Association between inflammatory bowel disease and the risk of parenteral malignancies: A two-sample Mendelian randomization study.

AIM: Using Mendelian Randomization (MR) analysis to investigate the potential causal association between Inflammatory Bowel Disease (IBD) and the occurrence of parenteral malignancies, in order to provide some reference for the parenteral malignancy prevention in patients with IBD. METHODS: This was a two-sample MR study based on independent genetic variants strongly linked to IBD selected from the Genome-Wide Association Study (GWAS) meta-analysis carried out by the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). Parenteral malignancy cases and controls were obtained from the FinnGen consortium and the UK Biobank (UKB) release data. Inverse Variance Weighted (IVW), weighted median, MR-Egger, and strength test (F) were utilized to explore the causal association of IBD with parenteral malignancies. In addition, Cochran's Q statistic was performed to quantify the heterogeneity of Instrumental Variables (IVs). RESULTS: The estimates of IVW showed that patients with IBD had higher odds of diffuse large B-cell lymphoma (OR = 1.2450, 95% CI: 1.0311‒1.5034). UC had potential causal associations with non-melanoma skin cancer (all p < 0.05), melanoma (OR = 1.0280, 95% CI: 0.9860‒1.0718), and skin cancer (OR = 1.0004, 95% CI: 1.0001‒1.0006). Also, having CD was associated with higher odds of non-melanoma skin cancer (all p < 0.05) and skin cancer (OR = 1.0287, 95% CI: 1.0022‒1.0559). In addition, results of pleiotropy and heterogeneity tests indicated these results are relatively robust. CONCLUSIONS: IBD has potential causal associations with diffuse large B-cell lymphoma and skin cancers, which may provide some information on the prevention of parenteral malignancies in patients with IBD. Moreover, further studies are needed to explore the specific mechanisms of the effect of IBD on skin cancers.

Exploration of the molecular linkage between endometriosis and Crohn disease by bioinformatics methods.

BACKGROUND: Endometriosis (EMT) is a common disease in reproductive-age woman and Crohn disease (CD) is a chronic inflammatory disorder in gastrointestinal tract. Previous studies reported that patients with EMT had an increased risk of CD. However, the linkage between EMT and CD remains unclear. In this study, we aimed to investigate the potential molecular mechanism of EMT and CD. METHODS: The microarray data of EMT and CD were downloaded from Gene Expression Omnibus. Common genes of EMT and CD were obtained to perform the Gene Ontology and Kyoto Encyclopedia of Gene Genomes enrichments. The protein-protein interaction network was constructed by Cytoscape software and the hub genes were identified by CytoHubba plug-in. Finally we predicted the transcription factors (TFs) of hub genes and constructed a TFs-hub genes regulation network. RESULTS: A total of 50 common genes were identified. Kyoto Encyclopedia of Gene Genomes enrichment showed that the common genes mainly enriched in MAPK pathway, VEGF pathway, Wnt pathway, TGF-beta pathway, and Ras pathway. Fifteen hub genes were collected from the protein-protein interaction network, including FMOD, FRZB, CPE, SST, ISG15, EFEMP1, KDR, ADRA2A, FZD7, AQP1, IGFBP5, NAMPT, PLUA, FGF9, and FHL2. Among them, FGF9, FZD7, IGFBP5, KDR, and NAMPT were both validated in the other 2 datasets. Finally TFs-hub genes regulation network were constructed. CONCLUSION: Our findings firstly revealed the linkage between EMT and CD, including inflammation, angiogenesis, immune regulation, and cell behaviors, which may lead to the risk of CD in EMT. FGF9, FZD7, IGFBP5, KDR, and NAMPT may closely relate to the linkage.

Association between inflammatory bowel disease and the risk of parenteral malignancies: A two-sample Mendelian randomization study

Abstract Aim: Using Mendelian Randomization (MR) analysis to investigate the potential causal association between Inflammatory Bowel Disease (IBD) and the occurrence of parenteral malignancies, in order to provide some reference for the parenteral malignancy prevention in patients with IBD. Methods: This was a two-sample MR study based on independent genetic variants strongly linked to IBD selected from the Genome-Wide Association Study (GWAS) meta-analysis carried out by the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). Parenteral malignancy cases and controls were obtained from the FinnGen consortium and the UK Biobank (UKB) release data. Inverse Variance Weighted (IVW), weighted median, MR-Egger, and strength test (F) were utilized to explore the causal association of IBD with parenteral malignancies. In addition, Cochran's Q statistic was performed to quantify the heterogeneity of Instrumental Variables (IVs). Results: The estimates of IVW showed that patients with IBD had higher odds of diffuse large B-cell lymphoma (OR = 1.2450, 95% CI: 1.0311‒1.5034). UC had potential causal associations with non-melanoma skin cancer (all p < 0.05), melanoma (OR = 1.0280, 95% CI: 0.9860‒1.0718), and skin cancer (OR = 1.0004, 95% CI: 1.0001‒1.0006). Also, having CD was associated with higher odds of non-melanoma skin cancer (all p < 0.05) and skin cancer (OR = 1.0287, 95% CI: 1.0022‒1.0559). In addition, results of pleiotropy and heterogeneity tests indicated these results are relatively robust. Conclusions: IBD has potential causal associations with diffuse large B-cell lymphoma and skin cancers, which may provide some information on the prevention of parenteral malignancies in patients with IBD. Moreover, further studies are needed to explore the specific mechanisms of the effect of IBD on skin cancers.

Ginsenoside Rk1 attenuates radiation-induced intestinal injury through the PI3K/AKT/mTOR pathway.

Radiation-induced intestinal injury (RIII) frequently occurs during radiotherapy; however, methods for treating RIII are limited. Ginsenoside Rk1 (RK1) is a substance that is derived from ginseng, and it has several biological activities, such as antiapoptotic, antioxidant and anticancer activities. The present study was designed to investigate the potential protective effect of Rk1 on RIII and the potential mechanisms. The results showed that RK1 treatment significantly improved the survival rate of the irradiated rats and markedly ameliorated the structural injury of the intestinal mucosa observed by histology. Treatment with RK1 significantly alleviated radiation-induced intestinal epithelial cell oxidative stress apoptosis. Moreover, RNA-Seq identified 388 differentially expressed genes (DEGs) and showed that the PI3K-AKT pathway might be a key signaling pathway by which RK1 exerts its therapeutic effects on RIII. The western blotting results showed that the p-PI3K, p-AKT and p-mTOR expression levels, which were increased by radiation, were markedly inhibited by Rk1, and these effects were reversed by IGF-1. The present study demonstrates that Rk1 can alleviate RIII and that the mechanism underlying the antiapoptotic effects of RK1 may involve the suppression of the PI3K/Akt/mTOR pathway. This study provides a promising therapeutic agent for RIII.

Focus on Radiation Protection Improves Both Correct Behavior and Procedural Performance During Simulation-Based Training - A Randomized Comparison.

BACKGROUND: To explore whether simulation-based endovascular training with focus on radiation safety could improve correct behavior without jeopardizing the learning of procedural skills. METHODS: Twenty-four residents without previous endovascular experience completed 10 clinical scenarios on a virtual-reality endovascular simulator with software for peripheral endovascular interventions. Participants were randomized to receive feedback (n = 12) or not (n = 12) on radiation protection (RP) performance after each case. Expert assessments were done at the first, second, fourth, seventh, and 10th case on RP and endovascular skills (ES). Automatic simulator metrics on procedure time, contrast dose, handling errors, and estimated radiation exposure to patient and operator were registered. Outcome metrics were analyzed by two-way mixed analysis of variance pairwise comparisons with independent t-tests. Correlations were explored using Pearson's r for internal consistency reliability. RESULTS: The RP performance was similar in both groups at their first attempt (P = 0.61), but the feedback group significantly outperformed the control group over time (P < 0.001 for all comparisons). The feedback group was however slower to learn the ES at start (P = 0.047 at second performance), but after 7 attempts no difference was shown (P = 0.59). The feedback group used more time (19.5 vs. 15.3 min; P = 0.007) but less contrast (60 vs. 100 mL; P < 0.001). The number of errors was the same in both groups, but all metrics regarding radiation exposure favored the feedback group (P-values from 0.001 to 0.008). CONCLUSIONS: Simulation-based training (SBT) is effective to acquire basic endovascular intervention skills and concurrently learn RP behavior when feedback on radiation culture is provided.

Effects of metformin on survival outcomes of pancreatic cancer: a meta-analysis.

BACKGROUND AND AIM: Recent epidemiological studies indicated that metformin might improve the survival of various cancers. However, its benefit on pancreatic cancer was controversial. METHODS: We performed this meta-analysis to investigate the benefit of metformin on pancreatic cancer. A comprehensive literature search was performed through PubMed, Cochrane Library and Embase. Relative risk (RR) and hazard ratio (HR) with 95% confidence interval (CI) were pooled. RESULTS: The meta-analysis of 2 randomized controlled trials including181 pancreatic patients, revealed that metformin use was not associated with an improved overall survival at 6 months (RR=0.90, 95% CI=0.67-1.21), overall survival (HR=1.19, 95% CI=0.86-1.63) and progression-free survival (HR=1.39, 95% CI=0.97-1.99). But the meta-analysis of 8 cohorts, involving 2805 pancreatic patients with diabetes, demonstrated a favorable result with improved overall survival (HR=0.78, 95% CI=0.66-0.92). CONCLUSIONS: Observations in the cohort studies supported a favorable role of metformin while the data from randomized controlled trials did not support that. Therefore, more high-quality RCTs are warranted.

Prognostic significance of neutrophil-to-lymphocyte ratio in rectal cancer: a meta-analysis.

BACKGROUND: Inflammatory responses play decisive roles in tumor development, immune surveillance, and responses to therapy. High neutrophil-to-lymphocyte ratio (NLR), as an inflammation index, has been reported to be a predictor for poor prognosis of various cancers. The purpose of this meta-analysis was to evaluate the prognostic value of NLR in patients with rectal cancer. METHODS: A comprehensive search of the literature was conducted through PubMed and EMBASE. Pooled hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the association between NLR and three outcomes: overall survival, disease-free survival, and recurrence-free survival. RESULTS: Seven cohorts involving 959 patients were included in this meta-analysis. Our pooled results demonstrated that elevated NLR was associated with poor overall survival (HR: 13.41, 95% CI: 4.90-36.72), disease-free survival (HR: 4.37, 95% CI: 2.33-8.19), and recurrence-free survival (HR: 3.64, 95% CI: 1.88-7.05). CONCLUSION: An elevated NLR is a valuable and easily available prognostic marker for rectal cancer. It is associated with unfavorable overall survival, disease-free survival, and recurrence-free survival. NLR could be a useful candidate factor for making treatment decisions for individual patients with rectal cancer.

The role of PTEN in chronic growth hormone-induced hepatic insulin resistance.

Chronic growth hormone (GH) therapy has been shown to cause insulin resistance, but the mechanism remains unknown. PTEN, a tumor suppressor gene, is a major negative regulator of insulin signaling. In this study, we explored the effect of chronic GH on insulin signaling in the context of PTEN function. Balb/c healthy mice were given recombinant human or bovine GH intraperitoneally for 3 weeks. We found that phosphorylation of Akt was significantly decreased in chronic GH group and the expression of PTEN was significantly increased. We further examined this effect in the streptozotocin-induced Type I diabetic mouse model, in which endogenous insulin secretion was disrupted. Insulin/PI3K/Akt signaling was impaired. However, different from the observation in healthy mice, the expression of PTEN did not increase. Similarly, PTEN expression did not significantly increase in chronic GH-treated mice with hypoinsulinemia induced by prolonged fasting. We conducted in-vitro experiments in HepG2 cells to validate our in-vivo findings. Long-term exposure to GH caused similar resistance of insulin/PI3K/Akt signaling in HepG2 cells; and over-expression of PTEN enhanced the impairment of insulin signaling. On the other hand, disabling the PTEN gene by transfecting the mutant PTEN construct C124S or siPTEN, disrupted the chronic GH induced insulin resistance. Our data demonstrate that PTEN plays an important role in chronic-GH-induced insulin resistance. These findings may have implication in other pathological insulin resistance.

Water intubation method can reduce patients' pain and sedation rate in colonoscopy: a meta-analysis.

Several randomized controlled trials (RCT) have shown that water infusion in lieu of air insufflation reduces sedation rate and pain score and increases cecal intubation rate in colonoscopy. The aim of the present study was to confirm the beneficial effects of the water intubation method over the air method. Electronic databases were searched to identify RCT reporting colonoscopy detection using the water method. The pooled data of sedation rate, pain score and other procedure-related outcomes were analyzed. Then, 15 full-text articles were selected and assessed. Nine trials with high-quality scores were enrolled into this meta-analysis including a total of 1414 participants. Pooled odds ratio (OR) of sedation rate was 0.392 (95% confidence interval (CI): 0.288-0.533, P = 0.000). Pooled weighted mean difference (WMD) of pain score was -1.543 (95% CI: -2.107--1.069,P = 0.000). Pooled OR of cecal intubation rate was 1.90 (95% CI: 1.29-2.82, P = 0.001). Pooled OR of polyp detection rate and adenoma detection rate were 0.805 (95% CI: 0.606-1.069, P = 0.134) and 0.913 (95% CI: 0.681-1.223, P = 0.168), respectively. Pooled WMD of cecal intubation time was 0.701 (95% CI: -0.486-1.889, P = 0.247). This meta-analysis confirmed that the water method significantly reduced sedation rate and degree of pain without decreasing cecal intubation rate and disease detection rate and without requiring more cecal intubation time, suggesting that the novel water method is better than the conventional air method in colonoscopy detection.