Publications by authors named "Shuixiang He"

72 Publications

Delphinidin modulates JAK/STAT3 and MAPKinase signaling to induce apoptosis in HCT116 cells.

Environ Toxicol 2021 May 6. Epub 2021 May 6.

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Delphinidin is an anthocyanin that belongs to the group of flavonoids that exert numerous biological activities. However, the molecular mechanisms underlying the anticancer effects of delphinidin remain poorly understood. In our study we analyzed delphinidin modulate STAT-3 and MAPKinase signaling thereby inhbits cell proliferation and promote apoptosis. Our study demonstrated that delphinidin treatment significantly reduced the viability of human colon cancer HCT116 in a concentration-dependent manner. We noticed that delphinidin effectively induced oxidative stress-mediated apoptosis by generating intracellular ROS, decreasing antioxidant levels, inducing lipid peroxidation, and single-strand break on colon cancer cells. In this study, we observed that delphinidin treatment alters the mitochondrial membrane potential, thereby induces apoptosis was closely associated with the induction of pro-apoptotic Bax, Caspase- 3,8 & 9, cytochrome C, and inhibition of anti-apoptotic protein expression. Studies on STAT-3 and MAPKinase signaling showed delphinidin inhibited the phosphorylation of these transcription factors' activity. Inhibition of STAT-3, p38, and ERK1/2 phosphorylation and modulation pro-apoptotic protein expression might be responsible for the anticancer activity of delphinidin in colon cancer cells.
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http://dx.doi.org/10.1002/tox.23152DOI Listing
May 2021

Analysis of the primary presenting symptoms and hematological findings of COVID-19 patients in Bangladesh.

J Infect Dev Ctries 2021 03 7;15(2):214-223. Epub 2021 Mar 7.

Department of Gastroenterology, First affiliated hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R.China.

Introduction: SARS-Cov-2 infection or COVID-19 is a global pandemic. In this manuscript, we investigated the primary symptoms and basic hematological presentations of SARS-CoV-2 infection among the Bangladeshi patients.

Methodology: This was a multicentre cross-sectional study done on COVID-19 patients tested positive by RT PCR in Bangladesh. Clinical features of mild to moderate degree of COVID-19 patients; hematological and biochemical admission day laboratory findings of moderate to severe degree hospitalized COVID-19 patients were analyzed.

Results: COVID-19 patients in Bangladesh commonly presented with fever, cough, fatigue, shortness of breath, and sore throat. But symptoms like myalgia, diarrhea, skin rash, headache, Abdominal pain/cramp, nausea, vomiting, restlessness, and a higher temperature of >100°F have a greater presentation rate and more frequent than other published studies. CRP and Prothrombin time was found to increase in all the patients. Serum ferritin, ESR, SGPT, and D-Dimer were increased among 53.85%, 80.43, 44%, and 25% patients. 17.39% of the patients had leucocytosis and neutrophilia, 28.26% presented with lymphocytopenia, and 62.52% had mild erythrocytopenia. The difference between the decrease hemoglobin count (higher in the male) and increased SGPT (higher in female) against gender was significant.

Conclusions: Our study had evaluated a different expression in presenting symptoms of COVID-19 patients in Bangladesh. CRP, Prothrombin time, serum ferritin, ESR, SGPT, D-Dimer, erythrocytopenia, and lymphocytopenia can be assessments for diagnosis and prognosis of COVID-19 disease. Decrease hemoglobin count (higher in the male) and increased SGPT (higher in female) establish these two markers as a good candidate for diagnostic value against gender.
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http://dx.doi.org/10.3855/jidc.13692DOI Listing
March 2021

Capsule endoscopy practice during the COVID-19 pandemic: Recommendations from the Capsule Endoscopy Group of the Chinese Society of Digestive Endoscopy.

Endosc Int Open 2021 Mar 18;9(3):E280-E283. Epub 2021 Feb 18.

Department of Gastroenterology, Changhai Hospital, Shanghai, China.

The Capsule Endoscopy Group of the Chinese Society of Digestive Endoscopy has issued recommendations for capsule endoscopy (CE) practice during the COVID-19 pandemic to standardize workflow, preventive strategies, and management of a CE unit and in so doing, ensure the safety of both medical staff and patients.
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http://dx.doi.org/10.1055/a-1333-6635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892273PMC
March 2021

EGFL7 as a novel therapeutic candidate regulates cell invasion and anoikis in colorectal cancer through PI3K/AKT signaling pathway.

Int J Clin Oncol 2021 Jun 26;26(6):1099-1108. Epub 2021 Feb 26.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yan Tower West Road, Xi'an, 710061, Shaanxi, China.

Background: Anoikis is a form of apoptosis, which inhibits metastatic cascade and deprives cancer cells with invasive capacity. Epidermal growth factor-like domain-containing protein 7 (EGFL7) is overexpressed in colorectal cancer (CRC) and is a potential biomarker for malignancy. The present study aimed was to investigate the effect and underlying mechanism of EGFL7 on CRC cell function.

Methods: EGFL7 expression in mutable human CRC cell lines and normal intestinal epithelial cell line HIEC were measured by qRT-PCR. To investigate the biological functions of EGFL7, loss-of-function experiments were performed by transfecting EGFL7 siRNA into SW620 and LoVo cells. Western blot analysis, MTT, invasion and anoikis assay were used to explore the underlying mechanism of EGFL7.

Results: EGFL7 was upregulated in several CRC cell lines as compared with normal intestinal epithelial cell line HIEC. Transfection of EGFL7 siRNA significantly decreased cell proliferation and invasion capacity of SW620 and LoVo cells. Additionally, EGFL7 inhibition markedly elevated anoikis through modulating anoikis marker proteins as reflected by increasing of cleaved-caspase-3 and cleaved-PAPR expression. Moreover, downregulation of EGFL7 inhibited PI3K and P-AKT expression. Furthermore, re-expression of PI3K remarkably reversed the effects of EGFL7 on SW620 cells.

Conclusion: Overall, our findings suggested that EGFL7 acts as an oncogene, regulated CRC invasion and anoikis through PI3K/AKT signaling, which provided a theoretical basis for EGFL7 as a potential therapeutic target of CRC treatment.
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http://dx.doi.org/10.1007/s10147-021-01888-xDOI Listing
June 2021

Automated Classification and Segmentation in Colorectal Images Based on Self-Paced Transfer Network.

Biomed Res Int 2021 20;2021:6683931. Epub 2021 Jan 20.

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710071, China.

Colorectal imaging improves on diagnosis of colorectal diseases by providing colorectal images. Manual diagnosis of colorectal disease is labor-intensive and time-consuming. In this paper, we present a method for automatic colorectal disease classification and segmentation. Because of label unbalanced and difficult colorectal data, the classification based on self-paced transfer VGG network (STVGG) is proposed. ImageNet pretraining network parameters are transferred to VGG network with training colorectal data to acquire good initial network performance. And self-paced learning is used to optimize the network so that the classification performance of label unbalanced and difficult samples is improved. In order to assist the colonoscopist to accurately determine whether the polyp needs surgical resection, feature of trained STVGG model is shared to Unet segmentation network as the encoder part and to avoid repeat learning of polyp segmentation model. The experimental results on 3061 colorectal images illustrated that the proposed method obtained higher classification accuracy (96%) and segmentation performance compared with a few other methods. The polyp can be segmented accurately from around tissues by the proposed method. The segmentation results underpin the potential of deep learning methods for assisting colonoscopist in identifying polyps and enabling timely resection of these polyps at an early stage.
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http://dx.doi.org/10.1155/2021/6683931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843175PMC
June 2021

Antiperistaltic effect and safety of l-menthol oral solution on gastric mucosa for upper gastrointestinal endoscopy in Chinese patients: Phase III, multicenter, randomized, double-blind, placebo-controlled study.

Dig Endosc 2021 Feb 1. Epub 2021 Feb 1.

Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Objective: The topical antispasmodic agent l-menthol is commonly used for gastric peristalsis suppression during diagnostic upper gastrointestinal (GI) endoscopy. We evaluated the efficacy and safety of a single dose l-menthol solution in suppressing gastric peristalsis during upper GI endoscopy in Chinese patients.

Methods: In this phase III, multicenter, randomized, double-blind, placebo-controlled study (ClinicalTrials.gov: NCT03263910), 220 patients scheduled to undergo upper GI endoscopy at five Chinese referral centers received a single dose of either 160 mg of l-menthol (n = 109) or placebo (n = 111). Both treatments were sprayed endoscopically on the gastric mucosa. An independent committee evaluated the degree of gastric peristalsis (peristaltic score: grade 1-5).

Results: At baseline, the proportion of patients with grade 1 peristalsis (no peristalsis) did not differ between the groups. The proportion of patients with grade 1 peristalsis post-treatment was significantly higher in the l-menthol group (40.37%, 44/109) versus the placebo group (16.22%, 18/111; P < 0.001); the difference between the groups was 24.15% (95% confidence interval: 12.67%-35.63%; P < 0.001). In the l-menthol group, 61.47% of patients had grade 1 peristalsis after endoscopy versus 24.55% in the placebo group (P < 0.001). The ease of intragastric examination correlated significantly with the grade of peristalsis. The incidence of adverse events was comparable between the groups (P = 0.340).

Conclusions: During upper GI endoscopy, a single dose of l-menthol solution (160 mg) sprayed on the gastric mucosa significantly attenuated gastric peristalsis versus placebo, thereby improving the visual stability without any safety concerns.
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http://dx.doi.org/10.1111/den.13941DOI Listing
February 2021

Endoscopy-assisted magnetic compression anastomosis for rectal anastomotic atresia.

Endoscopy 2021 Jan 27. Epub 2021 Jan 27.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.

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http://dx.doi.org/10.1055/a-1322-1899DOI Listing
January 2021

Comparing the Impact of Laparoscopic Sleeve Gastrectomy and Gastric Cancer Surgery on Resting-State Brain Activity and Functional Connectivity.

Front Neurosci 2020 26;14:614092. Epub 2020 Nov 26.

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Laparoscopic sleeve gastrectomy (LSG) is one of the most performed bariatric surgeries in clinical practice. Growing neuroimaging evidence shows that LSG induces brain functional and structural alterations accompany with sustained weight-loss. Meanwhile, for clinical treatment of gastric cancer, stomach removal surgery is a similar procedure to LSG. It is unclear if the gastric cancer surgery (GCS) would induce the similar alterations in brain functions and structures as LSG, and it would help to clarify the specificity of the LSG. We recruited 24 obese patients who received LSG in the LSG group and 16 normal weight patients with gastric cancer who received GCS as the control group. Functional magnetic resonance imaging was employed to investigate the differences and similarity of surgery's impact on resting-state brain activity and functional connectivity (RSFC) between LSG and GCS groups. Both LSG and GCS groups showed increased activities in the posterior cingulate cortex (PCC) and supplementary motor area (SMA) as well as the decreased RSFC of PCC- dorsomedial prefrontal cortex and SMA- dorsolateral prefrontal cortex. There were decreased resting-state activity of hippocampus and putamen in LSG group and increases in GCS group. In LSG group, resting-state activities of hippocampus and putamen were correlated with craving for high-caloric food and body mass index after surgery, respectively. These findings suggest LSG induced alterations in resting-state activity and RSFC of hippocampus and putamen specifically regulate the obese state and overeating behaviors in obese patients.
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http://dx.doi.org/10.3389/fnins.2020.614092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726325PMC
November 2020

Screening and identification of a CD44v6 specific peptide using improved phage display for gastric cancer targeting.

Ann Transl Med 2020 Nov;8(21):1442

Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background: Peptide probes can be applied for biomarker targeting to improve the diagnostic accuracy. Cluster of differentiation 44 (CD44) is up-regulated in gastric cancer (GC). Among all the variants of CD44, CD44v6 is reported the most promising biomarker for GC. The purpose of this study was generating and identification a peptide ligand specific to CD44v6.

Methods: A 12-mer phage peptide library was screened on CD44v overexpressed HEK-293 cells with an improved subtractive method. Five candidate sequences emerged. Candidate phages were selected using enzyme-linked immunosorbent assay and competitive inhibition assays. Then the sequence (designated ELT) was chosen for further study. Its binding affinity and specificity were verified on recombinant protein, GC cells, GC tissues and xenograft models based on BALB/c-nu/nu mice using dissociation constant calculation, immunofluorescence, immunohistochemistry and imaging separately.

Results: The dissociation constant of ELT with recombinant protein was 611.2 nM. ELT stained CD44v overexpressed HEK-293 but not the cell expressing wild-type CD44s. On GC cell lines, ELT co-stained with anti-CD44v6 antibody. ELT binding on tumor tissues significantly increased compared with that of paracancer tissues, also showed a linear positive correlation with CD44v6 expression. ELT specifically accumulated in tumor and eliminated in short time .

Conclusions: ELT can target GC and via CD44v6, indicating its potential to serve as a probe for GC targeting diagnosis and therapy.
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http://dx.doi.org/10.21037/atm-19-4781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723568PMC
November 2020

BRD4 modulates vulnerability of triple-negative breast cancer to targeting of integrin-dependent signaling pathways.

Cell Oncol (Dordr) 2020 Dec 2;43(6):1049-1066. Epub 2020 Oct 2.

Department of Pharmacology and Nutritional Sciences, Department of Molecular and Cellular Biochemistry, and Markey Cancer Center, College of Medicine, University of Kentucky, Lexington, KY, USA.

Purpose: Stemming from a myriad of genetic and epigenetic alterations, triple-negative breast cancer (TNBC) is tied to poor clinical outcomes and aspires for individualized therapies. Here we investigated the therapeutic potential of co-inhibiting integrin-dependent signaling pathway and BRD4, a transcriptional and epigenetic mediator, for TNBC.

Methods: Two independent patient cohorts were subjected to bioinformatic and IHC examination for clinical association of candidate cancer drivers. The efficacy and biological bases for co-targeting these drivers were interrogated using cancer cell lines, a protein kinase array, chemical inhibitors, RNAi/CRISPR/Cas9 approaches, and a 4 T1-Balb/c xenograft model.

Results: We found that amplification of the chromosome 8q24 region occurred in nearly 20% of TNBC tumors, and that it coincided with co-upregulation or amplification of c-Myc and FAK, a key effector of integrin-dependent signaling. This co-upregulation at the mRNA or protein level correlated with a poor patient survival (p < 0.0109 or p < 0.0402, respectively). Furthermore, we found that 14 TNBC cell lines exhibited high vulnerabilities to the combination of JQ1 and VS-6063, potent pharmacological antagonists of the BRD4/c-Myc and integrin/FAK-dependent pathways, respectively. We also observed a cooperative inhibitory effect of JQ1 and VS-6063 on tumor growth and infiltration of Ly6G myeloid-derived suppressor cells in vivo. Finally, we found that JQ1 and VS-6063 cooperatively induced apoptotic cell death by altering XIAP, Bcl2/Bcl-xl and Bim levels, impairing c-Src/p130Cas-, PI3K/Akt- and RelA-associated signaling, and were linked to EMT-inducing transcription factor Snail- and Slug-dependent regulation.

Conclusion: Based on our results, we conclude that the BRD4/c-Myc- and integrin/FAK-dependent pathways act in concert to promote breast cancer cell survival and poor clinical outcomes. As such, they represent promising targets for a synthetic lethal-type of therapy against TNBC.
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http://dx.doi.org/10.1007/s13402-020-00537-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716866PMC
December 2020

Screening value for gastrointestinal lesions of magnetic-controlled capsule endoscopy in asymptomatic individuals.

J Gastroenterol Hepatol 2021 May 14;36(5):1267-1275. Epub 2020 Oct 14.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background And Aim: Most patients with gastric tumors and precancerous lesions are asymptomatic, which often results in delayed diagnosis and treatment. Compared with conventional gastroscopy and capsule endoscopy, magnetic-controlled capsule endoscopy is a non-invasive, effective, and cost-efficient diagnostic modality for gastric examination. We retrospectively investigated magnetic-controlled capsule endoscopy as a screening tool for gastrointestinal lesions (particularly gastric tumors and precancerous lesions) in asymptomatic individuals.

Methods: In this retrospective study, 1757 patients who voluntarily underwent magnetic-controlled capsule endoscopy between January and December 2019 at nine medical centers across Shaanxi province based on strict inclusion and exclusion criteria were enrolled. The primary outcomes were gastric tumor and precancerous lesion detection rates and procedural safety.

Results: The upper and lower gastrointestinal lesion detection rates were 98.35% (1728/1757) and 21.61% (78/361), respectively; 2.28% of patients were diagnosed with gastric tumors including gastric cancer (4/1757) and submucosal tumors (36/1757). Three types of precancerous lesions were found in 591 patients (33.64%), including chronic atrophic gastritis (23.16%), gastric polyp (10.98%), and gastric ulcer (2.96%). For patients aged over 40 years, the detection rate of precancerous lesions was higher (14.36% vs 42.58%, P < 0.001). No patient was diagnosed with small intestinal cancer. No adverse events occurred.

Conclusions: Magnetic-controlled capsule endoscopy could be used as a promising novel screening modality for diagnosis of gastrointestinal lesions in asymptomatic individuals, specifically gastric tumors and precancerous lesions, with the advantages of safety, non-invasiveness, effectiveness, and cost-efficiency.
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http://dx.doi.org/10.1111/jgh.15282DOI Listing
May 2021

Downregulation of LINC00958 inhibits proliferation, invasion and migration, and promotes apoptosis of colorectal cancer cells by targeting miR‑3619‑5p.

Oncol Rep 2020 Oct 29;44(4):1574-1582. Epub 2020 Jul 29.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

The aberrant expression of long non‑coding RNAs (lncRNAs), including LINC00958, has been demonstrated in several types cancers. The present study aimed to investigate the role of LINC00958 in colorectal cancer (CRC) and identify the possible underlying mechanisms. The expression of LINC00958 and microRNA (miR)‑3619‑5p was detected in several human CRC cell lines using reverse transcription‑quantitative PCR. Then, short hairpin RNA (shRNA)‑LINC00958 was transfected into the cells. The results revealed that the expression of LINC00958 was notably upregulated, whereas miR‑3619‑5p was downregulated in CRC cells. Transfection with shRNA‑LINC00958 inhibited the proliferation, invasion and migration of CRC cells. Moreover, the rate of apoptosis was enhanced, accompanied by a decrease in the expression of Bcl‑2 and an increase in the expression of Bax and caspase‑3. A luciferase reporter assay was conducted to verify the target binding site between LINC00958 and miR‑3619‑5p. The luciferase reporter assay confirmed that miR‑3619‑5p could be directly targeted by LINC00958. Furthermore, the miR‑3619‑5p inhibitor reversed the effects of LINC00958 silencing on proliferation, invasion, migration and apoptosis. Taken together, the findings suggest that the downregulation of LINC00958 suppresses the proliferation, invasion and migration, and promotes the apoptosis of CRC cells by targeting miR‑3619‑5p in vitro, which provides a theoretical basis and therapeutic strategy for the treatment of CRC.
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http://dx.doi.org/10.3892/or.2020.7707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448424PMC
October 2020

The Prognosis Analysis of Liver Cirrhosis with Acute Variceal Bleeding and Validation of Current Prognostic Models: A Large Scale Retrospective Cohort Study.

Biomed Res Int 2020 16;2020:7372868. Epub 2020 Aug 16.

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background: Acute variceal bleeding is a major cause of death in liver cirrhosis. This large scale retrospective cohort study aims to analyze the prognosis of patients with cirrhosis and acute variceal bleeding and to validate the current prognostic models.

Methods: Patients with cirrhosis and acute variceal bleeding were enrolled from Jan 2019 to March 2020. The independent prognostic factors for in-hospital death were identified by logistic regression analyses. Area under curves (AUCs) was compared among Child-Pugh, cirrhosis acute gastrointestinal bleeding (CAGIB) score, and model for end-stage liver disease (MELD) and neutrophil-lymphocyte ratio (NLR) scores.

Results: Overall, 379 patients with liver cirrhosis and acute variceal bleeding were consecutively evaluated. The majority of the patients were males (59.1%) and the mean age of all patients were 53.7 ± 1.3 years (range 14-89). Hepatitis B virus (HBV) was the most common underlying cause of liver cirrhosis (54.1%). 72 (19%) patients had hepatocellular carcinoma. Multivariate logistic regression analyses showed that age, HCC, WBC, total serum bilirubin, serum creatinine, and ALT were independently associated with in-hospital death. And the odds ratios (ORs) for in-hospital death were 1.066 (95% CI 1.017-1.118, = 0.008), 7.19 (95% CI 2.077-24.893, = 0.001), 1.123 (95% CI 1.051-1.201, = 0.001), 1.014 (95% CI 1.005-1.023, = 0.003), 1.012 (95% CI 1.004-1.021, = 0.006), and 1.005 (95% CI 1.000-1.009, = 0.036), respectively. In the whole cohort with HCC patients, the AUCs of Child-Pugh, CAGIB, MELD and NLR scores were 0.842 (95% CI 0.801-0.878), 0.840 (95% CI 0.799-0.876), 0.798 (95% CI 0.754-0.838), and 0.688 (95% CI 0.639-0.735), respectively. The differences were statistically significant between Child-Pugh and NLR scores ( = 0.0118), and between CAGIB and NLR scores ( = 0.0354).

Conclusion: Child-Pugh and CAGIB scores showed better predictive performance for prognosis of patients with cirrhosis and acute variceal bleeding than NLR scores.
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http://dx.doi.org/10.1155/2020/7372868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448238PMC
May 2021

LncRNA SNAI3-AS1 promotes PEG10-mediated proliferation and metastasis via decoying of miR-27a-3p and miR-34a-5p in hepatocellular carcinoma.

Cell Death Dis 2020 08 11;11(8):685. Epub 2020 Aug 11.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, P. R. China.

During recent years, long noncoding RNAs (lncRNAs) have received focal attention due to their important function in cancer regulation. Though the relation between lncRNA SNAI3-AS1 and the development of hepatocellular carcinoma (HCC) has been described in our previous study, the role and the exact mechanism of SNAI3-AS1 are still unclear. In this study, qRT-PCR analysis revealed that the expression of SNAI3-AS1 was elevated and was correlated with the levels of PEG10 in HCC tissues. Through functional experiments, we determined that knockdown of SNAI3-AS1 and PEG10 inhibited the proliferation and metastasis, whereas overexpression of SNAI3-AS1 and PEG10 promoted the proliferation and metastasis of HCC cells. In addition, rescue experiments confirmed that upregulation of PEG10 partially restored cell function inhibition induced by SNAI3-AS1 knockdown. Therefore, we hypothesized that PEG10 may be regulated by SNAI3-AS1, which in turn mediates the malignant biological processes of HCC cells regulated by PEG10. Further bioinformatics analysis and mechanistic experiments showed that SNAI3-AS1 functions as a competing endogenous RNA (ceRNA) to activate PEG10 by acting as a sponge for miR-27-3p and miR-34a-5p. In summary, our study revealed that SNAI3-AS1 is a tumor regulator of PEG10 in the progression of HCC, and may contribute to the improvement of HCC diagnosis and therapy.
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http://dx.doi.org/10.1038/s41419-020-02840-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442791PMC
August 2020

Telephone-Based Reeducation of Drug Administration for Eradication: A Multicenter Randomized Controlled Study.

Gastroenterol Res Pract 2020 31;2020:8972473. Epub 2020 Jul 31.

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.

Poor adherence to treatment instructions may play an important role in the failure of eradication. The aim of this study was to evaluate the effects of telephone-based reeducation on 14-day quadruple . eradication therapy. In total, 162 patients were randomly assigned (1 : 1) to either the intervention group (patients received telephone-based reeducation on the 4, 7, and 10 days of the course) or the control group (patients received instructions only at the time of getting the prescriptions). All patients received a 14-day quadruple . eradication therapy. The primary outcome was the . eradication rate. The secondary outcomes included the symptom relief rates and the incidence rates of adverse events. Seventy-five patients in the reeducation group and 74 patients in the control group completed the follow-up. The . eradication rate in the reeducation group was statistically higher than that in the control group (intention-to-treat: 72.8% vs. 50.6%, = 0.006; per-protocol: 78.7% vs. 55.4%, = 0.003). However, the symptom relief rates and the adverse event rates in these two groups were not significantly different. Overall, the results from this study suggest that telephone-based reeducation can be potentially applied to improve the . eradication rate in clinical practice, without significantly increasing the adverse effects.
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http://dx.doi.org/10.1155/2020/8972473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415080PMC
July 2020

THBS4 promotes HCC progression by regulating ITGB1 via FAK/PI3K/AKT pathway.

FASEB J 2020 08 22;34(8):10668-10681. Epub 2020 Jun 22.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China.

Our research aims to identify the role of thrombospondin 4 (THBS4) in hepatocellular carcinoma (HCC). First, bioinformatic analysis was applied for detection the expression of THBS4 in HCC samples, and qRT-PCR and western blot were performed to explore the expression of THBS4 in HCC tissues and adjacent samples. Next, colony formation assay and cell viability assay were used to assess the function of THBS4 on HCC cells growth while transwell assay and scratch test were for metastasis. Meanwhile Xenograft tumor models were further conducted to verify the function of THBS4 in HCC. As for mechanism in deep, we investigated the influence of THBS4 on epithelial-mesenchymal transition (EMT) development and the interaction between THBS4 and integrin (ITG) family using multiple experiments, including western blot, immunofluorescence and immunoprecipitation (IP). As a result, our research discovered that the overexpression of THBS4 in both HCC patients' tissues and cell lines mediates HCC cells proliferation and metastasis in vitro and in vivo. In-depth, THBS4 regulated EMT progression and interacted with ITG family to modulate FAK/PI3K/AKT pathway. In conclusion, THBS4 as an oncogene interacts with integrinβ1 (ITGB1) to regulate HCC development via FAK/PI3K/AKT pathway.
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http://dx.doi.org/10.1096/fj.202000043RDOI Listing
August 2020

TRPC1 exacerbate metastasis in gastric cancer via ciRS-7/miR-135a-5p/TRPC1 axis.

Biochem Biophys Res Commun 2020 08 6;529(1):85-90. Epub 2020 Jun 6.

Department of Thoracic Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China. Electronic address:

Metastasis is frequently occurred in end-stage GC. Nevertheless, the initiation and progression of metastasis in GC remains unclear. The transient receptor potential canonical (TRPC) has been confirmed to be crucial for metastasis in many kinds of tumors, including GC. However, the molecular mechanisms regulating TRPC1 is unclear. Therefore, we investigated the role and mechanisms of TRPC1 in GC metastasis. We first evaluated the role of TRPC1 in GC by searching the public database, and tested the expression of TRPC1 in 50 paired GC tissues by qRT-PCR and IHC assays. Then, we generated BGC-823-shTRPC1 cells and MKN-45-TRPC1 cells to investigate the effects of TRPC1 on metastasis in vitro. For the mechanism study, we applied luciferase reporter assay, RNA pull-down assay, as well as RIP assay to validate the interation of ciRS-7, miR-135a-5p and TRPC1 in GC cells. This study, we showed that TRPC1 exacerbate EMT in gastric cancer via ciRS-7/miR-135a-5p/TRPC1 axis, and target TRPC1 could be beneficial for end-stage GC patients.
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http://dx.doi.org/10.1016/j.bbrc.2020.05.181DOI Listing
August 2020

Control measures to prevent Coronavirus disease 2019 pandemic in endoscopy centers: Multi-center study.

Dig Endosc 2020 Sep 3;32(6):914-920. Epub 2020 Sep 3.

Department of Gastroenterology, Peking University People's Hospital, Beijing, China.

Aims: To investigate control measures for COVID-19 pandemic in GIE centers in China.

Methods: This is a retrospective multi-center research, including seven centers. Data collection was from 1 February to 31 March 2020 and the same period in 2019.

Results: There were a total of 28 COVID-19 definite cases in these hospitals. Six out of seven GIE centers were arranged to shut down on 1 February, with a mean number of shutdown days of 23.6 ± 5.3. The actual workloads were only 10.3%-62.9% compared to those last year. All centers had a preoperative COVID-19 screening process. Epidemiological questionnaire, temperature taking and QR-code of journey were conducted. Chest CT scan was conducted during the shutdown period and continued in five centers after return to work. Antibody and nucleic acid test were applied in one to three centers. All endoscopists had advanced PPE. Five centers used surgical mask and the rest used N95 mask. Six centers used goggles or face shield. Five centers selected isolation gowns and the rest selected protective suits. The change frequency of these PPE was 4 h. Sterilizing measures were improved in six centers. Five centers utilized ultraviolet and six centers strengthened natural ventilation. Four and six centers used peracetic acid during the period of shutdown and return to work, alone or matched with OPA or acidified water.

Conclusions: Many effective control measures were conducted in GIE centers during the outbreak, including patients' volume limitation, preoperative COVID-19 screening, advanced PPE and disinfection methods.
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http://dx.doi.org/10.1111/den.13755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300959PMC
September 2020

The Effect of Helicobacter pylori Eradication in Patients with Gastroesophageal Reflux Disease: A Meta-Analysis of Randomized Controlled Studies.

Dig Dis 2020 12;38(4):261-268. Epub 2020 May 12.

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China,

Aim: Helicobacter pylori infection has been established as a definite risk factor for gastric cancer. However, the consequence of H. pylori eradication on the progression of gastroesophageal reflux disease (GERD) remains controversial. The purpose of our study was to investigate the relationship between H. pylori eradication and the development of GERD.

Methods: A comprehensive, English literature search was performed from January 1990 to April 2019. Only randomized controlled trials (RCT) that evaluated the effect of H. pylori eradication on GERD were included. Meta-analysis of pooled OR was performed using Review Manger 5.1.7.

Results: Seventeen articles with 6,889 subjects (intention-to-treat) that fulfilled the inclusion criteria were finally included in the analysis. Of them, 8 RCTs have the similar study design and inclusion criterion, which included patients with H. pylori infection but without GERD at baseline. The OR for the development of erosive GERD after H. pylori eradication was 1.67 (95% CI 1.12-2.48, p = 0.01). The OR for the development of GERD-related symptoms after H. pylori eradication in eradication group compared with control group was 1.04 (95% CI 0.84-1.29, p = 0.71). In addition, 9 RCTs included patients with both baseline H. pylori infection and GERD. The OR for the healing rates and relapse rates after H. pylori eradication in the H. pylori eradication group vs. control group was 0.92 (95% CI 0.47-1.82, p = 0.82) and 1.12 (95% CI 0.60-2.09, p = 0.71), respectively.

Conclusions: Our meta-analyses showed H. pylori eradication may lead to the development of new erosive GERD. However, eradication of H. pylori may affect neither the healing rates nor relapse rates of preexisting GERD.
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http://dx.doi.org/10.1159/000504086DOI Listing
August 2020

Exosomal miR-106a derived from gastric cancer promotes peritoneal metastasis via direct regulation of Smad7.

Cell Cycle 2020 05 8;19(10):1200-1221. Epub 2020 Apr 8.

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Peritoneal metastasis develops in more than half of patients with gastric cancer but influencing factors are poorly characterized. Exosomes are increasingly recognized as a new mediator in cancer directional metastasis through the transfer of nucleic acids or proteins to neighboring or distant cells. The role of exosomes in peritoneal metastasis and whether it could establish pre-metastatic milieu are largely unknown. Here, we assessed the migration of gastric cancer (GC) cells and identified that PKH26-labeled exosomes from GC cells can be ingested by peritoneal mesothelial cells (MCs). Additionally, miRNA (miR-106a) that highly enriched in GC-derived exosomes (GC-exos) and essential for destroying the mesothelial barrier was demonstrated through the observation of the injury of the MCs including migratory enhancement and imbalance of apoptosis and proliferation. Moreover, either stimulating miR-106a or treatment with GC-exos could inhibit the expression of Smad7, accompanied by the concurrent elevated α-SMA and fibronectin in MCs. Silencing of miR-106a abolished GC-exos-induced gene expression in MCs. The MCs regain the viability, apoptosis reduction and Smad7 expression after rescue experiment conducted in miR-106a-enriched GC-exos. Xenograft model suggested that exosomal miR-106a had a potential to promote tumor growth through targeting Smad7. Collectively, we revealed that the delivery of miR-106a from GC-exos plays a crucial role in gastric cancer peritoneal metastasis. MiR-106a: microRNA-106a; Smad7: small mothers against decapentaplegic 7; GC: gastric cancer; MCs: mesothelial cells; Exos: exosomes; HG: high-differentiated gastric cancer cells; LG: low-differentiated gastric cancer cells.
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http://dx.doi.org/10.1080/15384101.2020.1749467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217357PMC
May 2020

miR-204-5p Suppress Lymph Node Metastasis via Regulating CXCL12 and CXCR4 in Gastric Cancer.

J Cancer 2020 5;11(11):3199-3206. Epub 2020 Mar 5.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an JiaoTong University, 277 Yanta West Road, Xi'an, Shaanxi, China.

Gastric cancer (GC) exhibits a poor prognosis due to extensive invasion and lymphatic metastasis in the advanced stage. In this study, we firstly found that the expression of miR-204-5p markedly decreased in GC patients' tissue and serum, especially in GC with lymphatic metastasis. And ROC analysis showed miR-204-5p also served as a predicted factor for the lymphatic metastasis of GC. CXCL12 and CXCR4 were predicted and confirmed as the functional targets of miR-204-5p by Targetscan analysis, dual luciferase assay and western blotting analysis. In addition, we further determined that miR-204-5p suppresses migration and invasion in GC. This finding elucidates new functions and mechanisms for miR-204-5p in GC development and provides a new potential diagnostic marker and therapeutic targets for GC.
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http://dx.doi.org/10.7150/jca.33273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097947PMC
March 2020

Case report on a misleading case of appendiceal perforation presented with severe generalized convulsion.

Transl Pediatr 2020 Feb;9(1):81-85

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710000, China.

Appendicitis and convulsions are two common pathologies among children. Though appendicitis has some certain symptoms, they might present with atypical symptoms in young ages. Here we present a misleading case of a perforated appendix that presented with severe generalized convulsion, no significant abdominal symptoms and had a recent history of mild gastrointestinal problems. The primary symptoms and the related examination findings guided the differential diagnosis as viral encephalitis, febrile convulsion, and Epilepsy. The initial treatment was started accordingly with an aim to prevent further convulsion. But this case was later diagnosed as a case of peritonitis following perforated appendix and was operated successfully. After surgery, the patient recovered with no further attack of convulsion even following the postoperative withdrawal of sedative therapy. He was discharged on the 7 postoperative day and there were no major complaints on his follow-ups. Such misleading cases usually lead to misdiagnosis and might cause morbidity, even endanger the life of the patient. Therefore regarding children of sudden generalized convulsion with even minute abdominal findings or recent gastrointestinal history, it is necessary to pay attention and evaluate the abdomen by a CT or MRI besides the nervous system at the first impression.
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http://dx.doi.org/10.21037/tp.2020.02.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036636PMC
February 2020

The significance of IL-28B and CK-18 M30 levels in the diagnosis of non-alcoholic steatohepatitis in SD rats.

Pathol Res Pract 2020 Apr 26;216(4):152901. Epub 2020 Feb 26.

Department of Gastroenterology, Xi'an Jiaotong University First Affiliated Hospital, Xi'an, 710061, PR China. Electronic address:

Aims: To investigate the role of IL-28B and CK-18 M30 in the diagnosis of non-alcoholic steatohepatitis (NASH) in rats.

Methods: The rat NASH model was constructed by high-fat diet feeding and confirmed by liver tissue pathology analysis. The CK-18 M30, IL-28B, liver function and blood lipid were detected. The pathology of liver tissues was observed by H&E staining. The ROC curves of liver pathological scores, IL-28B, and CK-18 M30 were plotted and the sensitivity/specificity of each index was calculated.

Results: The liver tissue pathology at the end of the 12th week met NASH diagnostic criteria. The liver pathological scores of NASH model were higher than those of the control group (P < 0.05). Compared with the control group, the body weight of rats in the NASH group was lower (P < 0.05) and the liver index was higher (P < 0.05). Moreover, the serum levels of alanine aminotransferase, triglyceride, low-density lipoprotein, total cholesterol and CK-18 M30 in the NASH group were higher (P < 0.05) and positively correlated with liver pathological scores (P < 0.05), but IL-28B in serum and liver tissue was lower (P < 0.05) and negatively correlated with liver pathological scores (P < 0.05). According to the ROC curves, the sensitivity/specificity of each index was shown as following: liver pathological scores (1.000/1.000), IL-28B of liver tissue (1.000/0.857), serum CK-18 M30 plus IL-28B (0.857/1.000), serum IL-28B (0.857/0.857) and serum CK-18 M30 (1.000/0.857).

Conclusions: IL-28B level is related to the pathological changes of livers in SD rats during the development of NASH. The combination of serum CK-18 M30 level and serum IL-28B level may be a promising non-invasive detection method for the diagnosis of NASH.
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http://dx.doi.org/10.1016/j.prp.2020.152901DOI Listing
April 2020

Rectal Nonsteroidal Anti-Inflammatory Drugs for Endoscopic Retrograde Cholangiopancreatography Postoperative Pancreatitis Prevention: A Network Meta-Analysis.

J Clin Gastroenterol 2020 04;54(4):305-313

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an.

Background: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication of ERCP procedure. Nonsteroidal anti-inflammatory drugs (NSAIDs) are reported to be one protective pharmacological agent with great efficacy regarding this complication. Recently, more trails have addressed this issue and some inconsistent results appeared. Therefore, this study aims to evaluate the efficacy and safety of different rectal NSAIDs schemes to prevent PEP.

Materials And Methods: Eligible studies published on PubMed, the Cochrane Library, Embase, Web of Science before November 2018 were reviewed, and those which met the inclusion criteria were included in the analysis. The preventions were divided as placebo/no treatment, post-ERCP rectal diclofenac, pre-ERCP rectal diclofenac, post-ERCP rectal indomethacin, pre-ERCP rectal indomethacin, indomethacin using during ERCP, and pre-ERCP rectal naproxen. The main outcomes included the incidence of PEP and its severity. Other complications were also analyzed.

Results: A total of 23 randomized controlled trials were included. The results of network meta-analysis illustrated that compared with the control, post-ERCP rectal diclofenac, pre-ERCP rectal diclofenac, and indomethacin were significantly associated with lower incidences of PEP. Moreover, it is notable that pre-ERCP rectal NSAIDs might reduce the severity of pancreatitis. Also, rectal NSAIDs may lead to less occurrence of asymptomatic hyperamylasemia. On the basis of the clustered ranking, pre-ERCP diclofenac appeared to be the superior intervention for PEP with satisfying efficacy.

Conclusions: The present study showed that pre-ERCP diclofenac is the optimal prevention method for PEP. However, more high quality head-to-head randomized controlled trials and observational studies are expected in the future.
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http://dx.doi.org/10.1097/MCG.0000000000001322DOI Listing
April 2020

Analysis of the relationship between MIR155HG variants and gastric Cancer susceptibility.

BMC Gastroenterol 2020 Jan 20;20(1):17. Epub 2020 Jan 20.

Department of gastroenterology, First Affiliate Hospital of Xi'an JiaoTong University, #227 West Yanta Road, Xi'an, 710061, Shaanxi Province, China.

Background: Gastric cancer is one of the most common cancers in the world and a major cause of cancer-related death. This study aims to determine whether genetic variations in MIR155HG could be associated with gastric cancer risk.

Materials & Methods: A total of 506 gastric cancer patients and 500 healthy controls were enrolled in this study. Genotypes were examined with the MassARRAY platform and data management and analysis were conducted with the Typer Software. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated with logistic regression adjusting for age and gender to evaluate the associations between SNPs with gastric cancer in genetic model analysis.

Results: The "CC" genotype of rs4143370 decreased the risk of gastric cancer in genotype model (p = 0.020) and recessive model (p = 0.018). Inversely, the "CC" genotype of rs1893650 increased the risk of gastric cancer in genotype model (p = 0.023) and recessive model (p = 0.014). Stratified analysis showed that rs11911469 was associated with an increased risk of gastric cancer only among the male group in the dominant model (p = 0.039) and additive model (p = 0.030). The haplotype analysis showed a strong linkage disequilibrium among these six SNPs (rs4143370, rs77699734, rs11911469, rs1893650, rs34904192 and rs928883).

Conclusion: This study confirmed the relationship between SNPs of MIR155HG and the gastric cancer risk among the Chinese Han population. Our data may provide a new perspective to understand the aetiology of gastric cancer.
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http://dx.doi.org/10.1186/s12876-020-1169-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972026PMC
January 2020

Gastrectomy Versus Endoscopic Resection for Patients With Early-stage Gastric Adenocarcinoma: A Population-based Propensity Matching Study.

J Clin Gastroenterol 2020 Nov/Dec;54(10):871-878

Departments of Gastroenterology.

Background: This study aimed to compare the long-term results of patients who received these therapies.

Materials And Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried in this research for data of patients with early gastric adenocarcinoma who underwent gastrectomy or endoscopic resection from 2007 to 2015. Propensity score matching was selected to generate a balanced cohort. Competing-risk regression analysis was carried out on the matched cohort. Cancer-specific mortality (CSM) and other cause-specific mortality (OCSM) were compared using adjusted subdistribution hazard ratios (SHRs).

Results: In this study, 2214 patients with 191 underwent endoscopic treatment (ET) and 2023 who underwent surgery were identified. After propensity score matching, 474 patients were included in the analysis. The use of ET increased over time in patients, especially for those with cardia diseases. The ratio of 5-year CSM between ET and gastrectomy groups was 13.12% to 14.24% and the ratio of 5-year OCSM between them was 22.48% versus 14.31%. After adjusting for associated clinicopathologic factors, patients in both groups had similar CSM (SHR=0.87, 95% credible interval: 0.47-1.64, P=0.69) and OCSM (SHR=1.59, 95% credible interval: 0.94-2.68, P=0.08) in multivariable analysis.

Conclusion: The long-term prognosis appears equivalent t in patients with endoscopic resection and gastrectomy.
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http://dx.doi.org/10.1097/MCG.0000000000001306DOI Listing
December 2019

[Histone deacetylase 3 inhibitor alleviates alcohol-induced disruption of intestinal epithelial barrier via inhibiting nuclear factor κB].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2019 Sep;35(9):800-805

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. *Corresponding authors, E-mail:

Objective To investigate the role and mechanism of histone deacetylase 3 (HDAC3) in alcohol-induced inflammation and permeability of intestinal epithelial cells. Methods To select the proper concentration of alcohol, differentiated Caco-2 cells were treated with different concentrations (10, 25, 50, 100 and 200 mmol/L) of alcohol, and then cell viability was assayed by MTT assay; the mRNA and protein levels of HDAC3 were analyzed by real-time PCR and Western blot analysis. Differentiated Caco-2 cells were divided into three groups: control group, alcohol group (treatment with 50 mmol/L alcohol for 60 minutes), and alcohol combined with HDAC3 inhibitor group (pretreatment with 2 μmol/L RGFP966 1 hour before alcohol). ELISA was performed to detect tumor necrosis factor α (TNF-α) level in cell supernatant. Transepithelial electrical resistance (TER) was measured using a resistance meter. Western blot analysis was used to determine the protein levels relevant to tight junction (occludin and claudin-1) and NF-κB activation (IκB and phosphorylated NF-κBp65). Results Alcohol at 10, 25 and 50 mmol/L did not affect cell viability. The mRNA and protein expression levels of HDAC3 increased in a dose-dependent manner after alcohol treatment at these concentration s. Compared with the control group, TNF-α and phosphorylated NF-κBp65 levels increased, whereas TER and protein levels of occludin, claudin-1 and IκB decreased in the alcohol group. Compared with the alcohol group, TNF-α and phosphorylated NF-κBp65 levels were reduced, while TER and protein levels of occludin, claudin-1 and IκB were elevated in the alcohol combined with HDAC3 inhibitor group. Conclusion HDAC3 inhibition can attenuate alcohol-induced inflammation and permeability of intestinal epithelial cells, which may be related to the inactivation of NF-κB.
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September 2019

Management of Helicobacter pylori infection by clinicians: A nationwide survey in a developing country.

Helicobacter 2019 Dec 1;24(6):e12656. Epub 2019 Oct 1.

Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.

Background & Aims: Developing countries are making efforts to improve health management. Practice deviating from the guideline means inefficient control. The study aims to investigate the management of Helicobacter pylori (H pylori) infection from a developing country perspective.

Methods: An authoritative survey was conducted in 14th (2014) and 17th (2017) Congress of Gastroenterology China, respectively. The Maastricht V/Florence consensus report was invoked as the evaluation criterion.

Results: A total of 4182 valid samples were included in this study. Most of the respondents (94%) updated knowledge by lectures. Respondents had a different awareness rate of H pylori-related diseases, ranging from 45% to 95%. Up to 40% of the respondents did not follow the recommendations for the diagnosis. Choice accuracy of eradication regimens and antibiotic combinations was <70%. About 20% of the respondents did not pay attention to the confirmation after the eradication. The situation had been improved in 2017 when compared with that in 2014 (all P < .05). Multivariate logistic regression analysis revealed that influencing factors including nongastroenterologists, bachelor degree and below, the primary professional title, hospital location, and a small proportion of H pylori infection in daily practice related to the deviation of consensus (all P < .05).

Conclusions: Although the management of H pylori infection has been improved in a developing country, there is still a gap between the real-world practices and the consensus. Influencing factors should be taken into account in decision-making, and the corresponding population should be strengthened with precision training during the promotion of the guideline.
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http://dx.doi.org/10.1111/hel.12656DOI Listing
December 2019

The comprehensive pathophysiological changes in a novel rat model of postinflammatory visceral hypersensitivity.

FASEB J 2019 12 28;33(12):13560-13571. Epub 2019 Sep 28.

Department of Digestive Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

So far, a comprehensive animal model that can mimic both the central and peripheral pathophysiological changes of irritable bowel syndrome (IBS) is lacking. Here, we developed a novel IBS rat model combining trinitro-benzene-sulfonic acid (TNBS) and chronic unpredictable mild stress (CUMS) (designated as TC-IBS) and compared it with the TNBS-induced and CUMS-induced models. TC-IBS showed a pronounced depression phenotype with increased corticotropin-releasing hormone receptor (CRHR)1 and CRHR2 expression at the frontal cortex and increased serum ACTH concentration. Visceral hypersensitivity (VH), as evidenced by colorectal distention (CRD) test, was highest in TC-IBS, accompanied by increased serum 5-hydroxytryptamine (5-HT) level and colonic 5-HT receptor 3A (5-HTR)/5-HT receptor 2B expression, impaired tight junction protein expression including occludin, zonula occludens-1, and phosphorylated myosin light chain. Palonosetron, a second generation of 5-HTR antagonist, alleviated VH significantly in TC-IBS. 16S rRNA sequencing showed that TNBS plus CUMS induced a significant disturbance of the gut microbiota. Cytokine profile analysis of TC-IBS model indicated an innate immune activation both in serum and colonic mucosa. Further, fecal microbiota transplantation improved VH and some pathophysiological changes in TC-IBS. In summary, we established a postinflammatory IBS model covering multifactorial pathophysiological changes, which may help to develop therapies that target specific IBS subtype.-Ma, J., Li, J., Qian, M., He, N., Cao, Y., Liu, Y., Wu, K., He, S. The comprehensive pathophysiological changes in a novel rat model of postinflammatory visceral hypersensitivity.
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http://dx.doi.org/10.1096/fj.201901489RDOI Listing
December 2019

Long non-coding RNA SNAI3-AS1 promotes the proliferation and metastasis of hepatocellular carcinoma by regulating the UPF1/Smad7 signalling pathway.

J Cell Mol Med 2019 09 2;23(9):6271-6282. Epub 2019 Jul 2.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Emerging evidence has indicated that deregulation of long non-coding RNAs (lncRNAs) can contribute to the progression of human cancers, including hepatocellular carcinoma (HCC). However, the role and exact mechanism of most lncRNAs in tumours remains largely unknown. In the current study, we found a novel long non-coding RNA termed SNAI3-AS1 which was generally up-regulated in HCC tissues compared with normal control. Higher expression of SNAI3-AS1 was significantly correlated with shorter overall survival of HCC patients. Knockdown of SNAI3-AS1 inhibited the proliferation and metastasis of HCC cells in vitro, whereas overexpression of SNAI3-AS1 promoted the proliferation and metastasis of HCC cells. Further investigations showed that SNAI3-AS1 could affect HCC tumorigenesis by binding up-frameshift protein 1 (UPF1), regulating Smad7 expression and activating TGF-β/Smad pathway. Functionally, SNAI3-AS1 promoted HCC growth and metastasis by inducing tumour epithelial to mesenchymal transition (EMT). Taken together, these findings showed that SNAI3-AS1 promotes the progression of HCC by regulating the UPF1 and activating TGF-β/Smad pathway.
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http://dx.doi.org/10.1111/jcmm.14513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714236PMC
September 2019