RESUMO
The sequence-specific RNA-binding protein Pumilio (Pum) controls Drosophila development; however, the network of mRNAs that it regulates remains incompletely characterized. In this study, we use knockdown and knockout approaches coupled with RNA-seq to measure the impact of Pum on the transcriptome of Drosophila cells in culture. We also use an improved RNA coimmunoprecipitation method to identify Pum-bound mRNAs in Drosophila embryos. Integration of these data sets with the locations of Pum-binding motifs across the transcriptome reveals novel direct Pum target genes involved in neural, muscle, wing, and germ cell development and in cellular proliferation. These genes include components of Wnt, TGF-ß, MAPK/ERK, and Notch signaling pathways, DNA replication, and lipid metabolism. We identify the mRNAs regulated by the CCR4-NOT deadenylase complex, a key factor in Pum-mediated repression, and observe concordant regulation of Pum:CCR4-NOT target mRNAs. Computational modeling reveals that Pum binding, binding site number, clustering, and sequence context are important determinants of regulation. In contrast, we show that the responses of direct mRNA targets to Pum-mediated repression are not influenced by the content of optimal synonymous codons. Moreover, contrary to a prevailing model, we do not detect a role for CCR4-NOT in the degradation of mRNAs with low codon optimality. Together, the results of this work provide new insights into the Pum regulatory network and mechanisms and the parameters that influence the efficacy of Pum-mediated regulation.
Assuntos
Proteínas de Drosophila , Proteínas de Ligação a RNA , Transcriptoma , Animais , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Ribonucleases/metabolismo , Ribonucleases/genética , Regulação da Expressão Gênica no Desenvolvimento , Sítios de Ligação , Ligação Proteica , Drosophila/genética , Drosophila/metabolismoRESUMO
Understanding how function and structure are organized and their coupling with clinical traits in individuals with autism spectrum disorder (ASD) is a primary goal in network neuroscience research for ASD. Atypical brain functional networks and structures in individuals with ASD have been reported, but whether these associations show heterogeneous hierarchy modeling in adolescents and adults with ASD remains to be clarified. In this study, 176 adolescent and 74 adult participants with ASD without medication or comorbidities and sex, age matched healthy controls (HCs) from 19 research groups from the openly shared Autism Brain Imaging Data Exchange II database were included. To investigate the relationship between the functional gradient, structural changes, and clinical symptoms of brain networks in adolescents and adults with ASD, functional gradient and voxel-based morphometry (VBM) analyses based on 1000 parcels defined by Schaefer mapped to Yeo's seven-network atlas were performed. Pearson's correlation was calculated between the gradient scores, gray volume and density, and clinical traits. The subsystem-level analysis showed that the second gradient scores of the default mode networks and frontoparietal network in patients with ASD were relatively compressed compared to adolescent HCs. Adult patients with ASD showed an overall compression gradient of 1 in the ventral attention networks. In addition, the gray density and volumes of the subnetworks showed no significant differences between the ASD and HC groups at the adolescent stage. However, adults with ASD showed decreased gray density in the limbic network. Moreover, numerous functional gradient parameters, but not VBM parameters, in adolescents with ASD were considerably correlated with clinical traits in contrast to those in adults with ASD. Our findings proved that the atypical changes in adolescent ASD mainly involve the brain functional network, while in adult ASD, the changes are more related to brain structure, including gray density and volume. These changes in functional gradients or structures are markedly correlated with clinical traits in patients with ASD. Our study provides a novel understanding of the pathophysiology of the structure-function hierarchy in ASD.
Assuntos
Transtorno do Espectro Autista , Imageamento por Ressonância Magnética , Rede Nervosa , Humanos , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/patologia , Adolescente , Masculino , Feminino , Adulto , Adulto Jovem , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/patologia , Rede de Modo Padrão/diagnóstico por imagem , Rede de Modo Padrão/fisiopatologia , Rede de Modo Padrão/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Criança , Pessoa de Meia-IdadeRESUMO
Ulcerative colitis (UC) is an immune-mediated inflammatory disease that can lead to persistent damage and even cancer without any intervention. Conventional treatments can alleviate UC symptoms but are costly and cause various side effects. Tauroursodeoxycholic acid (TUDCA), a secondary bile acid derivative, possesses anti-inflammatory and cytoprotective properties for various diseases, but its potential therapeutic benefits in UC have not been fully explored. Mice were subjected to colitis induction using 3% dextran sulfate sodium (DSS). The therapeutic effect of TUDCA was evaluated by body weight loss, disease activity index (DAI), colon length, and spleen weight ratio. Tissue pathology was assessed using H&E staining, while the levels of pro-inflammatory and anti-inflammatory cytokines in colonic tissue were quantified via ELISA. Tight junction proteins were detected by immunoblotting and intestinal permeability was assessed using fluorescein isothiocyanate (FITC)-dextran. Moreover, the gut microbiota was profiled using high-throughput sequencing of the 16S rDNA gene. TUDCA alleviated the colitis in mice, involving reduced DAI, attenuated colon and spleen enlargement, ameliorated histopathological lesions, and normalized levels of pro-inflammatory and anti-inflammatory cytokines. Furthermore, TUDCA treatment inhibited the downregulation of intestinal barrier proteins, including zonula occludens-1 and occludin, thus reducing intestinal permeability. The analysis of gut microbiota suggested that TUDCA modulated the dysbiosis in mice with colitis, especially for the remarkable rise in Akkermansia TUDCA exerted a therapeutic efficacy in DSS-induced colitis by reducing intestinal inflammation, protecting intestinal barrier integrity, and restoring gut microbiota balance. SIGNIFICANCE STATEMENT: This study demonstrates the potential therapeutic benefits of Tauroursodeoxycholic acid (TUDCA) in ulcerative colitis. TUDCA effectively alleviated colitis symptoms in mice, including reducing inflammation, restoring intestinal barrier integrity and the dysbiosis of gut microbiota. This work highlights the promising role of TUDCA as a potentially alternative treatment, offering new insights into managing this debilitating condition.
Assuntos
Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Mucosa Intestinal , Ácido Tauroquenodesoxicólico , Animais , Ácido Tauroquenodesoxicólico/farmacologia , Ácido Tauroquenodesoxicólico/uso terapêutico , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Colite/tratamento farmacológico , Colite/induzido quimicamente , Colite/patologia , Colite/metabolismo , Colite/microbiologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Mucosa Intestinal/microbiologia , Camundongos Endogâmicos C57BL , Permeabilidade/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Colo/microbiologia , Citocinas/metabolismo , Proteínas de Junções Íntimas/metabolismoRESUMO
Few studies were devoted to investigating cerebral functional changes after acute cerebellar infarction (CI). The purpose of this study was to examine the brain functional dynamics of CI using electroencephalographic (EEG) microstate analysis. And the possible heterogenicity in neural dynamics between CI with vertigo and CI with dizziness was explored. Thirty-four CI patients and 37 age- and gender-matched healthy controls(HC) were included in the study. Each included subject underwent a 19-channel video EEG examination. Five 10-s resting-state EEG epochs were extracted after data preprocessing. Then, microstate analysis and source localization were performed using the LORETA-KEY tool. Microstate parameters such as duration, coverage, occurrence, and transition probability are all extracted. The current study showed that the duration, coverage, and occurrence of microstate(Ms) B significantly increased in CI patients, but the duration and coverage of MsA and MsD decreased. Compared CI with vertigo to dizziness, finding a decreased trend in the coverage of MsD and the transition from MsA and MsB to MsD. Taken together, our study sheds new light on the dynamics of cerebral function after CI, mainly reflecting increased activity in functional networks involved in MsB and decreased activity in functional networks involved in MsA and MsD. Vertigo and dizziness post-CI may be suggested by cerebral functional dynamics. Further longitudinal studies are needed to validate and explore the alterations in brain dynamics to what extent depict the clinical traits and their potential applications in the recovery of CI.
Assuntos
Mapeamento Encefálico , Tontura , Humanos , Tontura/etiologia , Encéfalo , Eletroencefalografia , Vertigem , InfartoRESUMO
Targeting specific molecular drivers of tumor growth is a key approach in cancer therapy. Among these targets, the low-density lipoprotein receptor-related protein 6 (LRP6), a vital component of the Wnt signaling pathway, has emerged as an intriguing candidate. As a cell-surface receptor and vital co-receptor, LRP6 is frequently overexpressed in various cancer types, implicating its pivotal role in driving tumor progression. The pursuit of LRP6 as a target for cancer treatment has gained substantial traction, offering a promising avenue for therapeutic intervention. Here, this comprehensive review explores recent breakthroughs in our understanding of LRP6's functions and underlying molecular mechanisms, providing a profound discussion of its involvement in cancer pathogenesis and drug resistance. Importantly, we go beyond discussing LRP6's role in cancer by discussing diverse potential therapeutic approaches targeting this enigmatic protein. These approaches encompass a wide spectrum, including pharmacological agents, natural compounds, non-coding RNAs, epigenetic factors, proteins, and peptides that modulate LRP6 expression or disrupt its interactions. In addition, also discussed the challenges associated with developing LRP6 inhibitors and their advantages over Wnt inhibitors, as well as the drugs that have entered phase II clinical trials. By shedding light on these innovative strategies, we aim to underscore LRP6's significance as a valuable and multifaceted target for cancer treatment, igniting enthusiasm for further research and facilitating translation into clinical applications.
Assuntos
Antineoplásicos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Terapia de Alvo Molecular , Neoplasias , Animais , Humanos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
BACKGROUND: Periprosthetic joint infection (PJI) is a severe complication of joint arthroplasty that causes significant pain and economic loss. This study aimed to determine whether the current evidence supports single-stage revision for PJI based on reinfection and reoperation rates. METHODS: We searched the PubMed, EBSCO, Medline, and Cochrane Library databases from inception to 30 May 2023 to identify studies that compared single-stage revision and two-stage revision for PJI. Data on reinfection and reoperation rates were pooled. RESULTS: This meta-analysis included a total of 40 studies with 8711 patients. Overall, there was no significant difference between single- and two-stage revision regarding the postoperative reinfection rate and reoperation rate. Subgroup analysis by surgery period and different surgical sites revealed no difference between the two groups in the reinfection and reoperation rates. CONCLUSIONS: Based on the available evidence, our study did not identify a significant difference in reinfection and reoperation rates between single- and two-stage revision for PJI. Given the limitations in inclusion/exclusion criteria and the observed heterogeneity, we acknowledge the complexity of drawing strong conclusions. Therefore, we suggest that the choice between single- and two-stage revision should be carefully considered on an individual basis, taking into account patient-specific factors and further research developments.
Assuntos
Infecções Relacionadas à Prótese , Ensaios Clínicos Controlados Aleatórios como Assunto , Reoperação , Humanos , Infecções Relacionadas à Prótese/cirurgia , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/etiologia , Reinfecção , Estudos ProspectivosRESUMO
OBJECTIVES: To assess and compare the effectiveness of various treatment approaches for laryngeal contact granulomas (LCG). METHODS: A retrospective analysis was conducted on a cohort of 45 patients diagnosed with LCG at the Second Affiliated Hospital of Xi'an Jiaotong University from October 2017 to May 2023. Based on the treatment modalities administered, patients were categorized into three groups: acid suppression alone, hormone injection combined with acid suppression, and surgery combined with acid suppression. Subsequently, the study compared differences in treatment efficacy and average healing time among these three groups, using various indicators. RESULTS: The findings indicate that the granuloma size in LCG patients with hoarseness (0.126, 95% CI 0.087-0.288) was significantly greater compared to LCG patients without hoarseness (0.047, 95% CI 0.014-0.083) (P = 0.001). However, there were no significant variations in age, morphology (unlobulated/lobulated), laterality ratio (left/right), sex ratio (male/female), history of tracheal intubation (non-intubation/intubation), and RFS score (RFS > 7/RFS ≤ 7) (P > 0.05), regardless of the presence of hoarseness symptoms. At the treatment observation endpoint of 3 months, the curative ratio in the group receiving hormone injection combined with acid suppression was found to be significantly higher compared to the group receiving acid suppression alone (P = 0.018). In addition, the average healing time of patients in the hormone injection combined with acid suppression group was notably shorter than that of the acid suppression alone group (P = 0.007). CONCLUSIONS: The combination of hormonal injections and acid suppression may enhance the curative ratio and expedite the healing time of LCG.
Assuntos
Granuloma Laríngeo , Rouquidão , Humanos , Masculino , Feminino , Estudos Retrospectivos , Rouquidão/etiologia , Rouquidão/terapia , Granuloma Laríngeo/cirurgia , Granuloma , HormôniosRESUMO
This study comprehensively compared the effects of laparoscopic and open radical cystectomies on postoperative wound infections and complications in patients with bladder cancer. We conducted a systematic search for relevant studies in PubMed, Embase, Google Scholar, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases, from database inception to October 2023. Two researchers independently screened the literature, extracted data, and assessed the quality based on the inclusion and exclusion criteria. Data analysis was performed using Stata 17.0 software. Overall, 16 studies involving 1427 patients with bladder cancer were included. The analysis revealed that, compared with open radical cystectomy, laparoscopic radical cystectomy significantly reduced the incidence of wound infections (odds ratio [OR] = 0.38, 95% confidence interval [CI]: 0.23-0.64, p < 0.001) and complications (OR = 0.35, 95%CI: 0.26-0.47, p < 0.001) and significantly shortened the hospital stay duration (standardised mean difference [SMD] = -1.85, 95%CI: -2.34 to -1.36, p < 0.001). Thus, this study determined that laparoscopic radical cystectomy for the treatment of bladder cancer effectively reduced the occurrence of wound infections and complications, and significantly shortened the patient's hospital stay, demonstrating notable therapeutic effectiveness worthy of clinical application.
Assuntos
Cistectomia , Laparoscopia , Infecção da Ferida Cirúrgica , Neoplasias da Bexiga Urinária , Humanos , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/epidemiologia , Neoplasias da Bexiga Urinária/cirurgia , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Cistectomia/efeitos adversos , Cistectomia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Tempo de Internação/estatística & dados numéricos , Idoso de 80 Anos ou maisRESUMO
This umbrella review aim to explore the effect of topical antibiotics in infection prevention after primary joint arthroplasty, and provide a specific theoretical basis for clinical treatment. The review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched PubMed, EMBASE, Medline, and the Cochrane Library on infection prevention by topical antibiotics from inception to 10 April 2023. The two researchers individually and strictly screened the literature according to the inclusion and exclusion criteria, performed the literature quality evaluation and data extraction, and used Stata 17 for data analysis. This study included six studies with one systematic review and five meta-analyses. The pooled analysis showed that topical antibiotic administration effectively reduced the incidence of overall infection and periprosthetic joint infection. However, it does not reduce the risk of superficial infection. Besides, the topic of antibiotics significantly increases the incidence of other sterile complications of the incision. According to the current evidence, topical application of antibiotics can reduce the incidence of overall infection and periprosthetic joint infection after primary joint arthroplasty. Although it increases the incidence of complications such as delayed healing of incisions, the pros and cons should be weighed in clinical decision making. However, they should not be discarded due to side effects.
Assuntos
Infecções Relacionadas à Prótese , Ferida Cirúrgica , Humanos , Antibacterianos/uso terapêutico , Artroplastia/efeitos adversos , Infecções Relacionadas à Prótese/prevenção & controle , Revisões Sistemáticas como Assunto , Metanálise como AssuntoRESUMO
Perception is an essential component of children's psychological development, which is foundational to children's ability to understand and adapt to their external environment. Perception is also a crucial tool for understand and navigating one's surroundings, enabling children to identify objects and react appropriately to settings or situations. Substantial evidence indicates that engaging in physical activity is beneficial for the development of children's perceptual abilities, as the two are closely intertwined. Still, more research is necessary to gain a full understanding of the impact of physical activity on children's perception. To further identify and quantify the effects of physical activity on a number of specific perceptions in children. Systematic review and meta-analysis. Searches were performed using five online databases (i.e., PubMed, SPORTDiscus, PsycINFO, Web of Science, and Cochrane Library) for articles published up to and including June 2023 to identify eligible citations. A total of 12 randomized controlled trials, encompassing 1,761 children under the age of 12, were analyzed. Overall, physical activity as an intervention showed a notable effect on the development of children's perceptions. The meta-analysis indicated that participating in physical activity for 30 minutes around, daily, had a greater impact on children's visual perception and executive functioning than on their motor perception, body perception, and global self-worth (SMD = 1.33, 95% CI: 0.75, 1.91, p < 0.001). The effects of physical activity on children's perception performance varied by participant characteristics, with physical activity having better effects on body perception and overall self-worth in children who were obese or overweight. Furthermore, physical activity can also enhance executive function and attention in children with developmental coordination disorders. The effects of physical activity on children's perception performance varied according to the intervention time, with different activity durations resulting in different perception performances. Therefore, parents and educators must prioritize an appropriate length of physical activity time for children to ensure their optimal growth and development. Registration and protocol CRD42023441119.
Assuntos
Função Executiva , Exercício Físico , Percepção , Humanos , Criança , Exercício Físico/psicologia , Percepção/fisiologia , Função Executiva/fisiologia , Desenvolvimento Infantil , Percepção Visual , Ensaios Clínicos Controlados Aleatórios como Assunto , Imagem CorporalRESUMO
Electroencephalogram-microstate analysis was conducted using low-resolution electromagnetic tomography (LORETA)-KEY to evaluate dynamic brain network changes in patients with acute large artery atherosclerotic cerebral infarction (LAACI) during the rest and sleep stages. This study included 35 age- and sex-matched healthy controls and 34 patients with acute LAACI. Each participant performed a 3-h, 19-channel video electroencephalogram test. Subsequently, 20 epochs of 2-s sleep spindles during stage N2 sleep and five epochs of 10-s electroencephalogram data in the resting state for each participant were obtained. In both the resting state and sleep spindles, patients with LAACI displayed altered neural oscillations. The parameters of microstate A (coverage, occurrence, and duration) increased during the resting state in the patients with LAACI compared with healthy controls. The coverage and occurrence of microstate B and D were reduced in the LAACI group compared with the healthy controls (p < 0.05). Moreover, during sleep spindles, the duration of microstate A and the transition probability from microstate A and B to C decreased, but the coverage of microstate B and the transition rate from microstate B to D increased (p < 0.05) in the LAACI group compared with the healthy controls. These results enable better understanding of how neural oscillations are modified in patients with LAACI during the resting state and sleep spindles. Following LAACI, the dynamic brain network undergoes changes during sleep spindles and the resting state. Continued long-term investigations are required to determine how well these changes in brain dynamics reflect the clinical characteristics of patients with LAACI.
Assuntos
Mapeamento Encefálico , Encéfalo , Humanos , Mapeamento Encefálico/métodos , Eletroencefalografia , Sono , Artérias , Infarto CerebralRESUMO
To investigate the efficacy of timolol in the treatment of facial hemangioma and the effect on the proliferation and apoptosis of hemangioma stem cells, 60 cases of children with IHs admitted to our hospital between 2020 and 2021 were selected and divided into two groups. The grouping was according to the lottery method, with 30 cases in each group. In the observation group, 0.5% timolol maleate eye drops were applied topically, and in the control group, propranolol hydrochloride tablets were administered orally to observe the efficacy of hemangioma, changes in hemangioma stem cells and the incidence of adverse reactions in both groups. Results showed that combined with the four-level score and ultrasound results, the number of effective treatment cases in the observation group was 28, which was higher than that in the control group, (P<0.05). The total number of adverse reactions in the observation group was 2, with an incidence rate. Under the intervention conditions of timolol, the proliferation level of hemangioma stem cells was inhibited, and the apoptosis rate of hemangioma stem cells increased with the increase of culture time (P<0.05). Among them, the apoptosis rate of the timolol group was higher than that of the blank control group at the same time point (P<0.05), and the difference was most significant at 48h (P<0.001). In conclusion, Timolol can effectively treat facial hemangioma in children, inhibit the proliferation of hemangioma stem cells and promote their apoptosis, with good curative effect, short treatment time and no obvious adverse reactions and it is economical and easy to accept.
Assuntos
Hemangioma , Neoplasias Cutâneas , Criança , Humanos , Lactente , Timolol/farmacologia , Timolol/uso terapêutico , Hemangioma/tratamento farmacológico , Resultado do Tratamento , Proliferação de CélulasRESUMO
BACKGROUND: Both osteoporosis and cognitive impairment affect overall health in elderly individuals. This study aimed to investigate the association between cognitive impairment and the risk of osteoporosis. METHODS: PubMed, Web of Science, and the Cochrane Library were searched for studies on the association between osteoporosis and cognitive impairment from their inception until August 2023. The random-effects model was used to calculate the pooled risk ratio (RR) of osteoporosis in patients with cognitive impairment. Subgroup analysis was used to detect the sources of heterogeneity. Sensitivity analysis was used to test the robustness of the pooled results. Funnel plots, Egger's test, and Begg's test were used to test publication bias. RESULTS: Ten studies involving 9,872 patients were included in this meta-analysis. The pooled results showed that patients with cognitive impairment had an increased risk of osteoporosis (RR = 1.56, 95% confidence interval [CI]: 1.30-1.87, p < 0.001). Subgroup analysis showed that patients with Alzheimer's disease (AD) are at 1.7-fold risk of osteoporosis compared with the control group (RR = 1.70, 95% CI: 1.23-2.37, p = 0.001), and sex, cognitive classification, study region, study design, and study quality might be the sources of heterogeneity. Sensitivity analysis showed robustness of the pooled results. No significant publication bias was found (Begg's test, p = 0.474; Egger's test, p = 0.065). CONCLUSION: Current evidence suggests that patients with cognitive impairment are at increased risk of osteoporosis, especially patients with AD.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Osteoporose , Humanos , Idoso , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Razão de ChancesRESUMO
Interstitial lung diseases (ILDs), or diffuse pulmonary lung disease, are a subset of lung diseases that primarily affect lung alveoli and the space around interstitial tissue and bronchioles. It clinically manifests as progressive dyspnea, and patients often exhibit a varied decrease in pulmonary diffusion function. Recently, variants in telomere biology-related genes have been identified as genetic lesions of ILDs. Here, we enrolled 82 patients with interstitial pneumonia from 2017 to 2021 in our hospital to explore the candidate gene mutations of these patients via whole-exome sequencing. After data filtering, a novel heterozygous mutation (NM_025099: p.Gly131Arg) of CTC1 was identified in two affected family members. As a component of CST (CTC1-STN1-TEN1) complex, CTC1 is responsible for maintaining telomeric structure integrity and has also been identified as a candidate gene for IPF, a special kind of chronic ILD with insidious onset. Simultaneously, real-time PCR revealed that two affected family members presented with short telomere lengths, which further confirmed the effect of the mutation in the CTC1 gene. Our study not only expanded the mutation spectrum of CTC1 and provided epidemiological data on ILDs caused by CTC1 mutations but also further confirmed the relationship between heterozygous mutations in CTC1 and ILDs, which may further contribute to understanding the mechanisms underlying ILDs.
Assuntos
Doenças Pulmonares Intersticiais , Encurtamento do Telômero , Humanos , Proteínas de Ligação a Telômeros/genética , Proteínas de Ligação a Telômeros/metabolismo , População do Leste Asiático , Mutação , Doenças Pulmonares Intersticiais/genética , Telômero/genéticaRESUMO
OBJECTIVE: To analyze the risk factors for recurrence of laryngeal amyloidosis (LA). METHODS: The clinical data of patients with LA admitted in the Otolaryngology Head and Neck Surgery Department of the Second Affiliated Hospital of Xi'an Jiaotong University from August 2009 to June 2022 were analyzed retrospectively; then, the risk factors for recurrence and their impacts on the recurrence time were also analyzed. RESULTS: Of the 44 patients with LA, the majority (38 cases, 86.4%) only involved one anatomical region and the others (6 cases, 13.6%) involved two laryngeal regions concurrently. Overall, the glottic region was the most commonly affected area (28 cases, 63.6%), followed by the supraglottic region (16 cases, 36.4%) and subglottic region (6 cases, 13.6%). In addition, all the lesions were categorized as isolated nodule (31.8%), submucosal localized deposition (52.3%), and submucosal diffuse deposition (15.9%) according to their morphologies under electronic laryngoscope. Finally, six patients (13.6%) had recurrence after operation with a median recurrence time of 24.5 months, and subglottic involvement was confirmed to be an independent risk factor for recurrence of LA by univariate and multivariate logistic regression analyses (P < 0.05). Meanwhile, the patients with subglottic involvement presented as submucosal diffuse deposition had a considerable shorter recurrence time (t = 5.759, P = 0.005). CONCLUSION: The subglottic involvement is an independent risk factor for recurrence of LA.
Assuntos
Amiloidose , Neoplasias Laríngeas , Laringe , Humanos , Neoplasias Laríngeas/cirurgia , Estudos Retrospectivos , Laringe/patologia , Fatores de RiscoRESUMO
OBJECTIVE: The changes in resting-state functional networks and their correlations with clinical traits remain to be clarified in migraine. Here we aim to investigate the brain spatio-temporal dynamics of resting-state networks and their possible correlations with the clinical traits in migraine. METHODS: Twenty Four migraine patients without aura and 26 healthy controls (HC) were enrolled. Each included subject underwent a resting-state EEG and echo planar imaging examination. The disability of migraine patients was evaluated by Migraine Disability Assessment (MIDAS). After data acquisition, EEG microstates (Ms) combining functional connectivity (FC) analysis based on Schafer 400-seven network atlas were performed. Then, the correlation between obtained parameters and clinical traits was investigated. RESULTS: Compared with HC group, the brain temporal dynamics depicted by microstates showed significantly increased activity in functional networks involving MsB and decreased activity in functional networks involving MsD; The spatial dynamics were featured by decreased intra-network FC within the executive control network( ECN) and inter-network FC between dorsal attention network (DAN) and ECN (P < 0.05); Moreover, correlation analysis showed that the MIDAS score was positively correlated with the coverage and duration of MsC, and negatively correlated with the occurrence of MsA; The FC within default mode network (DMN), and the inter-FC of ECN- visual network (VN), ECN- limbic network, VN-limbic network was negatively correlated with MIDAS. However, the FC of DMN-ECN was positively correlated with MIDAS; Furthermore, significant interactions between the temporal and spatial dynamics were also obtained. CONCLUSIONS: Our study confirmed the notion that altered spatio-temporal dynamics exist in migraine patients during resting-state. And the temporal dynamics, the spatial changes and the clinical traits such as migraine disability interact with each other. The spatio-temporal dynamics obtained from EEG microstate and fMRI FC analyses may be potential biomarkers for migraine and with a huge potential to change future clinical practice in migraine.
Assuntos
Mapeamento Encefálico , Transtornos de Enxaqueca , Humanos , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Transtornos de Enxaqueca/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Função ExecutivaRESUMO
Precise information of positions and sizes of atom clouds is required for atom-interferometry-based G measurements. In this work, characterizing atom clouds using a charge-coupled device (CCD) is presented. The parameters of atom clouds are extracted from fluorescence images captured by the CCD. For characterization, in-situ calibration of the magnification of the imaging system is implemented using the free-fall distance of atom clouds as the dimension reference. Moreover, influence of the probe beam on measuring the positions of atom clouds is investigated, and a differential measurement by reversing the direction of the probe beam is proposed to suppress the influence. Finally, precision at sub-mm level for characterizing atom clouds is achieved.
RESUMO
Inflammatory bowel disease (IBD) refers to a gamut of disorders that are characterized by chronic intestinal inflammation, including ulcerative colitis (UC) and Crohn's disease (CD), which often leads to mucosal ulceration and progressive loss of intestinal function. The etiopathogenesis of IBD has not been completely clarified, although multiple factors involving genetic modifications, host immune dysfunction, intestinal dysbiosis and environmental effects have been implicated. Currently, pharmacotherapies including both non-targeted and targeted biological agents are widely used for the clinical treatment of IBD. In addition, novel therapeutic approaches that target the intestinal microorganisms, such as fecal microbiota transplantation, antibiotics, probiotics and microbial metabolite inhibitors, are also under development. However, these treatments are either accompanied by side effects or cannot achieve complete clinical remission when used alone. The efficacy and safety of drugs are currently a clinical challenge. Thus, advanced drug delivery systems are needed for targeted delivery of drugs to the inflammatory sites and avoid absorption by healthy tissues. In this review, we have summarized the latest research on the pathogenesis of IBD and the emerging pharmacotherapies, and discussed potential therapeutic targets for innovative therapies.
Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Disbiose/complicações , Transplante de Microbiota Fecal , Humanos , Inflamação/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológicoRESUMO
Cultural-ecological theories posit that ethnic-racial identity (ERI) development is shaped by transactions between contexts of ethnic-racial socialization, yet research considering intersections among multiple contexts is limited. In this study, Black, Latino, White, and Asian American adolescents (N = 98; Mage = 16.26, SD = 1.09; 55.1% female identifying) participated in surveys and focus group discussions (2013-2014) to share insights into ERI development in context. Using consensual qualitative research, results indicated: (a) family ethnic-racial socialization intersects with community-based, peer, media, and school socialization; (b) ethnic-racial socialization occurs outside family through intersections between peer, school, community-based, and media settings; and (c) ethnic-racial socialization is embedded within systems of racial oppression across contexts. Discussion includes implications for future research and interventions supporting youth ERI.
Assuntos
Identificação Social , Socialização , Adolescente , Etnicidade , Feminino , Hispânico ou Latino , Humanos , Masculino , Grupos RaciaisRESUMO
BACKGROUND The association of radiotherapy with breast cancer survival in patients who underwent a mastectomy and had micrometastases in the sentinel lymph node is unclear. MATERIAL AND METHODS The survival benefit of radiotherapy was examined in patients with T0/1-T2N1mi breast cancer undergoing mastectomy plus sentinel lymph node biopsy (SLNB). Kaplan-Meier curves were employed for survival analysis and competing risk analysis, and a propensity score matching (PSM) cohort was enrolled to investigate whether such patients benefit from radiotherapy. RESULTS We identified 2864 patients in the SEER database from 2004 to 2015. All eligible patients were divided into the radiotherapy and the no-radiotherapy cohorts. With the median follow-up of 53 months, 5-year breast cancer-specific survival (BCSS) was 94.4% vs 95.2% (P=0.135), and 5-year overall survival (OS) was 91.2% vs 90.1% (P=0.466) in the radiotherapy cohorts and no-radiotherapy cohorts, respectively. The results of the competing risk analysis showed a comparable 5-year cumulative incidence of breast cancer-specific death (BCSD) in the radiotherapy and no-radiotherapy groups (5.5% vs 4.7%, P=0.107) but a higher 5-year cumulative incidence of other causes of death (OCD) in the no-radiotherapy cohort (3.3% vs 5.3%, P=0.011). No significant difference was observed for BCSS or OS in the PSM cohort. CONCLUSIONS Radiotherapy has no benefit for patients with T0/1-T2 breast cancer undergoing mastectomy with N1mi disease on SLNB. This analysis provides evidence that radiotherapy may safely be omitted in this group of patients.