Objective: To identify the core symptoms and bridge symptoms in the network structure among adolescents bullying victimization, anxiety and depressive symptoms, and to explore the interrelationships among these three variables, so as to provide a basis for the precise prevention of bullying behaviors and the improvement of adolescents psychological health conditions. Methods: From October to November 2023, a stratified cluster random sampling method was employed to select 4 759 middle and high school students from four cities in Guangxi: Beihai, Guigang, Hechi, and Laibin. The Chinese version of the Olweus Bully/Victim Questionnaire (OBVQ) was used to assess bullying victimization among adolescents, while the Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9) were utilized to assess anxiety and depressive symptoms, respectively. The Bootnet package (version 1.6) in R software (version 4.4.1) was used to construct a network structure and analyze the associations between bullying victimization, anxiety symptoms and depressive symptoms among adolescents. Results: The reporting rates of depressive symptoms, anxiety symptoms, and bullying victimization among adolescents in Guangxi were 24.67%, 16.33%, and 16.58%, respectively. Network analysis revealed that the node with the highest expected influence was "property being taken or damaged", with a standardized expected influence (EI) index of 2.09. The top two nodes in terms of bridge expected influence were "thoughts of self harm or suicide" and "irritability", with standardized bridge expected influence (BEI) indices of 2.15 and 1.27, respectively. The stronger associations were observed between the node "property being taken or damaged" and the nodes "physical attacks such as hitting, kicking, pushing, or shoving" and "ridiculed due to accent", with edge weights of 0.43 and 0.35, respectively. Conclusion Targeting preventive measures against the symptoms with the highest expected influence and bridge expected influence in the network of bullying victimization, anxiety and depressive symptoms among adolescents may be an effective approach to reduce the negative impact of bullying victimization, anxiety and depressive symptoms on adolescents.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Objective: To investigate the exposure to television advertising of sugar sweetened beverages and the use of persuasive marketing techniques among children and adolescents in Beijing, so as to provide evidence for reduing childrens intake of sugar sweetened beverages. Methods: From October 19, 2020 to November 16, 2021, 32 days were randomly selected. The top four popular channels of children and adolescents aged 3-18 years were defined. Each channel was monitored from 6:00:00 to 23:59:59 for each date. A total of 2 304 h was recorded. Advertisements involving sugar sweetened beverages broadcast before, during or after the program were included. The frequency and the use of persuasive marketing techniques were analyzed. Results: A total of 1 237 advertisements for sugar sweetened beverages were included, of which 50.93% were dairy beverages, 28.38% were teabased beverages, and 19.48% were vegetable protein beverages. The average frequency of sugar sweetened beverages advertisements on every channel was (0.62±1.29)piece/h. The frequency of sugar sweetened beverages advertisements on every local channel [(1.04±1.35)piece/h] and childrens channel [(1.11±1.61)piece/h] was separately higher than every national channel [(0.48±1.24)piece/h] and general channel [(0.12±0.48)piece/h] (t=-14.05, 31.64, P<0.01). There were seasonal differences in television advertising of sugar sweetened beverages, and were more frequent during lunch and dinner times. The most frequently used persuasive marketing techniques were "images of children" (74.54%), "nutritional message" (61.76%), "product composition details" (58.61%), "nutrition claim" (57.24%), and "nutrition function claim or other function claim" (53.11%). Conclusions Children and adolescents are often exposed to television advertisement of sugar sweetened beverages on childrens channels and during meal times. There is an urgent need to formulate relevant policies to regulate the marketing of sugar sweetened beverages advertisement and reduce children and adolescents intake.

Objective:To explore the clinical effect and safety of extended debridement combined with BAM bone-induced artificial bone repair in the treatment of Cierny-Mader type IV osteomyelitis.Methods:From January 2021 to December 2022, 106 patients with Cierny-Mader type IV osteomyelitis who were treated with allogeneic bone mixed with autologous bone in department of orthopedics of Sichuan Orthopedic Hospital were retrospectively selected as the study subjects. Among them, 54 patients who were combined with BAM bone-induced artificial bone mixed with autologous bone repair were included in observation group, and 52 patients who only received allogeneic bone mixed with autologous bone repair were enrolled as control group. The clinical related indicators (bone healing time, fracture healing time), clinical efficacy (Johner-Wruh tibial shaft fracture evaluation standard) at 1 year after surgery, inflammatory factors (white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin), limb function (American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS-AH)) and bone healing degree before surgery and at 1 year after surgery were compared between both groups. Chi-square test was used to compare the enumeration data between groups, and the independent sample t test was performed to compare the measurement data with normal distribution between groups.Results:At 1 year after surgery, the clinical healing indicators of bone healing time and fracture healing time and inflammatory factors such as WBC, ESR, CRP and procalcitonin with (21.19±2.16) weeks, (11.35±1.01) weeks, (6.15±0.73)×10 9/L, (9.10±1.05) mm/h, (8.09±1.11) mg/L and (0.05±0.01) μg/L in observation group were significantly shorter or lower than (24.32±2.39) weeks, (12.29±1.27) weeks, (7.86±0.89)×10 9/L, (10.10±1.32) mm/h, (9.26±1.23) mg/L and (0.08±0.01) μg/L in control group,and the differences were statistically significant ( t values were 7.08, 4.23, 10.83, 4.33, 5.15, and 15.44, respectively; all P<0.001). The clinical effective rate (85.19%(46/54)), AOFAS-AH score((84.83±12.17) points) and bone healing probability (94.44%(51/54)) were higher than (67.31%(35/52)), (79.17±11.25) points and 80.77% (42/52) in control group,with statistically significant differences (statistical values were χ2=4.70, t=2.48, and χ2=4.60, respectively; P values were 0.030, 0.015, and 0.032, respectively). Conclusion:Expanded debridement combined with BAM bone-induced artificial bone repair can effectively promote the bone tissue healing in patients with Cierny-Mader type IV osteomyelitis, relieve the inflammatory response, and improve the limb function, and it has good clinical efficacy and high safety.

Objective: To examine the exposure to television advertising of unhealthy food among children and adolescents in Beijing, in order to provide a basis for the formulation of marketing management policies with unhealthy food. Methods: Four weekdays and four weekend days were randomly selected during October 19, 2020 to January 17, 2021, excluding holidays and school holidays. The top five popular channels of children and adolescents aged 3 to 18 years old were selected. A total of 720 hours was included for coding and analysis. World Health Organization Nutrient Profile Model for the Western Pacific Region was used to classify food and assess the health level. Results: A total of 13 864 advertisings (ads) was monitored, 38.8% (5 376) of which were food ads. Furthermore, 49.9% (2 680) of food ads were unhealthy food ads, with a frequency of 2.00 per hour per channel. The top five most frequent food ads were infant formula for 12-36 months (26.7%), cheese (16.7%), savory snacks (12.2%), milk drinks (10.5%) and chocolate and candy (6.0%). The most frequently used marketing strategies for unhealthy food ads were brand benefit claims (96.8%) and promotional characters (67.9%). Conclusion Children and adolescents in Beijing are highly exposed to TV marketing of unhealthy foods. Marketing strategies such as brand benefit claims and promotional characters are employed to boost the impact of unhealthy food ads. There is an urgent need to introduce relevant policies to regulate TV marketing of unhealthy foods.

Acetaminophen (APAP) overdose is a major cause of liver injury. Neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ubiquitin ligase that has been implicated in the pathogenesis of numerous liver diseases; however, its role in APAP-induced liver injury (AILI) is unclear. Thus, this study aimed to investigate the role of NEDD4-1 in the pathogenesis of AILI. We found that NEDD4-1 was dramatically downregulated in response to APAP treatment in mouse livers and isolated mouse hepatocytes. Hepatocyte-specific NEDD4-1 knockout exacerbated APAP-induced mitochondrial damage and the resultant hepatocyte necrosis and liver injury, while hepatocyte-specific NEDD4-1 overexpression mitigated these pathological events both in vivo and in vitro. Additionally, hepatocyte NEDD4-1 deficiency led to marked accumulation of voltage-dependent anion channel 1 (VDAC1) and increased VDAC1 oligomerization. Furthermore, VDAC1 knockdown alleviated AILI and weakened the exacerbation of AILI caused by hepatocyte NEDD4-1 deficiency. Mechanistically, NEDD4-1 was found to interact with the PPTY motif of VDAC1 through its WW domain and regulate K48-linked ubiquitination and degradation of VDAC1. Our present study indicates that NEDD4-1 is a suppressor of AILI and functions by regulating the degradation of VDAC1.

Objective:To explore the characteristics of self-referential network (SRN) functional connectivity in subjective cognitive decline (SCD) patients with normal and impaired metacognition.Methods:Seventy-one subjects were selected from Alzheimer's Disease Neuroimaging Initiative (ADNI) database, with 25 cognitively normal controls and 46 SCD patients. The metacognitive level of SCD patients was assessed by Everyday Cognition Scale (ECog), and then, they were divided into a metacognitively normal group ( n=25, metacognitive scores>-0.074) and a metacognitively impaired group ( n=21, metacognitive scores≤-0.074). Results of Geriatric Depression Scale (GDS), Montreal Cognitive Scale (MoCA), Mini‐Mental State Examination (MMSE), Rey Auditory Word Learning Test (RAVLT), Logical Memory Scale, expressions of pathological markers (cerebrospinal fluid β-amyloid protein [Aβ], total tau protein [t-tau] and phosphorylated tau protein [p-tau]), brain glucose metabolism, and functional magnetic resonance imaging (fMRI) were collected and compared among the 3 groups. Independent component analysis (ICA) was used to extract SRN and analyze the different brain regions among the 3 groups; Pearson correlation was used to analyze the correlations of SRN functional connectivity changes with cognitive scales and pathological markers. Results:No significant differences in demographic characteristics (age and gender), scores of GDS, MoCA and MMSE, or levels of Aβ, t-tau, p-tau and brain glucose metabolism were noted among the 3 groups ( P>0.05). The metacognitive scores in metacognitively impaired group were significantly lower than those in metacognitively normal group and cognitively normal controls ( P<0.05). Significant difference in the functional connectivity of bilateral anterior cingulate gyrus and bilateral orbitofrontal cortex was noted among the 3 groups (TFCE-FWE correction, P<0.01, voxel>100); compared with the cognitively normal controls, the metacognitively impaired group showed significantly decreased functional connectivity of bilateral orbitofrontal cortex, while the metacognitively normal group showed enhanced functional connectivity of bilateral orbitofrontal cortex (TFCE-FWE correction, P<0.01, voxel>100); compared with the metacognitively normal group, the metacognitively impaired group had statistically decreased functional connectivity of bilateral orbitofrontal cortex (TFCE-FWE correction, P<0.01, voxel>100). Further correlation analysis showed that difference value of functional connectivity of bilateral orbitofrontal cortex between metacognitively impaired group and cognitively normal controls was negatively correlated with RAVLT-immediate scores ( r=-0.445, P=0.043); difference value of functional connectivity of bilateral orbitofrontal cortex between metacognitively impaired group and metacognitively normal group was negatively correlated with RAVLT-immediate scores ( r=-0.463, P=0.034). Conclusion:SCD patients with different metacognitive levels have characteristic SRN functional connectivity changes; impaired metacognition may be an early feature of Alzheimer's disease.

Objective To establish a novel rat model of chronic skeletal muscle composite injury in the lumbar region,to explore its mechanism and treatment method in depth.Methods Twenty-eight SD rats were randomly divided into control group(n = 10),Hitting injury model(HIM)group(n = 9),Composite damage model(CDM)group(n = 9)(vertical blow combined with forced prolonged sitting).Open field test,HE staining and PCR sequencing were performed 3 days after modeling.Results The open field distance of rats in HIM group was significantly shorter than that in the CDM group,and both groups had shorter distances than the control group.HE staining showed multiple muscle fiber breaks,significant widening of muscle gaps,uneven distribution of muscle nuclei,and visible congestion in the model group of simple blow injury;In the CDM group,muscle fibers were ruptured,the muscle gaps were slightly widened,and inflammatory cell infiltration was observed between the muscles,especially around the muscle fiber breakage,with muscle fiber nuclei gathering.A volcano plot of the sequencing result suggested significant differences in the Pf4 gene.GO analysis of muscle tissue in model group rats showed upregulation of oxygen binding and carrier activity pathways.Conclusions This study attempted to establish a composite skeletal muscle injury model to study the pathological changes of chronic skeletal muscle injury in the low back pain and evaluate the efficacy of treatment method.It has practical application value in animal experiments for chronic non-specific low back pain.

Preoperative sleep loss can amplify post-operative mechanical hyperalgesia. However, the underlying mechanisms are still largely unknown. In the current study, rats were randomly allocated to a control group and an acute sleep deprivation (ASD) group which experienced 6 h ASD before surgery. Then the variations in cerebral function and activity were investigated with multi-modal techniques, such as nuclear magnetic resonance, functional magnetic resonance imaging, c-Fos immunofluorescence, and electrophysiology. The results indicated that ASD induced hyperalgesia, and the metabolic kinetics were remarkably decreased in the striatum and midbrain. The functional connectivity (FC) between the nucleus accumbens (NAc, a subregion of the ventral striatum) and the ventrolateral periaqueductal gray (vLPAG) was significantly reduced, and the c-Fos expression in the NAc and the vLPAG was suppressed. Furthermore, the electrophysiological recordings demonstrated that both the neuronal activity in the NAc and the vLPAG, and the coherence of the NAc-vLPAG were suppressed in both resting and task states. This study showed that neuronal activity in the NAc and the vLPAG were weakened and the FC between the NAc and the vLPAG was also suppressed in rats with ASD-induced hyperalgesia. This study highlights the importance of preoperative sleep management for surgical patients.
Rats ; Animals ; Hyperalgesia/metabolism* ; Sleep Deprivation/metabolism* ; Rats, Sprague-Dawley ; Periaqueductal Gray/pathology* ; Proto-Oncogene Proteins c-fos/metabolism* ; Pain, Postoperative/pathology*

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.