Message from "The Surviving Sepsis Campaign Bundle: 2018 Update" / 医学研究生学报

The Surviving Sepsis Campaign Bundle: 2018 Update was published recently, in which the time of bundle care is reduced from 3 hours to 1 hour. This update not only reflects the advances in medical studies and practice, but also presents some requirements for normalized treatment of sepsis and management of and cooperation among medical institutions. The guidelines advanced in the "2018 Update", though still lacking high-quality clinical evidence for verification, have made us aware of the importance of early diagnosis and timely intervention of sepsis.

A National Multicenter Survey on Management of Pain, Agitation, and Delirium in Intensive Care Units in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p><p><b>TRIAL REGISTRATION</b>The study is registered at http://www.clinicaltrials.gov (No. ChiCTR-OOC-16009014, www.chictr. org.cn/index.aspx.).</p>

Aerosolized Amikacin as Adjunctive Therapy of Ventilator-associated Pneumonia Caused by Multidrug-resistant Gram-negative Bacteria: A Single-center Randomized Controlled Trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Aerosolized amikacin (AA) is a current option for the management of ventilator-associated pneumonia (VAP) caused by multidrug-resistant Gram-negative bacteria (MDR-GNB), as it is reported that AA could increase the alveolar level of the drug without increasing systemic toxicity. This study aimed to evaluate the efficacy and safety of AA as an adjunctive therapy for VAP caused by MDR-GNB.</p><p><b>METHODS</b>In this single-center, double-blind study conducted in a 36-bed general Intensive Care Unit (ICU) in a tertiary hospital from June 2014 to June 2016, 52 ICU patients with confirmed MDR-GNB VAP were randomized to two groups (AA group, n = 27 and placebo group, n = 25). Amikacin (400 mg, q8h) or saline placebo (4 ml, q8h) was aerosolized for 7 days. The attending physician determined the administration of systemic antibiotics for VAP. Patients were followed up for 28 days. Bacteriological eradication, clinical pulmonary infection score (CPIS), and serum creatinine were assessed on day 7 of therapy. New resistance to amikacin, cure rate of VAP, weaning rate, and mortality were assessed on day 28.</p><p><b>RESULTS</b>The baseline characteristics of patients in both groups were similar. At the end of the treatment, 13 of the 32 initially detected bacterial isolates were eradicated in AA group, compared to 4 of 28 in placebo group (41% vs. 14%, P= 0.024). As for patients, 11 of 27 patients treated with AA and 4 of 25 patients treated with placebo have eradication (41% vs. 16%, P= 0.049). The adjunction of AA reduced CPIS (4.2 ± 1.6 vs. 5.8 ± 2.1, P= 0.007). New drug resistance to amikacin and the change in serum creatinine were not detected in AA group. No significant differences in the clinical cure rate in survivors (48% vs. 35%, P= 0.444), weaning rate (48% vs. 32%, P= 0.236), and mortality (22% vs. 32%, P= 0.427) were detected between the two groups on day 28.</p><p><b>CONCLUSIONS</b>As an adjunctive therapy of MDR-GNB VAP, AA successfully eradicated existing MDR organisms without inducing new resistance to amikacin or change in serum creatinine. However, the improvement of mortality was not found.</p>

Depressant Effect of siRNA on the Expression and Replication of Hepatitis B Virus in HepG2.2.15 Cell / 实用儿科临床杂志

Objective To explore the siRNA as a new antiviral therapy,evaluate the inhibition effect of siRNA based on vector on the HBV of HepG2.2.15 cell,and observe the side effect and toxicity of siRNA vector on cells and the off-target effect of siRNA.Methods Three pairs of siRNA duplexes targeting HBV C gene were designed as double strands,and the duplex were annealed and ligated into the p-Silencer-Cmv 4.1-hygro vector.The ligation products were used to transform JM109 cells.The clones with shRNA were obtained,and the vectors were purified.After the initial identification of the vector with agarose gel and the size of the inserted sequence got examined by native polyacrylamide gel electrophoresis,furthermore the sequencing was further carried out.The recombinant plasmids were purified with ultrapure Midipreps DNA Purification System.Then HepG2.2.15 cells were transfected with the plasmid mixed with siPort XP-1.The expression of HBsAg and HBeAg were detected by immunofluorescence and Western blot,and the HBV RNA was investigated by RT-PCR.Furthermore the real-time quantitive PCR was carried out to detect the changes of HBV DNA.In order to evaluate the toxicity of the shRNA,MTT was used to examine the growth rate and curve of cells.The ELISA was performed to detect the changes of interferon-? (IFN-?).Results The Western blot showed that the HBsAg and HBeAg protein were suppressed with (81.15?0.69)%,(88.12?0.92)% respectively by vector p-C2 on the third day of post-transfection.It had the similar result indicated by immunofluorescence.And the RT-PCR showed that the specific siRNA targeting HBV C gene could markedly suppress the expression of HBV mRNA and the HBV C gene mRNA was inhibited with 96.9%.The real-time quantitive PCR showed that the specific functional siRNA could markedly suppress HBV DNA copy with two orders of magnitude,while the siRNA vector had no effect on the growth of cell showed by MTT detection.Compared with the non-transfected group and p-NC group,the IFN-? level was almost the same with siRNA p-C1,p-C2,p-C3 groups.Conclusions The siRNA based on the expression vector can suppress the expression and replication of HBV in HepG2.2.15 cell.The inhibition effect was specific and had a certain dependency on siRNA concentration.No toxicity effect was found in the study.And the drug resistance wouldn′t happen because the silence was based on the split of gene.