A Retrospective Analysis of the Efficacy of Endoscopic Variceal Ligation versus Endoscopic Tissue Adhesive Injection in the Treatment of Esophagogastric Variceal Bleeding.

BACKGROUND: The aim of the study was to investigate the effectiveness and safety of endoscopic variceal ligation (EVL) and endoscopic tissue adhesive injection (TAI) in the treatment of esophagogastric variceal bleeding (EVB). METHODS: A total of 245 patients with EVB who attended the First Affiliated Hospital of Bengbu Medical College from December 2017 to June 2021 were retrospectively collected. The participants were divided into the esophageal EVL (E-EVL) + gastric EVL (G-EVL) group (n = 103) and E-EVL + gastric TAI (G-TAI) group (n = 142), according to the procedure, comparing and assessing the clinical characteristics, laboratory results, operation time, rebleeding rate, efficacy, and complications. RESULTS: The E-EVL + G-EVL group had significantly less varicose vein diameter and operative time than the E-EVL + G-TAI group (p < 0.05). No statistical difference in the length of hospital stay between the two groups was noted (p > 0.05). The total rebleeding rate in the E-EVL + G-EVL group was 9.7%, whereas that of the E-EVL + G-TAI group was 11.9%; no statistical difference between the two groups was noted (p > 0.05). The overall effective rate of the E-EVL + G-EVL group was 90.21%, whereas that of the E-EVL + G-TAI group was 92.81%; no statistical difference between the two groups was observed (p > 0.05). The postoperative ulcer in the E-EVL + G-EVL group was smaller and more superficial than that in the E-EVL + G-TAI group, and the wound surface was smoother. CONCLUSION: Both EVL and TAI have good therapeutic effects on EVB. Furthermore, owing to its effectiveness in preventing rebleeding, no reduction in efficacy and no increase in complications, shortened operative time, smaller and superficial ulcer, and smoother wounds, gastric EVL is worthy of further clinical promotion.

Hereditary hemorrhagic telangiectasia with liver cirrhosis: a case report.

BACKGROUND: Hereditary hemorrhagic telangiectasia is an autosomal dominant hereditary hemorrhagic disease. Its main feature is an abnormal structure of the blood vessel wall. Cirrhosis of the liver is a common chronic progressive disease with one or more causes in which diffuse liver damage occurs after long-term or repeated injury. Liver cirrhosis can cause dilation of gastrointestinal capillaries. Many patients with hereditary hemorrhagic telangiectasia accompanied by gastrointestinal vascular malformations and liver cirrhosis may be diagnosed only with liver cirrhosis if the clinician does not pay attention to physical examination findings and family history. Moreover, general treatment measures, such as blood transfusion, iron supplementation, and application of hemostatic drugs, are less effective for bleeding in patients with hereditary hemorrhagic telangiectasia than in those with liver cirrhosis alone. CASE PRESENTATION: Here, we report the rare case of a 75-year-old Chinese man who was admitted to the hospital with repeated melena and epistaxis. He was diagnosed with unexplained liver cirrhosis, which was later confirmed as hereditary hemorrhagic telangiectasia. Subsequently, we implemented the treatment intervention of oral thalidomide combined with gastrointestinal argon plasma coagulation. A follow-up of more than 8 months showed that the treatment effect was excellent. CONCLUSIONS: If patients with liver cirrhosis and gastrointestinal vascular malformations also have a family history of epistaxis, special attention should be paid to targeted physical examination results, and the possibility of hereditary hemorrhagic telangiectasia should be considered. Moreover, for patients with hereditary hemorrhagic telangiectasia and both gastrointestinal bleeding caused by gastrointestinal capillaries and repeated epistaxis, when other general treatment measures are ineffective, thalidomide combined with gastrointestinal argon plasma coagulation may be an effective intervention.

Mir-488 alleviates chemoresistance and glycolysis of colorectal cancer by targeting PFKFB3.

BACKGROUND: Considering the boosting effect of glycolysis on tumor chemoresistance, this investigation aimed at exploring whether miR-488/PFKFB3 axis might reduce drug resistance of colorectal cancer (CRC) by affecting glycolysis, proliferation, migration, and invasion of CRC cells. METHOD: Totally, 288 CRC patients were divided into metastasis/recurrence group (n = 107) and non-metastasis/recurrence group (n = 181) according to their prognosis about 1 year after the chemotherapy, and their 3-year overall survival was also tracked. Besides, miR-488 expression was determined in peripheral blood of CRC patients and also in CRC cell lines (ie, W620, HT-29, Lovo, and HCT116). The targeted relationship between miR-488 and PFKFB3 was predicted by Targetscan software and confirmed by dual-luciferase reporter gene assay. Moreover, glycolysis and drug tolerance of CRC cells lines were assessed. RESULTS: MiR-488 expression was significantly decreased in metastatic/recurrent CRC patients than those without metastasis/recurrence (P < .05), and lowly expressed miR-488 was suggestive of unfavorable 3-year survival, large tumor size, poor differentiation, in-depth infiltration, and advanced Duke stage of CRC patients (P < .05). Besides, CRC cell lines transfected by miR-488 mimic demonstrated decreases in glucose uptake and lactate secretion, increases in oxaliplatin/5-Fu-sensistivity, as well as diminished capability of proliferating, invading, and migratory (P < .05), which were reversible by extra transfection of pcDNA3.1-PFKFB3 (ie, miR-488 mimic + pcDNA3.1-PFKFB3 group). Finally, the mRNA level of PFKFB3 was down-regulated by miR-488 mimic in CRC cell lines after being targeted by it (P < .05). CONCLUSION: The miR-488/PFKFB3 axis might clinically refine chemotherapeutic efficacy of CRC, given its modifying glycolysis and metastasis of CRC cells.

Chrysophanol exhibits inhibitory activities against colorectal cancer by targeting decorin.

Colorectal cancer (CRC) is a common human malignancy that accounts for 600,000 deaths annually worldwide. Chrysophanol, a naturally occurring anthraquinone compound, exhibits anti-neoplastic effects in various cancer cells. The aim of this study was to explore the biological effects of chrysophanol on CRC cells, and determine the underlying mechanism. Chrysophanol inhibited proliferation of and promoted apoptosis in CRC cells by activating the intrinsic mitochondrial apoptotic pathway. In addition, chrysophanol also suppressed tumor growth in vivo and increased the percentage of apoptotic cells in tumor xenografts, without general toxicity. Proteomic iTRAQ analysis revealed decorin (DCN) as the major target of chrysophanol. DCN was upregulated in the tumor tissues following chrysophanol treatment, and ectopic DCN expression markedly augmented the pro-apoptotic effects of chrysophanol in CRC cells. In contrast, DCN knockdown significantly abrogated chrysophanol-induced apoptosis in CRC cells. Taken together, chrysophanol exerts anti-neoplastic effects in vitro and in vivo in CRC cells by modulating DCN, there by highlighting its therapeutic potential in CRC.

Aloperine can reverse the cisplatin resistance of colorectal cancer cells via suppressing the HIF-1α/ERK signaling pathway.

Background: Aloperine can exert antitumor effects in colorectal cancer; however, it remains obscure whether aloperine can reverse the cisplatin resistance in colorectal cancer (CRC). Objective: To explore the roles of aloperine in the chemosensitivity of the DDP-resistant colorectal cancer cell line HT-29 (HT-29/DDP) and the related mechanism. Results: Aloperine can inhibit the proliferation of both HT-29 and HT-29/DDP cells in a dose-dependent manner; moreover, aloperine can significantly increase the sensitivity of HT-29/DDP cells to DDP; finally, HIF-1α and p-ERK was upregulated in HT-29/DDP cells and transient over-expression of HIF-1α has blocked aloperine+DDP induced anti-proliferative and pro-apoptotic effects on HT-29/DDP cells. Conclusion: We are reporting for the first time that aloperine can increase the sensitivity of HT-29/DDP cells to DDP and reverse cisplatin resistance via downregulating the HIF-1α /ERK signaling pathway.

Synthetic circular multi-miR sponge simultaneously inhibits miR-21 and miR-93 in esophageal carcinoma.

MicroRNAs (miRs) are post-transcriptional regulators involved in the initiation and progression of many tumors. Recently, naturally occurring circular RNAs (circRNAs) have been described in eukaryotic cells:;they comprise a new class of gene regulators. Naturally occurring circular miR sponges, which induce miR loss-of-function, can prevent endogenous onco-miRs from binding to their cognate mRNA targets. These findings suggest that synthetic (artificial) circular RNAs could be constructed as therapeutic molecular sponges to suppress harmful onco-miRs. Using enzymatic ligation, we designed and constructed a circular RNA containing both miR-21 and miR-93 binding sites. The synthetic circular sponge was resistant to digestion with RNase R. Luciferase assays and functional experiments showed that the circular multi-miR sponge was more stable than its linear counterpart. Moreover, endogenous miR-21 and miR-93 were inhibited by the circular sponge. In addition, the synthetic sponge significantly suppressed cellular proliferation and migration while promoting apoptosis in esophageal carcinoma cells. Finally, in a murine xenograft model, the circular sponge significantly inhibited tumor growth in vivo. Taken together, these findings establish that the design and construction of efficient artificial miR sponges represent a novel strategy to achieve miR loss-of-function in molecular cancer therapeutics.

Regulation of Proliferation and Epithelial-to-Mesenchymal Transition (EMT) of Gastric Cancer by ZEB1 via Modulating Wnt5a and Related Mechanisms.

BACKGROUND As a member of the zinc-finger E-box binding protein (ZEB) family, ZEB1 can modulate onset and progression of various tumors, but its regulatory effect or mechanism in GC has not been defined. MATERIAL AND METHODS GC tumor tissues and adjacent tissues were collected from GC patients across different TNM stages. Real-time PCR was used to measure ZEB1 expression to analyze its correlation with pathological features of tumors. Cultured GC cell lines SGC-7901 and MGC-803 were randomly assigned into control group, scramble group, and ZEB1 siRNA group. Real-time PCR was employed to analyze ZEB1 expression, and MTT approach was used to measure cell proliferation. Cell apoptosis was evaluated by flow cytometry. Wound healing assay was used to detect its effect on cell migration. Expression of E-cadherin and Vimentin involved in epithelial-to-mesenchymal transition (EMT) was measured by Western blot analysis, along with Wnt5a proteins. RESULTS GC tissues had upregulation of ZEB1 (P<0.05 compared to adjacent tissues), whose expression level was correlated with differentiation grade, lymph node metastasis, and tumor pathological stage (P<0.05). Transfection of ZEB1 siRNA into SGC-7901 or MGC-803 cells can suppress ZEB1 expression, inhibit tumor cell proliferation, enhance apoptosis, and inhibit cell migration. Transfected GC cells had higher E-cadherin expression and decreased Vimentin expression or Wnt5a expression (P<0.05 compared to the control group). CONCLUSIONS ZEB1 expression is increased in GC tumor tissues and is associated with pathological features. The downregulation of ZEB1 can facilitate cell apoptosis via mediating Wnt5a, further suppressing GC cell proliferation and migration, and reducing EMT occurrence.

RNA sequencing of esophageal adenocarcinomas identifies novel fusion transcripts, including NPC1-MELK, arising from a complex chromosomal rearrangement.

BACKGROUND: Studies of chromosomal rearrangements and fusion transcripts have elucidated mechanisms of tumorigenesis and led to targeted cancer therapies. This study was aimed at identifying novel fusion transcripts in esophageal adenocarcinoma (EAC). METHODS: To identify new fusion transcripts associated with EAC, targeted RNA sequencing and polymerase chain reaction (PCR) verification were performed in 40 EACs and matched nonmalignant specimens from the same patients. Genomic PCR and Sanger sequencing were performed to find the breakpoint of fusion genes. RESULTS: Five novel in-frame fusion transcripts were identified and verified in 40 EACs and in a validation cohort of 15 additional EACs (55 patients in all): fibroblast growth factor receptor 2 (FGFR2)-GRB2-associated binding protein 2 (GAB2) in 2 of 55 or 3.6%, Niemann-Pick C1 (NPC1)-maternal embryonic leucine zipper kinase (MELK) in 2 of 55 or 3.6%, ubiquitin-specific peptidase 54 (USP54)-calcium/calmodulin dependent protein kinase II γ (CAMK2G) in 2 of 55 or 3.6%, megakaryoblastic leukemia (translocation) 1 (MKL1)-fibulin 1 (FBLN1) in 1 of 55 or 1.8%, and CCR4-NOT transcription complex subunit 2 (CNOT2)-chromosome 12 open reading frame 49 (C12orf49) in 1 of 55 or 1.8%. A genomic analysis indicated that NPC1-MELK arose from a complex interchromosomal translocation event involving chromosomes 18, 3, and 9 with 3 rearrangement points, and this was consistent with chromoplexy. CONCLUSIONS: These data indicate that fusion transcripts occur at a stable frequency in EAC. Furthermore, our results indicate that chromoplexy is an underlying mechanism that generates fusion transcripts in EAC. These and other fusion transcripts merit further study as diagnostic markers and potential therapeutic targets in EAC. Cancer 2017;123:3916-24. © 2017 American Cancer Society.

The novel fusion transcript NR5A2-KLHL29FT is generated by an insertion at the KLHL29 locus.

BACKGROUND: Novel fusion transcripts (FTs) caused by chromosomal rearrangement are common factors in the development of cancers. In the current study, the authors used massively parallel RNA sequencing to identify new FTs in colon cancers. METHODS: RNA sequencing (RNA-Seq) and TopHat-Fusion were used to identify new FTs in colon cancers. The authors then investigated whether the novel FT nuclear receptor subfamily 5, group A, member 2 (NR5A2)-Kelch-like family member 29 FT (KLHL29FT) was transcribed from a genomic chromosomal rearrangement. Next, the expression of NR5A2-KLHL29FT was measured by quantitative real-time polymerase chain reaction in colon cancers and matched corresponding normal epithelia. RESULTS: The authors identified the FT NR5A2-KLHL29FT in normal and cancerous epithelia. While investigating this transcript, it was unexpectedly found that it was due to an uncharacterized polymorphic germline insertion of the NR5A2 sequence from chromosome 1 into the KLHL29 locus at chromosome 2, rather than a chromosomal rearrangement. This germline insertion, which occurred at a population frequency of 0.40, appeared to bear no relationship to cancer development. Moreover, expression of NR5A2-KLHL29FT was validated in RNA specimens from samples with insertions of NR5A2 at the KLHL29 gene locus, but not from samples without this insertion. It is interesting to note that NR5A2-KLH29FT expression levels were significantly lower in colon cancers than in matched normal colonic epithelia (P =.029), suggesting the potential participation of NR5A2-KLHL29FT in the origin or progression of this tumor type. CONCLUSIONS: NR5A2-KLHL29FT was generated from a polymorphism insertion of the NR5A2 sequence into the KLHL29 locus. NR5A2-KLHL29FT may influence the origin or progression of colon cancer. Moreover, researchers should be aware that similar FTs may occur due to transchromosomal insertions that are not correctly annotated in genome databases, especially with current assembly algorithms. Cancer 2017;123:1507-1515. © 2017 American Cancer Society.

Whole-Exome Sequencing Analyses of Inflammatory Bowel Disease-Associated Colorectal Cancers.

BACKGROUND & AIMS: A long duration of inflammatory bowel disease (IBD) increases the risk for colorectal cancer. Mutation analysis of limited numbers of genes has indicated that colorectal tumors that develop in patients with IBD differ from those of patients without IBD. We performed whole-exome sequencing analyses to characterize the genetic landscape of these tumors. METHODS: We collected colorectal tumor and non-neoplastic tissues from 31 patients with IBD and colorectal cancer (15 with ulcerative colitis, 14 with Crohn's disease, and 2 with indeterminate colitis) and performed whole-exome sequencing analyses of the microdissected tumor and matched nontumor tissues. We identified somatic alterations by comparing matched specimens. The prevalence of mutations in sporadic colorectal tumors was obtained from previously published exome-sequencing studies. RESULTS: Two specimens had somatic mutations in the DNA proofreading or mismatch repair genes POLE, MLH1, and MSH6 and the tumor cells had a hypermutable phenotype. The remaining tumors had, on average, 71 alterations per sample. TP53 was the most commonly mutated gene, with prevalence similar to that of sporadic colorectal tumors (63% of cases). However, tumors from the patients with IBD had a different mutation spectrum. APC and KRAS were mutated at significantly lower rates in tumors from patients with IBD than in sporadic colorectal tumors (13% and 20% of cases, respectively). Several genes were mutated more frequently or uniquely in tumors from patients with IBD, including SOX9 and EP300 (which encode proteins in the WNT pathway), NRG1 (which encodes an ERBB ligand), and IL16 (which encodes a cytokine). Our study also revealed recurrent mutations in components of the Rho and Rac GTPase network, indicating a role for noncanonical WNT signaling in development of colorectal tumors in patients with IBD. CONCLUSIONS: Colorectal tumors that develop in patients with IBD have distinct genetic features from sporadic colorectal tumors. These findings could be used to develop disease-specific markers for diagnosis and treatment of patients with IBD and colorectal cancer.

miR-488 acts as a tumor suppressor gene in gastric cancer.

MicroRNAs (miRNAs) are small, non-coding RNAs that modulate development, cell proliferation, and apoptosis. The deregulated expression of microRNAs is found in carcinogenesis including gastric cancer (GC). In this study, we showed that the expression levels of miR-488 were downregulated in GC tissues compared to in non-tumor tissues. In addition, the expression of miR-488 was also lower in GC cell lines in contrast with the gastric epithelial cell line (GES). In addition, the expression level of miR-488 was negatively correlated with the TNM stage in GC patients, and lower miR-488 expression was found in tumors with advanced TNM stage. The ectopic expression of miR-488 suppressed the GC cell proliferation, cell cycle, colony information, and migration. PAX6 was identified as a direct target gene of miR-488 in HGC-27. Moreover, we found that the expression level of PAX6 was upregulated in the GC tissues compared with the non-tumor tissues. The PAX6 expression level was correlated with the cancer TNM stage, and higher PAX6 expression was found in tumors with advanced TNM stage. Furthermore, there was an inverse correlation between PAX6 and miR-488 expression levels in GC tissues. Therefore, these studies demonstrated that miR-488 might act as a tumor suppressor miRNA in the development of GC.

MiR-141 Inhibits Gastric Cancer Proliferation by Interacting with Long Noncoding RNA MEG3 and Down-Regulating E2F3 Expression.

BACKGROUND: MiR-141 and long noncoding RNA MEG3 have been independently reported to be tumor suppressor genes in various cancers. However, their expression has never been previously associated with gastric cancer (GC). AIMS: To investigate the interaction of miR-141 and MEG3 in GC. METHODS: QRT-PCR was used to detect miR-141, MEG3, and E2F3 in gastric tissues and cells. CCK-8 and flow cytometry analysis were used to detect cell functions. Western blot and luciferase activity were used to identify E2F3 as one of the direct targets of miR-141. RESULTS: We found that expression of both miR-141 and MEG3 was significantly reduced in GC compared with levels in matched nonmalignant tissues. Positive correlation between miR-141 and MEG3 was found in both tumor tissues and control tissues. Furthermore, the over-expression of either miR-141 or MEG3 in 7901 and MKN45 cells inhibited cell proliferation and cell cycle progression and promoted cell apoptosis. E2F3 was identified as a target of miR-141, and its inhibition significantly reduced MEG3 expression. E2F3 expression was also found to be negatively associated with both MEG3 and miR-141. E2F3 over-expression partly reversed the changes caused by transfection of miR-141 mimic, and inhibition of miR-141 or MEG3 overrides MEG3- or miR-141-induced modulation of cell growth in GC. CONCLUSIONS: These findings together suggested that miR-141 could be interacting with MEG3 and targeting E2F3, and these factors may play important anti-tumor effects in GC pathogenesis and provide therapeutic targets in the clinics.

A metabolomics-driven model for early remission prediction following vedolizumab treatment in patients with moderate-to-severe active ulcerative colitis.

To predict early remission following anti-integrin therapy (vedolizumab [VDZ]) in patients with moderate-to-severe active ulcerative colitis (UC) using non-invasive biomarkers. The clinical data of a cohort of 33 patients with moderate-to-severe active UC admitted to the Department of Gastroenterology at Suzhou Municipal Hospital between January 2021 and December 2022 were collected. Of these, 9 patients declined VDZ treatment, and 21 received VDZ at doses of 300 mg weeks 0, 2, and 6, each administered within a 30-minute infusion period. The treatment regimen aimed to induce remission of clinical symptoms; hence, the same dose was administered every 8 weeks. At weeks 0 and 14, serum C-reactive protein (CRP) and erythrocyte sedimentation rate were measured using a modified Mayo score. In addition to clinical assessment, stool samples at baseline and weeks 14 were collected and evaluated using 16SrRNA gene sequencing and gas chromatography-mass spectrometry (GC-MS). Clinical remission was determined based on the clinical symptoms and partial Mayo scores. In patients who received VDZ, the strains of bifidobacterium longum (P = 0.022) and bacteroides sartorii (P = 0.039) significantly increased after treatment than before treatment. GC-MS analysis showed that taurine (P = 0.047) and putrescine (P = 0.035) significantly decreased after treatment. Furthermore, while acetamide exhibited a notable increase (P = 0.001), arachidic acid (P < 0.001) and behenic acid (P = 0.005) demonstrated statistically significant elevations. The combined prediction model of acetamide, taurine, and putrescine demonstrated a high predictive value of early remission in patients with moderate-to-severe active UC following VDZ treatment (area under the curve = 0.911, P = 0.014).

Risk prediction of cholangitis after stent implantation based on machine learning.

The risk of cholangitis after ERCP implantation in malignant obstructive jaundice patients remains unknown. To develop models based on artificial intelligence methods to predict cholangitis risk more accurately, according to patients after stent implantation in patients' MOJ clinical data. This retrospective study included 218 patients with MOJ undergoing ERCP surgery. A total of 27 clinical variables were collected as input variables. Seven models (including univariate analysis and six machine learning models) were trained and tested for classified prediction. The model' performance was measured by AUROC. The RFT model demonstrated excellent performances with accuracies up to 0.86 and AUROC up to 0.87. Feature selection in RF and SHAP was similar, and the choice of the best variable subset produced a high performance with an AUROC up to 0.89. We have developed a hybrid machine learning model with better predictive performance than traditional LR prediction models, as well as other machine learning models for cholangitis based on simple clinical data. The model can assist doctors in clinical diagnosis, adopt reasonable treatment plans, and improve the survival rate of patients.

Sinomenine hydrochloride improves DSS-induced colitis in mice through inhibition of the TLR2/NF-κB signaling pathway.

BACKGROUND: Sinomenine hydrochloride (SH) has anti-inflammatory and immunosuppressive effects, and its effectiveness in inflammatory diseases, such as rheumatoid arthritis, has been demonstrated. However, whether SH has a therapeutic effect on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice and its mechanism of action have not been clarified. This study aimed to investigate the therapeutic effects and mechanism of action of SH on UC. METHODS: Twenty-four mice were randomly divided into control, model, SH low-dose (SH-L, 20mg/kg), and SH high-dose (SH-H, 60mg/kg) groups with six mice in each group. Disease activity index (DAI), colonic mucosal damage index, and colonic histopathology scores were calculated. The expression levels of related proteins, genes, and downstream inflammatory factors in the Toll-like receptor 2/NF-κB (TLR2/NF-κB) signaling pathway were quantified. RESULTS: SH inhibited weight loss, decreased DAI and histopathological scores, decreased the expression levels of TLR2, MyD88, P-P65, P65 proteins, and TLR2 genes, and also suppressed the expression of inflammatory factors TNF-α, IL-1 ß, and IL-6 in the peripheral blood of mice. CONCLUSION: The therapeutic effect of SH on DSS-induced UC in mice may be related to the inhibition of the TLR2/NF-κB signaling pathway.

Establishment and validation of a clinical diagnostic model for gastric low-grade intraepithelial neoplasia.

OBJECTIVE: A clinical diagnostic model of gastric low-grade intraepithelial neoplasia (LGIN) was developed and validated to improve the identification of precancerous lesions in gastric cancer. METHODS: A retrospective analysis of 1211 patients with chronic atrophic gastritis (CAG) and 1089 patients with LGIN admitted to the Endoscopy Center of the First Affiliated Hospital of Bengbu Medical College from January 2016 to December 2021 was performed to record basic clinical and pathological information.A total of 1756 patients were included after screening and were divided unequally and randomly into 2 groups, one for establishing an LGIN predictive nomogram (70% of patients) and the other for external validation of the model (30% of patients). R software was used for statistical analysis. RESULTS: The nomogram was built with 10 predictors: age, sex, lesion location, intestinal metaplasia, multiple location, lesion size, erosion, edema, surface white fur, and form. The calibration curves showed good agreement between the predicted and actual diagnoses. The C-indexes were 0.841 (95% CI: 0.820-0.863) in the training dataset, 0.833 in the internal validation dataset, and 0.842 in the external validation dataset (Hosmer-Lemeshow test, P = .612), showing satisfactory stableness. CONCLUSIONS: This study provides a visual mathematical model that can be used to diagnose high-risk LGIN, improve follow-up or endoscopic treatment and the detection rate of precancerous gastric cancer lesions, reduce the incidence of gastric cancer, and provide a reliable basis for the treatment of LGIN.

Host receptor identification of a polyvalent lytic phage GSP044, and preliminary assessment of its efficacy in the clearance of Salmonella.

Salmonella and pathogenic Escherichia coli are important foodborne pathogens. Phages are being recognized as potential antibacterial agents to control foodborne pathogens. In the current study, a polyvalent broad-spectrum phage, GSP044, was isolated from pig farm sewage. It can simultaneously lyse many different serotypes of Salmonella and E. coli, exhibiting a broad host range. Using S. Enteritidis SE006 as the host bacterium, phage GSP044 was further characterized. GSP044 has a short latent period (10 min), high stability at different temperatures and pH, and good tolerance to chloroform. Genome sequencing analysis revealed that GSP044 has a double-stranded DNA (dsDNA) genome consisting of 110,563 bp with G + C content of 39%, and phylogenetic analysis of the terminase large subunit confirmed that GSP044 belonged to the Demerecviridae family, Epseptimavirus genus. In addition, the genomic sequence did not contain any lysogenicity-related, virulence-related, or antibiotic resistance-related genes. Analysis of phage-targeted host receptors revealed that the outer membrane protein (OMP) BtuB was identified as a required receptor for phage infection of host bacteria. The initial application capability of phage GSP044 was assessed using S. Enteritidis SE006. Phage GSP044 could effectively reduce biofilm formation and degrade the mature biofilm in vitro. Moreover, GSP044 significantly decreased the viable counts of artificially contaminated S. Enteritidis in chicken feed and drinking water. In vivo tests, a mouse model of intestinal infection demonstrated that phage GSP044 was able to reduce the number of colonized S. Enteritidis in the intestine. These results suggest that phage GSP044 may be a promising candidate biologic agent for controlling Salmonella infections.

Downregulation of CLDN6 inhibits cell migration and invasion and promotes apoptosis by regulation of the JAK2/STAT3 signaling pathway in hepatocellular carcinoma.

Background: High expression of CLDN6 in hepatocellular carcinoma (HCC) has been widely reported. During this research, CLDN6's effect on the infiltration, migration, and apoptosis of HCC cells was investigated. Methods: Initially, the knockdown and overexpression of CLDN6 in HCC cells were carried out by short interfering RNA (siRNA) and plasmid transfection. The transfection efficiency was detected by means of a quantitative real-time polymerase chain reaction (qRT-PCR) assay, immunofluorescence staining, and Western blot analysis. Transwell and wound-healing assays were employed for the detection of invasion and migration ability. CCK-8 assay and flow cytometry were utilized for the detection of apoptosis. Finally, analysis of the expression of pathway-related proteins (JAK2, STAT3, p-JAK2, and p-STAT3) and the regulation of apoptotic responses (by measurement of cleaved caspase-3, Bax, and Bcl-2 levels) was carried out. Results: When CLDN6 was knocked down, the cellular invasion and migration ability decreased, and apoptosis increased, which decreased p-JAK2, p-STAT3, and anti-apoptotic protein bcl-2 expression. Furthermore, an elevation was observed in cleaved caspase-3 and Bax expression levels. Contrarily, upon overexpression of CDLN6, the aforementioned experimental results were reversed. Conclusions: CLDN6 knockdown results in the inhibition of HCC cells' infiltration and migration and promotes apoptosis via downregulation of the JAK2/STAT3 signaling pathway.

LncRNA XIST/miR-137 axis strengthens chemo-resistance and glycolysis of colorectal cancer cells by hindering transformation from PKM2 to PKM1.

BACKGROUND: Glycolysis was an essential driver of chemo-resistance in colorectal cancer (CRC), albeit with limited molecular explanations. OBJECTIVE: We strived to elucidate the involvement of lncRNA XIST/miR-137/PKM axis in chemo-tolerance and glycolysis of CRC. METHODS: Altogether 212 pairs of tumor tissues and adjacent normal tissues were collected from CRC patients. Moreover, human CRC epithelial cell lines, including HT29, SW480, SW620 and LoVo, were purchased in advance, and their activity was estimated after transfection of si-XIST or miR-137 mimic. Furthermore, 5-FU/cisplatin-resistance of CRC cells was determined through MTT assay, and glycolytic potential of CRC cells was appraised based on oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). RESULTS: Highly-expressed XIST were predictive of severe symptoms and unfavorable 3-year survival of CRC patients (P< 0.05). Besides, silencing of XIST not only diminished proliferative, migratory and invasive power of CRC cells (P< 0.05), but also enhanced sensitivity of CRC cells responding to 5-FU/cisplatin (P< 0.05). Glycolytic potency of CRC cells was also undermined by si-XIST, with decreased maximal respiration and maximal glycolytic capacity in the si-XIST group as relative to NC group (P< 0.05). Nevertheless, miR-137 mimic attenuated the facilitating effect of pcDNA3.1-XIST on proliferation, migration, invasion, 5-FU/cisplatin-resistance and glycolysis of CRC cells (P< 0.05). Ultimately, ratio of PKM2 mRNA and PKM1 mRNA, despite being up-regulated by pcDNA3.1-XIST, was markedly lowered when miR-137 mimic was co-transfected (P< 0.05). CONCLUSIONS: LncRNA XIST/miR-137 axis reinforced glycolysis and chemo-tolerance of CRC by elevating PKM2/PKM1 ratio, providing an alternative to boost chemo-therapeutic efficacy of CRC patients.

Association Between H. pylori Infection and Colorectal Polyps: A Meta-Analysis of Observational Studies.

BACKGROUND: It has been suggested that Helicobacter pylori (H. pylori) infection is associated with hypergastrinemia and proliferation of colorectal mucosa via direct stimulation, dysbiosis of the gut microbiome, and changes in the gut microbiome, all of which may lead to the formation of colorectal polyps. However, the consensus remains lacking regarding whether H. pylori infection is independently associated with colorectal polyps and whether the association differs according to histological type of colorectal polyps. To summarize the current evidence regarding the relationship between H. pylori infection and colorectal polyps, we conducted a meta-analysis of related observational studies according to the histological types of colorectal polyps. METHODS: Observational studies investigating the association between H. pylori infection and colorectal polyps using multivariate analyses were included by search of PubMed, Embase, and Web of Science. A random-effects model was adopted to combine the results. RESULTS: Seventeen studies that include 322,395 participants were analyzed. It was shown that H. pylori infection was independently associated with overall colorectal polyps (odds ratio [OR]: 1.67, 95% CI: 1.24-2.24, p < 0.001; I 2 = 73%). According to the histological type of colorectal polyps, H. pylori infection was independently associated with adenomatous polyps (APs; OR: 1.71, 95% CI: 1.47-1.99, p < 0.001; I 2 = 86%), advanced APs (OR: 2.06, 95% CI: 1.56-2.73, p < 0.001; I 2 = 0%), and hyperplastic polyps (HPs; OR: 1.54, 95% CI: 1.02-2.30, p = 0.04; I 2 = 78%). Evidence based on only one study showed that H. pylori infection was not associated with sessile serrated polyps (SSPs; OR: 1.00, 95% CI: 0.93-1.07, p = 0.99). CONCLUSIONS: Current evidence from case-control and cross-sectional studies suggested that H. pylori infection was independently associated with colorectal APs, advanced APs, and HPs, but not with SSPs. These findings suggested H. pylori infection may be a possible risk factor of colorectal polyp, which is important for the prevention of colorectal polyp in the adult population.