Oxidized low-density lipoprotein activates extracellular signal-regulated kinase signaling to downregulate sortilin expression in liver sinusoidal endothelial cells.

BACKGROUND AND AIM: Both type 2 diabetes mellitus and non-alcoholic fatty liver disease are closely associated with elevated levels of low-density lipoprotein cholesterol and its oxidized form (ox-LDL). This study aimed to investigate the regulation of sortilin in liver tissue and its potential implications for lipid metabolism. METHODS: Sixty male Wistar rats were randomly divided into four groups: control group (n = 15), ox-LDL group (n = 15), PD98059 group (n = 15), and ox-LDL + PD98059 group (n = 15). Liver sinusoidal endothelial cells were extracted from liver tissue of the control group and were identified using an anti-CD31 antibody. Lipid droplet accumulation was observed by Oil red O and hematoxylin-eosin staining. The protein expression levels were detected by immunohistochemical staining, real-time reverse transcription-polymerase chain reaction, and western blot. Histopathologic examinations were performed by Gomori methenamine silver staining. RESULTS: The ox-LDL group exhibited increased lipid droplet accumulation. Further, ox-LDL activated the extracellular signal-regulated kinase (ERK)-mediated downregulation of sortilin expression, whereas blocking of ERK signaling by PD98059 increased sortilin protein expression. Consistently, hematoxylin-eosin staining showed that the structure of the hepatocytes was loose and disordered in arrangement, with lipid droplets present in the cytoplasm of the ox-LDL group. However, PD98059 significantly improved the integration of the scaffold structure. Gomori methenamine silver staining showed that the ox-LDL group had darker and more obvious fragmented silver nitrate deposits in the basement membrane and sinus space. CONCLUSIONS: Sortilin can protect liver sinusoidal endothelial cells from injury and maintain integration of the liver scaffold structure in ox-LDL-induced lipid-injured liver.

Delirium screening tools in the emergency department: A protocol for systematic review and meta-analysis.

BACKGROUND: Delirium is a common type of acute brain dysfunction among emergency department (ED) patients. The prevalence of delirium in the ED is up to 40%. Although screening instruments used to identify delirium have been developed, it is unclear which tool is the most accurate in the ED. To address this challenging, we systematically examine the accuracy of delirium screening tools used to assess the ED patients. METHODS: This study has been registered at the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY), and the registration number is INPLASY202110041. We will search the PubMed, EMBASE, PsycINFO, and the Cochrane Library. Studies involving patients which compared diagnostic instruments with the criteria in Diagnostic and Statistical Manual of Mental Disorders (DSM) as a reference standard will be included. We will use STATA 15.1 and MetaDiSC to make careful analysis of the results. The quality of included studies will be assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 scale. RESULTS: In this study, the accuracy of different screening methods among ED patients is assessed by a high-quality synthesis. The number of tools available for screening delirium in the ED, the information of studies including the countries, the study design, the sample size and the characteristic of studies, the quality of the studies and the results of meta-analysis. The systematic review and meta-analysis will be published in a peer-reviewed journal. CONCLUSION: According to the conclusion of the systematic review, evidence will be provided to judge which screening method is the best for the ED patients. The results will bring better understanding of screening methods in the ED and highlight gaps for future research.

Palmitate up-regulates laminin expression via ROS/integrin αvß3 pathway in HLSECs.

AIMS/INTRODUCTION: To investigate the roles of reactive oxygen species (ROS) and integrin αvß3 in palmitate-induced laminin expression of human liver sinusoidal endothelial cells (HLSECs). RESULTS: The protein expression of integrin αv, integrin ß3 and laminin are increased by palmitate in HLSECs in a time- and dose-dependent manner. NAC, the ROS inhibitor, significantly inhibited the up-regulation of protein expression of integrin αv, integrin ß3 and laminin by palmitate (P < 0.05). Palmitate markedly enhanced ROS formation (P < 0.05), which was not inhibited by LM609, the antibody of integrin αvß3. Palmitate significantly increased laminin synthesis (P < 0.05), which was attenuated by LM609 and NAC (P < 0.05). MATERIALS AND METHODS: HLSECs were treated with palmitate in the presence or absence of LM609 (10 µg/ml) or N-acetylcysteine (NAC) (2 mM). Expression of integrin αv, integrin ß3 and laminin were measured by RT-PCR and Western blot. Immunocytochemistry were used for examining laminin expression. The generation of ROS was measured using the fluorescent signal 2',7' dichloro-fluorescein diacetate (DCFH-DA). CONCLUSIONS: The results suggested that palmitate increases laminin expression through ROS/integrin αv/ß3 pathway.

A critical review to traumatic brain injury clinical practice guidelines.

The aim of this study was to assess the quality of clinical practice guidelines of traumatic brain injury (TBI) and investigate the evidence grading systems.A systematic search of relevant guideline websites and literature databases (including PubMed, NGC, SIGN, NICE, GIN, and Google) was undertaken from inception to May 2018 to identify and select TBI guidelines. Four independent reviewers assessed the eligible guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. The degree of agreement was evaluated with intraclass correlation coefficient (ICC).From 1802 records retrieved, 12 TBI guidelines were included. The mean scores for each AGREE II domain were as follows: scope and purpose (mean ± SD= 74.2 ±â€Š9.09); stakeholder involvement (mean± SD= 54.6 ±â€Š11.6); rigor of development (mean ± SD=70.1 ±â€Š13.6); clarity and presentation (mean ± SD=78.4 ±â€Š11.5); applicability (mean ± SD= 60.5 ±â€Š13.6); and editorial independence (mean ± SD=61.7 ±â€Š14.8). Ten guidelines were rated as "recommended." The ICC values ranged from 0.73 to 0.95. Seven grading systems were used by TBI guidelines to rate the level of evidence and the strength of recommendation.Most TBI guidelines got a high-quality rating, whereas a standardized grading system should be adopted to provide clear information about the level of evidence and strength of recommendation in TBI guidelines.

Targeted agents for patients with advanced/metastatic pancreatic cancer: A protocol for systematic review and network meta-analysis.

BACKGROUND: Pancreatic cancer (PC) is a devastating malignant tumor. Although surgical resection may offer a good prognosis and prolong survival, approximately 80% patients with PC are always diagnosed as unresectable tumor. National Comprehensive Cancer Network's (NCCN) recommended gemcitabine-based chemotherapy as efficient treatment. While, according to recent studies, targeted agents might be a better available option for advanced or metastatic pancreatic cancer patients. The aim of this systematic review and network meta-analysis will be to examine the differences of different targeted interventions for advanced/metastatic PC patients. METHODS: We will conduct this systematic review and network meta-analysis using Bayesian method and according to Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. To identify relevant studies, 6 electronic databases including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of science, CNKI (Chinese National Knowledge Infrastructure), and CBM (Chinese Biological Medical Database) will be searched. The risk of bias in included randomized controlled trials (RCTs) will be assessed using the Cochrane Handbook version 5.1.0. And we will use GRADE approach to assess the quality of evidence from network meta-analysis. Data will be analyzed using R 3.4.1 software. RESULTS AND CONCLUSION: To the best of our knowledge, this systematic review and network meta-analysis will firstly use both direct and indirect evidence to compare the differences of different targeted agents and targeted agents plus chemotherapy for advanced/metastatic pancreatic cancer patients. This is a protocol of systematic review and meta-analysis, so the ethical approval and patient consent are not required. We will disseminate the results of this review by submitting to a peer-reviewed journal.

Efficacy and tolerability of lanthanum carbonate in treatment of hyperphosphatemia patients receiving dialysis--a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy and tolerability of lanthanum carbonate (LC) in the treatment of hyperphosphatemia in dialysis patients. METHOD: Multiple databases were used to recruit the published clinical randomized controlled trials (RCTs) comparing LC with placebo for hyperphosphatemia in dialysis patients from inception to March 2013. Results were expressed using standardized mean difference (SMD) for continuous variables and pooled odd ratios (OR) for dichotomous outcomes. Study quality was assessed according to Cochrane Handbook 5.1 guidelines and statistical analysis was performed using RevMan 5.2 software. RESULTS: A total of 950 patients in seven placebo-controlled RCTs were included. Results showed that LC could effectively controlled hyperphosphatemia compared with placebo (SMD -1.06, 95% CI -1.27- -0.86, P < 0.00001). The proportion of subjects reaching the target in the LC group was higher than that in the placebo group (OR 6.88, 95% CI 4.39-10.78, P < 0.00001). LC-treated patients showed less change in serum PTH and Ca × Pi product from baseline compared to the placebo group (SMD -0.21, 95% CI -0.48-0.06, P = 0.007; SMD -0.90, 95% CI -1.13- -0.66, P < 0.00001, respectively). LC-treated patients experienced more side-effects, like vomiting and nausea, than controls (OR 3.10, 95% CI 1.35-7.08, P = 0.007; OR 2.74, 95% CI 1.22-6.19, P = 0.02, respectively). But overall, the incidence of drug-related adverse events was similar between placebo- and LC-treated patients (OR 1.21, 95% CI 0.66-2.22, P = 0.54). CONCLUSION: In the treatment of hyperphosphatemia in dialysis patients, LC is well tolerated and more effective than placebo during short-term trials. Furthermore, it helps to maintain PTH and Ca × Pi product levels within recommended ranges. LC is an ideal choice for second-line treatment of hyperphosphatemia after therapy failure or other contraindication for calcium agents. Its long-term security still needs further research.

Laparoscopic versus open surgery for rectal cancer: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Laparoscopic and open rectum surgery for rectal cancer remains controversial. This systematic review compared the short-term and long-term efficiency and complications associated with laparoscopic and open resection for rectal cancer. MATERIALS AND METHODS: We searched PubMed, Embase, Cochrane Library, ISI Web of Knowledge and the China Biology Medicine Database to identify potential randomized controlled trials from their inception to March 31, 2014 without language restriction. Additional articles were identified from searching bibliographies of retrieved articles. Two reviewers independently assessed the full-text articles according to the pre-specified inclusion and exclusion criteria as well as the methodological quality of included trials. The meta-analysis was performed using RevMan 5.2. RESULTS: A total of 16 randomized controlled trials involving 3,045 participants (laparoscopic group, 1,804 cases; open group, 1,241 cases) were reviewed. Laparoscopic surgery was associated with significantly lower intraoperative blood loss, earlier return of bowel movement and reduced length of hospital stay as compared to open surgery, although with increased operative time. It also showed an obvious advantage for minimizing late complications of adhesion-related bowel obstruction. Importantly, there were no significant differences in other postoperative complications, oncological clearance, 3-year and 5-year or 10 year recurrence and survival rates between two procedures. CONCLUSIONS: On the basis of this meta-analysis we conclude that laparoscopic surgery has advantages of earlier postoperative recovery, less blood loss and lower rates of adhesion-related bowel obstruction. In addition, oncological outcome is comparable after laparoscopic and open resection for rectal cancer.

Effectiveness and safety of pemetrexed versus docetaxel as a treatment for advanced non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Our aim was to conduct a meta-analysis to compare the efficacy and safety of pemetrexed and docetaxel for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We systematically searched the Cochrane Library, PubMed, Embase, China Biology Medicine Database for randomized controlled trials (RCTs) comparing the efficacy and toxicities of pemetrexed versus docetaxel as a treatment for advanced NSCLC. We limited the languages to English and Chinese. Two reviewers independently screened articles to identify eligible trials according to the inclusion and exclusion criteria and assessed the methodological quality of included trials, and then extracted data. The meta-analysis was performed using STATA12.0. RESULTS: Six RCTs involving 1,414 patients were identified. We found that there was no statistically significant differences in overall response rate, survival time, progression-free survival, disease control rate, and 1-2 yr survival rate (p>0.050) but it is worthy of mention that patients in the pemetrexed arms had significantly higher 3-yr survival rate (P=0.002). With regard to the grade 3 or 4 hematological toxicity, compared with docetaxel, pemetrexed led to lower rate of grade 3-4 febrile neutropenia, neutropenia, and leukocyts toxicity (p<0.001). There was no significant difference in anemia between the two arms (p=0.08). In addition, pemetrexed led to higher rate of grade 3-4 thrombocytopenia toxicity (p=0.03). As for the non-hematological toxicities, compared with docetaxel, pemetrexed group had lower rate of grade 3-4 diarrhea and alopecia. CONCLUSIONS: Pemetrexed was almost as effective as docetaxel in patients with advanced NSCLC. At the same time, pemetrexed might increase the 3-yr survival rate. As for safety, pemetrexed led to lower rate of grade 3-4 febrile neutropenia, neutropenia, leukocytes, diarrhea and alopecia toxicity. However, it was associated with a higher rate of grade 3-4 thrombocytopenia.

Laparoscopic versus open surgery for colon cancer: a meta-analysis of 5-year follow-up outcomes.

BACKGROUND: Colon cancer is one of the most common malignant tumors of digestive tract with a rather high incidence rate. Currently, surgery is the only radical therapy for colon cancer, while Laparoscopic colectomy (LAC) has become another focus since studies reported LAC could improve the short-time outcomes and quick recovery of patients compared with open colectomy (OC). However, it's still unclear whether LAC can better improve patients' long-time survival than OC. OBJECTIVE: We aimed to perform a meta-analysis to answer whether the 5-year recurrence and survival rate after LAC are comparable to those reported after OC in patient with colon cancer. METHODS: We searched Cochrane Library, PubMed, Embase, CBM, VIP, and CNKI for relevant studies. The time searched was from the establishment time of the databases to September 15, 2011. At the same time, we searched Google, Medical Martix and Baidu for more studies as well as a hand-search. We limited the language to English and Chinese. Two reviewers independently screened articles to identify randomized controlled trials (RCTs) according to the inclusion and exclusion criteria and assessed the methodological quality of included trials, and then extracted data. Meta-analysis was performed using RevMan5.0. RESULTS: Five RCTs involving 2695 patients reported long-term outcomes based on 5-year data and were included in the analysis. No significant differences between LAC and OC were found in the overall mortality (RR = 0.94; 95% CI (0.82, 1.09); P = 0.23, I(2) = 21%), total recurrence rate (RR = 0.94; 95% CI (0.81, 1.10); P = 0.24, I(2) = 27%), 5-year tumor free survival rate (RR = 1.00, 95% CI (0.94, 1.06); P = 0.96, I(2) = 0%). and overall 5-year survival (RR = 1.02; 95% CI (0.97, 1.07); P = 0.55, I(2) = 0%). CONCLUSIONS: This meta-analysis suggests that LAC was as effective and safe as OC for colon cancer.