Stratified Treatment in Pediatric Anaplastic Large Cell Lymphoma: Result of a Prospective Open-Label Multiple-Institution Study.

Purpose: The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. 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. Materials and 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 (VBL). 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% [95% Confidence Interval (CI), 69.0%-83.9%] and 92.3% (95% CI,86.1%-95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5%-95.5%, and 67.9% (95% CI, 55.4%-77.6%), 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% (95% CI, 68.6%-19.0%), 65.7% (95% CI, 47.6%-78.9%), 55.7% (95% CI, 26.2%-77.5%), and 70.7% (95% CI, 48.6%-84.6%), respectively. At the end of follow-up, one of the 5 patients who received maintenance therapy with VBL relapsed, and seven patients receiving ALK inhibitor maintenance therapy did not experience relapse. Conclusion: This study has confirmed the poor prognostic of MDD (+) ，high risk site and SC/LH ,but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

A Novel Control Strategy for Soft Open Point to Address Terminal Voltage Violations and Load Rate Imbalance in Low-Voltage Power Distribution Station Areas.

In low-voltage power distribution station areas (DSAs), sensor devices and communication networks are often inadequate. Therefore, the control strategies mainly used for soft open points (SOPs) based on global information in medium-voltage distribution networks are difficult to be directly applied to low-voltage DSAs. This paper proposes a novel control strategy for SOP that only requires collecting the local information of SOP and the load rate of transformers. It aims to address the issues faced of voltage violations at the end of feeders and the load rate imbalance among adjacent DSAs under the current high penetration of renewable energy sources. In this paper, first, a sensor network consisting of sensor devices located at the transformers and each port of the SOP is introduced for information collection. Then, based on the sensitivity relationship between the node voltage and the injected power, considering capacity and voltage safety constraints, the adjustable range of the active power output for each port of the SOP is derived. According to this range, the operating states of the DSAs are categorized into four scenarios. For each scenario, the adjustment amount of SOP output power is determined to achieve comprehensive regulation of terminal voltage and load rate of all DSAs interconnected by SOP. Finally, the effectiveness of the proposed strategy is verified based on a simulation model of three flexible interconnected DSAs established in MATLAB/Simulink.

Vemurafenib combined with chemotherapy achieved sustained remission in pediatric LCH: a multi-center observational study.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a myeloid neoplasia with potentially fatal consequences, and about 2/3 of cases involve the BRAFV600E kinase-activated mutation. Vemurafenib, a BRAF inhibitor, has demonstrated significant clinical improvements in LCH. However, the high relapse rate of LCH following cessation of vemurafenib therapy remains a major challenge, and alternative treatment strategies require further investigation. METHODS: In this retrospective multi-center study, we evaluated the efficacy and safety of vemurafenib combined with conventional chemotherapy in patients with severe or refractory LCH. RESULTS: Seventeen patients were enrolled in the study, with eleven classified as risk organ involvement (RO +). Six received the combination therapy as the primary treatment, and eleven after being refractory to prior chemotherapy. The overall response rate was 94.1%. Progression-free survival among all 17 patients was 70.6% (12/17) at a median follow-up of 32 months, and relapse-free survival among the 15 patients with discontinuation after a response was 73.3%(11/15) at a median follow-up of 34 months. Five of six patients (83.3%) with myeloid BRAFV600E mutations demonstrated molecular remission. The overall survival rate was 100%. Adverse events were mostly classified as grades 1 or 2. CONCLUSION: Our data suggest that the combination of vemurafenib and chemotherapy can achieve sustained clinical and molecular level relief in children with LCH, and side effects are tolerable.

Prognostic significance of multiparametric flow cytometry minimal residual disease at two time points after induction in pediatric acute myeloid leukemia.

BACKGROUND: Prompt response to induction chemotherapy is a prognostic factor in pediatric acute myeloid leukemia. In this study, we aimed to evaluate the prognostic significance of multiparametric flow cytometry-minimal residual disease (MFC-MRD), assessed at the end of the first and second induction courses. METHODS: MFC-MRD was performed at the end of the first induction (TP1) in 524 patients and second induction (TP2) in 467 patients who were treated according to the modified Medical Research Council (UK) acute myeloid leukemia 15 protocol. RESULTS: Using a 0.1% cutoff level, patients with MFC-MRD at the two time points had lower event-free survival and overall survival. Only the TP2 MFC-MRD level could predict the outcome in a separate analysis of high and intermediate risks based on European LeukemiaNet risk stratification and KMT2A rearrangement. The TP2 MFC-MRD level could further differentiate the prognosis of patients into complete remission or non-complete remission based on morphological evaluation. Multivariate analysis indicated the TP2 MFC-MRD level as an independent adverse prognostic factor for event-free survival and overall survival. When comparing patients with MFC-MRD ≥ 0.1%, those who underwent hematopoietic stem cell transplant during the first complete remission had significantly higher 5-year event-free survival and overall survival and lower cumulative incidence of relapse than those who only received consolidation chemotherapy. CONCLUSIONS: The TP2 MFC-MRD level can predict the outcomes in pediatric patients with acute myeloid leukemia and help stratify post-remission treatment.

A multicenter prospective study on the management of hepatoblastoma in children: a report from the Chinese Children's Cancer Group.

BACKGROUND: This study aimed to identify survival risk factors in Chinese children with hepatoblastoma (HB) and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group (CCCG) in 2016. METHODS: A multicenter, prospective study that included 399 patients with HB from January 2015 to June 2020 was conducted. Patient demographics, treatment protocols, and other related information were collected. Cox regression models and Kaplan-Meier curve methods were used. RESULTS: The 4-year event-free survival (EFS) and overall survival (OS) were 76.9 and 93.5%, respectively. The 4-year EFS rates for the very-low-risk, low-risk, intermediate-risk, and high-risk groups were 100%, 91.6%, 81.7%, and 51.0%, respectively. The 4-year OS was 100%, 97.3%, 94.4%, and 86.8%, respectively. Cox regression analysis found that age, tumor rupture (R +), and extrahepatic tumor extension (E +) were independent prognostic factors. A total of 299 patients had complete remission, and 19 relapsed. Patients with declining alpha-fetoprotein (AFP) > 75% after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those ≤ 75%. CONCLUSIONS: The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 therapy. Age ≥ 8 years, R + , and E + were independent risk factors for prognosis. Patients with a declining AFP > 75% after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.

Allogeneic hematopoietic stem cell transplantation corrects ligase IV deficiency.

BACKGROUND: Mutations in the DNA ligase IV (LIG4) gene cause a rare autosomal recessive disorder called LIG4 deficiency syndrome. The LIG4 deficiency is featured by severe disorders, including combined immunodeficiency disease, special face ("bird-head-like" face), developmental delays, pancytopenia, and radiosensitivity. Currently there are no curative treatment options except potentially by performing a hematopoietic stem cell transplantation (HSCT). CASE PRESENTATION: Here we reported the clinical course of a 4 and 1/2-year-old Chinese female with LIG4-deficiency featured with pancytopenia, severe growth retardation (weight of 13.5 kg, < 3rd percentile), length of 100 cm (<2d percentile), head circumference of 46 cm (<3rd percentile), and mild microcephaly. Despite regular IVIG administrations (5 g, once a month), the patient's thrombocytopenia had progressed. Eventually, the patient received HSCT that successfully normalized the LIG4 syndrome associated pancytopenia and corrected the LIG4 mutation. Despite progress the patient succumbed to thrombotic microangiopathy more than 3 months after HSCT. CONCLUSIONS: This case reports an example of partially successful HSCT as a treatment option for LIG4 syndrome. It is possible that individual factors influence the therapeutic effect of HSCT in LIG4 deficiency.

Case report: Multiple epstein-barr virus-associated smooth muscle tumours in a child with IL-2-inducible T-cell kinase mutation of undetermined clinical significance.

Background: EBV-associated smooth muscle tumours (EBV-SMTs) are uncommon neoplasms associated with immunodeficiency. The pathogenesis of EBV-SMTs is poorly understood. IL-2-inducible T-cell kinase (ITK), a member of the Tec family of tyrosine kinases, is the predominant Tec kinase in T cells. Researchers have shown that ITK is involved in the pathogenesis of autoimmune diseases and carcinogenesis, and the loss of ITK function due to mutation in patients can lead to EBV-associated lymphoproliferation. Multiple Epstein-Barr virus-associated smooth muscle tumours with ITK mutation have rarely been reported. Case presentation: A 6-year-old female child was admitted to the hospital due to recurrent bilateral hip pain for more than one year. Tumours were found in the lung, near the intracranial cavernous sinus and in the lumbar spine and paraspinal soft tissues by CT and MRI. The patient underwent vertebral tumour biopsy, which suggested low-grade myogenic or inflammatory myofibroblastic tumours, so the patient was given three courses of chemotherapy without symptom relief or mass reduction. The patient underwent lumbar mass resection, the pathological results indicated EBV-SMT, and a novel germline homozygous deletion mutation in the ITK gene was detected. The deletion mutation in this gene has not yet been reported and the clinical significance of the pathogenicity of the variant is unknown. Intrabronchial mass resection was performed under fibre bronchoscopy, and the pathological results indicated EBV-SMT. No significant recurrence or progression was observed after more than 2 years of follow-up. Conclusions: We present a rare case of multiple EBV-SMTs combined with ITK gene mutation. Some of the tumours were removed, and some were treated conservatively. There was no significant recurrence or progression after more than two years of follow-up. The optimal treatment regimen still needs to be further explored, and the relationship between ITK gene mutation at this locus and immunodeficiency and EBV-SMT warrants further investigation.

Clinical characteristics and prognosis analysis of patients with de novo ASXL1-mutated AML treated with the C-HUNAN-AML-15 protocol: A multicenter study by the South China Pediatric AML Collaborative Group.

BACKGROUND: ASXL1 mutation is an independent prognostic factor in adult acute myeloid leukemia (AML), but its effect on the prognosis of pediatric AML is poorly understood. AIMS: This study aimed to investigate the clinical characteristics and prognostic factors of ASXL1-mutant pediatric AML from a large Chinese multicenter cohort. METHODS: A total of 584 pediatric patients with newly diagnosed AML from 10 centers in South China were enrolled. The exon 13 of ASXL1 was amplified by polymerase chain reaction (PCR), and then analyzed the mutation status of the locus. (n = 59 for ASXL1-mut group, n = 487 for ASXL1-wt group). RESULTS: ASXL1 mutations were found in 10.81% of all patients with AML. A complex karyotype was significantly less common in the ASXL1-mut AML group than in the ASXL1-wt group (1.7% vs. 11.9%, p = 0.013). Furthermore, TET2 or TP53 mutations were predominantly found in the ASXL1+ group (p = 0.003 and 0.023, respectively). The 5-year overall survival (OS) and event-free survival (EFS) of the total cohort were 76.9% and 69.9%. In ASXL1-mut AML patients, a white blood cell (WBC) count ≥50 × 109 /L had significantly poorer 5-year OS and EFS than a WBC count <50 × 109 /L (78.0% vs. 44.6%, p = 0.001; 74.8% vs. 44.6%, p = 0.003, respectively), while receiving hematopoietic stem cell transplantation (HSCT) had a higher 5-year OS and EFS (84.5% vs. 48.5%, p = 0.024; 79.5% vs. 49.3%, p = 0.047, respectively). In the multivariate Cox regression analysis, patients with high-risk AML undergoing HSCT tended to have a better 5-year OS and EFS than those receiving chemotherapy as a consolidation (HR = 0.168 and 0.260, both p < 0.001), and WBC count ≥50 × 109 /L or failure to achieve complete response after the first course were independent adverse predictors of OS and EFS (HR = 1.784 and 1.870, p = 0.042 and 0.018; HR = 3.242 and 3.235, both p < 0.001). CONCLUSION: The C-HUANA-AML-15 protocol is a well-tolerated and effective in the treatment of pediatric AML. ASXL1 mutation is not an independent adverse prognosis predictor for survival in AML, whereas ASXL1-mut patients tend to have a poor prognosis if WBC count ≥50 × 109 /L, but they can benefit from HSCT.

A multicenter phase II trial of primary prophylactic PEG-rhG-CSF in pediatric patients with solid tumors and non-Hodgkin lymphoma after chemotherapy: An interim analysis.

BACKGROUND: Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) can be used in pediatric patients. This study assessed the safety and efficacy of PEG-rhG-CSF as a primary prophylactic drug against neutropenia after chemotherapy in pediatric patients with solid tumors or non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: This phase II study (between October 2020 and March 2022) enrolled pediatric patients with solid tumors or NHL treated with high-intensity chemotherapy and with grade ≥3 myelosuppression for at least 14 days during chemotherapy. Prophylactic PEG-rhG-CSF was given at 100 µg/kg body weight (maximum total dosage of 6 mg) once 24-48 h following chemotherapy for two cycles. The primary endpoint was the incidence of PEG-rhG-CSF-related adverse events (AEs). The key secondary endpoints were the rates of grade 3/4 neutropenia and febrile neutropenia (FN). RESULTS: This study included 160 pediatric patients with a median age of 6.22 (0.29, 18.00) years. Fifty-eight patients (36.25%) were diagnosed with sarcoma. AEs potentially related to PEG-rhG-CSF included bone pain (n = 32), fatigue (n = 21), pain at the injection site (n = 21), and myalgia (n = 20). The rates of grade 3/4 neutropenia and FN during treatment were 57.28% and 29.45%, respectively. CONCLUSION: PEG-rhG-CSF is well tolerated and effective in pediatric patients with solid tumors or NHL. These findings should be substantiated with further trials. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04547829.

RT-PCR demonstrates superior sensitivity and specificity in detecting the five neuroblastoma genes compared to the flow cytometry method for measurable residual disease.

Background: Exploring sensitive prognostic methods for patients with relapsed or refractory neuroblastoma (NB) is critical. The five NB genes (NB5) share a common trait: they are highly expressed in NB. Previous studies have identified their expression levels as markers for guiding micrometastasis. This study aimed to explore whether an improved NB5 detection method is superior to flow cytometry for predicting NB metastasis, measurable residual disease (MRD), and prognosis, and whether this result could serve as an independent factor to influence progression-free survival (PFS). Methods: We utilized reverse transcriptase polymerase chain reaction (RT-PCR) to assess the expression of NB5 (CHGA, DCX, DDC, PHOX2B, and TH) in bone marrow (BM), peripheral blood (PB), or cerebrospinal fluid (CSF) samples collected from 71 patients. The correlation between gene expression changes and clinical characteristics, as well as survival rates, based on 113 detections were analyzed. The NB5 detection results' sensitivity and specificity in all 71 patients collected from six research centers with a median follow-up of 14 months were assessed. Results: PB specimens showed 100% concordance with the BM specimens in terms of positive results. Furthermore, the BM specimens exhibited an additional 45.455% (5/11) positive results compared to the 34.091% (30/88) of PB specimens. The BM specimens were positive for NB5 assay, which was significantly higher than the positive results of flow cytometric MRD (15/88, 17.045%). NB5 was mainly expressed in newly diagnosed patients (P=0.043) and positive patients with flow cytometric MRD (P<0.001) or BM morphology (P<0.001). Positive rates of droplet digital PCR (ddPCR) were consistent with those of quantitative RT-PCR (qRT-PCR) in BM (13/18, 72.222%). However, in PB, the positive rate of ddPCR (2/5, 40.000%) was higher than that of qRT-PCR. A total of 38 specimens (BM, PB, CSF) were detected as positive under qRT-PCR. Among the positive results, the analysis revealed a significant difference between the CHGA and TH in pairwise comparisons (P=0.005). PFS analysis showed that among MRD-negative patients, the survival time of the NB5-positive group was significantly lower than that of NB5-negative group (27.408±10.791 vs. 35.961±3.084 months; P=0.034), and in the Cox regression model, risk stratification based on NB5 expression level was an independent prognostic factor for relapsed or refractory disease [95% confidence interval (CI):1.020 to 9.099, hazard ratio (HR) =3.046, P=0.046]. Combining the follow-up results, we found that the sensitivity and specificity of NB5 detection were both 100%. Conclusions: In our study, the improved NB5 detection method showed significantly higher sensitivity in assessing tumor relapse or residual disease compared to flow cytometric MRD. Moreover, it provided a more accurate assessment of treatment efficacy and prognosis. These findings support NB5 detection as an effective method for further stratification and monitoring of patients with relapsed or refractory NB.

[Recurrent epistaxis with coagulation disorders in a boy aged 2 years]. / 2岁男孩反复鼻衄伴凝血功能异常.

A boy, aged 2 years and 5 months, had recurrent epistaxis, and the coagulation function examination showed that activated partial thromboplastin time (APTT) was significantly prolonged. Further laboratory examinations showed that the prolonged APTT was not immediately corrected in the APTT correction test, with positive lupus anticoagulant and low prothrombin activity. The boy was diagnosed with hypoprothrombinemia-lupus anticoagulant syndrome. The condition was improved after treatment with glucocorticoid, immunoglobulin, and vitamin K1. The boy has been followed up for 6 months, and no epistaxis was observed. Prothrombin activity returned to normal, and lupus anticoagulant remained positive. This is a relatively rare disease, and for patients with bleeding symptoms and coagulation disorders, it is recommended to perform the tests such as APTT correction test, lupus anticoagulant testing, and coagulation factor dilution test, which can improve the detection rate of this disease, so as to achieve early diagnosis, provide rational treatment in the early stage, and improve the prognosis.

A Chinese Child Presented with Early T Cell Precursor Lymphoblastic Lymphoma.

T cell lymphoblastic lymphoma (T-LBL) is regarded as the leukemic phase of T cell acute lymphoblastic leukemia (T-ALL). The early T cell precursors ALL/LBL (ETP-LBL/ALL) are derived from thymic cells at the ETP differentiation stage and recognized as a high-risk subgroup of T-ALL/LBL. Most of these cases presented with ALL at the disease onset, but the ETP-LBL phase is uncommon. Here, we report a patient who presented with ETP-LBL at the disease onset. In this case, ALL developed even despite receiving chemotherapy, but the patient achieved a complete remission with intensive chemotherapy.

High EVI1 Expression Predicts Adverse Outcomes in Children With De Novo Acute Myeloid Leukemia.

BACKGROUND: A high ecotropic viral integration site 1 (EVI1) expression (EVI1 high) is an independent prognostic factor in adult acute myeloid leukemia (AML). However, little is known of the prognostic value of EVI1 high in pediatric AML. This study aimed to examine the biological and prognostic significance of EVI1 high in uniformly treated pediatric patients with AML from a large cohort of seven centers in China. METHODS: A diagnostic assay was developed to determine the relative EVI1 expression using a single real-time quantitative polymerase chain reaction in 421 newly diagnosed pediatric AML patients younger than 14 years from seven centers in southern China. All patients were treated with a uniform protocol, but only 383 patients were evaluated for their treatment response. The survival data were included in the subsequent analysis (n = 35 for EVI1 high, n = 348 for EVI1 low). RESULTS: EVI1 high was found in 9.0% of all 421 pediatric patients with de novo AML. EVI1 high was predominantly found in acute megakaryoblastic leukemia (FAB M7), MLL rearrangements, and unfavorable cytogenetic aberrance, whereas it was mutually exclusive with t (8; 21), inv (16)/t (16; 16), CEBPA, NPM1, or C-KIT mutations. In the univariate Cox regression analysis, EVI1 high had a significantly adverse 5-year event-free survival (EFS) and overall survival (OS) [hazard ratio (HR) = 1.821 and 2.401, p = 0.036 and 0.005, respectively]. In the multivariate Cox regression analysis, EVI1 high was an independent prognostic factor for the OS (HR = 2.447, p = 0.015) but not EFS (HR = 1.556, p = 0.174). Furthermore, EVI1 high was an independent adverse predictor of the OS and EFS of patients with MLL rearrangements (univariate analysis: HR = 9.921 and 7.253, both p < 0.001; multivariate analysis: HR = 7.186 and 7.315, p = 0.005 and 0.001, respectively). Hematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) provided EVI1 high patients with a tendential survival benefit when compared with chemotherapy as a consolidation (5-year EFS: 68.4% vs. 50.8%, p = 0.26; 5-year OS: 65.9% vs. 54.8%, p = 0.45). CONCLUSION: It could be concluded that EVI1 high can be detected in approximately 10% of pediatric AML cases. It is predominantly present in unfavorable cytogenetic subtypes and predicts adverse outcomes. Whether pediatric patients with EVI1 high AML can benefit from HSCT in CR1 needs to be researched further.

Brain-Targeted Polysorbate 80-Emulsified Donepezil Drug-Loaded Nanoparticles for Neuroprotection.

Most Alzheimer's disease drugs do not work efficiently because of the blood-brain barrier. Therefore, we designed a new nanopreparation (PS-DZP-CHP): cholesterol-modified pullulan (CHP) nanoparticle with polysorbate 80(PS) surface coverage, as donepezil (DZP) carrier to realize brain tissue delivery. By size analysis and isothermal titration calorimetry, we chose the optimal dosing ratio of the drug with nanomaterials (1:5) and designed a series of experiments to verify the efficacy of the nanoparticles. The results of in vitro release experiments showed that the nanoparticles can achieve continuous drug release within 72 h. The results of fluorescence observation in mice showed a good brain targeting of PS-DZP-CHP nanoparticles. Furthermore, the nanoparticle can enhance the drug in the brain tissue concentration in mice. DZP-CHP nanoparticles were used to pretreat nerve cells with Aß protein damage. The concentration of lactate dehydrogenase was determined by MTT, rhodamine 123 and AO-EB staining, which proved that DZP-CHP nanoparticles had a protective effect on the neurotoxicity induced by Aß25-35 and were superior to free donepezil. Microthermal perpetual motion meter test showed that PS-DZP-CHP nanoparticles have an affinity with apolipoprotein E, which may be vital for this nanoparticle targeting to brain tissue.

[Epstein-Barr virus-associated smooth muscle tumor in a girl].

A girl, aged 7 years, was admitted due to pain in both lower limbs for more than one year. Lumbar MRI showed soft tissue masses in the paravertebral region. Cerebral MRI showed nodular masses in the cavernous sinus at both sides. Chest CT showed high-density nodules in the outer basal segment of the right inferior lobe and the anterior segment of the left upper lobe of the lung. Biopsy of lumbar lesions showed Epstein-Barr (EB) virus-related smooth muscle tumor. Genetic testing showed a de novo mutation, c.725_730delAGAGTA (p.K242_S243del), in the ITK gene. The masses in the lumbar vertebra were removed by surgery, and then the pain in both lower limbs disappeared. This article reports a case of EB virus-related smooth muscle tumor with a deletion mutation in the ITK gene, which provides experience for the diagnosis and treatment of this disease.

Psychological interventions for enhancing resilience in parents of children with cancer: a systematic review and meta-analysis.

PURPOSE: Caring for children with cancer is considerably stressful for parents and may negatively affect their physical and psychological well-being. Resilience plays a pivotal role in maintaining psychological well-being in the face of stress and adversity. The aim of this systematic review was to evaluate the effectiveness of psychological interventions in promoting resilience among parents of children with cancer. METHODS: Five English databases and two Chinese databases were subjected to a systematic search from inception to March 2020. The methodological quality of the included randomised controlled trials was evaluated using the Cochrane risk of bias tool (RoB 2.0). Meta-analyses and descriptive analyses were used. Subgroup analyses of the intervention modes and time since diagnosis were also conducted. RESULTS: Five studies involving 308 participants were included. The systematic review identified three types of psychological intervention, namely resilience training, self-disclosure and peer support, which had different essential components and characteristics. The meta-analyses of three randomised controlled trials revealed that the psychological interventions enhanced parents' resilience with a large effect size (Hedges' adjusted g 0.92; 95% CI 0.22, 1.62; p = .01). CONCLUSION: Evidence supports the effectiveness of psychological interventions for enhancing resilience in the parents of children with cancer. Healthcare professionals can incorporate evidence-based psychological interventions to enhance resilience to help these parents better navigate adversity, adapt to their children's situations and improve their psychological well-being.

[Short-term effect of intensity-modulated radiotherapy for children with high-risk neuroblastoma: an analysis of 24 cases].

OBJECTIVE: To study the efficacy and safety of intensity-modulated radiotherapy (IMRT) in children with high-risk neuroblastoma (NB). METHODS: A retrospective analysis was performed on the medical data of 24 children with high-risk NB who were diagnosed and treated with IMRT in the Department of Hematology and Oncology, Hunan Provincial People's Hospital, from April 2018 to December 2020. The medical data included age, radiotherapy dose, times of radiotherapy, laboratory examination results, adverse reactions, and survival. RESULTS: All 24 children (14 boys and 10 girls) received IMRT, with a mean age of (65±23) months and a median age of 59 months. The primary tumor was located in the abdomen in 23 children and 1 child had primary tumor in the mediastinum. The median age was 41.5 months at the time of radiotherapy. The radiation dose of radiotherapy ranged from 14.4 to 36.0 Gy, with a mean dose of (22±3) Gy and a daily dose of 1.8-2.0 Gy. The radiotherapy was performed for a total number of 8-20 times, with a mean number of 11.9 times. Among these children, 6 received radiotherapy for the residual or metastatic lesion. Of all the 23 children, 3 experienced cough, 2 experienced diarrhea, and 1 experienced vomiting during radiotherapy. At 2 weeks after radiotherapy, serum creatinine ranged from 2.3 to 70.1 µmol/L and alanine aminotransferase ranged from 9.1 to 65.3 µ/L. Ten children experienced grade Ⅲ bone marrow suppression and 2 experienced grade Ⅳ bone marrow suppression 1 to 2 weeks after radiotherapy. Four children experienced grade Ⅲ bone marrow suppression and 1 experienced grade Ⅳ bone marrow suppression 3 to 4 weeks after radiotherapy. During a median follow-up time of 13.5 months, 23 children (96%) achieved stable disease and 1 died. Up to the follow-up date, second malignant tumor or abnormal organ function was not observed. CONCLUSIONS: IMRT can improve the local control rate of NB. IMRT appears to be safe in the treatment of children with NB.

[Recurrent thrombocytopenia with hemolytic anemia in a boy aged 3 years].

A boy, aged 3 years and 8 months, had recurrent thrombocytopenia with hemolytic anemia for more than 3 years. The physical examination showed no enlargement of the liver, spleen, and lymph nodes or finger deformities. Laboratory results showed a negative result of the direct antiglobulin test, normal coagulation function, and increases in bilirubin, lactate dehydrogenase and reticulocytes. The results of von Willebrand factor-cleaving protease ADAMTS13 activity assay showed extreme deficiency, and antibody assay showed negative ADAMTS13 inhibitory autoantibodies. Next-generation sequence showed compound heterozygous mutation in the ADAMTS13 gene. The boy was diagnosed with congenital thrombotic thrombocytopenic purpura. This disease may be easily misdiagnosed as Evans syndrome and is difficult to diagnose in clinical practice. The child had developed the disease since birth, but it took 3 years to make a confirmed diagnosis. Therefore, congenital thrombotic thrombocytopenic purpura should be considered for children with jaundice at birth, recurrent thrombocytopenia with hemolytic anemia, and negative results of the direct antiglobulin test. The detection of ADAMTS13 activity and ADAMTS13 inhibitory autoantibodies should be performed as soon as possible for a definite diagnosis, and gene detection should be performed to make a confirmed diagnosis when necessary.

[Immune dysregulation syndrome caused by STAT3 gene mutation: a complicated case study].

A boy, aged 4 years and 6 months, had disease onset of fever, cough, pale complexion, and weakness, with hepatosplenomegaly, lymphadenectasis, and pancytopenia. He had been having repeated respiratory and digestive tract infections. Gene detection showed a pathogenic heterozygous mutation, c.C2147 > T(p.T716M), in the STAT3 gene. The boy was thus diagnosed with immune dysregulation syndrome. Anti-infective therapy and irregular corticosteroid therapy had an unsatisfactory effect in the early stage, but the symptoms improved after regular corticosteroid therapy. This article reported the case of immune dysregulation syndrome caused by STAT3 gene mutation and summarized the epidemiology, clinical features, diagnosis, and treatment of this disease, which can provide a reference for early diagnosis, treatment, and future studies of this disease.

LncRNA NBR2 aggravates hepatoblastoma cell malignancy and promotes cell proliferation under glucose starvation through the miR-22/TCF7 axis.

Hepatoblastoma (HB) is the most commonly seen pediatric liver malignancy. With frequent mutations in CTNNB1 gene that encodes ß-catenin, hepatoblastoma has been considered as a Wnt/ß-catenin-activated malignant tumor. Altered glucose metabolism upon nutrient deprivation (glucose starvation) might also be a critical event in hepatoblastoma carcinogenesis. The present study provides a lncRNA NBR2/miR-22/TCF7 axis modulating proliferation, invasion, migration, and apoptosis of hepatoblastoma cells upon glucose starvation through Wnt and downstream TCF7 signaling pathways. The expression of NBR2 is significantly increased within hepatoblastoma tissue samples; moreover, under incubation with 0 mM glucose (glucose starvation), NBR2 expression is significantly upregulated. NBR2 silencing not only inhibited hepatoblastoma cell viability, invasion, and migration under normal culture condition but also promoted the cell apoptosis under glucose starvation. NBR2 silencing in hepatoblastoma cells also decreased TCF7 mRNA expression and TCF7 protein levels, as well as the protein levels of the cell cycle, glucose entrapment, and EMT markers. miR-22 is directly bound to both NBR2 and TCF7; lncRNA NBR2 counteracted miR-22-mediated repression on TCF7 via acting as a ceRNA. The effects of NBR2 silencing on TCF7 expression, hepatoblastoma cell phenotype, and cell cycle, glucose entrapment, and EMT markers were all significantly reversed by miR-22 inhibition. In conclusion, lncRNA NBR2 aggravates hepatoblastoma cell malignancy through competing with TCF7 for miR-22 binding, therefore counteracting miR-22-mediated repression on TCF7. LncRNA NBR2 might be a promising target to inhibit hepatoblastoma cell proliferation under glucose starvation.