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OBJECTIVES: Non-immune hydrops fetalis (NIHF) is the pathological accumulation of fluids in fetal compartments, without maternal isoimmunization. Fetal interventions (e.g. shunting, fetal paracentesis, fetal thoracocentesis, fetal pleurodesis) are used to alleviate fluid accumulations, but the outcome is uncertain because the underlying causes of NIHF vary. We aimed to explore the etiology and long-term outcome of NIHF after fetal intervention. METHODS: This was a retrospective review of fetuses with NIHF, defined by the presence of fetal ascites, pleural or pericardial effusion, skin edema or cystic hygroma, or a combination of these features, who underwent intervention at our institution during the period 2012-2021. Clinical surveillance, genetic analysis and viral infection screening were used to define the etiology. Chart reviews and telephone interviews were conducted to assess the long-term outcomes. RESULTS: In total, 55 fetuses were enrolled and 46 cases had final follow-up data after delivery. Etiology was identified in 33 cases, including four for which the underlying causes were not identified initially using small-gene-panel tests but which were later diagnosed with monogenic disorders by whole-exome sequencing (WES). Twenty-three cases with follow-up survived, having a follow-up period of 2-11 years at the time of writing, of which 17 were healthy. All 11 cases initially presenting as congenital chylothorax survived with favorable outcome. CONCLUSIONS: The etiologies of NIHF are heterogeneous, and the long-term (spanning 2-11 years) outcome of fetal intervention varies, according to the underlying etiology, with cases caused by congenital chylothorax having the best prognosis. Genome-wide tests, such as WES, may be helpful in determining the underlying condition in cases caused by a genetic disorder, and this may affect fetal therapy approaches in the future. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
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Quilotórax , Derrame Pleural , Embarazo , Femenino , Humanos , Hidropesía Fetal/etiología , Hidropesía Fetal/genética , Ascitis/diagnóstico por imagen , Ascitis/etiología , Estudios Retrospectivos , Quilotórax/complicaciones , Derrame Pleural/etiología , Derrame Pleural/complicacionesRESUMEN
OBJECTIVE: Rehabilitation of disabled children with autism has become a challenge for current rehabilitation centres. This study conducted psychological investigations on disabled children and analysed the symptoms and characteristics of autism in these children to develop more reasonable rehabilitation treatment plans that would help the children receive psychological counselling and effective rehabilitation. SUBJECTS AND METHODS: This study investigated 107 disabled children from the Disabled Rehabilitation Research Centre of the South China Minority Autonomous Region. Using the PEP-3 scale as a research tool, a questionnaire was developed to investigate and collect data on the mental health of disabled children. The survey was conducted from 2017 to 2021, and 107 children's mental health data were collected in the form of questionnaires based on PEP-3 evaluation indicators. After cleaning the data, the questionnaire data were screened and processed. Descriptive statistical and correlation analysis tools were used for model analysis to understand the overall data distribution and the potential relationships among various data variables. RESULTS: The results of correlation analysis showed that cognition, language expression, language understanding, emotion, and social interaction in the subtest of developmental behaviour were the main indicators of the degree of autism in children. These indicators had a strong and significant correlation with the comprehensive score. Moreover, these indicators had a significant correlation with the individual self-care and adaptive behaviours reported by the children's caregivers. Small muscles, big muscles, and imitation (vision and movement) indicators had a significant correlation with problematic behaviours and physical fitness, and language and cognitive indicators also had a strong correlation with emotion and social interaction. CONCLUSIONS: Emphasis should be placed on the improvement of the language and cognitive abilities of disabled children with autism, and corresponding rehabilitation plans, and training can be formulated according to children with different degrees of illness to get a better rehabilitation outcome. Further, identification of key indicators of autism will be of help in aiding the development of rehabilitation treatment for disabled children with autism and formulation of long-term rehabilitation plans.
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Trastorno Autístico , Niños con Discapacidad , Adaptación Psicológica , Cuidadores , Niño , Humanos , Encuestas y CuestionariosRESUMEN
Amphidynamic crystals, which possess crystallinity and support dynamic behaviours, are very well suited to the exploration of emergent phenomena that result from the coupling on the dynamic moieties. Here, dipolar rotors have been embedded in a crystalline metal-organic framework. The material consists of Zn(II) nodes and two types of ditopic bicyclo[2.2.2]octane-based linkers-one that coordinates to the Zn clusters through two 1,4-aza moieties, and a difluoro-functionalized derivative (the dipolar rotor) that coordinates through linked 1,4-dicarboxylate groups instead. Upon cooling, these linkers collectively order as a result of correlated dipole-dipole interactions. Variable-temperature, frequency-dependent dielectric measurements revealed a transition temperature Tc = 100 K, when a rapidly rotating, dipole-disordered, paraelectric phase transformed into an ordered, antiferroelectric one in which the dipole moments of the rotating linkers largely cancelled each other. Monte Carlo simulations on a two-dimensional rotary lattice showed a ground state with an Ising symmetry and the effects of dipole-lattice and dipole-dipole interactions.
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BACKGROUND AND PURPOSE: Fabry disease is an X-linked disease, and enzyme-based screening methods are not suitable for female patients. METHODS: In total, 1000 young stroke patients (18-55 years, 661 with ischaemic stroke and 339 with hypertensive intracerebral hemorrhage) were recruited. The Sequenom iPLEX assay was used to detect 26 Fabry related mutation genes. The frequency of Fabry disease in young stroke was reviewed and compared between Asian and non-Asian countries. RESULTS: Two male patients with ischaemic stroke were found to have a genetic mutation of IVS4+919G>A. There was no α-galactosidase A (GLA) gene mutation in female patients. The frequency in Asian stroke patients was 0.62% (male vs. female 0.63% vs. 0.58%) with 0.72% for ischaemic stroke and none for hemorrhagic stroke, compared to 0.88% (0.77% vs. 1.08%) with 0.83% for ischaemic stroke and 1.40% for hemorrhagic stroke reported in western countries. CONCLUSION: IVS4+919G>A is the GLA mutation in Taiwanese young ischaemic stroke patients. Fabry disease is more frequent among non-Asian patients compared to Asian patients.
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Isquemia Encefálica/genética , Enfermedad de Fabry/diagnóstico , Enfermedad de Fabry/genética , Pruebas Genéticas , Accidente Cerebrovascular/genética , Adolescente , Adulto , Factores de Edad , Isquemia Encefálica/epidemiología , Enfermedad de Fabry/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/epidemiología , Taiwán/epidemiología , Adulto JovenRESUMEN
Essentials Uncertainty remains about antiplatelets for vascular access patency in hemodialysis patients. 95 971 people under hemodialysis were followed in a claims database in Taiwan. Aspirin reduced vascular access failure rate and did not increase major bleeding rate. Clopidogrel, Aggrenox, and warfarin might increase major bleeding rate. SUMMARY: Background Dialysis adequacy is a major determinant of survival for patients with end-stage renal disease. Good vascular access is essential to achieve adequate dialysis. Objectives This study evaluated the impacts of different drugs on the vascular access failure rate of an arteriovenous fistula or an arteriovenous graft and the rate of major bleeding in hemodialysis patients. Patients and methods We studied patients with end-stage renal disease registered in the Taiwan National Health Insurance program from 1 January 1997 to 31 December 2012. A total of 95 971 patients were enrolled in our study. Vascular access dysfunction was defined as the need for thrombectomy or percutaneous angioplasty. Major bleeding was defined as emergency department visits or hospitalization with a primary diagnosis of gastrointestinal bleeding or intracerebral hemorrhage. The adjusted odds ratios between person-quarters with or without antiplatelet or oral anticoagulant use were calculated using a generalized estimating equation. Results The odds ratio of vascular access failure was 0.21 (0.11-0.39) for aspirin, 0.76 (0.74-0.79) for clopidogrel, 0.67 (0.59-0.77) for dipyridamole, 0.67 (0.53-0.86) for Aggrenox and 0.96 (0.90-1.03) for warfarin. The highest odds ratio for intracerebral hemorrhage was 5.33 (1.25-22.72) in younger patients using Aggrenox. The highest odds ratio for gastrointestinal bleeding was 1.34 (1.10-1.64) for clopidogrel. Conclusion Antiplatelet agents, but not warfarin, might reduce the vascular access thrombosis rate. The gastrointestinal bleeding rate was increased in the group using clopidogrel. Aggrenox should be used with caution in young individuals because it might increase the rate of intracerebral hemorrhage.
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Anticoagulantes/uso terapéutico , Derivación Arteriovenosa Quirúrgica/efectos adversos , Implantación de Prótesis Vascular/efectos adversos , Oclusión de Injerto Vascular/prevención & control , Fallo Renal Crónico/terapia , Inhibidores de Agregación Plaquetaria/uso terapéutico , Diálisis Renal , Trombosis/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Aspirina/uso terapéutico , Combinación Aspirina y Dipiridamol/uso terapéutico , Clopidogrel/uso terapéutico , Bases de Datos Factuales , Femenino , Hemorragia Gastrointestinal/inducido químicamente , Oclusión de Injerto Vascular/diagnóstico , Oclusión de Injerto Vascular/etiología , Humanos , Hemorragias Intracraneales/inducido químicamente , Fallo Renal Crónico/diagnóstico , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/efectos adversos , Factores Protectores , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Taiwán , Trombosis/diagnóstico , Trombosis/etiología , Insuficiencia del Tratamiento , Warfarina/uso terapéutico , Adulto JovenRESUMEN
We report a facile route for the green synthesis of trimethyl chitosan nitrate-capped silver nanoparticles (TMCN-AgNPs) with positive surface charge. In this synthesis, silver nitrate, glucose, and trimethyl chitosan nitrate (TMCN) were used as silver precursor, reducing agent, and stabilizer, respectively. The reaction was carried out in a stirred basic aqueous medium at room temperature without the use of energy-consuming or expensive equipment. We investigated the effects of the concentrations of NaOH, glucose, and TMCN on the particle size, zeta potential, and formation yield. The AgNPs were characterized by UV-vis spectroscopy, photon correlation spectroscopy, laser Doppler anemometry, transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The catalytic activity of the TMCN-AgNPs was studied by the reduction of 4-nitrophenol using NaBH4 as a reducing agent. We evaluated the antibacterial effects of the TMCN-AgNPs on Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus using the broth microdilution method. The results showed that both gram-positive and gram-negative bacteria were killed by the TMCN-AgNPs at very low concentration (<6.13µg/mL). Moreover, the TMCN-AgNPs also showed high antibacterial activity against clinically isolated multidrug-resistant A. baumannii strains, and the minimum inhibitory concentration (MIC) was ≤12.25µg/mL.
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Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/farmacología , Quitosano/química , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Nanopartículas del Metal/química , Plata/farmacología , Acinetobacter baumannii/crecimiento & desarrollo , Borohidruros/química , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Glucosa/química , Nanopartículas del Metal/ultraestructura , Pruebas de Sensibilidad Microbiana , Nitrofenoles/química , Oxidación-Reducción , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Plata/química , Hidróxido de Sodio/química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Electricidad EstáticaRESUMEN
Q fever (QF) is a worldwide zoonosis associated with outbreaks. Only a few nationwide studies regarding the surveillance and epidemiology of human QF have been reported. Although QF is endemic in Taiwan, a nationwide database investigation of the epidemiology and characteristics of QF and its associations with scrub typhus (ST), murine typhus (MT) and leptospirosis (LS) has never been reported. We analysed nationwide databases of suspected QF, ST, MT and LS cases from October 2007 to December 2014 obtained from the Centers for Disease Control, Taiwan. A total of 468 (4.2%) QF cases were identified among 11 109 suspected QF cases. QF cases were mainly distributed in the southern and Kaohsiung-Pingtung regions but rarely in the eastern region. Compared to non-QF cases, QF cases had significantly higher percentages of males (88.7 versus 66.2%) and high-risk occupations (farming, animal husbandry or veterinary medicine) (16.2 versus 10.5%). But the percentages of specific animal contact, including cattle (0.6 versus 0.8%) and goats (0.9 versus 1.0%), were low in both. The majority of suspected QF cases (89.4%) were simultaneously suspected with ST, MT or LS, and the combinations of suspected diseases differed between regions. The number of suspected QF cases from the eastern region decreased since 2009, which was not observed in other regions. A total of 1420 (12.8%) cases had confirmed diseases, including QF (453, 4.1%), QF+ST (7, 0.06%), QF+MT (4, 0.04%), QF+LS (4, 0.04%), MT (186, 1.7%), ST (545, 4.9%), ST+LS (11, 0.1%) and LS (210, 1.9%). Compared to cases of unknown disease, QF cases had larger percentages of high-risk occupations (16.2 versus 9.6%) but similar histories of animal contact (29.8 versus 25.1%). QF is an endemic disease in southern Taiwan. It is difficult to differentiate QF from ST, MT or LS only by high-risk occupations and history of animal contact, and co-infection of QF with these diseases should be considered.
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Coinfección/epidemiología , Leptospirosis/complicaciones , Fiebre Q/complicaciones , Tifus por Ácaros/complicaciones , Taiwán/epidemiología , Tifus Endémico Transmitido por Pulgas/complicaciones , Adulto , Anciano , Animales , Coinfección/microbiología , Bases de Datos Factuales , Femenino , Humanos , Leptospirosis/epidemiología , Masculino , Persona de Mediana Edad , Tifus por Ácaros/epidemiología , Tifus Endémico Transmitido por Pulgas/epidemiología , ZoonosisRESUMEN
The new allele B*39:01:15 differs from B*39:01:01 by a point mutation at position 315 (G>T) of exon 2.
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Alelos , Artritis Reumatoide/genética , Antígeno HLA-B39/genética , Mutación Puntual , Artritis Reumatoide/inmunología , Artritis Reumatoide/patología , Secuencia de Bases , Codón , Exones , Antígeno HLA-B39/inmunología , Prueba de Histocompatibilidad , Humanos , Datos de Secuencia Molecular , Alineación de Secuencia , Análisis de Secuencia de ADN , TaiwánRESUMEN
Tigecycline (TGC)-resistant extensively drug-resistant Acinetobacter baumannii (XDRAB) is an increasing threat in regard to nosocomial infections. The resistance-nodulation-cell division (RND) efflux pump has played an important role in TGC resistance. In this study, total 81 TGC-resistant XDRAB isolates were analyzed for their responses to the efflux pump inhibitor 1-(1-naphthylmethyl)-piperazine (NMP). We found that NMP could reduce by 4-fold or greater than 4-fold the minimum inhibitory concentration (MIC) of TGC in 45 isolates (55.6 %). After typing with pulsed-field gel electrophoresis (PFGE), group A appeared to be the major cluster with good synergistic response to NMP. Transcripts of the AdeABC efflux pump gene were consistently more correlated with TGC resistance than transcripts of the AdeFGJ or AdeIJK efflux pump genes in these isolates. Of the 81 isolates, the amino acid sequences of AdeR and AdeS were further classified and combined into 31 different codes. Although the dissemination of TGC-resistant XDRAB isolates was genetically diverse in our hospital, their responses to NMP conversion were still strain-dependent. We found that AdeRS combination codes were better than PFGE typing in separating groups of isolates with different sensitivity to NMP conversion.
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Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/efectos de los fármacos , Proteínas Bacterianas/genética , Proteínas de Transporte de Membrana/genética , Minociclina/análogos & derivados , Acinetobacter baumannii/genética , Acinetobacter baumannii/aislamiento & purificación , Acinetobacter baumannii/metabolismo , Antibacterianos/farmacología , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/metabolismo , Farmacorresistencia Bacteriana Múltiple , Electroforesis en Gel de Campo Pulsado , Humanos , Proteínas de Transporte de Membrana/metabolismo , Pruebas de Sensibilidad Microbiana , Minociclina/farmacología , TigeciclinaRESUMEN
BACKGROUND AND PURPOSE: Our aim was to investigate the influence of admission dehydration on the discharge outcome in acute ischaemic and hemorrhagic stroke. METHODS: Between January 2009 and December 2011, 4311 ischaemic and 1371 hemorrhagic stroke patients from the stroke registry of Chang Gung healthcare system were analyzed. The eligible patients were identified according to inclusion/exclusion criteria. In total, 2570 acute ischaemic and 573 acute hemorrhagic stroke patients were finally recruited. According to the blood urea nitrogen (BUN) to creatinine (Cr) ratio (BUN/Cr), these patients were divided into dehydrated (BUN/Cr ≥ 15) and non-dehydrated (BUN/Cr < 15) groups. Demographics, admission costs and discharge outcomes including modified Rankin scale (mRS) and Barthel index (BI) were examined. Data were analyzed using multivariate analysis of two-stage least squares including logistic and linear regression. RESULTS: Acute ischaemic stroke with admission dehydration had higher infection rates (P = 0.006), worse discharge BI (62.8 ± 37.4 vs. 73.4 ± 32.4, P < 0.001, adjusted P < 0.001), worse mRS (2.7 ± 1.6 vs. 2.3 ± 1.5, P < 0.001, adjusted P = 0.009) and higher admission costs (2470.8 ± 3160.8 vs. 1901.2 ± 2046.8 US dollars, P < 0.001, adjusted P = 0.013) than those without dehydration. However, acute hemorrhagic stroke with or without admission dehydration showd no difference in admission costs (P = 0.618) and discharge outcomes (BI, P = 0.058; mRS, P = 0.058). CONCLUSION: Admission dehydration is associated with worse discharge outcomes and higher admission costs in acute ischaemic stroke but not in hemorrhagic stroke.
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Isquemia Encefálica/complicaciones , Deshidratación , Hospitalización/economía , Admisión del Paciente/economía , Accidente Cerebrovascular/etiología , Anciano , Anciano de 80 o más Años , Costos y Análisis de Costo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Alta del Paciente , Valor Predictivo de las Pruebas , Sistema de Registros , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
Drug addiction behavior that is established and maintained by psychostimulants has been shown to be associated with the expression of brain-derived neurotrophic factor (BDNF) in the mesolimbic dopamine (DA) system. Cocaine has been used for most prior studies testing this effect of psychostimulants and therefore relatively little is known about its counterpart amphetamine (AMP). To fill this gap, the present study was designed to test whether BDNF mRNA expression levels in the DA terminal regions were changed specifically by d-AMP-induced conditioned place preference (CPP) followed by drug-primed reinstatement. The dose of d-AMP, 1mg/kg, was confirmed to significantly induce CPP. Using this dose, a group of rats was initially subjected to d-AMP CPP, which was followed by entry into an extinction protocol with an additional 3-day withdrawal before a drug-primed reinstatement test was carried out. Following extinction of d-AMP CPP, a lower dose of d-AMP, namely 0.75mg/kg, was able to significantly reinstate CPP. The BDNF mRNA levels in the selected brain areas were determined by real-time polymerase chain reaction (PCR) after the CPP and reinstatement. The BDNF mRNA level in the medial prefrontal cortex (mPFC) was significantly increased after the reinstatement, but not the CPP test. And, none of the other four assessed brain areas showed any change in BDNF mRNA level after d-AMP CPP or reinstatement. These findings support the notion that BDNF is involved in drug-seeking behavior and indicate that d-AMP reinstatement after extinction may be linked to an increase in BDNF mRNA expression in the mPFC.
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Factor Neurotrófico Derivado del Encéfalo/metabolismo , Condicionamiento Psicológico/efectos de los fármacos , Dextroanfetamina/farmacología , Inhibidores de Captación de Dopamina/farmacología , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Extinción Psicológica/efectos de los fármacos , Masculino , ARN Mensajero/metabolismo , Ratas , Ratas WistarRESUMEN
BACKGROUND: Functional outcome and the risk factors for stroke survivors have explored in previous study. However, a comprehensive understanding of the patterns and critical risk factors of functional recovery is limited. AIM: To explore the trajectory groups and determinants of functional recovery for ischemic stroke patients during 1 year after stroke. DESIGN: Longitudinal study. SETTING: Inpatient. POPULATION: First-time stroke patients. METHOD: A total of 367 first-time ischemic stroke patients from the Stroke Registry in the Chang Gung Hospital (SRICH) database were analyzed in this study. Study variables comprised demographic and disease characteristics, laboratory data, and functional outcome. The Latent Class Growth Analysis (LCGA) was used to identify various trajectory clusters and multinomial logistic regression was used to identify the predictors of functional recovery. RESULT: Five trajectory clusters of functional recovery were identified using the Barthel Index. Among five clusters of functional recovery, nearly 18% of first-ever ischemic stroke patients maintained functional dependence, whereas 82% of stroke patients demonstrated functional recovery; and the significant recovery time totaled three months after the stroke. Determinants for various trajectory clusters of functional recovery were body mass index and serum albumin level, especially a higher serum albumin concentration predicted a more favorable functional recovery. CONCLUSION: Our findings suggest that diverse functional recovery clusters persisted and serum albumin concentration at admission was a critical assessment factor. CLINICAL REHABILITATION: Such information could be useful for identifying the different rehabilitation needs of varying trajectory groups and for effectively improving functional ability among the ischemic stroke population.
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Albúminas/análisis , Recuperación de la Función , Rehabilitación de Accidente Cerebrovascular , Factores de Edad , Anciano , Análisis de Varianza , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Comorbilidad , Femenino , Humanos , Tiempo de Internación , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , TaiwánRESUMEN
Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol-â£miRNA-520h-â£PP2A/C-â£Akt â NF-κB â FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression.
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Antineoplásicos Fitogénicos/farmacología , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , MicroARNs/genética , Estilbenos/farmacología , Animales , Línea Celular , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Progresión de la Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Femenino , Células HEK293 , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Ratones , Ratones SCID , MicroARNs/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Proteína Fosfatasa 2/genética , Proteína Fosfatasa 2/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Resveratrol , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Hashimoto disease (HD) is an autoimmune thyroid disease resulting from complex interactions between genetic and environmental factors. The human leukocyte antigen (HLA) gene has been established to be involved in the susceptibility to HD. We aim to investigate the associations between HLA-B alleles and Han Chinese children with HD by both case-control and family-based studies. A total of 108 unrelated children with HD, 380 unrelated healthy controls, 58 trios of affected patients and their parents, and 75 trios of unaffected siblings and their parents were recruited. HLA-B genotyping was performed by polymerase chain reaction and detected with a sequence-specific oligonucleotide probes system. We found that B*46:01 allele (OR = 2.31, 95% CI 1.60-3.34, P(c) = 9.99 × 10(-5)) and carrier (OR = 3.28, 95% CI 2.10-5.11, P(c) = 1.35 × 10(-6)) were associated with HD risk. Transmission/disequilibrium test further confirmed an overtransmission of the B*46:01 (OR 2.55, 95% CI 1.36-6.10, P = 6.5 × 10(-3)). The findings were similar in females when stratified by gender. In conclusion, our results clearly identify that HLA-B*46:01 confers susceptibility to HD in Han Chinese children. Further studies with larger children cohort are required to confirm the role of B*46:01 in the development of HD.
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Pueblo Asiatico , Predisposición Genética a la Enfermedad , Antígenos HLA-B/genética , Enfermedad de Hashimoto/genética , Polimorfismo Genético , Adolescente , Adulto , Alelos , Estudios de Casos y Controles , Niño , Preescolar , Familia , Femenino , Frecuencia de los Genes , Antígenos HLA-B/inmunología , Haplotipos , Enfermedad de Hashimoto/inmunología , Prueba de Histocompatibilidad , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , HermanosRESUMEN
Graves disease (GD) is an autoimmune thyroid disease with a female preponderance and a wide range of ages at onset, and human leukocyte antigen (HLA) gene plays a primary role in the susceptibility to GD. We aim to investigate the associations between HLA-DRB1 alleles and Taiwanese children with GD by both case-control and family-based studies. A total of 241 unrelated children with GD, 539 healthy controls, 115 trios of affected patients and their parents, and 121 trios of unaffected siblings and their parents were recruited. HLA-DRB1 genotyping was performed by polymerase chain reaction and sequence-based typing assays. We found that DRB1*09:01 (OR=2.60, 95% CI 2.02-3.35, Pc=6.55×10(-13)) was associated with GD risk, while DRB1*12:02 (OR=0.32, 95% CI 0.20-0.53, Pc=4.55×10(-5)) was protective against GD. Transmission/disequilibrium test further confirmed an overtransmission of the DRB1*09:01 (OR 3.37, 95% CI 2.13-6.22, Pc=1.0×10(-5)) and an undertransmission of the DRB1*12:02 (OR 0.21, 95% CI 0.05-0.42, Pc=1.7×10(-3)). The findings were similar in females when stratified by gender. In conclusion, our results clearly identify that HLA-DRB1*09:01 confers susceptibility to GD and DRB1*12:02 exerts protection against GD development in Taiwanese children.
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Predisposición Genética a la Enfermedad , Enfermedad de Graves/genética , Enfermedad de Graves/inmunología , Cadenas HLA-DRB1/genética , Adolescente , Alelos , Aminoácidos/genética , Estudios de Casos y Controles , Niño , Preescolar , Familia , Femenino , Frecuencia de los Genes/genética , Humanos , Desequilibrio de Ligamiento/genética , Masculino , Hermanos , Taiwán/etnología , Adulto JovenRESUMEN
BACKGROUND: Activated androgen receptor binds to androgen-responsive elements (AREs) in genome to regulate target gene transcription and, consequently, mediates physiological or tumorigenic processes of the prostate. Our aim was to determine whether genetic variants in AREs are associated with clinical outcomes after androgen-deprivation therapy (ADT) in prostate cancer patients. PATIENTS AND METHODS: We systematically investigated 55 common single-nucleotide polymorphisms (SNPs) in the genome-wide insilico-predicted AREs in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT was assessed by Kaplan-Meier analysis and Cox regression model. RESULTS: In univariate analysis, two, five, and four SNPs were associated with disease progression, PCSM, and ACM, respectively. After adjusting for known prognostic factors, ARRDC3 rs2939244, FLT1 rs9508016, and SKAP1 rs6504145 remained as significant predictors for PCSM and FBXO32 rs7830622 and FLT1 rs9508016 remained as significant predictors for ACM in multivariate analysis. Moreover, strong combined genotype effects on PCSM and ACM were also observed (P(trend) < 0.001). CONCLUSION: Our results suggest that SNPs in AREs influence prostate cancer survival and may further advance our understanding of the disease progression.
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Arrestinas/genética , Fosfoproteínas/genética , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/genética , Receptores Androgénicos/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Anciano , Antagonistas de Andrógenos/uso terapéutico , Genotipo , Humanos , Estimación de Kaplan-Meier , Masculino , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/mortalidad , Elementos de Respuesta/genéticaRESUMEN
BACKGROUND: Accumulating evidence indicates that oestrogens have significant direct effects on normal prostate development and carcinogenesis. The majority of the biological activities of oestrogens are mediated through the oestrogen receptor (ER), which functions as a hormone-inducible transcription factor to regulate target gene expression by binding to oestrogen response elements (EREs) in the regulatory regions of target genes. Sequence variants in EREs might affect the ER-ERE interaction and subsequent physiological activities. Therefore, we tested whether common single-nucleotide polymorphisms (SNPs) inside EREs are related to the clinical outcomes of androgen-deprivation therapy (ADT) in men with prostate cancer. METHODS: We systematically evaluated 49 ERE SNPs predicted using a genome-wide database in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT was assessed using Kaplan-Meier analysis and a Cox regression model. RESULTS: Based on multiple hypothesis testing, BNC2 rs16934641 was found to be associated with disease progression; in addition, TACC2 rs3763763 was associated with PCSM, and ALPK1 rs2051778 and TACC2 rs3763763 were associated with ACM. These SNPs remained significant in multivariate analyses that included known clinicopathological predictors. Moreover, a combined genotype effect on ACM was observed when ALPK1 rs2051778 and TACC2 rs3763763 were analysed in combination. Patients with a greater number of unfavourable genotypes had a shorter time to ACM during ADT (P for trend <0.001). CONCLUSION: The incorporation of ERE SNPs into models with known predictors might improve outcome prediction in patients with prostate cancer receiving ADT.