Efficacy of artificial intelligence in reducing miss rates of GI adenomas, polyps, and sessile serrated lesions: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: The aim of this study was to determine if utilization of artificial intelligence (AI) in the course of endoscopic procedures can significantly diminish both the adenoma miss rate (AMR) and the polyp miss rate (PMR) compared with standard endoscopy. METHODS: We performed an extensive search of various databases, encompassing PubMed, Embase, Cochrane Library, Web of Science, and Scopus, until June 2023. The search terms used were artificial intelligence, machine learning, deep learning, transfer machine learning, computer-assisted diagnosis, convolutional neural networks, gastrointestinal (GI) endoscopy, endoscopic image analysis, polyp, adenoma, and neoplasms. The main study aim was to explore the impact of AI on the AMR, PMR, and sessile serrated lesion miss rate. RESULTS: A total of 7 randomized controlled trials were included in this meta-analysis. Pooled AMR was markedly lower in the AI group versus the non-AI group (pooled relative risk [RR], .46; 95% confidence interval [CI], .36-.59; P < .001). PMR was also reduced in the AI group in contrast with the non-AI control (pooled RR, .43; 95% CI, .27-.69; P < .001). The results showed that AI decreased the miss rate of sessile serrated lesions (pooled RR, .43; 95% CI, .20 to .92; P < .05) and diminutive adenomas (pooled RR, .49; 95% CI, .26-.93) during endoscopy, but no significant effect was observed for advanced adenomas (pooled RR, .48; 95% CI, .17-1.37; P = .17). The average number of polyps (Hedges' g = -.486; 95% CI, -.697 to -.274; P = .000) and adenomas (Hedges' g = -.312; 95% CI, -.551 to -.074; P = .01) detected during the second procedure also favored AI. However, AI implementation did not lead to a prolonged withdrawal time (P > .05). CONCLUSIONS: This meta-analysis suggests that AI technology leads to significant reduction of miss rates for GI adenomas, polyps, and sessile serrated lesions during endoscopic surveillance. These results underscore the potential of AI to improve the accuracy and efficiency of GI endoscopic procedures.

Peripheral blood mononuclear cell microRNAs are novel biomarkers for diagnosing and monitoring Crohn's disease.

Crohn's disease is a recurrent, progressive, immune-mediated inflammatory disease and merely manifests non-specific symptoms at early stage. In this study, we isolated peripheral blood mononuclear cells (PBMCs) to determine whether PBMC miRNAs are reliable biomarkers for Crohn's disease diagnosing and monitoring. 5 Crohn's disease patients and 5 healthy controls were recruited to find differentially expressed miRNAs by next generation sequencing. Candidate PBMC miRNAs were further validated by qRT-PCR in another cohort consisting of 86 Crohn's disease patients and 39 healthy controls. We found PBMC miR-582-5p could diagnose Crohn's disease with the area under receiver operating characteristic curve (AUROC) of 0.701(95%CI 0.606-0.796, p < .001). While PBMC miR-96-5p was significantly higher in active Crohn's disease and correlated with both clinical (ρ = 0.376, p < .001) and endoscopic activity (ρ = 0.512, p = .015). Furthermore, PBMC miR-96-5p had a better performance in recognizing active Crohn's disease with AUROC of 0.727 (95%CI 0.609-0.844, p = .001) than C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and fecal calprotectin. In conclusion, PBMC miR-582-5p may be further utilized as a diagnostic biomarker, while miR-96-5p may be a novel and valuable biomarker in monitoring disease activity.

Influence of Primary Tumor Resection on Survival of Patients With Metastatic Siewert Type II Adenocarcinoma of the Esophagogastric Junction: A Population-Based, Propensity-Matched Analysis.

OBJECTIVE: It remains unclear whether primary tumor resection improves survival in patients with metastatic Siewert type II adenocarcinoma of the esophagogastric junction (AEG). Therefore, our study attempted to investigate the prognostic value of primary tumor resection on metastatic AEG. METHODS: In total, 4200 patients diagnosed with metastatic AEG were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Patients were categorized into two groups according to the performance of primary tumor resection. Pearson's chi-square test, Kaplan-Meier survival curve, and Cox regression analysis were conducted in this study. In addition, propensity-score matching was conducted to match 323 patients who received primary tumor resection and another 323 patients without. RESULTS: Multivariate Cox regression analysis demonstrated that primary tumor resection was a significant prognostic factor in patients with metastatic AEG before matching. Moreover, in the matched cohort, metastatic AEG patients receiving primary tumor resection had significantly longer overall survival (hazard ratio [HR]: .54, 95% confidence interval [CI]: .46-.64, P < .001) and cancer-specific survival (HR: .53, 95% CI: .45-.63, P < .001). Subgroup analysis similarly revealed that primary tumor resection was significantly associated with better survival in most subgroups. CONCLUSION: The present population-based study identified that primary tumor resection led to significantly superior survival in patients with metastatic AEG. These findings are likely to contribute to the development of individualized therapy in metastatic AEG.

Circulating MiR-1290 as a potential diagnostic and disease monitoring biomarker of human gastrointestinal tumors.

BACKGROUND: Gastrointestinal tumors are a leading cause of mortality worldwide. As shown in our previous study, miR-1290 is overexpressed in colorectal cancer (CRC) and promotes tumor progression. We therefore aimed to explore the potential of circulating miR-1290 as a biomarker for gastrointestinal cancer. METHODS: A serum miRNA sequencing analysis was performed. Then, circulating miRNA detection technologies were established. The expression of miR-1290 was analyzed in gastrointestinal tumor cell lines and culture supernatants. Expression levels of circulating miR-1290 in clinical samples were examined. Associations between miR-1290 expression and clinicopathologic characteristics were analyzed. Xenograft models were generated to assess the fluctuation in serum miR-1290 levels during disease progression. RESULTS: Through miRNA sequencing, we identified that miR-1290 was overexpressed in serum samples from patients with CRC. We confirmed that human gastrointestinal tumor cells express and secrete miR-1290. The circulating miR-1290 levels was up-regulated in patients with pancreatic cancer (PC) (p < 0.01), CRC (p < 0.05), and gastric cancer (GC) (p < 0.01). High miR-1290 expression levels were associated with tumor size, lymphatic invasion, vascular invasion, distant metastasis, tumor differentiation and AJCC stage in patients with PC and CRC. The area under the curve (AUC) was 0.8857 in patients with PC, with 60.9% sensitivity and 90.0% specificity. The AUC was 0.7852 in patients with CRC, with 42.0% sensitivity and 90.0% specificity. In patients with GC, the AUC was 0.6576, with 26.0% sensitivity and 90.0% specificity. The in vivo model verified that the circulating miR-1290 level was significantly increased after tumor formation and decreased after drug treatment. CONCLUSIONS: Our findings indicate that circulating miR-1290 is a potential biomarker for gastrointestinal cancer diagnosis and monitoring.

Application of Artificial Intelligence in Gastrointestinal Endoscopy.

Artificial intelligence (AI), also known as computer-aided diagnosis, is a technology that enables machines to process information and functions at or above human level and has great potential in gastrointestinal endoscopy applications. At present, the research on medical image recognition usually adopts the deep-learning algorithm based on the convolutional neural network. AI has been used in gastrointestinal endoscopy including esophagogastroduodenoscopy, capsule endoscopy, colonoscopy, etc. AI can help endoscopic physicians improve the diagnosis rate of various lesions, reduce the rate of missed diagnosis, improve the quality of endoscopy, assess the severity of the disease, and improve the efficiency of endoscopy. The diversity, susceptibility, and imaging specificity of gastrointestinal endoscopic images are all difficulties and challenges on the road to intelligence. We need more large-scale, high-quality, multicenter prospective studies to explore the clinical applicability of AI, and ethical issues need to be taken into account.

Dilemma and Challenge of Immunotherapy for Pancreatic Cancer.

Pancreatic cancer is a tumor with a high degree of malignancy, morbidity, and mortality. Immunotherapy is another important treatment for pancreatic cancer in addition to surgery and chemotherapy, but its application in pancreatic cancer is very limited, which is related to the unique biological behavior of pancreatic cancer and the tumor microenvironment. The immunosuppressive microenvironment of pancreatic cancer is highly heterogeneous and presents challenges for immunotherapy. The transformation of tumor immunosuppressive microenvironment contributes to the response to tumor immunotherapy, such that the tumor undergoes functional reprogramming to change from immunologically "cold" to immunologically "hot." In this review, we summarized the research and progress in immunotherapy for pancreatic cancer, including immune checkpoint inhibitors, vaccines, adoptive T cell therapy, oncolytic viruses, and immunomodulators, and suggest that individualized, combination, and precise therapy should be the main direction of future immunotherapy in pancreatic cancer.

SLC1A3 promotes gastric cancer progression via the PI3K/AKT signalling pathway.

Gastric cancer is a major cause of mortality worldwide. The glutamate/aspartate transporter SLC1A3 has been implicated in tumour metabolism and progression, but the roles of SLC1A3 in gastric cancer remain unclear. We used bioinformatics approaches to analyse the expression of SLC1A3 and its role in gastric cancer. The expression levels of SLC1A3 were examined using RT-qPCR and Western bolting. SLC1A3 overexpressing and knock-down cell lines were constructed, and the cell viability was evaluated. Glucose consumption, lactate excretion and ATP levels were determined. The roles of SLC1A3 in tumour growth were evaluated using a xenograft tumour growth model. SLC1A3 was found to be overexpressed in gastric cancer, and this overexpression was associated with poor prognosis. In vitro and in vivo assays showed that SLC1A3 affected glucose metabolism and promoted gastric cancer growth. GSEA analysis suggested that SLC1A3 was positively associated with the up-regulation of the PI3K/AKT pathway. SLC1A3 overexpression activated the PI3K/AKT pathway and up-regulated GLUT1, HK II and LDHA expression. The PI3K/AKT inhibitor LY294002 prevented SLC1A3-induced glucose metabolism and cell proliferation. Our findings indicate that SLC1A3 promotes gastric cancer progression via the PI3K/AKT signalling pathway. SLC1A3 is therefore a potential therapeutic target in gastric cancer.

Myricetin inhibits NLRP3 inflammasome activation via reduction of ROS-dependent ubiquitination of ASC and promotion of ROS-independent NLRP3 ubiquitination.

Myricetin is a plant-derived flavonoid that exhibits diverse pharmacological properties. The NLRP3 (NLR family, pyrin domain-containing 3 protein) inflammasome is a cytosolic multiprotein complex that plays a critical role in the innate immune response and pathogenesis of multiple inflammatory disorders. The present study found that myricetin inhibited NLRP3 inflammasome assembly via promotion of reactive oxygen species (ROS)-independent ubiquitination of NLRP3 and reduction of ROS-dependent ubiquitination of ASC (apoptosis-associated speck-like protein containing a CARD), which disrupted the interaction between ASC and NLRP3 and inhibited ASC oligomerization. This effect was further confirmed in vivo using mouse models of lipopolysaccharide (LPS)-induced sepsis and alum-induced peritonitis. These results suggest the therapeutic value of myricetin by targeting NLRP3-driven inflammatory diseases.

Internet and WeChat used by patients with Crohn's disease in China: a multi-center questionnaire survey.

BACKGROUND: Currently, WeChat is widely used in disease education for patients with Crohn's disease (CD) in China. It is beneficial for the patients to actively engage in their disease management. METHODS: In this study, we examined the source and expectations of disease information for Chinese CD patients, analysing the content of popular WeChat public accounts and their potential association with medication adherence. RESULTS: Between November 24th, 2017 and April 10th, 2018, online questionnaires were sent to CD patients from eight different large urban hospitals in China. In all, 436 patients with CD were surveyed, and 342 patients responded. Patients most frequently visited Baidu (65%), WeChat (61%) and medical websites such as Haodaifu (35%) when searching for IBD-related information. Among ten WeChat IBD public accounts, the China Crohn's and Colitis Foundation (CCCF) (73%), "IBD Academic Officer" (21%) and "IBD in love" (21%) were the most popular. CD patients were most interested in information from the internet about diet and day-to-day health-related living with IBD (83%), an introduction to the disease (80%), and medication advances and side effects (80%). The correlation between the information provided by the top five WeChat public accounts and patients' expectations was low. Additionally, most patients (64%) had greater confidence in overcoming the disease after learning about CD through their internet searches. Medical adherence was also related to internet access and income (p < 0.05). CONCLUSIONS: WeChat has become a major source of information for IBD education in China, but the content of WeChat didn't fully meet patients' expectations. Therefore, future initiatives should aim to provide high-quality information that based on patients' demands.

Risk of gastric cancer among patients with gastric intestinal metaplasia.

Plenty of studies have assessed the association between intestinal metaplasia (IM) and gastric cancer risk, while the results were inconsistent. We aimed to assess the risk of gastric cancer among patients with IM. Systematic literature searches were conducted in PubMed, Embase and Cochrane databases. Baseline characteristics and outcomes from the included studies were extracted independently by two investigators. Either a fixed-effects or a random-effects model was used to composite the pooled OR for gastric cancer risk. Finally, a total of 21 studies, which comprised 402,636 participants and 4,535 gastric cancer patients, were finally included in the current meta-analysis. Compared with those participants without IM, IM patients were at a higher risk of gastric cancer (pooled OR = 3.58, 95% CI 2.71-4.73). We observed that incomplete IM (pooled OR = 9.48, 95% CI 4.33-20.78) but not complete IM (pooled OR = 1.55, 95% CI 0.91-2.65) was significantly associated with a higher gastric cancer risk. Besides, it appeared that gastric cancer risk was higher among patients with IM in the corpus (pooled OR = 7.39, 95% CI 4.94-11.06) than those with IM in the antrum only (pooled OR = 4.06, 95% CI 2.79-5.91). And the pooled ORs for gastric noncardia cancer and gastric cardia cancer were 4.98 (95% CI 3.12-7.95) and 1.93 (95% CI 1.15-3.24), respectively. In conclusion, patients with IM were at a higher risk of gastric cancer, especially for incomplete IM and IM in the corpus. The current evidence supports the use of IM subtypes in the surveillance of gastric cancer.

Association between intake of antioxidants and pancreatic cancer risk: a meta-analysis.

We conducted a meta-analysis to systematically evaluate the association between antioxidants intake and pancreatic cancer risk. Relevant articles were retrieved from PUBMED and EMBASE databases and standard meta-analysis methods were applied. Finally a total of 18 studies were included. Comparing the highest with lowest categories, higher dietary intakes of selenium, vitamin C, vitamin E, ß-carotene and ß-cryptoxanthin were significantly associated with reduced pancreatic cancer risk (for selenium, pooled OR = 0.47, 95%CI 0.26-0.85; for vitamin C, pooled OR = 0.68, 95%CI 0.57-0.80; for vitamin E, pooled OR = 0.70, 95%CI 0.62-0.81; for ß-carotene, pooled OR = 0.74, 95%CI 0.56-0.98; for ß-cryptoxanthin, pooled OR = 0.70, 95%CI 0.56-0.88). Lycopene intake was marginally associated with pancreatic cancer risk (pooled OR = 0.85, 95%CI 0.73-1.00), while no significant association was observed for α-carotene, lutein and zeaxanthin. In summary, higher dietary intake of selenium, vitamin C, vitamin E, ß-carotene and ß-cryptoxanthin was inversely associated with pancreatic cancer risk.

Aspirin use after diagnosis but not prediagnosis improves established colorectal cancer survival: a meta-analysis.

OBJECTIVE: The objective of this meta-analysis was to systematically assess the survival benefit of aspirin use before or after diagnosis for patients with colorectal cancer (CRC). DESIGN: Relevant studies were identified through searching PubMed, Embase and Cochrane databases before May 2014. Two investigators extracted data independently for baseline characteristics and outcomes from the included studies. Either a fixed-effects or a random-effects model was derived to composite the pooled HR for overall mortality and CRC-specific mortality of CRC. RESULTS: Seven studies on postdiagnosis aspirin therapy and seven studies on prediagnosis aspirin use were finally included in this meta-analysis. The overall survival benefit associated with postdiagnosis aspirin use represented an HR of 0.84 (95% CI 0.75 to 0.94). This effect was observed both in colon cancer (HR=0.78, 95% CI 0.64 to 0.96) and in rectal cancer (HR=0.90, 95% CI 0.83 to 0.98). Besides, the survival benefit of postdiagnosis aspirin use appeared to be confined to those patients with positive prostaglandin endoperoxide synthase 2 (PTGS2, also known as cyclooxygenase-2, COX-2) expression (HR=0.65, 95% CI 0.50 to 0.85) and with mutated PIK3CA tumours (HR=0.58, 95% CI 0.37 to 0.90). Aspirin use postdiagnosis was not associated with CRC-specific mortality (HR=0.77, 95% CI 0.52 to 1.14). We observed no evidence of an association between prediagnosis aspirin use and CRC overall mortality (HR=1.01, 95% CI 0.96 to 1.06) or CRC-specific mortality (HR=0.93, 95% CI 0.82 to 1.05). CONCLUSIONS: These findings provide further indication that postdiagnosis aspirin therapy improved CRC overall survival, especially for patients with positive PTGS2 (COX-2) expression and mutated PIK3CA tumours.

Association between dietary antioxidant vitamins intake/blood level and risk of gastric cancer.

We aimed to systematically evaluate the association between dietary intake/blood levels of antioxidant vitamins (vitamin C, vitamin E, ß-carotene, and α-carotene) and gastric cancer risk. Systematic literature searches were conducted until April 2013 in Pubmed and Embase to identify relevant studies. Either a fixed- or a random-effects model was adopted to estimate overall odds ratios (ORs). Dose-response, meta-regression, subgroup, and publication bias analyses were applied. Forty articles were finally included in the present study. Higher dietary intake of vitamin C, vitamin E, ß-carotene, and α-carotene was inversely associated with gastric cancer risk (for vitamin C, pooled OR=0.58, 95% CI 0.51-0.65; for vitamin E, pooled OR=0.65, 95% CI 0.57-0.74; for ß-carotene, pooled OR=0.59, 95% CI 0.49-0.70; for α-carotene, pooled OR=0.69, 95% CI 0.52-0.93). Subgroup analyses suggested the effects of these antioxidant vitamins were different in gastric cancer subtypes. As indicated by dose-response analysis, a 100 mg/day increment of vitamin C intake conferred an OR of 0.78 (95% CI 0.67-0.90); a 15 mg/day increment of vitamin E intake conferred an OR of 0.79 (95% CI 0.66-0.94); and a 5 mg/day increment in ß-carotene intake conferred an OR of 0.80 (95% CI 0.60-1.04). No significant association was observed between blood vitamin C, α-tocopherol, γ- tocopherol, ß-carotene and α-carotene levels and gastric cancer risk. In conclusion, dietary intake of vitamin C, vitamin E, ß-carotene and α-carotene was inversely associated with gastric cancer risk while no such association was observed for blood levels of these antioxidant vitamins, thus the results should be interpreted cautiously.

Association between dietary vitamin C intake/blood level and risk of digestive system cancer: a systematic review and meta-analysis of prospective studies.

Experimental studies have shown that vitamin C has anti-cancer effects, but previous meta-analyses have indicated that the role of vitamin C in digestive system cancers (DSCs) is controversial. In this study, a systematic review and meta-analysis of the relationship between dietary intake/plasma concentration of vitamin C and the risk of DSC was conducted, evaluating 32 prospective studies with 1 664 498 participants. Dose-response and subgroup analyses were also performed. Systematic literature searches were performed in PubMed, EMBASE and Web of Science databases until 9th September 2023. Vitamin C intake significantly reduced DSCs risk (RR = 0.88, 95% confidence interval (CI) 0.83 to 0.93). The subgroup analyses showed the risks of oral, pharyngeal, and esophageal (OPE) cancers (0.81, 0.72 to 0.93), gastric cancer (0.81, 0.68 to 0.95), and colorectal cancer (0.89, 0.82 to 0.98) were negatively correlated with vitamin C intake, and the effect of vitamin C was different between colon cancer (0.87, 0.77 to 0.97) and rectal cancer (1.00, 0.84 to 1.19). However, plasma vitamin C concentration was only inversely associated with gastric cancer risk (0.74, 0.59 to 0.92). Dose-response analysis revealed that 250 and 65 mg day-1 vitamin C intakes had the strongest protective effect against OPE and gastric cancers respectively. These estimates suggest that vitamin C intake could significantly reduce gastrointestinal cancer incidence, including OPE, gastric, and colon cancers. Plasma vitamin C has a significant reduction effect on the incidence of gastric cancer only, but additional large-scale clinical studies are needed to determine its impact on the incidence of DSCs.

Evaluating the efficacy of GIPR agonists on non-alcoholic fatty liver disease: A Mediation Mendelian Randomization Study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease worldwide while still lacks drugs for treatment or prevention. We aimed to investigate the causal role of glucose-dependent insulinotropic polypeptide receptor agonists (GIPRAs) on NAFLD and identify the mediated risk factors by which GIPRAs exert their therapeutic effects. METHODS: Genetic proxies of GIPRAs were identified as cis-SNPs of GIPR associated with both the gene expression level and HbA1c and analyses including colocalization and linkage disequilibrium (LD) were performed for validation. We then performed two-sample two-step mendelian randomization to determine the causal effect of GIPRAs on NAFLD. RESULTS: The MR analysis suggested genetic proxies of GIPRAs were causally associated with reduced risk of NAFLD (Odds ratio (OR): 0.46, 95 % confidence interval (95 % CI): 0.24-0.88, P = 0.02) and T2DM (OR: 0.10, 95 % CI: 0.07-0.13, P < 0.01). In addition, Mediation analysis showed evidence of indirect effect of GIPRAs on NAFLD via TRIG (0.88, [0.85-0.92], P < 0.01) and HDL-C (0.85, [0.80-0.90], P < 0.01). CONCLUSIONS: Our study provided strong evidence to support the causal role of GIPRAs on reducing the risk of NAFLD probably through improving lipid metabolism, especially TG and HDL-C, providing guidance for future clinical trials.

Risk of subsequent gastrointestinal disease assessed by skeletal muscle strength and mass in a prospective cohort study.

Skeletal muscle may mutually interact with gastrointestinal disease through metabolic homeostasis and nutritional status and therefore may be a marker for early risk detection. We conducted a prospective cohort analysis including 393,606 participants (mean age 56.0 years, 53.9% female) from the UK Biobank. The exposures were grip strength and skeletal muscle mass (SMM). The primary outcomes were 24 incident gastrointestinal diseases. During a mean follow-up of 12.1 years, we found that one sex-specific SD increase in grip strength and SMM were associated with reduced risk of 16 and 19 gastrointestinal diseases, respectively. For grip strength, the HRs ranged from 0.94 (for ulcerative colitis) to 0.80 (for liver cancers). For SMM, the HRs ranged from 0.92 (for colorectal cancer) to 0.51 (for non-alcoholic fatty liver disease). Our finding suggested that grip strength and SMM might be significant indicators for gastrointestinal diseases risk screen.

Drug-drug interaction of rabeprazole and clopidogrel in healthy Chinese volunteers.

PURPOSE: This study was aimed to determine the impact of rabeprazole (RBRZ) on the antiplatelet efficacy of clopidogrel (CPG) in healthy Chinese volunteers, and further to predict the effect of CYP2C19 genetic polymorphism on the efficacy of rabeprazole and clopidogrel. METHODS: The open-label, two period cross-over study was conducted in 20 healthy Chinese subjects with different CYP2C19 genotypes receiving clopidogrel, rabeprazole or the two drugs, respectively. All the volunteers were divided into two groups, poor metabolizers (PMs) and extensive metabolizers (EMs), depending on CYP2C19 genotypes. Blood samples were collected at baseline and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 h after administration. The plasma concentrations of rabeprazole and clopidogrel were analyzed by LC-MS/MS and ADP-induced platelet aggregation was detected by the optical turbidimetric method. RESULTS: There were no significant differences in the mean plasma concentration-time curves of clopidogrel (CPG), the inactive metabolite clopidogrel carboxylic acid (CPG-CA), the active metabolite clopidogrel-MP-Derivative (MP-AM), and rabeprazole (RBRZ) according to the co-administration of CPG and RBRZ. There were no major changes in the pharmacokinetics of CPG and RBRZ. The maximal ADP-induced platelet aggregation (2 µmol/L) was decreased in EMs compared with PMs. CONCLUSION: Co-administration of rabeprazol and clopidogrel did not affect the antiplatelet efficacy of clopidogrel. The CYP2C19 genetic polymorphism may impact the efficacy of clopidogrel.

Machine learning-derived multi-omics prognostic signature of pyroptosis-related lncRNA with regard to ZKSCAN2-DT and tumor immune infiltration in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) has become the most prevalent gastrointestinal malignant tumor, ranking third (10.2%) in incidence and second (9.2%) in death among all malignancies globally. The most common histological subtype of CRC is colon adenocarcinoma (COAD), although the cause of CRC remains unknown, as there are no valid biomarkers. METHODS: A thorough investigation was used to build a credible biomolecular risk model based on the pyroptosis-associated lncRNAs discovered for COAD prediction. Furthermore, Cibersort and Tumor Immune Dysfunction and Exclusion (TIDE), the methods of exploring tumor immune infiltration, were adopted in our paper to detect the effects of differential lncRNAs on the tumor microenvironment. Finally, quantitative real-time polymerase chain reaction (qPCR), as the approach of exploring expressions, was utilized on four different cell lines. RESULTS: Seven pyroptosis-related lncRNAs have been identified as COAD predictive risk factors. Cox analysis, both univariate and multivariate, revealed that the established signature might serve as a novel independent factor with prognostic meaning in COAD patients. ZKSCAN2-DT was shown to be considerably overexpressed in the COAD cell line when compared to normal human colonic epithelial cells. Furthermore, ssGSEA analysis results revealed that the immune infiltration percentage of most immune cells dropped considerably as ZKSCAN2-DT expression increased, implying that ZKSCAN2-DT may play an important role in COAD immunotherapy. CONCLUSION: Our research is the first to identify pyroptosis-related lncRNAs connected with COAD patient prognosis and to construct a predictive prognosis signature, directing COAD patient prognosis in therapeutic interventions.

Interleukin-17 and inflammatory bowel disease: a 2-sample Mendelian randomization study.

Introduction: Observational studies have discovered a contradictory phenomenon between interleukin-17 (IL-17) and inflammatory bowel disease (IBD). The study aimed to confirm the causal association between each subtype of IL-17 and IBD. Methods: We performed a 2-sample univariable and multivariable mendelian randomization (MR) to determine which subtype of IL-17 is causally related to IBD and its subtypes, and used a series of sensitivity analysis to examine the reliability of the main MR assumptions. Results: We found that IL-17B, IL-17E and IL-17RB were significantly associated with an increased risk of UC (IL-17B: OR: 1.26, 95% CI, 1.09-1.46, P < 0.01; IL-17E: OR: 1.17, 95% CI, 1.05-1.30, P < 0.01; IL-17RB: OR: 1.30, 95% CI, 1.20-1.40, P < 0.0001) while IL-17C and IL-17RC showed causal effects on the increased risk of CD (IL-17C: OR: 1.23, 95% CI, 1.21-1.26, P < 0.0001; IL-17RC: OR: 2.01, 95% CI, 1.07-3.75, P=0.03). The results of multivariable MR (MVMR) showed that the causal effects of IL-17B and IL-17E on UC were unilaterally dependent on IL-17RB, while the effects of IL-17C and IL-17RC on CD were interdependent. Discussion: Our study provided new genetic evidence for the causal relationships between each subtype of IL-17 and IBD, promoting future mechanistic research in IBD.

Integrated analysis of Mendelian Randomization and Bayesian colocalization reveals bidirectional causal association between inflammatory bowel disease and psoriasis.

BACKGROUND: Observational studies have suggested an association between inflammatory bowel disease [IBD] and psoriasis. However, the detailed genetic basis, causality, and direction of this association remain unclear. METHODS: Bidirectional two-sample Mendelian Randomization [MR] analysis was conducted using summary statistics from published genome-wide association studies. Bayesian Colocalization and multivariable MR [MVMR] analyses were performed to identify candidate variants and risk genes involved in the shared genetic basis between IBD, psoriasis, and their subtypes. RESULTS: Genetically predicted IBD and Crohn's disease [CD] were associated with an increased risk of psoriasis, psoriasis vulgaris [PsV], and psoriatic arthritis [PsA] (IBD on psoriasis: pooled odds ratio [OR] 1.09, 95% confidence interval [CI] 1.04-1.14, p = .0001; CD on psoriasis: pooled OR 1.10, 95% CI 1.06-1.15, p < .0001) and vice versa (psoriasis on IBD: pooled OR 1.11, 95%CI 1.02-1.21), whereas CD only exhibited a unidirectional association with psoriasis. Colocalization analysis revealed eight candidate genetic variants and risk genes (including LINC00824, CDKAL1, IL10, IL23R, DNAJC27, LPP, RUNX3, and RGS14) associated with a shared genetic basis. Among these, IL23R, DNAJC27, LPP, and RGS14 were further validated by MVMR analysis. CONCLUSION: Our findings indicated bidirectional causal associations between IBD and psoriasis (including PsV and PsA), which were attributed primarily to CD rather than Ulcerative colitis [UC]. Furthermore, we identified several candidate variants and risk genes involved in the shared genetic basis of IBD and psoriasis. Acquiring a better understanding of the shared genetic architecture underlying IBD and psoriasis would help improve clinical strategies.