Background:The management of pain, agitation, and delirium (PAD) in Intensive Care Unit (ICU) is beneficial for patients and makes it widely applied in clinical practice. Previous studies showed that the clinical practice of PAD in ICU was improving; yet relatively little information is available in China. This study aimed to investigate the practice of PAD in ICUs in China.Methods:A multicenter, nationwide survey was conducted using a clinician-directed questionnaire from September 19 to December 18, 2016. The questionnaire focused on the assessment and management of PAD by the clinicians in ICUs. The practice of PAD was compared among the four regions of China (North, Southeast, Northwest, and Southwest). The data were expressed as percentage and frequency. The Chi-square test, Fisher's exact test, and line-row Chi-square test were used.Results:Of the 1011 valid questionnaire forms, the response rate was 80.37%. The clinicians came from 704 hospitals across 158 cities of China. The rate of PAD assessment was 75.77%, 90.21%, and 66.77%, respectively. The rates of PAD scores were 45.8%, 68.94%, and 34.03%, respectively. The visual analog scale, Richmond agitation-sedation scale, and confusion assessment method for the ICU were the first choices of scales for PAD assessment. Fentanyl, midazolam, and dexmedetomidine were the first choices of agents for analgesic, sedation, and delirium treatment. While choosing analgesics and sedatives, the clinicians put the pharmacological characteristics of drugs in the first place (66.07% and 76.36%). Daily interruption for sedation was carried out by 67.26% clinicians. Most of the clinicians (87.24%) used analgesics while using sedatives. Of the 738 (73%) clinicians titrating the sedatives on the basis of the proposed target sedation level, 268 (26.61%) clinicians just depended on their clinical experience. Totally, 519 (51.34%) clinicians never used other nondrug strategies for PAD. The working time of clinicians was an important factor in the management of analgesia and sedation rather than their titles and educational background. The ratios of pain score and sedation score in the Southwest China were the highest and the North China were the lowest. The ratios of delirium assessment and score were the same in the four regions of China. Moreover, the first choices of scales for PAD in the four regions were the same. However, the top three choices of agents in PAD treatment in the four regions were not the same.Conclusions:The practice of PAD in China follows the international guidelines; however, the pain assessment should be improved. The PAD practice is a little different across the four regions of China; however, the trend is consistent.Trial Registration:The study is registered at http://www.clinicaltrials.gov (No. ChiCTR-OOC-16009014, www.chictr.org.cn/index.aspx.).

The GTS-21 substantially ameliorates LPS-induced ALI. This protection is predominantly associated with the inhibition of pulmonary AM M1 polarization and alteration in AM function.

Inflammatory cytokines belonging to high mobility group box (HMGB)1 play a key role in sepsis through yet unknown mechanisms. The inflammatory response is modulated by microRNAs (miRNAs or miRs) at multiple levels and is poorly understood. In this study, the regulation of HMGB1 by miRNAs was evaluated using 3-(2,4-dimethoxybenzylidene)anabaseine (GTS-21) to activate the cholinergic anti-inflammatory pathway (CAP) and decrease HMGB1 expression in RAW264.7 cells. Microarray-based miRNA expression profiling of RAW264.7 cells was used to screen target miRNAs through genetic screening, GO analysis and hierarchical clustering. The expression of miRNA targets in the serum, colon, spleen, livers and lungs of BALB/c mice was quantified by RT-qPCR. Serum protein levels were quantified by ELISA. Western blot analysis and RT-qPCR were used for verification in vitro. Using miRNA array analysis, we screened 3 miRNAs (miR‑205‑5b, miR‑196a and miR‑193b). Animal experiments with miR‑205‑5b indicated its high degree of expression in the serum, colon, spleen, liver and lungs following the downregulation of HMGB1 in the tissues. RAW264.7 cells transfected with miR‑205‑5b mimics downregulated HMGB1 protein expression, suggesting translational regulation. HMGB1 expression negatively correlated with miR‑205‑5b expression in LPS-induced sepsis. By contrast, HMGB1 expression in LPS-stimulated RAW264.7 cells was increased following transfection with miR‑205‑5b inhibitor. miR‑205‑5b is a critical mediator of cholinergic anti-inflammatory activity in late sepsis. The upregulation of miR‑205‑5b as a potential therapeutic target for the treatment of inflammatory diseases is a possible novel therapeutic strategy against late sepsis. The mechanisms involved include the by post-transcriptional suppression of HMGB1 in cells and tissues.