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1.
Genome Med ; 13(1): 57, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845891

RESUMO

BACKGROUND: Mutations in the DMD gene encoding dystrophin-a critical structural element in muscle cells-cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD. METHODS: In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46-54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors. RESULTS: Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member ß-dystroglycan. CONCLUSIONS: We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases.

2.
Materials (Basel) ; 14(6)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809446

RESUMO

Designing and synthesizing photothermal conversion materials with better storage capacity, long-term stability as well as low temperature energy output capability is still a huge challenge in the area of photothermal storage. In this work, we report a brand new photothermal conversion material obtained by attaching trifluoromethylated azobenzene (AzoF) to reduced graphene oxide (rGO). AzoF-rGO exhibits outstanding heat storage density and power density up to 386.1 kJ·kg-1 and 890.6 W·kg-1, respectively, with a long half-life (87.7 h) because of the H-bonds based on high attachment density. AzoF-rGO also exhibits excellent cycling stability and is equipped with low-temperature energy output capability, which achieves the reversible cycle of photothermal conversion within a closed system. This novel AzoF-rGO complex, which on the one hand exhibits remarkable energy storage performance as well as excellent storage life span, and on the other hand is equipped with the ability to release heat at low temperatures, shows broad prospects in the practical application of actual photothermal storage.

3.
Alzheimers Dement ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33792187

RESUMO

Facing considerable challenges associated with aging and dementia, China urgently needs an evidence-based health-care system for prevention and management of dementia. The Beijing Aging Brain Rejuvenation Initiative (BABRI) is a community-based cohort study initiated in 2008 that focuses on asymptomatic stages of dementia, aims to develop community-based prevention strategies for cognitive impairment, and provides a platform for scientific research and clinical trials. Thus far, BABRI has recruited 10,255 participants (aged 50 and over, 60.3% female), 2021 of whom have been followed up at least once at a 2- or 3-year interval. This article presents aims and study design of BABRI; summarizes preliminary behavioral and neuroimaging findings on mild cognitive impairment (MCI) and results of clinical trials on MCI; and discusses issues concerning early prevention in community, MCI diagnosis methods, and applications of database of aging and dementia. BABRI is proposed to build a systematic framework on brain health in old age.

4.
Int J Nanomedicine ; 16: 1889-1899, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33707944

RESUMO

Introduction: Sonodynamic therapy (SDT) has good targeting and non-invasive advantages in the treatment of solid cancers, and checkpoint blockade immunotherapy is also a promising treatment to cure cancer. However, their antitumor effects are not sufficient due to some inherent factors. Some studies that combined SDT with immunotherapy or nanoparticles have managed to enhance its efficiency to treat cancers. Methods: In this work, an effective therapeutic strategy that can potentiate the antitumor efficacy of anti-PD-L1 antibody (aPD-L1) is developed by the use of cascade immuno-sonodynamic therapy (immuno-SDT). Titanium dioxide (TiO2), a nanostructured agent for SDT, sonosensitizer Chlorin e6 (Ce6), and immunological adjuvant CpG oligonucleotide (CpG ODN), are used to construct a multifunctional nanosonosensitizer (TiO2-Ce6-CpG). Then, we conducted in vitro and in vivo experiments to explore the antitumor effect of TiO2-Ce6-CpG under ultrasound (US) treatment. Results: The characterization tests showed that the nanosonosensitizers are polycrystalline structure with homogeneous sizes, resulting in a good drug loading efficiency. The innovative nanosonosensitizers (TiO2-Ce6-CpG) can not only effectively inhibit tumor growth but also stimulate the immune system to activate the adaptive immune responses, using the TiO2-Ce6 to augment SDT and the immune adjuvant CpG to enhance the immune response. After combined with the aPD-L1, the synergistic effect could not only efficiently inhibit the primary tumor growth but also lead to an inhibition of the non-irradiated pre-existing distant tumors by inducing a strong tumor-specific immune response. Conclusion: In this study, we present an effective strategy for tumor treatment by combining nanosonosensitizer-augmented SDT and aPD-L1 checkpoint blockade. This work provides a promising strategy and offers a new vision for treating malignant tumors.


Assuntos
/uso terapêutico , Imunoterapia , Nanopartículas/química , Neoplasias/imunologia , Neoplasias/terapia , Terapia por Ultrassom , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Terapia Combinada , Células Dendríticas/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Imunidade/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Nanopartículas/ultraestrutura , Neoplasias/patologia , Oligodesoxirribonucleotídeos/química , Porfirinas/química , Espécies Reativas de Oxigênio/metabolismo , Titânio/química
5.
Environ Sci Technol ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33733744

RESUMO

The discovery of complete ammonia oxidation (comammox) has altered our understanding of nitrification, which is the rate-limiting process in the global nitrogen cycle. However, understanding the ecological role of comammox or its contribution to nitrification in both natural and artificial ecosystems is still in its infancy. Here, we investigated the community distribution and function of comammox bacteria in riparian ecosystems and analyzed interactions between comammox and other nitrogen cycling microorganisms. The comammox bacterial abundance and rate were higher in summer than in winter and higher in nonrhizosphere soils than in the rhizosphere. Fringe soils in the riparian zone comprise a comammox hotspot, where the abundance (2.58 × 108 copies g-1) and rate (0.86 mg N kg-1 d-1) of comammox were not only higher than at other sampling sites but also higher than those of other ammonia oxidation processes. The comammox rate correlated significantly positively with relative abundance of the comammox species Candidatus Nitrospira nitrificans but not with that of the species Candidatus Nitrospira nitrosa. Analysis of comammox interaction with other ammonia-oxidizing processes revealed ammonia-oxidizing archaea to dominate interface soils, comammox to dominate in fringe soils, and anaerobic ammonium oxidation (anammox) to dominate in interface sediments of the riparian zone. These results indicate that comammox may constitute an important and currently underestimated process of microbial nitrification in riparian zone ecosystems.

6.
Plant Physiol Biochem ; 162: 74-85, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33667969

RESUMO

Glucose-6-phosphate dehydrogenase (G6PD or G6PDH) plays an important role in response to salt stress in plants. However, much less is known about G6PD proteins in soybean (Glycine max L.). Here, we found that a soybean cytosolic G6PD gene, GmG6PD7, was induced by NaCl. We generated Arabidopsis transgenic lines overexpressing GmG6PD7. The seed germination rate and primary root length of Arabidopsis thaliana over-expressing GmG6PD7 under NaCl treatment were enhanced. Salt stress induced an obvious increase of the total and cytosolic G6PD activity and the marked decrease of ROS levels in the transgenic plants. At the same time, over-expressing GmG6PD7 in Arabidopsis affected the glutathione and NADPH level and activated ROS scavengers, suggesting that GmG6PD7 contributes to increase salinity tolerance by decreasing ROS accumulation. What's more, we found GmG6PD7 overexpression led to the up-regulation of abscisic acid (ABA) degradation gene and the down-regulation of ABA synthesis and ABA-responsive genes, which finally reduced ABA content to improve seed germination rate under salinity stress. It was noteworthy that GmG6PD7 can rescue the seed and root phenotype of Arabidopsis cytosolic G6PD mutant (Atg6pd5 and Atg6pd6) under salt stress, suggesting cytosolic G6PD may have a conserved function in soybean and Arabidopsis.

7.
Epigenomics ; 13(7): 513-530, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33683141

RESUMO

Aim: To explore the expression profiles and functions of circRNAs in hepatocellular carcinoma (HCC). Materials & methods: We obtained circRNA expression profiles through RNA sequencing. Expression levels of circRNAs were confirmed by quantitative real-time PCR. The effects on HCC progression were determined using Cell Counting Kit 8, clone formation and transwell assays. Results: We identified 114 upregulated and 144 downregulated circRNAs in HCC tissues. The results of quantitative real-time PCR showed that circGNAO1, circRNF180 and circMERTK were significantly downregulated in HCC tissues, whereas circSNX6 was significantly upregulated. CircRNF180 was associated with microvascular invasion. Overexpression of circRNF180 inhibits the proliferation, colony formation, migration and invasion of HCC cells. Conclusion: CircRNF180 may function as a tumor suppressor and could serve as a potential biomarker and therapeutic target in HCC.

8.
J Clin Nurs ; 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761152

RESUMO

AIMS AND OBJECTIVES: We explored dispatched nurses' experiences of wearing full gear personal protective equipment to care for patients with coronavirus disease-2019 (COVID-19) in Wuhan, China. BACKGROUND: Full gear personal protective equipment is the primary and foremost measure to prevent the contact and transmission of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2); however, working in full gear personal protective equipment may hinder nursing care activities and thus negatively affect patients' and nurses' health. DESIGN: This descriptive qualitative inquiry followed the COREQ guidelines. METHODS: Individual semi-structured telephone interviews were conducted in a purposive sample of 15 frontline nurses who were dispatched to the outbreak epicentre from March to April 2020. Verbatim transcripts were content analysed. RESULTS: Four themes emerged from the data: inadequate preparedness for working with full gear personal protective equipment, full gear personal protective equipment stimulated stress responses, coping strategies and professional growth. Participants learned a great deal from problem-focussed and emotion-focussed strategies to tackle challenges related to the prolonged wearing of full gear personal protective equipment for quality nursing care and reduced risk of exposure. They became more vigilant to the adherence to evolving protocols and appropriate training concerning full gear personal protective equipment use. CONCLUSIONS: Frontline nurses confronted various but diminishing challenges related to the use of full gear personal protective equipment when caring for patients with COVID-19 across the approximate 40-day period. Consistent use of coverall personal protective equipment to protect from SARS-CoV-2 in high exposure settings would be feasible if nurses were better prepared; therefore, scenario-based skill training concerning the prolonged use of full gear personal protective equipment should be offered regularly and intensively. RELEVANCE TO CLINICAL PRACTICE: This study informs future decisions concerning improved full gear personal protective equipment-related psychomotor training and promoting ways for nurses to cope with the stress that comes from working in highly contiguous environments.

9.
IUBMB Life ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33725395

RESUMO

Gastrointestinal symptoms and liver injury are common in patients with coronavirus disease 2019 (COVID-19). However, profiles of different pharmaceutical interventions used are relatively underexplored. Chinese herbal medicine (CHM) has been increasingly used for patients with COVID-19, but the efficacy of CHM used in COVID-19 on gastrointestinal symptoms and liver functions has not been well studied with definitive results based on the updated studies. The present study aimed at testing the efficacy of CHM on digestive symptoms and liver function (primary outcomes), the aggravation of COVID-19, and the time to viral assay conversion (secondary outcomes), among patients with COVID-19, compared with standard pharmacotherapy. The literature search was undertaken in 11 electronic databases from December 1, 2019 up to November 8, 2020. Appraisal of the evidence was conducted with Cochrane risk of bias tool or Newcastle Ottawa Scale. A random-effects model or subgroup analysis was conducted when significant heterogeneity was identified in the meta-analysis. The certainty of the evidence was assessed with the grading of recommendations assessment, development, and evaluation approach. Forty-eight included trials involving 4,704 participants were included. Meta-analyses favored CHM plus standard pharmacotherapy for COVID-19 on reducing the aggravation of COVID-19 and the time to viral assay conversion compared with standard pharmacotherapy. However, the present CHM as a complementary therapy for treating COVID-19 may not be beneficial for improving most gastrointestinal symptoms and liver function based on the current evidence. More well-conducted trials are warranted to confirm the potential efficacy of CHM furtherly.

10.
Drug Metab Dispos ; 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33674268

RESUMO

Ozanimod is approved for the treatment of relapsing forms of multiple sclerosis. Absorption, metabolism and excretion of ozanimod was investigated following a single oral dose of 1.0 mg 14C-ozanimod hydrochloride to six healthy subjects. In vitro experiments were conducted to understand the metabolic pathways and enzyme involved in the metabolism of ozanimod and its active metabolites. The total mean recovery of the administered radioactivity was ~63%, with ~26% and ~37% recovered from urine and feces, respectively. Based on exposure, the major circulating components were active metabolite CC112273 and inactive metabolite RP101124 and together accounted for 50% of the circulating total radioactivity exposure while ozanimod accounted for 6.7% of the total radioactive exposure. Ozanimod was extensively metabolized, with 13 metabolites identified including 2 major active metabolites (CC112273 and CC1084037) and 1 major inactive metabolite (RP101124) in circulation. Ozanimod is metabolized by three primary pathways including aldehyde dehydrogenase and alcohol dehydrogenase, cytochrome P450 (CYP) isoforms 3A4, 1A1, and reductive metabolism by gut microflora. The primary metabolite RP101075 is further metabolized to form major active metabolite CC112273 by monoamine oxidase B which further undergoes reduction by carbonyl reductases (CBR) to form CC1084037 or CYP2C8 mediated oxidation to form RP101509. CC1084037 is oxidized rapidly to form CC112273 by aldo-keto reductase (AKR) 1C1/1C2, and/or 3ß- and 11ß-hydroxysteroid dehydrogenase (HSD) and this reversible oxido-reduction between two active metabolites favors CC112273. Ozanimod example illustrates the need for conducting timely radiolabeled human ADME studies for characterization of disproportionate metabolites and assessment of exposure coverage during drug development. Significance Statement Absorption, metabolism, and excretion of ozanimod was characterized in humans and the enzymes involved in complex metabolism were elucidated. Disproportionate metabolites were identified, and the activity of these metabolites were determined.

11.
J Empir Res Hum Res Ethics ; : 1556264621995656, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33729908

RESUMO

This study analyzes the Institutional Review Board (IRB) quality and efficiency at a leading hospital in Central Southern China, under the first three years of a Human Research Protection Program (HRPP). We conducted a descriptive, retrospective analysis from 2015 through 2017. We extracted characteristics from the protocol archive in duplicate. Of 396 protocols submitted, 98% were approved. Mean protocol review time decreased from 23 to 15 calendar days, 344 serious adverse events SAEs were reviewed, and 93 conflicts of interest (COIs) were disclosed. IRB quality and efficiency mechanisms improved. Remaining needs include increased monitoring of COIs and unanticipated problem involving risks to subjects or others, distinctions between research types, and cooperation with specialized committees.

12.
Medicine (Baltimore) ; 100(7): e24514, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607781

RESUMO

BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-PTX) has exhibited clinical efficacy in breast cancer treatment, but toxicities can be yielded more at the same time. We did this meta-analysis aiming to unambiguously compare nab-PTX with conventional solvent-based paclitaxel in breast cancer patients of all stages. METHOD: Pubmed, EMBASE, Cochrane Library, Chinese Biomedical database, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical database, and WangFang database were searched for head-to-head randomized controlled trials of nab-PTX and solvent-based paclitaxel in breast cancer. Other sources will also be searched like Google Scholar and gray literatures. Two researchers will independently search the database and extract data from the articles. Risk of bias will be assessed using the Cochrane Collaboration's tool. Objective tumor response rate, chemotherapy completion rate after 4 or 6 cycles, and toxicity will be primary outcomes. Disease control rate, overall survival, and progression-free survival/disease-free survival will be included in secondary outcomes. Risk ratio with 95% confidence interval was used for dichotomous variables while hazard ratio was used for time-to-event outcomes. The following 3 data sets will all be considered when synthesizing the data: intention-to-treat population, those who actually received taxanes treatment, and those who were actually assessed. All the analyses were done using Review Manager Software 5.3. Any disagreements in study selection, data collection, and analysis will be resolved by a third investigator. RESULTS AND CONCLUSION: This study is aim to evaluate the efficacy and safety of nab-PTX compared with PTX in breast cancer treatment as well as to find the best dose or schedule and identify the benefit population. This meta-analysis could provide evidence for clinicians to make a better choice between nab-PTX and PTX in different specific contexts. PROSPERO REGISTRATION NUMBER: CRD42019117912.


Assuntos
Paclitaxel Ligado a Albumina/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Paclitaxel Ligado a Albumina/efeitos adversos , Antineoplásicos/efeitos adversos , Tomada de Decisão Clínica , Feminino , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
13.
J Med Chem ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33586434

RESUMO

It remains a big challenge to develop HDAC inhibitors effective for solid tumors. Previous studies have suggested that the feedback activation of JAK-STAT3 pathway represents a key mechanism leading to resistance to HDAC inhibitors in breast cancer, suggesting the therapeutic promise of JAK/HDAC dual inhibitors. In this work, we discovered a series of pyrrolo[2,3-d]pyrimidine-based derivatives as potent JAK and HDAC dual inhibitors. Especially, compounds 15d and 15h potently inhibited JAK1/2/3 and HDAC1/6 and displayed antiproliferative and proapoptotic activities in triple-negative breast cancer cell lines. Besides, compounds 15d and 15h also diminished the activation of LIFR-JAK-STAT signaling triggered by tumor-associated fibroblasts, which suggests that these compounds could potentially overcome the drug resistance caused by the tumor microenvironment. More importantly, compound 15d effectively inhibited the tumor growth in MDA-MB-231 xenograft tumor model. Overall, this work provides valuable leads and novel antitumor mechanisms for the treatment of the SAHA-resistant triple-negative breast cancers.

14.
J Cardiovasc Pharmacol ; 77(2): 170-181, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33538532

RESUMO

ABSTRACT: Oxidative stress, the renin-angiotensin system (RAS), and inflammation are some of the mechanisms involved in the pathogenesis of hypertension. The aim of this study is to examine the protective effect of the chronic administration of astaxanthin, which is extracted from the shell of crabs and shrimps, into hypothalamic paraventricular nucleus (PVN) in spontaneously hypertensive rats. Animals were randomly assigned to 2 groups and treated with bilateral PVN infusion of astaxanthin or vehicle (artificial cerebrospinal fluid) through osmotic minipumps (Alzet Osmotic Pumps, Model 2004, 0.25 µL/h) for 4 weeks. Spontaneously hypertensive rats had higher mean arterial pressure and plasma level of norepinephrine and proinflammatory cytokine; higher PVN levels of reactive oxygen species, NOX2, NOX4, IL-1ß, IL-6, ACE, and AT1-R; and lower PVN levels of IL-10 and Cu/Zn SOD, Mn SOD, ACE2, and Mas receptors than Wistar-Kyoto rats. Our data showed that chronic administration of astaxanthin into PVN attenuated the overexpression of reactive oxygen species, NOX2, NOX4, inflammatory cytokines, and components of RAS within the PVN and suppressed hypertension. The present results revealed that astaxanthin played a role in the brain. Our findings demonstrated that astaxanthin had protective effect on hypertension by improving the balance between inflammatory cytokines and components of RAS.

15.
Br J Haematol ; 192(5): 900-908, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33534930

RESUMO

The development of alloantibodies (inhibitors) against coagulation factor VIII (FVIII) is the most serious complication of FVIII replacement therapy in patients with haemophilia A (HA). We carried out a nationwide study focussing on patients with HA with inhibitors in China to evaluate the condition and management of this population. The study retrospectively analysed patient characteristics, clinical history, manifestation, treatment strategy as well as individual haemophilia care of 493 patients with inhibitors (466 with severe HA and 27 with non-severe HA) registered all over China. The median (interquartile range) age at diagnosis of FVIII inhibitors was 13 (5-28) years in patients with severe HA and 24 (10·5-39·5) years in patients with non-severe HA. Most patients (85%) had high-titre inhibitors. Prothrombin complex concentrate and recombinant activated coagulation factor VII were used respectively in 76·2% and 29·2% of patients for acute bleeding. Only 22·3% of patients underwent immune tolerance induction (ITI) treatment, of whom 64·9% achieved negative inhibitor titre. In patients who did not undergo ITI, the inhibitors turned negative in 17·7%, and patients with low peak inhibitor titre were more likely to acquire negative titre spontaneously (odds ratio 11·524, 95% confidence interval 5·222-25·432; P = 0·000). We recorded that 3·2% of the patients died from haemophilia-related life-threatening bleeding.

16.
Adv Mater ; 33(11): e2006689, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33569827

RESUMO

Antimony selenosulfide (Sb2 (S,Se)3 ) is an emerging low-cost, nontoxic solar material with suitable bandgap and high absorption coefficient. Developing effective methods for fabricating high-quality films would benefit the device efficiency improvement and deepen the fundamental understanding on the optoelectronic properties. Herein, equipment is developed that allows online introduction of precursor vapor during the reaction process, enabling sequential coevaporation of Sb2 Se3 and S powders for the deposition of Sb2 (S,Se)3 thin films. With this unique ability, it is revealed that the deposition sequence manipulates both the interfacial properties and optoelectronic properties of the absorber film. A power conversion efficiency of 8.0% is achieved, which is the largest value in vapor-deposition-derived Sb2 (S,Se)3 solar cells. The research demonstrates that multi-source sequential coevaporation is an efficient technique to fabricate high-efficiency Sb2 (S,Se)3 solar cells.

17.
Nutr Cancer ; : 1-13, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33432844

RESUMO

Although several epidemiological studies have investigated associations between poultry and fish consumption and pancreatic cancer (PC) risk, these findings have been inconsistent. The present study aimed to perform a meta-analysis to comprehensively evaluate these associations. We retrieved Eligible cohort studies and case-control studies published before February 2020 from the Medline, EMBASE, and Cochrane Library and applied a random or fixed effects model to calculate the pooled relative risk (RR) and the corresponding 95% confidence intervals (CI). Publication bias was detected using funnel plots, Begg's test, and Egger's test, and the study quality was evaluated using the Newcastle-Ottawa scale. We included 25 studies in the analyses. The pooled RR of PC for the highest vs. lowest poultry intake category was 1.14 (95% CI: 1.02-1.26) in cohort studies. There was no appreciable link between fish intake and PC risk (RR: 1.00, 95% CI: 0.93-1.07). Our results suggest that large amount of poultry intake may increase PC risk, while fish intake is unlikely to be linked to PC risk. These links require further investigation, particularly between poultry and PC.

18.
Pediatr Res ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33469186

RESUMO

BACKGROUND: Pomalidomide, an immunomodulatory drug, was investigated for pediatric brain tumors. The objectives of this analysis were to characterize the PK of pomalidomide and to examine exposure-response relationship in pediatric patients with recurrent or progressive primary brain tumors. METHODS: Nonlinear mixed effects modeling was employed in developing a population PK model of pomalidomide using a total of 343 concentrations from 70 patients. Logistic regression models were used for exposure-response analyses. RESULTS: The PK of pomalidomide was adequately described with a one compartment model with first-order absorption and elimination. Body surface area (BSA) was identified as a statistically significant covariate of apparent clearance and volume of distribution; however, the impact of BSA on exposure parameters was not deemed clinically relevant. Pomalidomide exposure was not associated with higher probabilities of treatment-emergent adverse events or pomalidomide dose interruptions during Cycle 1. Covariates such as BSA, weight, sex, age, and race had no significant effect on safety endpoints. The PK of pomalidomide in pediatric patients with brain tumors was generally consistent with that in adult patients with multiple myeloma after adjustment for BSA. CONCLUSIONS: This is the first study to characterize PK of pomalidomide in pediatric patients, which supports BSA-based dosing for pediatric patients. IMPACT: This is the first study to characterize PK of pomalidomide in pediatric patients, which supports BSA-based dosing for pediatric patients. There is no significant pomalidomide PK difference between adults and pediatrics. Pomalidomide exposure was not associated with higher probabilities of treatment-emergent adverse event or pomalidomide dose interruptions during Cycle 1.

19.
Prev Med ; 145: 106423, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33440190

RESUMO

Immunization programs have been challenged by vaccine crises. Between 2013 and 2018, China has experienced three major vaccine scandals and crises, which has partly impaired Chinese public trust in domestically produced vaccines. This study aims to explore the associations between parental trust toward CDC-released crisis communication information, parents' critical understanding of crisis information, parental confidence in vaccine efficacy, and parental vaccine decisions. A cross-sectional survey was conducted among 1065 expectant parents two weeks after the 2018 vaccine crisis was revealed. The proportion of parental hesitancy toward domestically produced vaccines and overall vaccination increased from 30.6% to 82.7% and 8.3% to 52.1%, respectively, after the crisis. Parents with higher levels of trust toward crisis communication information were less likely to report vaccine hesitancy toward both domestically produced vaccines and vaccines overall after the crisis. Parents with better critical understanding of crisis information were less likely to report a vaccine hesitancy toward overall vaccine and more likely to maintain a vaccine intention. Additionally, parents with lower levels of confidence in vaccine efficacy were more likely to became vaccine hesitant but were also more likely to maintain their vaccine intentions after the crisis. It is crucial to guarantee the safety of vaccines, maintain parental confidence in vaccine efficacy, and eliminate the potential risks that result in parental vaccine hesitancy. Future crisis communication strategies are encouraged to ensure timely responses to sustain public confidence.

20.
Biosens Bioelectron ; 177: 113000, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33485152

RESUMO

In this work, a molecularly imprinted photoelectrochemical (MIP-PEC) sensor based on a novel PEC composite of metal-organic frameworks (MOFs) and TiO2 (NH2-MIL-125(Ti)-TiO2) was established for the ultrasensitive and selective detection of oxytetracycline (OTC). This is the first attempt of applying MOFs in the construction of MIP-PEC sensor. The NH2-MIL-125(Ti)-TiO2 was synthesized by a simple one-step solvothermal method and modified onto the surface of indium tin oxide (ITO) electrode as the photosensitive layer. Subsequently, molecularly imprinted polymer (MIP) was modified as recognition element by electropolymerization. The NH2-MIL-125(Ti)-TiO2 showed an enhanced photocurrent response due to stronger light absorption capacity and matched energy band. Furthermore, MIP greatly improved the selectivity and sensitivity of the constructed PEC sensor. The photocurrent response of the MIP-PEC sensor was reduced after OTC recognition because the specific binding of OTC to the imprinted cavities blocked the electron transfer of the electrode. Under optimal experimental conditions, the MIP-PEC sensor exhibited a wide detection range from 0.1 nM to 10 µM with a low limit of detection (LOD) of 60 pM, as well as certain reproducibility, stability and good applicability in real samples. The proposed sensor provides ideas for the application of MOFs in the construction of PEC sensors and will offer an alternative method for the detection of other pollutants in the field of food safety.

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