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BACKGROUND: Kawasaki disease is a pediatric acute systemic vasculitis that specifically involves the coronary arteries. Timely initiation of immunoglobulin plus aspirin is necessary for diminishing the incidence of coronary artery abnormalities (CAAs). The optimal dose of aspirin, however, remains controversial. The trial aims to evaluate if low-dose aspirin is noninferior to moderate-dose in reducing the risk of CAAs during the initial treatment of Kawasaki disease. METHODS: This is a multi-center, prospective, randomized, open-label, blinded endpoint, noninferiority trial to be conducted in China. The planned study duration is from 2023 to 2026. Data will be analyzed according to intention-to-treat principles. Participants are children and adolescents under the age of 18 with Kawasaki disease, recruited from the inpatient units. A sample size of 1,346 participants will provide 80% power with a one-sided significance level of 0.025. Qualifying children will be randomized (1:1) to receive either intravenous immunoglobulin (2 g/kg) plus oral moderate-dose aspirin (30-50 mg·kg-1·d-1) until the patient is afebrile for at least 48 hours, or immunoglobulin plus low-dose aspirin (3-5 mg·kg-1·d-1) as initial treatment. The primary outcome will be the occurrence of CAAs at 8 weeks after immunoglobulin infusion. Independent blinded pediatric cardiologists will assess the primary endpoint using echocardiography. CONCLUSIONS: There is a shortage of consensus on the dose of aspirin therapy for Kawasaki disease due to the lack of evidence. The results of our randomized trial will provide more concrete evidence for the efficacy and adverse events of low- or moderate-dose aspirin in the acute phase of Kawasaki disease. TRIAL REGISTRATION: www.chictr.org.cn: ChiCTR2300072686.
Assuntos
Aspirina , Doença da Artéria Coronariana , Imunoglobulinas Intravenosas , Síndrome de Linfonodos Mucocutâneos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Aspirina/administração & dosagem , Aspirina/uso terapêutico , China/epidemiologia , Doença da Artéria Coronariana/prevenção & controle , Doença da Artéria Coronariana/etiologia , Vasos Coronários/diagnóstico por imagem , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Estudos de Equivalência como Asunto , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/complicações , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Wastewater treatment plants (WWTPs) have a certain removal capacity for polycyclic aromatic hydrocarbons (PAHs) and their derivatives, but some of them are discharged with effluent into the environment, which can affect the environment. Therefore, to understand the presence, sources, and potential risks of PAHs and their derivatives in WWTPs. Sixteen PAHs, three chlorinated polycyclic aromatic hydrocarbons (ClPAHs), three oxidized polycyclic aromatic hydrocarbons (OPAHs), and three methylated polycyclic aromatic hydrocarbons (MPAHs) were detected in the influent and effluent water of three WWTPs in China. The average concentrations of their influent ∑PAHs, ∑ClPAHs, ∑OPAHs, and ∑MPAHs ranged from 2682.50 to 2774.53 ng/L, 553.26-906.28 ng/L, 415.40-731.56 ng/L, and 534.04-969.83 ng/L, respectively, and the effluent concentrations ranged from 823.28 to 993.37 ng/L, 269.43-489.94 ng/L, 285.93-463.55 ng/L, and 376.25-512.34 ng/L, respectively. The growth of heat transport and industrial energy consumption in the region has a significant impact on the level of PAHs in WWTPs. According to the calculated removal efficiencies of PAHs and their derivatives in the three WWTPs (A, B, and C), the removal rates of PAHs and their derivatives were 69-72%, 62-71%, and 68-73%, respectively, and for the substituted polycyclic aromatic hydrocarbons (SPAHs), the removal rates were 41-49%, 31-40%, and 33-39%, respectively; moreover, the removal rates of PAHs were greater than those of SPAHs in the WWTPs. The results obtained via the ratio method indicated that the main sources of PAHs in the influent of WWTPs were the combustion of coal and biomass, and petroleum contamination was the secondary source. In risk evaluation, there were 5 compounds for which the risk quotient was considered high ecological risk. During chronic disease evaluation, there were 11 compounds with a risk quotient considered to indicate high risk. PAHs and SPAHs with high relative molecular masses in the effluent of WWTPs pose more serious environmental hazards than their PAHs counterparts.
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Hidrocarbonetos Policíclicos Aromáticos , Águas Residuárias , Poluentes Químicos da Água , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise , Medição de Risco , Águas Residuárias/química , Águas Residuárias/análise , China , Eliminação de Resíduos Líquidos , Monitoramento Ambiental , HumanosRESUMO
Objective: The objective of this experiment was to investigate the relationship between the circadian rhythm of blood pressure and left ventricular hypertrophy (LVH) in patients with hypertension. Methods: A total of 500 hypertension patients with documented circadian rhythm of blood pressure were selected for this study. The researchers collected general patient data and fasting blood samples. The following parameters were measured within subgroups of hypertensive patients: age, sex ratio, BMI, fasting blood glucose, total cholesterol, triacylglycerol, HDL-C, LDL-C, duration of hypertension, antihypertensive drug usage, and statin intake. Results: The results of the study showed that LVH hypertension had a significantly higher proportion of grade 3 hypertension compared to non-LVH hypertension (P < .001). Additionally, LVH hypertension displayed higher mean systolic blood pressure levels over a 24-hour period (P = .002), during daytime (P = .029), and during nighttime (P < .001). The 24-hour pulse pressure (P < .001) and pulse pressure index (P = 0.001) were also significantly higher in patients with LVH hypertension. Furthermore, the rate of blood pressure decline at night was significantly lower in the LVH hypertension group compared to the control group (P < .001). B-type natriuretic peptide (BNP) levels (P = .034) and left ventricular mass index (LVMI) (P < .001) were significantly higher in patients with LVH hypertension compared to non-LVH patients. Conclusions: The findings of this study suggest a close association between hypertensive LVH and the weakening or disappearance of the circadian rhythm of blood pressure. It was also observed that the level of blood pressure classification and plasma BNP levels were increased in patients with LVH hypertension.
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Hipertensão , Hipertrofia Ventricular Esquerda , Humanos , Pressão Sanguínea , Hipertensão/complicações , Anti-Hipertensivos/uso terapêutico , Ritmo CircadianoRESUMO
Electrochemical filtration can not only enrich low concentrations of pollutants but also produce reactive oxygen species to interact with toxic pollutants with the assistance of a power supply, making it an effective strategy for drinking water purification. In addition, the application of electrochemical filtration facilitates the reduction of pretreatment procedures and the use of chemicals, which has outstanding potential for maximizing process simplicity and reducing operating costs, enabling the production of safe drinking water in smaller installations. In recent years, the research on electrochemical filtration has gradually increased, but there has been a lack of attention on its application in the removal of low concentrations of pollutants from low conductivity water. In this review, membrane substrates and electrocatalysts used to improve the performance of electrochemical membranes are briefly summarized. Meanwhile, the application prospects of emerging single-atom catalysts in electrochemical filtration are also presented. Thereafter, several electrochemical advanced oxidation processes coupled with membrane filtration are described, and the related working mechanisms and their advantages and shortcomings used in drinking water purification are illustrated. Finally, the roles of electrochemical filtration in drinking water purification are presented, and the main problems and future perspectives of electrochemical filtration in the removal of low concentration pollutants are discussed.
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Água Potável , Poluentes Químicos da Água , Purificação da Água , Membranas Artificiais , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Filtração/métodosRESUMO
The Notch signaling pathway is related to endothelial dysfunction in coronary atherosclerosis. Our objective was to explore the role of Notch signaling in coronary microvascular dysfunction (CMD). CMD models were constructed by sodium laurate injection in vivo and homocysteine (Hcy) stimulation in vitro. The binding ability of Notch Intracellular Domain (NICD)/H3K9Ac/GCN5 (General Control Non-derepressible 5) to Neuregulin-1 (Nrg-1) promoter was examined by chromatin immunoprecipitation. Immunofluorescence staining was conducted to detect CD31 positive cells, NICD localization, and co-localization of NICD and GCN5. Flow cytometry and Tunel staining were conducted to identify the apoptosis. Hematoxylin and eosin staining, quantitative real-time PCR, western blot, immunohistochemical staining, co-immunoprecipitation, and double luciferase report analysis were also conducted. Notch signaling pathway-related protein levels were decreased, levels of Nrg-1 and the phosphorylation of ErbB2 and ErbB4 were enhanced in CMD models. Interference with Nrg-1 further increased the apoptosis in Hcy-induced cardiac microvascular endothelial cells (CMECs). Meanwhile, the activation of the Notch signaling pathway increased the levels of Nrg-1 and the phosphorylation of ErbB2 and ErbB4, as well as inhibited the apoptosis induced by Hcy. Furthermore, NICD and histone acetyltransferase enzyme GCN5 could regulate Nrg-1 promoter activity by affecting the expression of acetylation-modified protein H3K9Ac. In addition, NICD also interacted with GCN5. In vivo results also confirmed that the activation of the Notch signal alleviated CMD. Notch signaling pathway regulates Nrg-1 level through synergistic interaction with GCN5, thereby mitigating CMD.
Assuntos
Células Endoteliais , Isquemia Miocárdica , Humanos , Células Endoteliais/metabolismo , Neuregulina-1/metabolismo , Neuregulina-1/farmacologia , Código das Histonas , Apoptose , Transdução de Sinais , Receptor ErbB-4/metabolismo , Isquemia Miocárdica/metabolismo , Receptor Notch1RESUMO
Soil plays a vital role as a nutrient source for microflora and plants in ecosystems. The accumulation and proliferation of antibiotics resistance bacteria (ARB) and antibiotics resistance genes (ARGs) causes emerging soil contamination and pollution, posing new challenges for soil remediation, recovery, and conservation. Fertilizer application in agriculture is one of the most important sources of ARB and ARGs contamination in soils. The recent existing techniques for the remediation of soil polluted with ARB and ARGs are very limited in terms of ARB and ARGs removal in soil. Bioelectrochemical remediation using bioelectrochemical systems such as microbial fuel cells and microbial electrolysis cells are promising technologies for the removal of ARB and ARGs in soil. Herein, diverse sources of ARB and ARGs in soil have been reviewed, their effects on soil microbial diversity have been analyzed, and the causes of ARB and ARGs rapid proliferation in soil are explained. Bioelectrochemical systems used for the remediation of soil contaminated with ARB and ARGs is still in its infancy stage and presents serious disadvantage and limits, therefore it needs to be well understood and implemented. In general, merging soil contamination of ARB and ARGs is an increasing concern threatening the soil ecosystem while the remediation technologies are still challenging. Efforts need to be made to develop new, effective, and efficient technologies for soil remediation and conservation to tackle the spread of ARB and ARGs and overcome the new challenges posed by ARB and ARGs contamination in soil.
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Antibacterianos , Solo , Antibacterianos/farmacologia , Genes Bacterianos , Bactérias/genética , Ecossistema , Antagonistas de Receptores de Angiotensina/farmacologia , Resistência Microbiana a Medicamentos/genética , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Microbiologia do SoloRESUMO
BACKGROUND: Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are pivotal regulators involved in the pathogenic mechanism of multiple coronaviruses. Porcine deltacoronavirus (PDCoV) has evolved multiple strategies to escape the innate immune response of host cells, but whether ncRNAs are involved in this process during PDCoV infection is still unknown. RESULTS: In this study, the expression profiles of miRNAs, lncRNAs and mRNAs in IPEC-J2 cells infected with PDCoV at 0, 12 and 24 hours postinfection (hpi) were identified through small RNA and RNA sequencing. The differentially expressed miRNAs (DEmiRNAs), lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were screened from the comparison group of IPEC-J2 cells at 0 and 12 hpi as well as the comparison group of IPEC-J2 cells at 12 and 24 hpi. The target genes of these DEncRNAs were predicted. The bioinformatics analysis of the target genes revealed multiple significantly enriched functions and pathways. Among them, the genes that were associated with innate immunity were specifically screened. The expression of innate immunity-related ncRNAs and mRNAs was validated by RT-qPCR. Competing endogenous RNA (ceRNA) regulatory networks among innate immunity-related ncRNAs and their target mRNAs were established. Moreover, we found that the replication of PDCoV was significantly inhibited by two innate immunity-related miRNAs, ssc-miR-30c-3p and ssc-miR-374b-3p, in IPEC-J2 cells. CONCLUSIONS: This study provides a data platform to conduct studies of the pathogenic mechanism of PDCoV from a new perspective and will be helpful for further elucidation of the functional role of ncRNAs involved in PDCoV escaping the innate immune response.
Assuntos
MicroRNAs , RNA Longo não Codificante , Animais , Imunidade Inata/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA não Traduzido , SuínosRESUMO
The objective of this study is to accomplish a systematic review and meta-analysis of all randomized controlled trials that dissected the influence of tocotrienol supplementation on various anthropometric and cardiometabolic indices in all individuals, irrespective of health condition. This research was carried out in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. 17 eligible articles were included in the final quantitative analysis. Current study revealed that tocotrienol consumption was not associated with CRP, WC, MDA, BMI, IL-6, HbA1C, ALT, AST, creatinine TNF-α, FPG, BW, DBP, and SBP. We did observe an overall increase in BW (SMD: 0.063 kg, 95% CI: -0.200, 0.327, p = 0.637) and DBP (SMD: 0.249 mmHg, 95% CI: 0.053, 0.446, p = 0.013). In addition, a significant reduction in SBP was observed (SMD: -0.616 mmHg, 95% CI: -1.123, -0.110, p = 0.017). In summary, our meta-analysis revealed that tocotrienol consumption was associated with increase in BW and DBP and decrease in SBP. Significant associations were not observed for other outcomes.
Assuntos
Hipertensão , Tocotrienóis , Biomarcadores , Pressão Sanguínea , Suplementos Nutricionais , Glucose , Humanos , Inflamação , Fígado , Obesidade/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tocotrienóis/farmacologiaRESUMO
The combination of antibiotics and heavy metals (HMs) increases the toxicity range of influence and requires additional research attention. This article analyzed the toxicity mechanisms and damage of combined pollution. Cross-resistance, co-resistance, and co-regulation are the primary toxicity mechanisms. Combined pollution increases antibiotic resistance genes (ARGs), increases bacterial resistance, and promotes the horizontal transfer of ARGs, affecting the types and distribution of microorganisms. The hazard of combined pollution varies with concentration and composition. The physicochemical and biological technologies for eliminating combined pollution are primarily elaborated. Adsorption, photocatalytic degradation, and microbial treatment show high removal rates and good recyclability, indicating good application potential. This review provides a basis and reference for the further study the elimination of combined antibiotic and HM pollution.
Assuntos
Metais Pesados , Solo , Animais , Antibacterianos/análise , Genes Bacterianos , Gado , Metais Pesados/análise , Solo/química , ÁguaRESUMO
Biochar, carbonaceous material produced from biomass pyrolysis, has been demonstrated to have electron transfer property (associated with redox active groups and multi condensed aromatic moiety), and to be also involved in biogeochemical redox reactions. In this study, the enhanced removal of Cr(VI) by Shewanella oneidensis MR-1(MR-1) in the presence of biochars with different pyrolysis temperatures (300 to 800 °C) was investigated to understand how biochar interacts with Cr(VI) reducing bacteria under anaerobic condition. The promotion effects of biochar (as high as 1.07~1.47 fold) were discovered in this process, of which the synergistic effect of BMBC700(ball milled biochar) and BMBC800 with MR-1 was noticeable, in contrast, the synergistic effect of BMBCs (300-600 °C) with MR-1 was not recognized. The more enhanced removal effect was observed with the increase of BMBC dosage for BMBC700+MR-1 group. The conductivity and conjugated O-containing functional groups of BMBC700 particles themselves has been proposed to become a dominant factor for the synergistic action with this strain. And, the smallest negative Zeta potential of BMBC700 and BMBC800 is thought to favor decreasing the distance from microbe than other BMBCs. The results are expected to provide some technical considerations and scientific insight for the optimization of bioreduction by useful microbes combining with biochar composites to be newly developed.
Assuntos
Elétrons , Shewanella , Carvão Vegetal , CromoRESUMO
Soil is an essential part of our ecosystem and plays a crucial role as a nutrient source, provides habitat for plants and other organisms. Overuse of antibiotics has accelerated the development and dissemination of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). ARB and ARGs are recognized as emerging environmental contaminants causing soil pollution and serious risks to public health. ARB and ARGs are discharged into soils through several pathways. Application of manure in agriculture is one of the primary sources of ARB and ARGs dissemination in the soil. Different sources of contamination by ARB and ARGs were reviewed and analyzed as well as dissemination mechanisms in the soil. The effects of ARB and ARGs on soil bacterial community were evaluated. Furthermore, the impact of different sources of manure on soil microbial diversity as well as the effect of antibiotics on the development of ARB and ARGs in soils was analyzed. Human health risk assessments associated with the spreading of ARB and ARGs in soils were investigated. Finally, recommendations and mitigation strategies were proposed.
Assuntos
Antagonistas de Receptores de Angiotensina , Solo , Inibidores da Enzima Conversora de Angiotensina , Antibacterianos/toxicidade , Bactérias/genética , Resistência Microbiana a Medicamentos/genética , Ecossistema , Genes Bacterianos , Humanos , Microbiologia do SoloRESUMO
Antibiotic wastewater presents serious challenges in water treatment. Metal-organic frameworks (MOFs) have received significant attention as promising precursors and sacrificial templates in the preparation of porous carbon-supported catalysts. Herein, we investigated the sulfamethoxazole (SMX) degradation and electrochemical performance of microbial fuel cells (MFCs) that applied as-prepared Ni-MOF-74 and Ni-N-C (Ni-MOF-74 underwent pyrolysis treatment at different temperatures) as air-cathode catalyst. Firstly, the electrocatalytic activity towards oxygen reduction reaction (ORR) of the catalyst was investigated by rotating disk electrode. The results showed that electron transfer number for Ni-MOF-74 was 2.12, while that of 800Ni-N-C was 3.44, which was close to four-electron reduction. Applying Ni-MOF-74 in MFCs, a maximum power density of 446 mW/m2 was obtained, which was close to that of 800Ni-N-C. Besides, using Ni-MOF-74 as cathode catalyst, a chemical oxygen demand removal rate of about 84% was obtained, and the degradation rate of 10 mg/L SMX was 61%. The degradation rate decreased with increasing antibiotic concentration, but the average degradation efficiency increased stepwise. Additionally, the relative abundance of resistant gene sul1 in the reactors of the new catalytic material was about 62% lower than that of sul1 in the control (Pt/C) reactors, and the relative abundance of sul2 was about 73% lower. Moreover, cost assessments related to the catalyst performance are presented. The findings of this study demonstrated that Ni-MOF-74 could be considered as a two-electron transfer ORR catalyst, and offers a promising technique for preparation of Ni-N-C for use as four-electron transfer ORR catalysts. In comparison, Ni-MOF-74 could be a promising ORR catalyst of MFCs for antibiotic degradation.
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Fontes de Energia Bioelétrica , Antibacterianos , Resistência Microbiana a Medicamentos , Eletricidade , Eletrodos , SulfametoxazolRESUMO
Selection of appropriate fit-for-purpose in vitro and in silico models is critical for non-animal safety assessment of chemical-induced hepatoxicity. The present study evaluated the feasibility of integrating in vitro data from three-dimensionally (3D)-cultured HepaRG cells and physiologically based pharmacokinetic (PBPK) modeling to predict chemical-induced liver toxicity. A 3D organoid culture system was established using an ultralow attachment method. HepaRG cells cultured in a two-dimensional (2D) monolayer and under 3D conditions were exposed to acetaminophen (APAP) at concentrations of 0.16-20 mM. The results showed that the viability of both 3D- and 2D cultured cells was significantly decreased by APAP in a concentration-dependent manner. Furthermore, 3D cultures were more sensitive to APAP-induced mitochondrial damage than 2D cultures were, based on measurements of mitochondrial superoxide accumulation and mitochondrial membrane potential loss. PBPK simulations using nominal in vitro concentrations showed that the APAP concentration eliciting mitochondrial damage was closer to the predicted peak liver concentration in humans in 3D cultures than it was in 2D cultures. In summary, our results suggest that combining in vitro data from 3D HepaRG cultures and PBPK modeling provides a promising tool for assessment of liver injury.
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Acetaminofen/farmacocinética , Analgésicos não Narcóticos/farmacocinética , Técnicas de Cultura de Células , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Hepatócitos/efeitos dos fármacos , Modelos Biológicos , Células Cultivadas , Relação Dose-Resposta a Droga , Hepatócitos/metabolismo , HumanosRESUMO
The aim of this study was to explore how atrial natriuretic polypeptide (ANP) affects the properties and function of endothelial cells. Gene expression data GSE56976 generated at 0, 1, and 6 hours after ANP incubation in human umbilical vein endothelial cells (HUVEC) was used. Microarray data were preprocessed for differentially expressed genes (DEGs) in each time-dependent group. Next, gene ontology (GO), pathway analysis, and transcriptional regulation were performed. Co-expression clustering analysis of DEGs and functional enrichment analysis of co-expression modules were processed. RT-PCR analysis was performed to validate gene expression. DEGs were obtained and their counts were increased from 0 hours to 6 hours. No overlapping DEGs were obtained among the 3 groups. The DEGs of ANP_6hours, including TGFB2 (transforming growth factor, beta 2), LTF (lactotransferrin/lactoferrin), and ETV7 (Ets variant 7) were mainly related with cell apoptosis and immune responses. The DEGs in the network of ANP_0hour were mainly associated with epithelial ion transport processes. In addition, 3 co-expressed modules were detected. CSF2 (colony stimulating factor 2) and PF4 (platelet factor 4) of the blue module were related with cytolysis, while FXYD1 (FXYD domain containing ion transport regulator 1) and TGFB2 of the yellow module were mainly enriched in ion transport and the ovulation cycle. The expression of TGFB2 obtained by microarray analysis was consistent with that of RT-PCR. Ion transport could be affected promptly after ANP treatment, and subsequently, the cytolysis of vein endothelial cells may be promoted and endothelial permeability would be enhanced, followed by activated immune responses.
Assuntos
Apoptose , Fator Natriurético Atrial/farmacologia , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/metabolismo , Lactoferrina/genética , Proteínas Proto-Oncogênicas c-ets/genética , Fator de Crescimento Transformador beta2/genética , Células Cultivadas , Perfilação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Lactoferrina/biossíntese , Proteínas Proto-Oncogênicas c-ets/biossíntese , RNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Fator de Crescimento Transformador beta2/biossínteseRESUMO
BACKGROUND: Enterovirus 71 (EV71) outbreaks are a socioeconomic burden, especially in the western Pacific region. Results of phase 1 clinical trials suggest an EV71 vaccine has a clinically acceptable safety profile and immunogenicity. We aimed to assess the best possible dose and formulation, immunogenicity, and safety profile of this EV71 vaccine in healthy Chinese children. METHODS: This randomised, double-blind, placebo-controlled, phase 2 trial was undertaken at one site in Donghai County, Jiangsu Province, China. Eligible participants were healthy boys or girls aged 636 months. Participants were randomly assigned (1:1:1:1:1) to receive either 160 U, 320 U, or 640 U alum-adjuvant EV71 vaccine, 640 U adjuvant-free EV71 vaccine, or a placebo (containing alum adjuvant only), according to a blocked randomisation list generated by SAS 9.1. Participants and investigators were masked to the assignment. The primary endpoint was anti-EV71 neutralising antibody geometric mean titres (GMTs) at day 56, analysed according to protocol. The study is registered with ClinicalTrials.gov, number NCT01399853. FINDINGS: We randomly assigned 1200 participants, 240 (120 aged 611 months [infants] and 120 aged 1236 months [children]) of whom were assigned to each dose. 1106 participants completed the study and were included in the according-to-protocol analysis. The main reasons for dropout were withdrawal of consent and refusal to donate a blood sample. Infants who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (742·2 [95% CI 577·3954·3]), followed by those who received the 320 U formulation (497·9 [383·1647·0]). For children, those who received the 320 U formulation had the highest GMTs on day 56 (1383·2 [1037·31844·5]). Participants who received the vaccine had significantly higher GMTs than did who received placebo (p<0·0001). For the subgroup of participants who were seronegative at baseline, both infants and children who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (522·8 [403·9676·6] in infants and 708·4 [524·1957·6] in children), followed by those who received the 320 U adjuvant vaccine (358·2 [280·5457·5] in infants and 498·0 [383·4646·9] in children). 549 (45·8%) of 1200 participants (95 CI 42·948·6%) reported at least one injection-site or systemic adverse reaction, but the incidence of adverse reactions did not differ significantly between groups (p=0·36). The 640 U alum-adjuvant vaccine group had a significantly higher incidence of induration than did the 640 U adjuvant-free group (p=0·001). INTERPRETATION: Taking immunogenicity, safety, and production capacity into account, the 320 U alum-adjuvant formulation of the EV71 vaccine is probably the best possible formulation for phase 3 trials. FUNDING: The National Science and Technology Major Project (2011ZX10004-902) of the Chinese Ministry of Science and Technology, China's 125 National Major Infectious Disease Program (2012ZX10002-001), and Beijing Vigoo Biological.
Assuntos
Enterovirus Humano A/imunologia , Infecções por Enterovirus/prevenção & controle , Vacinas Virais/efeitos adversos , Anticorpos Antivirais/sangue , Formação de Anticorpos/efeitos dos fármacos , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Lactente , Masculino , Resultado do Tratamento , Vacinas Virais/imunologiaRESUMO
OBJECTIVE: To compare the methods of delineating the whole breast target volume based on surface marks, palpation and glandular tissue on CT images, and to explore the contouring criteria after breast-conserving surgery. METHODS: In 15 patients with breast cancer after breast-conserving surgery, the whole breast target was delineated in 3D CT simulation images each by three different methods. The target volume delineated according to anatomical marks were named CTVan, according to breast palpation named CTVpa, and according to glandular mammary tissue showing by CT images named CTVgl. The volumes of CTVan, CTVpa and CTVgl, and the degree of inclusion (DI) and conformal index (CI) between the targets were measured. RESULTS: The mean volumes of CTVan, CTVpa and CTVgl were (792.23 ± 282.25) cm(3), (618.33 ± 295.90) cm(3) and (196.83 ± 117.62) cm(3), respectively. The differences among the three methods were statistically significant (P < 0.001). The difference between CTVan and CTVpa had no statistical significance (P = 0.08), and both the differences between CTVan and CTVgl, and between CTVpa and CTVgl had statistical significance (both P < 0.001). The CI between CTVan and CTVpa (0.644 ± 0.122) was significantly larger than the CI between CTVan and CTVgl (0.264 ± 0.108), and the CI between CTVpa and CTVgl (0.328 ± 0.115)(P < 0.001). The DI of CTVan to CTVpa was 0.709 ± 0.144,DI of CTVgl to CTVan was 0.994 ± 0.005 and DI of CTVgl to CTVpa was 0.989 ± 0.008. The differences of inner, outer, upper and lower boundaries of CTVpa and CTVan were (3.35 ± 7.23) mm, (5.57 ± 13.37) mm, (1.75 ± 11.62) mm, and (11.25 ± 4.07)mm, respectively. The cranial and medial boundaries had a negative correlation with CTVpa (P < 0.05 for all). CONCLUSIONS: The differences among the three methods in the delineation of whole breast target volume are statistically significant. The target volume delineated according to the glandular mammary tissue displayed by CT scan is significantly smaller than that by the other two methods. Combination of breast palpation and anatomical marks may be helpful in delineating the whole breast target volume is relatively reasonable at present.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mama/patologia , Mastectomia Segmentar , Feminino , Humanos , Imageamento Tridimensional , Palpação , Tomografia Computadorizada por Raios XRESUMO
With an increase of diverse contaminants in the environment, particularly antibiotics, the maintenance and propagation of antibiotic resistance genes (ARGs) are promoted by co-selection mechanisms. ARGs are difficult to degrade, cause long-lasting pollution, and are widely transmitted in aquatic environments. Biochar is frequently used to remove various pollutants during environmental remediation. Thus, this review provides a thorough analysis of the current state of ARGs in the aquatic environment as well as their removal by using biochar. This article summarizes the research and application of biochar and modified biochar to remove ARGs in aquatic environments, in order to refine the following contents: 1) fill gaps in the research on the various ARG behaviors mediated by biochar and some influence factors, 2) further investigate the mechanisms involved in effects of biochar on extracellular ARGs (eARGs) and intracellular ARGs (iARGs) in aquatic environments, including direct and the indirect effects, 3) describe the propagation process and resistance mechanisms of ARGs, 4) propose the challenges and prospects of feasibility of application and subsequent treatment in actual aquatic environment. Here we highlight the most recent research on the use of biochar to remove ARGs from aquatic environments and suggest future directions for optimization, as well as current perspectives to guide future studies on the removal of ARGs from aquatic environments.
Assuntos
Carvão Vegetal , Resistência Microbiana a Medicamentos , Resistência Microbiana a Medicamentos/genética , Recuperação e Remediação Ambiental/métodos , Antibacterianos , Poluentes Químicos da ÁguaRESUMO
Previous studies reported microplastics (MPs), antibiotics, and antibiotic resistance genes (ARGs) in wastewater treatment plants (WWTPs). There is still a lack of research progress on the origin, fate, impact and hazards of MPs and ARGs in WWTPs. This paper fills a gap in this regard. In our search, we used "microplastics", "antibiotic resistance genes", and "wastewater treatment plant" as topic terms in Web of Science, checking the returned results for relevance by examining paper titles and abstracts. This study mainly explores the following points: (1) the origins and fate of MPs, antibiotics and ARGs in WWTPs; (2) the mechanisms of action of MPs, antibiotics and ARGs in sludge biochemical pools; (3) the impacts of MPs in WWTPs and the spread of ARGs; (4) and the harm inflicted by MPs and ARGs on the environment and human body. Contaminants in sewage sludge such as MPs, ARGs, and antibiotic-resistant bacteria enter the soil and water. Contaminants can travel through the food chain and thus reach humans, leading to increased illness, hospitalization, and even mortality. This study will enhance our understanding of the mechanisms of action among MPs, antibiotics, ARGs, and the harm they inflict on the human body.
Assuntos
Antibacterianos , Resistência Microbiana a Medicamentos , Microplásticos , Águas Residuárias , Microplásticos/toxicidade , Águas Residuárias/microbiologia , Antibacterianos/farmacologia , Antibacterianos/efeitos adversos , Resistência Microbiana a Medicamentos/genética , Humanos , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Esgotos/microbiologia , Genes Bacterianos , Eliminação de Resíduos Líquidos , Purificação da Água , Monitoramento Ambiental , Bactérias/genética , Bactérias/efeitos dos fármacos , Farmacorresistência Bacteriana/genéticaRESUMO
In recent years, owing to the overuse and improper handling of antibiotics, soil antibiotic pollution has become increasingly serious and an environmental issue of global concern. It affects the quality and ecological balance of the soil and allows the spread of antibiotic resistance genes (ARGs), which threatens the health of all people. As a promising soil remediation technology, bioelectrochemical systems (BES) are superior to traditional technologies because of their simple operation, self-sustaining operation, easy control characteristics, and use of the metabolic processes of microorganisms and electrochemical redox reactions. Moreover, they effectively remediate antibiotic contaminants in soil. This review explores the application of BES remediation mechanisms in the treatment of antibiotic contamination in soil in detail. The advantages of BES restoration are highlighted, including the effective removal of antibiotics from the soil and the prevention of the spread of ARGs. Additionally, the critical roles played by microbial communities in the remediation process and the primary parameters influencing the remediation effect of BES were clarified. This study explores several strategies to improve the BES repair efficiency, such as adjusting the reactor structure, improving the electrode materials, applying additives, and using coupling systems. Finally, this review discusses the current limitations and future development prospects, and how to improve its performance and promote its practical applications. In summary, this study aimed to provide a reference for better strategies for BES to effectively remediate soil antibiotic contamination.
Assuntos
Antibacterianos , Resistência Microbiana a Medicamentos , Microbiologia do Solo , Poluentes do Solo , Resistência Microbiana a Medicamentos/genética , Técnicas Eletroquímicas , Recuperação e Remediação Ambiental/métodos , Solo/química , Biodegradação AmbientalRESUMO
The demands of human life and industrial activities result in a significant influx of toxic contaminants into aquatic ecosystems. In particular, organic pollutants such as antibiotics and dye molecules, bacteria, and heavy metal ions are represented, posing a severe risk to the health and continued existence of living organisms. The method of removing pollutants from water bodies by utilizing the principle of the piezoelectric effect in combination with chemical catalytic processes is superior to other wastewater purification technologies because it can collect water energy, mechanical energy, etc. to achieve cleanliness and high removal efficiency. Herein, we briefly introduced the piezoelectric mechanisms and then reviewed the latest advances in the design and synthesis of piezoelectric materials, followed by a summary of applications based on the principle of piezoelectric effect to degrade pollutants in water for wastewater purification. Moreover, water purification technologies incorporating the piezoelectric effect, including piezoelectric effect-assisted membrane filtration, activation of persulfate, and battery electrocatalysis are elaborated. Finally, future challenges and research directions for the piezoelectric effect are proposed.