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Aim: Prior research has indicated a connection between CD4+ T cells and the development of anxiety, but the specific CD4+ T cell subsets linked to anxiety disorders remain uncertain. Our study seeks to investigate the relationship between distinct CD4+ T cell subsets and anxiety, as well as to explore whether CD4+ T cell subsets mediate the effect of chronic psychological stress on anxiety. Methods: 56 eligible matched participants were recruited in Peking Union Medical College Hospital. The diagnosis was made based on DSM-5 diagnostic criteria. The severity of anxiety and depression symptoms was assessed using the Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale, respectively. The Life Events Scale (LES) evaluated the chronic stress level. CD4+ T cell subsets were characterized using multiparametric flow cytometry. To assess the impact of CD4+ T cells on the effect of chronic psychological stress on anxiety, Partial Least Squares Structural Equation Modeling (PLS-SEM) analysis was employed. Results: We discovered fifteen notably distinct CD4+ T-cell subsets in anxiety disorder patients compared to healthy controls. Multiple linear regression analysis unveiled an association between anxiety severity and CD27+CD45RA- Th cells, CD27+CD28+ Tregs, and the total Life Events Scale (LES) score. The PLS-SEM analysis demonstrated that CD4+ T cell subsets and LES could explain 80.2% of the variance in anxiety. Furthermore, it was observed that CD27+CD28+ Th/Treg cells acted as inverse mediators of the effects of LES on anxiety (P = 0.031). Conclusions: Drug naïve anxiety disorder patients exhibited significant alterations in numerous CD4+ T-cell subsets. Specifically, the memory subset of CD27+CD45RA- Th cells and the naïve subset of CD27+CD28+ Treg cells were found to be independent factors associated with the severity of anxiety. Additionally, the CD27+CD28+ Th and Treg cell subsets played a significant mediating role in the influence of long-term psychological stress on anxiety.
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Dissociative neurological symptoms disorder (DNSD), or conversion disorder, frequently manifests with unexplained neurological symptoms, necessitating referral to psychiatry following preliminary diagnosis in neurology. We present a case of an adolescent female patient with gait disturbance as the predominant clinical presentation, and delve into the diagnosis and interdisciplinary intervention process. Given neuroimaging deviations detected and familial similar presentations, the organic etiology was confirmed. However, the aberrant gait remained unexplained ultimately prompting psychiatric consultation resulting in the diagnosis of DNSD. Interventions consisting of health education, suggestive therapy, and physiotherapy notably improved gait disturbance. However, at follow-up, the patient presented with a depressive episode. It was deduced that undiagnosed psychosocial factors, notably familial dynamics, likely contributed to this decline. Eventually, transformed relation patterns among family members as well as antidepressant treatment were instrumental in attaining symptom remission.
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With the widespread utilization of the sanitizing product benzethonium chloride (BEC) throughout the coronavirus pandemic, concerns have emerged regarding its potential hazards. Nevertheless, the long-term and multigenerational toxic effects of BEC on aquatic organisms remains unexplored. This study investigates acute and chronic toxicity, oxidative stress, mitochondrial membrane potential, ATP concentrations, and gene expression using Daphnia carinata as the model organism. Meanwhile, hierarchical clustering analysis was utilized to investigate phenotypic effects among different treatment groups. The integrated biomarker response index version 2 (IBRv2) was employed to estimate the deviation in toxic effects over two generations. These results indicated that D. carinata in the second generation exhibited higher survival rate and lower levels of oxidative stress than the first generation. However, the higher sublethal effects were found in the second generation as follows, the weakened growth performance, mitochondrial membrane potential depolarization, reduced ATP concentrations, and down-regulated gene expression. The mitochondrial toxicity induced by BEC may account for the distinct toxic effects exhibited in two generations. The findings here can assist with the evaluation of potential risk for BEC on aquatic organisms, and provide new insight into the cross-generational toxicity mechanisms of pollutants in aquatic ecosystems.
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Daphnia , Potencial de la Membrana Mitocondrial , Estrés Oxidativo , Animales , Daphnia/efectos de los fármacos , Daphnia/genética , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Adenosina Trifosfato/metabolismo , Contaminantes Químicos del Agua/toxicidadRESUMEN
MCPH1 has been identified as the causal gene for primary microcephaly type 1, a neurodevelopmental disorder characterized by reduced brain size and delayed growth. As a multifunction protein, MCPH1 has been reported to repress the expression of TERT and interact with transcriptional regulator E2F1. However, it remains unclear whether MCPH1 regulates brain development through its transcriptional regulation function. This study showed that the knockout of Mcph1 in mice leads to delayed growth as early as the embryo stage E11.5. Transcriptome analysis (RNA-seq) revealed that the deletion of Mcph1 resulted in changes in the expression levels of a limited number of genes. Although the expression of some of E2F1 targets, such as Satb2 and Cdkn1c, was affected, the differentially expressed genes (DEGs) were not significantly enriched as E2F1 target genes. Further investigations showed that primary and immortalized Mcph1 knockout mouse embryonic fibroblasts (MEFs) exhibited cell cycle arrest and cellular senescence phenotype. Interestingly, the upregulation of p19ARF was detected in Mcph1 knockout MEFs, and silencing p19Arf restored the cell cycle and growth arrest to wild-type levels. Our findings suggested it is unlikely that MCPH1 regulates neurodevelopment through E2F1-mediated transcriptional regulation, and p19ARF-dependent cell cycle arrest and cellular senescence may contribute to the developmental abnormalities observed in primary microcephaly.
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Puntos de Control del Ciclo Celular , Senescencia Celular , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Microcefalia , Animales , Ratones , Puntos de Control del Ciclo Celular/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Senescencia Celular/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/deficiencia , Factor de Transcripción E2F1/genética , Factor de Transcripción E2F1/metabolismo , Fibroblastos/metabolismo , Ratones Noqueados , Microcefalia/genética , Microcefalia/metabolismo , Microcefalia/patologíaRESUMEN
Introduction: Early detection of neuropsychiatric systemic lupus erythematosus (NPSLE) remains a challenge in clinical settings. Previous studies have found different autoantibodies as markers for NPSLE. This study aimed to describe the distribution of psychiatric syndromes in a group of patients with systemic lupus erythematosus (SLE) and to investigate the association between psychiatric syndromes and specific autoantibodies. Methods: This retrospective study was conducted at a single medical center in China. We reviewed medical records of hospitalized patients with SLE who were consulted by psychiatrists due to potential mental disorders. Results of serum autoantibodies and general laboratory tests were collected. The correlation between clinical variables was examined. Binary logistic regression analyses were used to determine factors related to NPSLE and different psychiatric diagnoses. Results: Among the 171 psychiatric manifestations in 160 patients, 141 (82.4%) were attributed to SLE. Acute confusional state (ACS) had the highest prevalence (57.4%). Anti-cardiolipin (ACL) antibody (X2 = 142.261, p < 0.001) and anti-ß2 glycoprotein I (-ß2GP1) antibody (X2 = 139.818, p < 0.001) varied significantly between groups, with the highest positive rate found in patients with mood disorders (27.3% and 18.2%). SLE disease activity index - 2000 (SLEDAI-2K) score excluding item ACS and item psychosis was a predictor of NPSLE (OR 1.172 [95% CI 1.105 - 1.243]). Conclusions: Disease activity reflected by SLEDAI-2K score is a predictor for NPSLE. Antiphospholipid antibodies are associated with mood disorders in SLE. Further separate investigation of neuropsychiatric disorders is needed in order to better comprehend NPSLE's pathological mechanism.
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Lupus Eritematoso Sistémico , Vasculitis por Lupus del Sistema Nervioso Central , Humanos , Estudios Retrospectivos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico , Autoanticuerpos , Anticuerpos Antifosfolípidos , Anticuerpos AnticardiolipinaRESUMEN
Platinum resistance represents a major barrier to the survival of patients with ovarian cancer (OC). Cdc2-like kinase 2 (CLK2) is a major protein kinase associated with oncogenic phenotype and development in some solid tumors. However, the exact role and underlying mechanism of CLK2 in the progression of OC is currently unknown. Using microarray gene expression profiling and immunostaining on OC tissues, we found that CLK2 was upregulated in OC tissues and was associated with a short platinum-free interval in patients. Functional assays showed that CLK2 protected OC cells from platinum-induced apoptosis and allowed tumor xenografts to be more resistant to platinum. Mechanistically, CLK2 phosphorylated breast cancer gene 1 (BRCA1) at serine 1423 (Ser1423) to enhance DNA damage repair, resulting in platinum resistance in OC cells. Meanwhile, in OC cells treated with platinum, p38 stabilized CLK2 protein through phosphorylating at threonine 343 of CLK2. Consequently, the combination of CLK2 and poly ADP-ribose polymerase inhibitors achieved synergistic lethal effect to overcome platinum resistance in patient-derived xenografts, especially those with wild-type BRCA1. These findings provide evidence for a potential strategy to overcome platinum resistance in OC patients by targeting CLK2.
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In modern times, a notable trend toward delayed childbearing has been observed in most developed countries. As a result, sperm aging and quality loss, as well as premature ovarian failure (POF), have emerged as major causes of infertility. The pathogenesis of sperm aging and POF is complex and has not been clearly elucidated. However, evidence from some studies has linked germ cell aging to epigenetic modifications. Epigenetics refers to the heritable changes in gene expression that occur in the absence of any alterations to the gene's nucleotide sequence. This paper systematically reviewed and analyzed the relevant literature to describe the relationship of DNA methylation, non-coding RNA regulation, histone modifications, chromatin remodeling, and RNA modifications with sperm aging and POF. In addition, we analyzed how sperm aging and POF can be mitigated via epigenetic interventions. This review could provide new therapeutic insights and guide strategies for improving sperm quality and ovarian function.
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Lung cancer is a leading cause of cancer deaths and imposes an enormous economic burden on patients. It is important to develop an accurate risk assessment model to determine the appropriate treatment for patients after an initial lung cancer diagnosis. The Cox proportional hazards model is mainly employed in survival analysis. However, real-world medical data are usually incomplete, posing a great challenge to the application of this model. Commonly used imputation methods cannot achieve sufficient accuracy when data are missing, so we investigated novel methods for the development of clinical prediction models. In this article, we present a novel model for survival prediction in missing scenarios. We collected data from 5,240 patients diagnosed with lung cancer at the Weihai Municipal Hospital, China. Then, we applied a joint model that combined a BN and a Cox model to predict mortality risk in individual patients with lung cancer. The established prognostic model achieved good predictive performance in discrimination and calibration. We showed that combining the BN with the Cox proportional hazards model is highly beneficial and provides a more efficient tool for risk prediction.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Teorema de Bayes , Pronóstico , Calibración , China/epidemiologíaRESUMEN
OBJECTIVE: This study aimed to understand the long-term symptom trajectories of Chinese patients with major depressive disorder (MDD) using piecewise latent growth modeling and growth mixture modeling. The investigation also aimed to identify the baseline characteristics indicative of poorer treatment outcomes. METHODS: A total of 558 outpatients with MDD were assessed using a sequence of surveys. The Hamilton Rating Scale for Depression (HRSD), Hamilton Anxiety Rating Scale (HAMA), and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) were used to evaluate baseline depression, anxiety, and cognitive function. Depression symptom severity was subsequently measured at the 1-month, 2-month, 6-month, 1-year, and 2-year follow-ups. RESULTS: Results indicated three depressive symptomology trajectories, including (a) severe, improving class (12.72 %), (b) partially responding, later deteriorating class (6.09 %), and (c) moderate, improving class (81.18 %). Logistic regression analyses showed that a history of cardiovascular disease (CVD) increased the odds of belonging to the partially responding, later deteriorating class, whereas higher baseline depression increased the odds of belonging to the severe, improving class compared to the moderate, improving class. Patients who experienced less depression relief during the first month of treatment had a lower probability of belonging to the moderate, improving class. LIMITATIONS: Participant attrition in this study may have inflated the estimated rate of treatment-resistant patients. CONCLUSIONS: The burden of CVD and poorer initial treatment response are plausible risk factors for poorer treatment outcomes, highlighting targets for intervention in Chinese MDD patients.
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Enfermedades Cardiovasculares , Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/psicología , Resultado del Tratamiento , Trastornos de Ansiedad , Ansiedad , DepresiónRESUMEN
The cerebral cortex is a pivotal structure integral to advanced brain functions within the mammalian central nervous system. DNA methylation and hydroxymethylation play important roles in regulating cerebral cortex development. However, it remains unclear whether abnormal cerebral cortex development, such as microcephaly, could rescale the epigenetic landscape, potentially contributing to dysregulated gene expression during brain development. In this study, we characterize and compare the DNA methylome/hydroxymethylome and transcriptome profiles of the cerebral cortex across several developmental stages in wild-type (WT) mice and Mcph1 knockout (Mcph1-del) mice with severe microcephaly. Intriguingly, we discover a global reduction of 5'-hydroxymethylcytosine (5hmC) level, primarily in TET1-binding regions, in Mcph1-del mice compared to WT mice during juvenile and adult stages. Notably, genes exhibiting diminished 5hmC levels and concurrently decreased expression are essential for neurodevelopment and brain functions. Additionally, genes displaying a delayed accumulation of 5hmC in Mcph1-del mice are significantly associated with the establishment and maintenance of the nervous system during the adult stage. These findings reveal that aberrant cerebral cortex development in the early stages profoundly alters the epigenetic regulation program, which provides unique insights into the molecular mechanisms underpinning diseases related to cerebral cortex development.
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Preterm labor/birth is the leading cause of perinatal mortality and morbidity worldwide. Previous studies demonstrated that T cells were crucial for maintaining maternal-fetal immune tolerance during the first trimester of pregnancy; however, their phenotypes and functions in labor and delivery remain largely unknown. We recruited three cohorts of women at delivery for T-cell immunophenotyping in the placentas, fetal membranes, umbilical cord blood, and maternal peripheral blood. Our data showed a differential enrichment of T cells during the third trimester of human pregnancy, with CD4+ T cells being more observable within the umbilical cord blood, whereas CD8+ T cells became relatively more abundant in fetal membranes. CD4+ and CD8+ T cells derived from fetal membranes were dominated by effector memory T cells and exhibited extensive expression of activation markers but decreased expression of homing receptor. In comparison with term births, fetal membrane CD8+ T cells, especially the central memory subset, were significantly increased in frequency and showed more profound activation in spontaneous preterm birth patients. Finally, using an allogeneic mouse model, we found that T-cell-activation-induced preterm birth could be alleviated by the depletion of CD8+ T but not CD4+ T cells in vivo. Collectively, we showed that CD8+ T cells in fetal membranes displayed a unique phenotype, and their activation was involved in the pathophysiology of spontaneous preterm birth, which provides novel insights into the immune mechanisms of preterm birth and potential targets for the prevention of this syndrome. © 2023 The Pathological Society of Great Britain and Ireland.
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Trabajo de Parto Prematuro , Nacimiento Prematuro , Embarazo , Animales , Ratones , Humanos , Femenino , Recién Nacido , Nacimiento Prematuro/inducido químicamente , Nacimiento Prematuro/prevención & control , Linfocitos T CD8-positivos , Membranas Extraembrionarias , FenotipoRESUMEN
Microplastics (MPs), a pervasive pollutant in aquatic environments, are increasingly recognized for their detrimental effects on aquatic organisms. However, the present understanding of their impact on phytoplankton, particularly freshwater microalgae, remains limited. Furthermore, previous studies have predominantly focused on MP particles, largely overlooking the most prevalent form of MPs in aquatic settings-fibers. In this study, we scrutinized the toxicological implications of microplastic fibers (MFs) spanning four distinct lengths (50 µm, 100 µm, 150 µm, and 200 µm) on the protein-nucleated algae Chlorella pyrenoidosa over a six-day period. The study unequivocally demonstrated that MFs markedly impeded C. pyrenoidosa growth, diminished photosynthetic pigment content, and induced oxidative stress, with all observed effects exhibiting a length-dependent correlation. Electron microscopy further revealed notable damage to algal cell membranes. Cell membrane shrinkage, cytoplasm outflow, and abnormalities in cell division were observed in the 150 µm and 200 µm groups. Furthermore, C. pyrenoidosa clustered around the 200 µm MF were notably denser compared to other groups. The present study demonstrated that MFs had length-dependent toxic effects on C. pyrenoidosa. These findings offer novel insights into the deleterious impact of MFs on aquatic organisms, underscoring the pivotal role of length in influencing their toxicity.
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Chlorella , Contaminantes Químicos del Agua , Microplásticos/metabolismo , Plásticos/metabolismo , Contaminantes Químicos del Agua/análisis , Estrés OxidativoRESUMEN
OBJECTIVE: The doctor-patient relationship (DPR) plays a crucial role in the Chinese healthcare system, functioning to improve medical quality and reduce medical costs. This study examined the psychometric properties of the Chinese version of the Difficult Doctor-Patient Relationship Questionnaire (DDPRQ-10) among general hospital inpatients in China. METHODS: The research recruited 38 resident doctors responsible for 120 participants, and factor analyses were used to assess the construct validity of the scale. Convergent validity was evaluated by examining the correlation between DDPRQ-10 and depressive symptoms, burnout, and self-efficacy, using the Patient Health Questionnaire Depression Scale-9 item (PHQ-9), and the Maslach Burnout Inventory (MBI). Both multidimensional item response theory (MIRT) and unidimensional item response theory (IRT) frameworks were used to estimate the parameters of each item. RESULTS: The Chinese version of DDPRQ-10 showed satisfactory internal consistency (Cronbach's alpha = 0.931), and fitted in a modified two-factor model of positive feelings and negative feelings (χ2/df = 1.494, GFI = 0.925, RMSEA = 0.071, SRMR = 0.008, CFI = 0.985, NFI = 0.958, NNFI = 0.980, TLI = 0.980, IFI = 0.986). Significant correlations with PHQ-9 with DDPRQ-10 and both subscales were revealed (r = 0.293 ~ 0.333, p < .001), while DDPRQ-10 score also significantly correlated with doctors' MBI score (r = -0.467, p < .001). The MIRT model of full scale and IRT models of both subscales showed high discrimination of all items (a = 2.30 ~ 10.18), and the test information within the range of low-quality relationship was relatively high. CONCLUSION: The Chinese version of DDPRQ-10 displayed satisfactory reliability and validity and thus was appropriate for measuring the DPR in Chinese medical settings.
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Agotamiento Profesional , Relaciones Médico-Paciente , Humanos , Psicometría , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Agotamiento Psicológico/diagnósticoRESUMEN
Importance: Despite the recommendations of lung cancer screening guidelines and the evidence supporting the effectiveness of population-based lung screening, a common barrier to effective lung cancer screening is that the participation rates of low-dose computed tomography (LDCT) screening among individuals with the highest risk are not large. There are limited data from clinical practice regarding whether opportunistic LDCT screening is associated with reduced lung-cancer mortality. Objective: To evaluate whether opportunistic LDCT screening is associated with improved prognosis among adults with lung cancer in mainland China. Design, Setting, and Participants: This cohort study included patients diagnosed with lung cancer at Weihai Municipal Hospital Healthcare Group, Weihai City, China, from 2016 to 2021. Data were analyzed from January 2022 to February 2023. Exposures: Data collected included demographic indicators, tumor characteristics, comorbidities, blood indexes, and treatment information. Patients were classified into screened and nonscreened groups on the basis of whether or not their lung cancer diagnosis occurred through opportunistic screening. Main Outcomes and Measures: Follow-up outcome indicators included lung cancer-specific mortality and all-cause mortality. Propensity score matching (PSM) was adopted to account for potential imbalanced factors between groups. The associations between LDCT screening and outcomes were analyzed using Cox regression models based on the matched data. Propensity score regression adjustment and inverse probability treatment weighting were used for sensitivity analysis. Results: A total of 5234 patients (mean [SD] baseline age, 61.8 [9.8] years; 2518 [48.1%] female) with complete opportunistic screening information were included in the analytical sample, with 2251 patients (42.91%) receiving their lung cancer diagnosis through opportunistic screening. After 1:1 PSM, 2788 patients (1394 in each group) were finally included. The baseline characteristics of the matched patients were balanced between groups. Opportunistic screening with LDCT was associated with a 49% lower risk of lung cancer death (HR, 0.51; 95% CI, 0.42-0.62) and 46% lower risk of all-cause death (HR, 0.54; 95% CI, 0.45-0.64). Conclusions and Relevance: In this cohort study of patients with lung cancer, opportunistic lung cancer screening with LDCT was associated with lower lung cancer mortality and all-cause mortality. These findings suggest that opportunistic screening is an important supplement to population screening to improve prognosis of adults with lung cancer.
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Neoplasias Pulmonares , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/epidemiología , Estudios de Cohortes , Detección Precoz del Cáncer/métodos , Tomografía Computarizada por Rayos X/métodos , PulmónRESUMEN
Microplastic pollution, especially microfibers (MFs), presents a critical global environmental challenge in natural water bodies. Yet, research on the toxic effects of MFs, particularly during early fish development, is limited. This study aimed to investigate MFs' toxic effects and mechanisms on early-stage zebrafish. Zebrafish embryos were exposed to varying concentrations of polyacrylonitrile microfibers (PanMfs) for 7 days. Results revealed PanMfs adhering to the embryos' surface, with higher concentrations accelerating heart rate and causing pericardial edema in post-hatching larvae. Larvae ingested PanMfs, leading to their accumulation in the intestines and increased levels of reactive oxygen species (ROS) and mitochondrial quantity. Notably, lipid metabolism and calcium ion related signaling pathways underwent significant changes. Low concentration MFs affected glycometabolism pathways, with potential roles for aldob and cacng1a, exhibiting pronounced increases in ROS levels. High concentration of MFs had the most profound impact on signal transduction-related pathways, and possibly triggering micromitophagy and apoptosis in zebrafish intestinal epithelial cells through the Kras/MAPK signaling pathway, with potential roles for kras and mapk9. Although ROS increase was somewhat alleviated, it resulted in decreased survival rates and restricted growth in high concentration of MFs group. These findings highlight the significant threat of MFs to the early survival of fish. MFs pollution prevention and control hold great significance in the conservation of fishery resources.
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Contaminantes Químicos del Agua , Pez Cebra , Animales , Pez Cebra/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/farmacología , Embrión no Mamífero , Plásticos , Contaminantes Químicos del Agua/toxicidad , LarvaRESUMEN
BACKGROUND: For better disease management and improved prognosis, early identification of co-morbid depression in diabetic patients is warranted. the WHO-5 well-being index (WHO-5) has been used to screen for depression in diabetic patients, and its Chinese version (WHO-5-C) has been validated. However, its psychometric properties remain to be further validated in the type 2 diabetes patient population. The aim of our study was to examine the reliability and validity of the WHO-5-C in patients with type 2 diabetes mellitus. METHODS: The cross-sectional study was conducted on 200 patients from July 2014 to March 2015. All patients should complete the WHO-5-C, the Patient Health Questionnaire-9 (PHQ-9), the 20-item Problem Areas in Diabetes Scale (PAID-20), the Mini International Neuropsychiatric Interview (M.I.N.I), and Hamilton Rating Scale for Depression (HAM-D). Internal consistency of WHO-5 was revealed by Cronbach's alpha, and constructive validity by confirmatory factor analysis (CFA). Relationship with PHQ-9, HAM-D, and PAID-20 was examined for concurrent validity, and ROC analysis was performed for criterion validity. RESULTS: The WHO-5-C presented satisfactory reliability (Cronbach's alpha = 0.88). CFA confirmed the unidimensional factor structure of WHO-5-C. The WHO-5-C had significant negative correlation with HAM-D (r = -0.610), PHQ-9 (r = -0.694) and PAID-20 (r = -0.466), confirming good concurrent validity. Using M.I.N.I as the gold standard, the cut-off value of WHO-5-C was 42, with a sensitivity of 0.83 and specificity of 0.75. CONCLUSION: The WHO-5-C holds satisfactory reliability and validity that is suitable for depression screening in type 2 diabetes patients as a short and convenient instrument.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/psicología , Estudios Transversales , Reproducibilidad de los Resultados , Cuestionario de Salud del Paciente , Psicometría , Organización Mundial de la Salud , Encuestas y Cuestionarios , Depresión/complicaciones , Depresión/diagnósticoRESUMEN
Introduction: Previous research has revealed a bidirectional relationship between type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD). A very limited proportion of patients with T2DM comorbid MDD received adequate psychiatric intervention. This study investigated the help-seeking behaviors of patients with T2DM comorbid with MDD during one-year follow-up. Methods: At a medical center in China, a cohort of outpatients with T2DM were assessed and diagnosed for comorbid depression at baseline and after one year. The Mini International Neuropsychiatric Interview was used to diagnose MDD, while The Patient Health Questionnaire-9 (PHQ-9) and The Hamilton Depression Scale 17-item (HAMD-17) were used for depression assessment. Mental health help-seeking behaviors of patients during follow-up period were also evaluated. Results: Out of the 203 patients with T2DM at baseline, 114 (56.2%) completed the follow-up. The prevalence of MDD in participants with T2DM was 12.8% at baseline and 22.8% at follow-up. Patients who completed the follow-up had a lower baseline PHQ-9 score (test statistic -2.068, p=0.039), HAMD-17 score (test statistic -2.285, p=0.022) than those who did not complete the follow-up. A total of 26 patients had comorbid MDD during the follow-up period, among which 8 patients (30.8%) voluntarily visited psychiatric clinics, while others did not seek assistance. The level of HbA1c at follow-up was higher in patients who sought help than in those who did not (8.1 ± 1.8% vs. 7.0 ± 0.7%), although the difference was not statistically significant. Conclusion: Voluntary psychiatric help-seeking for Chinese patients with comorbid T2DM and MDD is uncommon. It is crucial to increase awareness of depression among patients and healthcare professionals alike.
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Trastorno Depresivo Mayor , Diabetes Mellitus Tipo 2 , Aceptación de la Atención de Salud , Humanos , Comorbilidad , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/diagnóstico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/psicología , Pueblos del Este de Asia , Estudios de SeguimientoRESUMEN
BACKGROUND: An immunosuppressive tumor microenvironment in ovarian cancer facilitates tumor progression and resistance to immunotherapy. The function of MYB Proto-Oncogene Like 2 (MYBL2) in the tumor microenvironment remains largely unexplored. METHODS: A syngeneic intraovarian mouse model, flow cytometry analysis, and immunohistochemistry were used to explore the biological function of MYBL2 in tumor progression and immune escape. Molecular and biochemical strategies-namely RNA-sequencing, western blotting, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay, multiplex immunofluorescence, chromatic immunoprecipitation assay (CHIP) and luciferase assay-were used to reveal the mechanisms of MYBL2 in the OVC microenvironment. RESULTS: We found tumor derived MYBL2 indicated poor prognosis and selectively correlated with tumor associated macrophages (TAMs) in ovarian cancer. Mechanically, C-C motif chemokine ligand 2 (CCL2) transcriptionally activated by MYBL2 induced TAMs recruitment and M2-like polarization in vitro. Using a syngeneic intraovarian mouse model, we identified MYBL2 promoted tumor malignancyand increased tumor-infiltrating immunosuppressive macrophages. Cyclin-dependent kinase 2 (CDK2) was a known upstream kinase to phosphorylate MYBL2 and promote its transcriptional function. The upstream inhibitor of CDK2, CVT-313, reprogrammed the tumor microenvironment and reduced anti-PD-1 resistance. CONCLUSIONS: The MYBL2/CCL2 axis contributing to TAMs recruitment and M2-like polarization is crucial to immune evasion and anti-PD-1 resistance in ovarian cancer, which is a potential target to enhance the efficacy of immunotherapy.