Preoperative lymphocyte-to-monocyte ratio (LMR) could independently predict overall survival of resectable gastric cancer patients.

Preoperational hemogram parameters have been reported to be associated with the prognosis of several types of cancers. This study aimed to investigate the prognostic value of hematological parameters in gastric cancer in a Chinese population. A total of 870 gastric cancer patients who underwent radical tumorectomy were recruited from January 2008 to December 2012. Preoperative hematological parameters were recorded and dichotomized by time-dependent receiver operating characteristic curves. The survival curves of patients stratified by each hematological parameter were plotted by the Kaplan-Meier method and compared by log-rank test. Multivariate Cox proportional hazards models were used to select parameters independently correlated with prognosis. The median age of the patients was 60 years. The median follow-up time was 59.9 months, and the 5-year survival rate was 56.4%. Results from the univariate analyses showed that low lymphocyte count (<2.05 × 10/L), high neutrophil-to-white blood cell ratio (NWR > 0.55), low lymphocyte-to-white blood cell ratio (LWR < 0.23), low lymphocyte-to-monocyte ratio (LMR < 5.43), high neutrophil-to-lymphocyte ratio (NLR > 1.44), and high platelet-to-lymphocyte ratio (PLR > 115) were associated with poor survival of gastric cancer patients. Multivariate analysis showed that low LMR (HR: 1.49, 95% CI: 1.17-1.89, P = .001) was the only hematological factor independently predicting poor survival. These results indicate that preoperational LMR is an independent prognostic factor for patients with resectable gastric cancer.

Mitogen-activated protein kinase eight polymorphisms are associated with immune responsiveness to HBV vaccinations in infants of HBsAg(+)/HBeAg(-) mothers.

BACKGROUND: Infants born to hepatitis B surface antigen (HBsAg) positive mothers are at a higher risk for Hepatitis B virus (HBV) infection. Host genetic background plays an important role in determining the strength of immune response to vaccination. We conducted this study to investigate the association between Tumor necrosis factor (TNF) and Mitogen-activated protein kinase eight (MAPK8) polymorphisms and low response to hepatitis B vaccines. METHODS: A total of 753 infants of HBsAg positive and hepatitis Be antigen (HBeAg) negative mothers from the prevention of mother-to-infant transmission of HBV cohort were included. Five tag single nucleotide polymorphism (SNPs) (rs1799964, rs1800629, rs3093671, rs769177 and rs769178) in TNF and two tag SNPs (rs17780725 and rs3827680) in MAPK8 were genotyped using the MassARRAY platform. RESULTS: A higher percentage of breastfeeding (P = 0.013) and a higher level of Ab titers were observed in high responders (P < 0.001). The MAPK8 rs17780725 AA genotype increased the risk of low response to hepatitis B vaccines (OR = 3.176, 95% CI: 1.137-8.869). Additionally, subjects with the AA genotype may have a lower Ab titer than subjects with GA or GG genotypes (P = 0.051). Compared to infants who were breastfed, infants who were not breastfed had an increased risk of low response to hepatitis B vaccine (OR = 2.901, 95% CI:1.306-6.441). CONCLUSIONS: MAPK8 polymorphisms are associated with immune response to HBV vaccinations in infants of HBsAg(+)/HBeAg(-) mothers.

Role of RbBP5 and H3K4me3 in the vicinity of Snail transcription start site during epithelial-mesenchymal transition in prostate cancer cell.

EMT (epithelial-mesenchymal transition) occurs in a wide range of tumor types, and has been shown to be crucial for metastasis. Epigenetic modifications of histones contribute to chromatin structure and result in the alterations in gene expression. Tri-methylation of histone H3 lysine 4 (H3K4me3) is associated with the promoters of actively transcribed genes and can serve as a transcriptional on/off switch. RbBP5 is a component of the COMPASS/ -like complex, which catalyzes H3K4me3 formation. In this study, we found that in the process of TGF-Beta1 induced EMT in the prostate cancer cell line DU145, H3K4me3 enrichment and RbBP5 binding increased in the vicinity of Snail (SNAI1) transcription start site. Knocking-down of RbBP5 notably decreased Snail expression and EMT. Recruitment of RbBP5 and formation of H3K4me3 at Snail TSS during EMT depend on binding of SMAD2/3 and CBP at Snail TSS. This study links the SMAD2/3 signal with Snail transcription via a histone modification - H3K4me3. Furthermore, our research also demonstrates that RbBP5 and even WRAD may be a promising therapeutic candidates in treating prostate cancer metastasis, and that DU145 cells maintain their incomplete mesenchymal state in an auto/ paracrine manner.

Protective effect of an improved immunization practice of mother-to-infant transmission of hepatitis B virus and risk factors associated with immunoprophylaxis failure.

Although routine immunoprophylaxis has been known to reduce hepatitis B virus (HBV) transmission, immunoprophylaxis failure still occurs. The study aimed to investigate the protective efficacy of an improved immunoprophylaxis protocol to prevent mother-to-infant transmission of HBV and to explore the potential risk factors associated with immunoprophylaxis failure and low antibody response.A prospective observational cohort study was conducted from July 2012 to April 2015. A total of 863 HBsAg-positive mothers and their 871 infants (8 pairs of twins) were included in the study. Two different hepatitis B vaccine doses (20 or 10 µg) were administered to the infants based on the hepatitis B e-antigen (HBeAg) status of their mothers. Simultaneously, hepatitis B immunoglobulin (HBIG) was administered to the infants. Initial injections of HBIG and the hepatitis vaccine were given within 2 hours after birth. Rates of HBV infections among the infants were evaluated at 7 months of age. Factors associated with immunoprophylaxis failure and low responses to vaccination were analyzed by unconditional logistic regression..At 7 months of age, no immunoprophylaxis failure was observed in the 565 infants born to HBeAg-negative mothers. Among the 306 infants born to HBeAg-positive mothers, immunoprophylaxis failed in 16 infants (5.2%) of the infants and they were found to be HBsAg-positive. Further analysis showed that HBV DNA levels ≥10 IU/mL [odds ratio (OR) = 4.53, 95% confidence interval (95% CI): 1.19-17.34], delayed vaccination (OR = 4.14, 95% CI: 1.00-17.18), and inadequate initial injections (OR = 7.69, 95% CI: 1.71-34.59) were independently associated with immunoprophylaxis failure. Adequate titers of antibody to HBsAg (anti-HBs, ≥100 mIU/mL) were present in 96.5% of immunoprophylaxis-successful infants. For full-term infants, birth weights <3000 g were correlated with low immune responses to vaccination.This improved immunoprophylaxis protocol is effective in preventing perinatal transmission of HBV. Among infants with HBeAg-positive mothers, high HBV viral loads and inadequate and delayed initial injections were associated with immunoprophylaxis failure. The majority of the infants in our study produced adequate levels of protective anti-HBs titers after immunoprophylaxis. Additional efforts to further reduce perinatal transmission should be considered, especially for HBeAg-positive mothers.

A simple LC-ESI-MS/MS method for quantification of bacopaside I in rat plasma and its application to a pharmacokinetic study.

Bacopaside I is one of the main pseudojujubogenin glycosides isolated from Bacopa monniera. In the present study, a rapid and robust LC-ESI-MS/MS method was developed and validated to quantify bacopaside I in rat plasma. After plasma samples were deproteinized by methanol, the post-treatment samples were analyzed on a Zorbax Eclipse Plus C18 (2.1×50mm, 1.8µm) column using a mobile phase of acetonitrile and water (65:35, v/v). Detection was performed on a triple-quadrupole tandem mass spectrometer with selected reaction monitoring (SRM) mode via electrospray ionization source. This method covered a linearity range of 10-2000ng/mL with the lower limit of quantification of 10ng/mL. The intra- and inter-day precisions of analysis were less than 10.2%, and the accuracies were between -11.1% and 8.4% at the concentrations of 25, 150 and 1800ng/mL. The total run time was 6.0min. This method was successfully applied to the preclinical pharmacokinetic study of bacopaside I following intravenous or oral administration to rats.