RESUMO
Glioma stem cells (GSCs) contribute to the malignant growth of glioma, but little is known about the interaction between GSCs and tumor microenvironment. Here, we found that intense infiltration of regulatory T cells (Tregs) facilitated the qualities of GSCs through TGF-ß secretion that helped coordinately tumor growth. Mechanistic investigations indicated that TGF-ß acted on cancer cells to induce the core cancer stem cell-related genes CD133, SOX2, NESTIN, MUSASHI1 and ALDH1A expression and spheres formation via NF-κB-IL6-STAT3 signaling pathway, resulting in the increased cancer stemness and tumorigenic potential. Furthermore, Tregs promoted glioma tumor growth, and this effect could be abrogated with blockade of IL6 receptor by tocilizumab which also demonstrated certain level of therapeutic efficacy in xenograft model. Additionally, expression levels of CD133, IL6 and TGF-ß were found to serve as prognosis markers of glioma patients. Collectively, our findings reveal a new immune-associated mechanism underlying Tregs-induced GSCs. Moreover, efforts to target this network may be an effective strategy for treating glioma.
Assuntos
Glioma/imunologia , Glioma/metabolismo , Células-Tronco Neoplásicas/metabolismo , Transdução de Sinais , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Biomarcadores , Autorrenovação Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Glioma/mortalidade , Glioma/patologia , Humanos , Imunofenotipagem , Interleucina-6/metabolismo , Camundongos , NF-kappa B/metabolismo , Prognóstico , Fator de Transcrição STAT3 , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND: Clinical practice guidelines on normal childbirth were issued worldwide with a view to achieve evidence-based, cost-effective and universal intrapartum care. Effective implementation of guideline recommendations is impossible without a full evaluation and understanding of current practice and factors influencing adherence among midwives. AIM: This study aimed to explore midwives' adherence to clinical practice guidelines on normal childbirth and factors influencing the implementation of guideline recommendations in mainland China. DESIGN: We used a mixed-method sequential explanatory design. METHODS: A national level cross-sectional survey was conducted among 718 midwives to investigate their adherence to guideline recommendations on normal childbirth. Based on the findings of quantitative study phase, we developed the interview outline and performed semi-structured interviews with thirteen midwives to explore potential factors influencing their implementation of normal childbirth guidelines. An inductive thematic analysis was undertaken to identify themes, which were then deductively mapped to the Theoretical Domains Framework (TDF). RESULTS: Midwives' adherence to the guideline recommendations was relatively low, with non-adherence to thirteen guideline recommendations (41.94%) being observed. Six domains on the TDF and one additional theme were found to be factors influencing midwives' implementation of guideline recommendations on normal childbirth, with behavioural regulation, beliefs about consequences, professional roles and responsibilities being identified as barriers for interventions recommended against use, knowledge, environmental context and resources being identified as enablers for interventions recommended for use, and skills and women's preference being identified as barriers/enabler for both. CONCLUSION: Guideline adherence can be improved by multifaceted efforts at professional, organizational and maternal levels. The identification of barriers and enablers of guideline implementation provides a solid foundation for further reducing non-evidence-based intrapartum interventions.
Assuntos
Tocologia , Gravidez , Feminino , Humanos , Tocologia/métodos , Estudos Transversais , Parto Obstétrico/métodos , Parto , Fidelidade a Diretrizes , Pesquisa QualitativaRESUMO
OBJECTIVE: The aim of this study was to determine the effect of empowerment-based interventions on glucose metabolism control and psychosocial self-efficacy in people with type 2 diabetes mellitus (T2DM). METHODS: The Cochrane Library, Embase, PubMed, and Web of Science electronic databases were searched up to 22 February 2021 for randomized controlled trials (RCTs) that evaluated the effectiveness of empowerment-based intervention versus conventional treatment in type 2 diabetes cases. At least two investigators independently screened the literature, extracted data and evaluated the methodological quality. We calculated the pooled effect size using the mean difference (MD) or standard mean difference (SMD) with 95% confidence intervals (CIs) through RevMan V 5.4.1. RESULTS: Fifteen randomized controlled trials (RCTs) were eligible for inclusion in the present study. A total of 2344 adults (1128 in the intervention groups and 1216 in the control) were covered. Five of these studies involved 671 cases of psychosocial self-efficacy, and 4 studies included 622 cases of diabetes knowledge. The meta-analysis showed that compared to routine care, empowerment-based intervention was associated with reduced glycated hemoglobin levels (SMD -0.20; 95% CI -0.31 to -0.08; Zâ=â3.40, Pâ<â.001, I2â=â42%), increased diabetes empowerment scores (SMD 0.24; 95% CI 0.10-0.37; Zâ=â3.42, Pâ<â.001, I2â=â0%), and increased diabetes knowledge scores (SMD 0.96; 95% CI 0.55-1.36; Zâ=â4.61, Pâ<â.001, I2â=â80%). CONCLUSIONS: Empowerment-based intervention in adults with T2DM results in improvements in glycated hemoglobin, psychosocial self-efficacy and diabetes knowledge.