RESUMO
ABSTRACT: Background: Sepsis-associated acute lung injury (SA-ALI) is a serious threat to human health. A growing body of evidence suggested that circular RNAs may be involved in ALI progression. The aim of this study was to investigate the effect and mechanism of circ_0001226 on lipopolysaccharide (LPS)-induced BEAS-2B cells. Methods: BEAS-2B cells were stimulated with LPS to establish a SA-ALI cell model. The expression of circ_0001226, miR-940, and transforming growth factor beta receptor II (TGFBR2) were monitored by quantitative real-time polymerase chain reaction. Cell proliferation and apoptosis were evaluated by the Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine assay, and flow cytometry. The levels of interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α were calculated by enzyme-linked immunosorbent assay. Western blot was implemented to test the protein levels of PCNA, Bax, and TGFBR2. Dual-luciferase reporter assay and RNA pull-down assay were adopted to investigate the interaction between circ_0001226 and miR-940, as well as TGFBR2 and miR-940. Results: The levels of circ_0001226 and TGFBR2 were elevated, and miR-940 was decreased in SA-ALI serum specimens and LPS-evoked BEAS-2B cells. Besides that, circ_0001226 interference contributed to cell proliferation and restrained apoptosis and inflammation in LPS-induced BEAS-2B cells. Mechanically, circ_0001226 worked as a molecular sponge of miR-940 to regulate TGFBR2 expression. Conclusion: Circ_0001226 deficiency weakened LPS-mediated proliferation inhibition and inflammatory processes in BEAS-2B cells by binding miR-940 and regulating TGFBR2.
Assuntos
Lesão Pulmonar Aguda , MicroRNAs , Humanos , Lipopolissacarídeos/toxicidade , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Apoptose/genética , Proliferação de Células/genética , MicroRNAs/genéticaRESUMO
BACKGROUND It is reported that trauma hemorrhagic shock (THS) could resulted in organ injury and is related to a high mortality rate. Maresin-1 (MaR1), a derived medium through biosynthesis, is involved in inflammatory responses. However, the mechanism of MaR1 against acute lung injury needs to be further understood. This report aimed to explore whether MaR1 had a protective effect on lung injury. MATERIAL AND METHODS We constructed a THS-induced acute lung damage rat model and then treated the rats with MaR1. We determined Evan's blue dye (EBD) lung permeability, lung permeability index, wet/dry (W/D) weight ratio, nitric oxide (NO) concentration and inducible nitric oxide synthase (iNOS) expression in lung tissue samples. The inflammation-related cytokines levels in the bronchoalveolar lavage fluid (BALF) and serum of rats were determined by enzyme-linked immunosorbent assay (ELISA). Finally, the TLR4/p38MAPK/NF-kappaB pathway was analyzed by quantitative real-time polymerase chain reaction and western blot assay. RESULTS The increased EBD ratio, lung permeability index and W/D weight ratio, NO concentration and iNOS levels were suppressed by MaR1 treatment. THS-induced over-production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in BALF and serum was suppressed by MaR1. Besides, the TLR4/p38MAPK/NF-kappaB pathway activation in THS-induced rats were inhibited by MaR1 treatment. CONCLUSIONS Our study showed that MaR1 could effectively alleviated THS-induced lung injury via inhibiting the excitation of the TLR4/p38MAPK/NF-kappaB pathway in THS-induced rats, suggesting that MaR1 might be a novel agent for lung damage treatment.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Ácidos Docosa-Hexaenoicos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Choque Hemorrágico/complicações , Lesão Pulmonar Aguda/sangue , Animais , Líquido da Lavagem Broncoalveolar/química , Citocinas/sangue , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Resultado do Tratamento , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
OBJECTIVE: To explore the effective strategies of clinical pathway construction in intensive care unit (ICU). METHODS: From January 2016 to July 2018, 1 488 patients were discharged from ICU of Liuzhou Worker's Hospital of Guangxi Zhuang Autonomous Region. The pilot project of "postoperative monitoring of heart disease" with simpler route and less variation was selected first, and then the pilot project was promoted to "post-operative monitoring" after its success. The implementation of the clinical pathway was divided into three stages: the first stage, January 2016 to May 2017, for the pilot phase, a total of 87 patients were enrolled in the clinical pathway trial; the second stage, June 2017 to December 2017, surgical ICU "postoperative monitoring of heart disease" was put into the pathway 111 times; the third stage, January 2018 to July 2018, surgical ICU "postoperative monitoring of heart disease" was entered in the path 116 times; comprehensive ICU "postoperative care" was put into the path 96 times. After carefully analyzed the reasons and sum up the experience, internet+medical treatment (Liuzhou Worker's Hospital became the fifth deep partner of Tencent Inc in the internet+medical field, and carried out the plan and practice of "WeChat wisdom hospital 3.0" in 2017) was used, four aspects of connection, payment, security and ecological cooperation were upgraded, and the construction of 6 level of electronic medical record (EMR) was accelerated. At the same time, through diagnosis related groups system (DRGs), the concept of evidence-based medicine, quality management and continuous improvement as the leading factor, and combined with the construction status of hospital information system (HIS) and EMR system, step by step implementation and design of information management platform for clinical pathway were formulated. The completion rate of clinical pathway, average length of hospital stay, average cost, cure rate and improvement rate were the main observation parameters. RESULTS: In the first stage, none of the 87 patients who entered the clinical pathway completed the clinical pathway. In the second stage, the completion rate of surgical ICU clinical pathway was increased from 33.33% in June 2017 to 94.44% in December 2017, and up to 100% in October 2017, and the average completion rate from January to July 2018 was 94.00%. The completion rate of ICU clinical pathway was increased from 81.82% in January 2008 to 92.86% in July 2008. There was a significant difference in the overall clinical pathway completion rate from 2016 to 2018 (χ2 = 204.300, P = 0.000). After the effective implementation of clinical pathway in June 2017, the length of hospital stay of patients was significantly shortened as compared with that before implementation (days: 2.96±0.43 vs. 6.66±0.75, P < 0.01), and the daily cost was significantly reduced (Yuan: 3 550.92±755.51 vs. 6 171.48±377.29, P < 0.01). The average length of hospital stay was shortened by about 3.84 days (P < 0.01), and the average daily cost was reduced by about 2 108.39 Yuan (P < 0.01) after the implementation of clinical pathway by surgical ICU "postoperative monitoring of heart disease" as compared with those before implementation. The average length of hospital stay was shortened by about 2.98 days (P < 0.01) and the average daily cost was reduced by 5 094.13 Yuan (P < 0.01) after the implementation of clinical pathway by comprehensive ICU "post-operative monitoring" as compared with those before implementation. At the same time, the cure rate was increased from 1.16% (7/603) to 42.26% (105/227), and the improvement rate was decreased from 94.36% (569/603) to 52.86% (120/227, both P < 0.01) after the implementation of surgical ICU clinical pathway, but there was no significant difference in the cure rate or the improvement rate after the implementation of comprehensive ICU [2.77% (33/1 193) vs. 2.22% (2/90), 79.21% (945/1 193) vs. 97.78% (88/90), both P > 0.05]. CONCLUSIONS: Application of clinical pathway to control ICU quality and guide diagnosis and treatment, more refined diagnosis and treatment schemes including clinical guidelines, average length of stay, average cost of hospitalization, cost-efficiency ratio and so on were completed, which confirmed that the improvement of clinical pathway management strategy originated from clinical were needed. Informatization, intellectualization, standardization and effective control of medical cost of clinical pathway could improve medical quality and accurate management. The integration of ICU clinical pathway construction and HIS could promote the development of digital hospitals.