Corrigendum: Unveiling the key genes, environmental toxins, and drug exposures in modulating the severity of ulcerative colitis: a comprehensive analysis.

[This corrects the article DOI: 10.3389/fimmu.2023.1162458.].

Unveiling the key genes, environmental toxins, and drug exposures in modulating the severity of ulcerative colitis: a comprehensive analysis.

Background: As yet, the genetic abnormalities involved in the exacerbation of Ulcerative colitis (UC) have not been adequately explored based on bioinformatic methods. Materials and methods: The gene microarray data and clinical information were downloaded from Gene Expression Omnibus (GEO) repository. The scale-free gene co-expression networks were constructed by R package "WGCNA". Gene enrichment analysis was performed via Metascape database. Differential expression analysis was performed using "Limma" R package. The "randomForest" packages in R was used to construct the random forest model. Unsupervised clustering analysis performed by "ConsensusClusterPlus"R package was utilized to identify different subtypes of UC patients. Heat map was established using the R package "pheatmap". Diagnostic parameter capability was evaluated by ROC curve. The"XSum"packages in R was used to screen out small-molecule drugs for the exacerbation of UC based on cMap database. Molecular docking was performed with Schrodinger molecular docking software. Results: Via WGCNA, a total 77 high Mayo score-associated genes specific in UC were identified. Subsequently, the 9 gene signatures of the exacerbation of UC was screened out by random forest algorithm and Limma analysis, including BGN,CHST15,CYYR1,GPR137B,GPR4,ITGA5,LILRB1,SLFN11 and ST3GAL2. The ROC curve suggested good predictive performance of the signatures for exacerbation of UC in both the training set and the validation set. We generated a novel genotyping scheme based on the 9 signatures. The percentage of patients achieved remission after 4 weeks intravenous corticosteroids (CS-IV) treatment was higher in cluster C1 than that in cluster C2 (54% vs. 27%, Chi-square test, p=0.02). Energy metabolism-associated signaling pathways were significantly up-regulated in cluster C1, including the oxidative phosphorylation, pentose and glucuronate interconversions and citrate cycle TCA cycle pathways. The cluster C2 had a significant higher level of CD4+ T cells. The"XSum"algorithm revealed that Exisulind has a therapeutic potential for UC. Exisulind showed a good binding affinity for GPR4, ST3GAL2 and LILRB1 protein with the docking glide scores of -7.400 kcal/mol, -7.191 kcal/mol and -6.721 kcal/mol, respectively.We also provided a comprehensive review of the environmental toxins and drug exposures that potentially impact the progression of UC. Conclusion: Using WGCNA and random forest algorithm, we identified 9 gene signatures of the exacerbation of UC. A novel genotyping scheme was constructed to predict the severity of UC and screen UC patients suitable for CS-IV treatment. Subsequently, we identified a small molecule drug (Exisulind) with potential therapeutic effects for UC. Thus, our study provided new ideas and materials for the personalized clinical treatment plans for patients with UC.

Benign esophageal stricture model construction and mechanism exploration.

Esophageal stricture is a debilitating condition that negatively impacts patients' quality of life after undergoing endoscopic mucosal resection (EMR). Despite its significance, this disease remains underexplored due to the lack of a stable animal model. Under direct visualization with choledochoscopy, we retrogradely damaged the esophageal mucosal layer through the gastrostomy to create a rat model of esophageal stricture. The development of histological defects in the mucosal layer was assessed over a 2-week period after model induction. Then the models were evaluated using X-ray barium radiography, Hematoxylin-Eosin, Masson's trichrome, Sirius red, and Victoria blue staining, multiphoton microscopic imaging. Additionally, the molecular mechanisms of esophageal stricture were explored by conducting RNA transcriptome sequencing, PCR, immunohistochemistry, and immunofluorescence staining. We successfully established fifteen rat models of esophageal stricture by injuring the mucosal layer. In the model group, the mucosal defect initially occurs and subsequently repaired. The epithelium was absent and was plastically remodeled by collagen during the acute inflammatory phase (Day 1), proliferation phase (Day 7), anaphase of proliferation (Day 10), and plastic remodeling phase (Day 14). We observed increased expression of COL1A1, acta2, FGF, IL-1, and TGF-ß1 pathway in the model group. We established a highly repeatable rat model of esophageal stricture, and our results suggest that the mucosal defect of the esophagus is a critical factor in esophageal stricture development, rather than damage to the muscularis layer. We identified Atp4b, cyp1a2, and gstk1 as potential targets for treating esophageal stricture, while the TGF-ß pathway was found to play an important role in its development.

Systematic identification of key functional modules and genes in esophageal cancer.

BACKGROUND: Esophageal cancer is associated with high incidence and mortality worldwide. Differential expression genes (DEGs) and weighted gene co-expression network analysis (WGCNA) are important methods to screen the core genes as bioinformatics methods. METHODS: The DEGs and WGCNA were combined to screen the hub genes, and pathway enrichment analyses were performed on the hub module in the WGCNA. The CCNB1 was identified as the hub gene based on the intersection between DEGs and the greenyellow module in WGCNA. Expression levels and prognostic values of CCNB1 were verified in UALCAN, GEPIA2, HCMDB, Kaplan-Meier plotter, and TIMER databases. RESULTS: We identified 1,044 DEGs from dataset GSE20347, 1,904 from GSE29001, and 2,722 from GSE111044, and 32 modules were revealed by WGCNA. The greenyellow module was identified as the hub module in the WGCNA. CCNB1 gene was identified as the hub gene, which was upregulated in tumour tissues. Moreover, esophageal cancer patients with higher expression of CCNB1 showed a worse prognosis. However, CCNB1 'might not play an important role in immune cell infiltration. CONCLUSIONS: Based on DEGs and key modules related to esophageal cancer, CCNB1 was identified as the hub gene, which offered novel insights into the development and treatment of esophageal cancer.

Systematic Identification of Key Functional Modules and Genes in Gastric Cancer.

Gastric cancer (GC) is associated with high incidence and mortality rates worldwide. Differentially expressed gene (DEG) analysis and weighted gene coexpression network analysis (WGCNA) are important bioinformatic methods for screening core genes. In our study, DEG analysis and WGCNA were combined to screen the hub genes, and pathway enrichment analyses were performed on the DEGs. SBNO2 was identified as the hub gene based on the intersection between the DEGs and the purple module in WGCNA. The expression and prognostic value of SBNO2 were verified in UALCAN, GEPIA2, Human Cancer Metastasis Database, Kaplan-Meier plotter, and TIMER. We identified 1974 DEGs, and 28 modules were uncovered via WGCNA. The purple module was identified as the hub module in WGCNA. SBNO2 was identified as the hub gene, which was upregulated in tumour tissues. Moreover, patients with GC and higher SBNO2 expression had worse prognoses. In addition, SBNO2 was suggested to play an important role in immune cell infiltration. In summary, based on DEGs and key modules related to GC, we identified SBNO2 as a hub gene, thereby offering novel insights into the development and treatment of GC.

Prevalence of gastric cancer precursors in gastroscopy-screened adults by family history of gastric cancer and of cancers other than gastric.

BACKGROUND: People are at a high risk of gastric cancer if their first-degree relatives suffered from atrophic gastritis (AG), intestinal metaplasia (IM), intraepithelial neoplasia (IEN), dysplasia (DYS), or gastric cancer (GC). This study was performed to analyse the association between FDR-GC and GC precursors. METHODS: A cross-sectional study was performed to screen the prevalence of GC precursors from November 2016 to September 2019. A total of 1329 participants with FDR-GC, 193 participants with a family history of non-gastric cancer in FDRs (FDR-nGC), and 860 participants without a family history of cancer in FDRs (FDR-nC) were recruited in this study. The logistic regression model was used in this study. RESULTS: The prevalence of normal, Non-AG, AG/IM, IEN/DYS, and GC was 31.91, 44.21, 13.81, 8.73, and 1.34%, respectively. The prevalence of IEN/DYS was higher in people with FDR-GC and FDR-nGC (FDR-GC: odds ratio (OR) = 1.655; 95%CI, 1.153-2.376; FDR-nGC: OR = 1.984; 95%CI, 1.122-3.506) than those with FDR-nC. The younger the age at which FDRs were diagnosed with GC, the more likely the participants were to develop AG/IM (Ptrend = 0.019). The risk of precursors to GC was higher in participants whose FDR-GC was the mother than in those whose FDR-GC was the father or sibling (OR, non-AG: 1.312 vs. 1.007, 1.274; AG/IM: 1.430 vs. 1.296, 1.378; IEN/DYS: 1.988 vs. 1.573, 1.542). There was no statistically significant difference in non-AG (OR = 1.700; 95%CI, 0.940-3.074), AG/IM (OR = 1.291; 95%CI, 0.579-2.877), and IEN/DYS (OR = 1.265; 95%CI, 0.517-3.096) between participants with one or more FDR-GC. CONCLUSION: People with FDR-GC and FDR-nGC are at a high risk of IEN/DYS. When an FDR was diagnosed at a younger age, the risk of AG/IM was higher. The risk of GC precursors was higher in people whose FDR-GC was the mother.

The Immunomodulatory Effects and Mechanisms of Tim-3 Action in the Early Stage of Mice with Severe Acute Pancreatitis.

BACKGROUND: Tim-3 has been considered as an ideal target for the immunotherapy of inflammation, but it is unclear whether Tim-3 also plays an important role in acute pancreatitis (AP), as well. OBJECTIVE: To identify the immunomodulatory effects and mechanisms of Tim-3 action in the early stages of severe acute pancreatitis in mice. METHODS: Male BALB/c mice were randomly divided into sham injection group, severe acute pancreatitis group, and anti-Tim-3 treated group. Histopathological scores of the pancreas were calculated, pancreatic myeloperoxidase (MPO) activity was assessed. The concentrations of serum IL-6, IL-10, and TNF-α were evaluated by ELISA method. Quantitative RT-PCR was performed to detect the transcripts of Tim-3, IL-6, IL-10, TNF-α, and TLR4 in peritoneal macrophages. The levels of peritoneal macrophages Tim-3, TLR4, MyD88, and NF-kB p65 were measured by western blot analysis. RESULTS: The pathological scores of the anti-Tim-3 treated group (11.5 ± 1.3) significantly increased compared with the sham (1.3 ± 0.5) and SAP groups (6.9 ± 1.0). Furthermore, the downregulation of Tim-3 significantly aggravated mouse pancreatic tissue damage. It was further shown that Tim-3 negatively regulated the production of pro-inflammatory cytokines, IL-6 and TNF-α, as well as anti-inflammatory cytokine IL-10. Of note, the negative regulation of inflammatory cytokines by Tim-3 was mediated by the activation of TLR4/MyD88 NF-kB signaling pathway. CONCLUSION: Our study showed that Tim-3 might play an important role in the development of AP through regulating the inflammatory response.

Endoscopic versus laparoscopic resection of gastric gastrointestinal stromal tumors: a multicenter study.

Despite endoscopic resection has been performed to treat gastric gastrointestinal stromal tumor (GISTs). However, the safety and long-term outcomes remains controversial. This study aims to compare the safety and surgical outcomes of endoscopic versus laparoscopic resection of gastric GISTs. A total of 335 patients that were pathologically confirmed with gastric GISTs (tumor size ≤ 3.5 cm) were surgically treated with endoscopic resection (endoscopic group) or laparoscopic resection (laparoscopic group) in three institutions from March 1, 2011 to October 1 2014. These demographics, tumor characteristics, and outcomes were retrospectively analyzed for identification of outcomes and feasibility of endoscopic or laparoscopic resection. Of 335 patients, 262 and 73 patients underwent endoscopic and laparoscopic resection, respectively. The average tumor size was 1.33±0.78 cm in the endoscopic group and 1.97±0.93 cm in the laparoscopic group. The average operating time was 62.40±36.94 min in the endoscopic group and 112.81±55.69 cm in the laparoscopic group. Days of realimentation was 2.76±1.67 in the endoscopic group and 4.89±2.03 in the laparoscopic group. The average cost was $ 3246.01±1017.61 in the endoscopic group and $ 4884.81±1339.51 in the laparoscopic group. There was no postoperative mortality. Endoscopic resection for gastric GISTs is safe and feasible in tumors ≤ 3.5 cm. Because endoscopic resection showed good results with lower operating time, realimentation days, length of hospital stay and mean total cost, it is a minimally invasive and safe alternative approach which can achieve fast recovery and satisfactory outcomes for appropriately selected patients with gastric GISTs.

Silver-nanoparticle-coated biliary stent inhibits bacterial adhesion in bacterial cholangitis in swine.

BACKGROUND: One of the major limitations of biliary stents is the stent occlusion, which is closely related to the over-growth of bacteria. This study aimed to evaluate the feasibility of a novel silver-nanoparticle-coated polyurethane (Ag/PU) stent in bacterial cholangitis model in swine. METHODS: Ag/PU was designed by coating silver nanoparticles on polyurethane (PU) stent. Twenty-four healthy pigs with bacterial cholangitis using Ag/PU and PU stents were randomly divided into an Ag/PU stent group (n=12) and a PU stent group (n=12), respectively. The stents were inserted by standard endoscopic retrograde cholangiopancreatography. Laboratory assay was performed for white blood cell (WBC) count, alanine aminotransferase (ALT), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) at baseline time, 8 hours, 1, 2, 3, and 7 days after stent placements. The segment of bile duct containing the stent was examined histologically ex vivo. Implanted biliary stents were examined by a scan electron microscope. The amount of silver release was also measured in vitro. RESULTS: The number of inflammatory cells and level of ALT, IL-1beta and TNF-alpha were significantly lower in the Ag/PU stent group than in the PU stent group. Hyperplasia of the mucosa was more severe in the PU stent group than in the Ag/PU stent group. In contrast to the biofilm of bacteria on the PU stent, fewer bacteria adhered to the Ag/PU stent. CONCLUSIONS: PU biliary stents modified with silver nanoparticles are able to alleviate the inflammation of pigs with bacterial cholangitis. Silver-nanoparticle-coated stents are resistant to bacterial adhesion.

Intramuscular injection of mitomycin C combined with endoscopic dilation for benign esophageal strictures.

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of intramuscular injection of either mitomycin C or dexamethasone with endoscopic dilation for benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection. METHODS: Patients with benign esophageal strictures were retrospectively enrolled in this study and divided into three groups: mitomycin C group (mitomycin C injection with endoscopic dilation, dexamethasone group (dexamethasone injection and dilation) and dilation group (physiological saline injection and dilation). The patients' characteristics, locations of lesions, number of previous dilations, esophageal diameters after dilation, grades of dysphagia before and after the procedure and dysphagia-free period during the follow-up period were recorded. RESULTS: Altogether 74 patients including 25 in the mitomycin C group, 25 in the dexamethasone group and 24 in the dilation group were enrolled. The diameter of the esophagus before the procedure was 3.32 ± 0.90 mm, 3.92 ± 1.55 mm and 3.70 ± 1.30 mm, respectively, while that was increased to 12.77 ± 1.62 mm, 12.14 ± 1.28 mm and 12.73 ± 1.42 mm after endoscopic dilation in the mitomycin C, dexamethasone and conventional dilation groups. The dysphagia-free period was 4.88 ± 1.66 months in the mitomycin C group, 4.02 ± 1.77 months in the dexamethasone group and 2.41 ± 1.26 months in the dilation group (P < 0.05). CONCLUSION: Intramuscular injection of mitomycin C or dexamethasone may prolong the dysphagia-free period and decrease the frequency of repeat dilations compared with conventional endoscopic dilations in patients with benign esophageal strictures.

Cannulation of the intradiverticular papilla using a duodenoscope: is it a safe method?

Endoscopic cannulation of the biliary tract is a challenging technique in cases of periampullary diverticula. Many new devices and new manipulations for successful biliary cannulation have been reported. Endoscopy used to locate and cannulate a papilla hidden within a duodenal diverticulum is an effective method. However, the question of which endoscope should be chosen for this procedure, duodenoscope or gastroscope, waits to be answered.

Fecal microbiota transplantation for severe enterocolonic fistulizing Crohn's disease.

The concept of fecal microbiota transplantation (FMT) has been used in traditional Chinese medicine at least since the 4(th) century. Evidence from recent human studies strongly supports the link between intestinal bacteria and inflammatory bowel disease. We proposed that standardized FMT might be a promising rescue therapy for refractory inflammatory bowel disease. However, there were no reports of FMT used in patients with severe Crohn's disease (CD). Here, we report the successful treatment of standardized FMT as a rescue therapy for a case of refractory CD complicated with fistula, residual Barium sulfate and formation of intraperitoneal large inflammatory mass. As far as we know, this is the first case of severe CD treated using FMT through mid-gut.

Endoscopic retrieval of 28 foreign bodies in a 100-year-old female after attempted suicide.

Foreign body ingestion is a common emergency situation in children with one or a few objects having been ingested. Here we report our experience using endoscopic retrieval in a female centenarian with dyspnea and foreign bodies in the esophagus. She attempted suicide by swallowing 26 coins and two other foreign bodies. A gastroscope was used to remove all foreign bodies in the lower esophagus. In total, 26 coins, one ferrous ring and one cylindrical plastic object were retrieved. To our knowledge, this is the first clinical report on retrieval of so many foreign bodies in a single case.

MYH rs3219476 and rs3219472 polymorphisms and risk of cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a rare but devastating malignancy. Up to 90% of patients presenting with CCA have no identifiable risk factors. The base excision repair (BER) pathway has a principal role in the repair of mutations caused by oxidized or reduced bases. The MutY homolog (MUTYH, MYH) is one of the key proteins in the BER pathway, but the role of MYH in the tumorigenesis of CCA is largely unknown. In this study, we investigated the influence of MYH rs3219476 and rs3219472 polymorphisms on CCA incidence. MYH genotypes were detected using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. We found that for rs3219472, compared with subjects carrying the MYH G/G genotype, those with the A/A genotype had a 2.816-fold higher risk of CCA [odds ratio (OR)=2.816, 95% confidence interval (CI)=0.992-7.999, P=0.047). For rs3219476, compared with subjects carrying the MYH T/T genotype, those with the T/G genotype had a reduced risk of CCA (OR=0.359, 95% CI=0.17-0.758, P=0.006). Our findings suggest that since significantly increased CCA risk was found in individuals with a homozygous variant genotype for rs3219472, it may be a biomarker for screening individuals at high risk of developing the disease.