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Aim: To identify the optimal first-line treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC). Materials & methods: We conducted a network meta-analysis (CRD42023486863) to systematically evaluate the efficacy and safety of eight first-line treatment regimens for ES-SCLC, including 15 clinical trials. Results: Our analysis showed that the PD-1/PD-L1 + etoposide combined with platinum (EP) and PD-L1 + vascular endothelial growth factor (VEGF) + EP regimens significantly enhanced overall survival and progression-free survival, with subgroup analysis revealing that serplulimab ranked as the most promising option for improving overall survival. Integrating anti-angiogenesis drugs into immunochemotherapy presents potential benefits, with an increased incidence of adverse events necessitating further investigation. Conclusion: Our findings offer valuable insights for future research and for developing more effective treatment strategies for ES-SCLC, underscoring the critical need for continued innovation in this therapeutic area.
[Box: see text].
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INTRODUCTION: Orthodontic treatment using face mask protraction combined with an alternate rapid maxillary expansion and constriction/protraction face mask (Alt-RAMEC/PFM) protocol is effective in the early treatment of patients with class III malocclusion, but the stability of treatment outcomes represents a major concern. Previous studies have suggested that tonsillar hypertrophy can be a risk factor for class III malocclusion and tonsillectomy may prompt the normalisation of dentofacial growth. However, these studies had a low-to-moderate level of evidence. This study was designed to identify the impact of tonsillectomy before orthodontic treatment on the efficacy and stability of Alt-RAMEC/PFM protocols and the sleep quality and oral health in children with anterior crossbite and tonsillar hypertrophy. METHODS AND ANALYSIS: This is a two-arm, parallel-group, superiority cluster randomised controlled trial, with four clinics randomly assigned to the surgery-first arm and the orthodontic-first arm in a 1:1 ratio. The Alt-RAMEC protocol involves alternate activation and deactivation of the expander's jet screw over 6 weeks to stimulate maxillary suture distraction. Patients will be instructed to wear the PFM for a minimum of 14 hours per day. The primary outcomes are changes in Wits appraisal and the degree of maxillary advancement from baseline to the end of orthodontic treatment. Lateral cephalometric radiographs, polysomnography, Obstructive Sleep Apnoea-18 questionnaire and Oral Health Impact Profile-14 questionnaire will be traced, collected and measured. We will recruit 96 patients intofor the study. To assess differences, repeated multilevel linear mixed modelling analyses will be used. ETHICS AND DISSEMINATION: This study has been granted ethical approval by the Ethics Committee of the School & Hospital of Stomatology, Wuhan University (approval No. 2023-D10). Written informed consent will be obtained from the participants and their guardians. The results of the trial will be disseminated through academic conferences and journal publications. TRIAL REGISTRATION NUMBER: ChiCTR2300078833.
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Hipertrofia , Maloclusión de Angle Clase III , Técnica de Expansión Palatina , Tonsila Palatina , Tonsilectomía , Humanos , Tonsilectomía/métodos , Niño , Maloclusión de Angle Clase III/cirugía , Maloclusión de Angle Clase III/terapia , Tonsila Palatina/patología , Tonsila Palatina/cirugía , Femenino , Aparatos de Tracción Extraoral , Ensayos Clínicos Controlados Aleatorios como Asunto , Masculino , Resultado del Tratamiento , Calidad del Sueño , AdolescenteRESUMEN
BACKGROUD: Li-Fraumeni syndrome is a hereditary tumor syndrome characterized by an elevated risk of malignancy, particularly acute lymphoblastic leukemia (ALL), which can be caused by the heterozygous germline mutation. TP53 gene germline mutation is considered a potential risk factor and crucial prognostic parameter for acute leukemia development and diagnosis, but rarely occurs in adults, and its specific pathogenic significance in acute leukemia is unclear. CASE PRESENTATION: We describes a case of a 45-year-old woman diagnosed with ALL. Whole-exome sequencing approach identified one of the TP53 germline mutations from her bone marrow sample with possible pathogenic significance, c.848G>A (p.Arg283His) heterozygous missense mutation located on exon 8, which was further verified in her hair, oral mucous and nail samples. Family pedigree screening revealed that the same TP53 genetic variant was present in the patient's father and non-donor son, whereas not in the donor. Digital PCR observed that this point mutation frequency dropped post-transplantation but remained low during maintenance therapy when the patient was leukemia-free. CONCLUSION: This suspected Li-Fraumeni syndrome case report with a likely pathogenic heterozygous TP53 variant expands the cancer genetic spectrum. Screening her family members for mutations facilitates identifying the optimal relative donor and avoids unnecessary treatment by monitoring TP53 germline mutations for minimal residual disease following hematopoietic stem cell transplantation. Its potential roles in hematological malignant tumor development and clinical pathogenic implications necessitate further probing.
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Mutación de Línea Germinal , Síndrome de Li-Fraumeni , Leucemia-Linfoma Linfoblástico de Células Precursoras , Proteína p53 Supresora de Tumor , Humanos , Femenino , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Persona de Mediana Edad , Proteína p53 Supresora de Tumor/genética , Síndrome de Li-Fraumeni/genética , Síndrome de Li-Fraumeni/diagnóstico , LinajeRESUMEN
Tea drinking impacts aging and aging-related diseases. However, knowledge of anti-aging molecules other than the major catechins in complex tea extracts remains limited. Here we used Caenorhabditis elegans to analyze the longevity effects of tea extracts and constituents comprehensively. We found that the hot water extract of green tea prolonged lifespan and heathspan. Further, the MeOH fraction prolonged lifespan significantly longer than other fractions. Correlation analysis between mass spectroscopic data and anti-aging activity suggests that ester-type catechins (ETCs) are the major anti-aging components, including 4 common ETCs, 6 phenylpropanoid-substituted ester-type catechins (PSECs), 5 cinnamoylated catechins (CCs), 7 ester-type flavoalkaloids (ETFs), and 4 cinnamoylated flavoalkaloids (CFs). CFs (200 µM) are the strongest anti-aging ETCs (with the longest 73% lifespan extension). Green tea hot water extracts and ETCs improved healthspan by enhancing stress resistance and reducing ROS accumulation. The mechanistic study suggests that they work by multiple pathways. Moreover, ETCs modulated gut microbial homeostasis, increased the content of short-chain fatty acids, and reduced fat content. Altogether, our study provides new evidence for the anti-aging benefits of green tea and insights into a deep understanding of the chemical truth and multi-target mechanism.
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Behçet's syndrome (BS) is a variant vasculitis that can involve multiple organs with inflammatory manifestations. This study aimed to provide a more comprehensive analysis of the clinical phenotypes and characteristics of BS patients. We enrolled 2792 BS patients referred from China nationwide to Huadong Hospital Affiliated to Fudan University from October 2012 to December 2022. Detailed assessments of demographic information, clinical manifestations, laboratory results, gastroscopy, and medical imaging were conducted. Cluster analysis was performed based on 13 variables to determine the clinical phenotypes, and each phenotype was characterized according to the features of BS patients. A total of 1834 BS patients were included, while 958 invalid patients were excluded. The median age at onset was 31 years (IQR, 24-40 years), and the median disease duration was 10 years (IQR, 5-15 years). Eight clusters were identified, including mucocutaneous (n = 655, 35.7%), gastrointestinal (n = 363, 19.8%), articular (n = 184, 10%), ocular (n = 223, 12.2%), cardiovascular (n = 119, 6.5%), neurological (n = 118, 6.4%), vascular (n = 114, 6.2%), and hematological phenotype (n = 58, 3.2%). Ocular (RR = 1.672 (95% CI, 1.327-2.106); P < 0.001), gastrointestinal (RR = = 1.194 (95% CI, 1.031-1.383); P = 0.018), cardiovascular (RR = = 2.582 (95% CI, 1.842-3.620); P < 0.001), and vascular (RR = = 2.288 (95% CI, 1.600-3.272); P < 0.001) involvement were more prevalent in male BS patients, while the hematological (RR = 0.528 (95% CI, 0.360-0.776); P = 0.001) involvement was more common among female patients. BS presents significant heterogeneity and gender differences. The eight phenotypes of BS patients we propose hold the potential to assist clinicians in devising more personalized treatment and follow-up strategies. Key Points ⢠This cluster analysis divided adult-onset BS into eight clinical phenotypes. ⢠BS demonstrates a high level of clinical heterogeneity and gender differences. ⢠Hematologic phenotypes of BS present distinctive clinical characteristics.
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Edad de Inicio , Síndrome de Behçet , Fenotipo , Humanos , Síndrome de Behçet/epidemiología , Síndrome de Behçet/diagnóstico , Masculino , Femenino , Adulto , China/epidemiología , Estudios Transversales , Adulto Joven , Análisis por Conglomerados , Persona de Mediana EdadRESUMEN
The aims of this study were to investigate whether the ferroptosis is involved in intestinal Behçet's syndrome (IBS), and to identify if miR-141-3p could attenuate RAS-selective lethal 3 (RSL3)-induced ferroptosis and intestinal epithelial to mesenchymal transition (EMT) via directly inhabits zinc fnger E-box binding homeobox 1 (ZEB1). The expressions of ferroptosis-related proteins in the intestinal tissues of patients with IBS were investigated by immunohistochemistry and quantitative real-time PCR (qRT-PCR). Malondialdehyde (MDA) contents of the intestinal tissues and cells were detected. Serum from IBS patients and RSL3 were co-cultured with intestinal epithelial cells in vitro. In order to investigate whether RSL3-induced ferroptosis can be ameliorated by miR-141-3p, the intestinal epithelial cells were firstly stimulated with RSL3 and then incubated with miR-141-3p mimics. Western blot was used to measure the expression of EMT and ferroptosis-related proteins. Expression of GPX4 (22.51% ± 2.05%, 51.75% ± 3.47%, t = - 7.77, p = 0.000) and xCT (17.49% ± 1.57%, 28.73% ± 1.75%, t = - 4.38, p = 0.003) were significantly lower in intestinal mucosal tissues of patients with IBS compared with HC group. Compared with the HC samples, the IBS specimens had significantly higher MDA (t = 4.32, p = 0.01). Moreover, the relative mRNA levels of ferritin light chain (FTL) (t = 4.07, p = 0.02) and ferritin heavy chain (FTH) (t = 8.82, p = 0.001) in the intestinal tissues were significant higher in IBS patients than in HC group. Serum from IBS patients could induce intestinal epithelial cell ferroptosis in vitro. Moreover, miR-141-3p could attenuate intestinal epithelial cell ferroptosis-induced by RSL3 and intestinal EMT via targeting ZEB1 in vitro. Ferroptosis were induced in patients with IBS. Moreover, the serum from IBS patients could induce ferroptosis in vitro. miR-141-3p could attenuate intestinal epithelial cell ferroptosis and intestinal EMT via targeting ZEB1. Therefore, miR-141-3p may open new avenues for the treatment of IBS in the future. Key Points ⢠Ferroptosis in IBS is first reported in this study. ⢠In this study, we explored that the serum from IBS patients could induce ferroptosis in vitro and miR-141-3p could attenuate intestinal epithelial cell ferroptosis and intestinal EMT via targeting ZEB1.
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Síndrome de Behçet , Transición Epitelial-Mesenquimal , Ferroptosis , MicroARNs , Homeobox 1 de Unión a la E-Box con Dedos de Zinc , Humanos , MicroARNs/metabolismo , Masculino , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Femenino , Adulto , Síndrome de Behçet/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Persona de Mediana EdadRESUMEN
Background: Neuroinflammation plays a crucial part in the initial onset and progression of Alzheimer's disease (AD). NLRP3 inflammasome was demonstrated to get involved in amyloid-ß (Aß)-induced neuroinflammation. However, the mechanism of Aß-triggered activation of NLRP3 inflammasome remains poorly understood. Objective: Based on our previous data, the study aimed to identify the downstream signals that bridge the activation of TLR4 and NLRP3 inflammasome associated with Aß. Methods: BV-2 cells were transfected with TLR4siRNA or pretreated with a CLI-095 or NSC23766, followed by Aß1-42 treatment. APP/PS1 mice were injected intraperitoneally with CLI-095 or NSC23766. NLRP3 inflammasome and microglia activation was detected with immunostaining and western blot. G-LISA and Rac1 pull-down activation test were performed to investigate the activation of Rac1. Real-time PCR and ELISA were used to detect the inflammatory cytokines. Aß plaques were assessed by western blotting and immunofluorescence staining. Morris water maze test was conducted to determine the spatial memory in mice. Results: Rac1 and NLRP3 inflammasome were activated by Aß in both in vitro and in vivo experiments. Inhibition of TLR4 reduced the activity of Rac1 and NLRP3 inflammasome induced by Aß1-42. Furthermore, inhibition of Rac1 blocked NLRP3 inflammasome activation mediated by TLR4. Blocking the pathway by CLI095 or NSC23766 suppressed Aß1-42-triggered activation of microglia, reduced the expression of pro-inflammatory mediators and ameliorated the cognition deficits in APP/PS1 mice. Conclusions: Our study demonstrated that TLR4/Rac1/NLRP3 pathway mediated Aß-induced neuroinflammation, which unveiled a novel pathway and key contributors underlying the pathogenic mechanism of Aß.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Ratones Transgénicos , Proteína con Dominio Pirina 3 de la Familia NLR , Enfermedades Neuroinflamatorias , Receptor Toll-Like 4 , Proteína de Unión al GTP rac1 , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Péptidos beta-Amiloides/metabolismo , Receptor Toll-Like 4/metabolismo , Enfermedad de Alzheimer/metabolismo , Ratones , Proteína de Unión al GTP rac1/metabolismo , Enfermedades Neuroinflamatorias/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Microglía/metabolismo , Microglía/efectos de los fármacos , Inflamasomas/metabolismo , Masculino , Fragmentos de Péptidos/toxicidad , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , NeuropéptidosRESUMEN
OBJECTIVES: The biomechanics in achieving molar distalization may differ between fixed appliances and clear aligners in the control of tooth movement. The objective of this study was to compare the treatment effects between clear aligners (CA) and fixed appliances (FA) in patients treated with miniscrew-assisted molar distalization. METHODS: The sample consisted of 46 subjects with mild-to-moderate crowding. A total of 22 patients treated with clear aligners (age, 25.66â ±â 6.11 years old) and 24 patients treated with fixed appliances (age, 24.04â ±â 4.95 years old) for miniscrew-assisted molar distalization were included in this study. The dental and skeletal changes were evaluated by the pre- and post-treatment lateral cephalograms. RESULTS: Significant changes were found with the vertical variables SN-OP angle (2.24â ±â 3.22°, Pâ <â .05) and SN-MP angle (0.73â ±â 1.15°, Pâ <â .05) for the FA group when compared with the CA group (SN-OP angle 0.41â ±â 2.26° and SN-MP angle -0.21â ±â 1.38°, Pâ >â .05). Both treatment groups achieved a 2-3 mm. molar distalization with significant intrusion of the upper molars. The CA group showed significantly less distal tipping of molars (U6^PP angle -2.29â ±â 3.29° and L6^MP angle -2.92â ±â 2.49°, Pâ <â .05) compared to the FA group (-5.24â ±â 4.28° and -5.53â ±â 5.03°, Pâ <â .05). In addition, significant retraction and lingual inclination of the upper and lower incisors were found in both groups. LIMITATIONS: The changes of tooth position were evaluated by 2D lateral cephalograms, not 3D measurements. CONCLUSIONS: Compared to fixed appliances, clear aligners seemed to have better control of vertical dimension and distal tipping of molars in patients treated with miniscrew-assisted molar distalization.
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Tornillos Óseos , Cefalometría , Diente Molar , Métodos de Anclaje en Ortodoncia , Aparatos Ortodóncicos Fijos , Técnicas de Movimiento Dental , Humanos , Técnicas de Movimiento Dental/instrumentación , Técnicas de Movimiento Dental/métodos , Masculino , Femenino , Adulto , Métodos de Anclaje en Ortodoncia/instrumentación , Métodos de Anclaje en Ortodoncia/métodos , Adulto Joven , Diseño de Aparato Ortodóncico , Maloclusión/terapia , Resultado del Tratamiento , Maxilar , Mandíbula , Aparatos Ortodóncicos Removibles , Incisivo , Dimensión VerticalAsunto(s)
Carcinoma de Células Escamosas , Neoplasias Colorrectales Hereditarias sin Poliposis , Neoplasias Cutáneas , Humanos , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/complicaciones , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Pueblo Asiatico , China , Adulto , Pueblos del Este de AsiaRESUMEN
Inflammatory signals from immunological cells may cause damage to intestinal epithelial cells (IECs), resulting in intestinal inflammation and tissue impairment. Interferon-γ-inducible protein 16 (IFI16) was reported to be involved in the pathogenesis of Behçet's syndrome (BS). This study aimed to investigate how inflammatory cytokines released by immunological cells and IFI16 participate in the pathogenesis of intestinal BS. RNA sequencing and real-time quantitative PCR (qPCR) showed that the positive regulation of tumor necrosis factor-α (TNF-α) production in peripheral blood mononuclear cells (PBMCs) of intestinal BS patients may be related to the upregulation of polo like kinase 1 (PLK1) in PBMCs (P = 0.012). The plasma TNF-α protein level in intestinal BS was significantly higher than in healthy controls (HCs; P = 0.009). PBMCs of intestinal BS patients and HCs were co-cultured with human normal IECs (NCM460) to explore the interaction between immunological cells and IECs. Using IFI16 knockdown, PBMC-NCM460 co-culture, TNF-α neutralizing monoclonal antibody (mAb), stimulator of interferon genes (STING) agonist 2'3'-cGAMP, and the PLK1 inhibitor SBE 13 HCL, we found that PLK1 promotes the secretion of TNF-α from PBMCs of intestinal BS patients, which causes overexpression of IFI16 and induces apoptosis of IECs via the STING-TBK1 pathway. The expressions of IFI16, TNF-α, cleaved caspase 3, phosphorylated STING (pSTING) and phosphorylated tank binding kinase 1 (pTBK1) in the intestinal ulcer tissue of BS patients were significantly higher than that of HCs (all P < 0.05). PLK1 in PBMCs of intestinal BS patients increased TNF-α secretion, inducing IEC apoptosis via activation of the IFI16-STING-TBK1 pathway. PLK1 and the IFI16-STING-TBK1 pathway may be new therapeutic targets for intestinal BS.
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Apoptosis , Síndrome de Behçet , Proteínas de Ciclo Celular , Proteínas de la Membrana , Fosfoproteínas , Quinasa Tipo Polo 1 , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas , Transducción de Señal , Humanos , Síndrome de Behçet/patología , Síndrome de Behçet/metabolismo , Síndrome de Behçet/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/genética , Masculino , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Femenino , Adulto , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/patología , Células Epiteliales/metabolismo , Células Epiteliales/patología , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Mucosa Intestinal/patología , Mucosa Intestinal/metabolismo , Persona de Mediana EdadRESUMEN
OBJECTIVE: To investigate the impact of various degrees of white spot lesions (WSLs) of maxillary anterior teeth on the aesthetic perception and treatment satisfaction among orthodontic patients, orthodontists and other dental specialists and to evaluate the differences among the three groups. METHODS: A total of 45 orthodontic patients (OP), 45 orthodontists (OR) and 45 other dental specialists (OS) were recruited. Subjective evaluations of perceived aesthetics and treatment satisfaction were performed towards eight digitally generated photographs of maxillary anterior teeth with incremental degrees of WSLs using a numerical visual analogue scale (VAS) from 0 to 100. Data were collected and analysed with descriptive statistics, repeated one-way analysis of variance and multivariable generalized estimating equations. RESULTS: A total of 135 valid questionnaires were collected. Regarding aesthetic scores for WSLs, OP gave more positive scores than OR and OS (p < .05) towards excessive white spot formation without colouration and were more tolerant than OR (p < .05) towards excessive white spot formation with slight colouration. The level of treatment satisfaction for slight to severe WSLs without cavitation was higher in OP than OR. Patients with higher education levels had more negative scores for aesthetic perception and treatment satisfaction (p < .05). Patients who brushed teeth more frequently scored lower in treatment satisfaction (p < .05). CONCLUSIONS: Orthodontists were the most critical when evaluating aesthetics and treatment satisfaction for slight to severe WSLs without cavitation. For orthodontic patients, better oral hygiene habits and higher education levels were associated with more critical attitudes towards WSLs.
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Estética Dental , Ortodoncistas , Satisfacción del Paciente , Humanos , Femenino , Masculino , Ortodoncistas/psicología , Adulto , Encuestas y Cuestionarios , Adolescente , Especialidades Odontológicas , Adulto Joven , OrtodonciaRESUMEN
ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Neural networks for classification of cervical vertebrae maturation: a systematic review. Mathew R, Palatinus S, Padala S, Alshehri A, Awadh W, Bhandi S, Thomas J, Patil S. Angle Orthod. 2022 Nov 1;92(6):796-804. SOURCE OF FUNDING: No financial support was reported. TYPE OF STUDY/DESIGN: Systematic review.
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Vértebras Cervicales , Redes Neurales de la Computación , Humanos , Revisiones Sistemáticas como AsuntoRESUMEN
Type I interferons play a fundamental role in innate host defense against viral infections by eliciting the induction of an antiviral gene program that serves to inhibit viral replication. Activation of type I interferon is regulated by the IRF3 transcription factor, which undergoes phosphorylation-dependent activation by the upstream kinase, TBK1, during viral infection. However, the mechanisms by which TBK1 achieves activation to support signaling to IRF3 remain incompletely understood. Here we identified the E3 ubiquitin ligase, tripartite motif containing 28 (TRIM28), as a positive regulator of type I interferon activation by facilitating TBK1 signaling. Genetic deletion of TRIM28 via CRISPR-Cas9 editing resulted in impaired type I interferon activation upon both RNA and DNA virus challenge, corresponding with increased susceptibility to virus infections in TRIM28 knockout cells. Mechanistically, TRIM28 interacted with TBK1 and mediated the assembly of K63-linked ubiquitin chains onto TBK1, a post-translational modification shown to augment TBK1 signal transmission events. TRIM28 knockout cells further displayed defective TBK1 phosphorylation and complex assembly with IRF3, resulting in impaired IRF3 phosphorylation. Altogether, our data demonstrate TBK1 to be a novel substrate for TRIM28 and identify TRIM28 as an essential regulatory factor in controlling innate antiviral immune responses.
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Interferón Tipo I , Proteínas Serina-Treonina Quinasas , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal , Fosforilación , Interferón betaRESUMEN
OBJECTIVES: Behçet's syndrome (BS) is a rare disease of unknown etiology, with limited reports especially in pediatric BS. The clinical characteristics and phenotypes of pediatric BS as a highly heterogeneous variable vessel vasculitis were investigated in this study. METHODS: A cross-sectional study was conducted to compare clinical variables and descriptive characteristics of BS by age of onset and gender. Cluster analysis was then performed to identify the phenotypes of pediatric BS. RESULTS: A total of 2082 BS patients were included in this study, 1834 adults and 248 children. Compared with adult-onset BS, pediatric BS had a higher incidence of folliculitis [relative risks (RR) and 95% confidence interval (CI) 1.3 (1.0-1.5)], uveitis of the left eye [RR and 95% CI 2.3 (1.0-5.0)], intestinal ulcer complications [RR and 95% CI 2.1 (1.1-4.2)], pericarditis [RR and 95% CI 2.5 (1.0-6.2)], and psychiatric disorders [RR and 95% CI 2.8(1.0-7.9)], while the incidence of thrombocytopenia was lower [RR 0.2 (0.1-1.0)]. Among pediatric BS, females had more genital ulcers, while males were more likely to have skin lesions, panuveitis, vascular involvement, venous lesions, cardiac involvement, and aortic aneurysms. Cluster analysis classified pediatric BS into five clusters (C1-C5): C1 (n = 61, 24.6%) showed gastrointestinal (GI) involvement; C2 (n = 44, 17.7%) was the central nervous system (CNS) type where 23 cases overlapped joint involvement; in C3 (n = 35, 14.1%), all patients presented with arthritis or arthralgia; all patients in C4 (n = 29, 11.7%) manifested ocular involvement, with a few patients overlapping with GI involvement or joint damage; C5 (n = 79, 31.9%) was the mucocutaneous type, presenting both oral ulcers, genital ulcers, and skin lesions. CONCLUSIONS: The clinical features of pediatric and adult BS differ significantly. Male and female pediatric BS also have a distinct demography. Five phenotypes including GI, CNS, joint, ocular, and mucocutaneous types were identified for pediatric BS.
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Dental patient-centered outcomes can improve the relevance of clinical study results to dental patients and generate evidence to optimize health outcomes for dental patients. Dental patient-reported outcomes (dPROs) are of great importance to patient-centered dental care. They can be used to evaluate the health outcomes of an individual patient about the impact of oral diseases and treatment, and to assess the quality of oral health care delivery for a health care entity. dPROs are measured with dental patient-reported outcome measures (dPROMs). dPROMs should be validated and tested before wider dissemination and application to ensure that they can accurately capture the intended dPROs. Evidence suggests inadequate dPRO usage among dental trials, as well as potential flaws in some existing dPROMs. This Glossary presents a collection of main terms in dental patient-centered outcomes to help clinicians and researchers read and understand patient-centered clinical studies in dentistry.
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Evaluación de Resultado en la Atención de Salud , Medición de Resultados Informados por el Paciente , Humanos , Atención Dirigida al Paciente , Instituciones de Salud , Calidad de VidaRESUMEN
The emergence and rapid development of disruptive innovations are quickly turning our profession into personalized dentistry, built upon evidence-based, data-oriented, and patient-centered research. In order to help improve the quality and quantity of patient-centered evidence in dentistry, further promote the wide and standard use of dental patient-reported outcomes (dPROs) and dental patient-reported outcome measures (dPROMs), the Journal of Evidence-Based Dental Practice has put together this special issue, the third of a series entitled Dental Patient-Reported Outcomes Update. A total of 7 solicited articles are collected in this issue. To put them into a broader perspective, this review provides a concise summary of key, selected PRO and dPRO articles published during 2023. A brief introduction to those articles included in this Special Issue follows. Four main domains are covered in this Special Issue: (1) dPROs and digital dentistry, (2) standardization of dPRO-related methodology, (3) current usage of dPROs and dPROMs in published research, and (iv) the significance and relevance of dPRO usage.
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Odontología Basada en la Evidencia , Medición de Resultados Informados por el Paciente , HumanosRESUMEN
OBJECTIVE: To identify and summarize the presence and characteristics of dental patient-reported outcomes (dPROs) and dental patient-reported outcome measures (dPROMs) within comparative observational studies published in 5 leading orthodontic journals. METHODS: Electronic searching was performed to identify intervention (therapeutic or preventive) related comparative observational studies published in selected journals between 2015 and 2021. Two authors extracted the characteristics of each included study independently and in duplicate and summarized the dPROs and dPROMs used in these studies. All dPROs were classified into 2 general types (oral health-related quality of life [OHRQoL] and others), while dPROMs were divided into 3 categories (single-item questionnaires, generic multiple-item questionnaires, and specific multiple-item questionnaires). In addition, dPROMs were examined, if they evaluated the 4 dimensions of OHRQoL (oral function, orofacial pain, orofacial appearance, and psychosocial impact). RESULTS: A total of 683 observational studies were eligible and included of which 117 (17.1%) used dPROs and dPROMs. Seven different dPROs (OHRQoL, patients' satisfaction with treatment, preferences, concerns, compliance, duration, and unwanted events) and 33 different dPROMs (including 8 single-item questionnaires, 11 generic multiple-item questionnaires, and 14 specific multiple-item questionnaires) were identified in these studies. OHRQoL was the most commonly used dPRO (92/117, 78.6%), while Oral Health Impact Profile 14 (OHIP-14) was the most frequently used dPROM (20/92, 21.7%). In terms of study design, cross-sectional studies had the highest proportion of dPRO usage (62/148, 41.9%), followed by cohort studies (63/505, 12.5%) and case-control studies (1/30, 3.3%). CONCLUSIONS: Only one-sixth of comparative observational studies published in leading orthodontic journals could reflect patients' perspectives. Observational studies in orthodontics need to provide more patient-important information through the use of dPROs and dPROMs.
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Atención Odontológica , Calidad de Vida , Humanos , Estudios Transversales , Salud Bucal , Medición de Resultados Informados por el Paciente , Proyectos de Investigación , Encuestas y CuestionariosRESUMEN
BACKGROUND: The fat mass and obesity-associated protein (FTO) is an RNA demethylase that contributes to several physiological processes. Nonetheless, the impact of FTO on bone remodeling in the midpalatal suture while undergoing rapid maxillary expansion (RME) remains unclear. METHODS: First, to explore the expression of FTO in the midpalatal suture during RME, six rats were randomly divided into two groups: Expansion group and Sham group (springs without being activated). Then, suture mesenchymal stem cells (SuSCs) were isolated as in vitro model. The expression of FTO was knocked down by small interfering RNA to study the effect of FTO on the osteogenic differentiation of SuSCs. Finally, to evaluate the function of FTO in the process of bone remodeling in the midpalatal suture, ten rats were randomly divided into two groups: FB23-2 group (10 µM, a small molecule inhibitor of FTO) and DMSO group (control). RESULTS: Increased arch width and higher expression of OCN and FTO in the midpalatal area were observed in expansion group (Pâ <â .05). In the in vitro model, the mRNA expression levels of Runx2, Bmp2, Col1a1, Spp1, and Tnfrsf11b were decreased (Pâ <â .05) upon knocking down FTO. Additionally, the protein levels of RUNX2 and OPN were also decreased (Pâ <â 0.05). Adding FB23-2, a small-molecule inhibitor targeting FTO, to the medium of SuSCs caused a decrease in the mRNA expression levels of Runx2, Bmp2, Col1a1, Spp1, and Tnfrsf11b (Pâ <â 0.05). There was a statistically significant difference in evaluating the expression of OCN and OPN on the palatal suture between the FB23-2 and DMSO groups (Pâ <â .05). LIMITATION: The molecular mechanisms by which FTO regulates SuSCs osteogenesis remain to be elucidated. The FTO conditional knock out mouse model can be established to further elucidate the role of FTO during RME. CONCLUSION: FTO contributes to the osteogenic differentiation of SuSCs and plays a promoting role in midpalatal suture bone remodeling during the RME.
Asunto(s)
Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Técnica de Expansión Palatina , Animales , Ratas , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Remodelación Ósea , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Dimetilsulfóxido , Osteogénesis , ARN MensajeroRESUMEN
Thalidomide is a therapeutic option for patients with ß-thalassemia by increasing fetal hemoglobin and thereby reducing the requirement for blood transfusions. However, information on changes in erythropoiesis and iron homeostasis during thalidomide treatment is lacking. This study investigated the effects of thalidomide treatment on hematologic, erythropoietic, and ironstatus parameters in 22 patients with transfusion-dependent ß-thalassemia (TDT). Thalidomide significantly improved anemia endpoints, including increases in hemoglobin (p<0.001), red blood cells (p<0.001), and hematocrit (p<0.001), as well as reducing erythropoietin levels (p=0.033) and ameliorating erythropoiesis. Thalidomide treatment significantly reduced serum iron levels (p=0.018) and transferrin saturation (p=0.039) and increased serum transferrin levels (p=0.030). Thalidomide had no observed effect on serum ferritin or hepcidin, but changes in hepcidin (r=0.439, p=0.041) and serum iron (r=-0.536, p=0.010) were significantly correlated with hemoglobin increment. This comprehensive study indicates that thalidomide treatment can ameliorate erythropoiesis and iron homeostasis in patients with TDT, thus supporting the effectiveness of this drug.