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Cognitive Disengagement Syndrome (CDS) is a cluster of behavioral problems that severely affect an individual's functioning. Currently, there is no consensus on the main clinical features of CDS, and further exploration in large samples is needed. Using a cluster-stratified random sampling method, 72,106 children and adolescents were recruited from five provinces in mainland China for this study. Using both the traditional two-factor scoring method and the CBCL DSM-oriented scales, we assessed individual behavioral problems from psychopathological and DSM-oriented perspectives. Network analysis was employed to explore the relationship between CDS and behavioral problems. The various networks were compared by gender and age subgroups. Among 72,106 participants (mean age, 11.49 years; minimum age, 5 years; maximum age, 16 years), there were 36,449 males (50.5%) and 35,657 females (49.5%). From a psychopathological perspective, the motor symptoms node was associated with the sad node and the withdrawn node, while the cognitive symptoms node was linked to the nervous node and the self-conscious node. In terms of gender, males had stronger associations of the motor symptoms node with the sad node and the withdrawn node than females (P = 0.043), and weaker associations of the cognitive symptoms node with the nervous node than females (P = 0.027). In terms of growth stage, the adolescent group had stronger associations of the cognitive symptoms node with the nervous node and the self-conscious node than the child group (P = 0.016, 0.001). From DSM perspective, motor symptoms node were associated with sad node, and cognitive symptoms node were related to can't concentrate node, nervous node, and worthless node. With increasing age, there was an upward trend in the strength of the cognitive and motor symptoms node. CDS is closely linked to psychological and behavioral issues, especially internalizing problems, with differences observed by gender and growth stage. The connection between CDS and the affective, anxiety, and ADH symptoms is particularly pronounced.
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The Motor tic, Obsessions and Compulsions, Vocal tic Evaluation Survey (MOVES) is a widely used screening tool for Tourette syndrome (TS) and associated comorbidities. This study evaluated its applicability for children in China using 7,125 participants from the National Center for Children's Health (Beijing). Psychometric evaluations included exploratory and confirmatory factor analysis, yielding a 16-item, four-factor model that explained 55.11% of the variance and demonstrated good internal consistency (Cronbach's alpha = 0.88) and test-retest reliability (ICC = 0.86). The scale showed strong convergent, discriminant, and criterion-related validity and was significantly correlated with other established TS scales. The results affirm the reliability and validity of the MOVES for screening TS in Asian contexts, addressing a crucial gap in the region's TS assessment tools.
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BACKGROUND: Life events and parenting styles might play an important role in children's mental health. AIMS: This study aims to explore how life events and parenting styles influence children's mental health based on a Chinese sample. METHODS: A total of 3535 participants had at least one mental disorder (positive group), while a total of 3561 participants had no mental disorders (negative group). The Child Behavior Checklist (CBCL), Adolescent Self-Rating Life Events Check List (ASLEC) and Egna Minnen Beträffande Uppfostran (EMBU) were used for screening these two groups. RESULTS: CBCL total scores differed significantly by sex in the Positive group according to the Mann-Whitney tests (Z = -5.40, p < 0.001). Multiple regression analyses showed that the dimensions of punishment (p = 0.014) and other (p = 0.048) in the ASLEC scale can significantly predict CBCL total scores in the Positive group. Sex, age and overprotection from the father were risk factors (p < 0.001) according to binary logistic regression. CONCLUSIONS: Life events and parenting styles may have impacts on mental health. Fathers play a very important role in children's growth. Punitive education and fathers' overprotection might be risk factors for children's mental health. IMPACT: It is a large sample (3535) study of Chinese children and adolescents It provides evidence that life events and parenting styles have impacts on mental health and that fathers play a very important role in children's growth. It is conducive to the development of interventions for the mental health of children and adolescents.
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Trastornos Mentales , Salud Mental , Adolescente , Humanos , Niño , Masculino , Estudios Transversales , Relaciones Padres-Hijo , Responsabilidad Parental/psicología , Trastornos Mentales/psicología , PadreRESUMEN
INTRODUCTION: Premonitory urge (PU) is an aversive bodily sensation that signals the onset of tic disorder.To our knowledge, PU typically precedes the appearance of tic symptoms, and both age and tic severity are correlated with PU. However, inconsistent findings have also been reported. Hence, we conducted a meta-analysis to examine the relationship among premonitory symptoms, patient age and the severity of tic symptoms, as well as to summarize the research on the neural underpinnings of PU in Tourette syndrome (TS). METHODS: We conducted a literature search of relevant studies published between December 2005 and April 2022 using databases such as PubMed, Elsevier, PsycINFO, and Web of Science. Our analysis was carried out using R software with the assistance of the "meta" and "metafor" packages. RESULTS: Our meta-analysis included 22 studies with a total of 1236 tic disorder patients. The mean Premonitory Urge for Tics Scale (PUTS) score was 20.17, with a 95% confidence interval of [18.14, 21.68]. Through meta-regression, we found that age and tic severity play important moderating roles in PU severity (p < 0.0001). Neuroimaging studies suggest that PU is related to the insula, prefrontal cortex (PFC), anterior cingulate cortex (ACC), and supplementary motor area (SMA), regardless of the structural or functional level. CONCLUSIONS: Our meta-analysis confirmed the positive relationship between the severity of tics and PU and identified age as a significant factor influencing PU. The neural mechanisms underlying PU remain largely unknown, but evidence suggests that the insula, PFC, ACC, and SMA are related regions.
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Trastornos de Tic , Tics , Síndrome de Tourette , Humanos , Giro del Cíngulo , Neuroimagen , Trastornos de Tic/diagnóstico , Síndrome de Tourette/complicaciones , Síndrome de Tourette/diagnóstico por imagenRESUMEN
BACKGROUND: To date, no national-scale psychiatric epidemiological survey for children and adolescents has been conducted in China. In order to inform government officials and policymakers and to develop a comprehensive plan for service providers, there was a clear need to conduct an up-to-date systematic nationwide psychiatric epidemiological survey. METHODS: We conducted a two-stage large-scale psychiatric point prevalence survey. Multistage cluster stratified random sampling was used as the sampling strategy. Five provinces were selected by comprehensively considering geographical partition, economic development, and rural/urban factors. In Stage 1, the Child Behavior Checklist was used as the screening tool. In Stage 2, Mini-International Neuropsychiatric Interview for Children and Adolescents and a diagnostic process based on the Diagnostic and Statistical Manual were used to make the diagnoses. Sampling weights and poststratification weights were employed to match the population distributions. Exploratory analyses were also performed using socio-demographic factors. Prevalence in socio-demographic factor subgroups and overall were estimated. Rao-Scott adjusted chi-square tests were utilized to determine if between-group differences were present. Factor interactions were checked by logistic regression analyses. RESULTS: A total of 73,992 participants aged 6-16 years of age were selected in Stage 1. In Stage 2, 17,524 individuals were screened and diagnosed. The weighted prevalence of any disorder was 17.5% (95% CI: 17.2-18.0). Statistically significant differences in prevalence of any psychiatric disorder were observed between sexes [χ2 (1, N = 71,929) = 223.0, p < .001], age groups [χ2 (1, N = 71,929) = 18.6, p < .001] and developed vs. developing areas [χ2 (1, N = 71,929) = 2,129.6, p < .001], while no difference was found between rural and urban areas [χ2 (1, N = 71,929) = 1.4, p = .239]. Male, younger individuals, children, and adolescents from developed areas had higher prevalence of any psychiatric disorder. The prevalence of any psychiatric disorder was found to decrease with the age in the male group, while the female group increased with the age. Individuals diagnosed with attention-deficit hyperactivity disorder, oppositional defiant disorder, a tic disorder, conduct disorder, and major depression disorder had the highest rates of comorbidity. CONCLUSIONS: The prevalence of any psychiatric disorder we found is the highest ever reported in China. These results urgently need to be addressed by public mental health service providers and policymakers in order to provide access to the necessary treatments and to reduce the long-term negative impact of these conditions on families and the society as a whole.
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Trastorno Depresivo Mayor , Trastornos Mentales , Adolescente , Déficit de la Atención y Trastornos de Conducta Disruptiva , Niño , China/epidemiología , Comorbilidad , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Masculino , Trastornos Mentales/diagnóstico , Trastornos Mentales/epidemiología , PrevalenciaRESUMEN
BACKGROUND: Exposure and response prevention (ERP) is a form of cognitive behavioral therapy that can effectively relieve obsessive-compulsive symptoms and tic symptoms in patients with obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). However, the effect size of ERP-based therapy is still unclear. METHODS: In this study, we performed a meta-analysis to identify the efficacy of ERP-based therapy for individuals with OCD and TS. The standard mean difference (SMD) with a 95% confidence interval (CI) was calculated to assess the effect size of the efficacy for ERP-based therapy. We used subgroup and meta-regression analyses to explore the heterogeneity of the pooled SMD of ERP-based therapy for OCD. We also summarized the neuroimaging studies for ERP-based therapy for OCD. This meta-analysis was registered within the International Platform of Registered Systematic Review and Meta-analysis Protocols (number: INPLASY2021120112). RESULTS: A total of 18 studies including a total of 1057 patients with OCD and 3 studies including 267 with TS/chronic tic disorder were identified. We did not observe any indication of publication bias using Egger's funnel plot (p = 0.41). We observed a small-to-medium effect size of ERP for both OCD (SMD = -0.27, 95% CI: -0.53 to -0.01) and TS/chronic tic disorder (SMD = -0.35, 95% CI: -0.59 to -0.1). We found no heterogeneity of ERP-based therapy for OCD between the ERP-based therapy subgroup and medicine subgroup in the subgroup analysis (p = 0.72). We found no heterogeneity of ERP-based therapy for OCD between the child subgroup and adult subgroup in the subgroup analysis (p = 0.37). We used meta-regression analysis to identify the heterogeneity of ERP-based therapy for OCD and found that the sessions of therapy and publication year did not account for any significant heterogeneity (p > 0.05). The neurological mechanism of EPR-based therapy is unclear, but it may lie in changes in the prefrontal cortex and anterior cingulate cortex. CONCLUSIONS: In conclusion, we found that ERP-based therapy is effective for patients with OCD and TS/chronic tic disorder. We suggest a combination with other therapies and the development of online ERP services that might prove a promising new direction for healthcare providers.
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Trastorno Obsesivo Compulsivo , Trastornos de Tic , Síndrome de Tourette , Adulto , Niño , Familia , Giro del Cíngulo , Humanos , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/psicología , Trastorno Obsesivo Compulsivo/terapia , Síndrome de Tourette/diagnóstico , Síndrome de Tourette/psicología , Síndrome de Tourette/terapiaRESUMEN
Repetitive transcranial megnetic stimulation (rTMS) has been widely used in patients with psychiatric disorders. Previous studies revealed good efficacy of rTMS for patients with obsession-compulsive disorder (OCD) and Tic disorder (TD). OCD and TD are closely related and considered to etiologically overlap. Patients with the co-occurrence of OCD and TD are often identified. Therefore, we conducted a quick review of rTMS for the treatment of these two diseases to compare the similarities and differences of rTMS for OCD and TD, which might provide an indication for the treatment of the co-occurrence of OCD and TD. We searched articles published in PubMed, Wanfang, and Web of Science from January 2001 to January 2022. Both inclusion criteria and exclusion criteria were developed to identify the relevant included studies. Data on the frequency, target area, sample size, and number of males, especially the rTMS treatment procedure or parameters, were extracted in the included studies. We included 26 studies on OCD and 12 studies on TD in this quick review. A total of 996 participants were included. Based on the review of the included studies, lowfrequency rTMS might be used more than high-frequency rTMS, and the supplementary motor area (SMA) might show better efficacy than the dorsolateral prefrontal cortex (DLPFC) in OCD. For patients with TD, low-frequency rTMS located in the SMA might show good efficacy both in OCD and TD. Our quick review elaborated the treatment efficacy of rTMS for both patients with OCD and those with TD. It seems that the SMA is an important target choice for both OCD and TD patients. Low-frequency rTMS might be used more than high-frequency rTMS in both OCD and TD patients. In future studies, we should explore more about the efficacy of rTMS for patients with co-occurring OCD and TD, especially for the efficacy of targeted SMA with low frequency.
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Corteza Motora , Trastorno Obsesivo Compulsivo , Trastornos de Tic , Masculino , Humanos , Estimulación Magnética Transcraneal/métodos , Trastorno Obsesivo Compulsivo/terapia , Trastorno Obsesivo Compulsivo/etiología , Trastorno Obsesivo Compulsivo/psicología , Resultado del Tratamiento , Trastornos de Tic/terapia , Trastornos de Tic/etiologíaRESUMEN
BACKGROUND: To the best of our knowledge, although the Chinese version of the Yale Global Tic Severity Scale (YGTSS) is widely used in child psychiatry departments in China, there is very little evidence focusing on the psychometric characteristics of the Chinese version of YGTSS. In this present study, we aim to re-examine the structure of the Chinese version of YGTSS and investigate its reliability and validity. METHODS: A total of 367 children and adolescents with tic disorders aged 5-16 years old participated in the study. The Cronbach's alpha, test-retest reliability and concurrent validity will be calculated. Confirmatory Factor Analysis (CFA) also will be performed to assess the structure of YGTSS. RESULTS: The Cronbach's alpha of the motor tic subscale of YGTSS was 0.84, for the phonic tic subscale of YGTSS, it was 0.90, but for the whole scale, it was 0.58. The test-retest reliability of YGTSS was 0.84. For the results of CFA, the Comparative Fit Index (CFI) of YGTSS based on the Two-Factor Model and Three-Factor Model was 0.97 and 0.96 respectively. The measurement invariance analysis suggested that the Two-Factor model of YGTSS across different age and sex groups was at the accepted level (≥0.90). CONCLUSION: Overall, according to the results of this research, it suggested that the Chinese version of YGTSS showed good psychometric properties. It can be used in the assessment of tic disorders in the Chinese population. In the future, more comprehensive tools for assessing tics need to be further developed, which can cover the symptoms of premonitory urge and tic related obsessive-compulsive symptoms.
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Trastornos de Tic , Tics , Síndrome de Tourette , Adolescente , Niño , Preescolar , China , Humanos , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Trastornos de Tic/diagnóstico , Síndrome de Tourette/diagnósticoRESUMEN
BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder defined by the continual presence of primary motor and vocal tics. Grey matter abnormalities have been identified in numerous studies of TS, but conflicting results have been reported. This study was an unbiased statistical meta-analysis of published neuroimaging studies of TS structures. METHODS: A voxel quantitative meta-analysis technique called activation likelihood estimation (ALE) was used. The meta-analysis included six neuroimaging studies involving 247 TS patients and 236 healthy controls. A statistical threshold of p < 0.05 was established based on the false discovery rate and a cluster extent threshold of 50 voxels. RESULTS: We found that grey matter volumes were significantly increased in the bilateral thalamus, right hypothalamus, right precentral gyrus, left postcentral gyrus, left inferior parietal lobule, right lentiform nucleus, and left insula of TS patients compared to those of healthy controls. In contrast, grey matter volumes were significantly decreased in the bilateral postcentral gyrus, bilateral anterior cingulate, bilateral insula, left posterior cingulate and left postcentral gyrus of TS patients compared to those of healthy controls. CONCLUSIONS: Our present meta-analysis primarily revealed significant increases in grey matter volumes in the thalamus and lentiform nucleus, and decreased grey matter volumes in the anterior cingulate gyrus, of TS patients compared to those in healthy controls. Most of these identified regions are associated with cortico-striato-thalamo-cortical circuits. Further studies with larger sample sizes are needed to confirm these changes in grey matter volumes in TS patients.
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Sustancia Gris , Síndrome de Tourette , Encéfalo , Sustancia Gris/diagnóstico por imagen , Giro del Cíngulo , Humanos , Funciones de Verosimilitud , Imagen por Resonancia Magnética , Neuroimagen , Síndrome de Tourette/diagnóstico por imagenRESUMEN
Improving the mental health of children and adolescents is a critical priority in China. However, only minimal information is available concerning the prevalence of mental disorders. In the present study, a two-stage national survey has been completed in five regions of China. In the first stage, data from the Achenbach Child Behavior Checklist (CBCL) were collected for each participant to identify the prevalence of the behavioral and emotional problems in China. A multistage cluster stratified random sampling design was used, and a total of 71,929 individuals aged 6-16 years were collected. In this large cohort, 36,893 (49.86%) were males, and 49,015 (66.24%) were living in urban communities. Overall, 17.6% (90% confidence interval 17.4%, 17.9%) of the children and adolescents were identified as having behavioral and emotional problems. Moreover, age and sex effect was found for the CBCL scores. The boys' cohort had a higher prevalence of behavioral and emotional problems than girls (18.6% versus 16.6%). In the older cohort aged 12-16, the prevalence was higher than for the younger cohort aged 6-11 (19.0% versus 15.9%). Notably, it seems that the prevalence of the behavioral and emotional problems for children and adolescents had a rise in the past 30 years, but the scarcity of pediatric psychiatrists in China needs to be addressed. To reduce the behavioral and emotional problems, the whole society, including mental health providers, educators, and parents, needs to focus on and pay more attention to it. It will have long-term benefits for China.
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Síntomas Afectivos/psicología , Trastornos de la Conducta Infantil/psicología , Niño , China , Femenino , Humanos , Masculino , Trastornos Mentales/epidemiología , Prevalencia , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Early-onset schizophrenia is a severe and rare form of schizophrenia that is clinically and neurobiologically continuous with the adult form of schizophrenia. Neuregulin1 (NRG1)-mediated signaling is crucial for early neurodevelopment, which exerts its function by limited ß-secretase 1 (BACE1) proteolysis processing. However, circulating neuregulin1-ß1 (NRG1-ß1), an isoform of NRG1, and its cleavage enzyme BACE1 have not been studied in early-onset patients with schizophrenia. METHODS: In this study, we collected plasma and clinical information from 71 young patients (7â¯≤â¯age years ≤20) with schizophrenia and 53 age- and sex-matched healthy controls. Immunoassay was used to test levels of circulating NRG1-ß1 and BACE1 expression. We further analyzed the relationship of disease-onset age and gender with NRG1-ß1 and BACE1 levels. RESULTS: We found that circulating plasma levels of NRG1-ß1 were significantly decreased in young patients with early-onset schizophrenia. In males with childhood onset schizophrenia (COS), NRG1-ß1 was reduced and was inversely correlated with positive symptom of PANSS; moreover, these male patients with higher plasma BACE1 levels showed more severe general symptoms of PANSS and defective social functioning; whereas, no aforementioned results were found in adolescent-onset schizophrenia (AOS). Notably, young female patients with COS and AOS had no significant change in NRG1-ß1 and BACE1, which demonstrated a sex-dependent effect in early-onset schizophrenia. CONCLUSION: Our results suggest that decreased levels of NRG1-ß1 and its cleavage enzyme BACE1 contribute to increased risk of etiology of schizophrenia. Synthetic biomarkers may have clinical applications for the early diagnosis of male COS.
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Secretasas de la Proteína Precursora del Amiloide/sangre , Ácido Aspártico Endopeptidasas/sangre , Neurregulina-1/sangre , Esquizofrenia/sangre , Adolescente , Edad de Inicio , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Ácido Aspártico Endopeptidasas/metabolismo , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Esquizofrenia/etiología , Esquizofrenia/metabolismo , Factores Sexuales , Transducción de Señal , Adulto JovenAsunto(s)
COVID-19 , Trastornos Mentales , Niño , China/epidemiología , Humanos , Trastornos Mentales/epidemiología , Salud Mental , Pandemias , SARS-CoV-2RESUMEN
BACKGROUND AND PURPOSE: Neurexin-1ß and neuroligin-1 play an important role in the formation, maintenance, and regulation of synaptic structures. This study is to estimate the potential role of neurexin-1ß and neuroligin-1 in subarachnoid hemorrhage (SAH)-induced cognitive dysfunction. METHODS: In vivo, 228 Sprague-Dawley rats were used. An experimental SAH model was induced by single blood injection to prechiasmatic cistern. Primary cultured hippocampal neurons were exposed to oxyhemoglobin to mimic SAH in vitro. Specific small interfering RNAs and expression plasmids for neurexin-1ß and neuroligin-1 were exploited both in vivo and in vitro. Western blot, immunofluorescence, immunoprecipitation, neurological scoring, and Morris water maze were performed to evaluate the mechanism of neurexin-1ß and neuroligin-1, as well as neurological outcome. RESULTS: Both in vivo and in vitro experiments showed SAH-induced decrease in the expressions of neurexin-1ß and neuroligin-1 and the interaction between neurexin-1ß and neuroligin-1 in neurons. In addition, the interaction between neurexin-1ß and neuroligin-1 was reduced by their knockdown and increased by their overexpression. The formation of excitatory synapses was inhibited by oxyhemoglobin treatment, which was significantly ameliorated by overexpression of neurexin-1ß and neuroligin-1 and aggravated by the knockdown of neurexin-1ß and neuroligin-1. More importantly, neurexin-1ß and neuroligin-1 overexpression ameliorated SAH-induced cognitive dysfunction, whereas neurexin-1ß and neuroligin-1 knockdown induced an opposite effect. CONCLUSIONS: Enhancing the expressions of neurexin-1ß and neuroligin-1 could promote the interaction between them and the formation of excitatory synapses, which is helpful to improve cognitive dysfunction after SAH. Neurexin-1ß and neuroligin-1 might be good targets for improving cognitive function after SAH.
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Moléculas de Adhesión Celular Neuronal/metabolismo , Trastornos del Conocimiento/metabolismo , Trastornos del Conocimiento/fisiopatología , Proteínas del Tejido Nervioso/metabolismo , Hemorragia Subaracnoidea/metabolismo , Animales , Conducta Animal/fisiología , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Phenotype of chronic rhinosinusitis (CRS) may be an important determining factor of the efficacy of anti-inflammatory treatments. Although both glucocorticoids and macrolide antibiotics have been recommended for the treatment of CRS, whether they have different anti-inflammatory functions for distinct phenotypic CRS has not been completely understood. The aim of this study is to compare the anti-inflammatory effects of clarithromycin and dexamethasone on sinonasal mucosal explants from different phenotypic CRS ex vivo. METHODS: Ethmoid mucosal tissues from CRSsNP patients (n = 15), and polyp tissues from eosinophilic (n = 13) and non-eosinophilic (n = 12) CRSwNP patients were cultured in an ex vivo explant model with or without dexamethasone or clarithromycin treatment for 24 h. After culture, the production and/or expression of anti-inflammatory molecules, epithelial-derived cytokines, pro-inflammatory cytokines, T helper (Th)1, Th2 and Th17 cytokines, chemokines, dendritic cell relevant markers, pattern recognition receptors (PRRs), and tissue remodeling factors were detected in tissue explants or culture supernatants by RT-PCR or ELISA, respectively. RESULTS: We found that both clarithromycin and dexamethasone up-regulated the production of anti-inflammatory mediators (Clara cell 10-kDa protein and interleukin (IL)-10), whereas down-regulated the production of Th2 response and eosinophilia promoting molecules (thymic stromal lymphopoietin, IL-25, IL-33, CD80, CD86, OX40 ligand, programmed cell death ligand 1, CCL17, CCL22, CCL11, CCL5, IL-5, IL-13, and eosinophilic cationic protein) and Th1 response and neutrophilia promoting molecules (CXCL8, CXCL5, CXCL10, CXCL9, interferon-γ, and IL-12), from sinonasal mucosa from distinct phenotypic CRS. In contrast, they had no effect on IL-17A production. The expression of PRRs (Toll-like receptors and melanoma differentiation-associated gene 5) was induced, and the production of tissue remodeling factors (transforming growth factor-ß1, epidermal growth factor, basic fibroblast growth factor, platelet derived growth factor, vascular endothelial growth factor, and matrix metalloproteinase 9) was suppressed, in different phenotypic CRS by dexamethasone and clarithromycin in comparable extent. CONCLUSIONS: Out of our expectation, our explant model study discovered herein that glucocorticoids and macrolides likely exerted similar regulatory actions on CRS and most of their effects did not vary by the phenotypes of CRS.
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Antiinflamatorios/uso terapéutico , Claritromicina/uso terapéutico , Dexametasona/uso terapéutico , Modelos Biológicos , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Adulto , Antiinflamatorios/farmacología , Biomarcadores/metabolismo , Supervivencia Celular/efectos de los fármacos , Enfermedad Crónica , Claritromicina/farmacología , Citocinas/metabolismo , Células Dendríticas/metabolismo , Dexametasona/farmacología , Relación Dosis-Respuesta a Droga , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Mediadores de Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Mifepristona/farmacología , Fenotipo , Proyectos Piloto , Receptores de Reconocimiento de Patrones/metabolismo , Rinitis/complicaciones , Rinitis/genética , Sinusitis/complicaciones , Sinusitis/genética , Linfocitos T Colaboradores-Inductores/efectos de los fármacos , Linfocitos T Colaboradores-Inductores/metabolismoRESUMEN
RATIONALE: Although eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) exhibit distinct T-helper (Th) responses, the underlying mechanisms remain unclear. OBJECTIVES: To clarify the phenotypes and Th-cell polarizing functions of dendritic cells (DCs) in different types of CRSwNP. METHODS: DC subsets, their surface phenotypes, and Th-cell subsets were studied by means of immunohistochemistry and flow cytometry. The sorted lesional DCs were activated or cultured with autologous naive CD4(+) T cells, and cytokine production was determined by ELISA. Thymic stromal lymphopoietin and osteopontin expression were detected by means of reverse-transcriptase polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: Although elevated local Th1 and Th17 cells were noted in both eosinophilic and noneosinophilic CRSwNP, increased Th2 cells were found only in eosinophilic CRSwNP. Increased numbers of myeloid DCs, plasmacytoid DCs, and their activated subsets were found in both types of CRSwNP, but only myeloid DCs and plasmacytoid DCs from eosinophilic CRSwNP demonstrated an up-regulation of OX40 ligand (OX40L) and programmed death ligand 1(PD-L1) expression. Lesional DCs from both types of CRSwNP produced enhanced levels of IL-12, IL-6, and transforming growth factor-ß, and induced increased Th1 and Th17 responses; in contrast, only DCs from eosinophilic CRSwNP induced obviously enhanced Th2 responses, when cocultured with naive CD4(+) T cells. Blockade of OX40L and PD-L1 on lesional DCs from eosinophilic CRSwNP suppressed Th2 responses, but promoted Th1 responses in DC-T cell coculture. CONCLUSIONS: Distinct subsets of lesional DCs were found in eosinophilic and noneosinophilic CRSwNP, where OX40L/PD-L1(+) lesional DCs in eosinophilic CRSwNP could prime Th2 cells, whereas the low OX40L/PD-L1-expressing lesional DCs in noneosinophilic CRSwNP primarily induced Th1/Th17 cells.
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Células Dendríticas/inmunología , Pólipos Nasales/inmunología , Rinitis/inmunología , Sinusitis/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Células Cultivadas , Enfermedad Crónica , Humanos , Interleucina-7/metabolismo , Pólipos Nasales/complicaciones , Osteopontina/metabolismo , Fenotipo , Rinitis/complicaciones , Sinusitis/complicacionesRESUMEN
Ischemia-reperfusion (I/R) injury induces the generation of reactive oxygen species (ROS), which results in a poor prognosis for ischemic stroke patients. This study was designed to evaluate the time course of expression of the Nox family, a major source of ROS, and whether melatonin, a potent scavenger of ROS, influences these parameters in a rat model of cerebral I/R caused by middle cerebral artery occlusion (MCAO). After 2-hr occlusion, the filament was withdrawn to allow reperfusion. At 0, 3, 6, 12, 24, and 48 hr after reperfusion, brain tissue samples were obtained for assays. Among the Nox family, the mRNA and protein levels of Nox2 and Nox4 were increased both in the ischemic hemisphere and contralateral counterpart in the experimental I/R rats at 0 hr after reperfusion, peaked at 3 hr, and then returned to the basal level at 24 hr. Double-immunofluorescence staining further confirmed the expressions of Nox2 and Nox4 in three major types of brain cells, including neurons, astrocytes, and endothelial cells. In addition, melatonin (5 mg/kg) or its vehicle was injected intraperitoneally at 0.5 hr before MCAO. Compared with I/R + vehicle group, melatonin pretreatment diminished the increased expression of Nox2 and Nox4, reduced ROS levels, and inhibited cell apoptosis. Our findings suggested that the inhibition of Nox2 and Nox4 expressions by melatonin may essentially contribute to its antioxidant and anti-apoptotic effects during brain I/R.
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Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Glicoproteínas de Membrana/metabolismo , NADPH Oxidasas/metabolismo , Daño por Reperfusión/metabolismo , Animales , Western Blotting , Isquemia Encefálica/genética , Etiquetado Corte-Fin in Situ , Masculino , Melatonina , Glicoproteínas de Membrana/genética , Microscopía Fluorescente , NADPH Oxidasa 2 , NADPH Oxidasa 4 , NADPH Oxidasas/genética , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: T(H)17 responses have recently been implicated to play a role in allergic airway diseases, but their local expression in the setting of allergic rhinitis (AR) and their regulation in allergic airway diseases remain unclear. OBJECTIVE: We sought to investigate the regulatory role of Clara cell 10-kDa protein (CC10), an endogenous regulator of airway inflammation, on T(H)17 responses in the setting of AR. METHODS: Wild-type and homozygous CC10-null mice were used to establish an ovalbumin (OVA)-induced AR model. Human recombinant CC10 was given during sensitization or challenge. T(H)17 responses in human subjects and mice were examined by using flow cytometry, quantitative RT-PCR assay, immunohistochemistry, and ELISA. The direct effect of CC10 on T(H)17 cells and CD11c(+) dendritic cells (DCs) was studied by means of cell culture. Adoptive transfer was used to examine the influence of CC10-conditioned DCs on airway inflammation. The regulatory effect of CC10 on the expression of the CCL20 gene was tested by using the BEAS-2B cell line. RESULTS: Compared with those of control subjects, T(H)17 responses were enhanced in the nasal mucosa of patients with AR. CC10-null mice with AR showed enhanced T(H)17 responses, and CC10 treatment significantly decreased T(H)17 responses. CC10 had no direct effect on in vitro T(H)17 cell differentiation. CC10 could significantly decrease the expression of OX40 ligand, IL-23, and IL-6 but enhance CD86 and TGF-ß expression in DCs. Importantly, CC10 was able to inhibit T(H)17 cell polarization in the presence of OVA-pulsed DCs. CC10 pretreatment inhibited T(H)17 responses elicited by adoptive transfer of OVA-pulsed DCs. Furthermore, CC10 decreased the expression of CCL20 in BEAS-2B cells induced by inflammatory cytokines. CONCLUSION: T(H)17 responses are enhanced in patients with AR, and CC10 inhibits T(H)17 responses through modulation of the function of DCs.
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Células Dendríticas/inmunología , Rinitis Alérgica Perenne/inmunología , Células Th17/inmunología , Uteroglobina/inmunología , Traslado Adoptivo/métodos , Animales , Antígeno B7-2/inmunología , Estudios de Casos y Controles , Diferenciación Celular/inmunología , Línea Celular , Quimiocina CCL20/inmunología , Eosinófilos/inmunología , Células Epiteliales/inmunología , Humanos , Interleucina-23/inmunología , Interleucina-6/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Mucosa Nasal/inmunología , Neutrófilos/inmunología , Ligando OX40/metabolismo , Ovalbúmina/farmacología , Neumonía/inmunología , Receptores de Formil Péptido/inmunología , Proteínas Recombinantes/inmunología , Rinitis Alérgica , Rinitis Alérgica Perenne/inducido químicamente , Factor de Crecimiento Transformador beta/inmunología , Uteroglobina/deficienciaRESUMEN
BACKGROUND: Sleep problems are commonly observed in patients with tic disorders. Nevertheless, studies have demonstrated a wide variation in the prevalence of sleep disturbances among this population. Consequently, it remains ambiguous whether sleep issues are inherently characteristic of tic disorders or are influenced by external factors. METHODS: We conducted a comprehensive search across various databases and performed a meta-analysis to determine the prevalence of sleep problems in tic disorders. Additionally, we assessed pre-existing comorbidities and associated characteristics using meta-regression analysis. RESULTS: After including 33 studies in the final meta-analysis, we found that the pooled prevalence of sleep problems in tic disorders was 34% (95%CI: 26% to 43%). Meta-regression analysis revealed that the presence of co-occurring symptoms of ADHD (p < 0.05), obsession compulsive disorder/behaviours (p < 0.05), anxiety (p < 0.001), and mood disorders (p < 0.001) was associated with an increased likelihood of experiencing sleep problems. CONCLUSIONS: Our findings consistently indicate that individuals with tic disorders frequently encounter significant sleep problems. This underscores the importance of routinely screening for sleep problems during clinical assessments. Effectively managing sleep problems in patients with tic disorders is crucial not only for the well-being of the patients themselves but also for their families.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastorno Obsesivo Compulsivo , Trastornos del Sueño-Vigilia , Trastornos de Tic , Síndrome de Tourette , Humanos , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Prevalencia , Trastornos de Tic/epidemiología , Trastornos de Tic/complicaciones , Trastornos de Tic/diagnóstico , Trastorno Obsesivo Compulsivo/complicaciones , Trastornos del Sueño-Vigilia/epidemiologíaRESUMEN
Background: Autism Spectrum Disorders (ASD) are a collection of neurodevelopmental diseases characterized by poor social interaction and communication, a limited range of interests, and stereotyped behavior. High-functioning autism (HFA) indicates a subgroup of individuals with autism who possess cognitive and/or language skills that are within the average to above-normal range for their age. Transcutaneous auricular vagus nerve stimulation (taVNS) holds promise in children with HFA. However, few studies have used randomized controlled trials to validate the effectiveness of taVNS. Therefore, in this study, we intend to provide a study protocol to examine the therapeutic effects of taVNS in individuals diagnosed with HFA and to investigate the process of brain network remodeling in individuals with ASD using functional imaging techniques to observe alterations in large-scale neural networks. Methods and design: We planned to employ a randomized, double-blind experimental design, including 40 children receiving sham stimulation and 40 children receiving real stimulation. We will assess clinical scales and perform functional imaging examinations before and after the stimulation. Additionally, we will include age- and gender-matched healthy children as controls and conduct functional imaging examinations. We plan first to observe the therapeutic effects of taVNS. Furthermore, we will observe the impact of taVNS stimulation on the brain network. Discussion: taVNS was a low-risk, easy-to-administer, low-cost, and portable option to modulate the vagus system. taVNS may improve the social performance of HFA. Changes in the network properties of the large-scale brain network may be related to the efficacy of taVNS. Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR2300074035.