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Helicobacter pylori (Hp) infection is one of the main causes of gastric cancer. The virulence factors of Hp, cytotoxin⁃associated gene A (CagA) and vacuolating cytotoxin A (VacA), are closely related to the pathogenicity of Hp in European and American countries. However, the positivity rate of CagA is as high as 90% in East Asian countries, indicating that the above⁃mentioned virulence factors could not fully explain the differences in pathogenicity of Hp, and other pathogenic factors might be speculated. In our previous studies, thioredoxin⁃1 (Trx1) was found to be a virulence factor of highly pathogenic Hp, and a series of studies were conducted on Hp Trx1 in cytology, zoology and human histology. This article reviewed the progress in research on Hp Trx1.
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Objective:To preliminarily understand the living habits, medication taking and treatment status including the therapeutic regimen, compliance and short-term efficacy of patients with chronic atrophic gastritis and erosion in Beijing area.Methods:From April to September in 2019 at Peking Union Medical College Hospital, Peking University Third Hospital and Peking University Shougang Hospital, the outpatients with chronic atrophic gastritis and erosion diagnosed with endoscopy within two weeks before visiting were prospectively included in this non-interventional observation study. Chi square test was used for statistical analysis.Results:A total of 277 patients with chronic atrophic gastritis and erosion had complete follow-up data, of which male patients accounted for 49.8% (138/277). The common initial symptoms of patients with chronic atrophic gastritis and erosion included acid reflux, abdominal distension, epigastric pain and postprandial distension, which accounted for 60.3% (167/277), 59.6% (165/277) , 58.8% (163/277) and 52.3% (145/277), respectively. For treatment, 36.8% (102/277) of the patients only received lifestyle instruction without medication. Among the patients with medication treatment, the short-term efficacy of gastric mucosal protectants+ proton pump inhibitor+ gastro-kinetic agent for abnominal distension, postprandial distention, acid reflux and nausea was highest as compared with other therapeutic regimen, and the differences were statistically significant ( χ2=25.18, 19.49, 13.75, 8.84, all P<0.05). Conclusions:Chronic gastritis with erosion may be caused by a combination of multiple factors, and the symptoms of which lack specific. If necessary, gastroscopy may help the diagnosis. Individualized treatment strategies based on the symptoms of patients is needed for treatment.
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Gastric cancer is a malignant tumor with worldwide high incidence and threatening the human health severely. It is a disease induced by multiple factors. Exosomes play an important role in the pathogenesis and development of many malignant tumors including gastric cancer. Exosomes can transport specific contents to regulate local and distant cell communications, and are able to promote or inhibit the development of gastric cancer through regulating the growth and proliferation of tumor cells, relevant immune function and angiogenesis of tumors. This article reviewed the effects of exosomes and their contents on the pathogenesis and development of gastric cancer.
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Helicobacter pylori (Hp) is a Gram-negative bacterium selectively colonized in gastric mucosa, and is one of the main factors inducing chronic gastritis and even gastric cancer. Recent studies have shown that Hp infection induces various stress responses, including oxidative stress, nitrosative stress and endoplasmic reticulum stress. Hp can stimulate neutrophils, macrophages and gastric epithelial cells to express reactive oxygen species and reactive nitrogen species, resulting in excessive accumulation of reactive oxygen species and reactive nitrogen species, aggravating inflammation and damage to gastric mucosa. Such long-term inflammation and oxidative stress may increase the risk of cancer. In addition, Hp induced endoplasmic reticulum stress plays an important role in the early stages of precancerous lesion formation. This article reviewed the research progress of role of stress response induced by Hp infection in gastric mucosal diseases.
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Helicobacter pylori (Hp) is a microaerophilic Gram-negative bacterium that colonizes the gastric mucosa. After colonization, many proteins expressed by Hp, such as Helicobacter pylori urease (HPU), neutrophil-activating protein (NAP), outer membrane protein (OMP), cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA), may serve as antigens to mediate neutrophil chemotaxis. Thereafter, neutrophils infiltrate in gastric mucosa and play roles in mucosal immunity via secreting cytokines and releasing reactive oxygen species (ROS) and myeloperoxidase (MPO). This article reviewed the advances in study on the role of neutrophil infiltration in Hp infection-related diseases.
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Background: Long-term use of aspirin can cause varying degrees of gastric mucosal injuries. Hydrotalcite may play a protective role on gastric mucosal injuries through multiple mechanisms. Aims: To investigate the protective effect of hydrotalcite on aspirin-induced gastric mucosal injury and its possible mechanism in an in vitro study. Methods: Human gastric mucosal epithelial cell line GES-1 was selected and divided into three groups: normal control group, injury group and protection group. GES-1 cells in the latter two groups were co-cultured with aspirin (9 mmol/L), and cells in the protection group was further treated with hydrotalcite (0.6 mg/mL) after aspirin administration. After culturing for 12 hours, morphology of GES-1 cells was observed by inverted microscope and transmission electron microscope. Cell proliferation and apoptosis were assessed by MTT assay and flow cytometry, respectively. Proteomics was used to identify the differentially expressed proteins between injury group and protection group. Results: Compared with the injury group, GES-1 cells in the protection group remained in a relatively intact structure with higher survival rate and lower apoptosis rate (P<0.05). Proteomics revealed that the expressions of T-complex protein 1 subunit beta (TCP-1β) and thioredoxin-dependent peroxide reductase 3 (PRX3), which were related with protein folding and assembly, cytoskeleton function, and antioxidative stress, were up-regulated in GES-1 cells in the protection group. Conclusions: Hydrotalcite can reduce the aspirin-induced gastric mucosal injury via promoting cell proliferation and inhibiting apoptosis. Improvement of the structure and function of intracellular proteins and antioxidative stress might be implicated in its cytoprotective effect.
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Objective:To evaluate the clinical prognostic significance of molecular markers with high predictive value for lymph node metastasis (LNM) before operation in gastric cancer (GC).Methods:From January 2013 to December 2015, at Peking University Third Hospital, 85 patients with GC confirmed by preoperative biopsy under gastroendoscopy and receiving radical gastrectomy were selected. Among 85 patients with GC, 34 patients had LNM and the other 51 patients were without LNM. The expression levels of macrophage capping protein G (CapG), tyrosine kinase receptor B (TrkB), prosperohomeobox protein l (Prox-1), matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor receptor 3 (VEGFR3) were detected by immunohistochemistry (IHC) in preoperative gastric biopsy tissues. Chi-square test was performed to analyze the correlation between the expression of different markers and various clinicopathological characteristics. Receiver operating characteristic (ROC) curve was drawn to compare the predictive value of different markers on LNM of GC. Kaplan-Meier curve was applied to evaluate the impact of different markers on the prognosis of GC patients.Results:The positive expression rates of CapG, TrkB, Prox-1, MMP-2, VEGF-C and VEGFR3 of the LNM-positive group were higher than those of the LNM-negative group (85.3%, 29/34 vs. 35.3%, 18/51; 76.5%, 26/34 vs. 29.4%, 15/51; 67.6%, 23/34 vs. 11.8%, 6/51; 64.7%, 22/34 vs. 33.3%, 17/51; 61.8%, 21/34 vs. 29.4%, 15/51; 52.9%, 18/34 vs. 23.5%, 12/51, respectively), and the differences were statistically significant ( χ2=20.631, 18.093, 28.342, 8.086, 8.746 and 7.727, all P<0.01). The area under the ROC curve (AUC) values and 95% confidence interval ( CI) of CapG, TrkB, Prox-1, MMP-2, VEGF-C and VEGFR3 in predicting LNM of GC before operation were 0.787 (0.687 to 0.880), 0.772 (0.656 to 0.860), 0.761 (0.661 to 0.883), 0.724 (0.618 to 0.830), 0.687 (0.571 to 0.803) and 0.583 (0.452 to 0.715), respectively. Among them, the AUC values of CapG, Prox-1 and TrkB were relatively high. The expression levels of CapG and Prox-1 were correlated with invasion depth and TNM stage of GC ( χ2=4.792, 13.664, 4.204 and 19.948, all P<0.05). And TrkB expression was correlated with TNM stage of GC ( χ2=12.036, P<0.05). Kaplan-Meier curves revealed that the overall survival rates of CapG, TrkB or Prox-1 positive groups were significantly lower than those of CapG, TrkB or Prox-1 negative groups (70.2%, 33/47 vs. 94.7%, 36/38; 70.7%, 29/41 vs. 90.9%, 40/44; 69.0%, 20/29 vs. 87.5%, 49/56, respectively), and the differences were statistically significant ( χ2=9.820, 4.909 and 4.683, all P<0.05). Conclusions:CapG, TrkB and Prox-1 are markers with relatively high predictive value for LNM of GC, and all of them are correlated with the progression and poor prognosis of GC.
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LGR6 is a member of the G protein-coupled receptor family that plays a tumor-suppressive role in colon cancer. However, the relationship between LGR6 expression in patients and clinicopathological factors remains unclear. This study aimed to clarify whether the expression level of LGR6 is correlated with colon adenocarcinoma progression. Immunohistochemistry was used to detect LGR6 expression in colon adenoma tissues (n = 21), colon adenocarcinoma tissues (n = 156), and adjacent normal tissues (n = 124). The expression levels of LGR6 in colon adenoma and adenocarcinoma were significantly higher than those in normal colon epithelial tissues (P < 0.001). Low LGR6 expression predicted a short overall survival in patients with colon adenocarcinoma (log-rank test, P = 0.016). Univariate and multivariate survival analyses showed that, in addition to N and M classification, LGR6 expression served as an independent prognostic factor. Thus, low expression of LGR6 can be used as an independent prognostic parameter in patients with colon adenocarcinoma.
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With the development of endoscopic technology,the detection rate of early gastric cancer has increased in recent years. Lymph node metastasis is of crucial importance for planning appropriate treatment and determining prognosis in patients with early gastric cancer. Accurate assessment of lymph node status preoperatively can help for choosing the optimal treatment strategy,thereby reducing surgical injury,improving postoperative quality of life and improving the long-term outcome. This article reviewed the advances in research on clinical detection methods of lymph node metastasis in early gastric cancer.
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Inflammatory Bowel Disease ( IBD) comprises of ulcerative colitis ( UC) and Crohn′s disease ( CD ) , is lack of gold standard for diagnosis by now . To distinguish UC and CD requires comprehensive clinical manifestations , laboratory tests, radiological examinations , endoscopic characteristics and biopsies, etc.Taking the advantages of convenience , noninvasion, efficiency and economic, laboratory examinations especially great progress made in the research of anti-microbial antibodies , have a great value in diagnosis , differential diagnosis , therapeutic effect evaluation and prognosis judgment of IBD .
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Objective To explore the mechanism underlying the inhibitory effects of Hydrotalcite on Helicobacter pylori (H.pylori).Methods H.pylori international standard strain 26695 was resuscitated and incubated in Columbia solid culture medium and brucella broth.It was divided int6 blank control group,H.pylori injured group and H.pylori with Hydrotalcite group.H.pylori were treated by Hydrotalcite,and the viability changes of H.pylori were observed.The morphological changes of H.pylori were detected by Gram's stain.The changes of mycoproteins expression of H.pylori were examined by Coomassie blue stain.The effects of H.pylori on cell apoptosis of gastric epithelial cell line GES-1 was compared between groups with and without Hydrotalcite.Subcellular structure and attachment ability of H.pylori on GES-1 cells were observed with transmission electron microscopy and scanning electron microscopy.T test was performed for statistical analysis.Results Hydrotalcite could inhibit the growth of H.pylori.However there were no significant morphological changes of H.pylori.Many mycoproteins were regulated by Hydrotalcite.Without Hydrotalcite,a large amount of H.pylori attached on the cell surface of GES-1 promoted the apoptosis of GES-1 cell.Compared with blank control group,the apoptosis rate of GES-1 cells increased after treated by H.pylori ((5.52 ± 1.31)％ vs (28.96 ±3.14)％),and the difference was statistically significant (t=-11.94,P＜0.05).Hydrotalcite could prevent the attachment of H.pylori on cells,which reduced the apoptosis caused by H.pylori ((28.96 ±3.14) ％ vs (19.38 ± 1.91) ％),and the difference was stattstically significant (t =4.52,P ＜ 0.05).Conclusion Hydrotalcite has inhibitory effects on H.pylori in vitro and play a role in regulation of many mycoproteins.Hydrotalcite can reduce the attachment of H.pylori on gastric epithelial cells,and protect cells from H.pylori injury.
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Neuroendocrine neoplasm (NEN)is a group of heterogeneous tumor originated from the neuroendocrine system,and gastrointestinal neuroendocrine neoplasm (GI-NEN)is the mostly frequently seen. The incidence of GI-NEN is increasing year by year,but the efficacy of clinical treatment is unsatisfactory. In recent years,new progress has been achieved in medical therapy of GI-NEN,including somatostatin analogues,interferon,mTOR inhibitor,vascular endothelial growth factor inhibitor and chemotherapeutic drugs. Peptide receptor radionuclide therapy also provides an additional option for treatment of metastatic GI-NEN. This article reviewed the recent progress of drug treatment for GI-NEN.
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Objective: To investigate the effect of macrophage-capping protein (CapG) on migration and proliferation of human gastric cancer cell line.Methods: Real-time PCR method was used to detect the expression of CapG gene in four gastric cancer cell lines, and AGS cells with low expression and transfection were selected as the research objects.Specific primers were designed for CapG and recombinant plasmids synthesized.A lentivirus packaging system which could express CapG was constructed, and a cell line stably expressing CapG was established by infecting human gastric cancer cell line AGS cells.The effect of overexpression of CapG gene on the growth and proliferation of AGS cells was analyzed by CCK8 assay.Cells cratch and Transwell assay were used to analyze the effect of overexpression of CapG gene on AGS cell migration.Results: After the overexpression of CapG, the growth rate of AGS cells was slightly lower than that of the control group, but there was no significant difference between the two groups (t=2.424, P=0.073).Scratch test showed that the average narrowing distance of the scratches in the CapG experimental group was significantly reduced compared with the control group, the average narrowing distance of the CapG experimental group and the control group was 336.99 μm and 45.54 μm, the difference was statistically significant (t=14.97, P=0.004).The average number of cell penetra-ting membrane in the CapG experimental group and the eGFP control group was 176 and 70, the number of the cells in the CapG experimental group was significantly higher than that of the control group (t=40.00, P<0.001).Conclusion: The overexpression of CapG gene has no significant effect on the growth and proliferation of AGS cells of gastric cancer cell line.Overexpression of CapG gene can promote the migration of AGS cells of gastric cancer cell lines.
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Background: CKLF-like MARVEL transmembrane domain containing (CMTM) superfamily is involved in the occurrence and development of inflammation, cancer and a variety of diseases.Human CMTM3 has been proposed as a putative tumor suppressor gene.Aims: To investigate the expression of CMTM3 in Helicobacter pylori (Hp) infection-related chronic gastritis and its significance.Methods: Sixty cases of outpatients with chronic gastritis (30 Hp-positive and 30 Hp-negative) were enrolled for detection of CMTM3 and interleukin-6 (IL-6) expressions in gastric mucosa by immunohistochemistry.The correlation of expressions of CMTM3 and IL-6 was analyzed.Results: The positivity rates of CMTM3 and IL-6 in gastric mucosa were significantly higher in Hp-positive chronic gastritis than in Hp-negative ones (CMTM3: 63.3% vs.30.0%, P<0.05;IL-6: 73.3% vs.13.3%, P<0.01).In patients with Hp-positive chronic gastritis, CMTM3 and IL-6 were co-expressed in 53.3% (16/30) of the patients and localized in the same position.Expression of CMTM3 was positively correlated with IL-6 expression in Hp-positive chronic gastritis patients (r=0.58, P<0.05).Conclusions: CMTM3 is highly expressed in chronic gastritis patients with Hp infection.It may participate in the occurrence and development of Hp infection-related chronic gastritis with inflammatory cytokines such as IL-6.Hp infection might be one of the mechanisms involved in CMTM3 up-regulation.
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[Summary] Gastric cancer is seriously dangerous to human health with constantly high incidence .Human gastric mucosa can express gastrokines that can inhibit cancer cell growth .Gastrokines is expressed abundantly in normal tissues while downregulated or absent in gastric cancer and precancerous lesion .It plays an important role in the suppression of gastric cancer proliferation combining with the other factors such as helicobacter pylori infection or trefoil factors .In this paper we made a review about the suppression of gastrokines on gastric cancer cell proliferation .
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Bile reflux is not only related to diseases such as gastritis,esophagitis,pharyngitis,chorditis,bronchitis and pneumonia,but also related to residual gastric ulcer,residual gastric cancer,intestinal metaplasia,dysplasia and carcinogenesis. Risk factors related to bile reflux include various operation modes, various anastomosis methods, gallbladder stone, cholecystectomy and various non-operative factors such as age, gender, allergy, mental and psychological factors,congenital factors. This article reviewed the advances in study on risk factors related to bile reflux.
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Objective:To establish a Mongolian gerbils model by long-term infection of Helicobacter py-lori (Hp) with highly-expressed thioredoxin-1 (Trx1 ) gene and to investigate the histopathological findings of gastric mucosa in Mongolian gerbils.Methods:In this study,75 healthy male Mongolian ger-bils were randomly divided into 3 groups:Hp with highly-expressed Trx1 gene group (n =30),Hp with lowly-expressed Trx1 gene group (n =30),and control group (n =15).The animals underwent gastric perfusion of Hp suspension once a week for 5 weeks.The animals were sacrificed at the end of 4,20, 34,48,70,and 90 weeks after inoculation for detecting Hp colonization by rapid urease test and War-thin-Starry silver staining and histological examination,respectively.Results:(1)The Mongolian gerbil model of long-term infection of Hp with highly-expressed Trx1 gene and lowly-expressed Trx1 gene were successfully established.(2)The macroscopic mucosal lesions,including erythema,uneven,erosion, nodules,etc.could be observed in experimental groups.The severity of lesions and the time when lesions occurred in Hp with highly-expressed Trx1 gene group were heavier/earlier than that in Hp with lowly-ex-pressed Trx1 gene group.(3)Histopathologically,the gastric mucosa of Hp with highly-expressed Trx1 gene group showed the mild dysplastic hyperplasia of epithelial cells 34 weeks after the Hp inoculation, and the time was in the 48th week in Hp with lowly-expressed Trx1 gene group.At the end of the 90th week after Hp inoculation,the gastric adenocarcinoma could be detected in the two experimental groups (71.4% vs.42.8%).The difference between the two experimental groups did not reach statistical sig-nificance (P =0.592),which might be due to the small sample capacity and /or short observation time. In addition,there were 2 cases with severe epithelial dysplastic hyperplasia in Hp with highly-expressed Trx1 gene group,and only 3 cases with moderate epithelial dysplastic hyperplasia in Hp with lowly-ex-pressed Trx1 gene group.The uninfected control animals showed no abnormal findings throughout the en-tire observation period.Conclusion:Hp with highly-expressed /lowly-expressed Trx1 gene colonizes stab-ly in the glandular gastric mucosa of Mongolian gerbils.The histological changes after infection are similar to those of the Hp infected human being,and Hp with highly-expressed Trx1 gene cause the injury of gas-tric mucosa and the occurrence of gastric adenocarcinoma.Trx1 maybe the virulence factor that partici-pates in the pathogenesis of gastric cancer and Hp expressing high levels of Trx1 should be highly toxic for gastric diseases in China.
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CMTM3 and CMTM7 are two newly discovered anti-oncogenes,which exist in various kinds of organs and tissues and having multiple biological functions including cell proliferation,differentiation,migration,and apoptosis. Recently,it has been shown that these two anti-oncogenes have closely relationship with gastrointestinal tract tumor,which can inhibit the growth of esophageal,gastric,and colorectal cancer. In this review article,the advances in study of the relationship between these two anti-oncogenes and tumors of gastrointestinal tract were summarized.
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Objective To explore the clinical significance of typical reflux symptoms in the diagnosis of gastroesophageal reflux disease (GERD).Methods Consecutive patients older than 16 years,who initially visited department of gastroenterology at clinic of Peking University Third Hospital from May 9,2012 to Dec 31,2012,were required to complete a self-reported GERD questionnaire.Upper endoscopy was performed in some selected patients.Results A total of 18 987 patients were enrolled with a response rate of 91.5％.The prevalence of symptom-defined GERD was 13.6％ (2 579/18 987).A total of 4 357 (22.9％) patients underwent the upper endoscopy,and the diagnostic rates of reflux esophagitis,Barrett's esophagus,peptic ulcer disease,and upper gastrointestinal malignancy were 13.1％ (572/4 357),1.8％ (78/4 357),10.5％ (456/4 357),and 1.7％ (75/4 357),respectively.The incidence of reflux esophagitis was 22.7％ (216/951) in patients with reflux symptoms and 10.5％ (356/3 406) (P ＜0.001) in patients without reflux symptoms,2.7％ (26/951) and 1.5 ％ (52/3 406),respectively (P =0.013) for Barrett's esophagus; 6.8％ (65/951) and 11.5％ (391/3 406),respectively (P＜0.001) for peptic ulcer disease; 1.7％ (16/951) and 1.7％ (59/3 406),respectively (P =0.917) for upper gastrointestinal malignancy.Conclusions GERD is one of the major diseases at gastroenterology clinic.Typical reflux symptoms suggest a diagnosis of GERD.But some patients with peptic ulcer disease or upper gastrointestinal malignancy can also present typical reflux symptoms.Upper endoscopy is valuable to avoid the misdiagnosis of other disorders.
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<p><b>BACKGROUND</b>Helicobacter pylori (Hp) is a common and potentially curable cause of gastric mucosa lesion. This study investigated the relationship of Hp infection with histological changes in gastric mucosa and gastric cancer in Hp-positive patients compared with Hp-eradication patients followed up for ten years.</p><p><b>METHODS</b>From an initial group of 1 006 adults, 552 Hp-positive subjects were randomly assigned to a treatment group (T; n = 276) or a placebo group (P; n = 276). In the randomized, double-blind, placebo-controlled, parallel trial, T group subjects received oral doses of omeprazole, amoxicillin and clarithromycin for 1 week; those in the P group received a placebo. One month after treatment ended, a 13C urea breath test was performed, and Hp was undetectable in 88.89% of the T group. All subjects were followed at 1, 5, 8, and 10 years after treatment, with endoscopy and biopsies for histological examination.</p><p><b>RESULTS</b>Gastric mucosa inflammation was significantly milder in the T group than that in the P group one year after Hp eradication and this persisted for 10 years. Glandular atrophy and intestinal metaplasia (IM) had deteriorated in both groups during ten years. However, the increased score of glandular atrophy at both the gastric antrum and corpus, and IM only at the gastric antrum, in the P group was more obvious than that in the T group. During the 10 years, 9 patients were diagnosed with gastric cancer (2 in the T group; 7 in the P group; P = 0.176). When mucosal atrophy was absent at the gastric antrum and corpus when entering the study, the incidence of gastric cancer in the P group (n = 6) was much higher than that in the T group (n = 0, P = 0.013).</p><p><b>CONCLUSIONS</b>Hp eradication may significantly diminish and help halt progression of gastric mucosal inflammation and delay the development of IM and atrophy gastritis. Hp eradication is helpful for reducing the risk for gastric cancer, especially in the early stage of Hp infection.</p>