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1.
Artigo em Inglês | MEDLINE | ID: mdl-34603464

RESUMO

Acne vulgaris (AV) is a chronic skin disease involving inflammation of the pilosebaceous units. Propionibacterium acnes (P. acnes) hypercolonization is one pathogenic factor for AV. P. acnes that triggers interleukin-1ß (IL-1ß) by activating the pyrin domain-containing 3 protein (NLRP3) inflammasome of the NOD-like receptor family in human monocytes. Reactive oxygen species (ROS) acts as a trigger for the production of IL-8 and activates theNLRP3 inflammasome. IL-8 promotes the metastasis and multiplication of different cancerous cells, whereas keratinocyte proliferation and migration contribute to the progression of AV. A steroidal saponin called polyphyllin I (PPI) that is extracted from Paris polyphylla's rhizomes has anti-inflammatory properties. This study investigates the regulatory role of P. acnes in the secretion of IL-8 mediated by the CD36/NADPH oxidase 1 (NOX1)/ROS/NLRP3/IL-1ß pathway and the effects of PPI on the CD36/NOX1/ROS/NLRP3/IL-1ß/IL-8 pathway and human keratinocyte proliferation and migration. HaCaT cells were cultured and stimulated with 108 CFU/ml of P. acnes for 0, 6, 12, 18, 24, 30, and 36 hours. P. acnes induced IL-8 secretion from HaCaT cells via the CD36/NOX1/ROS/NLRP3/IL-1ß pathway. PPI inhibited the CD36/NLRP3/NOX1/ROS/IL-8/IL-1ß pathway and HaCaT cell proliferation and migration. PPI alleviates P. acnes-induced inflammatory responses and human keratinocyte proliferation and migration, implying a novel potential therapy for AV.

2.
ACS Nano ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606239

RESUMO

Stroke is a primary cause of death and disability worldwide, while effective and safe drugs remain to be developed for its clinical treatment. Herein, we report bioactive nanoparticle-derived multifunctional nanotherapies for ischemic stroke, which are engineered from a pharmacologically active oligosaccharide material (termed as TPCD) prepared by covalently conjugating a radical-scavenging compound (Tempol) and a hydrogen-peroxide-eliminating moiety of phenylboronic acid pinacol ester (PBAP) on ß-cyclodextrin. Of note, combined functional moieties of Tempol and PBAP on ß-cyclodextrin contribute to antioxidative and anti-inflammatory activities of TPCD. Cellularly, TPCD nanoparticles (i.e., TPCD NPs) reduced oxygen-glucose deprivation-induced overproduction of oxidative mediators, increased antioxidant enzyme expression, and suppressed microglial-mediated inflammation, thereby inhibiting neuronal apoptosis. After intravenous (i.v.) delivery, TPCD NPs could efficiently accumulate at the cerebral ischemic injury site of mice with middle cerebral artery occlusion (MCAO), showing considerable distribution in cells relevant to the pathogenesis of stroke. Therapeutically, TPCD NPs significantly decreased infarct volume and accelerated recovery of neurological function in MCAO mice. Mechanistically, efficacy of TPCD NPs is achieved by its antioxidative, anti-inflammatory, and antiapoptotic effects. Furthermore, TPCD NPs can function as a reactive oxygen species labile nanovehicle to efficiently load and triggerably release an inflammation-resolving peptide Ac2-26, giving rise to an inflammation-resolving nanotherapy (i.e., ATPCD NP). Compared to TPCD NP, ATPCD NP demonstrated notably enhanced in vivo efficacies, largely resulting from its additional inflammation-resolving activity. Consequently, TPCD NP-derived nanomedicines can be further developed as promising targeted therapies for stroke and other inflammation-associated cerebrovascular diseases.

3.
Sci Total Environ ; : 150992, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34662623

RESUMO

Although hormesis induced by heavy metals is a well-known phenomenon, the involved biological mechanisms are not fully understood. Zinc (Zn) is an essential micronutrient for wheat, an important crop contributing to food security as a main staple food; however, excessive Zn is detrimental to the growth of wheat. The aim of this study was to evaluate morphological and physiological responses of two wheat varieties exposed to a broad range of Zn concentrations (0-1000 µM) for 14 days. Hormesis was induced by Zn in both wheat varieties. Treatment with 10-100 µM Zn promoted biomass accumulation by enhancing the photosynthetic ability, the chlorophyll content and the activities of antioxidant enzymes. Increased root/shoot ratio suggested that shoot growth was severely inhibited when Zn concentration exceeded 300 µM by reducing photosynthetic ability and the content of photosynthetic pigments. Excessive Zn accumulation (Zn treatment of 300-1000 µM) in leaf and root induced membrane injuries through lipid peroxidation as malondialdehyde (MDA) content increased with increasing Zn concentration. The results show that MDA content was higher than other treatments by 16.1-151.1% and 15.0-88.3% (XN979) and 36.8-235.7% and 20.6-83.8% (BN207) in the leaves and roots under 1000 µM Zn treatment. To defend against Zn toxicity, ascorbate (AsA), glutathione (GSH), non-protein thiols (NPT) and phytochelatin (PC) content of both wheat varieties (except leaf GSH content of BN207) was increased, while, the activities of superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, and the content of soluble protein decreased by 300-1000 µM Zn. The results showed that AsA-GSH cycle and NPT and PC content of wheat seedlings play important roles in defending against Zn toxicity. This study contributes new insights into the physiological mechanisms underlying the hormetic response of wheat to Zn, which could be beneficial for optimizing plant health in changing environments and improving risk assessments.

4.
Future Microbiol ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34674547

RESUMO

Aim: The purpose of our study was to assess the differences between HIV-negative cryptococcal meningitis (CM) patients with and without autoimmune diseases. Methods: A total of 43 CM patients with autoimmune diseases and 67 without autoimmune diseases were enrolled for analysis. Results: CM patients with autoimmune diseases had higher fever, modified Rankin Scale scores, C-reactive protein and erythrocyte sedimentation rate, but had lower rates of visual and hearing symptoms, ventriculoperitoneal shunts, MRI meningeal enhancement and amphotericin B treatment, as well as lower cerebrospinal fluid pressure and fungal counts. When divided according to gender, each group had lower intracranial pressure and higher inflammation indicators. No differences in outcomes, sequelae and mortality hazard were found. Fluconazole treatment was a prognostic factor for CM without autoimmune diseases. Conclusions: Both antifungal and anti-inflammatory therapy should be considered in CM patients with autoimmune diseases.

5.
Nanomicro Lett ; 13(1): 203, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34611765

RESUMO

Metal-organic framework (MOF)-based materials with high porosity, tunable compositions, diverse structures, and versatile functionalities provide great scope for next-generation rechargeable battery applications. Herein, this review summarizes recent advances in pristine MOFs, MOF composites, MOF derivatives, and MOF composite derivatives for high-performance sodium-ion batteries, potassium-ion batteries, Zn-ion batteries, lithium-sulfur batteries, lithium-oxygen batteries, and Zn-air batteries in which the unique roles of MOFs as electrodes, separators, and even electrolyte are highlighted. Furthermore, through the discussion of MOF-based materials in each battery system, the key principles for controllable synthesis of diverse MOF-based materials and electrochemical performance improvement mechanisms are discussed in detail. Finally, the major challenges and perspectives of MOFs are also proposed for next-generation battery applications.

6.
Mol Immunol ; 140: 59-69, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34655920

RESUMO

The local immune microenvironment of the uterus plays an important role in a successful pregnancy. IP-10 (CXCL10) has been extensively studied in many immune-related diseases. However, the immune role of IP-10 in early pregnancy has not been fully recognized. This study mainly investigated the role of pro-inflammatory chemokine IP-10 in pregnancy. The levels of IP-10 and its receptor chemokine receptor 3 (CXCR3) were lower in the decidual tissues of an abortion-prone mice than in normal pregnant mice. Meantime, the expression of IP-10 and CXCR3 was higher in the decidual tissues of early pregnant women than in the endometrial tissues of non-pregnant women. IP-10 promoted the production of interleukin 17 (IL-17) and interferon gamma (IFN-γ), and also promoted the migration and differentiation of uterine decidual T cells to type 1 T helper (Th1) cells and Th17 cells. The abortion rate of early pregnant mice increased but the number of CD49b+, CD11b+, and CD3ε+ cells in the decidual tissues decreased upon treatment with anti-IP-10 antibody. Moreover, anti IP-10 antibody decreased the expression of RANTES but increased the expression of anti-inflammatory cytokines IL-6 and IL-10. A successful pregnancy requires the participation of IP-10. IP-10 participates in formation of the pro-inflammatory immune microenvironment during early pregnancy by regulating the distribution of immune cells and promoting the production of pro-inflammatory cytokines.

7.
Chem Sci ; 12(34): 11399-11405, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34667548

RESUMO

Here we report that Morita-Baylis-Hillman carbonates from diverse aldehydes and methyl vinyl ketones can be directly utilised as palladium-trimethylenemethane 1,4-carbodipole-type precursors, and both reactivity and enantioselectivity are finely regulated by adding a chiral ammonium halide as the ion-pair catalyst. The newly assembled intermediates, proposed to contain an electronically neutral π-allylpalladium halide complex and a reactive compact ion pair, efficiently undergo asymmetric [4 + 2] annulations with diverse activated alkenes or isatins, generally with high regio-, diastereo- and enantio-selectivity, and even switchable regiodivergent or diastereodivergent annulations can be well realised by tuning the substrate or catalyst assemblies. An array of control experiments, including UV/Vis absorption study and density functional theory calculations, are conducted to rationalise this new double activation mode combining a palladium complex and an ammonium halide as an ion-pair catalyst.

8.
Health Promot Chronic Dis Prev Can ; 41(10): 292-305, 2021 Oct.
Artigo em Inglês, Francês | MEDLINE | ID: mdl-34668684

RESUMO

INTRODUCTION: Having a better understanding of individual factors associated with e-cigarette initiation can help improve prevention efforts. Therefore, this study aimed to (1) identify baseline characteristics associated with e-cigarette initiation, and (2) determine whether changes in these baseline characteristics were associated with e-cigarette initiation. METHODS: This study used data from Year 6 (2017/18, baseline) and Year 7 (2018/19, follow-up) of the COMPASS study. The final sample included 12 315 students in Grades 9 to 11 who reported never having tried e-cigarettes at baseline. Students reported demographic information, other substance use, school behaviours, physical activity, sedentary behaviour, sleep, symptoms of anxiety and depression, and emotional regulation and flourishing scores. Hierarchical GEE models, stratified by gender, examined the association between (1) baseline characteristics and e-cigarette initiation at follow-up and (2) changes in baseline characteristics and e-cigarette initiation at follow-up. RESULTS: In total, 29% of students who had not yet initiated e-cigarette use reported initiating e-cigarette use at follow-up. Students in Grades 10 and 11 were less likely to initiate e-cigarette use. Other substance use, skipping school and meeting the physical activity guidelines at baseline and one-year changes to these behaviours were associated with e-cigarette initiation among both male and female students. Additionally, some differences were noted between females and males. CONCLUSION: Given that other health behaviours were associated with e-cigarette initiation, prevention approaches should target multiple health-risk behaviours to help prevent youth e-cigarette use. Additionally, school-based approaches may benefit by being implemented at the beginning of high school or in junior high school.

9.
Phys Chem Chem Phys ; 23(40): 22992-23004, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34611676

RESUMO

A self-consistent field theory formalism based on the wormlike chain model is developed to investigate the stress-strain relation for mesostructures in diblock copolymers under the influence of chain rigidity, involving the adjustable simulation cell in the non-orthogonal coordinates by means of optimization of free energy. We elucidate the effect of the chain persistency broadly spanning from the Gaussian chain to the rigid rodlike chain on the elastic response of mesophases that deviate from the initial equilibrium structures. We analytically and numerically demonstrate that our current approach in the long chain limit recovers to the Gaussian-chain-based theory. Being ascribed to the distinct conformational behaviors for flexible chains and rigid rodlike chains, the tensile and compressive stresses applied to lamellae exhibit asymmetric deformation behaviors and the shear stress applied to the initial equilibrium hexagonal cylinders results in noticeable deviations in the shape and spatial arrangement of cylindroids for various chain rigidity values. For the zero stress, in addition, our approach can be straightforwardly utilized to explore the optimal size and shape of the simulation cell in order to achieve a stress free configuration of systems.

10.
BMC Cancer ; 21(1): 1004, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496800

RESUMO

BACKGROUND: Dysregulation of long non-coding RNAs (lncRNAs) has been identified in ovarian cancer. However, the expression and biological functions of LINC00852 in ovarian cancer are not understood. METHODS: The expressions of LINC00852, miR-140-3p and AGTR1 mRNA in ovarian cancer tissues and cells were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. Gain- and loss-of-function assays were performed to explore the biological functions of LINC00852 and miR-140-3p in the progression of ovarian cancer in vitro. The bindings between LINC00852 and miR-140-3p were confirmed by luciferase reporter gene assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay. RESULTS: We found that LINC00852 expression was significantly up-regulated in ovarian cancer tissues and cells, whereas miR-140-3p expression was significantly down-regulated in ovarian cancer tissues. Functionally, LINC00852 knockdown inhibited the viability, proliferation and invasion of ovarian cancer cells, and promoted the apoptosis of ovarian cancer cells. Further investigation showed that LINC00852 interacted with miR-140-3p, and miR-140-3p overexpression suppressed the viability, proliferation and invasion of ovarian cancer cells. In addition, miR-140-3p interacted with AGTR1 and negatively regulated its level in ovarian cancer cells. Mechanistically, we found that LINC00852 acted as a ceRNA of miR-140-3p to promote AGTR1 expression and activate MEK/ERK/STAT3 pathway. Finally, LINC00852 knockdown inhibited the growth and invasion ovarian cancer in vivo. CONCLUSION: LINC00852/miR-140-3p/AGTR1 is an important pathway to promote the proliferation and invasion of ovarian cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Ovarianas/patologia , RNA Longo não Codificante/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Prognóstico , Receptor Tipo 1 de Angiotensina/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Neuropsychiatr Dis Treat ; 17: 2885-2904, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526769

RESUMO

Olanzapine effectively treats schizophrenia and bipolar I disorder (BD-I); however, its use is limited by the risk of significant weight gain and metabolic effects. OLZ/SAM, a combination of olanzapine and samidorphan, was recently approved in the United States for the treatment of adults with schizophrenia or BD-I. OLZ/SAM provides the efficacy of olanzapine while mitigating olanzapine-associated weight gain through opioid-receptor blockade. Here, we summarize OLZ/SAM clinical data characterizing pharmacokinetics, antipsychotic efficacy, weight mitigation efficacy, safety, and long-term treatment effects. In an acute exacerbation of schizophrenia, OLZ/SAM and olanzapine provided similar symptom improvements versus placebo at week 4. In stable outpatients with schizophrenia, OLZ/SAM treatment resulted in significantly less weight gain, reducing the risk for clinically significant weight gain and waist circumference increases of ≥5 cm by half, compared with olanzapine at week 24. Based on open-label extension studies, OLZ/SAM is safe and well tolerated for up to 3.5 years of treatment, while maintaining schizophrenia symptom control and stabilizing weight. The olanzapine component of OLZ/SAM was bioequivalent to branded olanzapine (Zyprexa); adjunctive OLZ/SAM had no clinically significant effects on lithium or valproate pharmacokinetics. Additionally, OLZ/SAM had no clinically relevant effect on electrocardiogram parameters in a dedicated thorough QT study. Overall, safety and tolerability findings from clinical studies with OLZ/SAM indicate a similar safety profile to that of olanzapine, with the exception of less weight gain. As OLZ/SAM contains the opioid antagonist samidorphan, it is contraindicated in patients using opioids and in those undergoing acute opioid withdrawal. Clinical trial results from more than 1600 subjects support the use of OLZ/SAM as a new treatment option for patients with schizophrenia or BD-I.

12.
Emerg Microbes Infect ; : 1-22, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34551677

RESUMO

Ceftazidime-avibactam (CAZ-AVI) shows promising activity against carbapenem-resistant Klebsiella pneumoniae (CRKP), however, CAZ-AVI resistance have emerged recently. Mutations in KPCs, porins OmpK35 and/or OmpK36, and PBPs are known to contribute to the resistance to CAZ-AVI in CRKP. To identify novel CAZ-AVI resistance mechanism, we generated 10 CAZ-AVI-resistant strains from 14 CAZ-AVI susceptible KPC-producing K. pneumoniae (KPC-Kp) strains through in vitro multipassage resistance selection using low concentrations of CAZ-AVI. Comparative genomic analysis for the original and derived mutants identified CAZ-AVI resistance-associated mutations in KPCs, PBP3 (encoded by ftsI), and LamB, an outer membrane maltoporin. CAZ-AVI susceptible KPC-Kp strains became resistant when complemented with mutated blaKPC genes. Complementation experiments also showed that a plasmid borne copy of wild-type lamB or ftsI gene reduced the MIC value of CAZ-AVI in the induced resistant strains. In addition, blaKPC expression level increased in four of the six CAZ-AVI-resistant strains without KPC mutations, indicating a probable association between increased blaKPC expression and increased resistance in these strains. In conclusion, we here identified a novel mechanism of CAZ-AVI resistance associated with mutations in porin LamB in KPC-Kp.

13.
Support Care Cancer ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550460

RESUMO

BACKGROUND AND OBJECTIVES: Outpatient parenteral antimicrobial therapy (OPAT) for infections has been in use for nearly 40 years, and although it has been found safe and efficacious, its use has been studied primarily among otherwise healthy patients. We aimed to develop and evaluate an OPAT program for patients with cancer, particularly solid tumors. METHODS: We implemented multiple quality improvement interventions between June 2018 and January 2020. We retrospectively and prospectively collected data on demographics, the completeness of infectious diseases (ID) physician consultation notes, rates of laboratory test result monitoring, ID clinic follow-up, and 30-day outcomes, including unplanned OPAT-related readmissions, OPAT-related emergency center visits, and deaths. RESULTS: Completeness of ID provider notes improved from a baseline of 77 to 100% (p < .0001) for antimicrobial recommendations, 75 to 97% (p < .0001) for follow-up recommendations, and 19 to 98% (p < .0001) for laboratory test result monitoring recommendations. Completion of laboratory tests increased from a baseline rate of 24 to 56% (p = .027). Thirty-day unplanned OPAT-related readmission, ID clinic follow-up, 30-day emergency center visit, and death rates improved without reaching statistical significance. CONCLUSIONS: Sustained efforts, multiple interventions, and multidisciplinary engagement can improve laboratory test result monitoring among solid tumor patients discharged with OPAT. Although demonstrating a decrease in unplanned readmissions through institution of a formal OPAT program among patients with solid malignancies may be more difficult compared with the general population, the program may still result in improved safety.

14.
PLoS One ; 16(9): e0258113, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34591939

RESUMO

A numerical model of the dynamic triaxial test of graded crushed stone was established based on DEM (Discrete Element Method) to study its dynamic characteristics. The influence of test conditions on simulation results was analysed through numerical simulation. A method for determining the test conditions was proposed, and the reliability of the simulation was verified. We studied the accumulation rule and failure standard of permanent deformation. We then determined the critical failure stress level. The prediction model of permanent deformation cumulative failure was then established. When the calculation time step is greater than 1E-4 s per step, the stability of the dynamic triaxial numerical test of graded crushed stone is good. The plastic deformation of the simulated specimen tends to be stable under 10,000 dynamic loading cycles. When the specimen height and diameter are greater than 20 and 10 cm, respectively, the specimen size has little influence on the simulated axial strain. The recommended specimen size is 10 cm (Ф) × 20 cm (h). The action time curve results are consistent with indoor measurement results, which proves the simulation's reliability. The critical failure stress is approximately linearly correlated with the confining pressure, and the cumulative failure equation of plastic deformation is established.

15.
Hum Vaccin Immunother ; : 1-8, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34586945

RESUMO

The mortality rate from COVID-19 appears to be higher in solid organ transplant (SOT) recipients when compared with other populations. Vaccination is a key strategy to prevent the COVID-19 pandemic. However, it is unclear how readily SOT recipients will get vaccinated against COVID-19. We conducted an internet-based survey to investigate the vaccination willingness among Chinese SOT recipients and further explore possible influencing factors. Eight hundred and thirteen respondents participated in the survey. Overall, 46 (5.7%) recipients were vaccinated against COVID-19, while 767 (94.3%) were not. Among those not vaccinated, 175 (22.8%) intended to be vaccinated, while 592 (77.2%) were categorized as vaccine-hesitant. The most common reason for vaccination hesitancy is fear of preexisting comorbidities, followed by fear of side effects and doctors' negative advice. Factors associated with vaccination willingness were as follows: with liver transplantation, the main source of information on COVID-19 vaccines was from medical doctors, scientists, and scientific journals, with at least college-level education, positive intention toward influenza vaccination during the current season, perceived importance of vaccination for SOT recipients, and having been vaccinated against influenza during the last season. Our survey indicated the necessity for SOT recipients to receive more comprehensive and accessible health education about vaccination and emphasized the critical role of transplantation physicians in promoting vaccine acceptance among SOT recipients. We hope that our survey results will help governments to better target communication in the ongoing COVID-19 vaccination campaign.

16.
PeerJ ; 9: e12114, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557356

RESUMO

Cervical cancer is one of the most common malignant tumors in women, and its morbidity and mortality are increasing year by year worldwide. Therefore, an urgent and challenging task is to identify potential biomarkers for cervical cancer. This study aims to identify the hub genes based on the GEO database and then validate their prognostic values in cervical cancer by multiple databases. By analysis, we obtained 83 co-expressed differential genes from the GEO database (GSE63514, GSE67522 and GSE39001). GO and KEGG enrichment analysis showed that these 83 co-expressed it mainly involved differential genes in DNA replication, cell division, cell cycle, etc.. The PPI network was constructed and top 10 genes with protein-protein interaction were selected. Then, we validated ten genes using some databases such as TCGA, GTEx and oncomine. Survival analysis demonstrated significant differences in CDC45, RFC4, TOP2A. Differential expression analysis showed that these genes were highly expressed in cervical cancer tissues. Furthermore, univariate and multivariate cox regression analysis indicated that CDC45 and clinical stage IV were independent prognostic factors for cervical cancer. In addition, the HPA database validated the protein expression level of CDC45 in cervical cancer. Further studies investigated the relationship between CDC45 and tumor-infiltrating immune cells via CIBERSORT. Finally, gene set enrichment analysis (GSEA) showed CDC45 related genes were mainly enriched in cell cycle, chromosome, catalytic activity acting on DNA, etc. These results suggested CDC45 may be a potential biomarker associated with the prognosis of cervical cancer.

17.
Chemosphere ; 287(Pt 2): 132065, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34496338

RESUMO

Human beings are extensively and concurrently exposed to multiple volatile organic compounds (VOCs, including some Class I human carcinogens), which may induce oxidative stress in human body. Data on urinary metabolites of VOCs (mVOCs) among young children are limited. No studies have examined their inter-day variability of mVOCs and their associations with oxidative stress biomarkers (OSBs) using repeated urine samples from children. In this study, we measured twenty one mVOCs and three OSBs [8-hydroxy-2'-deoxyguanosine (8-OHdG; for DNA), 8-hydroxyguanosine (8-OHG; for RNA], and 4-hydroxy nonenal mercapturic acid (HNEMA; for lipid)] in 390 urine samples of 130 children (three samples on three consecutive days provided by each participant) aged 0-7 years from September 2018 to January 2019 in Shenzhen, south China, and Wuhan, central China. HPMMA (3-hydroxypropyl-1-methyl mercapturic acid/N-Acetyl-S-(3-hydroxypropyl-1-methyl)-l-cysteine), 3HPMA (3-hydroxypropyl mercapturic acid/N-Acetyl-S-(3-hydroxypropyl)-l-cysteine), and ATCA (2-aminothiazoline-4-carboxylic acid) had higher specific gravity-adjusted median concentrations (1 383, 286, and 273 µg/L, respectively) than the others. Intraclass correlation coefficients of mVOCs ranged from 0.29 to 0.71. After false-discovery rate (FDR, defined as FDR q-value < 0.05) adjustment, linear mixed-effects models revealed that 14 mVOCs were positively associated with 8-OHdG (ß range: 0.09-0.37), 11 mVOCs were positively associated with 8-OHG (ß range: 0.08-0.30), and 11 mVOCs were positively associated with HNEMA (ß range: 0.21-0.70) in urine. Considering the weight of the mVOC index accounted for the associations, based on the weighted quantile sum regression model, parent compounds of DHBMA (3,4-dihydroxybutyl mercapturic acid/N-Acetyl-S-(3,4-dihydroxybutyl)-l-cysteine) and t,t-MA (trans,trans-muconic acid) should be listed as priority VOCs for management to mitigate health risks. For the first time, this study characterized the inter-day variability of urinary mVOCs and their associations with selected OSBs (8-OHdG, 8-OHG, and NHEMA) in young, healthy Chinese children.

18.
Brain Behav ; : e2350, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34520632

RESUMO

BACKGROUND: To analyze the application of neurally adjusted ventilatory assist in ventilator weaning of infants. METHODS: A total of 25 infants (15 boys and 10 girls) who were mechanically ventilated by PICU in Hubei Maternal and Child Health Hospital were selected as the study subjects. After the improvement of the basic disease, regular spontaneous breathing, and the withdrawal of the ventilator, all the children obtained the electrical activity of the diaphragm (EAdi) signal. Then, each child was given CPAP and NAVA mode mechanical ventilation 1 h before the withdrawal of the ventilator. Each detection index was recorded 30 min after each mode of ventilation. RESULTS: Two of the 25 children were tracheotomized because of respiratory muscle weakness and could not be converted to NAVA mode without the EAdi signal. Hemodynamic indexes were not statistically different between the two groups of CPAP and NAVA. PaCO2 is not significantly different in the two modes, and both were at normal levels. The PIP in NAVA mode is lower than that in CPAP mode (p < .05), and its EAdi signal was correspondingly low. There were significant differences in the peak pressure (Ppeak), mean pressure (Pmean), and compliance and mean arterial pressure (p < .01) between the CPAP and NAVA model ventilation in 23 patients. CONCLUSION: NAVA can significantly improve the coordination of patients. The therapeutic effect of NAVA was better, which was beneficial to the prognosis of patients and had positive application value in the withdrawal of ventilators in patients.

19.
Front Pharmacol ; 12: 718208, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34483927

RESUMO

Catecholaminergic polymorphic ventricular tachycardia is a primary arrhythmogenic syndrome with genetic features most commonly seen in adolescents, with syncope and sudden death following exercise or agitation as the main clinical manifestations. The mechanism of its occurrence is related to the aberrant release of Ca2+ from cardiomyocytes caused by abnormal RyR2 channels or CASQ2 proteins under conditions of sympathetic excitation, thus inducing a delayed posterior exertional pole, manifested by sympathetic excitation inducing adrenaline secretion, resulting in bidirectional or polymorphic ventricular tachycardia. The mortality rate of the disease is high, but patients usually do not have organic heart disease, the clinical manifestations may not be obvious, and no significant abnormal changes in the QT interval are often observed on electrocardiography. Therefore, the disease is often easily missed and misdiagnosed. A number of genetic mutations have been linked to the development of this disease, and the mechanisms are different. In this paper, we would like to summarize the possible genes related to catecholaminergic polymorphic ventricular tachycardia in order to review the genetic tests currently performed, and to further promote the development of genetic testing techniques and deepen the research on the molecular level of this disease.

20.
Front Oncol ; 11: 718761, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490117

RESUMO

Purpose: Breast cancer type 1 susceptibility (BRCA) mutations not only increase breast cancer (BC) risk but also result in poor survival and prognosis for BC patients. This study will analyze the effect and safety of therapeutic regimens for the treatment of BC patients with germline BRCA (gBRCA) mutations by network meta-analysis. Methods: Public databases were searched from inception to 29 April 2021. Frequentist network meta-analysis was conducted to analyze the benefit of chemotherapy and targeted drug-related strategies. Results: Seventeen articles were included in the analysis. For progression-free survival (PFS), olaparib (hazard ratio (HR): 0.58; 95% confidence interval (CI): 0.43 - 0.79), platinum (HR: 0.45; 95% CI: 0.22 - 0.89), and talazoparib (HR: 0.54; 95% CI: 0.41 - 0.71) were significantly better than platinum-free chemotherapy (Chemo). The results based on indirect comparisons showed that veliparib (Vel) + platinum + Chemo was also significantly better than Chemo (HR: 0.37; 95% CI: 0.20 - 0.69). For overall survival (OS), olaparib was significantly better than Chemo only in the population who did not receive prior chemotherapy. For pathologic complete response (pCR), bevacizumab+Chemo had a significant advantage over platinum agents (OR: 3.64; 95% CI: 1.07 - 12.39). Olaparib and talazoparib both showed significantly higher objective response rates (ORRs) than Chemo. Conclusion: The PFS results suggested that olaparib, talazoparib, and Vel+platinum agent+Chemo were ideal regimens for overall, TNBC, and advanced BC patients with gBRCA mutations. Whether PARPis are suitable for patients with gBRCA mutations who have received prior platinum therapy still needs to be clarified.

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