The impact of depression-mediated gut microbiota composition on Irritable Bowel Syndrome: A Mendelian study.

OBJECTIVE: This study uses a two-sample Mendelian randomization (MR) analysis to delineate the causal influence of gut microbiota on the occurrence of irritable bowel syndrome (IBS), concurrently assessing the potential mediating function of depression within this framework. METHODS: Several two-sample MR methods were used to assess the causal repercussions of gut microbiota on the onset of both IBS and depression. Following this, gut microbiota and depression, which demonstrated notable causal associations, were integrated as exposure variables in a multivariable Mendelian randomization (MVMR) framework to construct a model encompassing gut microbiota, depression, and IBS. Mediation effects were assessed by examining the indirect pathway of gut microbiota → depression → IBS. RESULTS: Two-sample MR analysis unveiled a statistically significant causal association (P < 0.05) between specific bacterial group within the gut microbiota, notably p_Actinobacteria(OR = 0.829225), c_Clostridia(OR = 0.798897), s_Desulfovibrio_piger(OR = 1.163912), g_Streptococcus(OR = 1.132735), c_Actinobacteria(OR = 0.829224), and the onset of IBS. In the MVMR analysis, the relationship between depression and IBS was significant across Model 3, Model 7, Model 8, and Model 13 (P < 0.05). Assessment of mediation effects revealed that c_Clostridia and o_Clostridiales indirectly impacted IBS through depression, with masking effect ratios of 168.46 % and 168.44 %, respectively. CONCLUSION: These findings underscore a resilient causal association between the composition of gut microbiota and the initiation of IBS. Furthermore, depression serves as a mediator for particular groups of gut bacteria, thereby contributing to the development of IBS. These observations imply that interventions targeting mental health may potentially alleviate the risk of IBS onset attributable to adverse configurations of gut microbiota.

Observation of the application effect of low-volume polyethylene glycol electrolyte lavage solution (PEG-ELS) combined with ascorbic acid tablets in bowel preparation for colonoscopy in hospitalized patients.

Background: This study explored the effectiveness and safety of low-volume polyethylene glycol electrolyte lavage solution (PEG-ELS) combined with ascorbic acid tablets (PEG-ELS/Asc) in bowel preparation for a colonoscopy. Methods: A total of 240 hospitalized patients who underwent a colonoscopy in Wenzhou People's Hospital, Wenzhou Third Clinical College of Wenzhou Medical University from July 2020 to June 2022 were randomly divided into two groups, with 120 patients each. All of the participants were given a low-residue or residue-free diet one day before the examination and fasted after dinner (completed before 18:00) the day before the examination. The 2-L PEG-ELS/Asc group took 2-L PEG-ELS plus 10 g ascorbic acid tablets once orally, while the 3-L PEG-ELS group took 3-L PEG orally on several occasions. The primary endpoint was the achievement of preparation adequacy and an overall colon cleansing score of ≥6, both assessed by blinded investigators using the Boston Bowel Preparation Scale (BBPS). The bowel cleansing effect, polyp detection rate, adverse reaction rate, oral drug tolerance rate, renal function, and electrolyte level changes were also compared between the two patient groups. Results: There were no significant differences in the success rate of bowel preparation, the detection rate of polyps, or the adverse reaction rate between the two groups (P > 0.05). The tolerance rate of bowel preparation in the 2-L PEG-ELS/Asc group was significantly higher than that in the 3-L PEG-ELS group (93.3% vs. 80.23%) (P < 0.05). The levels of creatinine, serum potassium, serum sodium, and serum chlorine of the two groups before and after bowel preparation were within the normal range. In addition, the intestinal cleaning effect of the two preparation schemes for the hospitalized patients with diabetes and constipation is worse than that of those without these conditions (P < 0.05). Conclusion: The effectiveness and safety of using 2-L PEG-ELS/Asc in bowel preparation for a colonoscopy in hospitalized patients were not inferior to using 3-L PEG-ELS. For patients with diabetes and constipation, the cleansing effect of the two bowel preparation options was not very satisfactory, and further clinical research is needed in this regard.

Hsa_circ_0072309 is a prognostic biomarker and is correlated with immune infiltration in gastric cancer.

Background: Hsa_circ_0072309 has been identified as a tumor suppressor in several carcinomas. However, its precise role in gastric cancer (GC) remains largely unknown. This study was aimed to explore the precise role of Hsa_circ_0072309 in GC. Methods: The transcriptional and clinical data of stomach adenocarcinoma were downloaded using the University of California SantaCruz (UCSC) Xena browser. The circular RNA (circRNA) datasets were obtained from the Gene Expression Omnibus (GEO) database. The expression profile and survival analysis of differentially expressed micro RNAs (DEMIs) and differentially expressed messenger RNAs (DEMs) were performed. Correlations between the expression and immune infiltration of the DEMS were studied. Additionally, the expression of hsa_circ_0072309 in GC tissues and cell lines were validated, and the relationship between its expression and clinical features was investigated. Gain- and loss-of function experiments and molecular interaction experiments were also conducted. Results: Overall, 7 differentially expressed circRNAs, 13 DEMIs, and 17 DEMs were screened. Two DEMIs (hsa_miR-34a-3p and hsa_miR-326) and five DEMs (C7, MARCKSL1, UBE2T, OLR1, and HOXC11) showed significant differences in the high- and low-risk groups. The most significantly enriched Gene Ontology terms were the circadian regulation of gene expression and protein binding. The most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways were the PI3K-Akt and Ras signal pathways. Additionally, six genes were significantly correlated with immune infiltration. The real-time quantitative PCR (RT-qPCR) results revealed a significant downregulation of hsa_circ_0072309 in GC tissues related to tumor size, vascular invasion, and lymph node metastasis. A hsa_circ_0072309 overexpression suppressed whereas a hsa_circ_0072309 knockdown promoted GC cells proliferation and migration in vitro; in addition, hsa_circ_0072309 could directly bind to has-miR-34a-3p and has-miR-330-5p. Conclusions: Hsa_circ_0072309 is a potential diagnostic biomarker for GC, and complement component 7 may be a tumor suppressor. These may potentially predict the prognosis of patients with GC and may become new therapeutic targets.

Comprehensive analysis of circular RNA-associated competing endogenous RNA networks and immune infiltration in gastric cancer.

BACKGROUND: Circular RNA (circRNA) has been proved to be an important regulator of gastric cancer (GC). However, the role and regulatory mechanism of circrna related competitive endogenous RNA (ceRNA) in GC have not been established. METHODS: CircRNA data and clinical data were obtained from the GEO and TCGA databases. The ceRNA networks were constructed and a function enrichment analysis was completed. Additionally, correlations between hub genes expression, immune cell infiltration, and clinical phenotypes were determined. The differentially expressed circRNAs and their downstream microRNAs (miRNAs) were validated by quantitative real-time polymerase chain reaction, and the hub genes were validated by western blot analysis. The migration and invasion ability of overexpressed hsa_circ_0002504 was determined by a transwell assay. RESULTS: The ceRNA network contained 2 circRNAs, 3 miRNAs, and 55 messenger RNAs (mRNAs). 323 biological processes terms, 53 cellular components terms, 51 molecular functions terms, and 4 signaling pathways were revealed by the function enrichment analysis. The GSEA analysis revealed that the hub genes were positively correlated with the axon guidance and adhesion molecules pathways. The correlation analysis revealed that overexpressed EPHA4 and KCNA1 indicated poor tissue differentiation and were associated with clinically advanced stages of GC. The in vitro experiments showed that hsa_circ_0002504 was significantly down-regulated in GC cell lines. In addition, the overexpression of hsa_circ_0002504 led to a significant downregulation of hsa-miR-615-5p and hsa-miR-767-5p, as well as an upregulation of EPHA4, KCNA1, and NCAM1. Furthermore, it suppressed the migration and invasion ability of GC cells. CONCLUSIONS: Hsa_circ_0002504 is a potential diagnostic biomarker for GC. High expression of EPHA4 and KCNA1 may indicate poor prognosis.

Assessing whether serum ceruloplasmin promotes non-alcoholic steatohepatitis via regulating iron metabolism.

Background: Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD). The diagnostic gold standard for detecting NASH still relies upon an invasive pathological biopsy. There is, therefore, a need to identify non-invasive diagnostic markers. Oxidative stress mediates fatty liver progression to NASH. Imbalanced iron metabolism produces many reactive oxygen species (ROS). Ceruloplasmin is associated with oxidase and iron metabolism-related activities. The current study aimed to determine whether there was a correlation between ceruloplasmin levels and NASH and whether such a relationship may be associated with altered iron metabolism in NASH patients. Methods: A total of 135 NAFLD patients were enrolled in this study. A pathological biopsy confirmed that 60 of those patients had NAFLD activity scores (NAS) 5, while the remaining 75 had NAS<5. Results: Receiver operating characteristic (ROC) curves confirmed that serum ceruloplasmin and ferritin levels were predictors of NAS 5 and NAS<5, with area under the curve (AUC) values of 0.80 and 0.81, respectively. The serum ceruloplasmin levels in NAS 5 patients were significantly lower than those in NAS<5 patients (p< 0.001). Serum ceruloplasmin levels were also negatively correlated with ferritin levels. Lower serum ceruloplasmin levels were associated with more severe histopathological findings. Conclusions: Low serum ceruloplasmin and high serum ferritin are correlated with NASH. A high concentration of serum ferritin is a viable clinical biomarker of NASH, and low serum ceruloplasmin may participate in the occurrence of NASH by regulating iron load, which can be used as a non-invasive diagnostic marker of NASH.

Effects of dyslipidemia on E antigen seroconversion of patients with chronic hepatitis B treated by nucleoside (acid) analogs.

BACKGROUND: The prevalence of dyslipidemia in China is increasing annually. Current studies suggest that dyslipidemia affects the antiviral efficacy of hepatitis C virus (HCV) therapies, while recent studies suggest that serum lipids influence the response rates of chronic hepatitis B (CHB) patients receiving PEGylated interferon-alpha (Peg IFN-α) treatment. However, the role of dyslipidemia in the efficacy of nucleoside (acid) analogues (NAs) in CHB patients remains unclear. METHODS: From January 2010 to December 2013, data from 179 treatment-naive patients with CHB who were hepatitis B e antigen (HBeAg)-positive and had visited the first affiliated hospital of Wenzhou Medical University were assessed. Of these patients, 68 were assigned to the dyslipidemia group (diagnosed with CHB complicated with dyslipidemia) and 111 to the normolipidemic group. The following 3 treatment strategies were performed for all CHB patients over a 5-year period: lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy, telbivudine (LdT) monotherapy, and entecavir (ETV) monotherapy. Serum assessments, blood biochemistry, HBV serological markers, HBV DNA before treatment and HBeAg serological conversion and virological responses at different timepoints after treatment were compared between the two groups. Measurement data were compared by τ tests and enumeration data by χ2 tests. Correlation analysis was performed using binary logistic regression analysis. RESULTS: The rates of HBeAg seroconversion in the dyslipidemia group at years 1, 2, 3, and 4 were 10.3, 13.2, 17.6, and 22.1%, respectively, which were not significantly lower than those of the normolipidemic group (11.7, 16.2, 18.0 and 33.3%; χ2 = 0.085, 0.293, 0.004, and 2.601, respectively; Ρ > 0.05). However, the rates of HBeAg seroconversion in the dyslipidemia group were significantly lower than those in the normolipidemic group at year 5 (27.9% vs. 43.2%, χ2 = 4.216, Ρ < 0.05). Univariate logistic regression analysis revealed significant differences in group, gender, PTA, ALT, AST, CR, and LDL-C between groups with and without seroconversion. Multivariate regression analysis demonstrated that dyslipidemia (OR = 1.993, Ρ = 0.038) and male gender (OR = 2.317, Ρ = 0.029) were risk factors associated with HBeAg seroconversion. CONCLUSIONS: During antiviral therapy, dyslipidemia affects HBeAg seroconversion in CHB patients treated with NAs, but does not affect the virological response.

Pan-Cancer Analysis Identifies Liver Metastases as Negative Predictive Factor for Immune Checkpoint Inhibitors Treatment Outcome.

This study aimed to investigate the predictive value of liver metastases (LM) in patients with various advanced cancers received immune-checkpoint inhibitors (ICIs). First, clinical and survival data from a published cohort of 1,661 patients who received ICIs therapy were downloaded and analyzed. Second, a retrospective review of 182 patients with advanced non-small-cell lung cancer (NSCLC) who received PD-1/PD-L1 monotherapy was identified. Third, a meta-analysis of published trials was performed to explore the impact of LM on the efficacy of anti-PD-1/PD-L1 based therapy in advanced lung cancers. Pan-cancer analysis revealed that patients with LM had significantly shorter overall survival (OS) than those without LM (10 vs. 20 months; P < 0.0001). Subgroup analysis showed that the presence of LM was associated with markedly shorter OS than those without LM in ICI monotherapy group (P < 0.0001), but it did not reach the statistical significance in ICI-based combination therapy (P = 0.0815). In NSCLC, the presence of LM was associated with significantly inferior treatment outcomes in both pan-cancer and real-world cohort. Interestingly, ICI-based monotherapy and combination therapy could simultaneously prolong progression-free survival (PFS) and OS than chemotherapy in patients without LM. However, ICI-based monotherapy could not prolong PFS than chemotherapy in patients with LM while ICI-based combination therapy could dramatically prolong both PFS and OS. Together, these findings suggested that the presence of LM was the negative predictive factor in cancer patients received ICIs monotherapy, especially in NSCLC. ICI-based combination therapy might overcome the intrinsic resistance of LM to ICIs while the optimal combinatorial strategies remain under further investigation.

Predictive Value of KDM5C Alterations for Immune Checkpoint Inhibitors Treatment Outcomes in Patients With Cancer.

Lysine (K)-specific demethylase 5C (KDM5C) plays a significant role in the tumor cell proliferation, invasion, drug resistance and the regulation of tumor-related gene expression. Here, we aimed to investigate its predictive value in patients with cancers received immune checkpoint inhibitors (ICIs). We explored the predictive value of KDM5C alterations and the association between KDM5C alteration and immune landscape by using published cohort with clinical outcome and sequenced data from online database. The frequency of KDM5C alterations was 2.1% across 48045 tumor samples with different cancers from 185 studies. KDM5C alterations were correlated with markedly inferior overall survival (OS, 53 vs. 102 months, P<0.0001) than those without. However, in ICI-treated group, patients with KDM5C alterations had a substantially prolonged OS than the wild-type group (not reached vs. 18 months, P=0.0041). The predictive value of KDM5C alterations for ICI treatment outcome was not observed in patients with microsatellite-stable tumors (P=0.2875). Intriguingly, patients with non-small-cell lung cancer and KDM5C alterations receiving ICI had the better progression-free survival than wild type group (13.2 vs. 3.2 months, P=0.0762). Mechanistically, KDM5C altered tumors had dramatically higher TMB level and was associated with significantly higher level of CD8+ T cell infiltration and T effector signature. In conclusion, KDM5C alterations was correlated with enhanced tumor immunogenicity and inflamed anti-tumor immunity, thus resulting in better treatment outcome in cancer patients receiving ICIs.

Impact of gender and age on the occurrence of gastric polyps: data analysis of 69575 southeastern Chinese patients.

BACKGROUND/AIMS: Current epidemiological data suggest that the incidence of gastric polyps (GP) is rare, and its etiology and pathogenesis are still not clear. This study analyzed and compared the occurrence and pathological types of GPs in southeast Chinese patients according to gender and age. MATERIALS AND METHODS: This was a retrospective study of patients diagnosed with GP (n=2125) in Wenzhou People's Hospital (China) between January 2004 and December 2013. The relationships between the detection rate, the characteristics of GP, and the patients' demographic data were analyzed. RESULTS: The detection rate of GP was 2.3% and 3.9% in males and females, respectively (p<0.01). The detection rate increased with increasing age in both genders. Polyps in the gastric antrum and gastric body were the most prevalent in both genders. Similarly, inflammatory polyps and hyperplastic polyps were the most prevalent in both genders. Hyperplastic polyps were more common in females than in males (28.6% vs. 24.2%, p<0.05), while there was no difference for inflammatory polyps, fundic GP, and adenoma (p>0.05). Age had no impact on the pathology of GP (p>0.05). CONCLUSIONS: The incidence of GPs was associated with gender and age.