Objective: To investigate the current status of screen exposure among preschool children in Shanghai and its association with family screen environment, so as to provide a scientific basis for family screen management. Methods: Using a convenient sampling method, a total of 349 preschool children aged 4-6 years were selected from 36 kindergarten classes in Xuhui District and Pudong New Area in Shanghai during April to June in 2023. Demographic characteristics and family screen environment were surveyed through an online questionnaire. Screen exposure of children was assessed using a diary method, with parents recording the activities over a 7day period. Multiple Logistic regression analysis was employed to identify factors influencing childrens screen content. Results: The average daily screen exposure time for children was (61.2±40.2) minutes, with an average of (12.4±17.6) minutes spent on educational screen content, 80.8% predominantly watched noneducational screen content. The percentages of time spent on educational screen content for 4yearold boys, 4yearold girls, 5yearold boys, 5yearold girls, 6yearold boys, and 6yearold girls were 20.1%, 14.7%, 21.3%, 21.9%, 20.6%, and 26.9%, respectively. Multivariate Logistic regression showed that children aged 5yearold (OR=0.49, 95%CI=0.25-0.96) and 6yearold (OR=0.45, 95%CI=0.21-0.95) were negatively associated with more noneducational screen content (P<0.05). However, occasional (OR=2.02, 95%CI=1.09-3.75) and sometimes (OR=4.50, 95%CI=1.70-11.90) using electronic devices to calm young child when crying, as well as children using electronic devices without adult supervision (OR=1.81, 95%CI=1.01-3.24) were positively associated with more noneducational screen content (P<0.05). Conclusions Preschool children in Shanghai exhibit high exposure to noneducational screen content, and family screen environment and parentchild interaction are associated with noneducational screen exposure. Strategies for family screen management should be developed to regulate childrens screen exposure behaviors, allowing electronic devices to play a positive role in their developmental process.

Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

Cyclin-dependent kinase 9 (CDK9) activity is correlated with worse outcomes of triple-negative breast cancer (TNBC) patients. The heterodimer between CDK9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction (PPI) may offer promising avenues for selective CDK9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CˆN ligand and tested their activity against the CDK9-cyclin T1 PPI. Complex 1 bound to CDK9 via an enthalpically-driven binding mode, leading to disruption of the CDK9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDK9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.

Genomic instability remains an enabling feature of cancer and promotes malignant transformation. Alterations of DNA damage response (DDR) pathways allow genomic instability, generate neoantigens, upregulate the expression of programmed death ligand 1 (PD-L1) and interact with signaling such as cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling. Here, we review the basic knowledge of DDR pathways, mechanisms of genomic instability induced by DDR alterations, impacts of DDR alterations on immune system, and the potential applications of DDR alterations as biomarkers and therapeutic targets in cancer immunotherapy.

The human brain undergoes rapid development during childhood, with significant improvement in a wide spectrum of cognitive and affective functions. Mapping domain- and age-specific brain activity patterns has important implications for characterizing the development of children’s cognitive and affective functions. The current mainstay of brain templates is primarily derived from structural magnetic resonance imaging (MRI), and thus is not ideal for mapping children’s cognitive and affective brain development. By integrating task-dependent functional MRI data from a large sample of 250 children (aged 7 to 12) across multiple domains and the latest easy-to-use and transparent preprocessing workflow, we here created a set of age-specific brain functional activity maps across four domains: attention, executive function, emotion, and risky decision-making. Moreover, we developed a toolbox named Developmental Brain Functional Activity maps across multiple domains that enables researchers to visualize and download domain- and age-specific brain activity maps for various needs. This toolbox and maps have been released on the Neuroimaging Informatics Tools and Resources Clearinghouse website (http://www.nitrc.org/projects/dbfa). Our study provides domain- and age-specific brain activity maps for future developmental neuroimaging studies in both healthy and clinical populations.

OBJECTIVE: To study the significance of the level of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in serum and bronchoalveolar lavage fluid (BALF), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Sequential Organ Failure Assessment (SOFA) score in evaluating the conditions and prognosis of children with severe pneumonia. METHODS: A total of 76 children with severe pneumonia who were admitted from August 2017 to October 2019 were enrolled as the severe pneumonia group. According to the treatment outcome, they were divided into a non-response group with 34 children and a response group with 42 children. Ninety-four children with common pneumonia who were admitted during the same period of time were enrolled as the common pneumonia group. One hundred healthy children who underwent physical examination in the outpatient service during the same period of time were enrolled as the control group. The serum level of sTREM-1, APACHE II score, and SOFA score were measured for each group, and the level of sTREM-1 in BALF was measured for children with severe pneumonia. The correlation of the above indices with the severity and prognosis of severe pneumonia in children was analyzed. RESULTS: The severe pneumonia group had significantly higher serum sTREM-1 level, APACHEII score, and SOFA score than the common pneumonia group and the control group (P<0.05). For the children with severe pneumonia, the non-response group had significant increases in the levels of sTREM-1 in serum and BALF and SOFA score on day 7 after admission, while the response group had significant reductions in these indices, and there were significant differences between the two groups (P<0.05). Positive correlation was found between any two of serum sTREM-1, BALF sTREM-1, and SOFA score (P<0.05). APACHE II score was not correlated with serum sTREM-1, BALF sTREM-1, and SOFA score (P>0.05). CONCLUSIONS The level of sTREM-1 in serum and BALF and SOFA score can be used to evaluate the severity and prognosis of severe pneumonia in children.
APACHE ; Bronchoalveolar Lavage Fluid ; Child ; Humans ; Organ Dysfunction Scores ; Pneumonia ; Prognosis ; ROC Curve ; Sepsis ; Triggering Receptor Expressed on Myeloid Cells-1

Objective To conduct bibliometric analysis of the relevant literature in the environmental field published from 1982 to 2018 collected by the Web of Science citation database and further explore the frontier research dynamics and hotspots in the environmental field. Methods The word "oil spill*" was used as the subject term for retrieval. A knowledge map of hotspots in oil spill research was built through software VOSviewer and the clustering relations between them were explored. The frequency and relevance of the keywords in the corresponding literature were obtained by the matrix of keywords built through the Thomson Data Analyzer （TDA） software. Results The four main research hotspots of marine oil spill pollution were oil spill numerical simulation and model prediction, oil spill exposure toxicity and risk assessment, oil spill component and source analysis and oil spill pollution characteristics and treatment. Conclusion The study analyzes the main content of the four research hotspots and the current research progress and provides scientific basis for further understanding of the mechanism of marine oil spill occurrence, migration and transformation, implementation of oil spill treatment and repair as well as more accurate assessment of eco-environment damage.
Accidents ; Bibliometrics ; Petroleum Pollution/adverse effects* ; Risk Assessment ; Software

PURPOSE: Little is known about combination of the circulating Epstein-Barr viral (EBV) DNA and tumor volume in prognosis of stage II nasopharyngeal carcinoma (NPC) patients in the intensity modulated radiotherapy (IMRT) era. We conducted this cohort study to evaluate the prognostic values of combining these two factors. MATERIALS AND METHODS: By Kaplan-Meier, we compare the differences of survival curves between 385 patients with different EBV DNA or tumor volume levels, or with the combination of two biomarkers mentioned above. RESULTS: Gross tumor volume of cervical lymph nodes (GTVnd, p < 0.001) and total tumor volume (GTVtotal, p < 0.001) were both closely related to pretreatment EBV DNA, while gross tumor volume of nasopharynx (GTVnx, p=0.047) was weakly related to EBV DNA. EBV DNA was significantly correlated with progress-free survival (PFS, p=0.005), locoregional-free survival (LRFS, p=0.039), and distant metastasis-free survival (DMFS, p=0.017), while GTVtotal, regardless of GTVnx and GTVnd, had a significant correlation with PFS and LRFS. The p-values of GTVtotal for PFS and LRFS were 0.008 and 0.001, respectively. According to GTVtotal and pretreatment EBV DNA level, patients were divided into a low-risk group (EBV DNA 0 copy/mL, GTVtotal < 30 cm³; EBV DNA 0 copy/mL, GTVtotal ≥ 30 cm³; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm³) and a high-risk group (EBV DNA > 0 copy/mL, GTVtotal ≥ 30 cm³). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant. CONCLUSION: Pretreatment plasma EBV DNA and tumor volume were both closely correlated with prognosis of stage II NPC patients in the IMRT era. Combination of EBV DNA and tumor volume can refine prognosis and indicate for clinical therapy.
Biomarkers ; Cohort Studies* ; DNA* ; Herpesvirus 4, Human* ; Humans ; Lymph Nodes ; Nasopharynx ; Plasma ; Prognosis ; Radiotherapy* ; Tumor Burden*

BACKGROUND:The study aimed to compare the therapeutic effect of recombinant tissue plasminogen activator (rt-PA) on the onset of acute cerebral infarction (ACI) at different time points of the first 6 hours.METHODS:A retrospective analysis was conducted in 74 patients who received rt-PA thrombolysis treatment within 4.5 hours after ACI and another 15 patients who received rt-PA thrombolysis treatment between 4.5-6 hours after ACI.RESULTS:National Institute of Health Stroke Scale (NIHSS) scores were statistically decreased in both groups (P>0.05) at 24 hours and 7 days after ACI. There was no significant difference in modified ranking scores and mortality at 90 days after the treatment between the two groups (P>0.05).CONCLUSIONS:The therapeutic effect and mortality of rt-PA treatment in patients with ACI between 4.5-6 hours after the onset of the disease were similar to those in patients who received rt-PA within 4.5 hours after the onset of this disease. Therefore, intravenous thrombolytic therapy for ACI within 4.5-6 hours after ACI was effective and safe.

OBJECTIVETo investigate the role of dynactin 1 (Dctn1) in the process of mouse spermiogenesis.

METHODSWestern blot and indirect immunofluorescence were used to analyze the expression and location of Dctn1 in the mouse testis and spermatozoa. The highest efficiency of small interference RNA (siRNA) was verified by GC2-spd cell line in vitro and in vivo studies, respectively. Dctn1 siRNA mixed with the indicator (0.4% trypan blue) was injected into the seminiferous tubules of 3-week-old ICR mice through rete testis microinjection, and negative control siRNA injected into the control testes. The normal group included 3-week-old ICR mice that did not receive any treatment. Spermatozoa were collected from the cauda epididymis 3 weeks after siRNA injection for morphological analysis.

RESULTSDctn1 was mainly localized in the tail of spermatozoa. After interference, the sperm tail abnormality in the Dctn1 siRNA group was (23.57 +/- 0.55)%, significantly higher than (12.35 +/- 2.29)% in the control (P < 0.01, n = 3), and it was (3.37 +/- 0.69)% in the normal group.

CONCLUSIONDctn1 plays an important role in mouse spermiogenesis, and mainly affects the formation of the tail of spermatozoa.

Animals ; Dynactin Complex ; Male ; Mice ; Mice, Inbred ICR ; Microinjections ; Microtubule-Associated Proteins ; genetics ; metabolism ; RNA, Small Interfering ; Rete Testis ; metabolism ; Seminiferous Tubules ; metabolism ; Sperm Count ; Sperm Motility ; Spermatogenesis ; Spermatozoa ; metabolism ; Testis ; metabolism