Alterations of the salivary microbiota in gastroesophageal reflux disease.

OBJECTIVES: Gastroesophageal reflux disease (GERD) is among the most prevalent gastrointestinal disorders. The oral microbiota plays an important role in human health and may be altered by the presence of GERD. Here, we aimed to investigate the alterations of salivary microbiota in GERD patients. METHODS: We collected clinical information and salivary samples from 60 individuals. All participants underwent combined pH/impedance monitoring measurement and submitted samples for salivary microbiota sequencing. According to acid exposure time and DeMeester score, participants were divided into two groups: GERD + (Group G) and GERD - (Group C). RESULTS: There was no significant difference in alpha diversity between study groups. Regarding beta diversity, principal coordinate analysis plots indicated that the microbiota composition data of the participants were grouped within partial overlapping clusters. The statistical analysis of the distance matrices was performed using the Adonis test (p = 0.017). Based on linear discriminant analysis effect size, the relative abundances of the phylum Bacteroidetes, class Bacteroidia, order Bacteroidales, family Prevotellaceae, and genus unidentified_Prevotellaceae were enriched in Group G. Compared with Group C, the phylum Actinobacteria, classes unidentified_Actinobacteria and Bacilli, orders Micrococcales and Lactobacillales, families Micrococcaceae and Streptococcaceae, and genuses Rothia and Streptococcus were decreased in Group G. At the genus level, the abundances of Streptococcus and Rothia were negatively correlated with DeMeester score and acid exposure time. CONCLUSIONS: This study revealed alterations of the salivary microbiota in GERD patients, suggesting that acid reflux changes the oral ecosystem.

A Novel Epithelial-Mesenchymal Transition Gene Signature Correlated With Prognosis, and Immune Infiltration in Hepatocellular Carcinoma.

Background: Although many genes related to epithelial-mesenchymal transition (EMT) have been explored in hepatocellular carcinoma (HCC), their prognostic significance still needs further analysis. Methods: Differentially expressed EMT-related genes were obtained through the integrated analysis of 4 Gene expression omnibus (GEO) datasets. The univariate Cox regression and Lasso Cox regression models are utilized to determine the EMT-related gene signature. Based on the results of multivariate Cox regression, a predictive nomogram is established. Time-dependent ROC curve and calibration curve are used to show the distinguishing ability and consistency of the nomogram. Finally, we explored the correlation between EMT risk score and immune immunity. Results: We identified a nine EMT-related gene signature to predict the survival outcome of HCC patients. Based on the EMT risk score's median, HCC patients in each dataset were divided into high and low-risk groups. The survival outcomes of HCC patients in the high-risk group were significantly worse than those in the low-risk group. The prediction nomogram based on the EMT risk score has better distinguishing ability and consistency. High EMT risk score was related to immune infiltration. Conclusion: The nomogram based on the EMT risk score can reliably predict the survival outcome of HCC patients, thereby providing benefits for medical decisions.

An m6A-Related lncRNA Signature Predicts the Prognosis of Hepatocellular Carcinoma.

Objective: The purpose of this study was to establish an N6-methylandenosine (m6A)-related long non-coding RNA (lncRNA) signature to predict the prognosis of hepatocellular carcinoma (HCC). Methods: Pearson correlation analysis was used to identify m6A-related lncRNAs. We then performed univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct an m6A-related lncRNA signature. Based on the cutoff value of the risk score determined by the X-title software, we divided the HCC patients into high -and low-risk groups. A time-dependent ROC curve was used to evaluate the predictive value of the model. Finally, we constructed a nomogram based on the m6A-related lncRNA signature. Results: ZEB1-AS1, MIR210HG, BACE1-AS, and SNHG3 were identified to comprise an m6A-related lncRNA signature. These four lncRNAs were upregulated in HCC tissues compared to normal tissues. The prognosis of patients with HCC in the low-risk group was significantly longer than that in the high-risk group. The M6A-related lncRNA signature was significantly associated with clinicopathological features and was established as a risk factor for the prognosis of patients with HCC. The nomogram based on the m6A-related lncRNA signature had a good distinguishing ability and consistency. Conclusion: We identified an m6A-related lncRNA signature and constructed a nomogram model to evaluate the prognosis of patients with HCC.

Development and Validation of an Autophagy-Related Gene Signature for Predicting the Prognosis of Hepatocellular Carcinoma.

PURPOSE: Autophagy is a lysosomal degradation pathway that is essential for maintaining the homeostasis of the intracellular environment. Mounting evidence indicates that autophagy plays an essential role in the occurrence and development of hepatocellular cancer (HCC). This research is aimed at exploring the prognostic value of autophagy-related genes (ARGs) in HCC patients. METHODS: The Wilcoxon test was used to identify differentially expressed ARGs in The Cancer Genome Atlas (TCGA) HCC cohort. Then, the TCGA cohort was randomly divided into training and testing groups. Cox and LASSO regression models were used to screen for autophagy-related genes that affect overall survival (OS) in the TCGA training group. Based on the coefficient of risk genes, we constructed an autophagy-related gene signature for predicting the prognosis of HCC patients. Finally, we validated the prognostic significance of autophagy-related gene signature using the TCGA testing group and three external datasets. RESULTS: ATG10, BIRC5, GAPDH, and TMEM74 are risk genes for OS. According to the optimal cutoff value of risk score in each HCC dataset, HCC patients can divide into high- and low-risk groups. ARG risk score can significantly distinguish HCC patients with different survival outcomes. Meanwhile, the ARG risk score is independently correlated with OS in multiple HCC cohorts. CONCLUSIONS: The autophagy-related risk score can effectively screen high-risk HCC patients and provide guidance for clinical prevention and treatment of HCC.

[The effect of exogenous glial cell line-derived neurotrophic factor on expression of gastric and colonic Akt, MAPK in slow transit constipation rats].

OBJECTIVE: To study the expression of Akt and MAPK in the stomach and colon of slow transit constipation (STC) in rats, as well as the effect of exogenous glial cell line-derived neurotrophic factor (GDNF) on it. METHODS: Forty-four SD rats were divided into control group and model group randomly. The STC model group was established by gastric irrigation of rhubarb for 3.5 months. The control group was received normal saline. After model building, each group was equally divided into 2 subgroup randomly, administrated with exogenous GDNF and normal saline by vein injection for one week respectively. The expression of Akt and MAPK in stomach and colon was detected by immunohistochemistry. RESULTS: (1) The expression of Akt in the stomach tended to weaker in STC rats comparing with the normal rats (P > 0.05), but it was stronger in STC plus GDNF group than in STC group (P < 0.05). (2) The expression of Akt and MAPK in the colon was weaker in STC group than in the normal group (all P < 0.05), and was stronger in STC plus GDNF group than in STC group (all P < 0.05). (3) The expression of MAPK in the stomach in STC group was weaker than in normal group (P < 0.05), and was stronger in STC plus GDNF group than in STC group (P < 0.01). There was no significant difference among STC plus GDNF group, normal group and GDNF group (P > 0.05). CONCLUSIONS: Long term consumption of rhubarb could induce STC by down-regulating the expression of Akt and MAPK in digestive tract. Exogenous GDNF may have a potential role on the etiology of STC.