Using the Chinese version of Memorial Delirium Assessment Scale to describe postoperative delirium after hip surgery

Objective:: Memorial Delirium Assessment Scale (MDAS) assesses severity of delirium. However, whether the MDAS can be used in a Chinese population is unknown. Moreover, the optimal postoperative MDAS cutoff point for describing postoperative delirium in Chinese remains largely to be determined. We therefore performed a pilot study to validate MDAS in the Chinese language and to determine the optimal postoperative MDAS cutoff point for delirium. Methods:: Eighty-two patients (80 ± 6 years, 21.9% male), who had hip surgery under general anesthesia, were enrolled. The Confusion Assessment Method (CAM) and Mini-Mental State Examination (MMSE) were administered to the patients before surgery. The CAM and MDAS were performed on the patients on the first, second and fourth postoperative days. The reliability and validity of the MDAS were determined. A receiver operating characteristic (ROC) curve was used to determine the optimal Chinese version MDAS cutoff point for the identification of delirium. Results:: The Chinese version of the MDAS had satisfactory internal consistency (α = 0.910). ROC analysis obtained an average optimal MDAS cutoff point of 7.5 in describing the CAM-defined postoperative delirium, with an area under the ROC of 0.990 (95% CI 0.977–1.000, P < 0.001). Conclusions:: The Chinese version of the MDAS had good reliability and validity. The patients whose postoperative Chinese version MDAS cutoff point score was 7.5 would likely have postoperative delirium. These results have established a system for a larger scale study in the future

Released dsDNA‐triggered inflammasomes serve as intestinal radioprotective targets

Abstract Objectives Intestinal mucositis is the major side effect during abdominal or pelvic radiotherapy, but the underlying immunogen remains to be further characterised and few radioprotective agents are available. This study investigated the role of dsDNA‐triggered inflammasomes in intestinal mucositis during radiotherapy. Methods Pro‐inflammatory cytokines were detected by ELISA. Radiation‐induced intestinal injury in mice was analyzed by means of survival curves, body weight, HE staining of intestines, and intestinal barrier integrity. Western blot, immunofluorescence staining, co‐immunoprecipitation assay and flow cytometry were used to investigate the regulatory role of dsDNA on inflammasomes. Results Here, we show that a high level of IL‐1β and IL‐18 is associated with diarrhoea in colorectal cancer (CRC) patients during radiotherapy, which accounts for intestinal radiotoxicity. Subsequently, we found that the dose‐dependently released dsDNA from the intestinal epithelial cells (IECs) serves as the potential immunogenic molecule for radiation‐induced intestinal mucositis. Our results further indicate that the released dsDNA transfers into the macrophages in an HMGB1/RAGE‐dependent manner and then triggers absent in melanoma 2 (AIM2) inflammasome activation and the IL‐1β and IL‐18 secretion. Finally, we show that the FDA‐approved disulfiram (DSF), a newly identified inflammasome inhibitor, could mitigate intestinal radiotoxicity by controlling inflammasome. Conclusion These findings indicate that the extracellular self‐dsDNA released from the irradiated IECs is a potential immunogen to stimulate immune cells and trigger the subsequent intestinal mucositis, while blunting the dsDNA‐triggered inflammasome in macrophages may represent an exciting therapeutic strategy for side effects control during abdominal radiotherapy

Transcriptional positive cofactor 4 promotes breast cancer proliferation and metastasis through c-Myc mediated Warburg effect

Abstract Background The human positive cofactor 4 (PC4) is initially identified as a transcriptional cofactor and has an important role in embryonic development and malignant transformation. However, the clinical significance and the molecular mechanisms of PC4 in breast cancer development and progression are still unknown. Methods We investigated PC4 expression in 114 cases of primary breast cancer and matched normal breast tissue specimens, and studied the impact of PC4 expression as well as the molecular mechanisms of this altered expression on breast cancer growth and metastasis both in vitro and in vivo. Results PC4 was significantly upregulated in breast cancer and high PC4 expression was positively correlated with metastasis and poor prognosis of patients. Gene set enrichment analysis (GSEA) demonstrated that the gene sets of cell proliferation and Epithelial-Mesenchymal Transition (EMT) were positively correlated with elevated PC4 expression. Consistently, loss of PC4 markedly inhibited the growth and metastasis of breast cancer both in vitro and in vivo. Mechanistically, PC4 exerted its oncogenic functions by directly binding to c-Myc promoters and inducing Warburg effect. Conclusions Our study reveals for the first time that PC4 promotes breast cancer progression by directly regulating c-Myc transcription to promote Warburg effect, implying a novel therapeutic target for breast cancer

Is the Best Evidence Good Enough: Quality Assessment and Factor Analysis of Meta-Analyses on Depression

<div><p>Background</p><p>The quality of meta-analyses (MAs) on depression remains uninvestigated.</p><p>Objective</p><p>To assess the overall reporting and methodological qualities of MAs on depression and to explore potential factors influencing both qualities.</p><p>Methods</p><p>MAs investigating epidemiology and interventions for depression published in the most recent year (2014–2015) were selected from PubMed, EMBASE, PsycINFO and Cochrane Library. The characteristics of the included studies were collected and the total and per-item quality scores of the included studies were calculated based on the two checklists. Univariate and multivariate linear regression analyses were used to explore the potential factors influencing the quality of the articles.</p><p>Results</p><p>A total of 217 MAs from 74 peer-reviewed journals were included. The mean score of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was 23.0 of 27 and mean score of Assessment of Multiple Systematic Reviews (AMSTAR) was 8.3 of 11. Items assessing registration and protocol (14.2%, 37/217) in PRISMA and item requiring a full list of included and excluded studies (16.1%, 40/217) in AMSTAR had poorer adherences than other items. The MAs that included only RCTs, pre-registered, had five more authors or authors from Cochrane groups and the MAs found negative results had better reporting and methodological qualities.</p><p>Conclusions</p><p>The reporting and methodological qualities of MAs on depression remained to be improved. Design of included studies, characteristics of authors and pre-registration in PROSPERO database are important factors influencing quality of MAs in the field of depression.</p></div

Different MMSE Score Is Associated with Postoperative Delirium in Young-Old and Old-Old Adults

<div><p>Background</p><p>Postoperative delirium is one of the most common postoperative complications in geriatric patients. Mini-mental state examination (MMSE) assesses cognitive function in patients and is associated with postoperative delirium. However, whether there is an age-dependent relationship between preoperative MMSE score and postoperative delirium remains unknown.</p><p>Methods</p><p>We therefore set out to investigate the association between preoperative MMSE score and postoperative delirium in young-old (≤80 year-old, 75.46±4.69 years, 27.0% male, n = 63) and old-old (>80 year-old, 84.51±3.46 years, 20.9% male, n = 67) participants, who had repairs of hip fractures under general anesthesia. The Confusion Assessment Method and Memorial Delirium Assessment Scale were administrated before surgery, and on the first, second and fourth days after surgery, to assess the incidence and severity of the delirium, respectively. A receiver operating characteristic curve analysis was used to calculate the optimal cutoff score of MMSE in predicting postoperative delirium.</p><p>Results</p><p>Thirty-four (26.2%) of 130 patients (80.12±6.12 years, 23.8% male) developed postoperative delirium. Preoperative MMSE scores were negatively associated with higher incidences and greater severity of postoperative delirium. The optimal cutoff scores of MMSE associated with postoperative delirium for young-old and old-old participants were 18.4 and 21.4, with a sensitivity of 60% and 83.8%, and a specificity of 92.5% and 62.8%, respectively.</p><p>Conclusion</p><p>The data demonstrated the optimal cutoff score of MMSE associated with postoperative delirium in young-old adults might be lower than that in old-old adults. Pending further investigation, these findings suggest that the association between preoperative MMSE score and postoperative delirium is age-dependent.</p></div