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BACKGROUND: Few studies assessed myocardial inflammation using Cardiovascular Magnetic Resonance Imaging in Kawasaki disease (KD) patients. PURPOSE: To quantify myocardial edema in KD patients using T2 mapping and explore the independent predictors of T2 values. STUDY TYPE: Prospective. SUBJECTS: Ninety KD patients including 40 in acute phase (26 males, 65.0%) and 50 in chronic phase (34 males, 68.0%). Thirty-one healthy volunteers (21 males, 70.0%). FIELD STRENGTH/SEQUENCE: 3.0 T T2-weighted Turbo Spin Echo-Short Time of Inversion Recovery sequence, True fast imaging with steady precession flash sequence and fast low-angle shot 3D spoiled gradient echo sequence. ASSESSMENT: T2 values were compared among KD groups and controls. STATISTICAL TEST: Student's t test and Fisher's exact test; One-way analysis of variance; Pearson correlation analysis; Receiver operating curve analysis; Multivariable linear regression. RESULTS: Global T2 value of KD patients in acute phase was the highest, followed by those of chronic-phase patients and controls (38.83 ± 2.41 msec vs. 37.55 ± 2.28 msec vs. 36.05 ± 1.64 msec). Regional T2 values showed a same trend. There were no significant differences in global and regional T2 values between KD patients with and without coronary artery (CA) dilation, no matter in acute or chronic phase (all KD patients: P = 0.51, 0.51, 0.53, 0.72; acute KD: P = 0.61, 0.37, 0.33, 0.83; chronic KD: P = 0.65, 0.79, 0.62, 0.79). No significant difference was observed in global T2 values between KD patients with Z score > 5.0 and 2.0 < Z score ≤ 5.0 (P = 0.65). Multivariate analysis demonstrated that stage of disease (ß = -0.123) and heart rate (ß = 0.280) were independently associated with global T2 values. DATA CONCLUSION: The degree of myocardial edema was more severe in acute-phase than in chronic-phase KD patients. Myocardial edema persists in patients regardless of the existence or degree of CA dilation. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.
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Síndrome Mucocutáneo Linfonodular , Masculino , Niño , Humanos , Estudios Prospectivos , Miocardio/patología , Imagen por Resonancia Magnética/métodos , EdemaRESUMEN
BACKGROUND : There are limited data on the feasibility of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasia (SEN) located at or adjacent to esophageal varices. We aimed to evaluate the outcomes of ESD in these patients. METHODS: This multicenter retrospective study included cirrhotic patients with a history of esophageal varices with SEN located at or adjacent to the esophageal varices who underwent ESD. RESULTS: 23 patients with SEN (median lesion size 30 mm; 16 squamous cell neoplasia and seven Barrett's esophagus-related neoplasia) were included. The majority were Child-Pugh B (57â%) and had small esophageal varices (87â%). En bloc, R0, and curative resections were achieved in 22 (96â%), 21 (91â%), and 19 (83â%) of patients, respectively. Severe intraprocedural bleeding (nâ=â1) and delayed bleeding (nâ=â1) were successfully treated endoscopically. No delayed perforation, hepatic decompensation, or deaths were observed. During a median (interquartile range) follow-up of 36 (22-55) months, one case of local recurrence occurred after noncurative resection. CONCLUSION: ESD is feasible and effective for SEN located at or adjacent to esophageal varices in cirrhotic patients. Albeit, the majority of the esophageal varices in our study were small in size, when expertise is available, ESD should be considered as a viable option for such patients.
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Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Várices Esofágicas y Gástricas , Humanos , Estudios Retrospectivos , Resección Endoscópica de la Mucosa/efectos adversos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/cirugía , Esofagoscopía/efectos adversos , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Cirrosis Hepática/complicaciones , Resultado del TratamientoRESUMEN
Ionic liquids have drawn great interest as electrolytes for energy storage applications in which they form characteristic electrical double layers at electrode interfaces. For ionic liquids at carbon electrode interfaces, their double layers are subject to nanoscale structuring of the electrode surface, involving altered ion structure and interactions that significantly influence the double layer capacitance. In this regard, we investigate the modulation of ionic liquid double layers by electrode surface roughness and the resulting effects on the ion structure, interaction, and capacitance. We performed fixed voltage molecular dynamics simulations to compute the differential capacitance profiles for the ionic liquids [BMIm+][TFSI-] and [BMIm+][FSI-] at model carbon electrode interfaces with the surface channel width at subnanometer and nanometer scales. We find that both [BMIm+][TFSI-] and [BMIm+][FSI-] exhibit enhanced differential capacitance for the electrode surface with a subnanometer channel width relative to the flat graphene surface, but the most pronounced enhancements for these two ionic liquids unexpectedly appear at different applied potential regimes. For [BMIm+][TFSI-], the nanostructured electrode shows significant enhancement of capacitance at high positive potential. For [BMIm+][FSI-], on the other hand, this enhancement is small at positive polarization but noticeable at low negative potential. We demonstrate that differences in these capacitance trends is due to differences in ion correlation that arise from a steric constraint of nanostructured electrode surface on the voltage-mediated restructuring of ions closest to the electrode interface. For example, the TFSI- and FSI- anions tend to structure with their charged and nonpolar groups in contact with the positive electrode surface when the constraint on these close-contact anions is relaxed. This anion structuring largely retains the cation association near the nanostructured electrode, resulting in only a slight increase in capacitance at positive polarization. Our simulations highlight the sensitive dependence of the innermost ion structure on the electrode surface nanostructure and applied voltage and the resulting influence on ion correlation and capacitance of ionic liquid double layers.
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BACKGROUND: Circulating miRNAs (c-miR) have been shown to be potential biomarkers in sarcopenia, but the miRNAs response to aerobic exercise in older people remains inconclusive. We sought to examine the exercise benefits on physical fitness and miRNAs, and to explore the mediating effect of miRNAs on training-induced fitness changes. METHODS: This controlled trial recruited 58 community-dwelling older adults and randomized them into exercise group (EX) and control group (CON). EX received 8-week supervised moderate intensity cycling training 3x/week. C-miR expression (c-miR-21, c-miR-126, c-miR-146a, c-miR-222), physical fitness (body composition, cardiorespiratory fitness, muscular fitness) and physical activity level (PAL, measured as in daily step counts) were evaluated at baseline, post-training, and post-16-week follow-up. The mediating effect of miRNA expression onto exercise-induced physical fitness change was determined by causal mediation analysis (CMA). RESULTS: Exercise significantly improved body fat and cardiorespiratory fitness in older people while maintaining muscle mass and strength, and augmented expression of c-miR-126, c-miR-146a, and c-miR-222 for up to 16 weeks post-training. Notably, older people in EX had substantially higher daily step counts than CON throughout the study even after the active training period. However, CMA revealed no significant indirect effect but a potential mediating effect of c-miR-21, but not the rest, onto the body composition, cardiorespiratory fitness, and lower limb strength. CONCLUSION: An eight-week supervised MICT program promoted a higher level of physical activity up to 16 weeks post-training, which induces better cardiorespiratory fitness and resists decline in muscular measures. C-miRNA, especially c-miR-21, potentially mediates the training effect upon fitness.
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MicroARN Circulante , Ejercicio Físico , Vida Independiente , Aptitud Física , Humanos , Anciano , Masculino , Aptitud Física/fisiología , Femenino , Ejercicio Físico/fisiología , Estudios de Seguimiento , MicroARN Circulante/sangre , Anciano de 80 o más AñosRESUMEN
Aneuploidy is one of the main causes of miscarriage and in vitro fertilization failure. Mitotic abnormalities in preimplantation embryos are the main cause of mosaicism, which may be influenced by several endogenous factors such as relaxation of cell cycle control mechanisms, defects in chromosome cohesion, centrosome aberrations and abnormal spindle assembly, and DNA replication stress. In addition, incomplete trisomy rescue is a rare cause of mosaicism. However, there may be a self-correcting mechanism in mosaic embryos, which allows some mosaicisms to potentially develop into normal embryos. At present, it is difficult to accurately diagnose mosaicism using preimplantation genetic testing for aneuploidy. Therefore, in clinical practice, embryos diagnosed as mosaic should be considered comprehensively based on the specific situation of the patient.
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Aneuploidia , Blastocisto , Desarrollo Embrionario , Fertilización In Vitro , Mosaicismo , Diagnóstico Preimplantación , Humanos , Mosaicismo/embriología , Blastocisto/metabolismo , Femenino , Diagnóstico Preimplantación/métodos , Desarrollo Embrionario/genética , Embarazo , Pruebas Genéticas , Aborto Espontáneo/genética , Aborto Espontáneo/patologíaRESUMEN
In recent decades, there has been a consistent decline in semen quality across the globe, with environmental pollution emerging as the predominant factor. Persistent organic pollutants (POPs) have garnered considerable attention due to their potent biological toxicity and resistance to natural degradation. Within this class of pollutants, polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons (HAHs) have been identified as detrimental agents that can disrupt cellular physiological functions by activating aryl hydrocarbon receptor (AhR). However, the precise role of AhR in the adverse effects of environmental pollutants on male mammalian fertility remains incompletely understood. This article provides a comprehensive review of the impact of various environmental pollutants, specifically PAHs such as benzo[a]pyrene, 3-methylcholanthrene, and 7,12-dimethylbenzo[a]anthracene, HAHs including 2,3,7,8-tetrachlorodibenzo-p-dioxins, polychlorinated biphenyls, polybrominated diphenyl ethers, and the pollutant complex PM2.5, as well as cigarette smoke condensates, on male mammalian reproductive function. Additionally, this review focuses on the role of the AhR in mediating these effects. The objective of this review is to elucidate the involvement of AhR in the regulation of male mammalian fertility, thereby offering insights for prospective investigations into the interplay between AhR and male reproductive function, as well as the etiology of idiopathic male infertility in clinic.
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Contaminantes Ambientales , Infertilidad Masculina , Hidrocarburos Policíclicos Aromáticos , Receptores de Hidrocarburo de Aril , Receptores de Hidrocarburo de Aril/metabolismo , Masculino , Animales , Contaminantes Ambientales/toxicidad , Contaminantes Ambientales/efectos adversos , Humanos , Hidrocarburos Policíclicos Aromáticos/efectos adversos , Hidrocarburos Policíclicos Aromáticos/toxicidad , Infertilidad Masculina/inducido químicamente , Infertilidad Masculina/etiología , Infertilidad Masculina/metabolismo , Bifenilos Policlorados/efectos adversos , Bifenilos Policlorados/toxicidad , Fertilidad/efectos de los fármacos , Éteres Difenilos Halogenados/efectos adversos , Éteres Difenilos Halogenados/toxicidad , Contaminantes Orgánicos Persistentes/efectos adversos , Contaminantes Orgánicos Persistentes/metabolismoRESUMEN
A series of 2,3-dihalo-1,1,1,4,4,4-hexafluorobutanes and 2-halo-1,1,1,4,4,4-hexafluorobut-2-enes were prepared from commercially available hydrofluoroolefins 1,1,1,4,4,4-hexafluorobut-2-enes and their 1H, 19F and 13C chemical shifts measured. Some reactions of synthesized 2-halo-1,1,1,4,4,4-hexafluorobut-2-enes have been investigated. A simple, one-pot procedure for the preparation of a new allene (1,1,4,4,4-pentafluorobuta-1,2-diene) and some of its transformations is presented.
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Noncoding RNAs (ncRNAs) regulation of various diseases including cancer has been extensively studied. Reactive oxidative species (ROS) elevated by oxidative stress are associated with cancer progression and drug resistance, while autophagy serves as an ROS scavenger in cancer cells. However, the regulatory effects of ncRNAs on autophagy and ROS in various cancer cells remains complex. Here, we explore how currently investigated ncRNAs, mainly miRNAs and lncRNAs, are involved in ROS production through modulating antioxidant genes. The regulatory effects of miRNAs and lncRNAs on autophagy-related (ATG) proteins to control autophagy activity in cancer cells are discussed. Moreover, differential expression of ncRNAs in tumor and normal tissues of cancer patients are further analyzed using The Cancer Genome Atlas (TCGA) database. This review hypothesizes links between ATG genes- or antioxidant genes-modulated ncRNAs and ROS production, which might result in tumorigenesis, malignancy, and cancer recurrence. A better understanding of the regulation of ROS and autophagy by ncRNAs might advance the use of ncRNAs as diagnostic and prognostic markers as well as therapeutic targets in cancer therapy.
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MicroARNs , Neoplasias , Estrés Oxidativo , ARN Largo no Codificante , Antioxidantes/metabolismo , Autofagia/genética , Humanos , MicroARNs/genética , Recurrencia Local de Neoplasia , Neoplasias/genética , Neoplasias/terapia , Estrés Oxidativo/genética , ARN Largo no Codificante/genética , ARN no Traducido/genética , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Previous evidence suggests that higher blood uric acid (UA) levels are associated with adverse cardiovascular outcomes during pregnancy and subsequent birth outcomes. However, it has been relatively unclear whether these associations persist in normotensive pregnant women. METHODS: The study was based on a retrospective analysis of 18,250 mother-infant pairs in a large obstetric center in China. Serum UA concentrations in early pregnancy (median: 17.6, IQR: 16.3, 18.6 gestational weeks) were assessed. Hyperuricemia was defined as ≥ one standard deviation (SD) of the reference value for the corresponding gestational age. Outcomes of gestational diabetes mellitus (GDM), preterm birth (PB), low birth weight (LBW), macrosomia, small for gestational age (SGA) and large for gestational age (LGA) were extracted from the medical records. RESULTS: The mean maternal UA level was 0.22 ± 0.05 mmol/L, and 2,896 (15.9%) subjects had hyperuricemia. After adjustment for several covariates, UA was associated with several adverse outcomes. The ORs (95%CI) per one SD increase in serum UA concentration were 1.250 (1.136, 1.277) for GDM, 1.137 (1.060, 1.221) for PB, 1.134 (1.051, 1.223) for LBW, and 1.077 (1.020, 1.137) for SGA, respectively. Similar adverse associations were found between hyperuricemia and GDM, PB (ORs: 1.394 and 1.385, P < 0.001), but not for LBW, macrosomia, SGA, and LGA. Adverse associations tended to be more pronounced in subjects with higher BMI for outcomes including PB, LBW, and SGA (P interaction = 0.001-0.028). CONCLUSION: Higher UA levels in early pregnancy were associated with higher risk of GDM, PB, LBW, and SGA in normotensive Chinese women.
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Diabetes Gestacional , Hiperuricemia , Nacimiento Prematuro , Embarazo , Femenino , Recién Nacido , Humanos , Diabetes Gestacional/epidemiología , Macrosomía Fetal/epidemiología , Macrosomía Fetal/etiología , Ácido Úrico , Estudios Retrospectivos , Resultado del Embarazo/epidemiología , Hiperuricemia/epidemiología , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Aumento de Peso , Retardo del Crecimiento FetalRESUMEN
BACKGROUND: Acute appendicitis is one of the most common abdominal emergencies, with management approaches that vary depending on the available resources and setting. However, there is a lack of studies on the differences of surgical outcomes and quality of care between tertiary care hospitals and regional hospitals. METHODS: This multicenter retrospective study included 2158 consecutive adult patients between January 2014 and June 2018 at three hospitals. The patient cohort was divided into regional hospital group (N = 1223) and tertiary care hospital group (N = 935). Baseline characteristics and perioperative outcomes were compared, and factors associated with surgical delay and postoperative complication were investigated. RESULTS: Patients in tertiary care hospital group had longer surgical waiting time (17.3 vs. 12.0 h, p < 0.001), higher risks of surgical delay exceeding 24 h (OR = 2.94, 95% CI 2.17-4.01, p < 0.001), longer operation time (64 vs. 50 min, p < 0.001), more appendix perforation (22.4 vs. 13.3%, p < 0.001), and higher hospital cost compared with regional hospital group. In multivariate analysis, factors associated with surgical delay were tertiary care hospital (OR = 2.94, 95% CI 2.18-4.01, p < 0.001) and delay diagnosis (OR = 18.7, 95% CI 11.7-30.1, p < 0.001), while those associated with postoperative complications were older age (OR = 1.02, 95% CI 1.00-1.04, p = 0.013), male sex (OR = 2.38, 95% CI 1.11-5.52, p = 0.031), surgical delay (OR = 2.99, 95% CI 1.30-6.47, p = 0.007), and appendix perforation (OR = 5.61, 95% CI 2.72-11.85, p < 0.001). CONCLUSIONS: Patients at tertiary care hospitals had longer waiting time, more surgical delays, and appendix perforations, and these were risk factors of postoperative complications. Establishing an effective referral system to redirect appendicitis patients with less complex medical histories from tertiary care hospitals to regional hospitals may enhance the quality of patient care and outcomes, while also reducing medical costs.
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Apendicitis , Humanos , Adulto , Masculino , Apendicitis/diagnóstico , Apendicitis/cirugía , Apendicitis/etiología , Estudios Retrospectivos , Centros de Atención Terciaria , Apendicectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
KRAS mutant lung adenocarcinomas remain intractable for targeted therapies. Genetic interrogation of KRAS downstream effectors, including the MAPK pathway and the interphase CDKs, identified CDK4 and RAF1 as the only targets whose genetic inactivation induces therapeutic responses without causing unacceptable toxicities. Concomitant CDK4 inactivation and RAF1 ablation prevented tumor progression and induced complete regression in 25% of KRAS/p53-driven advanced lung tumors, yet a significant percentage of those tumors that underwent partial regression retained a population of CDK4/RAF1-resistant cells. Characterization of these cells revealed two independent resistance mechanisms implicating hypermethylation of several tumor suppressors and increased PI3K activity. Importantly, these CDK4/RAF1-resistant cells can be pharmacologically controlled. These studies open the door to new therapeutic strategies to treat KRAS mutant lung cancer, including resistant tumors.
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Adenocarcinoma del Pulmón/genética , Quinasa 4 Dependiente de la Ciclina/genética , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogénicas c-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteína p53 Supresora de Tumor/metabolismo , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Animales , Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Quinasa 4 Dependiente de la Ciclina/metabolismo , Progresión de la Enfermedad , Resistencia a Antineoplásicos , Silenciador del Gen , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos C57BL , Mutación , Proteínas Proto-Oncogénicas c-raf/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Proteína p53 Supresora de Tumor/genéticaRESUMEN
BACKGROUND: The benefit of routine lymphadenectomy (LD) in improving outcomes for patients with primary intrahepatic cholangiocarcinoma (ICC) undergoing curative hepatectomy remains unclear. MATERIALS AND METHODS: This study enrolled 269 consecutive patients who underwent liver resection for primary ICC from January 2009 to July 2020 in West China Hospital. The association of the nodal status with disease-free survival (DFS) and overall survival (OS) was analyzed using the Cox proportional hazards model and 1:1 propensity score matching (PSM) analysis. RESULTS: Seventy-five (27.9%) patients underwent curative liver resection combined with LD (LD+ group), while 194 (72.1%) patients received curative liver resection without LD (LD- group and Nx group). Among the LD+ group, metastatic disease was present in 36 patients (48%, N1 group) and absent in 39 patients (N0 group). During the follow-up period, 116 patients (43.1%) experienced tumor recurrence and 101 patients (37.5%) died due to recurrence. Multivariate analysis revealed that lymph node metastasis (N1, HR 3.682, 95% CI 1.949-6.957, p < 0.001) was associated with worse OS, while LD+ status (HR 0.504, 95% CI 0.298-0.853, p = 0.011) was associated with improved OS. Adjuvant therapy was a protective factor for both DFS (HR 0.602, 95% CI, 0.447-0.810, p = 0.001) and OS (HR 0.683, 95% CI 0.484-0.963, p = 0.030). After 1:1 PSM, the LD+ patients (n = 74) displayed similar 1-, 3- and 5-year DFS rates (40.0, 7.9 and 7.9% vs. 29.0, 13.7 and 13.7%, p = 0.741) and OS rates (56.0, 26.6 and 22.2% vs. 58.9, 25.6, and 16.4%, p = 0.644) to the LD- patients (n = 74). Additionally, among the 75 LD+ patients, 48 patients underwent hepatic hilar lymphadenectomy (HHL), and 27 patients underwent extended hepatic hilar lymphadenectomy (EHL). Both DFS (p = 0.504) and OS (p = 0.215) were similar between the HHL and EHL groups. CONCLUSION: Routine LD and adjuvant therapy may contribute to improved OS according to the crude analysis. LD could provide accurate staging without excessive risk and guide adjuvant therapy based on the tumor stage, potentially resulting in better survival. These results suggest that a routine LD should be considered during curative hepatectomy for ICC.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Hepatectomía/efectos adversos , Puntaje de Propensión , Estudios Retrospectivos , Recurrencia Local de Neoplasia/cirugía , Colangiocarcinoma/cirugía , Colangiocarcinoma/patología , Escisión del Ganglio Linfático , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/cirugía , PronósticoRESUMEN
Manoalide provides preferential antiproliferation of oral cancer but is non-cytotoxic to normal cells by modulating reactive oxygen species (ROS) and apoptosis. Although ROS interplays with endoplasmic reticulum (ER) stress and apoptosis, the influence of ER stress on manoalide-triggered apoptosis has not been reported. The role of ER stress in manoalide-induced preferential antiproliferation and apoptosis was assessed in this study. Manoalide induces a higher ER expansion and aggresome accumulation of oral cancer than normal cells. Generally, manoalide differentially influences higher mRNA and protein expressions of ER-stress-associated genes (PERK, IRE1α, ATF6, and BIP) in oral cancer cells than in normal cells. Subsequently, the contribution of ER stress on manoalide-treated oral cancer cells was further examined. ER stress inducer, thapsigargin, enhances the manoalide-induced antiproliferation, caspase 3/7 activation, and autophagy of oral cancer cells rather than normal cells. Moreover, N-acetylcysteine, an ROS inhibitor, reverses the responses of ER stress, aggresome formation, and the antiproliferation of oral cancer cells. Consequently, the preferential ER stress of manoalide-treated oral cancer cells is crucial for its antiproliferative effect.
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Estrés del Retículo Endoplásmico , Neoplasias de la Boca , Estrés Oxidativo , Humanos , Apoptosis , Línea Celular Tumoral , Endorribonucleasas/metabolismo , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Proteínas Serina-Treonina Quinasas/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Postoperative cognitive dysfunction (POCD) is a prevalent disorder after anaesthesia in the elderly patients. Roflumilast (RF), a phosphodiesterase 4 (PDE-4) inhibitor, could improve cognition with no side effects. Here, we sought to explore the efficacy of RF in the improvement of cognitive dysfunction caused by sevoflurane (Sev). Sprague-Dawley rats were anaesthetized, and the hippocampal neurons were treated with Sev to develop in vivo and in vitro POCD models, followed by RF administration. The mechanism of the PKA-CREB and MEK/ERK pathways in the pathogenesis of POCD was explored. Sev impaired the cognitive functions of rats, significantly reduced cyclic adenosine monophosphate (cAMP) concentrations and blocked the PKA-CREB and MEK/ERK pathways. Moreover, the Sev-treated rats and neurons exhibited enhanced apoptosis and reactive oxygen species (ROS). After treatment with RF, rats had better learning and memory function, and the activity of neurons in hippocampus and cortex was improved. Loss-of-function assay indicated that PKA-CREB and MEK/ERK signalling impairment reduced cAMP levels and promoted apoptosis and ROS in rat hippocampus and neurons. Generally, RF promotes neuronal activity in rats after Sev treatment by maintaining cAMP levels and sustaining the activation of PKA-CREB and MEK/ERK pathways. This might offer novel sights for POCD therapy.
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Anestesia , Disfunción Cognitiva , Aminopiridinas , Animales , Benzamidas , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/metabolismo , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/farmacología , Ciclopropanos , Hipocampo/metabolismo , Sistema de Señalización de MAP Quinasas , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/farmacología , Inhibidores de Fosfodiesterasa/farmacología , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Sevoflurano/farmacologíaRESUMEN
BACKGROUND: Tumor resistance is a global challenge for tumor treatment. Cancer stem cells (CSCs) are the main population of tumor cells for drug resistance. We have reported that high aldehyde dehydrogenase (ALDH) activity represents a functional marker for cervical CSCs. Here, we aimed at disulfiram (DSF), an ALDH inhibitor, that has the potential to be used for cervical cancer treatment. METHODS: MTT assay, western blot, vector construction and transfection, cell sorting and in vivo anti-tumor assays were performed using cervical cancer cell lines SiHa and HeLa. Cell cycle distribution and cell apoptosis were carried out by flow cytometry. The cytotoxicity of DSF was detected by MTT assay and cervical cancer xenograft models. RESULTS: DSF was cytotoxic to cervical cancer cell lines in a copper (Cu)-dependent manner. Disulfiram/copper (DSF/Cu) complex induced deregulation of S-phase and inhibited the expression of stemness markers in cervical cancer cells. Furthermore, DSF/Cu could also reduce the cancer stem cell-like LGR5+ cells which lead to cisplatin resistance in cervical cancer cells. DSF/Cu complex had the greater antitumor efficacy on cervical cancer than cisplatin in vitro and in vivo. CONCLUSION: Our findings indicate that the cytotoxicity of DSF/Cu complex may be superior to cisplatin because of targeting LGR5-positive cervical cancer stem-like cells in cervical cancer. Thus, the DSF/Cu complex may represent a potential therapeutic strategy for cervical cancer patients.
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Antineoplásicos , Cobre , Disulfiram , Neoplasias del Cuello Uterino , Antineoplásicos/farmacología , Línea Celular Tumoral , Cisplatino/farmacología , Cobre/farmacología , Disulfiram/farmacología , Femenino , Humanos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVES: To determine if dynamic CT can differentiate local progression from radioactive seed-induced peritumoral reaction (RSIPR) after brachytherapy with iodine-125 radioactive seeds (BIRS) for advanced hepatic malignancies. METHODS: Enhanced CT images of seed-implanted lesions between 2006 and 2018 were retrospectively evaluated. Hounsfield units of peritumoral parenchyma were measured and assessed quantitatively. The classification, conversion, consequences, and serological indicators during follow-up were recorded and quantified. Statistical differences were analyzed using a Pearson χ2 test. RESULTS: RSIPR was observed in 201 of 290 (69.3%) lesions (161 patients; median age, 55 years; range, 26-79 years), while local progression occurred in 53 lesions. The low density of local progression was much lower than that of RSIPR (p < 0.001), and the former did not exhibit iso-/high density in the portal or equilibrium phase. Ring-like enhancement in progressive lesions was also quite different from RSIPR. Local progression rate was lower for lesions with RSIPR than for those without RSIPR (14.9% vs 25.8%; p = 0.03), and their doses were different (397.2 Gy vs 120.3 Gy, p < 0.001). CONCLUSIONS: Radioactive seed-induced peritumoral reaction has characteristic manifestations on CT images, which is associated with a higher dose of lesions and lower local progression rate. Notably, the enhancement pattern of local progression was distinct from RSIPR and was clearly distinguishable on dynamic-enhanced CT. KEY POINTS: ⢠Radioactive seed-induced peritumoral reaction after brachytherapy with 125I seeds for liver malignancies has characteristic manifestations on CT images, which is associated with a higher dose of lesions (397.2 Gy vs 120.3 Gy, p < 0.001), as a focal radiation injury. ⢠Lesions with RSIPR were less likely to develop local progression, while those without RSIPR had a higher rate of local progression (14.9% vs 25.8%; p = 0.03). ⢠The enhancement pattern of local progression after brachytherapy was distinct from radioactive seed-induced peritumoral reaction and was clearly distinguishable on dynamic-enhanced CT.
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Braquiterapia , Neoplasias Hepáticas , Braquiterapia/métodos , Humanos , Radioisótopos de Yodo , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Persona de Mediana Edad , Dosificación Radioterapéutica , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Thyroid function is known to be closely linked with type 2 diabetes, but data on the association between thyroid function and gestational diabetes mellitus (GDM) are inconsistent. METHODS: A total of 2849 pregnant women were included in this retrospective study. Serum concentrations of thyroid indicators (free tetraiodothyronine, FT4; thyroid-stimulating hormone, TSH; and thyroid peroxidase antibody, TPO Ab) were obtained from a clinical laboratory. The presence of GDM were drawn from medical records. The clinical subtypes of thyroid function (euthyroidism, subclinical hypothyroidism, hyperthyroidism, and isolated hypothyroxinemia) were categorized according to the thresholds of the 2.5th/97.5th and 10th/90th percentiles of TSH and FT4 concentrations. A concentration of > 34 IU/L was defined as indicating TPO Ab-positivity. RESULTS: Two hundred and thirty-five (8.25%) of the 2849 women were TPO Ab-positive. Higher serum concentrations of FT4 (top vs. bottom tertiles) was found to be negatively associated with the risk of GDM. The corresponding odds (OR) values (top tertile vs. bottom tertile) were 0.71 [95% confidence interval (CI): 0.54, 0.93]. No significant associations were observed between the extremely 2.5th/97.5th or 10th/90th percentiles of FT4 concentration, TSH concentration, thyroid function subtypes (vs. euthyroidism), TPO Ab-positivity (vs. -negativity), and the GDM risk. The corresponding results remained similar when TPO Ab-positive subjects were excluded. CONCLUSIONS: A negative association with the risk of GDM was observed for the highest FT4 concentrations tertile. No significant associations were found between the TSH concentration, thyroid function subtypes, TPO Ab positivity, and the GDM risk.
Asunto(s)
Diabetes Gestacional , Enfermedades de la Tiroides/complicaciones , Hormonas Tiroideas/sangre , Adulto , Biomarcadores/sangre , China , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Pruebas de Función de la TiroidesRESUMEN
Alcohol sales and consumption have increased during the coronavirus disease 2019 pandemic, but their downstream effects on alcohol-related liver disease (ALD) are unclear. We analyzed inter-hospital escalation-of-care referrals to our tertiary care inpatient liver unit across 18 months through December 2020. There was a significant rise in severe ALD with recent unhealthy drinking in our regional community during the pandemic.
Asunto(s)
COVID-19 , Hepatopatías , Consumo de Bebidas Alcohólicas/epidemiología , COVID-19/epidemiología , Hospitales , Humanos , Pandemias , Derivación y ConsultaRESUMEN
The materials used for the fabrication of solid-phase microextraction fiber coatings in the past five years are summarized in the current review, including carbon, metal-organic frameworks, covalent organic frameworks, aerogel, polymer, ionic liquids/poly (ionic liquids), metal oxides, and natural materials. The preparation approaches of different coatings, such as sol-gel technique, in-situ growth, electrodeposition, and glue methods, are briefly reviewed together with the evolution of the supporting substrates. In addition, the limitations of the current coatings and the future development directions of solid-phase microextraction are presented.
RESUMEN
OBJECTIVE: To compare the prevalence of chromosomal abnormalities detected in products of conception (POCs) between recurrent pregnancy loss and sporadic pregnancy loss. METHODS: A systematic search was performed in the PubMed and Embase databases from inception to December 31, 2020. Relevant studies analysing the association between the number of pregnancy losses and the incidence of chromosomal abnormalities were included. Independent data extraction was conducted and study quality was assessed. Meta-analyses were carried out to calculate odds ratios by using fixed- or random-effects models according to statistical homogeneity. RESULTS: A total of 8320 POCs in 19 studies were identified for the meta-analyses. The incidence of chromosomal abnormalities in sporadic pregnancy loss was significantly higher than that in recurrent pregnancy loss. In subgroup analyses, the following studies reported a high incidence of abnormal outcomes of sporadic pregnancy loss: studies with ≥ 300 samples, studies published before 2014, studies conducted in European and American countries, and studies with analyses using conventional karyotype techniques. Moreover, the incidence of chromosomal abnormalities in women with two pregnancy losses was significantly higher than that in women with three or more pregnancy losses. However, there was no difference in the distribution of abnormal types between sporadic and recurrent pregnancy loss or between two and three or more pregnancy losses. CONCLUSIONS: The prevalence of chromosomal abnormalities detected in POCs was lower in recurrent pregnancy loss than in sporadic pregnancy loss, and decreased with an increasing number of pregnancy losses.