALL and 12 children with immune thrombocytopenia (ITP) were subjected to bone marrow aspiration and methylation-specific polymerase chain reaction analysis, and modified telomeric repeat amplification protocol assay analyses, to evaluate CDKN2B methylation and telomerase activity, respectively. The results of the present study demonstrated that, of these 72 children with ALL, 31 exhibited CDKN2B methylation at diagnosis (43.1%), whereas 41 exhibited no CDKN2B methylation (36.9%). However, no CDKN2B methylation was detected in the ITP controls. Furthermore, the mean level of telomerase activity was 39.52±39.33 total product generated (TPG) units in children with ALL, which was significantly increased compared with 2.49±2.27 TPG units in the ITP controls (P=0.002). The mean levels of telomerase were 49.09±44.43 and 29.99±32.43 TPG units in children with ALL with and without CDKN2B methylation, respectively (P=0.041), therefore children with ALL exhibited significantly increased levels of telomerase. The increased telomerase activity was significantly associated with increased risk of childhood ALL (P=0.023). A total of 22/31 children with ALL with methylated CDKN2B (71.0%) and 17/41 children with ALL with unmethylated CDKN2B (41.46%) exhibited increased telomerase activity (>15 TPG units). The results of the present study suggest that hypermethylation of CDKN2B CpG islands and hyperactivity of telomerase are common events in childhood ALL, and hypermethylation of CDKN2B CpG islands was significantly associated with upregulated telomerase activity (P=0.013).

Mobile learning is a learning method developed to meet requirements of the era with the development of Internet. In order to promote the development of mobile learning, the theoretical basis, principles, expression forms and characteristics of micro-mobile learning are studied in this paper. Moreover, we summarized the developing platform and technology together with the realization mode of micro-mobile learning content expression forms. Some feasible designs and development methods were proposed for providing some useful information to the study of micro-mobile learning.

To confirm the clinical therapeutic effects of acupuncture and moxibustion on Bell's palsy.480 cases from 4 hospitals were enrolled for this study, among whom 439 cases completed the whole course of the study. The patients were randomly divided into the following 3 groups, a control group(treated with prednisone, vitamin B1, vitamin B12 and dibazol), an acu-moxibustion group (treated with filiform needle plus moxibustion), and a basic treatment plus acu-moxibustion group (treated with oral medicine like those in the control group plus acupuncture, and with moxibustion like in the acu-moxibustion group). The whole treatment course lasted 4 weeks. The therapeutic effects were evaluated according to the symptoms and signs, House-Brackmann grading scale and facial disability indexes(FDI).All the 4 centers (hospitals) completed this study well, with no statistically significant difference found among the 4 centers in therapeutic effects. The patients with different conditions were well distributed in the 3 groups, thus the basic general data were comparable (P0.05). The therapeutic effects of the two treatment groups were better than the control group (respectively P0.05 and P0.01), and it was the best in the acu-moxibustion group (P0.01).Acupuncture and moxibustion may exert definite therapeutic effects on Bell's palsy, better than that of the basic treatment group or the basic treatment plus acu-moxibustion group.