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Sepsis, the most severe manifestation of infection, poses a major challenge to health-care systems around the world. Limited ability to clean and remove the pathogen renders difficulty in septic patients to recover from the phase of immunoparalysis. The present study found the vital role of CX3CR1 internalization on sepsis-induced immunoparalysis. A mouse model with cecal ligation and puncture (CLP) and cell model with lipopolysaccharides (LPS) were employed to explore the relationship between CX3CR1 internalization and septic immunoparalysis. Immunoparalysis model in mice was established 4 days after CLP with significantly decreased proinflammatory cytokines. Flow cytometry analysis found a decreased surface expression of CX3CR1 during immunoparalysis, which was associated with reduced mRNA level and increased internalization of CX3CR1. G-protein coupled receptor kinase 2 (GRK2) and ß-arrestin2 were significantly increased during septic immunoparalysis and involved in the internalization of CX3CR1. TLR4-/- or TLR4 inhibitor-treated macrophages exhibited an inhibited expression of GRK2 and ß-arrestin2, along with reduced internalization of CX3CR1. Moreover, the knockdown of GRK2 and ß-arrestin2 inhibited the internalization of CX3CR1 and led to a higher response on the second hit, which was associated with an increased activation of NF-κB. The critical association between internalization of CX3CR1 and immunosuppression in sepsis may provide a novel reference for clinical therapeutics.
RESUMEN
PURPOSE: Postoperative nausea and vomiting (PONV) is a frequent complication in postoperative period. The aim of the current meta-analysis was to assess the efficacy of dexmedetomidine on PONV. METHODS: Two researchers independently searched PubMed, Embase and Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs). The meta-analysis was performed with Review Manager. RESULTS: Eighty-two trials with 6,480 patients were included in this meta-analysis. Dexmedetomidine reduced postoperative nausea (Risk Ratio (RR) = 0.61, 95% confidence interval (CI): 0.50 to 0.73) and vomiting (RR = 0.48, 95% CI: 0.36 to 0.64) compared with placebo, with an effective dose of 0.5 ug/kg (RR = 0.46, 95% CI: 0.34 to 0.62) and 1.0 ug/kg (RR = 0.29, 95% CI: 0.12 to 0.75), respectively. The antiemetic effect can only be achieved intravenously, not epidurally or intrathecally. The efficacy of dexmedetomidine was similar to that of widely used agents, such as propofol, midazolam etc., but better than opioid analgesics. Moreover, application of dexmedetomidine reduced intraoperative requirement of fentanyl (Standard Mean Difference = -1.91, 95% CI: -3.20 to -0.62). CONCLUSIONS: The present meta-analysis indicates that dexmedetomidine shows superiority to placebo, but not to all other anesthetic agents on PONV. And this efficacy may be related to a reduced consumption of intraoperative opioids.
RESUMEN
PURPOSE: Postoperative nausea and vomiting (PONV) is a frequent complication in postoperative period. The aim of the current meta-analysis was to assess the efficacy of dexmedetomidine on PONV. METHODS: Two researchers independently searched PubMed, Embase and Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs). The meta-analysis was performed with Review Manager. RESULTS: Eighty-two trials with 6,480 patients were included in this meta-analysis. Dexmedetomidine reduced postoperative nausea (Risk Ratio (RR) = 0.61, 95% confidence interval (CI): 0.50 to 0.73) and vomiting (RR = 0.48, 95% CI: 0.36 to 0.64) compared with placebo, with an effective dose of 0.5 µg/kg (RR = 0.46, 95% CI: 0.34 to 0.62) and 1.0 µg/kg (RR = 0.29, 95% CI: 0.12 to 0.75), respectively. The antiemetic effect can only be achieved intravenously, not epidurally or intrathecally. The efficacy of dexmedetomidine was similar to that of widely used agents, such as propofol, midazolam etc., but better than opioid analgesics. Moreover, application of dexmedetomidine reduced intraoperative requirement of fentanyl (Standard Mean Difference = -1.91, 95% CI: -3.20 to -0.62). CONCLUSIONS: The present meta-analysis indicates that dexmedetomidine shows superiority to placebo, but not to all other anesthetic agents on PONV. And this efficacy may be related to a reduced consumption of intraoperative opioids.
RESUMEN
BACKGROUND: Traditional Chinese medicine (TCM) has been used for treatment of sepsis in China, but results still remain equivocal. To evaluate the safety and efficacy of TCM for sepsis, we conducted this Meta-analysis. METHODS: Databases searched included randomized controlled trials (RCTs) published in PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) (up to December 2014). The studies included used routine therapy treating sepsis in the control group and TCM was added on that basis in the experimental group. Methodological quality was assessed by Cochrane criteria for risk of bias. RESULTS: Ten RCTs with 691 participants were identified and analyzed. In the meta-analysis, TCM plus routine therapy reduced the 28-day mortality compared to routine therapy alone, [RR = 0.67; 95% CI: 0.51~0.87; P = 0.002]; The decrease in length of ICU-stay [MD = -1.82; 95% CI: -2.60~-1.04; P<0.00001]; Acute physiology and chronic health evaluation system (APACHE II) score [MD = -2.95; 95% CI: -3.99~-1.91; P<0.00001]; Serum inflammatory factors concentration after treatment [SMD = -0.50; 95% CI:-0.68~-0.33; P<0.00001], including TNF-α [SMD = -0.61; 95% CI: -0.85~-0.38; P<0.00001] and IL-6 [SMD = -0.40; 95% CI: -0.75~-0.04; P = 0.03] in subgroup analysis all had statistical significance. CONCLUSION: Addition of TCM has better effects in participants with sepsis, while more high-quality studies are needed to draw firm conclusion.
