Causal associations between dietary factors and colorectal cancer risk: a Mendelian randomization study

BackgroundPrevious epidemiological studies have found a link between colorectal cancer (CRC) and human dietary habits. However, the inherent limitations and inevitable confounding factors of the observational studies may lead to the inaccurate and doubtful results. The causality of dietary factors to CRC remains elusive.MethodsWe conducted two-sample Mendelian randomization (MR) analyses utilizing the data sets from the IEU Open GWAS project. The exposure datasets included alcoholic drinks per week, processed meat intake, beef intake, poultry intake, oily fish intake, non-oily fish intake, lamb/mutton intake, pork intake, cheese intake, bread intake, tea intake, coffee intake, cooked vegetable intake, cereal intake, fresh fruit intake, salad/raw vegetable intake, and dried fruit intake. In our MR analyses, the inverse variance weighted (IVW) method was employed as the primary analytical approach. The weighted median, MR-Egger, weighted mode, and simple mode were also applied to quality control. Heterogeneity and pleiotropic analyses were implemented to replenish the accuracy of the results.ResultsMR consequences revealed that alcoholic drinks per week [odds ratio (OR): 1.565, 95% confidence interval (CI): 1.068–2.293, p = 0.022], non-oily fish intake (OR: 0.286; 95% CI: 0.095–0.860; p = 0.026), fresh fruit intake (OR: 0.513; 95% CI: 0.273–0.964; p = 0.038), cereal intake (OR: 0.435; 95% CI: 0.253–0.476; p = 0.003) and dried fruit intake (OR: 0.522; 95% CI: 0.311–0.875; p = 0.014) was causally correlated with the risk of CRC. No other significant relationships were obtained. The sensitivity analyses proposed the absence of heterogeneity or pleiotropy, demonstrating the reliability of the MR results.ConclusionThis study indicated that alcoholic drinks were associated with an increased risk of CRC, while non-oily fish intake, fresh fruit intake, cereal intake, and dried fruit were associated with a decreased risk of CRC. This study also indicated that other dietary factors included in this research were not associated with CRC. The current study is the first to establish the link between comprehensive diet-related factors and CRC at the genetic level, offering novel clues for interpreting the genetic etiology of CRC and replenishing new perspectives for the clinical practice of gastrointestinal disease prevention

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Investigation and analysis of the sources and intervention effects of glaucoma related knowledge among community residents

AIM:To investigate the effect of glaucoma knowledge education among community residents and knowledge source, and to provide reference for improving the awareness rate of glaucoma knowledge among residents.METHODS: From July 1, 2023 to September 30, 2023, a total of 752 residents live in two communities of Jinhua city were randomly selected to investigate the source of glaucoma prevention and treatment knowledge. In addition, comprehensive health education intervention lasted for 3 mo, awareness rate of core knowledge of glaucoma was investigated before and after the intervention, and the effect of the intervention was evaluated.RESULTS: The source of glaucoma related knowledge for radio and television was 33.4%; the mobile network was 40.9%; the health education was 21.5%. The overall awareness rate of glaucoma related knowledge before education intervention was 32.7%; the overall awareness rate after intervention was 48.4%, and the comparison before and after intervention was statistically significant(χ2=37.130, P<0.001). The awareness rate of 18 questions were statistically significant before and after the intervention(χ2≥13.341, P<0.001).CONCLUSION: The awareness rate of glaucoma related knowledge among residents was low, and mobile phone network and radio and television were the main sources of glaucoma related knowledge, so the education intervention was an effective means to improve glaucoma related knowledge

Identification of a novel cuproptosis-associated lncRNA model that can improve prognosis prediction in uterine corpus endometrial carcinoma

Uterine corpus endometrial carcinoma (UCEC) is a common female reproductive system cancer. Cuproptosis, a new type of mitochondrial respiration-regulated cell death, is associated with several cancer types. Here, we developed a cuproptosis-associated long non-coding RNA (lncRNA) model to predict the prognosis of patients with UCEC and their response to immune-based treatments. RNA sequencing (RNA-seq) and somatic mutation data for UCEC were obtained from The Cancer Genome Atlas (TCGA) database. LncRNAs co-expressed with cuproptosis-related genes were screened. Patients were randomly divided into two groups, one of which was used as training group to build the model, while the other group served as the validation group. A prognostic model comprising 13 cuproptosis-associated lncRNAs was constructed, and each lncRNA was individually related to patient prognosis. Our model clearly distinguished between risk variables in afflicted individuals. The risk score can provide a more accurate prognostic prediction compared with other clinical covariates. Patient groups at various risk groups were different according to tumor mutational burden and tumor immune dysfunction and exclusion analysis. We identified drugs for which patient populations at various risk groups showed higher sensitivity. Our model may contribute to immune related research and clinical decision-making for optimized treatment

Flexural properties of electrothermal deicing composite laminates:Experimental and numerical study

The electrothermal deicing composites usually experience flexural deformations, but fewer studies have been done on their flexural properties. In this study, specimens were manufactured by using the autoclave curing and spray metal multi-layer deposition technology. Three-point bending tests were conducted. A progressive damage model using user-defined material subroutine and cohesive elements was proposed to understand the damage evolution. A steady-state heat transfer model was established to obtain the temperature field. It is shown that the damage distributions obtained from the numerical modeling correlate well with experimental observations

Inhibitory Control and Hedonic Response towards Food Interactively Predict Success in a Weight Loss Programme for Adults with Obesity

Objective: Low inhibitory control and strong hedonic response towards food are considered to contribute to overeating and obesity. Based on previous research, the present study aimed at examining the potentially crucial interplay between these two factors in terms of long-term weight loss in people with obesity. Methods: BMI, inhibitory control towards food, and food liking were assessed in obese adults prior to a weight reduction programme (OPTIFAST® 52). After the weight reduction phase (week 13) and the weight loss maintenance phase (week 52), participants' BMI was re-assessed. Results: Baseline BMI, inhibitory control and food liking alone did not predict weight loss. As hypothesised, however, inhibitory control and food liking interactively predicted weight loss from baseline to week 13 and to week 52 (albeit the latter effect was less robust). Participants with low inhibitory control and marked food liking were less successful in weight reduction. Conclusion: These findings underscore the relevance of the interplay between cognitive control and food reward valuation in the maintenance of obesity

Inhibitory Control in Bulimic-Type Eating Disorders: A Systematic Review and Meta-Analysis

<div><p>The aim of this meta-analysis was to summarise data from neuropsychological studies on inhibitory control to general and disease-salient (i.e., food/eating, body/shape) stimuli in bulimic-type eating disorders (EDs). A systematic literature search was conducted to identify eligible experimental studies. The outcome measures studied included the performance on established inhibitory control tasks in bulimic-type EDs. Effect sizes (Hedges' <i>g</i>) were pooled using random-effects models. For inhibitory control to general stimuli, 24 studies were included with a total of 563 bulimic-type ED patients: 439 had bulimia nervosa (BN), 42 had anorexia nervosa of the binge/purge subtype (AN-b), and 82 had binge eating disorder (BED). With respect to inhibitory control to disease-salient stimuli, 12 studies were included, representing a total of 218 BN patients. A meta-analysis of these studies showed decreased inhibitory control to general stimuli in bulimic-type EDs (<i>g</i> = −0.32). Subgroup analysis revealed impairments with a large effect in the AN-b group (<i>g</i> = −0.91), impairments with a small effect in the BN group (<i>g</i> = −0.26), and a non-significant effect in the BED group (<i>g</i> = −0.16). Greater impairments in inhibitory control were observed in BN patients when confronted with disease-salient stimuli (food/eating: <i>g</i> = −0.67; body/shape: <i>g</i> = −0.61). In conclusion, bulimic-type EDs showed impairments in inhibitory control to general stimuli with a small effect size. There was a significantly larger impairment in inhibitory control to disease salient stimuli observed in BN patients, constituting a medium effect size.</p></div