Sepsis is an excessive inflammatory condition with a high mortality rate and limited prediction and therapeutic options. In this study, for the first time, to our knowledge, we found that downregulation and/or blockade of T cell Ig and mucin domain protein 3 (Tim-3), a negative immune regulator, correlated with severity of sepsis, suggesting that Tim-3 plays important roles in maintaining the homeostasis of sepsis in both humans and a mouse model. Blockade and/or downregulation of Tim-3 led to increased macrophage activation, which contributed to the systemic inflammatory response in sepsis, whereas Tim-3 overexpression in macrophages significantly suppressed TLR-mediated proinflammatory cytokine production, indicating that Tim-3 is a negative regulator of TLR-mediated immune responses. Cross-talk between the Tim-3 and TLR4 pathways makes TLR4 an important contributor to Tim-3–mediated negative regulation of the innate immune response. Tim-3 signaling inhibited LPS–TLR4–mediated NF-κB activation by increasing PI3K–AKT phosphorylation and A20 activity. This negative regulatory role of Tim-3 reflects a new adaptive compensatory and protective mechanism in sepsis victims, a finding of potential importance for modulating innate responses in these patients.
ObjectivesSenior medical students, who are future doctors, should be prepared to use antimicrobials appropriately and will be important partners in antimicrobial stewardship. This survey was designed to investigate the attitudes and perceptions of senior medical students regarding antimicrobial use and resistance.MethodologyWe performed a multi-center survey involving a questionnaire handed out to all fourth year medical students from five representative teaching hospitals in Central China. The survey was completed within 1 month (October to November, 2015). Antimicrobial stewardship programs were taught in all of the teaching hospitals, yet only part of the respondents took part in it.ResultsA total of 611 out of 728 students completed our survey. The majority of the respondents (92 %) believed that inappropriate use of antimicrobials causes antimicrobial resistance and agreed with the importance of a strong knowledge of antimicrobials in their medical careers. Most students (67 %) rated their education concerning antimicrobial use and resistance as useful or very useful, but only 25 % recalled having courses on this subject. The overall mean number of correct answers on a section of 11 knowledge questions was 3.78 (standard deviation 1.57, P value for score between hospitals <0.001).ConclusionsWe should make an effort to optimize curriculum system in Chinese institutions, and this may contribute to making our future doctors better prepared for antimicrobial stewardship and prudent antimicrobial prescribing.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-3454-0) contains supplementary material, which is available to authorized users.
As part of the Carbon Capture and Storage (CCS) process, pipeline transportation of dense phase CO2 is the safest and most economic option for delivering captured CO2 to a storage site .However, in the event of pipeline rupture an enormous mass of CO2 may be released very rapidly, presenting several risks to the pipeline and surrounding population including the significantly increased risk of brittle fracture in the pipe wall. The study of pressure variation and phase change in CO 2 during pipeline blowdown can contribute to the understanding of brittle fracture initiation and propagation, as well as downstream CO 2 diffusion behaviour. As part of the CO2QUEST project, a reusable, industrial scale pipeline experimental apparatus with a total length of 258 m and the inner diameter of 233 mm was fabricated to study CO 2 pipeline blowdown. A dual-disc blasting device was used to remotely control the opening of the pipeline, three different orifice diameters were used in experiments (15 mm, 50 mm and Full Bore Rupture). Different initial conditions in the inventory were achieved by heating the charged * Corresponding author.
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