Objective: To understand the impact of childhood trauma on psychological distress among upper grade elemetary school students, and to explore the mediating role of leisure activities in the relationship, so as to provide a basis for developing mental health intervention strategies. Methods: From August to November 2024, a combination of convenience sampling and stratified cluster random sampling was employed to recruit 1 373 fourth to sixth grade students from four primary schools in Harbin. The Childhood Trauma Questionnaire(CTQ), a self designed leisure activity scale (including active and passive leisure activities), and the Kessler Psychological Distress Scale (K10) were used to assess childhood trauma experiences, leisure activities, and levels of psychological distress. Spearman correlation analysis and linear regression analysis were conducted to explore the relationships among childhood trauma, leisure types, leisure time, and psychological distress. Based on the mediation analysis framework proposed by Hayes (Model 4), the mediating role of leisure types in the relationship between childhood trauma and psychological distress was examined. Results: Totally 19.1% of the upper elemetary school students exhibited psychological distress, while 30.2% had experienced childhood trauma. During school days, 64.6% of the students were reported of having leisure time concentrated between 1 and 5 hours per day, whereas 67.4% reported leisure time exceeding 5 hours per day on weekends. After controlling for potential demographic confounders such as gender, grade, ethnicity, household registration, being an only child, parents educational level, co residence, and whether parents are first time married,linear regression analysis showed that childhood trauma experience had positive predictive effect on psychological distress in upper primary school students( β =0.20, P <0.01). Leisure time showed no statistically significant association with psychological distress, both on school days ( β =-0.58 to -0.56) and weekends ( β =0.26- 0.98 )(all P >0.05). Active leisure activities were negatively associated with psychological distress ( β =-0.20), while passive leisure activities were positively associated with psychological distress ( β =0.29)(both P <0.01). Leisure type partially mediated the relationship between childhood trauma and psychological distress, accounting for 11.7% of the indirect effect. Conclusion Childhood trauma experiences positively predict psychological distress in upper elementary school students, and affect psychological distress through active leisure and passive leisure.

Tauopathies, including Alzheimer's disease (AD), are a series of neurodegenerative diseases characterized by pathological accumulation of the microtubule-associated protein tau. Since the abnormal modification and deposition of tau in nerve cells are crucial for tauopathy etiology, methods for reducing tau levels, such as promoting tau degradation, may become effective strategies for disease treatment. Herein, we identified that sorafenib significantly reduced total tau and phosphorylated tau levels through screening FDA-approved drugs. We showed that sorafenib treatment attenuated cognitive deficits and tau pathologies in PS19 tauopathy model mice. Mechanistically, we found that sorafenib inhibited multiple kinases involved in tau phosphorylation and promoted autophagy. Importantly, we further demonstrated that sorafenib also promoted the expression of the E3 ubiquitin ligase FBXW7, which could bind tau and mediate tau degradation through the ubiquitin-proteasome pathway. Finally, we showed that FBXW7 expression decreased in the brains of AD patients and tauopathy model mice, and that overexpression of FBXW7 in the hippocampus attenuated cognitive deficits and tau pathologies in PS19 mice. These results suggest that sorafenib may be a promising treatment option for tauopathies by promoting tau degradation and reducing tau phosphorylation, and that targeting FBXW7 could also serve as an alternative therapeutic strategy for tauopathies.

Objective:To evaluate the efficacy of bevacizumab in reducing dyspnea, avoiding tracheostomy, and assessing the overall safety and effectiveness of the treatment in patients with juvenile-onset recurrent respiratory papillomatosis (JORRP).Methods:This study included 19 patients with JORRP treated with Bevacizumab at the Department of Otolaryngology-Head and Neck Surgery, BenQ Medical Center, from March 2022 to June 2024. The age of patients ranged from 1.0 to 27.0 years (10.47±8.45 years), with age at onset ranging from 0.5 to 15.0 years (3.66±3.70 years). The cohort included 11 males and 8 females. Bevacizumab was administered intravenously at a dose of 10 mg/kg every three weeks for three sessions. Efficacy was evaluated by comparing the standardized lesion volume pre-and post-treatment, with statistical analysis performed using R software (4.3.1).Results:Among the 19 patients, 11 presented with dyspnea before treatment. All patients experienced varying degrees of dyspnea relief within 72 hours following the initial treatment, and only one patient had mild dyspnea by the second treatment session three weeks later. The average reduction rates at 24 and 48 hours post-initia treatment were 25.75% and 47.16%, respectively. Following three treatment cycles, the average cumulative reduction rate was 67.47%, significantly higher than after the first treatment ( Z=3.38, P=0.002). Throughout the treatment period, no adverse events that of grade 2 or higher were noted. Conclusions:Bevacizumab can rapidly alleviate dyspnea symptoms and significantly reduce lesion volume in JORRP patients, exhibiting satisfactory overall safety and effectiveness. However additional large-scale prospective studies are warranted to validate its long-term safety and efficacy.

Objective: To explore the impact of sleep quality, experience of childhood maltreatment, and their interaction on depressive symptoms among middle school students, so as to provide the reference for early intervention of depressive symptoms among middle school students. Methods: From September to December 2023, a questionnaire survey was conducted among 1 231 students from two secondary schools in Harbin, Heilongjiang Province by a convenient sampling method. The survey included general demographic information, Childhood Trauma Questionnaire Short Form, Pittsburgh Sleep Quality Index and Short Version of Center for Epidemiological Studies Depression Scale. The Chi square test was used to analyze the differences in depressive symptom, sleep quality and childhood maltreatment among students with different demographic characteristics. Correlation analysis was conducted using Logistic regression, and interaction analysis was performed by both additive and multiplicative interaction models. Results: The detection rate of depressive symptoms among middle school students was 22.7%, and the rate for high school students (35.2%) was significantly higher than that for middle school students (17.0%) ( χ 2=50.35, P <0.01). The detection rates of depressive symptoms among middle school students with a history of childhood maltreatment and poor sleep quality were 45.8% and 44.0%, respectively. Multivariate Logistic regression analysis showed that compared to students without a history of childhood maltreatment, students with a history of childhood maltreatment had a higher risk of depressive symptoms ( OR =4.49，95% CI =3.31~ 6.09 , P <0.01);students with poor sleep quality had a higher risk of depressive symptoms than students with good sleep quality ( OR = 5.99，95% CI =4.37~8.22, P <0.01).The interaction results showed that the presence of childhood maltreatment and poor sleep quality had an additive interaction on the occurrence of depression in middle school students. Compared with students without childhood maltreatment and having good sleep quality, students with childhood maltreatment and poor sleep quality had a 22.49 times higher risk of developing depression ( OR =22.49，95% CI =14.22~35.59, P <0.01). Conclusion Depressive symptoms among middle school students are associated with childhood maltreatment and poor sleep quality, and there is an additive interaction between childhood maltreatment and poor sleep quality on the impact of depressive symptoms.

An 85-year-old male patient received immunotherapy with toripalimab (240 mg by intravenous infusion on day 1, 21 days as one treatment cycle). After one week of the first medication, the patient experienced fatigue, poor appetite, weight loss, gradually developed mild ptosis of the right eyelid, shortness of breath and palpitations after activity, which were progressively aggravated. The patient also developed unclear speech, choking on water, and difficulty breathing. Laboratory tests showed alanine aminotransferase (ALT) 93 U/L, aspartate aminotransferase (AST) 171 U/L, creatine kinase (CK) 2 982 U/L, creatine kinase isoenzyme (CK-MB) 110 U/L, lactate dehydrogenase (LDH) 603 U/L, and high-sensitivity troponin T (hs-cTnT) 243 ng/L. All indicators of thyroid function were abnormal. Based on results of the laboratory tests, neurophysiological examination, and electrocardiogram examination, combined with the patient′s clinical symptoms, immune-mediated hepatitis of grade 2, immune-mediated myocarditis of grade 3, myasthenia gravis of grade 3, immune-mediated myositis of grade 2, and thyroid dysfunction of grade 1 were diagnosed, which was considered to be induced by toripalimab. Toripalimab was stopped. After treatments with glucocorticoids, liver-protective drugs, and symptomatic treatments, above-mentioned indicators showed a downward trend. After 27 days of treatments, the patient′s clinical symptoms were improved significantly. Laboratory tests showed ALT 123 U/L, AST 68 U/L, CK 116 U/L, CK-MB 42 U/L, LDH 305 U/L. The thyroid function indicators were all normal. After 57 days of treatments, above symptoms in the patient basically disappeared, and laboratory indicators tended to be normal.

Objective To analyze the characteristics of brain functional networks in patients with post-stroke aphasia(PSA)during a Chinese word-picture matching task.Methods A total of 18 PSA patients in Dongzhimen Hospital from January,2018 to December,2021 were enrolled as PSA group,and nine healthy controls matched for sex,age and education were included as the control group.The Chinese Rehabilitation Research Center Aphasia Examination(CRRCAE)and task-state electroencephalogram(EEG)data based on a Chinese word-picture matching paradigm were collected.Source-space reconstruction was applied to EEG signals to construct functional connectivity matrices.Graph-theoretical analysis was used to com-pute global network properties,and network-based statistics were used to identify subnetwork differences be-tween groups.Correlations between global network properties and CRRCAE subscales were further analyzed.Results The global properties of each frequency band were higher in the control group(unmatched)than in PSA group and the control group(matched)(P<0.01).Subnetworks connections enhanced in the alpha band in the frontal,temporal,parietal,occipital lobes and limbic system(23 nodes,31 edges,P<0.05),and weakened connections in the frontal,temporal,limbic system and basal ganglia(20 nodes,26 edges,P<0.01)in PSA group;in the beta band,subnetwork connections enhanced in the frontal,temporal lobes,basal ganglia and limbic system(15 nodes,23 edges,P<0.01);in the theta band,subnetwork connections weakened in the left frontal and temporal lobes(10 nodes,11 edges,P<0.05),and enhanced in the right frontal and temporal lobes(7 nodes,7 edges,P<0.05).Under the matched condition,the global properties of the alpha and beta bands in PSA group were positive-ly correlated with reading(r=0.511 to 0.650,all P<0.05),and the local efficiency and average clustering coeffi-cient of the theta band were negatively correlated with repetition(r=-0.500 to-0.505,all P<0.05);under the unmatched condition,the local efficiency and average clustering coefficient of the alpha and beta bands in PSA group were positively correlated with reading(r=0.522 to 0.642,all P<0.05),and the global efficiency and lo-cal efficiency of the alpha band were positively correlated with auditory comprehension(r=0.486 to 0.496,all P<0.05).The comparison between the task state and the resting state further revealed that compensatory connec-tion enhanced in the alpha band in the frontal lobe and limbic system(6 nodes,5 edges,P<0.05)and in the beta band in the frontal,temporal,parietal,occipital lobes and limbic system(38 nodes,52 edges,P<0.01)in PSA pa-tients.Conclusion The core network damage characteristics of PSA patients are abnormally decreased global properties across multiple frequency bands and frequency-specific abnormal network reorganization,suggesting the overall brain network efficiency decline coexists with local compensation.This provides an objective basis for the neuroelec-trophysiological evaluation and targeted intervention of PSA.

Objective To analyze the characteristics of brain functional networks in patients with post-stroke aphasia(PSA)during a Chinese word-picture matching task.Methods A total of 18 PSA patients in Dongzhimen Hospital from January,2018 to December,2021 were enrolled as PSA group,and nine healthy controls matched for sex,age and education were included as the control group.The Chinese Rehabilitation Research Center Aphasia Examination(CRRCAE)and task-state electroencephalogram(EEG)data based on a Chinese word-picture matching paradigm were collected.Source-space reconstruction was applied to EEG signals to construct functional connectivity matrices.Graph-theoretical analysis was used to com-pute global network properties,and network-based statistics were used to identify subnetwork differences be-tween groups.Correlations between global network properties and CRRCAE subscales were further analyzed.Results The global properties of each frequency band were higher in the control group(unmatched)than in PSA group and the control group(matched)(P<0.01).Subnetworks connections enhanced in the alpha band in the frontal,temporal,parietal,occipital lobes and limbic system(23 nodes,31 edges,P<0.05),and weakened connections in the frontal,temporal,limbic system and basal ganglia(20 nodes,26 edges,P<0.01)in PSA group;in the beta band,subnetwork connections enhanced in the frontal,temporal lobes,basal ganglia and limbic system(15 nodes,23 edges,P<0.01);in the theta band,subnetwork connections weakened in the left frontal and temporal lobes(10 nodes,11 edges,P<0.05),and enhanced in the right frontal and temporal lobes(7 nodes,7 edges,P<0.05).Under the matched condition,the global properties of the alpha and beta bands in PSA group were positive-ly correlated with reading(r=0.511 to 0.650,all P<0.05),and the local efficiency and average clustering coeffi-cient of the theta band were negatively correlated with repetition(r=-0.500 to-0.505,all P<0.05);under the unmatched condition,the local efficiency and average clustering coefficient of the alpha and beta bands in PSA group were positively correlated with reading(r=0.522 to 0.642,all P<0.05),and the global efficiency and lo-cal efficiency of the alpha band were positively correlated with auditory comprehension(r=0.486 to 0.496,all P<0.05).The comparison between the task state and the resting state further revealed that compensatory connec-tion enhanced in the alpha band in the frontal lobe and limbic system(6 nodes,5 edges,P<0.05)and in the beta band in the frontal,temporal,parietal,occipital lobes and limbic system(38 nodes,52 edges,P<0.01)in PSA pa-tients.Conclusion The core network damage characteristics of PSA patients are abnormally decreased global properties across multiple frequency bands and frequency-specific abnormal network reorganization,suggesting the overall brain network efficiency decline coexists with local compensation.This provides an objective basis for the neuroelec-trophysiological evaluation and targeted intervention of PSA.

An 85-year-old male patient received immunotherapy with toripalimab (240 mg by intravenous infusion on day 1, 21 days as one treatment cycle). After one week of the first medication, the patient experienced fatigue, poor appetite, weight loss, gradually developed mild ptosis of the right eyelid, shortness of breath and palpitations after activity, which were progressively aggravated. The patient also developed unclear speech, choking on water, and difficulty breathing. Laboratory tests showed alanine aminotransferase (ALT) 93 U/L, aspartate aminotransferase (AST) 171 U/L, creatine kinase (CK) 2 982 U/L, creatine kinase isoenzyme (CK-MB) 110 U/L, lactate dehydrogenase (LDH) 603 U/L, and high-sensitivity troponin T (hs-cTnT) 243 ng/L. All indicators of thyroid function were abnormal. Based on results of the laboratory tests, neurophysiological examination, and electrocardiogram examination, combined with the patient′s clinical symptoms, immune-mediated hepatitis of grade 2, immune-mediated myocarditis of grade 3, myasthenia gravis of grade 3, immune-mediated myositis of grade 2, and thyroid dysfunction of grade 1 were diagnosed, which was considered to be induced by toripalimab. Toripalimab was stopped. After treatments with glucocorticoids, liver-protective drugs, and symptomatic treatments, above-mentioned indicators showed a downward trend. After 27 days of treatments, the patient′s clinical symptoms were improved significantly. Laboratory tests showed ALT 123 U/L, AST 68 U/L, CK 116 U/L, CK-MB 42 U/L, LDH 305 U/L. The thyroid function indicators were all normal. After 57 days of treatments, above symptoms in the patient basically disappeared, and laboratory indicators tended to be normal.

Objective:To evaluate the efficacy of bevacizumab in reducing dyspnea, avoiding tracheostomy, and assessing the overall safety and effectiveness of the treatment in patients with juvenile-onset recurrent respiratory papillomatosis (JORRP).Methods:This study included 19 patients with JORRP treated with Bevacizumab at the Department of Otolaryngology-Head and Neck Surgery, BenQ Medical Center, from March 2022 to June 2024. The age of patients ranged from 1.0 to 27.0 years (10.47±8.45 years), with age at onset ranging from 0.5 to 15.0 years (3.66±3.70 years). The cohort included 11 males and 8 females. Bevacizumab was administered intravenously at a dose of 10 mg/kg every three weeks for three sessions. Efficacy was evaluated by comparing the standardized lesion volume pre-and post-treatment, with statistical analysis performed using R software (4.3.1).Results:Among the 19 patients, 11 presented with dyspnea before treatment. All patients experienced varying degrees of dyspnea relief within 72 hours following the initial treatment, and only one patient had mild dyspnea by the second treatment session three weeks later. The average reduction rates at 24 and 48 hours post-initia treatment were 25.75% and 47.16%, respectively. Following three treatment cycles, the average cumulative reduction rate was 67.47%, significantly higher than after the first treatment ( Z=3.38, P=0.002). Throughout the treatment period, no adverse events that of grade 2 or higher were noted. Conclusions:Bevacizumab can rapidly alleviate dyspnea symptoms and significantly reduce lesion volume in JORRP patients, exhibiting satisfactory overall safety and effectiveness. However additional large-scale prospective studies are warranted to validate its long-term safety and efficacy.