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BACKGROUND AND AIM: Circular ubiquitin-like, containing PHD and ring finger domains 1 (circUHRF1) is aberrantly upregulated in human hepatocellular carcinoma (HCC) tissues. However, the underlying molecular mechanisms remain obscure. The present study aimed at elucidating the interactive function of circUHRF1-G9a-ubiquitin-like, containing PHD and ring finger domains 1 (UHRF1) mRNA-eukaryotic translation initiation factor 4A3 (EIF4A3)-PDZ and LIM domain 1 (PDLIM1) network in HCC. METHODS: Expression of circUHRF1, mRNAs of G9a, UHRF1, PDLIM1, epithelial-mesenchymal transition (EMT)-related proteins, and Hippo-Yap pathway components was determined by quantitative polymerase chain reaction (Q-PCR), immunofluorescence, or Western blot analysis. Tumorigenic and metastatic capacities of HCC cells were examined by cellular assays including Cell Counting Kit-8, colony formation, wound healing, and transwell assays. Molecular interactions between EIF4A3 and UHRF1 mRNA were detected by RNA pull-down experiment. Complex formation between UHRF1 and PDLIM1 promoter was detected by chromatin immunoprecipitation assay. Co-immunoprecipitation was performed to examine the binding between UHRF1 and G9a. RESULTS: Circular ubiquitin-like, containing PHD and ring finger domains 1, G9a, and UHRF1 were upregulated, while PDLIM1 was downregulated in HCC tissue samples and cell lines. Cellular silencing of circUHRF1 repressed HCC proliferation, invasion, migration, and EMT. G9a formed a complex with UHRF1 and inhibited PDLIM1 transcription. CONCLUSION: Eukaryotic translation initiation factor 4A3 regulated circUHRF1 expression by binding to UHRF1 mRNA promoter. circUHRF1 increased the stability of G9a and UHRF1 mRNAs through recruiting EIF4A3. Overexpression of circUHRF1 aggravated HCC progression through Hippo-Yap pathway and PDLIM1 inhibition. By elucidating the molecular function of circUHRF1-G9a-UHRF1 mRNA-EIF4A3-PDLIM1 network, our data shed light on the HCC pathogenesis and suggest a novel therapeutic strategy for future HCC treatment.
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Carcinoma Hepatocelular , ARN Helicasas DEAD-box , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/tratamiento farmacológico , ARN Mensajero/genética , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Proteínas de Homeodominio/uso terapéutico , Ubiquitina/genética , Ubiquitina/metabolismo , Ubiquitina/uso terapéutico , Dominios RING Finger , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/uso terapéutico , Proteínas Potenciadoras de Unión a CCAAT/química , Proteínas Potenciadoras de Unión a CCAAT/genética , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Factores de Iniciación de Péptidos/genética , Factores de Iniciación de Péptidos/metabolismo , Factores de Iniciación de Péptidos/uso terapéutico , Proliferación Celular/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/genética , Factor 4A Eucariótico de Iniciación/genética , Factor 4A Eucariótico de Iniciación/metabolismoRESUMEN
INTRODUCTION: Postoperative pain remains incompletely controlled for decades. Recently, multimodal analgesia is emerging as a potential approach in the management of postoperative pain. Therein, S(+)-ketamine is appealing as an adjuvant drug in multimodal analgesia due to its unique pharmacological advantages. This pragmatic clinical trial (SAFE-SK-A trial) is designed to investigate the analgesic effect and safety of S(+)-ketamine for acute postoperative pain in adults and explore the optimal strategy of perioperative intravenous S(+)-ketamine in a real-world setting. METHODS AND ANALYSIS: This multicentre, randomised, open-label, positive-controlled, pragmatic clinical trial (SAFE-SK-A study) is planned to conduct in 80 centres from China and recruit a total of 12 000 adult participants undergoing a surgical procedure under general anaesthesia. Patient recruitment started in June 2021 and will end in June 2022. Participants will be randomised in a ratio of 2:1 to either receive perioperative intravenous S(+)-ketamine plus conventional anaesthesia or conventional anaesthesia only. Given the pragmatic nature of the study, no specific restriction as to the administration dosage, route, time, synergistic regimen or basic analgesics. Primary endpoints are the area under the broken line of Numerical Rating Scale (NRS) scores for pain intensity and the total opioid consumption within 48 hours postoperative. Secondary endpoints are postoperative NRS scores, the anaesthesia recovery time, time of first rescue analgesia, the incidence of rescue analgesia, the incidence of postoperative delirium, patient questionnaire for effect, changes from baseline in cognitive function and anxiety and depression, as well as the adverse events and pharmacoeconomic outcomes. The general linear model will be used for the primary endpoint, and appropriate methods will be used for the secondary endpoints. ETHICS AND DISSEMINATION: This trial has been approved by the local Institutional Review Board (S2021-026-02) and conducted following the Declaration of Helsinki. Results of this trial will be publicly disclosed and published in scientific journals. TRIAL REGISTRATION NUMBER: NCT04837170; Pre-results.
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Ketamina , Adulto , Analgésicos/uso terapéutico , Analgésicos Opioides/uso terapéutico , Humanos , Ketamina/uso terapéutico , Estudios Multicéntricos como Asunto , Dimensión del Dolor , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
AIMS: Barrett's esophagus (BE) predisposes to the development of esophageal neoplasia, including high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). A systematic literature review and meta-analysis were performed to assess the accuracy of within-patient comparisons of narrow band imaging (NBI) and confocal laser endomicroscopy (CLE) for diagnosis of HGD/EAC in patients with BE. METHODS: The following databases were examined up to April 2016 without language restriction: PubMed, Embase, Medline, Web of Science and the Cochrane Library. The QUADAS-2 tool for assessing the quality of included studies was used. The meta-analysis included pooled additional detection rate (ADR), diagnostic accuracy, and 95% confidence intervals (CI). The I2 and Q-test were used to determine study heterogeneity. RESULTS: Five studies involving 251 patients, reported within-patient comparisons of NBI and CLE, were eligible for meta-analysis. Compared with NBI, pooled ADR of CLE for per-lesion detection of neoplasia in patients with BE was 19.3% (95% CI: 0.05-0.33, I2=74.6%). The pooled sensitivity of NBI was 62.8% (95% CI: 0.56-0.69, I2=94.6%), which was lower (not significantly) than that of CLE (72.3%, 95% CI: 0.66-0.78, I2=89.3%). The pooled specificity of NBI and CLE were similar [85.3% (95% CI: 0.84-0.87, I2=92.1%) vs 83.8% (95% CI: 0.82-0.85, I2=96.8%)]. CONCLUSIONS: When compared with NBI, CLE significantly increased the per-lesion detection rate of esophageal neoplasia, HGD, and EAC in BE patients. Whether CLE is superior to NBI in neoplasia detection at per-patient level needs to be further investigated.
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Adenocarcinoma/patología , Esófago de Barrett/patología , Neoplasias Esofágicas/patología , Esofagoscopía/métodos , Microscopía Confocal/métodos , Imagen de Banda Estrecha , HumanosRESUMEN
OBJECTIVE: To establish an improved method for stereotactic location of the supraoptic nucleus in rats. METHODS: Twenty-four SD rats were randomly divided into experimental group (12 rats) and control group (12 rats) for oblique (20° to the left) stereotactic puncture (OSP group) and vertical stereotactic puncture (VSP group), respectively, both targeting the supraoptic nucleus (SON). The surgical data and postoperative (within 24) mortality of the rats were compared between the two groups. RESULTS: The nucleus locating time was longer in OSP group than in VSP group (59.55∓3.64s vs 27.44∓2.18 s, P=0.000), and the postoperative mortality rate of the rats did not differ significantly between the groups (0 vs 44.4%, P=0.082). In OSP group, compared with VSP group, the procedure was associated with a lowered rupture rate of the superior sagittal sinus (11.1% vs 88.9%, P=0.003), a shortened hemostatic time after craniotomy (52.89∓24.05 s vs 157.445 ime a s, P=0.000) and after puncture (24.33 reas 45 s vs 133.89∓28.81 s, P=0.000), and also a shortened operation time (178.89 on tims vs 362.44 timees, P=0.000). CONCLUSION: The improved method for locating supraoptic nucleus in rats is convenient, stable and reproducible, and helps to avoid important blood vessels and specific nuclei according to the needs of different experiments and allows the operators to choose different surgical paths.
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Punciones , Núcleo Supraóptico/diagnóstico por imagen , Núcleo Supraóptico/cirugía , Animales , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Although several risk factors for acute kidney injury (AKI) have been identified, early detection of AKI in acute decompensated heart failure patients remains a challenge. The aim of this study was to develop and validate a risk score for early prediction of AKI in acute decompensated heart failure patients. METHODS AND RESULTS: A total of 676 consecutive acute decompensated heart failure participants were prospectively enrolled from 6 regional central hospitals. Data from 507 participants were analyzed. Participants from 4 of the 6 hospitals (n=321) were used to develop a risk score and conduct internal validation. External validation of the developed risk score was conducted in participants from the other 2 hospitals (n=186). Sequential logistic regression was used to develop and validate the risk score. The c statistic and calibration plot were used to assess the discrimination and calibration of the proposed risk score. The overall occurrence of AKI was 33.1% (168/507). The risk score, ranging from 0 to 55, demonstrated good discriminative power with an optimism-corrected c statistic of 0.859. Similar results were obtained from external validation with c statistic of 0.847 (95% CI 0.819-0.927). The risk score had good calibration with no apparent over- or under-prediction observed from calibration plots. CONCLUSIONS: The novel risk score is a simple and accurate tool that can help clinicians assess the risk of AKI in acute decompensated heart failure patients, which in turn helps them plan and initiate the most appropriate disease management for patients in time.
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Lesión Renal Aguda/epidemiología , Síndrome Cardiorrenal/epidemiología , Insuficiencia Cardíaca/epidemiología , Insuficiencia Renal Crónica/epidemiología , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Angiotensinógeno/orina , China/epidemiología , Estudios de Cohortes , Femenino , Humanos , Lipocalina 2/orina , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de RiesgoRESUMEN
The scaly-sided merganser (Mergus squamatus) is an endangered bird species on the IUCN Red List with the estimated global population of less than 2,500 individuals at present. In the present study, we studied the complete mitochondrial genome (mtDNA) and the phylogenetic of M. squamatus by PCR amplification and GenBank data. The genome was 16,595 bp in length and contained 37 genes (13 protein coding genes, two rRNAs, and 22 tRNAs) and a non-coding control region (D-loop). All protein-coding genes of M. squamatus mtDNA start with a typical ATG codon, except ND1, COI, and COII uses GTG as their initial codon. TAA, T- and TAG as the terminate codon occurred very commonly in the sequence. All tRNA genes can be folded into canonical cloverleaf secondary structure except for tRNA(Ser) (AGY) and tRNA(Leu) (CUN), which lose ''DHU'' arm. The genome sequences had been deposited in GenBank under accession number HQ833701. Based on the concatenated nucleotide sequences of mtDNA genes (Cyt b and D-loop), we reconstructed phylogenetic trees and discussed the phylogenetic relationships among ten Anatidae species. The results are different from the present classification, and we support Lophodytes cucullatus and Mergullus albellus to be members of the genus Mergus.
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Patos/genética , Especies en Peligro de Extinción , Genoma Mitocondrial/genética , Filogenia , Animales , Emparejamiento Base , Secuencia de Bases , Análisis por Conglomerados , Codón/genética , Cartilla de ADN/genética , Patos/clasificación , Componentes Genómicos/genética , Datos de Secuencia Molecular , Conformación de Ácido Nucleico , Análisis de Secuencia de ADNRESUMEN
The shallow lake wetlands in the middle and lower Yangtze River floodplain are important wintering and stopover habitats for migratory waterbirds on the East Asia-Australia Flyway. With increasing fishery practices in recent years, however, the wetlands have deteriorated significantly and now threaten wintering waterbirds. To gain insight into the influence of deteriorating wetlands on waterbirds, we conducted a survey of wintering waterbird species, population size, and distribution across 11 belt transects in Caizi Lake and Shengjin Lake, two shallow lakes along the Yangtze River in Anhui Province from November 2007-April 2008 and from November 2008-April 2009, respectively. The impacts of different fishery patterns on the distribution of waterbirds were also analyzed. A total of 43 waterbirds species belong to 7 orders of 12 families were counted during the surveys, of which 38 were found in Caizi Lake with a density of 8.2 ind./hm(2), and 42 in Shengjin Lake with a density of 3.5 ind./hm(2). Geese (Anser cygnoides), bean geese (Anser fabalis), tundra swan (Cygnus columbianus), and dunlin (Calidris alpina) were the dominant species in the two shallow lakes. Species number and individual assemble reached maximum at the end of December and in early January of the following year, without coincidence of the largest flock for different ecological groups. Based on waterbird diversity across the 11 belt transects and the fishery patterns, habitats could be divided into three groups. Gruiformes, Anseriformes and Charadriiformes had relatively higher densities in the natural fishery zones and lower densities in the cage fishery zones; whereas, the density of Ardeidae showed little change across all lake zones. It is important to develop sustainable fishery patterns in shallow lakes along the middle and lower Yangtze River floodplain to better protect resources of wintering waterbirds.
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Aves/clasificación , Aves/crecimiento & desarrollo , Ecosistema , Animales , China , Conservación de los Recursos Naturales , Lagos/análisis , Filogenia , Densidad de Población , Dinámica Poblacional , Estaciones del AñoRESUMEN
AIM: To clone cDNAs of thrombin-like enzymes (TLEs) from venom gland of Deinagkistrodon acutus and analyze the mechanisms by which their structural diversity arose. METHODS: Reverse transcription-polymerase chain reaction and gene cloning techniques were used, and the cloned sequences were analyzed by using bioinformatics tools. RESULTS: Novel cDNAs of snake venom TLEs were cloned. The possibilities of post-transcriptional recombination and horizontal gene transfer are discussed. A phylogenetic tree was constructed. CONCLUSION: The cDNAs of snake venom TLEs exhibit great diversification. There are several types of structural variations. These variations may be attributable to certain mechanisms including recombination.