RESUMO
Epilepsy is one of the most common disorders in children, with an incidence rate of approximately 5%. Although an increasing number of genes have been demonstrated to be pathogenic factors in epilepsy, evidence for a potential pathogenic role of ATP6V1A remains limited. Herein, the clinical and genetic data of a 5-year-old boy who experienced seizures at 9 months of age are collected. Genetic variants are screened using whole-exome sequencing (WES), and the effects of the candidate variants are further validated at both the RNA and protein levels. WES reveals a heterozygous variant [NM_001690.4: c .1132 C>T, p.Leu378Phe] of the ATP6V1A gene. This variant is not reported in the public database, but is predicted to be deleterious by multiple software packages, and classified as a variant of unknown significance following the American College of Medical Genetics and Genomics guidelines. Quantitative PCR and western blotting further confirm its down-regulatory role in both the RNA and protein expression of ATP6V1A. This case report confirms the pathogenicity of ATP6V1A in epilepsy with solid experimental evidence, thereby expanding the phenotype spectrum of ATP6V1A variants. More importantly, we show that seizures triggered by ATP6V1A variants could be controlled by Levetiracetam, crucially rescuing the development of the patient.
Assuntos
Epilepsia , ATPases Vacuolares Próton-Translocadoras , Pré-Escolar , Humanos , Masculino , População do Leste Asiático , Epilepsia/genética , Epilepsia/patologia , Mutação , Linhagem , RNA , Convulsões , ATPases Vacuolares Próton-Translocadoras/genética , LactenteRESUMO
The Mannich reaction is commonly used to introduce N atoms into compound molecules and is thus widely applied in drug synthesis. The Mannich reaction accounts for a certain proportion of structural modifications of natural products. The introduction of Mannich bases can significantly improve the activity, hydrophilicity, and medicinal properties of compounds; therefore, the Mannich reaction is widely used for the structural modification of natural products. In this paper, the application of the Mannich reaction to the structural modification of natural products is reviewed, providing a method for the structural modification of natural products.
Assuntos
Produtos Biológicos , Produtos Biológicos/farmacologia , Bases de Mannich/químicaRESUMO
Dietary consumption of contaminated vegetables is the main route of human exposure to polycyclic aromatic hydrocarbons (PAHs). However, there is a lack of research on PAHs in vegetables from northwest China. In this study, the concentrations, sources, and risk assessment of PAHs in the soil and vegetables of Urumqi, an urbanized city in Xinjiang, China, were investigated. The total concentrations of 16 PAHs in soil and vegetable samples ranged 10.58-77.20 and 93.7-1071.8 ng/g, with average values of 2.86 and 242.76 ng/g, respectively. Among vegetable samples, the concentrations were in the order: leafy vegetables (299.08 ng/g) > fruits (192.65 ng/g) > vegetable roots (152.05 ng/g). The source apportionment of PAHs was identified using positive matrix factorization. The primary sources of PAHs in soil samples are oil spills, traffic emissions, coal combustion, and coke combustion. The main sources of PAHs in vegetable samples are oil spills and burning of grass, wood, coal, and coke. In soil samples, the ecological risk caused by PAHs is at a safe level, and the incremental lifetime cancer risks (ILCRs) of ingestion exposure exceed 1.0 × 10-6, which will pose potential risks to human body. The ILCRs of vegetable samples revealed that all groups had potential risks from onion and cabbage consumption (ILCRs > 1.0 × 10-6). In particular, adult women had a higher risk of cancer (ILCRs > 1.0 × 10-4). These results emphasize the importance of combating PAHs pollution in vegetable bases.
Assuntos
Coque , Neoplasias , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Adulto , Feminino , Humanos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Verduras , Monitoramento Ambiental/métodos , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Medição de Risco , Carvão Mineral/análise , Solo , ChinaRESUMO
In this study, an anaerobic-aerobic coupling system under intermittent electrical stimulation was used to improve the biodegradation of synthetic wastewater containing fluoroquinolones (FQs). The effect of electrical stimulation on FQ removal performance is more pronounced with appropriate voltage and hydraulic retention time. In addition, the combination of anaerobic-anodic and aerobic-cathodic chambers is more conducive to improving the removal efficiency of FQs. Under 0.9 V, the removal efficiencies of ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin were significantly improved in the anaerobic-anodic and aerobic-cathodic system. The contribution of the anaerobic/aerobic anodic chambers to FQ removal was greater than that of the anaerobic/aerobic cathodic chambers. Electrical stimulation selectively enriched electroactive bacteria related to biodegradation (Desulfovibrio and Terrimonas), antibiotic-resistant bacteria (Atopobium and Neochlamydia), and nitrifying bacteria (SM1A02 and Reyranella). This study indicated the potential effectiveness of intermittent electrical stimulation in treating fluoroquinolone-containing wastewater in a biofilm reactor. However, electrical stimulation led to an increase in mobile genetic elements , induced horizontal gene transfer and enriched resistant bacteria, which accelerated the spread of antibiotic-resistant genes (ARGs) in the system, indicating that the diffusion of ARGs remains a challenge.
Assuntos
Antibacterianos , Fluoroquinolonas , Antibacterianos/farmacologia , Fluoroquinolonas/farmacologia , Fluoroquinolonas/análise , Fluoroquinolonas/metabolismo , Águas Residuárias , Bactérias/genética , Bactérias/metabolismo , Estimulação Elétrica , Genes BacterianosRESUMO
Diclofenac, ibuprofen, and carbamazepine are frequently detected in the environment, where they pose a threat to organisms and ecosystems. We developed anaerobic-aerobic coupled upflow bioelectrochemical reactors (AO-UBERs) with different voltages, hydraulic retention times (HRTs), and types of electrode conversion, and evaluated the ability of the AO-UBERs to remove the three pharmaceuticals. This study showed that when a voltage of 0.6 V was applied, the removal rate of ibuprofen was slightly higher in the system with aerobic cathodic and anaerobic anodic chambers (60.2 ± 11.0%) with HRT of 48 h than in the control systems, and the removal efficiency reached stability faster. Diclofenac removal was 100% in the 1.2 V system with aerobic anodic and anaerobic cathodic chambers, which was greater than in the control system (65.5 ± 2.0%). The contribution of the aerobic cathodic-anodic chambers to the removal of ibuprofen and diclofenac was higher than that of the anaerobic cathodic-anodic chambers. Electrical stimulation barely facilitated the attenuation of carbamazepine. Furthermore, biodegradation-related species (Methyloversatilis, SM1A02, Sporomusa, and Terrimicrobium) were enriched in the AO-UBERs, enhancing pharmaceutical removal. The current study sheds fresh light on the interactions of bacterial populations with the removal of pharmaceuticals in a coupled system.
Assuntos
Eliminação de Resíduos Líquidos , Poluentes Químicos da Água , Reatores Biológicos/microbiologia , Anaerobiose , Diclofenaco , Ibuprofeno , Poluentes Químicos da Água/análise , Ecossistema , Carbamazepina , Preparações FarmacêuticasRESUMO
OBJECTIVES: Air temperature has been considered a modifiable and contributable variable in COVID-19 transmission. Implementation of non-pharmaceutical interventions (NPIs) has also made an impact on COVID-19 transmission, changing the transmission pattern to intrahousehold transmission under stringent containment measures. Therefore, it is necessary to re-estimate the influence of air temperature on COVID-19 transmission while excluding the influence of NPIs. DESIGN, SETTING AND PARTICIPANTS: This study is a data-based comprehensive modelling analysis. A stochastic epidemiological model, the ScEIQR model (contactable susceptible-exposed-infected-quarantined-removed), was established to evaluate the influence of air temperature and containment measures on the intrahousehold spread of COVID-19. Epidemic data on COVID-19, including daily confirmed cases, number of close contacts, etc, were collected from the National Health Commission of China. OUTCOME MEASURES: The model was fitted using the Metropolis-Hastings algorithm with a cost function based on the least squares method. The LOESS (locally weighted scatterplot smoothing) regression function was used to assess the relationship between air temperature and rate of COVID-19 transmission within the ScEIQR model. RESULTS: The ScEIQR model indicated that the optimal temperature for spread of COVID-19 peaked at 10â (50â), ranging from 5â to 14â (41â-57.2â). In the fitted model, the fitted intrahousehold transmission rate (ß') of COVID-19 was 10.22 (IQR 8.47-12.35) across mainland China. The association between air temperature and ß' of COVID-19 suggests that COVID-19 might be seasonal. Our model also validated the effectiveness of NPIs, demonstrating that diminishing contactable susceptibility (Sc) and avoiding delay in diagnosis and hospitalisation (η) were more effective than contact tracing (κ and ρ). CONCLUSIONS: We constructed a novel epidemic model to estimate the effect of air temperature on COVID-19 transmission beyond implementation of NPIs, which can inform public health strategy and predict the transmission of COVID-19.
Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Busca de Comunicante/métodos , Humanos , Quarentena , TemperaturaRESUMO
The findings and recommendations of the 2019 consensus conference in organ donation, held in Kunming, China, are here reported. The main objective of the conference was to gather relevant information from experts involved in the field. The data and opinions provided allowed to propose a series of recommendations for "One Belt & One Road Countries" on how to achieve self-sufficiency in organ donation. Leadership in organ donation should be results-oriented and goal-driven based on the principles of excellence, empowerment, and engagement, providing the means, resources, and strategies necessary to reach the goal in earnest. Management includes good governance and transparency of a national registry of patients in the waiting list, donors, transplants, transplant teams, quality, and safety programs with continuous educational training of health care professionals. Mandatory monitoring, auditing and evaluation of quality must be incorporated into donation practices as relevant points in innovation, as well as the adoption of already established and novel processes and technologies. Achievement of self-sufficiency in organ donation is a crucial step to fight against transplant tourism and to prevent organ trafficking. Based on recommendations arising from the conference, each country could review and develop individualized action plans adjusted to its own circumstances and reality.
Assuntos
Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Humanos , Liderança , Doadores de Tecidos , Listas de EsperaRESUMO
BACKGROUND: Injuries are of growing public health concern in China, and the trends of urban-rural injury mortality disparity for the last decade are still being explored. This study aims to analyze trends in injury mortality disparity between urban and rural areas of China by region, sex, and age from 2010 to 2016. METHODS: Using data from the Disease Surveillance Points system (DSPs) collected by the Chinese Center for Disease Control and Prevention (CDC) from 2010 to 2016, injury age-standardized mortality rates (ASMRs) and rate ratios (RRs) were calculated for different groups. Chi-square tests were used to compare differences in rates between urban and rural residents. The time trends of injury ASMRs were assessed via the annual percentage change (APC), and RRs were used to analyze urban-rural mortality disparity. RESULTS: The crude injury mortality rate of rural areas was 1.5 times higher than that of urban areas. The urban-rural RR of injury ASMR decreased from 1.8 to 1.5 (APC = 5.0%) over time, from 2.0 to 1.7 (APC = 4.7%) for eastern regions, from 1.9 to 1.5 (APC = 5.4%) and from 1.6 to 1.3 (APC = 4.5%) among males and females, respectively. Further decreases were from 2.0 to 1.4 (APC = 7.8%), from 1.9 to 1.6 (APC = 6.4%), and from 1.8 to 1.2 (APC = 5.7%) in the 5-14, 45-64, and 65+ year age groups, respectively. The urban-rural RRs of ASMRs for fall, drowning and suicide decreased from 1.3 to 1.2 (APC = - 3.0%), from 2.3 to 1.6 (APC = - 13.8%) and from 2.1 to 1.6 (APC = - 9.9%,), respectively. CONCLUSIONS: The urban-rural injury mortality disparity was large, but showed a significant decreasing trend in China. Residents of eastern regions, males/females, 5-14/45+ year age groups in the urban-rural injury mortality disparity all decreased gradually during the investigated period.
Assuntos
População Rural/tendências , População Urbana/tendências , Ferimentos e Lesões/mortalidade , Acidentes por Quedas/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , China/epidemiologia , Afogamento/mortalidade , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Suicídio/tendências , Estados Unidos , Ferimentos e Lesões/epidemiologia , Adulto JovemRESUMO
Early Infantile Epileptic Encephalopathy (EIEE) presents shortly after birth with frequent, severe seizures and progressive disturbance of cerebral function. This study was to investigate a cohort of Chinese children with unexplained EIEE, infants with previous genetic diagnoses, causative brain malformations, or inborn errors of metabolism were excluded. We used targeted next-generation sequencing to identify potential pathogenic variants of 308 genes in 68 Han Chinese patients with unexplained EIEE. A filter process was performed to prioritize rare variants of potential functional significance. In all cases where parental testing was accessible, Sanger sequencing confirmed the variants and determined the parental origin. In 15% of patients (n = 10/68), we identified nine de novo pathogenic variants, and one assumed de novo pathogenic variant in the following genes: CDKL5 (n = 2), STXBP1 (n = 2), SCN1A (n = 3), KCNQ2 (n = 2), SCN8A (n = 1), four of the variants are novel variants. In 4% patients (n = 3/68), we identified three likely pathogenic variants; two assumed de novo and one X-linked in the following genes: SCN1A (n = 2) and ARX (n = 1), two of these variants are novel. Variants were assumed de novo when parental testing was not available. Our findings were first reported in Han Chinese patients with unexplained EIEE, enriching the EIEE mutation spectrum bank.
Assuntos
Povo Asiático , Espasmos Infantis/epidemiologia , Fatores Etários , Eletroencefalografia , Feminino , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Fenótipo , Vigilância da População , Fatores de Risco , Espasmos Infantis/diagnóstico , Espasmos Infantis/genética , Tomografia Computadorizada por Raios XRESUMO
The aim of this study was to investigate the use of contrast-enhanced ultrasound (CEUS) for the detection of splenic artery steal syndrome (SASS) after orthotopic liver transplantation (OLT). Two hundred forty-seven patients underwent OLT. Blood tests and color Doppler flow imaging (CDFI) were performed at various time points after the operation. CEUS and celiac angiography were used for patients suspected of having SASS. If the diagnosis of SASS was confirmed, splenic artery embolization was performed to enhance hepatic artery flow. CEUS and angiography were performed for the assessment of postinterventional clinical outcomes. Three of the 247 patients died postoperatively, and 8 patients were suspected of having SASS because of elevated liver enzyme levels and slim or undetectable hepatic artery blood signals by CDFI at various points after the operation. In these 8 patients, CEUS showed a delayed and weak contrast-enhanced blood signal in the hepatic artery associated with a rapid and intense enhancement of the portal vein blood. No narrowing of the hyperintense signal was observed in the hepatic artery by CEUS. The 8 diagnoses of SASS were proven by celiac angiography, which showed delayed perfusion of the hepatic artery and rapid filling of the splenic artery. Immediately after the interventional procedure, CEUS demonstrated a significantly enlarged hyperintense blood signal in the hepatic artery. In conclusion, approximately 3.27% of SASS cases occur after OLT. SASS can be identified as a sluggish and weak hyperintense blood signal in the hepatic artery without the narrowing and interruption of the hypointense signal in CEUS imaging. CEUS is an effective imaging modality for the detection of SASS after OLT.
Assuntos
Meios de Contraste/farmacologia , Transplante de Fígado/métodos , Complicações Pós-Operatórias/diagnóstico por imagem , Artéria Esplênica/diagnóstico por imagem , Ultrassonografia/métodos , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Estudos Retrospectivos , Esplenopatias/diagnóstico por imagem , Esplenopatias/etiologia , Síndrome , Fatores de Tempo , Ultrassonografia Doppler/métodosRESUMO
OBJECTIVE: To assess the value of the model for end-stage liver disease (MELD) in predicting the early-stage outcome of liver transplantation in patients with end-stage liver disease. METHODS: The MELD scores of 87 liver transplantation recipients with end-stage liver disease were calculated, and their early-stage complications and mortality were analyzed. RESULTS: The incidence of severe complications was 20.7%; in these recipients, with the 28-day and 3-month survival rates of 89.7%; and 88.5%;, respectively. The mean MELD scores showed significant differences between the complication-free group and survival group (14.6 vs 12.9, P<0.05), and also between the complication group and death group (21.6 vs 29.4, P<0.05). Compared to patients with MELD no greater than 15, patients with MELD between 16 and 24 showed significantly increased complication rate but had comparable survival rate (P>0.05); but in patients with MELD no less than 25, the survival rate was significantly decreased with also increased complication rate. CONCLUSIONS: A higher MELD score before liver transplantation is associated with greater likeliness of early-stage complication rate and mortality. High MELD score (over 25) can be a useful index in predicting severe complications and death in patients undergoing liver transplantation.