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.

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.

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.

Catalase catalyzed tannic acid-Fe3+ network coating: A theranostic strategy for intestinal barrier restoration.

Epithelial barrier impairment of intestinal inflammation leads to the leakage of bacteria, antigens and consequent persistent immune imbalance. Restoring the barrier function holds promise for management of intestinal inflammation, while the theragnostic strategies are limited. In this study, we developed a novel coating by catalase (CAT)-catalyzed polymerization of tannic acid (TA) and combined chelation network with Fe3+. TA-Fe3+ coating was self-polymerized in situ along the small intestinal mucosa, demonstrating persistent adhesion properties and protective function. In enteritis models, sequential administration of TA-Fe3+ complex solution effectively restored the barrier function and alleviated the intestinal inflammation. Overexpressed CAT in inflammatory lesion is more favorable for the in situ targeting growth of TA-Fe3+ coating onto the defective barrier. Based on the high longitudinal relaxivity of Fe3+, the pathologically catalyzed coating facilitated the visualization of intestinal barrier impairment through MRI. In conclusion, the novel TA-Fe3+ delivery coating proposed an alternative approach to promote theranostic intervention for intestinal diseases.

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.

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.].

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.

Natural Orifice Translumenal Endoscopic Surgery (NOTES): patients' perceptions and attitudes.

BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) has generated a surge of enthusiasm among researchers by virtue of its challenge to the dogma and potential benefits. However, no data is available in the medical literature about NOTES' acceptance by patients in Asia. The aim of the study is to survey patients' perceptions and attitudes towards NOTES. METHODS: It is a questionnaire-based multi-center study on inpatient subjects with various gastrointestinal disorders from 14 hospitals in 12 cities of China. Procedural details with the benefits and risks of NOTES, laparoscopic surgery, and conventional surgery were explained to all registered candidates. They were required to choose and cite reasons for adopting one of the above three surgical techniques as the preferred mode of treatment. The reasons for selection of the surgical treatment were: safety, efficacy, cost, postoperative pain, abdominal wounds, and scarring. RESULTS: There were 1,797 cases, including 976 (54.3%) males and 821 females (45.7%). Based on their comprehension of the procedure, 802 (44.6%) patients opted for NOTES, 757 (42.1%) for laparoscopic surgery, and 238 (13.2%) for conventional surgery. NOTES was mainly selected by the young and educated persons, especially females and by those with past exposure to laparoscopy or conventional surgery. The choice of treatment was significantly correlated with age (P=0.0021), education (P=0.0209), past medical history (laparoscopy, P=0.0134; open surgery, P<0.0001), and department of admission (P=0.0173). The preference for NOTES was based on safety (37.3%), cost (17.6%), elimination of postoperative scars (16.1%), abdominal wounds (16.0%), and efficacy (13.1%). CONCLUSIONS: The vast majority of patients prefer mini-invasive surgery to conventional surgery. The potential recipients of NOTES are educated and younger age groups. However, a few consider NOTES as a safe and effective intervention at present.

A De Novo mutation of STK11 gene in a Chinese patient with Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome (PJS) is an autosomal-dominant inherited disorder characterized by mucocutaneous pigmentation, hamartomatous polyposis of the gastrointestinal tract, and an increased risk for the development of both gastrointestinal and extraintestinal malignancies. Germline mutation of the STK11 gene, which encodes a serine-threonine kinase, is responsible for PJS. We collected blood samples from a Chinese PJS family consisting of a total of four individuals (one male and three females) including one PJS patient. The whole coding region of STK11 was amplified by polymerase chain reaction and products analyzed by direct sequencing. Molecular analysis of the STK11 gene in this case of PJS revealed a substitution of thymine 217 for adenine (C.217T > A) in exon 1, resulting in a change of codon 73 from cysteine to serine (C73S). The point mutation was not found in normal individuals in this PJS family or in 100 control individuals. The results presented here enlarge the spectrum of mutations of the STK11 gene by identifying a de novo mutation in a PJS patient and further support the hypothesis that STK11 mutations are disease-causing mutations for PJS.

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.

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.

Risk factors for ERCP-related complications: a prospective multicenter study.

OBJECTIVES: To investigate the potential risk factors for endoscopic retrograde cholangiopancreatography (ERCP) complications and to identify whether the risk factors are different for pancreatitis and asymptomatic hyperamylasemia. METHODS: Consecutive ERCP procedures were studied at 14 centers in China from May 2006 to April 2007. The complications after the patients' first-only procedures were evaluated. Multivariate analysis based on the first-only procedures was used to identify the risk factors. RESULTS: A total of 3,178 procedures were performed on 2,691 patients. Overall, complications developed in 213 (7.92%) patients, pancreatitis in 116 (4.31%), and asymptomatic hyperamylasemia in 396 (14.72%). In the multivariate analysis, female gender (adjusted odds ratios (ORs): 1.52, 95% confidence interval (CI): 1.14-2.02, P=0.004), periampullary diverticulum (OR: 2.02, 95% CI: 1.49-2.73, P<0.001), cannulation time >10 min (OR: 1.51, 95% CI: 1.08-2.10, P=0.016), > or =1 pancreatic deep wire pass (OR: 1.80, 95% CI: 1.33-2.42, P<0.001), and needle-knife precut (OR: 2.70, 95% CI: 1.42-5.14, P=0.002) were risk factors for overall complications. Female gender (OR: 1.84, 95% CI: 1.25-2.70, P=0.002), age < or =60 year (OR: 1.59, 95% CI: 1.06-2.39, P=0.025), cannulation time>10 min (OR: 1.76, 95% CI: 1.13-2.74, P=0.012), > or =1 pancreatic deep wire pass (OR: 2.77, 95% CI: 1.79-4.30, P<0.001), and needle-knife precut (OR: 4.34, 95% CI: 1.92-9.79, P<0.001) were risk factors for pancreatitis. Cannulation time>10 min (OR: 1.96, 95% CI: 1.52-2.54, P<0.001), > or =1 pancreatic deep wire pass (OR: 2.24, 95% CI: 1.74-2.89, P<0.001), needle-knife precut (OR: 2.34, 95% CI: 1.32-4.14, P=0.004), and major papilla pancreatic sphincterotomy (OR: 1.71, 95% CI: 1.23-2.37, P=0.001) were risk factors for asymptomatic hyperamylasemia. CONCLUSIONS: Patient-related factors are as important as procedure-related factors in determining high-risk predictors for post-ERCP overall complications and pancreatitis. However, the risk factors for asymptomatic hyperamylasemia may be mostly procedure related.

How safe and successful are live demonstrations of therapeutic ERCP? A large multicenter study.

OBJECTIVES: Live demonstrations of endoscopic retrograde cholangiopancreatography (ERCP) have a high educational value and contribute significantly to endoscopy development and training. However, the success and safety of live demonstration have been questioned. The aim of this study was to evaluate the success rate and complications of therapeutic ERCP among patients who participated in live demonstrations. METHODS: Patients who underwent therapeutic ERCP during live demonstrations at gastrointestinal endoscopy conferences in China between January 2002 and December 2007 were included. The matched control for each patient was a patient admitted to the same ERCP unit with similar indication, who received ERCP by an endoscopist with similar experience as those who performed the live demonstration. Patient's age, gender, indication, success rate, and complications of ERCP were collected and compared. ERCP outcomes between local and visiting faculty were also compared. RESULTS: In total, 36 conferences with live ERCP demonstrations involving 406 patients were held in 14 endoscopy centers. There were no significant differences in patients' gender, age, and indications between live demonstrations and controls. The overall complication rate of ERCP in live demonstrations was not significantly different compared with controls (10.3% vs. 8.6%, P=0.473). However, the success rate was significantly lower in live demonstrations than in controls (94.1% vs. 97.5%, P=0.021). The success and complication rates of ERCP performed by local faculty, domestic visiting, and foreign visiting faculties were similar. CONCLUSIONS: Although the success rate of therapeutic ERCP performed during live demonstrations was lower than that of routine procedures, the overall complication rate did not significantly increase. ERCP performed by visiting endoscopists was as safe as that done by local faculty in live demonstrations.

Serum proteomic-based analysis of pancreatic carcinoma for the identification of potential cancer biomarkers.

To identify new biomarkers that improve the early diagnosis and lead to possible therapeutic targets in pancreatic carcinoma, we performed a proteomic approach to compare serum protein expression patterns of pancreatic carcinoma patients with that of gastric cancer patients, other pancreatic disease patients, and healthy volunteers. By two-dimensional gel electrophoresis (2-DE) analyses and mass spectroscopic identification, 10 protein spots were found significantly changed in pancreatic carcinoma and 5 proteins including cyclin I, Rab GDP dissociation inhibitor beta (GDI2), alpha-1 antitrypsin precursor, Haptoglobin precursor, and Serotransferrin precursor were successfully identified. The increased levels of cyclin I and GDI2 found to be associated with pancreatic carcinoma were further confirmed by Western blot analyses in an independent series of serum samples and/or pancreatic juice samples. Applying immunohistochemistry, we further validated expression of cyclin I and GDI2 in additional pancreatic carcinomas. These results indicate that cyclin I and GDI2 may be potential molecular targets for pancreatic cancer diagnostics and therapeutics.

[Comparative study of ultrasonography, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography in common duct stones].

OBJECTIVE: To compare the diagnostic value study the technique of ultrasonography, magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) in common duct stones. METHODS: Three hundreds and eighty-four patients suspected common duct stones from August 2005 to October 2007 were undergone abdominal ultrasonography, MRCP and ERCP. RESULTS: There was stone in common duct in 370 and no stones in 14 of 384 patients. Ultrasonography indicated stones 268 cases, 8 false positive result was among them. MRCP diagnosed stones in 362 cases and false positive result in 6 cases, ERCP diagnosed stones 370 cases. The diagnostic accuracy of ultrasonography, MRCP and ERCP was 70.3% (260/370), 96.2% (356/370) and 100% respectively. CONCLUSIONS: The diagnostic accuracy of ultrasonography for common duct stone was little higher, US should be used as a primary checking method. There was higher concordance between MRCP and ERCP for common duct stone. Combination of MRCP and ERCP can improve diagnostic accuracy of common duct stone.

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.