Abstract Background To examine the factor structure and psychometric properties of the Patient Health Questionnaire for Adolescents (PHQ-A) in Chinese children and adolescents with major depressive disorder (MDD). Methods A total of 248 MDD patients aged between 12 and 18 years were recruited and evaluated by the Patient Health Questionnaire for Adolescents (PHQ-A), the Center for Epidemiological Survey Depression Scale (CES-D), the Mood and Feelings Questionnaire (MFQ), and the improved Clinical Global Impression Scale, Severity item (iCGI-S). Thirty-one patients were selected randomly to complete the PHQ-A again one week later. Confirmatory factor analysis (CFA) was used to test the construct validity of the scale. Reliability was evaluated by Macdonald Omega coefficient. Pearson correlation coefficient was used to assess the item-total correlation and the correlation of PHQ-A with CES-D and MFQ respectively. Spearman correlation coefficient was used to assess test-retest reliability. The optimal cut-off value, sensitivity, and specificity of the PHQ-A were achieved by estimating the Receiver Operating Characteristics (ROC) curve. Results CFA reported adequate loadings for all items, except for item 3. Macdonald Omega coefficient of the PHQ-A was 0.87. The Spearman correlation coefficient of the test-retest reliability was 0.70. The Pearson correlation coefficients of the PHQ-A with CES-D and MFQ were 0.87 and 0.85, respectively (p < 0.01). By taking the iCGI-S as the remission criteria for MDD, the optimal cut-off value, sensitivity and specificity of the PHQ-A were 7, 98.7%, 94.7% respectively. Conclusion The PHQ-A presented as a unidimensional construct and demonstrated satisfactory reliability and validity among the Chinese children and adolescents with MDD. A cut-off value of 7 was suggested for remission.

Introduction: Delirium is a common acute brain dysfunction syndrome in patients admitted to intensive care units (ICUs). Family engagement strategies, based on the theory of multi-sensory stimulation to ameliorate sensory deprivation in patients, may be an effective and scalable method to reduce the burden of delirium. Methods: /design: This is a assessor-blinded, randomised controlled trial of the feasibility of multi-sensory stimulation (MS) in patients with delirium. A total of 72 mechanically ventilated patients (n = 24 in each group) admitted to the ICU will be randomised to routine non-pharmacological delirium care (control), family multi-sensory stimulation and nurse multi-sensory stimulation groups. All participants except the control group will receive multi-sensory stimulation, including visual, auditory, tactile and kinesthetic stimulation, for 5 days. Our primary aim is to determine the feasibility of the study procedure (recruitment, eligibility, retention and attrition rates, appropriateness of clinical outcome measures), feasibility, acceptability and safety of the intervention (adverse events, satisfaction and other). Our secondary objective is to assess the preliminary efficacy of the MS protocol in reducing the incidence, duration and severity of delirium. Sedation levels and delirium severity will be assessed twice daily. Enrolled participants will be followed in hospital until death, discharge or up to 28 days after treatment. Ethics and dissemination: The current study was approved by the Ethics Review Board of Huazhong University of Science and Technology Union Shenzhen Hospital, China (KY-2023-031-01). The results of this study will be presented at scientific conferences and submitted for publication in peer-reviewed journals. Trial registration number: ChiCTR2300071457.

OBJECTIVE:The pathogenesis of sepsis is complex, and the sepsis-induced systemic proinflammatory phase is one of the key drivers of organ failure and consequent mortality. Akkermansia muciniphila (AKK) is recognised as a functional probiotic strain that exerts beneficial effects on the progression of many diseases; however, whether AKK participates in sepsis pathogenesis is still unclear. Here, we evaluated the potential contribution of AKK to lethal sepsis development. DESIGN:Relative abundance of gut microbial AKK in septic patients was evaluated. Cecal ligation and puncture (CLP) surgery and lipopolysaccharide (LPS) injection were employed to establish sepsis in mice. Non-targeted and targeted metabolomics analysis were used for metabolites analysis. RESULTS:We first found that the relative abundance of gut microbial AKK in septic patients was significantly reduced compared with that in non-septic controls. Live AKK supplementation, as well as supplementation with its culture supernatant, remarkably reduced sepsis-induced mortality in sepsis models. Metabolomics analysis and germ-free mouse validation experiments revealed that live AKK was able to generate a novel tripeptide Arg-Lys-His (RKH). RKH exerted protective effects against sepsis-induced death and organ damage. Furthermore, RKH markedly reduced sepsis-induced inflammatory cell activation and proinflammatory factor overproduction. A mechanistic study revealed that RKH could directly bind to Toll-like receptor 4 (TLR4) and block TLR4 signal transduction in immune cells. Finally, we validated the preventive effects of RKH against sepsis-induced systemic inflammation and organ damage in a piglet model. CONCLUSION:We revealed that a novel tripeptide, RKH, derived from live AKK, may act as a novel endogenous antagonist for TLR4. RKH may serve as a novel potential therapeutic approach to combat lethal sepsis after successfully translating its efficacy into clinical practice.

BACKGROUND:Depression is a common psychological problem in adolescents worldwide. Although the World Health Organization recommends that members of this population engage in physical activity to reduce depressive symptoms, compliance with this recommendation is often low. Furthermore, although behavioral activation (BA) is recommended as a treatment for adolescents with depression, the reported effect size is small. Compared with traditional exercises, gamified physical activity (GPA) can be particularly appealing to adolescents because it is perceived as an enjoyable experience. In this study, we integrated BA and GPA to create behavioral activation play therapy (BAPT). We designed a clinical trial to investigate the feasibility, acceptability, and effectiveness of this treatment in adolescents with depression.METHODS:This study is a randomized controlled trial (RCT) with a three-arm, assessor-blinded design, conducted to validate the effectiveness and applicability of BAPT for treating adolescent with depression. We will recruit 258 participants and randomly assign them to a BAPT group, BA group, or GPA group using a ratio of 1:1:1. Based on conventional strategies for treatment and care, the three groups will receive nine BAPT sessions, nine BA sessions, or nine GPA sessions, respectively. We will compare the outcomes of the BAPT with those of the BA and GPA interventions.DISCUSSION:This is the first RCT to explore the effectiveness and applicability of BAPT in adolescents with depression. This study will provide evidence that may help to decrease depressive symptoms in adolescents, and will demonstrate the treatment effectiveness in terms of increasing levels of physical activity, reducing the rate of non-suicidal self-injury behaviors, and improving sleep quality. We will also assess the presence of side effects and the treatment adherence of patients receiving BAPT.TRIAL REGISTRATION:Trial registration: Chinese Clinical Trial Registry, ChiCTR2300072671. Registered on 20 June 2023.

BACKGROUND:Perinatal depression has attracted increasing attention. However, a detailed investigation of the network structure of depression is still lacking. We aim to examine the similarities and differences between the Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire (PHQ-9) from a network perspective. METHODS:A cross-sectional study was conducted from August 2020 to March 2022. We followed the STROBE checklist to report our research. Pregnant women (n = 2484) were recruited. All participants completed the EPDS and PHQ-9. We mainly used network analyses for statistical analysis and constructed two network models: the EPDS and PHQ-9 models. RESULTS:The detection rates of prenatal depression measured by the EPDS and PHQ-9 were 30.2 % and 28.2 %, respectively. In the EPDS network, the EPDS8 'sad or miserable' node (strength = 1.2161) was the most central node, and the EPDS10 'self-harming' node (strength = 0.4360) was the least central node. In the PHQ-9 network, the PHQ4 'fatigue' node (strength = 0.9815) was the most central node, and PHQ9 'suicide' was the least central symptom (strength = 0.5667). For both models, 'sad' acted as an important central symptom. CONCLUSIONS:Psychological symptoms may be more important in assessing depression using the EPDS, while physical symptoms may be more influential in assessing depression using the PHQ-9. For both the EPDS and PHQ-9, "sad" was an important central symptom, suggesting that it may be the most important target for further maternal depression interventions in the future.

Hashimoto's thyroiditis (HT) is an autoimmune disorder with unclear molecular mechanisms. While current diagnosis is well-established, understanding of the gut-thyroid axis in HT remains limited. This study aimed to uncover novel molecular signatures in HT by integrating gut metagenome and host transcriptome data (miRNA/mRNA), potentially elucidating disease pathogenesis and identifying new therapeutic targets. We recruited 31 early HT patients and 30 healthy controls in a two-stage study (discovery and validation). Blood and fecal samples underwent RNA and metagenomic sequencing, respectively. Integrative analysis included differential expression, weighted correlation network, correlation and random forest analyses. Regression models and ROC curve analysis were used to evaluate the significance of identified molecular signatures in HT. Integrative analysis revealed subtle changes in gut microbiota diversity and composition in early HT, increased abundance of Bacillota_A and Spirochaetota at the phylum level, and significant differences in 24 genera and 67 species. Ecological network analysis indicated an imbalance in the gut microbiota with reduced inhibitory interactions against pathogenic genera in HT. Functional analysis showed changes in infection- and immune-related pathways. Three characteristic species (Salaquimonas_sp002400845, Clostridium_AI_sp002297865, and Enterocloster_citroniae) were identified as most relevant to HT. Analysis of miRNA and mRNA expression profiles uncovered pathways related to immune response, inflammation, infection, metabolism, proliferation, and thyroid cancer in HT. Based on correlations with HT and interactions between them, six characteristic RNAs (hsa-miR-548aq-3p, hsa-miR-374a-5p, GADD45A, IRS2, SMAD6, WWTR1) were identified. Furthermore, our study uncovered significant gut microbiota-host transcriptome interactions in HT, revealing enrichment in metabolic, immune, and cancer-related pathways, particularly with strong associations among those 9 key molecular signatures. The validation stage confirmed improved HT classification accuracy by combining these signatures (AUC = 0.95, ACC = 0.85), suggesting their potential significance in understanding HT pathogenesis. Our study reveals novel molecular signatures linking gut microbiome and host transcriptome in HT, providing new insights into the disease pathogenesis. These findings not only enhance our understanding of the gut-thyroid axis but also suggest potential new directions for therapeutic interventions in HT.

Sepsis, a critical condition resulting from the systemic inflam-matory response to a severe microbial infection, represents a global public health challenge. However, effective treatment or intervention to prevent and combat sepsis is still lacking. Here, we report that hyodeoxycholic acid (HDCA) has excellent anti-inflammatory properties in sepsis. We discovered that the plasma concentration of HDCA was remarkably lower in patients with sepsis and negatively correlated with the severity of the disease. Similar changes in HDCA levels in plasma and cecal content samples were observed in a mouse model of sepsis, and these changes were associated with a reduced abundance of HDCA-producing strains. Interestingly, HDCA administration significantly decreased systemic inflammatory responses, prevented organ injury, and prolonged the survival of septic mice. We demonstrated that HDCA suppressed excessive activation of inflammatory macrophages by competitively blocking lipopolysaccharide binding to the Toll-like receptor 4 (TLR4) and myeloid differentiation factor 2 receptor complex, a unique mechanism that characterizes HDCA as an endogenous inhibitor of inflammatory signaling. Additionally, we verified these findings in TLR4 knockout mice. Our study highlights the potential value of HDCA as a therapeutic molecule for sepsis.

The Hospital Anxiety and Depression Scale (HADS) is a widely used screening tool for depression and anxiety in patients with medical illnesses. This study aimed to explore the psychometric properties of the HADS in screening for patients with major depression using item response theory method. A total of 460 patients with major depression completed the HADS. Rasch analyses were used to examine unidimensionality, item fit, local dependency, reliability, ordering of categories, differential item functioning (DIF) and targeting. The HADS showed a two-dimensional construct. All items fit the Rasch model. Three pairs of items showed minor but inconsiderate local dependency. Both subscales had acceptable reliability. None of the items displayed disordered categories or DIF. All items were well targeted, and participants with high and low levels of distress were less targeted than those with moderate levels of distress. Finally, a conversion table to transform the raw scores into interval measures was generated. The HADS demonstrated adequate psychometric properties in assessing depression and anxiety in patients with major depression. It was more appropriate for assessing moderate than high or low levels of distress. The conversion table can be used for more precise measurement. These results may pave the way for efficient and sensitive methods of analyzing depression symptom response in research and in clinical practice. La Hospital Anxiety and Depression Scale (HADS) [Escala Hospitalaria de Ansiedad y Depresión] es una herramienta ampliamente utilizada para detección de la depresión y la ansiedad en pacientes con enfermedades médicas. Este estudio tuvo como objetivo explorar las propiedades psicométricas de la HADS en la detección de pacientes con depresión mayor utilizando el método de la teoría de respuesta al ítem. Un total de 460 pacientes con depresión mayor completaron el HADS. Se utilizó el análisis de Rasch para examinar la unidimensionalidad, el ajuste de los ítems, la dependencia local, la confiabilidad, el orden de las categorías, el funcionamiento diferencial de los ítems (DIF) y la focalización. La HADS mostró una construcción bidimensional. Todos los ítems se ajustaban al modelo de Rasch. Tres pares de ítems mostraron una dependencia local menor pero desconsiderada. Ambas subescalas tuvieron una confiabilidad aceptable. Ninguno de los ítems mostró categorías desordenadas o DIF. Todos los ítems estaban bien dirigidos y los participantes con niveles altos y bajos de angustia fueron menos objetivo que aquellos con niveles moderados de angustia. Finalmente, se generó una tabla de conversión para transformar las puntuaciones brutas en medidas de intervalo. El HADS demostró propiedades psicométricas adecuadas para evaluar la depresión y la ansiedad en pacientes con depresión mayor. Fue más apropiado para evaluar niveles de angustia moderados que altos o bajos. La tabla de conversión se puede utilizar para una medición más precisa. Estos resultados pueden allanar el camino para métodos eficientes y sensibles para analizar la respuesta a los síntomas de depresión en la investigación y en la práctica clínica.

ObjectiveThe pathogenesis of sepsis is complex, and the sepsis-induced systemic proinflammatory phase is one of the key drivers of organ failure and consequent mortality.Akkermansia muciniphila(AKK) is recognised as a functional probiotic strain that exerts beneficial effects on the progression of many diseases; however, whether AKK participates in sepsis pathogenesis is still unclear. Here, we evaluated the potential contribution of AKK to lethal sepsis development.DesignRelative abundance of gut microbial AKK in septic patients was evaluated. Cecal ligation and puncture (CLP) surgery and lipopolysaccharide (LPS) injection were employed to establish sepsis in mice. Non-targeted and targeted metabolomics analysis were used for metabolites analysis.ResultsWe first found that the relative abundance of gut microbial AKK in septic patients was significantly reduced compared with that in non-septic controls. Live AKK supplementation, as well as supplementation with its culture supernatant, remarkably reduced sepsis-induced mortality in sepsis models. Metabolomics analysis and germ-free mouse validation experiments revealed that live AKK was able to generate a novel tripeptide Arg-Lys-His (RKH). RKH exerted protective effects against sepsis-induced death and organ damage. Furthermore, RKH markedly reduced sepsis-induced inflammatory cell activation and proinflammatory factor overproduction. A mechanistic study revealed that RKH could directly bind to Toll-like receptor 4 (TLR4) and block TLR4 signal transduction in immune cells. Finally, we validated the preventive effects of RKH against sepsis-induced systemic inflammation and organ damage in a piglet model.ConclusionWe revealed that a novel tripeptide, RKH, derived from live AKK, may act as a novel endogenous antagonist for TLR4. RKH may serve as a novel potential therapeutic approach to combat lethal sepsis after successfully translating its efficacy into clinical practice.

Background:Cognition has long been regarded as a significant factor influencing individuals' lives. Prior studies have underscored that self-esteem is associated with cognition, and there exists a knowledge gap regarding whether self-esteem remains associated with subsequent cognitive performance during adolescence, a crucial period for neurological development and influencing adult outcomes.Methods:We conducted this population-based study using longitudinal data stretching three waves (2014, 2016, and 2018) of surveys from the nationally representative China Family Panel Studies (CFPS) to explore the association between adolescents' self-esteem in 2014 and cognitive performance in 2014, 2016, and 2018.Results:The results of the present study showed that self-esteem during adolescence in 2014 was significantly associated with cognitive performance in 2014, 2016, and 2018. This association remained robust after an extensive range of covariate adjustments (e.g., adolescents, parental, and family characteristics).Conclusion:The findings in this study provide further insight into the understanding of the related factors for cognitive development across the life course and highlight the importance of improving individual self-esteem during adolescence.

目的 调查肾癌术后患者重返工作的影响因素并构建预测模型.方法 2022年4-12月,采用便利抽样法选取广东省某三级甲等肿瘤医院肾癌术后1个月的患者228例开展横断面调查,通过Logistic回归分析,分析其重返工作的影响因素并构建预测模型.结果 被调查的228例肾癌术后患者,重返工作56例(24.56％);肾癌术后患者重返工作的影响因素:主要有教育程度、焦虑抑郁情绪、重返工作自我效能、手术类型(均P＜0.05);预测模型的受试者工作特征曲线下面积为0.828、灵敏度为0.875、特异度为0.703、正确率为74.60％;拟合优度(x2=7.993,P=0.434).结论 肾癌术后患者重返工作率较低,构建的肾癌术后患者重返工作预测模型能预测其术后未重返工作的风险,可进一步开展临床验证,并为后续制订肾癌术后患者重返工作干预措施提供依据.

目的 探讨产妇及其配偶产后抑郁情绪与心理弹性、二元应对的主客体互倚关系,为制定针对性干预措施提供新视角.方法 便利抽样选取珠海市 3 所三级甲等医院 232 对产妇其及配偶为研究对象,采用一般资料问卷、爱丁堡产后抑郁量表、心理弹性量表、二元应对问卷对其进行调查.结果 232 名产妇产后抑郁情绪总分为 10(7,13)分、二元应对总分为(126.82±21.18)分、心理弹性总分为(59.57±17.56)分;232 名产妇配偶产后抑郁情绪总分为 7(5,10)分、二元应对总分为(124.43±19.63)分、心理弹性总分为(63.17±16.75)分.产妇及其配偶二元应对、心理弹性分别负向预测自身产后抑郁情绪,即主体效应显著.产妇及其配偶二元应对、心理弹性分别负向预测对方产后抑郁情绪,即客体效应显著.结论 产妇及其配偶产后抑郁情绪与心理弹性、二元应对存在主客体互倚关系.医护人员应将夫妻视为一个共同体及早进行干预.

Abstract Background Prenatal depression is one of the most prevalent psychiatric disorders among maternal. Perceived stress plays an important role in the onset of prenatal depression, however, the underlying mechanisms between them are not well understood. We aimed to explore the mechanisms from rumination(risk factors) and cognitive reappraisal(protective factors) perspectives, which may be used to design interventions to improve prenatal depression. Methods A multicenter cross-sectional survey of 1055 maternal were enrolled using a convenience sampling method from June 2020 to January 2021 and was conducted in five hospitals in Guangzhou, southeastern China. A moderated mediation model was performed to examine the role of rumination(Ruminative Responses Scale, RRS), and cognitive reappraisal(Emotional Regulation Questionnaire, ERQ) in the relationship between perceived stress(Perceived Stress Scale 10, PSS-10) and prenatal depression(Edinburgh Postpartum Depression Scale, EPDS). Results The prevalence of prenatal depression was 37.53%. There was a significant correlation among perceived stress, rumination, cognitive reappraisal, and prenatal depression(all P < 0.001). Rumination played a partial mediating role in the relationship between perceived stress and prenatal depression, accounting for 58.92% of the total effect. Moreover, the indirect effect of rumination in this link was moderated by cognitive reappraisal. This mediation effect was stronger for pregnant women with lower levels of cognitive reappraisal(P < 0.001). Conclusions The study provides powerful evidences through a large maternal sample for the mediating role of rumination and the moderating role of cognitive reappraisal between perceived stress and prenatal depression. Ongoing clinical care and targeted interventions may need to carry out from the perspective of rumination according to the different cognitive levels of maternal.