Endoscopic resection of large subepithelial esophageal lesions via submucosal tunneling endoscopic resection and endoscopic submucosal dissection: a single-center, retrospective cohort study.

BACKGROUND: This study aimed to compare the clinical outcomes between submucosal tunneling endoscopic resection (STER) and endoscopic submucosal dissection (ESD) for large subepithelial esophageal lesions (SELs) and analyze risk factors for perforation and piecemeal resection. METHODS: The clinicopathological features and outcomes of endoscopic treatment of 56 patients with SELs with diameters ≥30 mm, diagnosed between June 2017 and December 2020, were reviewed in this retrospective cohort study. Patients were divided into two groups (ESD group and STER group). RESULTS: The complete resection rates of the STER and ESD groups were 88.1% and 78.6%, respectively (p = .398). The operation time of STER was longer than ESD (p = .03), while the hospital stay of STER was shorter than ESD (p = .02). The rate of major adverse events associated with ESD was considerably higher than STER group (p = .035). The extraluminal growth pattern was a risk factor for piecemeal resection, and ESD was an independent risk factor for perforation. Regarding tumors with extraluminal growth patterns, the ESD group's perforation rate was significantly higher than the STER group (p = .009). There were no recurrence or metastases found during a mean follow-up of 24.4 months. CONCLUSION: The STER technique has advantages of shorter hospital stays and fewer major adverse events than ESD. The extraluminal growth pattern seems to be a risk factor for piecemeal resection in both ESD and STER. STER appears to be a preferable choice for large SELs with extraluminal growth patterns.

Novel evidence for an oncogenic role of microRNA-21 in colitis-associated colorectal cancer.

OBJECTIVE: miR-21 was found to be overexpressed in the colon tissues and serum of patients with UC and colorectal cancer (CRC); however, the exact roles of miR-21 in colitis-associated CRC remain unclear. The aim of our study was to investigate the biological mechanisms of miR-21 in colitis-associated colon cancer (CAC). DESIGN: miR-21 expression was examined in the tumours of 62 patients with CRC from China and 37 colitis-associated neoplastic tissues from Japan and Austria. The biological functions of miR-21 were studied using a series of in vitro, in vivo and clinical approaches. RESULTS: miR-21 levels were markedly upregulated in the tumours of 62 patients with CRC, 22 patients with CAC, and in a mouse model of CAC. Following azoxymethane and dextran sulfate sodium intervention, miR-21-knockout mice showed reduced expression of proinflammatory and procarcinogenic cytokines (interleukin (IL) 6, IL-23, IL-17A and IL-21) and a decrease in the size and number of tumours compared with the control mouse group. The absence of miR-21 resulted in the reduced expression of Ki67 and the attenuated proliferation of tumour cells with a simultaneous increase in E-cadherin and decrease in ß-catenin and SOX9 in the tumours of CAC mice. Furthermore, the absence of miR-21 increased the expression of its target gene PDCD4 and subsequently modulated nuclear factor (NF)-κB activation. Meanwhile, miR-21 loss reduced STAT3 and Bcl-2 activation, causing an increase in the apoptosis of tumour cells in CAC mice. CONCLUSIONS: These observations provide novel evidence for miR-21 blockade to be a key strategy in reducing CAC.

Specific miRNA and its target in neutrophils after traumatic injury.

Traumatic injury is a leading cause of mortality and morbidity. MicroRNAs (miRNAs) regulate the cellular responses when traumatic injury occurs. Previously, we reported that miR-3945, miR-125a-5p, miR-363-3p, and miR-150-5p were significantly altered in neutrophils of patients who suffered traumatic injury. In the present study, by comparing neutrophils of patients suffering from major trauma with neutrophils of patients with a inflammatory disease, we found that the variation trend of miR-150-5p was relatively different in the process of these two diseases. Gene Ontology and pathway analysis of miR-150-5p revealed that it may activate the mitogen-activated protein kinase and Toll-like receptor signaling pathways and cell adhesion molecules when the traumatic injury occurs. In addition, protein kinase C alpha (PRKCA) was also identified as a direct target of miR-150-5p by establishing a miRNA-mRNA network, and this target was validated via dual-luciferase reporter and western blot analysis. Our results suggested that the expression of miR-150-5p was down-regulated in neutrophils after a major traumatic injury. miR-150-5p and its identified target PRKCA play important roles in the development of traumatic process.

Identification of a miRNA signature in neutrophils after traumatic injury.

Traumatic injury is the cause of significant mortality and morbidity. The molecular mechanisms underlying traumatic injury logically involve changes in gene expression that may be regulated through microRNAs (miRNAs). However, the association between miRNA deregulation and traumatic injury is largely unknown. The purpose of the present study is to address this issue. In this study, we used microarray profiling to evaluate the differential expressions of miRNAs in neutrophils obtained from patients with major trauma (injury severity scores >16), relative to healthy individuals. This neutrophilic miRNA signature was further validated using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Genes and signaling pathways related to trauma-induced deregulated miRNAs were investigated in silico using the ontology-based and network mapping algorithms of Gene Ontology and Kyoto Encyclopedia of Genes or Genomes. Results showed that 13 miRNAs in neutrophils of major trauma patients were significantly and differentially expressed compared with the miRNA profiles of healthy controls. The results of qRT-PCR and in silico analysis revealed that miR-23a-5p, miR-30e-3p, miR-223-5p, miR-3945, miR-155-5p, and miR-150-5p were likely participants in the traumatic pathogenesis of these patients. In conclusion, neutrophils associated with traumatic injury were found to have a unique miRNA signature. Changes in signaling pathways due to deregulated miRNAs may be involved in the pathological processes of traumatic injury.

Conventional versus hybrid knife endoscopic submucosal dissection in large colorectal laterally spreading tumors: A propensity score analysis.

Background: Colorectal endoscopic submucosal dissection (CR-ESD) has become a promising treatment for laterally spreading tumors (LSTs), but is accompanied by great challenges. .: This study aimed to evaluate the efficacy and safety of CR-ESD with a hybrid knife, versus the conventional technique for LSTs ≥30 mm in diameter, and analyze the risk factors for piecemeal resection and perforation. Methods: Patients eligible for CR-ESD were divided into two groups according to the use of the hybrid knife (HK group) or the use of the conventional technique, with an interchange of injection and hook knife (C-group). We performed propensity score matching (PSM) to compare the HK group and the C-group. Risk predictors for perforation and piecemeal resection were identified. Results: PSM identified 61 (132 patients) and 61 (129 patients) patients in the C-group and the HK group, respectively. Resection speed was significantly faster in the HK group than in the C-group (18.86 vs. 13.33 mm2/min, P < 0.001). The rate of knife exchange was significantly lower in the HK group than in the C-group (1.6% vs. 49.2%, P < 0.001). Multivariate analysis revealed that unfavorable locations, including the splenic flexure, hepatic flexure, or cecum, were predictive of piecemeal resection. The presence of severe fibrosis and a semilunar fold were independent risk factors for perforation. Conclusions: : The use of a hybrid knife appears to increase CR-ESD resection speed. The indicators for piecemeal resection or perforation in CR-ESD identified herein might help to assess the technical difficulties of CR-ESD.

Minimally invasive management of large duodenal lipoma: endoscopic submucosal dissection.

OBJECTIVE: This study was performed to compare the clinical outcomes of large duodenal lipomas (DLs) of ≥2 cm between endoscopic submucosal dissection (ESD) and endoscopic full-thickness resection (EFTR). METHODS: This retrospective study included patients who underwent endoscopic resection of large DLs from June 2017 to March 2021 at our hospital. Clinicopathologic features, clinical outcomes, and follow-up endoscopy findings were retrospectively reviewed. RESULTS: Twenty-three patients (12 men) with a mean age of 57.4 years were included. The median tumor size was 28.4 ± 13.3 mm. ESD was performed in 19 patients, and EFTR was performed in 4. Complete resection was achieved in 21 patients. The operative time and postoperative hospital stay were significantly shorter in the ESD than EFTR group. Four patients in the EFTR group developed a fever; no other adverse events occurred. No patients required surgical intervention. During the average follow-up of 21.1 months, no residual tumor, recurrence, or metastasis was observed. CONCLUSION: Both ESD and EFTR provide minimally invasive, localized treatment of selected DLs. ESD might have some advantages in resecting large DLs in terms of procedure time and hospitalization.

Identification and analysis of genes associated with papillary thyroid carcinoma by bioinformatics methods.

The molecular mechanism of the occurrence and development of papillary thyroid carcinoma (PTC) has been widely explored, but has not been completely elucidated. The present study aimed to identify and analyze genes associated with PTC by bioinformatics methods. Two independent datasets were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between PTC tissues and matched non-cancerous tissues were identified using GEO2R tool. The common DEGs in the two datasets were screened out by VennDiagram package, and analyzed by the following tools: KOBAS, Database for Annotation, Visualization, and Integrated Discovery (DAVID), Search tool for the retrieval of interacting genes/proteins (STRING), UALCAN and Gene expression profiling interactive analysis (GEPIA). A total of 513 common DEGs, including 259 common up-regulated and 254 common down-regulated genes in PTC, were screened out. These common up-regulated and down-regulated DEGs were most significantly enriched in cytokine-cytokine receptor interaction and metabolic pathways, respectively. Protein-protein interactions (PPI) network analysis showed that the up-regulated genes: FN1, SDC4, NMU, LPAR5 and the down-regulated genes: BCL2 and CXCL12 were key genes. Survival analysis indicated that the high expression of FN1 and NMU genes significantly decreased disease-free survival of patients with thyroid carcinoma. In conclusion, the genes and pathways identified in the current study will not only contribute to elucidating the pathogenesis of PTC, but also provide prognostic markers and therapeutic targets for PTC.

Effect of Lactobacillus plantarum on Intestinal Infection in Multiple Drug-Resistant Bacteria Mice.

BACKGROUND: This study aimed to determine the effects of probiotic Lactobacillus plantarum on colitis in mice with multiple drug-resistant bacteria, and to judge the intervention function of probiotics in the resistance of pathogenic bacteria. METHODS: Male BALB/C mice were divided into four groups. The colonic tissues were collected for pathology observation, permeability, transepithelial electrical resistance (TER), and tight junction protein expression detection at death, and the feces were collected for detecting drug susceptibility of MDR-PA. RESULTS: MDR-PA mice developed severe intestinal inflammation and tissue damage in which paracellular permeability was increased, in conjunction with decreased expression and redistribution. LP administration attenuated colitis of MDR-PA mice. The drug susceptibility diameter of MDR-PA has increased. CONCLUSION: Probiotics can treat diarrhea of mice by MDR-PA and protect the intestinal barrier function. Probiotics can weaken the resistance of multiple drug resistance in Pseudomonas aeruginosa to some extent.

Alternative splicing of VEGFA, APP and NUMB genes in colorectal cancer.

AIM: To investigate alternative splicing in vascular endothelial growth factor A (VEGFA), amyloid beta precursor protein (APP), and Numb homolog (NUMB) in colorectal cancer (CRC). METHODS: Real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and PCR-restriction fragment length polymorphism analyses were performed to detect the expression of VEGFA, APP, and NUMB mRNA in 20 CRC tissues and matched adjacent normal tissues, as well as their alternative splicing variants. RESULTS: qRT-PCR analysis revealed that the expression of APP, NUMB, and VEGFA165b mRNA were significantly downregulated, while VEGFA mRNA was upregulated, in CRC tissues (all P < 0.05). PCR-restriction fragment length polymorphism analysis revealed that the expression of VEGFA165a/b in CRC tissues was significantly higher than in adjacent normal tissues (P < 0.05). Compared with adjacent normal tissues, the expression of NUMB-PRR(S) in CRC tissues was significantly decreased (P < 0.05), and the expression of NUMB-PRR(L) was increased (P < 0.05). CONCLUSION: Alternative splicing of VEGFA, APP, and NUMB may regulate the development of CRC, and represent new targets for its diagnosis, prognosis, and treatment.

Biliary stenting with or without sphincterotomy for malignant biliary obstruction: a meta-analysis.

AIM: To investigate the benefits of endoscopic sphincterotomy (EST) before stent placement by meta-analysis of randomized controlled trials (RCTs). METHODS: PubMed, EMBASE, Cochrane Library, and Science Citation Index databases up to March 2014 were searched. The primary outcome was incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) and successful stent insertion rate. The secondary outcomes were the incidence of post-ERCP bleeding, stent migration and occlusion. The free software Review Manager was used to perform the meta-analysis. RESULTS: Three studies (n = 338 patients, 170 in the EST group and 168 in the non-EST group) were included. All three studies described a comparison of baseline patient characteristics and showed that there were no statistically significant differences between the two groups. Three RCTs, including 338 patients, were included in this meta-analysis. Most of the analyzed outcomes were similar between the groups. Although EST reduced the incidence of PEP, it also led to a higher incidence of post-ERCP bleeding (OR = 0.34, 95%CI: 0.12-0.93, P = 0.04; OR = 9.70, 95%CI: 1.21-77.75, P = 0.03, respectively). CONCLUSION: EST before stent placement may be useful in reducing the incidence of PEP. However, EST-related complications, such as bleeding and perforation, may offset this effect.

Does hyoscine butylbromide really improve polyp detection during colonoscopy? A meta-analysis of randomized controlled trials.

AIM: To investigate the benefits of hyoscine butylbromide in polyp detection during colonoscopy by a meta-analysis of available randomized controlled trials (RCTs). METHODS: Databases, including PubMed, EMBASE, the Cochrane Library, and the Science Citation Index up to September 2013, were searched. The primary outcome was polyp detection rate, and the secondary outcome was adenoma detection rate. The meta-analysis was performed using the free software Review Manager. Differences observed between the treated and the control groups were expressed as odds ratio (OR) with a 95% confidence interval (CI). A fixed-effects model was used to pool data when statistical heterogeneity was absent. If statistical heterogeneity was present (P < 0.05), a random-effects model was used. RESULTS: The initial search identified nine articles. After screening, five RCTs with a total of 1998 patients were included in this meta-analysis. Of the five studies, all described a comparison of baseline patient characteristics and showed that there was no statistically significant difference between the two groups. Among the 1998 patients, 1006 received hyoscine butylbromide and 992 were allocated to the control group, and the polyp detection rate was reported. There were no significant differences between the treated and the control group (OR = 1.09, 95%CI: 0.91-1.31, P = 0.33). Four RCTs included 1882 patients, of whom 948 received hyoscine butylbromide, and the adenoma detection rate was reported. There were no significant differences between the treated and the control group (OR = 1.13, 95%CI: 0.92-1.38, P = 0.24). CONCLUSION: The use of hyoscine butylbromide did not significantly improve the polyp detection rate during colonoscopy.

Meta-analysis of stapled hemorrhoidopexy vs LigaSure hemorrhoidectomy.

AIM: To compare outcome of stapled hemorrhoidopexy (SH) vs LigaSure hemorrhoidectomy (LH) by a meta-analysis of available randomized controlled trials (RCTs). METHODS: Databases, including PubMed, EMBASE, the Cochrane Library, and the Science Citation Index updated to December 2012, were searched. The main outcomes measured were operating time, early postoperative pain, postoperative urinary retention and bleeding, wound problems, gas or fecal incontinence, anal stenosis, length of hospital stay, residual skin tags, prolapse, and recurrence. The meta-analysis was performed using the free software Review Manager. Differences observed between the two groups were expressed as the odds ratio (OR) with 95%CI. A fixed-effects model was used to pool data when statistical heterogeneity was not present. If statistical heterogeneity was present (P < 0.05), a random-effects model was used. RESULTS: The initial search identified 10 publications. After screening, five RCTs published as full articles were included in this meta-analysis. Among the five studies, all described a comparison of the patient baseline characteristics and showed that there was no statistically significant difference between the two groups. Although most of the analyzed outcomes were similar between the two operative techniques, the operating time for SH was significantly longer than for LH (P < 0.00001; OR= -6.39, 95%CI: -7.68 - -5.10). The incidence of residual skin tags and prolapse was significantly lower in the LH group than in the SH group [2/111 (1.8%) vs 16/105 (15.2%); P = 0.0004; OR= 0.17, 95%CI: 0.06-0.45). The incidence of recurrence after the procedures was significantly lower in the LH group than in the SH group [2/173 (1.2%) vs 13/174 (7.5%); P = 0.003; OR= 0.21, 95%CI: 0.07-0.59]. CONCLUSION: Both SH and LH are probably equally valuable techniques in modern hemorrhoid surgery. However, LigaSure might have slightly favorable immediate postoperative results and technical advantages.

ACF7 regulates colonic permeability.

Colonic paracellular permeability is regulated by various factors, including dynamics of the cytoskeleton. Recently, ACF7 has been found to play a critical role in cytoskeletal dynamics as an essential integrator. To elucidate the physiological importance of ACF7 and paracellular permeability, we conditionally knocked out ACF7 in the intestinal mucosa of mice. Histopathological findings indicated that ACF7 deficiency resulted in significant interstitial proliferation and columnar epithelial cell rearrangement. Decreased colonic paracellular permeability was detected using a Ussing chamber and the FITC-inulin method. In order to clarify the underlying mechanism, we further analyzed the expression levels of three important tight junction proteins. Downregulation of ZO-1, occludin and claudin-1 was identified. Immunofluorescence provided strong evidence that ZO-1, occludin and claudin-1 were weakly stained. We hypothesized that ACF7 regulates cytoskeleton dynamics to alter mucosal epithelial arrangement and colonic paracellular permeability.

MicroRNA-21 knockout improve the survival rate in DSS induced fatal colitis through protecting against inflammation and tissue injury.

BACKGROUND: MicroRNA-21 (miR-21) is overexpressed in most inflammatory diseases, but its physiological role in gut inflammation and tissue injury is poorly understood. The goal of this work is to understand the role of miR-21 in colitis and damage progression of intestine in a genetically modified murine model. METHODS: Experimental colitis was induced in miR-21 KO and wild-type (WT) mice by 3.5% dextran sulphate sodium (DSS) administration for 7 days. Disease activity index(DAI), blood parameters, intestinal permeability, histopathologic injury, cytokine and chemokine production, and epithelial cells apoptosis were examined in colons of miR-21 KO and WT mice. RESULTS: miR-21 was overexpressed in intestine of inflammatory bowel diseases (IBD) and acute intestinal obstruction (AIO) patients when compared with normal intestinal tissues. Likewise, miR-21 was up-regulated in colon of IL-10 KO mice when compared with control mice. WT mice rapidly lost weight and were moribund 5 days after treatment with 3.5% DSS, while miR-21 KO mice survived for at least 6 days. Elevated leukocytes and more severe histopathology were observed in WT mice when compared with miR-21 KO mice. Elevated levels of TNF-α and macrophage inflammatory protein-2(MIP-2) in colon culture supernatants from WT mice exhibited significant higher than miR-21 KO mice. Furthermore, CD3 and CD68 positive cells, intestinal permeability and apoptosis of epithelial cells were significantly increased in WT mice when compared with miR-21 KO mice. Finally, we found that miR-21 regulated the intestinal barrier function through modulating the expression of RhoB and CDC42. CONCLUSION: Our results suggest that miR-21 is overexpressed in intestinal inflammation and tissue injury, while knockout of miR-21 in mice improve the survival rate in DSS-induced fatal colitis through protecting against inflammation and tissue injury. Therefore, attenuated expression of miR-21 in gut may prevent the onset or progression of inflammatory bowel disease in patients.