Impact of the COVID-19 pandemic on the demographic and disease burden of pediatric malignant solid tumors in China: a single-center, cross-sectional study.

Background: With the development of the novel coronavirus disease 2019 (COVID-19), China implemented measures in an attempt to control the infection rate. We conducted a single-center, cross-sectional study to ascertain the impact of the COVID-19 pandemic on the equitable availability of medical resources for children diagnosed with malignant solid tumors in China. Methods: Data on the demographics, clinical characteristics, and medical expenses of 876 patients diagnosed with neuroblastoma, rhabdomyosarcoma (RMS), Wilms tumor, hepatoblastoma (HB), Ewing sarcoma (ES), and central nervous system (CNS) tumors from 2019 to 2021, during the COVID-19 pandemic, were retrospectively collected from the National Center for Children's Health. The Pearson χ2 test and Mann-Whitney test were performed to analyze the differences among variables. Results: Except for the regional origin of children with tumors during the epidemic, no significant differences were found in the demographic or clinical characteristics of patients at initial diagnosis. The number of patients from northern China and northeastern China who attended Beijing Children's Hospital (BCH) increased after the outbreak of COVID-19 (P=0.001). There was no significant alteration observed in the frequency of hospitalizations per individual per annum (P=0.641) or the mean expense incurred per individual per hospitalization (P=0.361). In addition, the medical insurance coverage rate of real-time settlement increased year by year. Conclusions: After the COVID-19 outbreak, the origin of patients with solid tumor who visited BCH was concentrated in the northern region of China. COVID-19 had no impact on the other demographic factors, clinical characteristics, or economic burden of patients with pediatric malignant solid tumors.

Discovery of the First-in-Class G9a/GLP PROTAC Degrader.

Aberrantly expressed lysine methyltransferases G9a and GLP, which catalyze mono- and dimethylation of histone H3 lysine 9 (H3K9), have been implicated in numerous cancers. Recent studies have uncovered both catalytic and noncatalytic oncogenic functions of G9a/GLP. As such, G9a/GLP catalytic inhibitors have displayed limited anticancer activity. Here, we report the discovery of the first-in-class G9a/GLP proteolysis targeting chimera (PROTAC) degrader 10 (MS8709), as a potential anticancer therapeutic. 10 induces G9a/GLP degradation in a concentration-, time-, and ubiquitin-proteasome system (UPS)-dependent manner. Futhermore, 10 does not alter the mRNA expression of G9a/GLP and is selective for G9a/GLP over other methyltransferases. Moreover, 10 displays superior cell growth inhibition to the parent G9a/GLP inhibitor UNC0642 in prostate, leukemia, and lung cancer cells and has suitable mouse pharmacokinetic properties for in vivo efficacy studies. Overall, 10 is a valuable chemical biology tool to further investigate the functions of G9a/GLP and a potential therapeutic for treating G9a/GLP-dependent cancers.

Discovery of the First-in-class G9a/GLP PROTAC Degrader.

Aberrantly expressed lysine methyltransferases G9a and GLP, which catalyze mono- and di-methylation of histone H3 lysine 9 (H3K9), have been implicated in numerous cancers. Recent studies have uncovered both catalytic and non-catalytic oncogenic functions of G9a/GLP. As such, G9a/GLP catalytic inhibitors have displayed limited anticancer activity. Here, we report the discovery of the first-in-class G9a/GLP proteolysis targeting chimera (PROTAC) degrader, 10 (MS8709), as a potential anticancer therapeutic. 10 induces G9a/GLP degradation in a concentration-, time, and ubiquitin-proteasome system (UPS)-dependent manner, does not alter the mRNA expression of G9a/GLP and is selective for G9a/GLP over other methyltransferases. Moreover, 10 displays superior cell growth inhibition to the parent G9a/GLP inhibitor UNC0642 in prostate, leukemia, and lung cancer cells and has suitable mouse pharmacokinetic properties for in vivo efficacy studies. Overall, 10 is a valuable chemical biology tool to further investigate the functions of G9a/GLP and a potential therapeutic for treating G9a/GLP-dependent cancers.

Pediatric spindle cell/sclerosing rhabdomyosarcoma with FUS-TFCP2 fusion: a case report and literature review.

Background: FUS-TFCP2 gene fusion is a recently identified and highly distinct molecular subtype of spindle cell/sclerosing rhabdomyosarcoma (RMS), with fewer than 40 cases being reported to date. Due to its low incidence, clinical studies on this subtype are limited. Here, we report a new case of this rare entity to describe and summarize its unique clinical characteristics and treatment process, aiming to emphasize the importance of molecular testing for spindle cell/sclerosing RMS and increase the understanding of this subtype. By summarizing and comparing with previous reports on RMS with the EWSR1/FUS-TFCP2 fusion mutation, we hope to make some new hints for its management. Case Description: In this report, we describe a rare case of spindle cell/sclerosing RMS in a 13-year-old boy, who had a massive destructive lesion involving the mandible. Next-generation sequencing of tumor tissue revealing a FUS-TFCP2 fusion. The tumor was extremely aggressive and showed resistance to polychemotherapy, after 4 cycles of multi drug combined chemotherapy, the primary tumor still continued to grow, and suspicious chest metastasis occurred. Even after aggressive total resection of the primary tumor and postoperative chemotherapy, systemic metastasis to the vertebra and chest could not be prevented yet, ultimately with a fatal outcome within 6 months. We additionally summarize 37 cases of RMS with the EWSR1/FUS-TFCP2 fusion mutation reported in the literature. This subtype was found to be almost exclusively primary in bone and histologically showed a common origin of epithelium and muscle. The high aggressiveness made the conventional standard chemoradiotherapy ineffective. Because most tumors of this subtype express ALK protein, ALK inhibitors seem to be a new target for its therapy. Conclusions: Spindle cell/sclerosing RMS with FUS-TFCP2 fusion has its unique clinical characteristics and progression. It shows a marked skeletal predilection and an aggressive clinical course, typically resistant to traditional standard treatments for RMS. Therefore, molecular detection is crucial in managing this subtype. Once the diagnosis is clear, a more aggressive treatment plan is needed. In addition, almost all cases were found to have a positive expression of ALK. So ALK inhibitors can be a choice of targeted therapy.

Attitude and Performance for Online Learning during COVID-19 Pandemic: A Meta-Analytic Evidence.

The COVID-19 pandemic prominently hit almost all the aspects of our life, especially in routine education. For public health security, online learning has to be enforced to replace classroom learning. Thus, it is a priority to clarify how these changes impacted students. We built a random-effect model of a meta-analysis to pool individual effect sizes for published articles concerning the attitudes and performance towards online learning. Databases included Google Scholar, PubMed and (Chinese) CNKI repository. Further, a moderated analysis and meta-regression were further used to clarify potential heterogenous factors impacting this pooled effect. Forty published papers (n = 98,558) were screened that were eligible for formal analysis. Meta-analytic results demonstrated that 13.3% (95% CI: 10.0-17.5) of students possessed negative attitudes towards online learning during the COVID-19 pandemic. A total of 12.7% (95% CI: 9.6-16.8) students were found to report poor performance in online learning. Moderated analysis revealed poor performance in online learning in the early pandemic (p = 0.006). Results for the meta-regression analysis showed that negative attitudes could predict poor learning performance significantly (p = 0.026). In conclusion, online learning that is caused by COVID-19 pandemic may have brought about negative learning attitudes and poorer learning performance compared to classroom learning, especially in the early pandemic.

Malignant histiocytosis associated with mediastinal germ cell tumor: A case report.

BACKGROUND: Germ cell tumors (GCTs) account for 2% of human malignancies but are the most common malignant tumors among males aged 15-35. Since 1983, an association between mediastinal GCT (MGCT) and hematologic malignancies has been recognized. CASE SUMMARY: We report a case in which malignant histiocytosis was associated with mediastinal GCTs. The clinical data of a male patient with MGCT admitted to Beijing Children's Hospital were collected retrospectively. The patient was first diagnosed according to imaging and pathological features as having MGCT, and was treated with surgery and chemotherapy. One year after stopping chemotherapy, imaging showed metastases in the right supraclavicular, mediastinum, hilar region and retroperitoneal lymph node, right pleura, right lung, and right para-cardiac margin. Pathological diagnosis of the liver nodular and hilar lymph nodes included systemic juvenile xanthogranuloma and Rosai-Dorfman lesions with malignant transformation (i.e., morphological characteristics and immunophenotype of histiocytic sarcoma). Following diagnosis, the patient accepted chemotherapy with vindesine, cytarabine and dexamethasone. Positron emission tomography-computed tomography showed partial remission. The patient was followed-up for 10 mo after the diagnosis of malignant histiocytosis, and no sign of progression or relapse was observed. CONCLUSION: Physicians should recognize the possibility of hematologic malignancies being associated with MGCT. Suitable sites should be selected for pathological examination.

Case report: Clinical features and prognosis of two Infants with rhabdomyosarcoma of the tongue.

Background: Rhabdomyosarcoma (RMS) is the most common soft tissue tumor in children, and its most common pathological types include embryonal RMS and alveolar RMS. In contrast, spindle cell RMS (SRMS) is a rare type. Moreover, the tongue is a rare primary site of RMS, and infancy is a rare age at onset. Case presentation: Two infants were diagnosed with lingual RMS at 3 and 5 months after birth, respectively, and were admitted to Beijing Children's Hospital. The pathological type in both cases was SRMS. Both were classified as low-risk and were treated with surgery and chemotherapy. Case 1 was in complete remission at the latest follow-up, and Case 2 had a relapse 10 months after stopping chemotherapy, achieving complete remission after the multimodal treatment of chemotherapy, surgery, and radiotherapy. The venous blood gene test of the two infants did not indicate a pathogenic mutation or a possible pathogenic mutation related to RMS. In Case 1, variants of the CDK4 and BRCA1 genes, both with unknown significance and a possible relation to RMS, were detected. In Case 2, three gene variants of unknown significance that were possibly associated with RMS-TRIP13, APC, and RAD54L-were identified. Conclusion: Lingual RMS in infants is rare. Its clinical manifestations lack specificity, and early recognition is complex. The success and timing of local treatment are important prognostic factors. Genetic testing may be helpful for the early detection of tumor susceptibility and the estimation of prognosis.

Pain management of newly diagnosed sarcoma patients at a single center.

BACKGROUND: Systematic pain management of children is insufficient in China, and there is no literature on pain in children with sarcoma. METHODS: Clinical data of 188 patients with newly diagnosed sarcoma admitted to the Medical Oncology Department of Beijing Children's Hospital was collected from October 2018 to December 2020. Children experiencing pain received analgesic treatment and regular assessment. RESULTS: Thirty-seven patients (19.7%) suffered from pain. Six cases (16.2%) had mild pain, 17 (46.0%) moderate, and 14 (37.8%) severe. Daily lives of 31 patients were affected by pain. Twenty-six cases had bone invasion. The analgesic rate was 54.1% before admission and 89.2% after admission. Nine cases were treated with oral morphine regularly, and their pain was relieved before chemotherapy; the dose of morphine was 0.14 ±â€…0.034 mg/kgQ4H when the target was reached. No serious adverse reactions were observed. The period of morphine application after chemotherapy was 5 to 9 days, and there was no withdrawal reaction. CONCLUSION: Pain in children with newly diagnosed sarcoma was mainly moderate to severe, and the incidence of pain in sarcoma with bone invasion was higher, with greater intensity. Patients who received standardized pain assessment and regular analgesics reached pain relief quickly, and no serious adverse reactions were observed within the recommended dosage.

Development levels of pediatric palliative care teams and the extent of palliative care understanding and implementation among pediatric oncologists in China.

IMPORTANCE: Pediatric palliative care (PPC) is an interdisciplinary collaboration that focuses on the prevention and relief of patient suffering. PPC has emerged as a critical field of medical expertise and practice. However, no information is available regarding the progress of PPC in the Chinese mainland. OBJECTIVE: This study investigated the geographic distribution, team structure, and services of PPC teams in the Chinese mainland. It also investigated the level of understanding and implementation among pediatric oncologists regarding PPC. METHODS: The PPC subspecialty group of the Pediatrics Society of the Chinese Medical Association included 45 PPC teams. The team structure and services were investigated using questionnaires mailed to the team leader of each PPC team. In addition, we sent questionnaires regarding the level of PPC understanding and implementation of PPC practices to 170 pediatric oncologists in 11 hospitals. RESULTS: The geographical distribution of PPC teams is uneven in China. Most PPC teams are concentrated in the eastern provincial capital of China. Most PPC teams had limited staff and services. The level of PPC understanding was considerably limited across all demographics; most pediatric oncologists reported "some understanding" (n = 71, 41.8%) or "poor understanding" (n = 50, 29.4%). Only 62.9% of pediatric oncologists had experience providing advice to family members regarding PPC matters. INTERPRETATION: China is currently experiencing a critical shortage of PPC resources. Most pediatric oncologists had a limited understanding of PPC and reported limited practical implementation of PPC, which leads to underutilization of PPC resources.

Antisolvent solvothermal synthesis of MAPbBr3 nanocrystals for efficient solar photodecomposition of methyl orange.

Exploring high performance photocatalysts is of great importance to relieve the environment pollution issues. In this paper, we introduce a facile antisolvent solvothermal method to synthesize methylammonium lead tribromide perovskite (MAPbBr3) nanocrystals and successfully employ them as efficient photocatalysts. Compared to the room temperature synthesized MAPbBr3 (RT-MAPbBr3), the antisolvent solvothermal synthesized MAPbBr3 (AS-MAPbBr3) has multiple outstanding properties, such as improved crystallinity with lower grain boundary density, enhanced light absorption in visible range, suitable band gap of 2.31 eV and extended photoluminescence (PL) lifetime as long as 2627.82 ns. By taking advantages of the above merits, the AS-MAPbBr3 exhibits efficient photocatalytic performance by decomposition of methyl orange under solar light. A high apparent rate constant of 101.2 × 10-3 is achieved along with excellent cyclability, which significantly outperforms the RT-MAPbBr3 (56.0 × 10-3) and P25 (16.5 × 10-3). The underlying mechanism for MO photocatalytic degradation is deeply explored and proposed. Our present study suggests that the antisolvent solvothermal method can be a promising method to synthesize perovskite nanocrystals, and might also provide some insights in developing a series of high performance perovskite based photocatalysts.

Learning Target-Domain-Specific Classifier for Partial Domain Adaptation.

Unsupervised domain adaptation (UDA) aims at reducing the distribution discrepancy when transferring knowledge from a labeled source domain to an unlabeled target domain. Previous UDA methods assume that the source and target domains share an identical label space, which is unrealistic in practice since the label information of the target domain is agnostic. This article focuses on a more realistic UDA scenario, i.e., partial domain adaptation (PDA), where the target label space is subsumed to the source label space. In the PDA scenario, the source outliers that are absent in the target domain may be wrongly matched to the target domain (technically named negative transfer), leading to performance degradation of UDA methods. This article proposes a novel target-domain-specific classifier learning-based domain adaptation (TSCDA) method. TSCDA presents a soft-weighed maximum mean discrepancy criterion to partially align feature distributions and alleviate negative transfer. Also, it learns a target-specific classifier for the target domain with pseudolabels and multiple auxiliary classifiers to further address the classifier shift. A module named peers-assisted learning is used to minimize the prediction difference between multiple target-specific classifiers, which makes the classifiers more discriminant for the target domain. Extensive experiments conducted on three PDA benchmark data sets show that TSCDA outperforms other state-of-the-art methods with a large margin, e.g., 4% and 5.6% averagely on Office-31 and Office-Home, respectively.

Antibacterial effect of Blumea balsamifera DC. essential oil against Haemophilus parasuis.

Haemophilus parasuis (H. parasuis), the cause of the Glasser's disease, is a potentially pathogenic gram-negative organism that colonizes the upper respiratory tract of pigs. The extraction of Blumea balsamifera DC., as a traditional Chinese herb, has shown great bacteriostatic effect against several common bacteria. To study the antibacterial effect on H. parasuis in vitro, this study evaluated the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Blumea balsamifera DC. essential oil (BBO) as well as morphological changes in H. parasuis treated with it. Furthermore, changes in expression of total protein and key virulence factors were also assessed. Results showed that the MIC and MBC were 0.625 and 1.25 µg/mL, respectively. As the concentration of BBO increased, the growth curve inhibition became stronger. H. parasuis cells were damaged severely after treatment with BBO for 4 h, demonstrating plasmolysis and enlarged vacuoles, along with broken cell walls and membranes. Total protein and virulence factor expression in H. parasuis was significantly downregulated by BBO. Taken together, these results indicated a substantial antibacterial effect of BBO on H. parasuis.

Cognitive and psychological outcomes of pediatric allogeneic hematopoietic stem cell transplantation survivors in a single center in China.

To investigate the cognitive and psychological outcomes of pediatric allogeneic HSCT survivors in China.A total of 135 3 to 18 years old children and adolescents who underwent allo-HSCT and survived at least 3 months post-HSCT were recruited and completed the assessments. Cognitive and psychological functions were assessed via age-appropriate standardized measures. Clinical information was extracted from the medical records.Forty one 3 to 6 years old children completed Psychological Questionnaires for 3 to 6 years Children. The scores of 21(51.2%) children in cognitive development dimension, 18(43.9%) in motor development dimension, 16(39.0%) in language development and social development dimension, 15(36.6%) in emotion and will dimension and 14(34.1%) in living habits dimension were less than the standard. Fifty six 8 to 16 years old children and adolescents completed the Depression Self-rating Scale for Children and 9 (16.1%) of these met the criteria of depression. Sixty nine 7 to 16 years old children and adolescents completed the screening for Child Anxiety Related Disorders and 7 (10.1%) of these met the criteria of anxiety, especially social phobia and school phobia. Eighty nine 6 to 18 years old children and adolescents completed the Symptom Checklist-90 and 43.8% to 77.5% of these experienced mild symptoms like obsession-compulsion (77.5%), hostility (64%), and interpersonal sensitivity (60.7%). Children treated with total body irradiation (TBI) showed more cognitive impairments like motor deficits than those without TBI. Also older children and adolescents had more symptoms like psychoticism.These findings demonstrated cognitive and psychological late effects of pediatric allo-HSCT survivors in a single center in China and highlighted that the survivors conditioned with TBI had more cognitive impairments and older children and adolescents had more symptoms. Early intervention in these children and adolescents might minimize the cognitive losses and psychological effects.

An Appraisal of Lung Nodules Automatic Classification Algorithms for CT Images.

Lung cancer is one of the most deadly diseases around the world representing about 26% of all cancers in 2017. The five-year cure rate is only 18% despite great progress in recent diagnosis and treatment. Before diagnosis, lung nodule classification is a key step, especially since automatic classification can help clinicians by providing a valuable opinion. Modern computer vision and machine learning technologies allow very fast and reliable CT image classification. This research area has become very hot for its high efficiency and labor saving. The paper aims to draw a systematic review of the state of the art of automatic classification of lung nodules. This research paper covers published works selected from the Web of Science, IEEEXplore, and DBLP databases up to June 2018. Each paper is critically reviewed based on objective, methodology, research dataset, and performance evaluation. Mainstream algorithms are conveyed and generic structures are summarized. Our work reveals that lung nodule classification based on deep learning becomes dominant for its excellent performance. It is concluded that the consistency of the research objective and integration of data deserves more attention. Moreover, collaborative works among developers, clinicians, and other parties should be strengthened.

CGRP receptor activity in mice with global expression of human receptor activity modifying protein 1.

BACKGROUND AND PURPOSE: CGRP is a potent vasodilator and nociceptive neuropeptide linked to migraine. CGRP receptors are heterodimers of receptor activity modifying protein 1 (RAMP1) and either calcitonin receptor-like receptor (CLR; forms canonical CGRP receptor) or calcitonin receptor (CT receptor; forms AMY1 receptor). The goal of this study was to test whether transgenic mice globally expressing human RAMP1 have increased CGRP receptor activity and whether the receptors are sensitive to human selective antagonist telcagepant. EXPERIMENTAL APPROACH: cAMP production was measured in primary cultures of aortic smooth muscle and trigeminal ganglia neurons from global hRAMP1 mice and non-transgenic littermates. Functional activity and inhibition were compared with clonal cell lines expressing combinations of CLR or CT receptors with RAMP1. KEY RESULTS: Cultured smooth muscle from global hRAMP1 mice had a 10-fold greater CGRP-induced cAMP maximal response (Rmax) than non-transgenic littermates, with similar EC50 s. In contrast, cultured trigeminal ganglia from global hRAMP1 mice had a 40-fold leftward shift of the EC50 , with similar Rmax values as littermates. In both hRAMP1 cultures, telcagepant blocked CGRP-induced cAMP production, but was not effective in non-transgenic cultures. IC50 values were closer to those observed for CT receptor/hRAMP1 than CLR/hRAMP1 in clonal cell lines. CONCLUSIONS AND IMPLICATIONS: Overexpression of hRAMP1 increases CGRP signalling by changing the maximal response or ligand sensitivity, depending on tissue type. Furthermore, telcagepant inhibited transgenic hRAMP1 CGRP receptors, but the degree of inhibition suggests that the transgenic mice are only partially humanized or both canonical CGRP and AMY1 receptors are functional in trigeminal ganglia neurons and vascular smooth muscle.

Genome Sequence of Enterobacter cloacae Strain SENG-6, a Bacterium Producing Histo-Blood Group Antigen-Like Substances That Can Bind with Human Noroviruses.

Enterobacter sp. strain SENG-6, isolated from healthy human feces, produces histo-blood group antigen (HBGA)-like substances that can bind with human noroviruses. Based on the genome sequence analysis, strain SENG-6 belongs to the species Enterobacter cloacae The genome sequence of this strain should help identify genes associated with the production of HBGA-like substances.

[Nursing experience helping a client with schizophrenia improve her family relationships: application of reality therapy].

Reality therapy has been demonstrated to be an effective strategy in achieving behavioral change. This case study used reality therapy as a therapeutic communication tool to help improve the family relationships of a client with schizophrenia. We used a four-tiered questioning technique to address, respectively, the aspects of "want," "doing/direction," "evaluation" and "plan" (WDEP). Nursing interventions were held between October 21st and November 19th, 2010. The authors used the reality therapy framework and WDEP system to guide the client to explore her inner needs, review problems objectively, and determine where efforts could be focused most effectively. Better appreciation of her abilities and strengths and encouragement of effective actions helped improve client relationships with her family members. This study introduced reality therapy and shared clinical experiences in order to help readers better understand reality therapy as an alternative framework of communication in nursing care.

Neurotensin negatively modulates Akt activity in neurotensin receptor-1-transfected AV12 cells.

Neurotensin (NT) regulates a variety of biological processes primarily through interaction with neurotensin receptor-1 (NTR1), a heterotrimeric G-protein-coupled receptor (GPCR). Stimulation of NTR1 has been linked to activation of multiple signaling transduction pathways via specific coupling to G(q), G(i/o), or G(s), in various cell systems. However, the function of NT/NTR1 in the regulation of the Akt pathway remains unknown. Here, we report that activation of NTR1 by NT inhibits Akt activity as determined by the dephosphorylation of Akt at both Ser473 and Thr308 in AV12 cells constitutively expressing human NTR1 (NTR1/AV12). The inactivation of Akt by NT was rapid and dose-dependent. This effect of NT was completely blocked by the specific NTR1 antagonist, (S)-(+)-[1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazol-3-yl)-carbonylamino] cyclohexylacetic acid (SR 48527), but unaffected by the less active enantiomer ((R)-(-)-[1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazol-3-yl)-carbonylamino] cyclohexylacetic acid (SR 49711)), indicating the stereospecificity of NTR1 in the negative regulation of Akt. In addition, NT prevented insulin- and epidermal growth factor (EGF)-mediated Akt activation. Our results provide insight into the role of NT in the modulation of Akt signaling and the potential physiological significance of Akt regulation by NT.

[Effects of organic manure on the conformation and biological availability of soil Cd].

Pot experiments were conducted to investigate the effect of organic manure on the conformation and availability of both native and added Cd in red soil and moisture soil under rice planting. Most of the added Cd existed in exchangeable form, while the native Cd existed more evenly in four forms. The organic manure did not influence apparently on the forms of native Cd, whereas influenced significantly on those of the added Cd. From tillering to mature stage, the exchangeable form of the native Cd increased, while that of the added Cd decreased. The application of organic manure could promote the uptake of Cd under the treatments without adding Cd. Under the treatments of adding Cd, the application of the organic manure could depress the uptake of Cd, and the effect of applying pig's manure was stronger than that of applying peat. There existed a significant antagonism between the accumulation of Cd and Fe in rice roots.