RESUMO
Diallyl disulfide (DADS), an organic component of allicin abstracted from garlic, possesses multi-target antitumor activity. DJ-1 performs a vital function in promoting AKT aberrant activation via down-regulating phosphatase and tensin homologue (PTEN) in tumors. It is unknown the involvement of DJ-1 in epithelial-mesenchymal transition (EMT) of gastric cancer (GC) cells. The purpose of this study is to investigate whether diallyl disulfide (DADS) intervenes in the role of DJ-1 in GC. Based on the identification that the correlation between high DJ-1 and low PTEN expression in GC was implicated in clinical progression, we illuminated that down-regulation of DJ-1 by DADS aided in an increase in PTEN expression and a decrease in phosphorylated AKT levels, which was in line with the results manifested in the DJ-1 knockdown and overexpressed cells, concurrently inhibiting proliferation, EMT, migration, and invasion. Furthermore, the antagonistic effects of DADS on DJ-1 were observed in in vivo experiments. Additionally, DADS mitigated the DJ-1-associated drug resistance. The current study revealed that DJ-1 is one of potential targets for DADS, which hopefully provides a promising strategy for prevention and adjuvant chemotherapy of GC.
Assuntos
Compostos Alílicos , Proliferação de Células , Dissulfetos , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Proteína Desglicase DJ-1 , Neoplasias Gástricas , Dissulfetos/farmacologia , Proteína Desglicase DJ-1/metabolismo , Proteína Desglicase DJ-1/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Compostos Alílicos/farmacologia , Humanos , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linhagem Celular Tumoral , Animais , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genética , Movimento Celular/efeitos dos fármacos , Camundongos , Camundongos Nus , Camundongos Endogâmicos BALB CRESUMO
MiR-4732-5p was previously found to be dysregulated in nipple discharge of breast cancer. However, the expression and function of miR-4732-5p in breast cancer remain largely unknown. Here, the expression of miR-4732-5p was detected using quantitative real-time PCR in breast cancer tissues and cell lines. Cell proliferation, apoptosis, migration and invasion assays were performed to examine the effects of miR-4732-5p in breast cancer. In addition, mRNA sequencing, bioinformatics analysis, Western blot and luciferase assays were performed to identify the target of miR-4732-5p. Overall, miR-4732-5p was significantly down-regulated in breast cancer tissues, especially in lymph node metastasis (LNM)-negative tissues, compared with adjacent normal tissues. However, it was more highly expressed in LNM-positive breast cancer tissues, compared with LNM-negative ones. Expression of miR-4732-5p was positively correlated with lymph node metastasis, larger tumour size, advanced clinical stage, high Ki-67 levels and poor prognosis. MiR-4732-5p promoted cell proliferation, migration and invasion in breast cancer. MiR-4732-5p directly targeted the 3'-UTR of tetraspanin 13 (TSPAN13) and suppressed TSPAN13 expression at the mRNA and protein levels. These results suggested that miR-4732-5p may serve as a tumour suppressor in the initiation of breast cancer, but as a tumour promoter in breast cancer progression by targeting TSPAN13.
Assuntos
Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Tetraspaninas/genética , Regiões 3' não Traduzidas , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagomirs/genética , Antagomirs/metabolismo , Apoptose/genética , Sequência de Bases , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Humanos , Metástase Linfática , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Transdução de Sinais , Análise de Sobrevida , Tetraspaninas/metabolismoRESUMO
BACKGROUND: Trauma team activation criteria have a variable performance in the paediatric population. We aimed to identify predictors for high-level resource utilisation during trauma resuscitation in the ED. METHODS: A retrospective study was conducted in the ED of a tertiary paediatric hospital. Patient data were collected from trauma surveillance registry and analysis was performed to identify significant predictors. We then assessed the sensitivity and specificity of proposed models with respect to observed patient outcomes. RESULTS: Among 11 282 cases, the mean age was 6.1±4.9 (SD) years old. Fall was the most common mechanism of injury in 7364 (65.3%) patients. Eighty-eight (0.8%) patients required at least one high-level resource. Significant predictors for high-resource utilisation were overall GCS of <14 (relative risk (RR) 38.841, 95% CI 21.328 to 70.739, p<0.001), high-risk mechanisms of fall from height and motor vehicle collision (RR 7.863, 95% CI 4.687 to 13.192, p<0.001), as well as age-specific tachycardia (RR 1.796, 95% CI 1.145 to 2.817, p=0.0108). A model consisting of GCS and high-risk mechanism would under-triage 21 (0.2%) patients and over-triage 681 (6.0%) patients. When age-specific tachycardia was added, 8 (0.1%) less patients would be under-triaged but an additional 3251 (28.9%) patients would be over-triaged. CONCLUSION: As utilisation of high-level resources in paediatric trauma was rare, it was difficult to find an appropriate balance between under-triage and over-triage. Between the two, minimising the proportion of under-triage is more important as patient safety is paramount in paediatric trauma care.
Assuntos
Utilização de Instalações e Serviços/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Ressuscitação/estatística & dados numéricos , Ferimentos e Lesões/terapia , Criança , Pré-Escolar , Utilização de Instalações e Serviços/organização & administração , Utilização de Instalações e Serviços/normas , Feminino , Escala de Coma de Glasgow/estatística & dados numéricos , Hospitais Pediátricos/organização & administração , Hospitais Pediátricos/normas , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Lactente , Masculino , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/organização & administração , Padrões de Prática Médica/normas , Sistema de Registros/estatística & dados numéricos , Ressuscitação/normas , Estudos Retrospectivos , Singapura , Centros de Atenção Terciária/organização & administração , Centros de Atenção Terciária/normas , Centros de Atenção Terciária/estatística & dados numéricos , Centros de Traumatologia/organização & administração , Centros de Traumatologia/normas , Centros de Traumatologia/estatística & dados numéricos , Triagem/organização & administração , Triagem/normas , Triagem/estatística & dados numéricos , Ferimentos e Lesões/diagnósticoRESUMO
Speech comprehension is a central cognitive function of the human brain. In cognitive neuroscience, a fundamental question is to understand how neural activity encodes the acoustic properties of a continuous speech stream and resolves multiple levels of linguistic structures at the same time. This paper reviews the recently developed research paradigms that employ electroencephalography (EEG) or magnetoencephalography (MEG) to capture neural tracking of acoustic features or linguistic structures of continuous speech. This review focuses on two questions in speech processing: (1) The encoding of continuously changing acoustic properties of speech; (2) The representation of hierarchical linguistic units, including syllables, words, phrases and sentences. Studies have found that the low-frequency cortical activity tracks the speech envelope. In addition, the cortical activities on different time scales track multiple levels of linguistic units and constitute a representation of hierarchically organized linguistic units. The article reviewed these studies, which provided new insights into the processes of continuous speech in the human brain.
Assuntos
Eletroencefalografia , Magnetoencefalografia , Fala , Estimulação Acústica , Humanos , Fala/fisiologia , Percepção da FalaRESUMO
Long term synaptic plasticity, such as long term potentiation (LTP), has been widely accepted as a cellular mechanism underlying memory. Recently, it has been unraveled that Shp2 plays a role in synaptic plasticity and memory in Drosophila and mice, revealing significant and conserved effects of Shp2 in cognitive function. However, the exact mechanism underlying this function of Shp2 in synaptic plasticity and memory still remains elusive. Here, we examine the regulation of Shp2 in hippocampal LTP and contextual fear conditioning. We find that Shp2 is rapidly recruited into spines after LTP induction. Furthermore, the phosphorylation level of Shp2 at Tyr-542 is elevated after LTP stimuli either in cultured hippocampal neurons or acute slices. Notably, contextual fear conditioning also regulates the phosphorylation level of Shp2 at Tyr-542, suggesting fine-tuned regulation of Shp2 in LTP and memory formation. By using a Shp2-specific inhibitor and adeno-associated virus-Cre mediated Shp2 knock-out in cultured neurons, we provide evidence that the phosphatase activity of Shp2 is critical for activity-dependent AMPA receptor surface trafficking. Collectively, our results have revealed a regulatory mechanism of Shp2 underlying LTP and memory, broadening our understanding of Shp2 in cognitive function.
Assuntos
Hipocampo/fisiologia , Potenciação de Longa Duração/fisiologia , Memória/fisiologia , Neurônios/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Receptores de AMPA/metabolismo , Animais , Cognição/fisiologia , Drosophila melanogaster , Técnicas de Silenciamento de Genes , Hipocampo/citologia , Camundongos , Neurônios/citologia , Transporte Proteico/fisiologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Ratos , Ratos Sprague-Dawley , Receptores de AMPA/genéticaRESUMO
Prams and strollers are commonly used in daily childcare. We aim to study the type and severity of injuries associated with prams and strollers in an Asian population. We performed a retrospective review of children below the age of 6 who presented to a tertiary paediatric hospital in Singapore, from January 2012 to June 2015, with such injuries. There were 248 pram-related and stroller-related injuries. The median age was 12.5â months old. 69 (27.8%) sustained open wounds, 17 (6.9%) suffered fractures or dislocations and 2 children had significant head injuries. 29 patients (11.7%) sustained injuries while on stairs or escalators. Most of the injuries (197 cases, 79.4%) occurred despite adult supervision. The need for intervention was associated with older age and entrapment injuries (p<0.001). Only appropriately sized prams and strollers without exposed hinges should be used. These should not be deployed on stairs and escalators.
Assuntos
Acidentes por Quedas/estatística & dados numéricos , Traumatismos Craniocerebrais/epidemiologia , Fraturas Ósseas/epidemiologia , Equipamentos para Lactente , Luxações Articulares/epidemiologia , Síndromes de Compressão Nervosa/epidemiologia , Lesões dos Tecidos Moles/epidemiologia , Distribuição por Idade , Pré-Escolar , Traumatismos Craniocerebrais/etiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Desenho de Equipamento , Segurança de Equipamentos , Feminino , Fraturas Ósseas/etiologia , Humanos , Incidência , Lactente , Equipamentos para Lactente/efeitos adversos , Recém-Nascido , Luxações Articulares/etiologia , Masculino , Síndromes de Compressão Nervosa/etiologia , Estudos Retrospectivos , Singapura/epidemiologia , Lesões dos Tecidos Moles/etiologia , Lesões dos Tecidos Moles/prevenção & controleRESUMO
OBJECTIVES: We describe the demographics of pediatric patients with trauma transferred using private transport (PT) versus emergency medical services (EMS) and evaluate the potential impact on their treatment and outcome. METHODS: We accessed data from our national trauma registry, a prospectively collected database. Data were extracted on all patients with trauma admitted to our institution between January 2011 and June 2013, with injury severity score (ISS) higher than 8. We categorized unstable injuries as head injuries, spinal injuries, or proximal long bone fractures. Major trauma was defined as the presence of any of the following: ISS of 16 or higher, intensive care unit (ICU) admission or death. RESULTS: Ninety children were studied, including 27 major trauma and 66 unstable injuries; 69 patients (77%) used PT. Most patients with major trauma (17/27, 63%) and unstable injuries (50/66, 76%) used PT. Compared with EMS patients, PT patients were younger, smaller, took longer for emergency department physician review and stayed longer in the emergency department. Rates of ICU admission were similar in both groups, but length of stay in ICU and total hospital stay were shorter in the PT group despite similar proportions of major trauma and unstable injuries as well as median ISS. Each group had 1 mortality. CONCLUSIONS: Most children with major trauma and unstable injuries were brought by PT, risking deterioration en route. Nevertheless, this does not seem to translate to worse outcomes overall.
Assuntos
Serviços Médicos de Emergência/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Transporte de Pacientes/estatística & dados numéricos , Ferimentos e Lesões/terapia , Adolescente , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Mortalidade Hospitalar , Humanos , Lactente , Tempo de Internação/estatística & dados numéricos , Masculino , Estudos Prospectivos , Sistema de Registros , Singapura , Transporte de Pacientes/métodos , Ferimentos e Lesões/epidemiologiaRESUMO
Cerebral hypoxia/ischemia rapidly induces inflammation in the brain, which is characterized by microglial activation and the release of inflammatory cytokines. We have previously demonstrated that miR-181c can directly regulate tumor necrosis factor (TNF)-α production post-transcriptionally. Here, we determined that hypoxia up-regulated TLR4 expression but down-regulated miR-181c expression in primary microglia. We also demonstrated that miR-181c suppresses TLR4 by directly binding its 3'-untranslated region. In addition, miR-181c inhibited NF-κB activation and the downstream production of proinflammatory mediators, such as TNF-α, IL-1ß, and iNOS. Knocking down TLR4 in microglia significantly decreased TLR4 expression and inhibited NF-κB activation and the downstream production of proinflammatory mediators, whereas ectopic TLR4 expression significantly abrogated the suppressed inflammatory response induced by miR-181c. Therefore, our study identified an important role for the miR-181c-TLR4 pathway in hypoxic microglial activation and neuroinflammation. This pathway could represent a potential therapeutic target for cerebral hypoxic diseases associated with microglial activation and the inflammatory response. Cerebral hypoxia/ischemia induces microglial activation and the release of inflammatory cytokines. We found that hypoxia down-regulated miR-181c in primary microglia. In addition, miR-181c inhibited TLR4 expression through binding to its 3'UTR, thus inhibiting NF-kB activation and the production of downstream proinflammatory mediators. Therefore, the miR-181c-TLR4 pathway may be a potential therapeutic target for the treatment of cerebral hypoxic diseases.
Assuntos
Glucose/deficiência , Mediadores da Inflamação/metabolismo , MicroRNAs/metabolismo , Microglia/metabolismo , Oxigênio/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Hipóxia Celular/fisiologia , Células Cultivadas , Feminino , Redes Reguladoras de Genes/fisiologia , Ratos , Ratos Sprague-Dawley , Receptor 4 Toll-Like/antagonistas & inibidoresRESUMO
BACKGROUND: Our study investigated the associations of metabolic syndrome (MS) and metabolic indicators with prostate cancer (PCa) risk in the Chinese Han ethnic population. MATERIAL AND METHODS: We studied 101 PCa patients (without/with MS) and 120 healthy controls. Clinical data, including waist circumference, BMI, TG, FINS, FBG, and PCa-related indicators, were collected. The correlations between MS and PCa were analyzed. RESULTS: Compared to PCa, PV and Gleason scores increased and PSA levels decreased in PCa with MS group (all P<0.001). PV was positively correlated with BMI, FINS, and HOMA-IR (r=0.459, P<0.001; r=0.421, P=0.001; r=0.490, P=0.003, respectively), and was negatively correlated with HDL-C (r=-0.378, P<0.001). PSA level in MS patients was negatively correlated with BMI (r=-0.125, P<0.001), TG (r=-0.256, P<0.001) and FBG (r=-0.183, P<0.001). Large PV, high TG, low HDL-C, high LDL-C, and high FBG were associated with an increased risk of PCa (P<0.001, OR=1.10, 95%CI: 1.009-3.304; P<0.001, OR=2.91, 95%CI: 1.612-5.241; P<0.001, OR=7.89, 95%CI: 3.908-15.947; P=0.015, OR=1.87, 95%CI: 1.131-3.077; P=0.004, OR=2.17, 95%CI: 1.280-3.686, respectively). MS-related indicators showed a positive relationship with PCa (P<0.001, OR=1.90, 95%CI: 1.107-10.629). CONCLUSIONS: Our study shows that MS and metabolic indicators are associated with an increased risk of PCa, pointing to a novel therapeutic approach for PCa management.
Assuntos
Síndrome Metabólica/complicações , Neoplasias da Próstata/etiologia , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Glicemia/metabolismo , Índice de Massa Corporal , Estudos de Casos e Controles , China , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Humanos , Resistência à Insulina , Calicreínas/sangue , Modelos Logísticos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Gradação de Tumores , Tamanho do Órgão , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Fatores de Risco , Triglicerídeos/sangue , Circunferência da CinturaRESUMO
OBJECTIVE: To investigate the efficacy and adverse effects of dapoxetine in the treatment of premature ejaculation. METHODS: We randomly assigned outpatients with premature ejaculation in the proportion of 2:1 to receive 30 mg dapoxetine on demand (n =78) or 50 mg sertraline qd for one month (n = 39). Follow-up was accomplished in 95 cases, 63 in the dapoxetine group and 32 in the sertraline group. We recorded the intravaginal ejaculatory latency time (IELT), clinical global impression of change (CGIC) score, and adverse reactions of the patients and compared them between the two groups. RESULTS: IELT was significantly increased in both the dapoxetine (from [0.87 ± 0.31] to [2.84 ± 0.68] min, P < 0.05) and the sertraline group (from [0.84 ± 0.28] to [2.71 ± 0.92] min, P < 0.05) after medication. Based on the CGIC scores in premature ejaculation, the rate of excellence or effectiveness was 36.5% in the dapoxetine and 37. 5% in the sertraline group, and the rate of improvement was 63.5% in the former and 71.9% in the latter. The incidence rates of dizziness, nausea, headache, and diarrhea were slightly higher (P > 0.05) while those of fatigue, somnolence, and dry mouth significantly higher (P < 0.05) in the sertraline than in the dapoxetine group. CONCLUSION: On-demand oral medication of dapoxetine is effective and well-tolerated for the treatment of premature ejaculation.
Assuntos
Benzilaminas/uso terapêutico , Naftalenos/uso terapêutico , Ejaculação Precoce/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Sertralina/administração & dosagem , Benzilaminas/efeitos adversos , Método Duplo-Cego , Ejaculação/efeitos dos fármacos , Ejaculação/fisiologia , Humanos , Masculino , Naftalenos/efeitos adversos , Pacientes Ambulatoriais , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Sertralina/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
THE AIM OF THIS STUDY: The aim of this study was to verify whether prohibitin is a novel autoantigen in rheumatoid arthritis. MATERIAL AND METHODS: First, recombinant human prohibitin (rhPHB) protein was cloned, expressed, and purified. Then the anti-prohibitin autoantibodies were detected by western blotting by using rhPHB protein to incubate sera from patients with rheumatoid arthritis (RA). Next, immunoprecipitation was employed to further illustrate whether anti-prohibitin antibodies exist in RA patients. And finally, autoantibodies against the rhPHB protein were investigated using a homemade ELISA kit through the assessment of 258 real clinical samples. RESULTS: It was revealed that anti-prohibitin antibodies existed in the sera of patients with RA. Reactivity of serum IgG against rhPHB was detected in 26 of 86 RA patients (30.3%), 7 of 86 systemic lupus erythematosus (SLE) patients (8.1%), and 1 of 86 apparently healthy donors (HC) (1.2%). CONCLUSIONS: Prohibitin was proved to be a novel autoantigen and the corresponding anti-prohibitin autoantibodies were present in the RA patients' blood circulation.
RESUMO
With the development of genomic study, researchers found that it is insufficient to predict protein expression from quantitative mRNA data in large scale, which is contrary to the traditional opinion that mRNA expression correlates with protein abundance at the single gene level. To try to solve the apparent conflicting views, here we set up a series of research models and chose soluble cytokines as targets. First, human peripheral blood mononuclear cell (PBMC) from one health donor was treated with 16 continuously changing conditions, the protein and mRNA profile were analyzed by multiplex Luminex and genomic microarray, respectively. Among the tested genes, around half mRNA correlated well with their corresponding proteins (ρ > 0.8), however if we put all the genes together, the correlation coefficient for the 16 conditions varied from 0.29 to 0.71. Second, PBMC from 14 healthy donors were stimulated with the same condition and it was found that the correlation coefficient went down (ρ < 0.6). Third, 28 rheumatoid arthritis (RA) patients were tested for their response to the same external stimuli and it turned out different individual displayed different protein expression pattern as expect. Lastly, autoimmune disease cohorts (8 diseases including RA, 103 patients in total) were assayed on the whole view. It was observed that there was still some similarity in the protein profile among patients from the single disease type although completely different patterns were displayed across different disease categories. This study built a good bridge between single gene analysis and the whole genome study and may give a reasonable explanation for the two conflicting views in current biological science.
Assuntos
Citocinas/genética , Citocinas/metabolismo , Proteoma , Transcriptoma , Análise por Conglomerados , Biologia Computacional , Perfilação da Expressão Gênica , Humanos , Leucócitos Mononucleares/metabolismo , ProteômicaRESUMO
Purpose: This study aimed to investigate the effect of Salvia miltiorrhiza on colorectal cancer, as well as the mechanisms involved. Methods: The active compounds of Salvia miltiorrhiza and the associated genes in colorectal cancer were sourced from publicly available databases. Targets associated with colorectal cancer were identified by searching the GeneCards and OMIM databases. Subsequently, the Cytoscape 3.6.0 software was employed to create a regulatory network that illustrates the relationships among active ingredients, colorectal cancer, and their corresponding targets. The String database was utilized to generate a PPI network. Molecular docking studies, conducted with AutoDock Vina, verified the binding capabilities of these active components to core targets. The findings from network pharmacology analysis were corroborated through in vitro experiments. Results: In this study, we identified 39 active components derived from Salvia miltiorrhiza that are predicted to target 544 genes associated with colorectal cancer through network pharmacology. Through a combined analysis of network pharmacology, we isolated three key targets: SRC, IL6, and INS. Molecular docking results convincingly demonstrated Salvia miltiorrhiza's strong binding affinity to these targets. Additionally, in vitro experiments confirmed that Salvia miltiorrhiza effectively inhibited the progression of colorectal cancer via regulating the INS/SRC/IL6 pathway. Conclusion: Salvia miltiorrhiza emerges as a compelling herbal intervention for colorectal cancer. This study lays the foundation for potential future clinical trials assessing the efficacy of Salvia miltiorrhiza in the management of colorectal cancer.
Assuntos
Neoplasias Colorretais , Medicamentos de Ervas Chinesas , Salvia miltiorrhiza , Simulação de Acoplamento Molecular , Interleucina-6 , Farmacologia em Rede , Tecnologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Medicina Tradicional ChinesaRESUMO
BACKGROUND: Circular RNAs (circRNAs) represent a subset of non-coding RNAs implicated in the regulation of diverse biological processes, including tumorigenesis. However, the expression and functional implications of circ0060467 in hepatocellular carcinoma (HCC) remain elusive. In this study, we aimed to elucidate the role of circ0060467 in modulating the progression of HCC. METHODS: Differentially expressed circRNAs in HCC tissues were identified through circRNA microarray assays. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays revealed the upregulation of circ0060467 in both HCC cell lines and tissues. Various assays were conducted to investigate the roles of circ0060467 in HCC progression. Additionally, RNA immunoprecipitation (RIP) assays and luciferase assays were carried out to assess the interactions between circ0060467, microRNA-6085 (miR-6085), apoptosis-inducing factor mitochondria-associated 2 (AIFM2), and glutathione peroxidase 4 (GPX4) in HCC. RESULTS: Microarray and qRT-PCR analyses demonstrated a marked elevation of circ0060467 in HCC tissues and cell lines. Knockdown of circ0060467 suppressed HCC cell proliferation. Luciferase reporter and RIP assays confirmed the binding of circ0060467, AIFM2, and GPX4 to miR-6805. Subsequent experiments revealed that circ0060467 competes with AIFM2 and GPX4, thereby inhibiting cancer cell ferroptosis by binding to miR-6085 and promoting hepatocellular carcinoma progression. CONCLUSIONS: Collectively, circ0060467 modulates the levels of AIFM2 and GPX4, crucial regulators of tumor cell ferroptosis, by acting as a sponge for miR-6085 in HCC. Thus, circ0060467 may represent a novel diagnostic marker and therapeutic target for HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , RNA Circular/genética , MicroRNAs/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Luciferases/metabolismo , Linhagem Celular TumoralRESUMO
Introduction: We aim to investigate the functional outcomes and long-term health-related quality of life (HRQOL) in children with major trauma associated with traumatic brain injury (TBI). Method: We performed a retrospective review of records among patients >2 and ≤16 years old in a tertiary paediatric hospital between January 2014 and October 2019 with major trauma (Injury Severity Score of ≥16) and TBI of all severities. We recorded each child's Glasgow Outcome Scale-Extended Pediatric Version (GOS-E Peds) at 12 months post-injury and Pediatric Quality of Life Inventory (PedsQL) scores at 6 and 12 months post-injury based on the parent proxy-report scales. Results: We included 53 patients with a median age of 9.0 years old (interquartile range 2.3-15.5). Most injuries were due to falls (30, 56.6%) or road traffic collisions (15, 28.3%); 41 patients (77.3%) required intensive care while 30 patients (56.6%) underwent neurosurgical intervention. Most patients (43, 81.1%) had GOS-E Peds scores of ≤2 at 12 months post-injury. We reported a significant mean difference between the 6- and 12-month parent-reported scores for physical functioning (6.6, 95% confidence interval [CI] 0.3-12.8, P=0.041), psychosocial functioning (4.1, 95% CI 1.0-7.2, P=0.012) and overall scores (5.0, 95% CI 1.4-8.7, P=0.008). Compared with the validated PedsQL scores, our mean scores were higher across all domains at 12 months. Conclusion: With current standard of care, parents of children with major trauma and TBI reported gains in quality of life, physical, psychosocial and overall function between 6 and 12 months post-injury.
Assuntos
Lesões Encefálicas Traumáticas , Cuidadores , Escala de Resultado de Glasgow , Qualidade de Vida , Humanos , Lesões Encefálicas Traumáticas/psicologia , Criança , Estudos Retrospectivos , Masculino , Feminino , Pré-Escolar , Adolescente , Cuidadores/psicologia , Acidentes de Trânsito/estatística & dados numéricos , Acidentes por Quedas/estatística & dados numéricos , Escala de Gravidade do Ferimento , Singapura/epidemiologiaRESUMO
Perampanel is a first-in-class α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist and a novel anti-seizure medication. It is currently used as adjunctive treatment for partial seizures in patients over 12 years of age. With the increasing clinical application of perampanel, monitoring its concentration under certain clinical conditions is important. This study developed a rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry method to quantify perampanel in human plasma. Protein precipitation with acetonitrile was performed for sample preparation. Perampanel and perampanel-d5 (internal standard) were analyzed under gradient conditions using a C18 column. The mobile phase was composed of 0.1% (v/v) formic acid in water (solvent A) and 0.1% (v/v) formic acid in acetonitrile (solvent B) at a flow rate of 0.4 mL/min. Mass detection was performed using multiple reaction monitoring in the positive ionization mode. The proposed method was validated over a range of 0.5-500 ng/mL for perampanel. The linearity (r2 value) was higher than 0.999, and the linear equation was y = 0.00116x + 0.0116. The accuracy of the low-, middle-, and high-quality control samples was between 103% and 113%, and the intra- and inter-day precisions were below 6.81%. The quality of the proposed method was evaluated in accordance with the US Food and Drug Administration Bioanalytical Method Validation Guidance for Industry. The plasma concentrations of perampanel in 25 patients were successfully determined to be 38.7-577.7 ng/mL using the validated method.
Assuntos
Epilepsia , Espectrometria de Massas em Tandem , Estados Unidos , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Reprodutibilidade dos Testes , Acetonitrilas , SolventesRESUMO
PURPOSE: Although holmium laser enucleation of the prostate has been proven to be an excellent technique for the treatment of benign prostatic hyperplasia, it has not been widely applied due to technical difficulties and longer operative time. We modified the current technique of enucleation and present our initial experience. MATERIALS AND METHODS: A total of 189 patients with benign prostatic hyperplasia underwent prostatectomy with our modified technique for holmium laser enucleation of the prostate. Intraoperative and postoperative data were prospectively collected. For followup International Prostate Symptom Score, quality of life, maximal flow rate and post-void residual urine were recorded. RESULTS: Mean±SD preoperative prostate volume was 78.1±24.3 cc and 60.9±39.2 gm tissue were enucleated. Mean operative and enucleation times were 54.7±21.1 and 36.5±16.3 minutes, respectively. Mean serum hemoglobin decrease was 0.98±0.72 gm/dl. Mean catheter time was 1.2±0.5 days and mean postoperative hospital stay was 4.9±3.4 days. Serious complications were not observed. Three patients complained of transient stress incontinence which resolved within 3 months. Significant improvement occurred in International Prostate Symptom Score, quality of life, maximal flow rate and post-void residual urine volume at 3 and 6-month followup compared with the preoperative baseline. CONCLUSIONS: The modified holmium laser enucleation of the prostate technique is effective and safe when treating benign prostatic hyperplasia.
Assuntos
Lasers de Estado Sólido/uso terapêutico , Próstata/cirurgia , Prostatectomia/métodos , Hiperplasia Prostática/cirurgia , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
To improve the effect of urban agricultural garden landscape planning and design, this paper combines the agricultural Internet of Things technology to construct a smart garden planning and design system. Moreover, this paper selects the LEACH protocol that can support monitoring for a long time according to actual application needs, introduces the latest swarm intelligence optimization algorithm, the gray wolf algorithm, to optimize some of the problems in the LEACH protocol, and conducts simulation experiments on the improved algorithm. The simulation experiment results show that the improved algorithm has obvious advantages in cluster head selection, data transmission within the cluster, and route maintenance. After constructing a smart garden planning system based on the agricultural Internet of Things, the effect of the agricultural Internet of Things data processing in this paper is evaluated. Finally, this paper constructs a garden simulation system and analyzes the performance of the system. The results verify that the agricultural Internet of Things has a good effect in the planning and design of smart gardens.
Assuntos
Jardins , Internet das Coisas , Algoritmos , Simulação por Computador , InternetRESUMO
BACKGROUND: The paediatric massive transfusion protocol (MTP) is activated in the paediatric population for both trauma and non-trauma related indications. While it helps to improve the efficiency and efficacy of the delivery of blood products, it can also result in increased wastage. We aimed to evaluate the wastage rates from our paediatric MTP activations from 2013 to 2018. METHOD: As part of an audit, we retrospectively reviewed the records of the paediatric patients who had MTP activations. We collected the following data: reason for MTP activation, weight of patient, number of cycles of MTP required, blood products used, blood products wasted, deviation from our institution's recommended MTP blood product ratio, and reason for wastage. RESULT: We had 26 paediatric MTP activations within the audit period. There was an overall wastage rate of 1.5%, with wastage occurring in 3 out of 26 patients. The reason for all wastage was demise of the patient. Most patients' transfusion ratios deviated from our institution's MTP protocol. CONCLUSION: Our wastage rates are low likely because of clear MTP activation guidelines and a flexible MTP workflow.
RESUMO
Improving the patient's quality of life (QOL) is the most important goal of epilepsy management. We performed this study to determine the factors associated with QOL in people with epilepsy and to assess whether there are gender differences in these determinants. Patients were interviewed using the Quality of Life in Epilepsy Inventory-31(QOLIE-31), the Adverse Event Profile (AEP), the Self-Rating Anxiety Scale (SAS), and the Hamilton Depression Rating Scale (HAMD). Two hundred forty-seven patients (152 men, 95 women) were included in the analysis. Among all patients, regressive analyses showed that AEP score was the strongest predictor of the QOLIE-31 overall score, accounting for 10.4% of the variance. The next strongest predictors were the number of currently used antiepileptic drugs (AEDs) (3.6%), the HAMD score (2.5%), and the SAS score (1.2%). Importantly, there were gender differences in these predictors of QOL. The strongest predictors of the QOLIE-31 overall score in women were the AEP score and the number of AEDs. In contrast, the strongest predictors in men were the SAS score, the AEP score and the frequency of seizures. These results indicate that perceived adverse effects of treatments and number of AEDs exerted greater effects on QOL in women, whereas anxiety and seizure-related variables had a stronger impact on QOL among men. Accordingly, it may be necessary to individualize interventions to improve the QOL of people with epilepsy.