ADAR1 Alleviates Inflammation in a Murine Sepsis Model via the ADAR1-miR-30a-SOCS3 Axis.

Adenosine deaminase acting on double-stranded RNA 1 (ADAR1) mediates adenosine-to-inosine (A-to-I) RNA editing events. ADAR1 is highly expressed in "septic" macrophages and in small intestinal tissues of mice with sepsis. Overexpression of ADAR1 suppresses inflammation and intestinal damage. However, the specific underlying mechanism is unclear. This study was conducted to explore how microRNA (miRNA) regulates the anti-inflammatory mechanism of macrophages following ADAR1 upregulation. A murine sepsis model was established by cecal ligation and puncture (CLP). Mice were randomly assigned to sham, CLP, and CLP+ADAR1 groups. Hematoxylin and eosin (HE) staining and fluorescence isothiocyanate-dextran were used to evaluate intestinal injury and permeability. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, and Luminex assays were performed to detect changes in the expression of inflammatory cytokines. Adenoviruses were used to express ADAR1 in RAW 264.7 cells. Ribonucleoprotein immunoprecipitation analysis was conducted to detect the binding of ADAR1 and miRNAs. A dual-luciferase reporter assay was used to detect the binding of miRNAs and regulatory factors. We observed that ADAR1 significantly increased the expression of suppressor of cytokine signaling 3 (SOCS3) in macrophages and reduced the expression of interleukin-6 in macrophages and the serum, thereby reducing intestinal permeability and mucosal injury in mice with sepsis. The RNA-ribonucleoprotein immunoprecipitation binding assay and qRT-PCR demonstrated a direct interaction between ADAR1 and pri-miR-30a. The luciferase assay demonstrated that SOCS3 was significantly inhibited by miR-30a-5p, the mature product of miR-30a. Thus, ADAR1 exerts a protective effect against sepsis by reducing inflammation and organ damage via the ADAR1-miR-30a-SOCS3 axis.

Composition and Associated Factors of Radiological Examination in Major Trauma Patients: A Prospective Observational Study.

The care of major trauma patients continues to be a challenge for emergency physicians and trauma surgeons. We found that the total number of radiological examinations for major trauma patients in this study was high and mainly comprised radiography and computed tomography (CT), with CT being more commonly adopted. The number of CT scans was positively correlated with severity of injury and intensive care unit length of stay. Further study is warranted to optimize radiological examinations involving major trauma patients.

U50488H improves organ function after septic shock / 中华急诊医学杂志

Objective To investigate the effect of U50488H on the ultrastructure and organ function in septic shock rats. Methods Forty SD male rats were randomly(random number) divided into 5 groups: sham group, septic shock group, U50488H+septic shock group, nor-BNI+U50488H+septic shock group, and nor-BNI+septic shock group, with 8 rats in each group. Cecal ligation and puncture (CLP) was performed to induce septic shock in the septic shock group. Rats in the U50488H+septic shock group were treated with U50488H injection by intravenous at the shock point, and other procedures were the same as the septic shock group. Rats in the nor-BNI+U50488H+septic shock group were treated with nor-BNI injection by intravenous 3.5 h after abdomen closed, and other procedures were the same as the U50488H+septic shock group. Except for U50488H injection, rats in the nor-BNI+septic shock group received procedures the same as the nor-BNI+U50488H+septic shock group. Albumin, cardiac troponin I (cTnI) and N terminal pro B type natriuretic peptide (NT-proBNP) in serum were measured at abdomen-closed, 3, 6, and 12 h after CLP. The changes of histology and ultramicro structure under electron microscope of lung, heart, liver and kidney of rats were observed at 12 h after CLP. Statistical analysis was performed using SPSS 19.0. Comparison among groups was carried out using ANOVA, and Student's t-test was used for multiple comparisons as post-hoc. Results At 6 and 12 h of CLP, serum albumin of the septic shock group were significantly lower than those of the sham group (P<0.01), while those in the cTnI and NT-pro BNP groups were higher at 3, 6, and 12 h of CLP (P<0.01). Compared with the septic shock group, serum albumin of the U50488H+septic shock group increased significantly (P<0.01), whereas the serum levels of cTnI and NT-pro BNP decreased remarkably at 3, 6 and 12 h of CLP (P < 0.05, P < 0.01, respectively). Compared with the sham group, the alveolar wall was severely damaged, the alveolar septum and blood vessel wall were thickened obviously; the myocardial fiber was swollen, necrotic, and the infiltration of central granulocyte was increased significantly; hepatocyte showed edema, vacuolar-like steatosis, fatty degeneration, spotty and focal necrosis; and slight edema and vacuolar degeneration were found in the glomerulus endothelial in the septic shock group. Compared with the septic shock group, the ultrastructural damage of the lung, heart, liver and kidney of the U50488H+ septic shock group was significantly improved. All the above effects of U50488H could be blocked by nor-BNI (a selective κ-opioid receptor antagonist) (P<0.01). Conclusions U50488H can promote the recovery of serum albumin, and protect organ function in septic shock rats.

Hypotensive resuscitation for traumatic hemorrhagic shock: a systematic review / 中华急诊医学杂志

Objective To systematically review the efficacy of hypotensive resuscitation for traumatic-hemorrhagic shock.Methods Randomized controlled trails (RCTs) or quasi-Randomized controlled trails (qRCTs) were searched in Pubmed,Embase and the Corchrane Library from inception to August 2015.Two reviewers respectively picked out the useful data and performed quality evaluation.Metaanalysis was carried out with RevMan 5.3 software,risk ratio (RR) and its 95％ confidence interval (CI) were pooled to estimate the enumeration data,and GRADE 3.6.1 software was used to rate the level of evidence.Results The results of meta-analysis and GRADE rating system which included 4 studies showed that:compared with conventional resuscitation,hypotensive resuscitation was associated with lower total mortality [RR =0.77,95％ CI:0.62-0.95,P =0.01;n =984,GRADE rating:moderate],and 24-hour mortality [RR =0.47,95％ CI:0.24-0.91,P =0.03;n =281,GRADE rating:moderate],but the subgroup analysis of total mortality showed that there were no significant differences in mortality between the subgroup of blunt or penetrating trauma and the subgroup of penetrating trauma.Conclusions Hypotensive resuscitation reduced total mortality and 24-hour mortality,and the quality of the evidence was moderate.The future studies should do further research to explore the efficacy of hypotensive resuscitation for different types of trauma.