The Predictive Value of Serum DAO, HDC, and MMP8 for the Gastrointestinal Injury in the Early Stage of Acute Pancreatitis in an Animal Model and a Clinical Study.

Purpose: This study was aimed at exploring the use of the acute gastrointestinal injury (AGI) grade and sensitive biomarkers to investigate gastrointestinal (GI) injury in early stage of acute pancreatitis (AP). Patients and Methods: The AGI grade was used to evaluate intestinal function. Any GI injury above grade I (grades II-IV) was considered as severe. An AP rat model was created by retrograde injection of 4% sodium taurocholate. The pancreatic and intestinal histopathology scores were calculated by hematoxylin-eosin staining. Human and rat sera were assessed using ELISA. Tight junction (TJ) proteins were detected by Western blotting. Results: In clinical study, the GI injury rate in mild acute pancreatitis (MAP), moderate severe acute pancreatitis (MSAP), and severe acute pancreatitis (SAP) groups was 26.8%, 78.4%, and 94.8%, respectively (P < 0.05). Diamine oxidase (DAO), histidine decarboxylase (HDC), and matrix metalloproteinase 8 (MMP8) serum levels were higher in AP patients than in healthy people (P < 0.05). Patients with GI injury had higher serum levels of DAO, HDC, and MMP8 than those without GI injury (P < 0.05). In animal experiments, the serum levels of DAO, HDC, and MMP8 were higher in the AP group than in normal and sham-operated (SO) groups (P < 0.05). The expressions of tricellulin, claudin-1, ZO-1, and occludin were significantly lower in the AP group than in normal and SO groups (P < 0.05). Conclusion: The serum levels of DAO, HDC, and MMP8 are novel biomarkers of GI injury in the early stage of AP; their elevation indicates the development of GI injury in AP. The intestinal TJ disruption may be a primary mechanism of GI injury and requires more in-depth research.

A modified Ranson score to predict disease severity, organ failure, pancreatic necrosis, and pancreatic infection in patients with acute pancreatitis.

Background: Although there are several scoring systems currently used to predict the severity of acute pancreatitis, each of them has limitations. Determine the accuracy of a modified Ranson score in predicting disease severity and prognosis in patients with acute pancreatitis (AP). Methods: AP patients admitted or transferred to our institution were allocated to a modeling group (n = 304) or a validation group (n = 192). A modified Ranson score was determined by excluding the fluid sequestration parameter and including the modified computed tomography severity index (CTSI). The diagnostic performance of the modified Ranson score was compared with the Ranson score, modified CTSI, and bedside index of severity in acute pancreatitis (BISAP) score in predicting disease severity, organ failure, pancreatic necrosis and pancreatic infection. Results: The modified Ranson score had significantly better accuracy that the Ranson score in predicting all four outcome measures in the modeling group and in the validation group (all p < 0.05). For the modeling group the modified Ranson score had the best accuracy for predicting disease severity and organ failure, and second-best accuracy for predicting pancreatic necrosis and pancreatic infection. For the verification group, it had the best accuracy for predicting organ failure, second-best accuracy for predicting disease severity and pancreatic necrosis, and third-best accuracy for predicting pancreatic infection. Conclusion: The modified Ranson score provided better accuracy than the Ranson score in predicting disease severity, organ failure, pancreatic necrosis and pancreatic infection. Relative to the other scoring systems, the modified Ranson system was superior in predicting organ failure.

The prognostic value of excision repair cross-complementation group 1 (ERCC1) in patients with small cell lung cancer (SCLC) receiving platinum-based chemotherapy: evidence from meta-analysis.

Recently, the correlation between the efficacy of platinum-based chemotherapy and ERCC1 expression in patients with SCLC has attracted wide-spread attention, and a lot of investigations have been conducted, whereas conflicting results were presented. Therefore, we performed the present meta-analysis of eligible studies to derive a more precise evaluation of the association between ERCC1 expression and the clinical outcome in SCLC patients receiving platinum-based chemotherapy. A literature search for relevant studies was conducted in the electronic databases of PubMed, EMBASE and Web of Science. The inclusive criteria were SCLC patients treated by platinum-based chemotherapy, and evaluated the relationship between ERCC1 expression and the clinical outcomes [including overall response rate (ORR), overall survival (OS) or progression-free survival (PFS)]. Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) was calculated to assess the risk. A total of nine studies including 1129 patients were included in final analysis. Our analysis indicated that positive/high ERCC1 expression was associated with unfavorable OS (HR = 1.18, 95%CI = 1.02-1.37) and PFS (HR = 1.46, 95%CI = 1.14-1.88). Subgroup analysis according to disease stage suggested the significant relationship was found in limited stage (LS-SCLC), but not in extensive stage (ES-SCLC). However, no significant association was found between ERCC1 expression and ORR. Our analysis suggested ERCC1 expression may be a prognostic factor in SCLC patients receiving platinum-based chemotherapy, especially for LS-SCLC.

The prognostic role of the class III ß-tubulin in non-small cell lung cancer (NSCLC) patients receiving the taxane/vinorebine-based chemotherapy: a meta-analysis.

BACKGROUND: A number of studies have examined the relationship between the expression of the class III ß-tubulin (TUBB3) and the treatment responses to the taxane/vinorebine-based chemotherapy in patients with non-small cell lung cancer (NSCLC). However, the results of these studies were inconsistent and inconclusive. Therefore, we conducted an up-to-date meta-analysis to evaluate the prognostic role of TUBB3 in the taxane/vinorebine-based chemotherapy. METHODS: A literature search for relevant studies was conducted in PubMed, Embase, and CNKI. The inclusion criteria were the taxane/vinorebine-based chemotherapy in patients with NSCLC and the evaluation of the clinical outcomes in relation to the expression of TUBB3. The clinical outcomes analyzed in this study included the overall response rate (ORR), overall survival (OS), and event-free survival (EFS). Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were calculated to assess the risk associated with the TUBB3 expression in the taxane/vinorebine-based chemotherapy. RESULTS: A total of 28 studies with 2401 NSCLC patients were qualified for this meta-analysis. We found that the positive or high level of TUBB3 expression was associated with a poorer ORR (OR = 0.24, 95% CI = 0.16-0.36, p<0.001), an unfavorable OS (HR = 1.52, 95% CI = 1.27-1.82, p<0.001), and a worse EFS (HR = 1.47, 95% CI = 1.24-1.74, p<0.001) compared to the negative or low level of TUBB3 expression. The statistically significant associations between TUBB3 and chemotherapy responses were also observed in the stratified subgroup analysis, which included the analysis by ethnic subgroup (Asian and Caucasian), chemotherapy regimen (taxane-based and vinorebine-based), TUBB3 detection method (IHC and PCR), and treatment strategy (surgery plus adjuvant chemotherapy and palliative chemotherapy). CONCLUSIONS: The expression level of TUBB3 may be a useful biomarker to predict the clinical outcomes of the taxane/vinorebine-based chemotherapy in patients with NSCLC.

Prognostic significance of Tet methylcytosine dioxygenase 2 (TET2) gene mutations in adult patients with acute myeloid leukemia: a meta-analysis.

Tet methylcytosine dioxygenase 2 (TET2) gene mutations have recently been recognized in acute myeloid leukemia (AML). We performed a meta-analysis to evaluate the controversial prognostic significance of TET2 mutations in AML. Eight studies, covering 2552 patients with AML, were included in this analysis. Pooled hazard ratios (HRs) indicated that TET2 mutations had a poor prognostic impact on the survival of patients with AML. The combined HR for overall survival (OS) was 1.53 and the summary HR for event-free survival (EFS) was 1.64. Additionally, TET2 mutations appeared to be an adverse prognostic indicator in both patients with cytogenetically normal (CN)-AML (HR for OS: 1.43 and HR for EFS: 1.76) and subgroups of patients with favorable-risk genotypes (HR for EFS: 2.35) and intermediate-I-risk genotypes (HR for EFS: 1.57). These findings indicate that TET2 mutations have an adverse impact on prognosis and may help to justify risk-adapted therapeutic strategies for patients with AML.

Association between phosphodiesterase 4D polymorphism SNP83 and ischemic stroke.

Iceland scientists identified the relationship between the PDE4D gene and ischemic stroke (IS) in 2003. Since then, many researches have emerged to estimate this association, but the results are contradictory. In order to confirm this association, we conduct this meta-analysis with a larger sample size. PubMed, Embase and four Chinese databases were searched to identify the relevant studies through January 2013. The odds ratio (OR) with 95% confidence interval (CI) was used to calculate the association between the SNP83 polymorphism and IS risk. Twenty-five publications comprised of 8878 cases and 12306 controls were included in this meta-analysis. There was a significant association between SNP83 and IS risk, especially in Asian and Chinese populations, but not in Caucasians (dominant model: OR=0.87, 95% CI=0.69-1.11; recessive model: OR=0.95, 95% CI=0.84-1.07; allele model: OR=0.95, 95% CI=0.84-1.08; co-dominant model 1: OR=0.96, 95% CI=0.85-1.08; co-dominant model 2: OR=0.95, 95% CI=0.83-1.09). The cumulative meta-analysis among the overall population and Chinese population indicated a stable trend of association between SNP83 and IS from 2009 to 2012. In conclusion, we found an association between SNP83 and IS in the overall population and in the Asian and Chinese populations, but not among Caucasians.