Metabolomic differences of seminal plasma between boars with high and low average conception rates after artificial insemination.

Seminal plasma is a complex biological fluid containing many metabolites including amino acids, fructose, carbohydrates and lipids Metabolites play important roles in multiple biological processes, but details and significance of the seminal plasma metabolome related to boar fertility are unknown. The aim of the present study was to compare the comprehensive metabolome of seminal plasma from boars with different conception rate after artificial insemination and to identify the potential biomarkers. Semen samples were collected from boars which divided into two groups according to the conception rates in the offspring. Seminal plasma metabolites were isolated, purified, and then subjected to Ultra-high Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (UHPLC-qTOF-MS) procession. A total of 576 (Positive ion mode) and 377 (Negative ion mode) metabolites were identified in seminal plasma. Metabolites were identified and categorized according to their major chemical classes, including carboxylic acids and derivatives, organooxygen compounds, amino acids, peptides, and alogues, fatty amides, fatty acyls, benzene and substituted derivatives, purine nucleotides, pyrimidine nucleotides, glycosyl compounds, fatty acids and conjugates. The results showed that 4-Aminobenzoate, Pro-Asn, Ile-Tyr, Homoveratric acid and D-Biotin were higher in semen of boar with higher conception rate (HG) versus lower conception rate (LG) (p < .05), whereas L-Serine, Butoxyacetic acid, S-Methyl-5'-thioadenosine, Capsaicin and 1-O-(cis-9-Octadecenyl)-2-O-acetyl-sn-glycero-3-phosphocholine (PAF) were lower in HG than in LG (p < .05). These metabolites may be considered as candidate biomarkers for different fertility in boars.

Phase III randomized, placebo-controlled, double-blind study of monosialotetrahexosylganglioside for the prevention of oxaliplatin-induced peripheral neurotoxicity in stage II/III colorectal cancer.

BACKGROUND: Monosialotetrahexosylganglioside (GM1) is a neuroprotective glycosphingolipid that repairs nerves. Oxaliplatin-based chemotherapy is neurotoxic. This study assessed the efficacy of GM1 for preventing oxaliplatin-induced peripheral neurotoxicity (OIPN) in colorectal cancer (CRC) patients receiving oxaliplatin-based chemotherapy. METHODS: In total, 196 patients with stage II/III CRC undergoing adjuvant chemotherapy with mFOLFOX6 were randomly assigned to intravenous GM1 or a placebo. The primary endpoint was the rate of grade 2 or worse cumulative neurotoxicity (NCI-CTCAE). The secondary endpoints were chronic cumulative neurotoxicity (EORTC QLQ-CIPN20), time to grade 2 neurotoxicity (NCI-CTCAE or the oxaliplatin-specific neuropathy scale), acute neurotoxicity (analog scale), rates of dose reduction or withdrawal due to OIPN, 3-year disease-free survival (DFS) and adverse events. RESULTS: There were no significant differences between the arms in the rate of NCI-CTCAE grade 2 or worse neurotoxicity (GM1: 33.7% vs placebo: 31.6%; P = .76) or neuropathy measured by the EORTC QLQ-CIPN20 or time to grade 2 neurotoxicity using NCI-CTCAE and the oxaliplatin-specific neuropathy scale. GM1 substantially decreased participant-reported acute neurotoxicity (sensitivity to cold items [P < .01], discomfort swallowing cold liquids [P < .01], throat discomfort [P < .01], muscle cramps [P < .01]). The rates of dose reduction or withdrawal were not significantly different between the arms (P = .08). The 3-year DFS rates were 85% and 83% in the GM1 and placebo arms, respectively (P = .19). There were no differences in toxicity between the arms. CONCLUSION: Patients receiving GM1 were less troubled by the symptoms of acute neuropathy. However, we do not support the use of GM1 to prevent cumulative neurotoxicity. (ClinicalTrials.gov number, NCT02251977).

Meta-analysis on inoperable pancreatic cancer: a comparison between gemcitabine-based combination therapy and gemcitabine alone.

AIM: To compare gemcitabine-based combination therapy and gemcitabine (GEM) alone in patients with advanced pancreatic cancer (APCa) through meta-analysis. METHODS: MEDLINE and EMBASE searches were supplemented by information from trial registers of randomized controlled trials (RCTs) for GEM-based combination therapy and GEM alone for APCa. A quantitative meta-analysis was carried out by two reviewers based on the inclusion criteria from all available RCTs. The meta-analysis involved overall survival (OS), objective remission rate (ORR), clinical benefit rate (CBR), time to progress/progress free survival (TTP/PFS) and toxicity. RESULTS: The meta-analysis included 22 RCTs. There was significant improvement in the GEM combination group with regard to the 6-mo survival rate (RD = 0.04, 95% CI 0.01-0.06, P = 0.008), 1-year survival rate (RD = 0.03, 95% CI 0.01-0.05, P = 0.01), ORR (RD = 0.04, 95% CI 0.01-0.07, P = 0.02), CBR (RD = 0.10, 95% CI 0.02-0.17, P = 0.01) and 6-mo TTP/PFS (RD = 0.07, 95% CI 0.04-0.10, P < 0.00001). However, the Grade 3-4 toxicity set by WHO was higher for the GEM combination group for neutropenia (RD = 0.05, 95% CI 0.01-0.10, P = 0.02), thrombocytopenia (RD = 0.05, 95% CI 0.02-0.08, P = 0.002) and vomiting/nausea (RD = 0.03, 95% CI 0.00-0.05, P = 0.02). CONCLUSION: GEM-based combination therapy may improve the overall survival and palliation in optimal patients with APCa as compared with GEM alone.

Meta-analysis of inoperable pancreatic cancer: gemcitabine combined with cisplatin versus gemcitabine alone.

OBJECTIVES: To compare the therapeutic effects of gemcitabine (GEM) monotherapy with GEM-cisplatin (DDP) combination chemotherapy in patients with advanced stage pancreatic cancer (APCa) through meta-analysis. METHODS: MEDLINE and EMBASE searches were supplemented by information from trial registers of randomized controlled trials (RCTs) for GEM-DDP combination chemotherapy and GEM alone in APCa. A quantitative meta-analysis using updated information based on inclusion criteria from all available RCTs was carried out by two reviewers. The primary meta-analysis involved the overall survival (OS), objective remission rate (ORR) and toxicity. RESULTS: The meta-analysis included six RCTs. There was no significant advantage for the GEM-DDP combination group in 6-month survival rate (P = 0.24) or clinical benefit rate (P = 0.58). There was a marginal significant improvement for the GEM-DDP combination group in ORR (RD = 6%, P = 0.05; RD, risk difference = risk in the GEM-DDP combination group - risk in the GEM alone group). Moreover, there was a significant improvement for the combination group in 6-month TTP/TTF (RD = 9%, P = 0.02). WHO grade 3-4 toxicity was higher for the GEM-DDP combination group in terms of neutropenia (RD = 6%, P = 0.08), thrombocytopenia (RD = 8%, P = 0.17) and vomiting/nausea (RD = 11%, P = 0.07); none reached significant difference. CONCLUSION: GEM-DDP combination should not be recommended and GEM monotherapy remains the standard treatment for patients with APCa.

[A meta-analysis of clinical efficiency of two methodologies of cholangiopancreatography].

OBJECTIVE: To compare the efficiency of endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonance cholangiopancreatography (MRCP) in patients with suspected biliary tract or pancreatic diseases. METHODS: Find those prospective comparison trials about the efficiency of ERCP and MRCP in patients with suspected biliary tract or pancreatic diseases from many kinds of database, such as MEDLINE, EMBASE and so on. According to inclusion criteria, two operant choose suitable papers for this study. Collect corresponding original data and make a meta-analysis to compare the sensitivity and specificity of ERCP and MRCP in choledocholithiasis, strictures and malignant tumor. RESULTS: Finally we get 6 articles from 302 ones. To diagnose choledocholithiasis, strictures and malignant tumor, the difference of sensitive between ERCP's and MRCP's is not significant. When it comes to the specificity of ERCP and MRCP in those diseases, ERCP is better than MRCP only in strictures, OR is 6.17 (95% CI 1.35-20.24), P = 0.02. However, we find ERCP is better than MRCP not only in total sensitivity but specificity of biliary tract or pancreatic diseases, OR is 1.72 (95% CI 1.04-2.85) and 4.05 (95% CI 1.32-12.42) respectively, P = 0.04, 0.01. CONCLUSIONS: ERCP is better than MRCP, to biliary tract or pancreatic diseases, in not only sensitivity but specificity. Doctors should think much about patients' situation, tolerance and cost-effectiveness, when they make a decision which examination should patients take.

[Meta-analysis on gemcitabine of fixed-dose rate infusion plus oxaliplatin as first-line therapy for advanced pancreatic cancer].

BACKGROUND & OBJECTIVE: Recent clinical trials showed that gemcitabine (GEM) of fixed-dose rate infusion has certain effect on advanced pancreatic cancer. Some meta-analyses suggest that GEM plus cisplatin (DDP) or its analogues is better than GEM alone in treating advanced pancreatic cancer. This study was to evaluate the efficacy of GEM of fixed-dose rate infusion plus oxaliplatin (GEMOX regimen) as first-line therapy for advanced pancreatic cancer by meta-analysis. METHODS: Two reviewers performed the meta-analysis of all relative studies through searching the international literature, including MEDLINE, EMBASE, ASCO abstracts. This meta-analysis included all randomized evidences to compare GEMOX regimen with GEM alone with respect to overall survival rate and adverse events in patients with advanced pancreatic cancer. RESULTS: Two randomized controlled trials (including 869 patients) were screened from 182 reports. GEMOX regimen was better than GEM alone in terms of 6-month survival rate [risk difference (RD)=0.09, 95% confidence interval (CI)=0.03-0.16, P=0.005], 1-year survival rate (RD=0.05, 95% CI=-0.01-0.11, P=0.08), and objective remission rate (RD=0.06, 95% CI=0.02-0.10, P=0.006). WHO grade 3-4 adverse events analysis revealed that GEMOX was associated with a reduction in anemia (RD=-0.05, 95% CI=-0.08 - -0.01, P=0.01); the addition of oxaliplatin, however, significantly increased neuropathy (RD= 0.14, 95% CI=0.04-0.24, P=0.009) and nausea/vomiting (RD=0.13, 95% CI=0.08-0.18, P<0.001). The occurrence rates of neutropenia and thrombocytopenia were similar in the 2 groups. CONCLUSION: Analyses of the available evidences suggest GEMOX regimen is promising as the first-line therapy for advanced pancreatic cancer, which encourages further clinical trials.