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Introduction: Workplace violence against healthcare workers has become a serious global public health problem. The incidence of workplace violence towards Psychiatric nurses is higher than in all other medical institutions, up to 84.2% per year. It not only negatively affects many aspects of healthcare workers' lives, but also destroys the harmony of the nurse-patient relationship and reduces the quality of nursing care. The number of psychiatric nurses in China was approximately 96,000, far lower than most other countries and unable to meet the growing demand for mental health. However, the increase in workplace violence has future exacerbates the current shortage of nurses. Therefore, it is necessary to develop effective strategies to prevent psychiatric nurses from suffering from workplace violence, thereby to reduce nurse turnover and improve the quality of nursing care. A comprehensive understanding of psychiatric nurses' preferences and priorities for preventing workplace violence is an important prerequisite before formulating strategies and taking measures. Unfortunately, to date, no research has investigated the psychiatric nurses' preferences. Therefore, a discrete choice experiment (DCE) is conducting to explore the psychiatric nurses' preferences for workplace violence prevention. This article reports on methodological details of the DCE. Methods and analysis: Six attributes were developed through a literature review, one-on-one interviews and focus group discussions. D-efficient design in NGENE was used to generate choice sets. SPSS 24.0 will be used for descriptive analysis of social Demography, and Stata 16.0 will be used for analysis of DCE data. A multinomial logit model will be used to preliminarily explore trade-offs between workplace violence prevention characteristics included in the choice tasks. Then, in a mixed logit model, we plan to choose some arbitrarily defined base violence prevention program and will use the nlcom command to evaluate the probability of an alternative violence prevention program. Ethics and dissemination: The study was approved by the relevant ethics committees. Our findings will emphasize priority intervention areas based on the preferences of psychiatric nurses and provide references for hospitals to develop and improve workplace violence prevention strategies. The results will be shared through seminars, policy briefs, peer-reviewed journal articles and online blogs.
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Enfermagem Psiquiátrica , Violência no Trabalho , Humanos , Violência no Trabalho/prevenção & controle , Violência no Trabalho/psicologia , Violência no Trabalho/estatística & dados numéricos , China , Grupos Focais , Comportamento de Escolha , Atitude do Pessoal de Saúde , Masculino , Feminino , Adulto , Projetos de PesquisaRESUMO
Introduction: Depression threatens people's lives and imposes huge economic burden. Antidepressant therapy is the first-line treatment for depression, and patient adherence to medication is the key to successful treatment. Depression patients have poor medication adherence, which leads to failure of depression management and significantly poorer clinical outcomes. Incorporating patient preferences into clinical decisions can improve uptake rates, optimize treatment adherence. A discrete choice experiment (DCE) can elicit and quantify individual preferences. Previous DCE studies were conducted in developed countries and ignored the influences of factors other than the medication. This paper outlines an ongoing DCE that aims to (1) explore medication-management-related characteristics that may affect depression patients' adherence to antidepressant, (2) elicit how depression patients consider the trade-offs among different medication managements. Methods: The six attributes and their levels were developed through a literature review, semi-structured interviews and experts and focus group discussions. A fractional factorial design in the software Ngene 1.2 version was used to generate 36 choice sets, and they were divided into 3 blocks. A mixed logit model will be used to explore the patients' preferences, willingness to pay and uptake rate of depression patients for medication management attributes. Results: The final questionnaire consists of three parts. The first is the introduction, which introduces the purpose of the study and the requirements of completing the questionnaire. This was followed by a general information questionnaire, which included sociodemographic characteristics. The last part is DCE tasks, which include 13 DCE choice sets, and each choice set include two alternative and one "opt-out" option. The pilot-test results showed the questionnaire was easy to understand and could be used in formal surveys. Conclusion: Our study shows how the development process of the study can be conducted and reported systematically and rigorously according to the theoretical foundation and design principles in DCE.
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BACKGROUND: Emerging evidence has shown that myeloid cells that infiltrate into the peri-infarct region may influence the progression of ischemic stroke by interacting with microglia. Properdin, which is typically secreted by immune cells such as neutrophils, monocytes, and T cells, has been found to possess damage-associated molecular patterns (DAMPs) properties and can perform functions unrelated to the complement pathway. However, the role of properdin in modulating microglia-mediated post-stroke neuroinflammation remains unclear. METHODS: Global and conditional (myeloid-specific) properdin-knockout mice were subjected to transient middle cerebral artery occlusion (tMCAO). Histopathological and behavioral tests were performed to assess ischemic brain injury in mice. Single-cell RNA sequencing and immunofluorescence staining were applied to explore the source and the expression level of properdin. The transcriptomic profile of properdin-activated primary microglia was depicted by transcriptome sequencing. Lentivirus was used for macrophage-inducible C-type lectin (Mincle) silencing in microglia. Conditioned medium from primary microglia was administered to primary cortex neurons to determine the neurotoxicity of microglia. A series of cellular and molecular biological techniques were used to evaluate the proinflammatory response, neuronal death, protein-protein interactions, and related signaling pathways, etc. RESULTS: The level of properdin was significantly increased, and brain-infiltrating neutrophils and macrophages were the main sources of properdin in the ischemic brain. Global and conditional myeloid knockout of properdin attenuated microglial overactivation and inflammatory responses at the acute stage of tMCAO in mice. Accordingly, treatment with recombinant properdin enhanced the production of proinflammatory cytokines and augmented microglia-potentiated neuronal death in primary culture. Mechanistically, recombinant properdin served as a novel ligand that activated Mincle receptors on microglia and downstream pathways to drive primary microglia-induced inflammatory responses. Intriguingly, properdin can directly bind to the microglial Mincle receptor to exert the above effects, while Mincle knockdown limits properdin-mediated microglial inflammation. CONCLUSION: Properdin is a new medium by which infiltrating peripheral myeloid cells communicate with microglia, further activate microglia, and exacerbate brain injury in the ischemic brain, suggesting that targeted disruption of the interaction between properdin and Mincle on microglia or inhibition of their downstream signaling may improve the prognosis of ischemic stroke.
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Lesões Encefálicas , Isquemia Encefálica , AVC Isquêmico , Camundongos , Animais , Microglia/metabolismo , AVC Isquêmico/metabolismo , Properdina/metabolismo , Properdina/farmacologia , Doenças Neuroinflamatórias , Macrófagos/metabolismo , Infarto da Artéria Cerebral Média/patologia , Lesões Encefálicas/metabolismo , Isquemia Encefálica/metabolismo , Camundongos Endogâmicos C57BLRESUMO
The NLRP3 inflammasome is involved in the neuroinflammatory pathway of Alzheimer's disease (AD). The aim of this study is to explore the roles and underlying mechanisms of ginkgolide (Baiyu®) on amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and a murine microglial cell line, BV-2. In the present study, the APP/PS1 mice were administered with ginkgolide, followed by a Morris water maze test. The mice were then euthanized to obtain brain tissue for histological and Aß analysis. Additionally, BV-2 cells were pretreated with ginkgolide and then incubated with Aß1-42 peptide. NLRP3, ASC, and caspase-1 mRNA and protein expression in brain tissue of mice and BV-2 cells were quantified by real-time PCR and western blotting, as well as reactive oxygen species (ROS) production, interleukin (IL)-1ß and IL-18 levels by lucigenin technique and ELISA. Compared with the APP/PS1 mice, ginkgolide-treated mice demonstrated the shortened escape latency, reduced plaques, less inflammatory cell infiltration and neuron loss in the hippocampi of APP/PS1 mice. The levels of NLRP3, ASC, caspase-1, ROS, IL-1ß, and IL-18 were also decreased in the brain tissue of APP/PS1 mice or Aß1-42-treated BV-2 cells following ginkgolide treatment. Ginkgolide exerted protective effects on AD, at least partly by inactivating the NLRP3/caspase-1 pathway.
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Doença de Alzheimer , Animais , Camundongos , Doença de Alzheimer/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18 , Peptídeos beta-Amiloides/metabolismo , Doenças Neuroinflamatórias , Espécies Reativas de Oxigênio , Caspase 1/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Transtornos da Memória , Camundongos Transgênicos , Modelos Animais de DoençasRESUMO
Immune cell infiltration in response to myocyte death regulates extracellular matrix remodeling and scar formation after myocardial infarction (MI). Caspase-recruitment domain family member 9 (CARD9) acts as an adapter that mediates the transduction of pro-inflammatory signaling cascades in innate immunity; however, its role in cardiac injury and repair post-MI remains unclear. We found that Card9 was one of the most upregulated Card genes in the ischemic myocardium of mice. CARD9 expression increased considerably 1 day post-MI and declined by day 7 post-MI. Moreover, CARD9 was mainly expressed in F4/80-positive macrophages. Card9 knockout (KO) led to left ventricular function improvement and infarct scar size reduction in mice 28 days post-MI. Additionally, Card9 KO suppressed cardiomyocyte apoptosis in the border region and attenuated matrix metalloproteinase (MMP) expression. RNA sequencing revealed that Card9 KO significantly suppressed lipocalin 2 (Lcn2) expression post-MI. Both LCN2 and the receptor solute carrier family 22 member 17 (SL22A17) were detected in macrophages. Subsequently, we demonstrated that Card9 overexpression increased LCN2 expression, while Card9 KO inhibited necrotic cell-induced LCN2 upregulation in macrophages, likely through NF-κB. Lcn2 KO showed beneficial effects post-MI, and recombinant LCN2 diminished the protective effects of Card9 KO in vivo. Lcn2 KO reduced MMP9 post-MI, and Lcn2 overexpression increased Mmp9 expression in macrophages. Slc22a17 knockdown in macrophages reduced MMP9 release with recombinant LCN2 treatment. In conclusion, our results demonstrate that macrophage CARD9 mediates the deterioration of cardiac function and adverse remodeling post-MI via LCN2.
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Traumatismos Cardíacos , Infarto do Miocárdio , Animais , Camundongos , Proteínas Adaptadoras de Sinalização CARD , Lipocalina-2/genética , Macrófagos/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Infarto do Miocárdio/metabolismoRESUMO
Background: The Swanson Nolan, and Pelham scale version IV (SNAP-IV) is the most critical tool for ADHD screening and diagnosis, which has two scoring methods. ADHD requires symptom assessment in multiple scenarios, and parent and teacher reports are indispensable for diagnosing ADHD. But the differences of assessment results from fathers, mothers and teachers, and the consistency of results from different scoring methods are unknown. Therefore, we carried out this study to understand the differences in the scores of fathers, mothers and teachers using SNAP-IV for children with ADHD and to explore the differences in scoring results under different scoring methods. Methods: The SNAP-IV scale and Demographics Questionnaire and Familiarity Index were used to survey fathers, mothers and head teachers. Measurement data are expressed as the mean ± standard deviation (x ± s). The enumeration data were described by frequency and percentage. ANOVA was used to compare group differences in mothers', fathers', and teachers' mean SNAP-IV scores. The Bonferroni method was used for post hoc multiple comparison tests. Cochran's Q test was used to compare the differences in the abnormal rate of SNAP-IV score results of mothers, fathers and teachers. Dunn's test was used for post hoc multiple comparison tests. Results: There were differences in scores among the three groups, and the differences showed inconsistent trends across the different subscales. Differences between groups were calculated again with familiarity as a control variable. The results showed the familiarity of parents and teachers with the patients did not affect the differences in their scores. The evaluation results were different under two assessment methods. Conclusion: Results concluded that fathers did not appear to be an appropriate candidate for evaluation. When using the SNAP-V for assessment, it should be comprehensively considered from both the scorer and symptom dimensions.
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BACKGROUND: Implicit rationing of nursing care can adversely affect patient safety and the quality of care, and increase nurses' burnout and turnover tendency. Implicit rationing care occurs at the nurse-to-patient level (micro-level), and nurses are direct participants. Therefore, the strategies based on experience of nurses to reduce implicit rationing care have more reference value and promotion significance. The aim of the study is to explore the experience of nurses to reduce implicit rationing care, thereby to provide references for conducting randomized controlled trials to reduce implicit rationing care. METHODS: This is a descriptive phenomenological study. Purpose sampling was conducted nationwide. There are 17 nurses were selected and semi-structured in-depth interviews were conducted. The interviews were recorded, transcribed verbatim and analyzed via thematic analysis. RESULTS: Our study found that nurses' reported experience of coping with implicit rationing of nursing care contained three aspects: personal, resource, and managerial. Three themes were extracted from the results of the study: (1) improving personal literacy; (2) supplying and optimizing resources and (3) standardizing management mode. The improvement of nurses' own qualities are the prerequisites, the supply and optimization of resources is an effective strategy, and clear scope of work has attracted the attention of nurses. CONCLUSION: The experience of dealing with implicit nursing rationing includes many aspects. Nursing managers should be grounded in nurses' perspectives when developing strategies to reduce implicit rationing of nursing care. Promoting the improvement of nurses' skills, improving staffing level and optimizing scheduling mode are promising measures to reduce hidden nursing rationing.
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Liquidambarines A - C (1-3), three new abietane-type diterpenoids, together with five known compounds (4-8) were isolated from the resin of Liquidambar formosana Hance. Their structures were elucidated by the combination of spectroscopic and computational methods. We explored their anti-inflammatory potential by analyzing the protein expression of iNOS and COX-2. Compounds 1 and 3 exhibit significant anti-inflammatory activities without cytotoxicity. These experimental studies suggest these new abietane-type diterpenoids have the potential to be candidates for inflammation-associated diseases.
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Background: Gastric cancer is a common cancer worldwide and is responsible for over one million new cases in 2020 and an estimated 769,000 deaths, ranking fifth for incidence and fourth for mortality globally. Incidence rates are highest in Eastern Asia and Eastern Europe. Gastric cancer is highly heterogeneous and progresses rapidly. The prognosis of gastric cancer with liver metastases is poor, and clinical treatment remains challenging. Human epidermal growth factor receptor 2 (HER2) positivity is correlated to a bad prognosis for gastric cancer. Trastuzumab combined with systemic chemotherapy is the preferred treatment for HER2-positive advanced gastric cancer. However, intravenous chemotherapy has severe systemic toxicity, which reduces the local drug concentration and tumor uptake rate, and the effect is unsatisfactory. Case summary: We reported a 66-year-old patient with HER2-positive advanced gastric cancer with jaundice due to multiple liver metastases, after 6 cycles of trastuzumab combined with hepatic arterial infusion chemotherapy (HAIC), the tumor retracted significantly, the jaundice subsided, and the patient recovered well. The patient achieved disease control with an intensive regimen followed by less toxic maintenance therapy. Trastuzumab combined with capecitabine maintenance therapy followed up for more than 16 months. Conclusion: HAIC plus trastuzumab may be a tolerable treatment option for patients with severe liver metastases from HER2-positive gastric cancer to achieve local control and prolong survival.
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[This corrects the article DOI: 10.3389/fpsyt.2021.802513.].
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Aims: To explore the public's preference for psychological interventions through a discrete choice experiment and to provide references for formulating psychological intervention policies and establishing psychological intervention procedures in response to public health emergencies. Methods: This study is a discrete choice experiment. Attributes and levels were identified through literature reviews, in-depth interviews, focus group discussions, and expert consultations. Experimental design principles were applied to generate choice sets containing different attribute levels and develop a survey instrument. Convenience sampling was conducted nationwide, and 1,045 participants were investigated. A mixed logit model was used to evaluate the public's preferences. Results: All attributes in our study were found to have a significant influence on the public's preferences for psychological interventions during the COVID-19 pandemic. The public's preferences for providers and duration were influenced by the public's levels of education and classifications. Furthermore, the most ideal scenario was found to be a one-on-one psychological intervention provided by family and friends through social network platforms, for which the frequency is twice per week, and the duration of each intervention is 0.5-1 h. Conclusions: The public's preferences for psychological interventions during the COVID-19 pandemic are affected by the method, form, frequency, provider, and duration of interventions. Our findings provide references for the formulation of psychological intervention policies and the establishment of psychological intervention procedures in response to public health emergencies.
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SYNOPSIS: NF-κB signaling has been reported to play a key regulatory role in the pathogenesis of Alzheimer's disease (AD). The purpose of this study is to investigate the effects of ginkgolide on cell viability in an AD cellular model involving an APP/PS1 double gene-transfected HEK293 cell line (APP/PS1-HEK293) and further explore the mechanisms of action related to NF-κB signaling. The optimal time point and concentration of ginkgolide for cell proliferation were screened using a cell counting kit-8 assay. Based on the results, an in vitro study was performed by co-culture of APP/PS1-HEK293 with different dosages of ginkgolide, followed by an enzyme-linked immunosorbent assay to measure the levels of supernatant tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6, as well as western blotting and real-time polymerase chain reaction to detect intracellular protein and mRNA expression of NF-κB p65, IκBa, Bcl-2, and Bax. APP/PS1-HEK293 cells exhibited the highest cell viability at a concentration of 100 µg/ml after 48 h of treatment with ginkgolide. The supernatant levels of TNF-α, IL-1ß, and IL-6 in the high-dosage ginkgolide-treated groups were lower than those in the control group. Compared with the control group, there were decreased intracellular protein and mRNA expression of NF-κB p65 and Bax, but increased protein and mRNA expression of IκBa in both high-dosage and low-dosage groups. Ginkgolide may enhance cell viability, indicative of its neuroprotective effects on AD, at least partially via suppression of the NF-κB signaling pathway involving anti-apoptosis and anti-inflammation mechanisms. Therefore, ginkgolide might be a promising therapeutic agent against AD.
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Doença de Alzheimer , NF-kappa B , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Ginkgolídeos/farmacologia , Células HEK293 , Humanos , Interleucina-6 , NF-kappa B/metabolismo , RNA Mensageiro , Transdução de Sinais , Fator de Necrose Tumoral alfa/farmacologia , Proteína X Associada a bcl-2RESUMO
PURPOSES: The purposes of this discrete choice experiment are as follows: (1) to investigate the preferences of gastric cancer survivors for follow-up care, and (2) to quantify the importance of follow-up care-related characteristics that may affect the gastric cancer survivors' choices of their follow-up, so as to provide references for the development of the follow-up strategy of gastric cancer survivors. METHODS: Discrete choice experimental design principle was applied to develop the survey instrument. All questionnaires were filled out by the respondents and collected on site. A mixed logit model was used to estimate gastric cancer survivors' preferences. Willingness to pay estimates and simulations of follow-up uptake rates were calculated. RESULTS: All six attributes are significantly important for the follow-up care of gastric cancer survivors (p < 0.05). Achieving very thorough follow-up contents was the most valued attribute level (coefficient = 1.995). Specialist doctors are the most preferred providers followed by specialist nurses, and gastric cancer survivors were willing to pay more for these attribute levels. Changes in attribute levels affected uptake rate of follow-up. When the multiple attribute levels were changed at the same time, a very thorough follow-up content was provided by the same specialist doctor (specialist nurse), and the probability of receiving follow-up increases by 95.82% (94.90%). CONCLUSIONS: The characteristics of follow-up care in our study reflect the health management services' expectations of gastric cancer survivors. A dedicated specialist nurse involved in follow-up care should be developed to contribute to solve the complex and multifaceted personal needs of gastric cancer survivors.
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Sobreviventes de Câncer , Neoplasias Gástricas , Assistência ao Convalescente , Comportamento de Escolha , Humanos , Preferência do Paciente , Neoplasias Gástricas/terapia , Inquéritos e Questionários , SobreviventesRESUMO
Ischemic stroke is a severe and acute neurological disorder with limited therapeutic strategies currently available. Oxidative stress is one of the critical pathological factors in ischemia/reperfusion injury, and high levels of reactive oxygen species (ROS) may drive neuronal apoptosis. Rescuing neurons in the penumbra is a potential way to recover from ischemic stroke. Endogenous levels of the potent ROS quencher glutathione (GSH) decrease significantly after cerebral ischemia. Here, we aimed to investigate the neuroprotective effects of γ-glutamylcysteine (γ-GC), an immediate precursor of GSH, on neuronal apoptosis and brain injury during ischemic stroke. Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) were used to mimic cerebral ischemia in mice, neuronal cell lines, and primary neurons. Our data indicated that exogenous γ-GC treatment mitigated oxidative stress, as indicated by upregulated GSH and decreased ROS levels. In addition, γ-GC attenuated ischemia/reperfusion-induced neuronal apoptosis and brain injury in vivo and in vitro. Furthermore, transcriptomics approaches and subsequent validation studies revealed that γ-GC attenuated penumbra neuronal apoptosis by inhibiting the activation of protein kinase R-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1α (IRE1α) in the endoplasmic reticulum (ER) stress signaling pathway in OGD/R-treated cells and ischemic brain tissues. To the best of our knowledge, this study is the first to report that γ-GC attenuates ischemia-induced neuronal apoptosis by suppressing ROS-mediated ER stress. γ-GC may be a promising therapeutic agent for ischemic stroke.
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Dipeptídeos/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , AVC Isquêmico/tratamento farmacológico , Neurônios/efeitos dos fármacos , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Apoptose , Infarto da Artéria Cerebral Média/complicações , AVC Isquêmico/etiologia , AVC Isquêmico/metabolismo , AVC Isquêmico/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de SinaisRESUMO
INTRODUCTION: Follow-up care is important for gastric cancer survivors, but follow-up strategies for gastric cancer survivors remain inconsistent, and compliance of gastric cancer survivors with follow-up care is very low. Understanding the needs and preferences of gastric cancer survivors is conducive to developing appropriate and acceptable follow-up strategies, thereby improving patient compliance. Discrete choice experiments can quantify individual needs and preferences. However, to date, there is no discrete choice experiment on the preferences of gastric cancer survivors, and no studies have examined how gastric cancer survivors make choices based on different characteristics of follow-up. This paper outlines an ongoing discrete choice experiment that aims to (1) explore follow-up service-related characteristics that may affect gastric cancer survivors' choices about their follow-up, (2) elicit how gastric cancer survivors consider the trade-offs among different follow-up service options using discrete choice experiment, (3) determine whether gastric cancer survivors' needs and preferences for follow-up vary due to the economy, politics, technology and culture in different regions. METHODS AND ANALYSIS: Six attributes were developed through a literature review, semistructured interviews and experts and focus group discussions. A fractional factorial design was used to evaluate the interaction between attributes. A multiple logit model will be used to understand the trade-off between the follow-up characteristics of gastric cancer survivors. A mixed logit model will be used to explore the willingness to pay and uptake rate of gastric cancer survivors for follow-up attributes and further explore the preferences of different groups. ETHICS AND DISSEMINATION: This study was approved by the ethics committee of the School of Nursing, Jilin University. The results of this study will be shared through online blogs, policy briefs, seminars and peer-reviewed journal articles and will be used to modify the current strategy of gastric cancer survivors' follow-up services according to economic development and regional culture.
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Sobreviventes de Câncer , Neoplasias , Comportamento de Escolha , Grupos Focais , Seguimentos , Humanos , Preferência do Paciente , SobreviventesRESUMO
Ischemic stroke is a devastating disease with high morbidity and mortality rates, and the proinflammatory microglia-mediated inflammatory response directly affects stroke outcome. Previous studies have reported that JLX001, a novel compound with a structure similar to that of cyclovirobuxine D (CVB-D), exerts antiapoptotic, anti-inflammatory and antioxidative effects on ischemia-induced brain injury. However, the role of JLX001 in microglial polarization and nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome regulation after ischemic stroke has not been fully investigated. In this study, we used the middle cerebral artery occlusion (MCAO) method to establish a focal cerebral ischemia model and found that JLX001 attenuated the brain infarct size and improved cerebral damage. Moreover, the expression levels of proinflammatory cytokines (interleukin [IL]-1ß and tumor necrosis factor [TNF]-α) were significantly reduced while those of the anti-inflammatory cytokine IL-10 were increased in the JLX001-treated group. Immunofluorescence staining and flow cytometry revealed an increased number of anti-inflammatory phenotypic microglia and a reduced number of proinflammatory phenotypic microglia in JLX001-treated MCAO mice. Western blotting analysis showed that JLX001 inhibited the expression of NLRP3 and proteins related to the NLRP3 inflammasome axis in vivo. Furthermore, JLX001 reduced the number of NLRP3/Iba1 cells in ischemic penumbra tissues. Finally, mechanistic analysis revealed that JLX001 significantly inhibited the expression of proteins related to the NF-κB signaling pathway. Additionally, pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor, ameliorated cerebral ischemia-reperfusion injury by suppressing microglial polarization towards the proinflammatory phenotype and NLRP3 activation in vivo, further suggesting that these protective effects of JLX001 were mediated by inhibition of the NF-κB signaling pathway. These results suggest that JLX001 is a promising therapeutic approach for ischemic stroke.
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Isquemia Encefálica/tratamento farmacológico , Inflamassomos/efeitos dos fármacos , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Triterpenos/uso terapêutico , Animais , Western Blotting , Isquemia Encefálica/imunologia , Isquemia Encefálica/metabolismo , Polaridade Celular/efeitos dos fármacos , Citometria de Fluxo , Imunofluorescência , Inflamassomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Fármacos Neuroprotetores/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Triterpenos/farmacologiaRESUMO
INTRODUCTION: Hypoglycemic drugs affect the bone quality and the risk of fractures in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and insulin on bone mineral density (BMD) in T2DM. METHODS: In this single-blinded study, a total of 65 patients with T2DM were randomly assigned into four groups for 52 weeks: the exenatide group (n = 19), dulaglutide group (n = 19), insulin glargine group (n = 10), and placebo (n = 17). General clinical data were collected, and BMD was measured by dual-energy X-ray absorptiometry. RESULTS: Compared with baseline, the glycosylated hemoglobin (HbA1c) decreased significantly in the exenatide (8.11 ± 0.24% vs. 7.40 ± 0.16%, P = 0.007), dulaglutide (8.77 ± 0.37% vs. 7.06 ± 0.28%, P < 0.001), and insulin glargine (8.57 ± 0.24% vs. 7.23 ± 0.25%, P < 0.001) groups after treatment. In the exenatide group, the BMD of the total hip increased. In the dulaglutide group, only the BMD of the femoral neck decreased (P = 0.027), but the magnitude of decrease was less than that in the placebo group; the BMD of L1-L4, femoral neck, and total hip decreased significantly (P < 0.05) in the placebo group, while in the insulin glargine group, the BMD of L2, L4, and L1-4 increased (P < 0.05). Compared with the placebo group, the BMD of the femoral neck and total hip in the exenatide group and the insulin glargine group were increased significantly (P < 0.05); compared with the exenatide group, the BMD of L4 in the insulin glargine group was also increased (P = 0.001). CONCLUSIONS: Compared with the placebo, GLP-1RAs demonstrated an increase of BMD at multiple sites of the body after treatment, which may not exacerbate the consequences of bone fragility. Therefore, GLP-1RAs might be considered for patients with T2DM. This trial is registered with ClinicalTrials.gov NCT01648582.
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Densidade Óssea , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Exenatida/farmacologia , Exenatida/uso terapêutico , Feminino , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/farmacologia , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Humanos , Fragmentos Fc das Imunoglobulinas/farmacologia , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Insulina Glargina/farmacologia , Insulina Glargina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão/farmacologia , Proteínas Recombinantes de Fusão/uso terapêuticoRESUMO
BACKGROUND: It is very necessary to implement gastric cancer screening in China to reduce the mortality of gastric cancer, but there are no national screening guidelines and programs. Understanding of individual preferences is conducive to formulating more acceptable screening strategies, and discrete choice experiments can quantify individual preferences. In addition, the first-degree relatives of gastric cancer patients are at high risk for gastric cancer. Compared with those without a family history of gastric cancer, the risk of gastric cancer in first-degree relatives of gastric cancer patients is increased by 60%. Therefore, a discrete choice experiment was carried out to quantitatively analyse the preferences of first-degree relatives of gastric cancer patients for gastric cancer screening to serve as a reference for the development of gastric cancer screening strategies. METHODS: A questionnaire was designed based on a discrete choice experiment, and 342 first-degree relatives of gastric cancer patients were investigated. In STATA 15.0 software, the data were statistically analysed using a mixed logit model. RESULTS: The five attributes included in our study had a significant influence on the preferences of first-degree relatives of gastric cancer patients for gastric cancer screening (P < 0.05). Participants most preferred the sensitivity of the screening program to be 95% (coefficient = 1.424, P < 0.01) with a willingness to pay 2501.902 Yuan (95% CI, 738.074-4265.729). In addition, the participants' sex and screening experiences affected their preferences. An increase in sensitivity 35 to 95% had the greatest impact on the participants' willingness to choose a gastric cancer screening program. CONCLUSION: The formulation of gastric cancer screening strategies should be rooted in people's preferences. The influence of sex differences and screening experiences on the preferences of people undergoing screening should be considered, and screening strategies should be formulated according to local conditions to help them play a greater role.
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Comportamento de Escolha/fisiologia , Detecção Precoce de Câncer/psicologia , Família/psicologia , Preferência do Paciente/psicologia , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/psicologia , Inquéritos e QuestionáriosRESUMO
AIMS: To evaluate the compliance of patients after gastrectomy in taking oral nutritional supplementation and to explore the promoting and hindering factors. DESIGN: A mixed-methods design with an explanatory sequential approach was employed. METHODS: We conducted a 12-week longitudinal study to evaluate the oral nutritional supplementation compliance of 122 patients after gastric cancer surgery and the factors that affected their compliance. After the quantitative phase, we selected the interview subjects and developed the interview outline based on the analysis of the quantitative results. In-depth interviews (n = 15) were conducted to explain and supplement the quantitative phase results. Data were collected from October 2019 to May 2020. RESULTS: The average overall compliance rate of oral nutritional supplementation in patients with gastric cancer over 12 weeks was 30.59%. Adverse reactions to oral nutritional supplementation, the identity of the main caregivers and the patient's financial ability were independent factors that affected patient compliance. In subsequent interviews, we extracted four themes: social support plays an important role in patients taking oral nutritional supplementation, adverse reactions discourage patients from continuing to take oral nutritional supplementation, patients' attitudes affect their motivation to take oral nutritional supplementation, and the different needs of patients for oral nutritional supplementation affect patient compliance. CONCLUSION: Patients' compliance with oral nutritional supplementation after gastric cancer surgery is very low. Health education should pay more attention to the management of adverse reactions and the role of patients' peers and family members. Oral nutritional supplementation products should be diversified to provide patients with more choices. IMPACT: This study clarifies the factors that hinder and promote oral nutritional supplementation compliance and provides an important reference for the establishment and revision of health education strategies for patients after gastric cancer surgery.
Assuntos
Gastrectomia , Neoplasias Gástricas , Suplementos Nutricionais , Humanos , Estudos Longitudinais , Cooperação do Paciente , Neoplasias Gástricas/cirurgiaRESUMO
INTRODUCTION: Postoperative malnutrition is a major issue in patients with gastric cancer. The European Society for Clinical Nutrition and Metabolism recommends oral nutritional supplements (ONS) as a first-line nutritional therapy to prevent malnutrition in patients with cancer. However, adherence to ONS is unsatisfactory. The overall aim of this study was to evaluate the adherence of patients with gastric cancer to ONS and to explore the promoting and hindering factors. METHODS AND ANALYSIS: In this study, we will use mixed methods with an explanatory sequential approach for data collection and analysis. In the first phase, a 12-week longitudinal study will be performed to identify changes in trends of oral nutritional supplementation adherence in 135 patients with gastric cancer, the impact of adherence on nutritional indicators and clinical outcomes and ONS adherence-related factors. The primary endpoints include patient adherence to ONS, weight, body mass index and grip strength followed by 30-day readmission rate, complications and adverse reactions. In the second stage, qualitative research will be implemented to provide in-depth insight into the quantitative results. Finally, quantitative and qualitative results will be combined for analysis and discussion to put forward suggestions for improving patients' ONS adherence. ETHICS AND DISSEMINATION: This research protocol has been approved by the Ethics Committee of the School of Nursing, Jilin University, China (No. 2019101601). Results will be disseminated in peer-reviewed journals and conferences, and sent to participating practices. TRIAL REGISTRATION NUMBER: ChiTR2000032425.