Systemic inflammation, resulting from massive release of pro-inflammatory molecules into the circulatory system, is a major risk factor for severe illness, but the precise mechanisms underlying its control are incompletely understood. We observed that prostaglandin E2 (PGE2) through its receptor EP4 is down-regulated in human systemic inflammatory disease. Mice with reduced PGE2 synthesis develop systemic inflammation, associated with translocation of gut bacteria, which can be prevented by treating with EP4 agonists. Mechanistically, we demonstrate that PGE2–EP4 signaling directly acts on type 3 innate lymphoid cells (ILCs), promoting their homeostasis and driving them to produce interleukin-22 (IL-22). Disruption of the ILC/IL-22 axis impairs PGE2–mediated inhibition of systemic inflammation. Hence, PGE2–EP4 signaling inhibits systemic inflammation through ILC/IL-22 axis–dependent protection of gut barrier dysfunction.

No abstract

The geriatric nutritional risk index (GNRI) has been reported as a useful tool for predicting the prognosis of many diseases; however, there is currently little research on the relationship between GNRI and outcomes in elderly colorectal cancer (CRC) patients. This study aimed to explore the value of GNRI in evaluating postoperative complication risk and long-term prognosis in elderly CRC patients. Patients and Methods: The medical records of 230 CRC patients aged≥65 years who underwent surgery between January 2012 and December 2014 were retrospectively analyzed. Patients were divided into abnormal and normal GNRI groups by modified binary classification. Logistic regression analysis was used to evaluate the correlation between GNRI and complication risk. The Kaplan-Meier method with log-rank test was used to construct survival curves. The Cox proportional hazard model was used for univariate, multivariate and subgroup survival analyses to assess the relationship between GNRI and long-term prognosis. Results: Multivariate logistic regression analysis showed that GNRI (p = 0.009, HR 2.280, 95% CI: 1.224-4.247) was an independent risk factor for postoperative complications in elderly CRC patients. Kaplan-Meier survival curves revealed that the abnormal GNRI group had significantly lower disease-free survival (DFS; p = 0.005) and overall survival (OS; p=0.007) than the normal GNRI group had, especially in TNM I stage. In multivariate survival analysis, GNRI was an independent prognostic factor for DFS (p = 0.003, HR 1.842, 95% CI: 1.229-2.760) and OS (p = 0.003, HR 1.852, 95% CI: 1.231-2.787). Conclusion: GNRI is a simple and effective tool for predicting the risk of postoperative complications and the long-term prognosis of postoperative elderly CRC patients and can provide a scientific basis for early nutrition interventions in elderly CRC patients.

Background: Several epidemiological studies have assessed the association of sugary drinks consumption with cancer, but the results remain controversial. Objective: We performed this analysis to evaluate possible causal relationship between sugary drinks consumption and cancer risk and mortality. Methods: We searched PubMed, Embase, and Web of Science databases in English. Observational studies evaluating the association of sugary drinks intake with cancer were included. Random-effects meta-analysis was used to calculate the risk estimates. Results: A total of 71 observational articles with 32 case-control and 39 cohort studies were included in the meta-analysis. 60 addressed cancer risk, and 11 reported cancer mortality. Compared with the lowest level, the highest level of sugar-sweetened beverages (SSB) consumption showed an increased overall cancer risk (RR=1.12 95% CI: 1.06-1.19, P=0.000) and mortality (RR=1.07 95% CI: 1.01-1.14, P=0.029), and fruit juice intake showed a positive association with cancer risk in cohort studies (RR=1.06 95% CI: 1.01-1.11, P=0.013). Subgroup analyses based on cancer type indicated that risk of breast cancer, hepatocellular carcinoma, colorectal cancer, and prostatic cancer mortality had a positive association with SSB consumption. For dose-response analysis, evidence of a linear association was found between overall cancer risk and SSB or fruit juice consumption, and the risk increase by 4% for one servings/d increment in SSB intake and 14% in fruit juice. Conclusions: Our findings suggest the consumption of sugary beverages may increase the risk and mortality of cancer, especially risk of breast cancer, hepatocellular carcinoma, colorectal cancer, and prostatic cancer, and mortality of breast cancer, though the evidence was limited.

Background The effect of the geriatric nutritional risk index (GNRI) on the prognosis of patients with gastrointestinal malignancy remains unclear. The aim of our study was to systematically explore the value of the GNRI in evaluating postoperative complications and long-term outcomes in gastrointestinal malignancy. Methods A systematic literature search was conducted using electronic databases to report the impact of the GNRI on postoperative complications and long-term outcomes of patients with gastrointestinal malignancies as of August 2020. The hazard ratio (HR) with a 95% confidence interval (CI) was used to evaluate the impact of the GNRI on long-term outcomes. The risk ratio (RR) with 95% CI was used to assess the impact of the GNRI on postoperative complications. Result A total of nine studies with 2,153 patients were enrolled in our meta-analysis. The results suggested that a low GNRI was correlated with poor overall survival of patients with gastrointestinal malignancy (HR = 1.94, 95% CI 1.65–2.28, p < 0.001). Patients with a low GNRI had a higher risk of complications than patients with a high GNRI (OR = 2.19, 95% CI 1.57–3.05, p < 0.001). In addition, patients with a low GNRI had shorter relapse-free survival (HR = 2.45, 95% CI 1.50–4.00, p < 0.001) and disease-free survival (HR = 1.84, 95% CI 1.23–2.76, p = 0.003) than those with a high GNRI. However, the GNRI was not an independent factor affecting cancer-specific survival (HR = 1.60, 95% CI 0.91–2.82, p = 0.101). Conclusion Based on existing evidence, the GNRI was a valuable predictor of complications and long-term outcomes in patients with gastrointestinal malignancy.

Hes1 is a transcription factor that influences cell proliferation and differentiation. However, the effect of Hes1 on invasiveness and the underlying mechanism remain unknown. In the current study, we found that Hes1 suppressed cell apoptosis, promoted cell growth, induced EMT phenotype and cytoskeleton reconstruction, and enhanced the metastatic potential of colon cancer cells in vitro and in vivo. Furthermore, we indicated that Bmi-1 mediated Hes1-induced cell proliferation and migration, downregulated PTEN and activated the Akt/GSK3β pathway, consequently induced EMT and cytoskeleton reconstruction, ultimately leading to enhanced invasiveness of cancer cells. In addition, we also found that both Hes1 and Bmi-1 could directly regulate PTEN by associating at the PTEN locus, and played important roles in regulating PTEN/Akt/GSK3β pathway. Our results provide functional and mechanistic links between Hes1 and Bmi-1/PTEN/Akt/GSK3β signaling in the development and progression of colon cancer.

BackgroundObservational studies have shown inconsistent results regarding alcohol consumption and risk of fatty liver. We performed a meta-analysis of published literature to investigate the association between alcohol consumption and fatty liver disease (FLD).MethodsWe searched Medline, Embase, Web of Science, and several Chinese databases, identifying studies that reported an association between alcohol consumption and the risk of FLD.ResultsA total of 16 studies with 76,608 participants including 13 cross-sectional studies, two cross-sectional following longitudinal studies, and one cohort study met the inclusion criteria. For light to moderate alcohol consumption (LMAC), there was a 22.6% reduction in risk of FLD (odds ratio [OR] = 0.774, 95% confidence interval CI [0.695–0.862], P <0.001), and subgroup analysis showed that a greater reduction in risk of FLD was found in the female drinkers (30.2%) and the drinkers with BMI ≥25 kg/m2(31.3%) compared with the male drinkers (22.6%) and the drinkers with BMI <25 kg/m2(21.3%), respectively. For heavy alcohol consumption, there was no significant influence on risk of FLD (OR = 0.869, 95% CI [0.553–1.364], P = 0.541) in Japanese women, but there was a 33.7% reduction in risk of FLD (OR = 0.663, 95% CI [0.574–0.765], P < 0.001) in Japanese men and a significant increased risk of FLD (OR = 1.785, 95% CI [1.064–2.996], P = 0.028) in Germans.ConclusionLMAC is associated with a significant protective effect on FLD in the studied population, especially in the women and obese population. However, the effect of heavy alcohol consumption on FLD remains unclear due to limited studies and small sample sizes.

GMDs are frequent events in malignancy patients. Hyperglycemia and hypoglycemia are found in the same kinds or different kinds of cancers, and the incidence of hyperglycemia is higher than that of hypoglycemia. Characteristics of GMDs were dissimilar in different cancers and different ages. Hyperglycemia was a risk factor for many cancers.