Abstract Adverse childhood experiences (ACEs) exposure is a pressing and severe global public health issue. Children and adolescents exposed to multiple ACEs are highly susceptible to toxic stress and impaired physiological functioning, which significantly jeopardize their physical and mental health. Effective prevention and intervention strategies can reduce the prevalence of ACEs and mitigate their severe impacts, thereby minimizing the long term detrimental consequences on future outcomes. The review provides a comprehensive review of intervention strategies across four dimensions: individual, family, school, and public services/policy, so as to establish a theoretical foundation for implementing effective interventions for children and adolescents exposed to adverse childhood experiences.

BACKGROUND: Ferroptosis-related genes play a crucial role in regulating intracellular iron homeostasis and lipid peroxidation, and they are involved in the regulation of tumor growth and drug resistance. The expression of ferroptosis-related genes in tumor tissues can be used to predict patients' future survival times, aiding doctors and patients in anticipating disease progression. Based on the sequencing data of lung adenocarcinoma (LUAD) patients from The Cancer Genome Atlas (TCGA) database, this study identified genes involved in the regulation of ferroptosis, constructed a prognostic model, and evaluated the predictive performance of the model. METHODS: A total of 1467 ferroptosis-related genes were obtained from the GeneCards database. Gene expression profiles and clinical data from 541 LUAD patients were collected from the TCGA database. The expression data of all ferroptosis-related genes were extracted, and differentially expressed genes were identified using R software. Survival analysis was performed on these genes to screen for those with prognostic value. Subsequently, a prognostic risk scoring model for ferroptosis-related genes was constructed using LASSO regression model. Each LUAD patient sample was scored, and the patients were divided into high-risk and low-risk groups based on the median score. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated. Kaplan-Meier survival curves were generated to assess model performance, followed by validation in an external dataset. Finally, univariate and multivariate Cox regression analyses were conducted to evaluate the independent prognostic value and clinical relevance of the model. RESULTS: Through survival analysis, 121 ferroptosis-related genes associated with prognosis were initially identified. Based on this, a LUAD prognostic risk scoring model was constructed using 12 ferroptosis-related genes (ALG3, C1QTNF6, CCT6A, GLS2, KRT6A, LDHA, NUPR1, OGFRP1, PCSK9, TRIM6, IGF2BP1 and MIR31HG). The results indicated that patients in the high-risk group had significantly shorter survival time than those in the low-risk group (P<0.001), and the model demonstrated good predictive performance in both the training set (1-yr AUC=0.721) and the external validation set (1-yr AUC=0.768). Risk scores were significantly associated with the prognosis of LUAD patients in both univariate and multivariate Cox regression analyses (P<0.001), suggesting that this score is an important prognostic factor for LUAD patients. CONCLUSIONS This study successfully established a LUAD risk scoring model composed of 12 ferroptosis-related genes. In the future, this model is expected to be used in conjunction with the tumor-node-metastasis (TNM) staging system for prognostic predictions in LUAD patients.
Humans ; Ferroptosis/genetics* ; Prognosis ; Adenocarcinoma of Lung/pathology* ; Lung Neoplasms/pathology* ; Male ; Female ; Gene Expression Regulation, Neoplastic ; Middle Aged ; ROC Curve

ObjectiveTo investigate the effects of jujuboside A （JuA） on the learning and memory abilities and histopathological changes in the rat model of vascular cognitive impairment （VCI） and explore the potential mechanisms by which JuA treats VCI. MethodsA total of 50 male SPF-grade SD rats were randomized into a sham operation group （n=10）， a blank control group （n=10）， and a modeling group （n=30）. The rats in the modeling group underwent bilateral carotid artery ligation （2-VO） for the modeling of VCI. After stabilization， the VCI rats were randomized into model， JuA （20 mg·kg^-¹）， and donepezil （0.45 mg·kg^-¹） groups. After 4 weeks of gavage， the novel object recognition and Morris water maze tests were conducted to evaluate the learning and memory abilities of rats. Nissl staining was employed to evaluate the morphology and number of hippocampal neurons. Real-time PCR was employed to measure the mRNA levels of glycogen synthase kinase-3β （GSK-3β）， cAMP response element-binding protein （CREB）， B cell lymphoma-2 （Bcl-2）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） in the hippocampal tissue. Western blot was employed to quantify the protein levels of GSK-3β， p-GSK-3β， p-CREB， Bcl-2， PI3K， p-PI3K， Akt， and p-Akt in the hippocampal tissue. ResultCompared with the sham operation group， the model group exhibited declines in the learning and memory abilities （P<0.01）， neuronal damage and decreased neurons in the hippocampal CA1 region （P<0.01）， up-regulation in the mRNA level of GSK-3β （P<0.01）， and down-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2， as well as the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.01）. In comparison to the model group， both the JuA and donepezil groups demonstrated improvements in the learning and memory abilities （P<0.05， P<0.01）， with reduced neuronal damage and increased neurons （P<0.05， P<0.01）. In addition， the two groups showed down-regulation in the mRNA level of GSK-3β （P<0.01） and up-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2 and the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.05， P<0.01）. There were no statistically significant differences between the blank control and sham operation groups in terms of the learning and memory abilities， neuron count， and mRNA and protein levels of PI3K/Akt/GSK-3β pathway-related factors. ConclusionJuA can ameliorate the cognitive impairment in the rat model of VCI by activating the PI3K/Akt signaling pathway， reducing the apoptosis of hippocampal neurons， and alleviating the hippocampal neuronal damage.

Objective To explore the distribution characteristics and influencing factors of nasal colonized bacteria of healthcare workers(HCWs)in pediatric intensive care unit(PICU).Methods A cross-sectional study was con-ducted.Nasal swab specimens from 104 HCWs in the PICU of a hospital were collected for bacterial culture and an-timicrobial susceptibility testing.According to the identification and antimicrobial susceptibility testing results of strains,distribution characteristics of colonized bacteria was analyzed.Basic information of studied subjects were collected through questionnaire survey,and risk factors for colonized bacterial infection were conducted using logis-tic regression analysis.Results Among 104 specimens,colonized bacteria were detected from 66 specimens,with an overall detection rate of 63.46％.Gram-positive bacteria was mainly Staphylococcus aureus,with a detection rate of 34.62％(n=36),out of which methicillin-resistant Staphylococcus aureus(MRSA)accounted for 2.88％(n=3).Gram-negative bacteria was mainly Klebsiella spp.,with a detection rate of 21.15％(n=22).Multiva-riate logistic regression analysis showed that HCWs with junior professional titles(OR=11.400,95％CI:2.329-55.801,P=0.003)was an independent risk factor for Staphylococcus aureus colonization,and male(OR=4.260,95％CI:1.160-15.653,P=0.029)was an independent risk factor for Klebsiella spp.colonization.Conclusion Nasal cavity of HCWs in PICU has a high detection rate of colonized bacteria,with Staphylococcus aureus and Klebsiella spp.being the major colonized bacteria.

As a chronic progressive lung disease with poor prognosis,the pathogenesis of idiopathic pulmonary fibrosis(IPF)has not yet been clarified,and its treatment is still being explored.Animal models are important tools for studying the pathogenesis and therapeutic effects of diseases.Based on the similarity between animal models and human of IPF in terms of disease phenotype,this paper will review the research progress of IPF animal models in terms of the fibrosis mechanism induced by drugs and environmental factors,histopathological alterations,fibrosis stage,modelling time,etc.,and describe the advantages and disadvantages of different animal models,their characteristics and application profiles.

Objective:Using graph theory analysis, this study compares the topological and node attributes of the brain network to explore the differences in gray matter structural and functional network topological properties between bipolar depression (BD) patients with and without obsessive-compulsive symptoms (OCS).Methods:A total of 90 BD patients (27 males, 63 females; median age 19.0(22.0, 25.0) years) were recruited from the psychiatric outpatient and inpatient departments of the First Affiliated Hospital of Jinan University between March 2018 and December 2022. Fifty healthy controls (19 males, 31 females; median age: 23.0 (20.0, 27.0) years) were also enrolled. The BD patients were divided into two groups based on the presence of OCS: 53 with OCS (OCS group) and 37 without OCS (NOCS group). Resting-state structural and functional MRI data were collected for all participants to construct gray matter structural and functional networks. Graph therory analysis was applied to calculate network topological metrics such as small-world properties. The structural and functional network topological properties were compared among the BD-OCS, BD-nOCS, and control groups. Partial correlation analysis was conducted to examine the association between network topological metrics with significant group differences and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. Support vector machines (SVM) were used with these metrics as classification feature values to improve diagnostic accuracy through pairwise group classification.Results:Structural network analysis of gray matter: compared to HC group, both OCS group and NOCS group showed increased shortest path length and standardized characteristic path length (shortest path length: 0.78 and 0.80 vs. 0.69; normalized characteristic path length: 0.48 and 0.49 vs. 0.43), and decreased global efficiency (0.21 and 0.21 vs. 0.24) compared to the HC group (permutation test, all P<0.05). Compared to NOCS and HC groups, the OCS group showed increased nodal centrality and betweenness centrality in the right rolandic operculum and left superior occipital gyrus (permutation test, all P<0.05). Functional network analysis of gray matter: compared to the NOCS group, the OCS group showed increased node efficiency and decreased betweenness centrality in the cerebellum ( t=2.15, -3.04; all P<0.05); compared to HC groups, the OCS group showed decreased betweenness centrality in the cerebellum and left inferior frontal gyrus, along with increased node centrality and nodal efficiency in the right transverse temporal gyrus ( t=-2.99, -3.61, 3.06, 3.10; all P<0.05). In the OCS group, betweenness centrality in the left inferior frontal gyrus positively correlated with Y-BOCS scale obsessive thinking score ( r=0.303, P=0.034). Nodal centrality and node efficiency of the right transverse temporal gyrus negatively correlated with Y-BOCS total score ( r=-0.301, -0.311) and Y-BOCS obsessional thinking scores ( r=-0.385, -0.380) separately(all P<0.05). SVM classification: the combined network features achieved an area under the curve of 0.80 in distinguising OCS from NOCS patients. Conclusion:BD-OCS and BD-nOCS patients both exhibit consistent changes in gray matter structural network topology, with the OCS group displaying more pronounced nodal topological abnormalities. Multi-network feature integration demostrates potential for diagnostic classfication.

Objective:To evaluate the effects of nasal endoscopy in curettage of large mandibular cyst.Methods:20 cases of large mandibular cyst admitted to Xianyang Hosptial of Yan'an University from January 2022 to December 2023 were included.The curet-tage of mandibular cyst was performed under general anesthesia through intraoral incision by nasal endoscopy-assisted illumination and enlargement of the lesion area during the operation.The application effects were evaluated from the aspects of surgical incision length,nerve injury and cyst recurrence.Results:During operation,the surgical filed of view was clear and the operation was suc-ceeded in all cases.There was no complication in and after the nasal endoscopy-assisted curettage,no cyst recurrence was observed during 1-year follow-up.Conclusion:Nasal endoscopy-assisted curettage of large mandibular cyst is effective and safe.

Objective To explore the differences in terahertz(THz)signal characteristics between normal and ischemic liver tissues of New Zealand rabbits using THz time-domain spectroscopy(THz-TDS),thereby providing a novel detection technique for the pathological detection of liver tissues.Methods Liver ischemia models were established in New Zealand rabbits.The THz scanning signal maps of normal and ischemic liver tissues were obtained using a reflective THz-TDS system,and the acquired signals were subjected to principal component analysis.Results Both normal and ischemic liver tissues displayed two distinct peaks in their THz signals.However,the amplitude of the THz signal in ischemic liver tissue was higher than that in normal liver tissue,with significant differences also observed in their signal morphologies.Principal component analysis results revealed a clear clustered distribution between the signals of normal and ischemic liver tissues,indicating that THz-TDS could effectively distinguish between the two tissue types.Conclusion THz-TDS can be applied to the detection of ischemic liver tissue,providing experimental evidence to support further research on the early diagnosis of liver ischemia and exhibiting broad prospects for clinical application.

BACKGROUND:Previous studies have found that Jiangu Formula can play a dual role in anti-osteoporosis therapy by inhibiting bone resorption and promoting bone formation,but its mechanism of action has not been elucidated.OBJECTIVE:To investigate the effect of Jiangu Formula on the coupling mechanism between bone resorption and bone formation at the cellular and molecular levels.METHODS:Serum containing Jiangu Formula was prepared and its toxicity to bone marrow derived macrophages was determined using MTT assay.The cell proliferation ability of MC3T3-E1 cells that treated Jiangu Formula medicated serum was measured by using cell counting kit-8 method.Tartrate resistant acid phosphatase staining was used to determine the bone resorption inhibition effect of serum containing Jiangu Formula on osteoclast differentiation.The Jiangu Fang conditional culture medium was prepared and the promoting effect of the conditional culture medium on bone formation of MC3T3-E1 was determined through alkaline phosphatase staining.The effect of serum containing Jiangu Formula on the mRNA levels of osteoclast associated sphingosine kinase 2,collagen triple helix repeat containing 1,and slit homolog 3 coupled genes,as well as the effect of conditioned culture medium on the mRNA levels of bone formation related secreted phosphoprotein 1,alkaline phosphatase,Sp7 transcription factor,and secreted protein acidic and rich in cysteine genes,were determined by RT-qPCR method.RESULTS AND CONCLUSION:(1)The MTT and cell counting kit-8 methods showed that serum containing Jiangu Formula had no significant cytotoxic effects at a concentration of<5%.(2)Tartrate resistant acid phosphatase staining results indicated that serum containing Jiangu Formula dose-dependently inhibited osteoclast differentiation at 2.5%,1.25%,and 0.63%concentrations.(3)The alkaline phosphatase staining results showed that the osteoclast conditioned medium of Jiangu Formula promoted osteoblast differentiation in a dose-dependent manner.(4)In addition,RT-qPCR results showed that serum containing 0.63%Jiangu Formula could increase the mRNA levels of osteoclast derived slit homolog 3 and sphingosine kinase 2 coupling factors,and the conditional culture medium could increase the mRNA expression levels of bone formation related secreted phosphoprotein 1,Sp7 transcription factor,and secreted protein acidic and rich in cysteine.To conclude,the serum containing Jiangu Formula can promote bone formation while inhibiting bone resorption,and its mechanism may be related to the mRNA expression of the coupling factors osteoclast derived slit homolog 3 and sphingosine kinase 2 that promote bone resorption and bone formation.

Objective To explore the distribution characteristics and influencing factors of nasal colonized bacteria of healthcare workers(HCWs)in pediatric intensive care unit(PICU).Methods A cross-sectional study was con-ducted.Nasal swab specimens from 104 HCWs in the PICU of a hospital were collected for bacterial culture and an-timicrobial susceptibility testing.According to the identification and antimicrobial susceptibility testing results of strains,distribution characteristics of colonized bacteria was analyzed.Basic information of studied subjects were collected through questionnaire survey,and risk factors for colonized bacterial infection were conducted using logis-tic regression analysis.Results Among 104 specimens,colonized bacteria were detected from 66 specimens,with an overall detection rate of 63.46％.Gram-positive bacteria was mainly Staphylococcus aureus,with a detection rate of 34.62％(n=36),out of which methicillin-resistant Staphylococcus aureus(MRSA)accounted for 2.88％(n=3).Gram-negative bacteria was mainly Klebsiella spp.,with a detection rate of 21.15％(n=22).Multiva-riate logistic regression analysis showed that HCWs with junior professional titles(OR=11.400,95％CI:2.329-55.801,P=0.003)was an independent risk factor for Staphylococcus aureus colonization,and male(OR=4.260,95％CI:1.160-15.653,P=0.029)was an independent risk factor for Klebsiella spp.colonization.Conclusion Nasal cavity of HCWs in PICU has a high detection rate of colonized bacteria,with Staphylococcus aureus and Klebsiella spp.being the major colonized bacteria.