Multidimensional stressors and depressive and anxiety symptoms in adolescents: A network analysis through simulations.

BACKGROUND: Existing research has established associations between various stressors and adolescent mental health, primarily from a variable-level perspective. However, a symptom-level understanding about which stressors and symptoms might play a important role is scarce. METHODS: The sample consisted of 15,570 adolescents aged 10 to 19. Participants completed questionnaires which assessed multidimensional stressors, depressive symptoms, anxiety symptoms, and demographic information. Network analysis was conducted to explore the relationships between stressors and depressive and anxiety symptoms. Additionally, to identify effective targets for the treatment and prevention of adolescent mental health issues, symptom-specific intervention simulations were performed on the network to investigate changes in symptom values in response to the alleviation and aggravation of specific stressors and symptoms. RESULTS: Findings revealed that academic stressors exhibited stronger associations with anxiety symptoms than other stressors, particularly nervousness. Family relationships were more closely linked to depressive symptoms than other stressors, particularly suicidal ideation. Academic stressors emerged as an effective intervention target, and uncontrollable worry as an important prevention target. With the exception of academic stressors, simulating aggravation interventions on symptoms resulted in more changes in overall symptom activation than alleviation interventions. LIMITATIONS: A cross-sectional design did not uncover network changes over time and the sample was non-clinical. CONCLUSIONS: This study highlights the importance of addressing academic stressors to alleviate adolescents' depressive and anxiety symptoms and reveals that uncontrollable worry is a key prevention target. The findings are helpful for clinicians and educators to develop effective strategies to protect adolescents' mental health.

Mesenchymal stem cells overexpressing PBX1 alleviates haemorrhagic shock-induced kidney damage by inhibiting NF-κB activation.

Mesenchymal stem cells (MSCs) have favourable outcomes in the treatment of kidney diseases. Pre-B-cell leukaemia transcription factor 1 (PBX1) has been reported to be a regulator of self-renewal of stem cells. Whether PBX1 is beneficial to MSCs in the treatment of haemorrhagic shock (HS)-induced kidney damage is unknown. We overexpressed PBX1 in rat bone marrow-derived mesenchymal stem cells (rBMSCs) and human bone marrow-derived mesenchymal stem cells (hBMSCs) to treat rats with HS and hypoxia-treated human proximal tubule epithelial cells (HK-2), respectively. The results indicated that PBX1 enhanced the homing capacity of rBMSCs to kidney tissues and that treatment with rBMSCs overexpressing PBX1 improved the indicators of kidney function, alleviated structural damage to kidney tissues. Furthermore, administration with rBMSCs overexpressing PBX1 inhibited HS-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and the release of proinflammatory cytokines, and further attenuated apoptosis. We then determined whether NF-κB, an important factor in NLRP3 activation and the regulation of inflammation, participates in HS-induced kidney damage, and we found that rBMSCs overexpressing PBX1 inhibited NF-κB activation by decreasing the p-IκBα/IκBα and p-p65/p65 ratios and inhibiting the nuclear translocation and decreasing the DNA-binding capacity of NF-κB. hBMSCs overexpressing PBX1 also exhibited protective effects on HK-2 cells exposed to hypoxia, as shown by the increase in cell viability, the mitigation of apoptosis, the decrease in inflammation, and the inhibition of NF-κB and NLRP3 inflammasome activation. Our study demonstrates that MSCs overexpressing PBX1 ameliorates HS-induced kidney damage by inhibiting NF-κB pathway-mediated NLRP3 inflammasome activation and the inflammatory response.

Factor structure and measurement invariance of the 8-item CES-D: a national longitudinal sample of Chinese adolescents.

BACKGROUND: The 8-item Center for Epidemiologic Studies Depression Scale (CES-D 8) has been widely used to measure depressive symptoms in many large-scale surveys. Due to its brevity, it can lower costs, relieve respondent burdens, and ensure data quality. However, its factor structure and measurement invariance across gender and time among adolescents have not been adequately evaluated. This study investigated its factor structure and measurement invariance across gender and time among adolescents. METHODS: The data was drawn from the China Family Panel Studies (CFPS) conducted in 2018 and 2020, with 3099 participants (46.82% girls) aged 11 to 18 in 2018. First, exploratory and confirmatory factor analyses were used to examine the factor structure of the CES-D 8. Next, multi-group confirmatory factor analysis was conducted to test its measurement invariance across gender and time. Finally, a longitudinal cross-gender test was conducted to further confirm the stability of the scale. RESULTS: A two-factor structure was identified among the adolescents, including Negative Symptoms and Diminished Happiness Feeling. Measurement invariance across gender and time, as well as the longitudinal cross-gender invariance, was supported, with configural, factor loadings, thresholds and residual invariance. CONCLUSIONS: The factor structure of the CES-D 8 remains stable across gender and time among adolescents, indicating that it is a promising instrument for measuring depressive symptoms, especially in large-scale and longitudinal surveys.

Psychometric Evaluation of the Affective Reactivity Index Among Children and Adolescents in China: A Multi-Method Assessment Approach.

The Affective Reactivity Index (ARI) is one of the most studied scales for assessing youth irritability, but little is known about its measurement performance in community populations. This study applied item response theory (IRT), network analysis, and classical test theory (CTT) to examine the psychometric properties of the ARI in a sample of n = 395 community-based children (Mage = 13.44, SD = 2.51) and n = 403 parents. In this sample, the ARI demonstrated good reliability, as well as convergent and concurrent validity. The one-factor structure was supported by both confirmatory factor analysis (CFA) and network analysis. IRT analysis revealed that the ARI effectively distinguished between various levels of irritability within the community population. Network analysis identified "Loses temper easily,""Gets angry frequently," and "Often loses temper" are central aspects of irritability. The findings support the ARI as a brief, reliable, and valid instrument to assess irritability in community children and adolescents.

Sirtuin3 confers protection against acute pulmonary embolism through anti-inflammation, and anti-oxidative stress, and anti-apoptosis properties: participation of the AMP-activated protein kinase/mammalian target of rapamycin pathway.

An increasing number of studies have suggested that oxidative stress and inflammation play momentous roles in acute pulmonary embolism (APE). Honokiol, a bioactive biphenolic phytochemical substance, is known for its strong anti-oxidative and anti-inflammatory effects, and it served as an activator of sirtuin3 (SIRT3) in the present study. The purposes of the study were to explore the effects of honokiol on APE rats and investigate whether the function of honokiol is mediated by SIRT3 activation. In the study, the rats received a right femoral vein injection of dextran gel G-50 particles (12 mg/kg) to establish the APE model and were subsequently administered honokiol and/or a selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl)pyridine (3-TYP; 5 mg/kg) intraperitoneally. The results showed that SIRT3 activation by honokiol attenuated the loss in lung function, ameliorated the inflammatory response and oxidative damage, and inhibited apoptosis in lung tissues of the rats with APE but that this was reversed by 3-TYP. In addition, we found that the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway might be activated by honokiol but restrained by 3-TYP. These results indicated that honokiol was capable of suppressing the adverse effects of APE and that this was diminished by SIRT3 suppression, implying that activation of SIRT3 might serve as a therapeutic method for APE.

Mental health and its influencing factors of maintenance hemodialysis patients: a semi-structured interview study.

BACKGROUND: Maintenance hemodialysis (MHD) is a commonly used renal replacement therapy for end-stage renal disease patients. MHD patients have undergone multiple physiological stressors, which may cause physical problems and affect their mental health; however, few qualitative studies have been done on the mental health of MHD patients. Such qualitative research becomes the basis for further quantitative research and is critical to validating its results. Therefore, the current qualitative study used a semi-structured interview format, and aimed to explore the mental health and its influencing factors of MHD patients who are not receiving intervention treatment to determine how best to ameliorate their mental health. METHODS: Based on the application of Grounded Theory, semi-structured face-to-face interviews were conducted with 35 MHD patients, following consolidated criteria for reporting qualitative studies (COREQ) guidelines. Two indicators (emotional state and well-being) were used to assess MHD patients' mental health. All interviews were recorded, after which two researchers independently performed data analyses using NVivo. RESULTS: Acceptance of disease, complications, stress and coping styles, and social support were found to be the influencing factors of MHD patients' mental health. High acceptance of disease, healthy coping styles, and high social support were positively correlated with mental health. In contrast, low acceptance of disease, multiple complications, increased stress, and unhealthy coping styles were negatively correlated with mental health. CONCLUSION: One's acceptance of the disease played a more significant role than other factors in affecting MHD patients' mental health.

KDM4A, involved in the inflammatory and oxidative stress caused by traumatic brain injury-hemorrhagic shock, partly through the regulation of the microglia M1 polarization.

BACKGROUND: Microglial polarization and the subsequent neuroinflammatory response and oxidative stress are contributing factors for traumatic brain injury (TBI) plus hemorrhagic shock (HS) induced brain injury. In the present work, we have explored whether Lysine (K)-specific demethylase 4 A (KDM4A) modulates microglia M1 polarization in the TBI and HS mice. RESULTS: Male C57BL/6J mice were used to investigate the microglia polarization in the TBI + HS model in vivo. Lipopolysaccharide (LPS)-induced BV2 cells were used to examine the mechanism of KDM4A in regulating microglia polarization in vitro. We found that TBI + HS resulted in neuronal loss and microglia M1 polarization in vivo, reflected by the increased level of Iba1, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, malondialdehyde (MDA) and the decreased level of reduced glutathione (GSH). Additionally, KDM4A was upregulated in response to TBI + HS and microglia were among the cell types showing the increased level of KDM4A. Similar to the results in vivo, KDM4A also highly expressed in LPS-induced BV2 cells. LPS-induced BV2 cells exhibited enhanced microglia M1 polarization, and enhanced level of pro-inflammatory cytokines, oxidative stress and reactive oxygen species (ROS), while this enhancement was abolished by the suppression of KDM4A. CONCLUSION: Accordingly, our findings indicated that KDM4A was upregulated in response to TBI + HS and microglia were among the cell types showing the increased level of KDM4A. The important role of KDM4A in TBI + HS-induced inflammatory response and oxidative stress was at least partially realized through regulating microglia M1 polarization.

MKK4 Knockdown Plays a Protective Role in Hemorrhagic Shock-Induced Liver Injury through the JNK Pathway.

Hemorrhagic shock (HS) triggers tissue hypoxia and organ failure during severe blood loss, and the liver is sensitive to HS. Mitogen-activated protein kinase kinase 4 (MKK4) activates the c-Jun NH2-terminal kinase (JNK) pathway, and its expression is upregulated in the serum of HS patients and mouse livers at 1 h post-HS. However, the function of MKK4 in HS-induced liver injury is unclear. The role of MKK4 was investigated in vivo using rat models of HS. Before HS, lentivirus harboring shRNA against MKK4 was injected into rats via the tail vein to knock down MKK4 expression. HS was induced by bloodletting via intubation of the femoral artery followed by resuscitation. The results showed that MKK4 knockdown reduced HS-induced apoptosis in the liver by decreasing Bax expression and the cleavage of caspase 3 and promoting Bcl-2 expression. Moreover, the generation of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) in the liver was promoted, while superoxide dismutase (SOD) activity was inhibited by HS. However, the effect of HS on oxidative stress was abrogated by MKK4 knockdown. Furthermore, MKK4 knockdown restored MMP and complex I and complex III activities and promoted ATP production, suggesting that HS-induced mitochondrial dysfunction in the liver was ameliorated by MKK4 knockdown. The inhibitory effect of MKK4 knockdown on the phosphorylation and activation of the JNK/c-Jun pathway was confirmed. Overall, MKK4 knockdown may suppress oxidative stress and subsequent apoptosis and improve mitochondrial function in the liver upon HS by inhibiting the JNK pathway. The MKK4/JNK axis was shown to be a therapeutic target for HS-induced liver injury in this study.

PTPRO knockdown protects against inflammation in hemorrhage shock-induced lung injury involving the NF-κB signaling pathway.

BACKGROUND: Hemorrhage shock (HS) is characterized by decreased tissue oxygenation and organ damage due to severe blood loss. Protein tyrosine phosphatase receptor type O (PTPRO) is abnormally up-regulated in the rat lungs after trauma/HS. METHODS: To elucidate the regulatory mechanism of PTPRO in lung inflammation following HS, we established a rat model of HS via withdrawing blood by a catheter inserted into the femoral artery followed by resuscitation. The rats were infected with lentivirus harboring short hairpin RNA (shRNA) targeting PTPRO by intratracheal instillation. RESULTS: PTPRO was significantly up-regulated in rat lungs after HS. PTPRO knockdown enhanced epithelial integrity and reduced capillary leakage by up-regulating tight junction proteins zonula occludens-1 (ZO-1) and occludin (OCC) in the lungs. Besides, HS-induced myeloperoxidase activity and inflammatory cell infiltration was mitigated by PTPRO knockdown. The expression of inflammatory cytokines/chemokines (TNF-α, IL-6, MIP-2, MCP-1, and KC) in the lungs and bronchoalveolar lavage fluid was regressed after PTPRO knockdown. The nuclear factor kappa B (NF-κB) pathway was involved in HS-induced lung inflammation. PTPRO down-regulation inhibited the NF-κB pathway activation by suppressing the phosphorylation of NF-κB and its translocation from the cytoplasm into the nucleus in HS. CONCLUSION: Taken together, we demonstrated that PTPRO knockdown may contribute to attenuating inflammation in HS-induced lung injury via inhibiting NF-κB pathway activation.

Tyrosine kinase nonreceptor 1 (TNK1) knockdown ameliorates hemorrhage shock-induced kidney injury via inhibiting macrophage M1 polarization.

Hemorrhage shock (HS) is a major threat to patients with trauma and spontaneous bleeding, resulting in multi-organ failure including the kidney. Tyrosine kinase nonreceptor 1 (TNK1) has been shown to be upregulated in the kidney of experimental HS and patients with severe trauma. The study aims to investigate the role of TNK1 and the underlying mechanism in HS-induced kidney injury. A model of HS was established with femoral artery bloodletting, followed by resuscitation in Sprague-Dawley rats. Renal expression of TNK1 was abnormally induced by HS in rats. Knockdown of TNK1 alleviated HS-induced cell apoptosis and the level of proinflammatory cytokines (TNF-α, IL-6 and IL-1ß) in the kidney. The expression of M1 macrophage markers (CD86 and iNOS) and the activation of STAT1 were inhibited by TNK1 knockdown in HS rats. In vitro, human monocyte THP-1 cells were treated with 20 ng/mL interferon-gamma plus 100 ng/mL lipopolysaccharide to induce M1 polarization. TNK1 knockdown exerted inhibitory effect on macrophage M1 polarization, M1-type inflammatory cytokine production and STAT1 activation in THP-1 cells. In conclusion, downregulation of TNK1 alleviates HS-induced kidney injury by suppressing macrophage M1 polarization, inflammation and kidney cell apoptosis, in which the deactivation of STAT1 signaling may be involved.

Stress-induced phosphoprotein 1 restrains spinal cord ischaemia-reperfusion injury by modulating NF-κB signalling.

Spinal cord injury (SCI), a major cause of disability, causes high global disease and economic burdens. Stress-induced phosphoprotein 1 (STIP1) has been identified to be involved in spinal cord ischaemia-reperfusion injury (SCII); however, the effect of STIP1 on SCII remains unclear until now. This study aimed to examine the role of STIP1 in SCII and unravel the possible mechanisms. Western blotting and immunohistochemical staining showed that STIP1 expression rapidly increased and then decreased in rat spinal cord following SCII treatment. Neurological function scoring, HE staining, immunohistochemical staining and Western blotting revealed that STIP1 overexpression alleviated SCII-induced motor dysfunction of hind limbs, neuronal loss and inflammation in spinal cord, and inhibited activity of nuclear factor kappa B (NF-κB) signalling in rats. Immunoprecipitation identified that STIP1 was co-located with Iba-1. In addition, STIP1 was found to ameliorate oxygen and glucose deprivation (OGD)-induced inflammation and activation of NF-κB signalling in mouse microglia BV2 cells, and STIP1 resulted in decrease of heat shock protein family A member 8 (HSPA8), increase of IκBß expression and reduced binding of IκBß to HSPA8 in BV2 cells. The results of the present study demonstrate that STIP1 alleviates ischaemia/reperfusion-induced neuronal injury and inflammation in rat spinal cord and mouse microglial cells by deactivating NF-κB signalling. These findings may provide novel insights for the clinical diagnosis and treatment of SCI.