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1.
Neurol Sci ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488928

RESUMO

BACKGROUND: Observational studies have indicated that psychiatric disorders are the most common comorbidities in pediatric epilepsy. However, the existence and direction of a causal relationship between the two remains controversial. This study aims to investigate the association between common childhood psychiatric disorders and epilepsy using a two-sample, bidirectional Mendelian randomization (MR) approach. METHODS: Genetic instruments were obtained from the most recent and largest genome-wide association studies (GWAS), including datasets for epilepsy (N_case = 29,994, N_control = 52,538), attention deficit hyperactivity disorder (ADHD) (N_case = 38,691, N_control = 186,843), autism spectrum disorder (ASD) (N_case = 18,381, N_control = 27,969), and Tourette syndrome (TS) (N_case = 4,819, N_control = 9488). MR analyses were conducted using the inverse variance weighted (IVW) method, weighted median method, and MR-Egger regression. RESULTS: No reliable evidence was found to suggest a causal effect of ADHD, ASD, or TS on epilepsy, nor was there any reliable evidence indicating that epilepsy increases the risk of these three psychiatric disorders. These findings remained consistent across various sensitivity analyses. CONCLUSION: Although observational studies have highlighted a high comorbidity rate between pediatric epilepsy and psychiatric disorders like ADHD and ASD, the MR analysis did not confirm a causal relationship between them. This suggests that previous studies might have been influenced by confounding biases or other biases, potentially overestimating the true relationship. A deeper understanding of the mechanisms underlying these comorbidities is crucial for refining the treatment of pediatric epilepsy.

2.
Mol Biotechnol ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429624

RESUMO

Intraventricular hemorrhage results in posthemorrhagic hydrocephalus (PHH). Neonatal hydrocephalus remains a challenging disease due to the high failure rate of all management strategies. We evaluated long noncoding RNA growth arrest-specific 5 (GAS5)-mediated network in neonatal hydrocephalus, providing a new direction for the treatment of hydrocephalus. The PHH model was constructed in neonatal rats after intracerebroventricular injection with GAS5, miR-325-3p, and chaperonin containing T-complex protein 1, subunit 8 (CCT8) plasmids, or oligonucleotides. Next, behavioral tests, measurement of serum inflammation, observation of brain tissue pathology, and calculation of hemoglobin and brain water contents were implemented. GAS5, miR-325-3p, and CCT8 expression, in combination with their interactions, was checked. As the results reported, collagenase infusion induced hydrocephalus, impairing neurological function, enhancing inflammation and neuronal apoptosis, and increasing hemoglobin and brain water contents. GAS5 and CCT8 were up-regulated, while miR-325-3p was down-regulated in hydrocephalic rats. Downregulating GAS5/CCT8 or upregulating miR-325-3p could inhibit inflammatory response and improve neurological function in young hydrocephalic rats. GAS5 promotes CCT8 expression through sponge adsorption of miR-325-3p. GAS5 silencing-mediated protections against hydrocephalus were counteracted by CCT8 overexpression. In summary, GAS5 aggravates neonatal hydrocephalus and inflammatory responses in a way of leasing miR-325-3p-involved regulation of CCT8.

3.
World J Pediatr Surg ; 7(1): e000641, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38374897

RESUMO

Objective: The study aimed to explore the association between the site of interictal epileptic discharges (IEDs) on postoperative electroencephalogram (EEG) and seizure recurrence after antiepileptic drug (AED) withdrawal. The study hypothesizes that the concordance of IED sites with surgical sites indicates incomplete resection of epileptic focus, while non-concordance of IED sites with surgical sites indicates postoperative changes or cortical stimulation. The former has a higher risk of seizure recurrence. Methods: We retrospectively analyzed the postoperative EEG pattern of 182 consecutive children who underwent resection surgery. To identify the risk factors for seizure recurrence, we compared the attributes of seizure recurred and seizure-free groups by univariate and multivariate analyses. AED tapering was standardized, involving a 25% reduction in the dose of a single type of AED every 2 weeks, independent of the presurgical AED load. Results: We attempted AED withdrawal in 116 (63.7%) children. Twenty-eight (24.1%) children experienced seizure recurrence during or after AED withdrawal. A greater number of AEDs used at the time of surgery (p=0.005), incomplete resection (p=0.001), and presence of IED on postoperative EEG (p=0.011) are predictors of seizure recurrence. The completeness of resection and seizure recurrence after AED withdrawal were related to the presence of IED on the EEG, but not to the concordance of IED with surgical sites. Conclusion: For children with abnormal EEG, the decision to discontinue AED should be made more cautiously, regardless of the relative location of the discharge site and the surgical site.

4.
Int J Mol Sci ; 25(3)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38338716

RESUMO

Transcription factors within microglia contribute to the inflammatory response following intracerebral hemorrhage (ICH). Therefore, we employed bioinformatics screening to identify the potential transcription factor tonicity-responsive enhancer-binding protein (TonEBP) within microglia. Inflammatory stimuli can provoke an elevated expression of TonEBP in microglia. Nevertheless, the expression and function of microglial TonEBP in ICH-induced neuroinflammation remain ambiguous. In our recent research, we discovered that ICH instigated an increased TonEBP in microglia in both human and mouse peri-hematoma brain tissues. Furthermore, our results indicated that TonEBP knockdown mitigates lipopolysaccharide (LPS)-induced inflammation and the activation of NF-κB signaling in microglia. In order to more deeply comprehend the underlying molecular mechanisms of how TonEBP modulates the inflammatory response, we sequenced the transcriptomes of TonEBP-deficient cells and sought potential downstream target genes of TonEBP, such as Pellino-1 (PELI1). PELI has been previously reported to mediate nuclear factor-κB (NF-κB) signaling. Through the utilization of CUT & RUN, a dual-luciferase reporter, and qPCR, we confirmed that TonEBP is the transcription factor of Peli1, binding to the Peli1 promoter. In summary, TonEBP may enhance the LPS-induced inflammation and activation of NF-κB signaling via PELI1.


Assuntos
Hemorragia Cerebral , Microglia , Fatores de Transcrição NFATC , Animais , Humanos , Camundongos , Hemorragia Cerebral/genética , Hemorragia Cerebral/metabolismo , Inflamação/genética , Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/metabolismo , Microglia/metabolismo , Doenças Neuroinflamatórias , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
5.
Epilepsy Behav ; 151: 109645, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38244419

RESUMO

OBJECTIVE: People with epilepsy desire to acquire accurate information about epilepsy and actively engage in its management throughout the long journey of living with seizures. ChatGPT is a large language model and we aimed to assess the accuracy and consistency of ChatGPT in responding to the common concerns of people with epilepsy and to evaluate its ability to provide emotional support. METHODS: Questions were collected from the International League against Epilepsy and the China Association against Epilepsy. The responses were independently assessed by two board-certified epileptologists from the China Association against Epilepsy, and a third reviewer resolved disagreements. The reviewers assessed its ability to provide emotional support subjectively. RESULTS: A total of 378 questions related to epilepsy and 5 questions related to emotional support were included. ChatGPT provided "correct and comprehensive" answers to 68.4% of the questions. The model provided reproducible answers for 82.3% questions. The model performed poorly in answering prognostic questions, with only 46.8% of the answers rated as comprehensive. When faced with questions requiring emotional support, the model can generate natural and understandable responses. SIGNIFICANCE: ChatGPT provides accurate and reliable answers to patients with epilepsy and is a valuable source of information. It also provides partial emotional support, potentially assisting those experiencing emotional distress. However, ChatGPT may provide incorrect responses, leading users to inadvertently accept incorrect and potentially dangerous advice. Therefore, the direct use of ChatGPT for medical guidance is not recommended and its primary use at present is in patients education.


Assuntos
Epilepsia , Humanos , Epilepsia/terapia , Convulsões , Certificação , China , Idioma
6.
Epilepsy Behav ; 150: 109556, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38029661

RESUMO

OBJECTIVE: The timing of antiseizure medication (ASM) withdrawal in children after epilepsy surgery remains controversial and lacks recognized standards. Given the various negative effects of ASM on development in children, this study aimed to evaluate the safety and feasibility of early ASM withdrawal after epileptic resection surgery. METHODS: We retrospectively assessed the seizure outcomes and ASM profiles of children who had undergone epileptic resection surgery between August 2015 and August 2020 and attempted ASM reduction in the early postoperative phase. Tapering the dose of ASM was attempted when children were seizure-free with no interictal epileptiform discharges (IEDs) on electroencephalogram (EEG) for at least 6 months postoperatively. RESULTS: This study included 145 children with a median follow-up duration of 40 months. Early ASM tapering was attempted postoperatively in 99 (68.3 %) children. Postoperative ASM discontinuation was attempted in 87 (60.0 %) children. Nine (9.1 %) children experienced seizure recurrence during the ASM reduction stage, and 10 (11.5 %) experienced recurrence after ASM discontinuation. Incomplete resection (P = 0.003) and postoperative seizures before ASM tapering (P = 0.003) were independent predictors of seizure recurrence during and after early ASM withdrawal. SIGNIFICANCE: ASM withdrawal is viable and safe to be initiated in children who are seizure-free postoperatively and have no IEDs on the scalp EEG for at least 6 months. Children with incomplete resection and postoperative seizures before ASM withdrawal are at a higher risk of seizure recurrence and may need to continue ASM for a longer period.


Assuntos
Epilepsia , Síndrome de Abstinência a Substâncias , Criança , Humanos , Estudos Retrospectivos , Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Epilepsia/cirurgia , Convulsões/tratamento farmacológico , Convulsões/etiologia , Eletroencefalografia , Síndrome de Abstinência a Substâncias/etiologia , Recidiva
7.
Neurosurg Rev ; 46(1): 170, 2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37433938

RESUMO

An external ventricular drain (EVD) is used to facilitate cerebrospinal fluid (CSF) removal in medulloblastoma patients suffering from hydrocephalus. It is essential to recognize that EVD management plays a crucial role in influencing the incidence of drain-related complications. However, the ideal method for EVD management remains undetermined. Our research sought to examine the safety of EVD placement and the impact of EVD on the incidences of intracranial infections, postresection hydrocephalus, and posterior fossa syndrome (PFS). We conducted a single-center observational study involving a cohort of 120 pediatric medulloblastoma patients who were treated from 2017 to 2020. The rates of intracranial infection, postresection hydrocephalus, and PFS were 9.2%, 18.3%, and 16.7%, respectively. EVD did not influence the occurrence of intracranial infection (p = 0.466), postresection hydrocephalus (p = 0.298), or PFS (p = 0.212). A gradual EVD weaning protocol correlated with an elevated incidence of postresection hydrocephalus (p = 0.033), whereas a rapid weaning approach resulted in 4.09 ± 0.44 fewer drainage days (p < 0.001) than the gradual weaning strategy. EVD placement (p = 0.010) and intracranial infection (p = 0.002) were linked to delayed speech return, whereas a longer duration of drainage was conducive to the recovery of language function (p = 0.010). EVD insertion was not correlated with the incidence of intracranial infection, postoperative hydrocephalus, or PFS. The optimal EVD management method should encompass a rapid EVD weaning strategy, followed by prompt drain closure. We have presented additional evidence to improve the safety of EVD insertion and management in neurosurgical patients to ultimately facilitate the establishment of standardized institutional/national implementation and management protocols.


Assuntos
Neoplasias Cerebelares , Vazamento de Líquido Cefalorraquidiano , Hidrocefalia , Meduloblastoma , Humanos , Criança , Hidrocefalia/cirurgia , Meduloblastoma/complicações , Meduloblastoma/cirurgia , Neoplasias Cerebelares/complicações , Neoplasias Cerebelares/cirurgia , Resultado do Tratamento
8.
Pediatr Neurol ; 146: 95-102, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37454398

RESUMO

BACKGROUND: There are insufficient data on pediatric patients with medulloblastoma who require cerebrospinal fluid (CSF) diversion following resection. Therefore, this study aimed to determine the incidence and the characteristics associated with it in this subset of patients. METHODS: We conducted a single-center, retrospective, observational cohort study of patients aged 18 years or less who underwent medulloblastoma resection at our department between 2010 and 2021. The primary outcome was the incidence of CSF diversion surgery required after resection. Participant demographics, tumor biology, and interventions were analyzed using univariate- and multivariate-adjusted models. RESULTS: Of the 183 patients admitted to our department, 131 (71.6%) participated in this study. The incidence of permanent CSF diversion was 26.0% (95% confidence interval [CI]: 18.7 to 34.3). Factors independently associated with requirement of permanent CSF diversion were medulloblastoma volume >46.4 cm3 (odds ratio [OR]: 2.919, 95% CI: 1.191 to 7.156) and CSF channel invasion (OR: 2.849, 95% CI: 1.142 to 7.102). The duration of manifestation may be a covariate of tumor volume with increased risk of requirement for permanent CSF diversion (OR: 1.006, 95% CI: 1.000 to 1.013), and tumor volume may be a predictor in patients who underwent subtotal resection (OR: 4.900, 95% CI: 0.992 to 24.208, P = 0.05). Finally, patients who required permanent CSF diversion were divided according to medulloblastoma molecular subgroups, and no significant differences were found. CONCLUSION: We report major predictive factors for permanent CSF diversion surgery in patients with medulloblastoma. Our study suggests that the presence of postresection hydrocephalus is not high enough to warrant permanent, prophylactic CSF diversion in all patients.


Assuntos
Neoplasias Cerebelares , Hidrocefalia , Meduloblastoma , Humanos , Criança , Meduloblastoma/epidemiologia , Meduloblastoma/cirurgia , Meduloblastoma/complicações , Estudos Retrospectivos , Incidência , Neoplasias Cerebelares/epidemiologia , Neoplasias Cerebelares/cirurgia , Neoplasias Cerebelares/complicações , Fatores de Risco , Hidrocefalia/etiologia
9.
Childs Nerv Syst ; 39(9): 2527-2532, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37171608

RESUMO

BACKGROUND: Artery of Percheron (AOP) as main feeder artery of arteriovenous malformation (AVM) is extremely rare. Two cases of thalamic AVM fed by AOP have been reported to date and only one AVM been removed by microsurgery when attempt of intervention embolization failed. Midbrain AVM fed by AOP has not been reported yet. CASE PRESENTATION: Here, we presented the first successful embolized case of midbrain AVM supplied by the AOP in a 10-year-old boy, who suffered dual oculomotor nerve palsy and secondary hemorrhage before embolization. During endovascular embolization, selective angiography by 1.2 Fr. Magic microcatheter showed an intranidal aneurysm located on the distal AOP. Two injections of a 1:4 ratio mixture of NBCA-MS completely occlude the nidus and intranidal aneurysm with no complications occurred. The child recovered well and the oculomotor deficits improved. CONCLUSION: This case highlighted that AOP is a clinically significant branch associated with AVM in midbrain and thalamus. Moreover, intervention embolization of midbrain AVM fed by AOP is a considerable therapeutic strategy.


Assuntos
Embolização Terapêutica , Aneurisma Intracraniano , Malformações Arteriovenosas Intracranianas , Masculino , Humanos , Criança , Malformações Arteriovenosas Intracranianas/complicações , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/terapia , Artérias , Aneurisma Intracraniano/diagnóstico por imagem , Radiografia
10.
Transl Pediatr ; 12(4): 681-694, 2023 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-37181029

RESUMO

Background: Epilepsy is a chronic disease that is characterized by transient brain dysfunction caused by an abrupt abnormal neuronal discharge. Recent studies have indicated that the pathways related to inflammation and innate immunity play significant roles in the pathogenesis of epilepsy, suggesting an interrelationship between immunity and inflammatory processes and epilepsy. However, the immune-related mechanisms are still not precisely understood; therefore, this study aimed to explore the immune-related mechanisms in epilepsy disorders, highlight the role of immune cells at the molecular level in epilepsy, and provide therapeutic targets for patients with epilepsy. Methods: Brain tissue samples from healthy and epileptic individuals were collected for transcriptome sequencing to identify differentially expressed genes (DEGs) and differentially expressed (DE)-long coding RNAs (lncRNAs). Based on interactions from the miRcode, starBase2.0, miRDB, miRTarBase, TargetScan, and ENCORI databases, a lncRNA-associated competitive endogenous RNA (ceRNA) network was created. Gene ontology and the Kyoto encyclopedia of genes analyses established that the genes in the ceRNA network were mainly enriched in immune-related pathways. Immune cell infiltration, screening, and protein-protein interaction analyses of the immune-related ceRNAs, and correlation analysis between immune-related core messenger RNA (mRNA) and immune cells were also performed. Results: Nine hub genes (EGFR, GRB2, KRAS, FOS, ESR1, MAPK1, MAPK14, MAPK8, and PPARG) were obtained. Also, 38 lncRNAs, one miRNA (hsa-miR-27a-3p), and one mRNA (EGFR) comprised the final core ceRNA network. Mast cells, plasmacytoid dendritic cells, and immature dendritic cells all showed positive correlations with EGFR, while Cluster of differentiation 56 dim natural killer cells (CD56dim natural killer cells) showed negative correlations. Finally, we employed an epilepsy mouse model to validate EGFR, which is consistent with disease progression. Conclusions: In conclusion, the pathophysiology of epilepsy was correlated with EGFR. Thus, EGFR could be a novel biomarker of juvenile focal epilepsies, and our findings provide promising therapeutic targets for epilepsy.

11.
Int J Mol Sci ; 24(9)2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37176030

RESUMO

Intracerebral hemorrhage (ICH) is a severe cerebrovascular disease with a high disability rate and high mortality, and pyroptosis is a type of programmed cell death in the acute phase of ICH. Neuronal Per-Arnt-Sim domain protein 4 (Npas4) is a specific transcription factor highly expressed in the nervous system, yet the role of NPAS4 in ICH-induced pyroptosis is not fully understood. NLR family Pyrin-domain-containing 6 (NLRP6), a new member of the Nod-like receptor family, aggravates pyroptosis via activating cysteine protease-1 (Caspase-1) and Caspase-11. In this study, we found that NPAS4 was upregulated in human and mouse peri-hematoma brain tissues and peaked at approximately 24 h after ICH modeling. Additionally, NPAS4 knockdown improved neurologic dysfunction and brain damage induced by ICH in mice after 24 h. Meanwhile, inhibiting NPAS4 expression reduced the levels of myeloperoxidase (MPO)-positive cells and Caspase-1/TUNEL-double-positive cells and decreased cleaved Caspase-1, cleaved Caspase-11, and N-terminal GSDMD levels. Consistently, NPAS4 overexpression reversed the above alternations after ICH in the mice. Moreover, NPAS4 could interact with the Nlrp6 promoter region (-400--391 bp and -33--24 bp) and activate the transcription of Nlrp6. Altogether, our study demonstrated that NPAS4, as a transcription factor, can exacerbate pyroptosis and transcriptionally activate NLRP6 in the acute phase of intracerebral hemorrhage in mice.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Camundongos , Humanos , Animais , Piroptose/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Hemorragia Cerebral/genética , Hemorragia Cerebral/metabolismo , Caspase 1/genética , Caspase 1/metabolismo , Fatores de Transcrição , Inflamassomos/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
12.
Medicina (Kaunas) ; 59(4)2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37109743

RESUMO

Background and Objectives: After failed epilepsy surgery, patients often revert to an antiseizure medication (ASM) ASM regimen, which can be adjusted or optimized in three ways: increasing the dose, alternative therapy, and combination therapy. It is unclear which type of antiseizure medication adjustment method can improve outcomes. Materials and Methods: Children who underwent failed epileptic resection surgery at the Department of Neurosurgery, Children's Hospital of Chongqing Medical University between January 2015 and December 2021 were included in this cohort, who were reviewed for whether they underwent adjustment of ASM with increased dose, alternative therapy, or combination therapy. The seizure outcome and quality of life (QoL) were assessed. Two-tailed Fisher exact test and Mann-Whitney U test were used for statistical analysis. Results: Sixty-three children with failed surgery were included for further analysis, with a median follow-up time of 53 months. The median seizure recurrence time was 4 months. At the last follow-up, 36.5% (n = 23) of patients achieved seizure freedom, 41.3% (n = 26) achieved seizure remission, and 61.9% (n = 39) had a good QoL. None of the three types of ASM adjustment improved children's outcomes, whether considered in terms of seizure-free rate, seizure remission rate, or QoL. Early recurrences were significantly associated with decreased probability of seizure freedom (p = 0.02), seizure remission (p = 0.02), and a good QoL (p = 0.01). Conclusions: Children who underwent failed epilepsy surgery remains some potential for late seizure remission from ASM. Yet adjusting ASM regimen does not increase the probability of seizure remission nor does it improve the QoL. Clinicians should complete evaluations and consider the need for other antiepileptic treatment as soon as possible after surgery failed, especially when dealing with children with an early recurrence.


Assuntos
Epilepsia , Qualidade de Vida , Criança , Humanos , Epilepsia/tratamento farmacológico , Epilepsia/cirurgia , Anticonvulsivantes/uso terapêutico , Convulsões/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento
13.
Childs Nerv Syst ; 39(8): 2115-2122, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37081233

RESUMO

BACKGROUND: Neonatal posthemorrhagic hydrocephalus remains a common complication in preterm infants, with high rates of mortality and morbidity, placing parents at high risk of anxiety and depression. We sought to investigate the neurodevelopmental outcomes of infants with posthemorrhagic hydrocephalus who underwent surgery and the psychological effect on their parents. METHODS: We retrospectively analysed all infants with posthemorrhagic hydrocephalus born between 2014 and 2020 in the Children's Hospital of Chongqing Medical University, China. The neurodevelopmental outcomes of 28 patients were evaluated by the Pediatric Stroke Outcome Measure score, and the psychological states of the parents of survivors were assessed by the Hospital Anxiety and Depression Scale. RESULTS: The families of the 28 patients were followed up for a median duration of 3 years; 6 (21.4%) patients died within 6 months after discharge, 12 (42.9%) patients had moderate to severe dysfunction, and only 10 (35.7%) patients had good outcomes. Regarding the 22 parents of the survivors, 5 (22.7%) and 4 (18.2%) had borderline anxiety and depression symptoms, respectively. Two (9.1%) caregivers had exact anxiety and depression symptoms. Leukomalacia after intraventricular haemorrhage was associated with adverse neurological outcomes. The infants' histories of epileptic seizures during the neonatal period were associated with the anxiety of their parents. CONCLUSION: The overall outcome of posthemorrhagic hydrocephalus patients is unsatisfactory, and children with leukomalacia after haemorrhage tend to have poor outcomes. A history of epileptic seizures during the course of the disease may exacerbate the anxiety of the caregivers.


Assuntos
Hidrocefalia , Recém-Nascido Prematuro , Lactente , Recém-Nascido , Humanos , Criança , Estudos Retrospectivos , Hidrocefalia/cirurgia , Hidrocefalia/complicações , Hemorragia Cerebral/complicações , Convulsões/complicações
14.
Molecules ; 28(6)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36985672

RESUMO

Menispermi Rhizoma, the rhizome of Menispermum dauricum DC., is a traditional Chinese medicine, which has the effect of clearing away heat and detoxification, dispelling wind, and relieving pain. It is often used in the treatment of sore throat, enteritis, dysentery, and rheumatism. The chemical constituents of M. Rhizoma mainly include alkaloids, phenolic acids, quinones, cardiotonic glycosides, and so on. Modern pharmacological studies have proved that M. Rhizoma has the effects of anti-tumour, anti-inflammation, anti-oxidation, bacteriostasis, cardio-cerebrovascular protection, anti-depression and anti-Alzheimer's disease. In recent years, the chemical constituents of M. Rhizoma have been found continuously, and the pharmacological studies have deepened gradually. This paper reviews the research progress on the chemical composition and pharmacological effects of M. Rhizoma, to provide a basis for further research and development of its medicinal value.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Menispermum , Medicamentos de Ervas Chinesas/química , Rizoma/química , Alcaloides/análise , Medicina Tradicional Chinesa , Menispermum/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/análise
15.
Turk Neurosurg ; 33(4): 683-690, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36482854

RESUMO

AIM: To construct a prediction nomogram model for the postoperative seizure outcomes in children with focal cortical dysplasia (FCD). MATERIAL AND METHODS: We retrospectively reviewed the clinical data of 97 children with epilepsy secondary to FCD who had undergone resection surgery at Children's Hospital of Chongqing Medical University from June 2013 to September 2019. Univariate and multivariate Cox proportional hazards regression were used to explore the predictors of postoperative persistent seizure, and a nomogram prediction model for postoperative seizure outcome was developed. The C-index was chosen to evaluate the discriminability of the nomogram with internal validation. Calibration curves and decision curve analysis were used to evaluate consistency and clinical efficacy, respectively. RESULTS: The complete resection of epileptogenic focus and the pathological type of FCD were independent predictors of persistent seizure in children with epilepsy secondary to FCD after surgery. Based on multivariate Cox proportional hazard regression, a predictive nomogram for epilepsy outcome was established and validated via the bootstrap method with 1000 resamples. The nomogram showed superior prediction accuracy (C-index = 0.883); by drawing and reviewing the calibration curve and decision curve, the nomogram presented good consistency and clinical efficacy. CONCLUSION: A nomogram prediction model of postsurgery seizure outcome in children with epilepsy secondary to FCD was constructed based on four variables, providing a reliable and convenient tool for individual seizure outcome prediction.


Assuntos
Epilepsia , Displasia Cortical Focal , Humanos , Criança , Nomogramas , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Procedimentos Neurocirúrgicos/métodos , Convulsões/etiologia , Convulsões/cirurgia , Epilepsia/cirurgia , Resultado do Tratamento
16.
Oncogene ; 41(37): 4295-4306, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35978151

RESUMO

SMARCE1 gene, encoding a core subunit of SWI/SNF chromatin remodeling complex, is situated on chromosome 17q21-ter region that is frequently gained in neuroblastoma. However, its role in the tumorigenesis remains unknown. Here, we showed that high expression of SMARCE1 was associated with poor prognosis of patients with neuroblastoma, especially those with MYCN amplification. Knockdown of SMARCE1 reduced proliferation, colony formation, and tumorigenicity of neuroblastoma cells. Mechanistically, SMARCE1 directly interacted with MYCN, which was necessary for MYCN-mediated transcriptional activation of downstream target genes including PLK1, ODC1, and E2F2. Overexpression of PLK1, ODC1 or E2F2 significantly reversed the inhibiting effect of SMARCE1 knockdown on the proliferation, colony formation, and tumorigenicity of MYCN-amplified neuroblastoma cells. Moreover, we revealed that MYCN directly regulated SMARCE1 transcription through binding to a non-canonical E-box of SMARCE1 promoter, thus enhancing SMARCE1-MYCN cooperativity. These findings establish SMARCE1 is a critical oncogenic factor in neuroblastoma and provide a new potential target for treatment of neuroblastoma with 17q21-ter gain and MYCN amplification.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neuroblastoma , Carcinogênese/genética , Linhagem Celular Tumoral , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Ligação a DNA/genética , Humanos , Proteína Proto-Oncogênica N-Myc/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Neuroblastoma/genética , Neuroblastoma/metabolismo , Ativação Transcricional/genética
17.
J Cardiothorac Surg ; 17(1): 34, 2022 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-35282839

RESUMO

BACKGROUND: Traumatic asphyxia (TA) is a rarely reported disease characterized as thoraco-cervico-facial petechiae, facial edema and cyanosis, subconjunctival hemorrhage and neurological symptoms. This study aimed to report 51 children of TA at the pediatric medical center of west China. METHODS: Scanned medical reports were reviewed and specific variables as age, sex, cause of injury, clinical manifestations and associated injuries were analyzed using SPSS 25.0. RESULTS: The average age of patients was 5.3 ± 2.9 (1.3-13.2) year-old. Thirty (58.8%) were boys and 21 (41.2%) were girls. Most TAs occurred during vehicle accident, object compression and stampede. All patients showed facial petechiae (100.0%, CI 93.0-100.0%), 25 (49.0%, CI 34.8-63.2%) out of 51 presented with facial edema, 29 (56.9%, CI 42.8-70.9%) presented with subconjunctival hemorrhage, including bilateral 27 and unilateral 2. Six patients had facial cyanosis (11.8%, CI 2.6-20.9%). Other symptoms were also presented as epileptic seizure, vomiting, incontinence, paraplegia, etc. The most frequent companion injury was pulmonary contusion (76.5%, CI 64.4-88.5%). Other companion injuries included mediastinal emphysema, fracture, cerebral contusion and hemorrhage, hypoxic-ischemic brain injury, abdominal organ contusion, mastoid hemorrhage, hematocele of paranasal sinuses, spinal cord injury, hepatic insufficiency, myocardial injury and retinal hemorrhage and edema. Treatment was mainly supportive. No death occurred in our study. The prognosis is rather good if without damage of central nervous system. CONCLUSION: TA could bring out multiple symptoms, among which retinal hemorrhage and edema, spinal cord injury and viscera impairment have been less observed. Comprehensive physical and auxiliary examination should be performed considering TA. Its prognosis is rather good with focus on life-threatening complications.


Assuntos
Asfixia , Traumatismos da Medula Espinal , Adolescente , Asfixia/complicações , Criança , Pré-Escolar , Feminino , Hemorragia , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos
18.
Biochem Biophys Res Commun ; 599: 148-155, 2022 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-35182941

RESUMO

Actin-like 6A (ACTL6A) is a core subunit of the SWI/SNF chromatin remodeling complex and is highly expressed in several types of human cancers including glioblastoma. Recent studies verified that ACTL6A regulates the proliferation, differentiation, and migration of cancer cells. In this study, we identified ACTL6A as an important regulator of DNA replication. ACTL6A knockdown could impair the DNA replication initiation in glioblastoma cells. The regulation of DNA replication by ACTL6A was mediated through regulating the expression of the CDC45-MCM-GINS (CMG) complex genes. Further investigation revealed that ACTL6A transcriptionally regulates MCM5 expression. Furthermore, ACTL6A knockdown induced DNA damage and diminished the activity of the ATR-Chk1 pathway, which ultimately led glioblastoma cells to apoptosis and death. Taken together, our findings highlight the critical role of ACTL6A in DNA replication and ATR-Chk1 pathway, and reveal a potential target for therapeutic intervention in glioblastoma.


Assuntos
Actinas/genética , Apoptose/genética , Proteínas Cromossômicas não Histona/genética , Replicação do DNA , Proteínas de Ligação a DNA/genética , Glioblastoma/genética , Glioblastoma/patologia , Actinas/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Quinase 1 do Ponto de Checagem/genética , Quinase 1 do Ponto de Checagem/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Transdução de Sinais/fisiologia
20.
Front Neurol ; 13: 1066953, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36619929

RESUMO

Objective: Epilepsy dramatically affects the quality of life (QoL) of children, and resection surgery can improve their QoL by reducing seizures or completely controlling them. Children who have postoperative seizures tend to show a poorer QoL. The aim of the present study was to investigate the QoL of children with seizures after resection surgery and its influencing factors. Methods: In the present study, we retrospectively reviewed 151 consecutive children who underwent resection surgery. We then divided them into two groups, seizure and seizure-free groups, according to the seizure outcomes 1 year after surgery. Variables were categorized into a number of factor types such as preoperative factors, surgery-related factors, postoperative factors, and family factors. QoL and seizure outcomes more than 3 years after surgery were assessed according to the ILAE seizure outcome classification and the CHEQOL-25 scale. Results: Forty-three (28.5%) of the 151 children had seizures 1 year after surgery, and two children died during the follow-up period. The mean CHEQOL-25 scale for children with seizures was 63.5 ± 18.2, and 20 (48.8%) patients had poor QoL. Surgery-related factors, such as surgical complications and surgical sequelae, were not statistically associated with QoL. Preoperative language development retardation or language dysfunction [odds ratio (OR) = 29.3, P = 0.012) and postoperative ILAE seizure outcome classification (OR = 1.9, P = 0.045)] were significantly associated with QoL. Significance: Children with seizures after resection surgery had a relatively poor QoL. Surgery-related factors, such as surgical complications and surgical sequelae, cannot predict the QoL. Preoperative language development retardation or language dysfunction and postoperative ILAE seizure outcome classification were independent predictors of the quality of life (QoL). For children who could not achieve the expected freedom from seizure after surgery, a lower ILAE grade (ILAE 1-3) is also an acceptable outcome since it predicts a higher QoL.

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