Pepsinogen,secreted from the gastric mucosa,is the precursor of pepsin.It is categorized as pepsinogen 1 and pepsinogen 2 based on its immunogenicity.The pepsinogen content that can enter the blood circulation through...Pepsinogen,secreted from the gastric mucosa,is the precursor of pepsin.It is categorized as pepsinogen 1 and pepsinogen 2 based on its immunogenicity.The pepsinogen content that can enter the blood circulation through the capillaries of the gastric mucosa is approximately 1%and remains stable all the time.The pepsinogen content in serum will change with the pathological changes of gastric mucosa.Therefore,the level of pepsinogen in serum can play a role in serologic biopsy to reflect the function and morphology of different regions of gastric mucosa and serve as an indicator of gastric disease.This study conducts relevant research on serum pepsinogen 1,pepsinogen 2,and the ratio of pepsinogen 1 to pepsinogen 2,and reviews their important value in clinical diagnosis of Helicobacter pylori infection,gastric ulcer,and even gastric carcinoma,providing ideas for other researchers.展开更多
AIM: To explore the correlation between Helicobacter pylori(H. pylori)-associated gastric diseases and colorectal neoplasia.METHODS: Patients included in this study underwent a colonoscopy and esophago-gastro-duodenos...AIM: To explore the correlation between Helicobacter pylori(H. pylori)-associated gastric diseases and colorectal neoplasia.METHODS: Patients included in this study underwent a colonoscopy and esophago-gastro-duodenoscopy(EGD) along with histopathological measurement between March 2012 and March 2015 at Qi-Lu Hospital of Shandong University, who also had results of H. pylori detection. A total of 233 cases were selected. Demographic data, H. pylori infection status(including results of rapid urease tests and gastric mucosa pathological examinations) and histopathological examination results of gastric and colorectal mucosa were gathered and analyzed. The statistical analysis focused on the prevalence of colorectal neoplasms among patients with various histopathological categories of the stomach. ORs and their 95%CI were calculated to describe the strengths of the associations.RESULTS: The incidence rates of colorectal adenoma without high-grade intraepithelial neoplasia(HGIEN)(OR = 2.400, 95%CI: 0.969-5.941), adenoma with HGIEN(5.333, 1.025-27.758) and adenocarcinoma(1.455, 0.382-5.543) were all higher for patients with H. pylori-associated gastritis than for those in the control group. The incidence rate of colorectal adenoma with HGIEN(3.218, 0.767-13.509) was higher in patients with intestinal metaplasia than in the control group, while the incidence rates of adenoma without HGIEN(0.874, 0.414-1.845) and adenocarcinoma(0.376, 0.096-1.470) were lower in the intestinal metaplasia group than in the control group. The incidence rate of colorectal adenoma without HGIEN(3.111, 1.248-7.753) was significantly higher in the gastric intraepithelial neoplasia group than in the control group, while the rates of adenoma with HGIEN(1.481, 0.138-15.941) and adenocarcinoma(2.020, 0.561-7.272) were higher in the gastric intraepithelial neoplasia group. Incidence rates of colorectal adenoma without HGIEN(1.067, 0.264-4.314), adenoma with HGIEN(2.667, 0.231-30.800) and adenocarcinoma(2.182, 0.450-10.585) were all higher in the gastric adenocarcinoma group than in the control group.CONCLUSION: H. pylori infection as well as H. pylori-associated gastric diseases are risk factors for colorectal neoplasia.展开更多
Objective: To investigate the difference in susceptibilities to allitridi of Helicobacter pylori (H.pylori) strains in different gastric diseases and the associations with different genotypes. Methods: H.pylori st...Objective: To investigate the difference in susceptibilities to allitridi of Helicobacter pylori (H.pylori) strains in different gastric diseases and the associations with different genotypes. Methods: H.pylori strains were isolated from gastric antral biopsy specimens and identified. DNA was isolated from H.pylori strains. Different genotypes were determined by polymerase chain reaction(PCR), and the allitridi MICs were determined by agar dilution methods. MIC50 was calculated. Results: The susceptibilities of H, pylori strains varied among different gastric diseases. H.pylori strains in superficial gastritis were significantly more susceptible to allitridi than those in atrophic gastritis (relative median potency was 0.49, 95% confidence interval was from 0.24 to 0.80), strains in superficial gastritis were significantly more susceptible than those in gastric cancer (relative median potency was 0.32, 95% confidence interval was from 0.06 to 0.68) and strains in atrophic gastritis were significantly more susceptible than those in gastric cancer(relative median potency was 0.16, 95% confidence interval was from 0.02 to 0.40). The susceptibilities of H.pylori strains with different genotypes varied among different gastric diseases. In atrophic gastritis, strains with vacAsl+ were significantly more susceptible to allitridi than those with vacAsl(relative median potency was 0.21, 95% confidence interval was from 0.04 to 0.73). In gastric cancer, strains with vacAmlb+ were significantly more susceptible than those with vacAmlb-(relative median potency was 0.07, 95% confidence interval was from 0.03 to 0.49). Conclusion: The vacA genotypes play an important role in the susceptibility to allitridi in different gastric diseases.展开更多
Altered micro RNA(mi RNA) associated with gastric cancer(GC) development and mi R-17 and mi R-106 b were differentially expressed in GC tissues. This study detected serum levels of mi R-17 and mi R-106 b expressio...Altered micro RNA(mi RNA) associated with gastric cancer(GC) development and mi R-17 and mi R-106 b were differentially expressed in GC tissues. This study detected serum levels of mi R-17 and mi R-106 b expression in GC, benign gastric disease(BGD) and healthy controls to assess them as tumor markers for GC. Serum samples from 40 GC, 32 BGD(10 gastric ulcer, 14 gastric polyps, and 8 gastric ulcer with polyps) and 36 healthy individuals were subjected to quantitative reverse transcription polymerase chain reaction(q RT-PCR) analysis of mi R-17 and mi R-106 b expression. The data showed that the serum levels of mi R-17 and mi R-106 b were significantly reduced in healthy individuals and BGD patients compared to GC patients. There was a significant association of mi R-17 and mi R-106 b expression with age, but not with other clinicopathological features, such as gender, tumor differentiation, stage and lymphatic metastasis. Further analysis showed that, in discriminating GC patients from healthy controls, mi R-17 could yield a receiver-operating characteristic(ROC) area under the curve(AUC) of 0.879 with 80.6% sensitivity and 87.5% specificity and mi R-106 b could yield an AUC of 0.856 with 75.0% sensitivity and 92.5% specificity. The combined AUC of mi R-17 and mi R-106 b was 0.913 with 83.3% sensitivity and 87.5% specificity. Collectively, these data suggest that detection of serum mi R-17 and mi R-106 b levels should be further evaluated as novel non-invasive biomarkers in early GC detection and surveillance of disease progression.展开更多
BACKGROUND Three-dimensional organoid culture systems have been established as a robust tool for elucidating mechanisms and performing drug efficacy testing.The use of gastric organoid models holds significant promise...BACKGROUND Three-dimensional organoid culture systems have been established as a robust tool for elucidating mechanisms and performing drug efficacy testing.The use of gastric organoid models holds significant promise for advancing personalized medicine research.However,a comprehensive bibliometric review of this burgeoning field has not yet been published.AIM To analyze and understand the development,impact,and direction of gastric organoid research using bibliometric methods using data from the Web of Science Core Collection(WoSCC)database.METHODS This analysis encompassed literature pertaining to gastric organoids published between 2010 and 2023,as indexed in the WoSCC.CiteSpace and VOSviewer were used to depict network maps illustrating collaborations among authors,institutions and keywords related to gastric organoid.Citation,co-citation,and burst analysis methodologies were applied to assess the impact and progress of research.RESULTS A total of 656 relevant studies were evaluated.The majority of research was published in gastroenterology-focused journals.Globally,Yana Zavros,Hans Clevers,James M Wells,Sina Bartfeld,and Chen Zheng were the 5 most productive authors,while Hans Clevers,Huch Meritxell,Johan H van Es,Marc Van de Wetering,and Sato Toshiro were the foremost influential scientists in this area.Institutions from the University Medical Center Utrecht,Netherlands Institute for Developmental Biology(Utrecht),and University of Cincinnati(Cincinnati,OH,United States)made the most significant contributions.Currently,gastric organoids are used mainly in studies investigating gastric cancer(GC),Helicobacter pylori-infective gastritis,with a focus on the mechanisms of GC,and drug screening tests.CONCLUSION Key focus areas of research using gastric organoids include unraveling disease mechanisms and enhancing drug screening techniques.Major contributions from renowned academic institutions highlight this field’s dynamic growth.展开更多
BACKGROUND Type I Helicobacter pylori(H.pylori)infection causes severe gastric inflammation and is a predisposing factor for gastric carcinogenesis.However,its infection status in stepwise gastric disease progression ...BACKGROUND Type I Helicobacter pylori(H.pylori)infection causes severe gastric inflammation and is a predisposing factor for gastric carcinogenesis.However,its infection status in stepwise gastric disease progression in this gastric cancer prevalent area has not been evaluated;it is also not known its impact on commonly used epidemiological gastric cancer risk markers such as gastrin-17(G-17)and pepsinogens(PGs)during clinical practice.AIM To explore the prevalence of type I and type II H.pylori infection status and their impact on G-17 and PG levels in clinical practice.METHODS Thirty-five hundred and seventy-two hospital admitted patients with upper gastrointestinal symptoms were examined,and 523 patients were enrolled in this study.H.pylori infection was confirmed by both 13C-urea breath test and serological assay.Patients were divided into non-atrophic gastritis(NAG),nonatrophic gastritis with erosion(NAGE),chronic atrophic gastritis(CAG),peptic ulcers(PU)and gastric cancer(GC)groups.Their serological G-17,PG I and PG II values and PG I/PG II ratio were also measured.RESULTS A total H.pylori infection rate of 3572 examined patients was 75.9%,the infection rate of 523 enrolled patients was 76.9%,among which type I H.pylori infection accounted for 72.4%(291/402)and type II was 27.6%;88.4%of GC patients were H.pylori positive,and 84.2%of them were type I infection,only 11.6%of GC patients were H.pylori negative.Infection rates of type I H.pylori in NAG,NAGE,CAG,PU and GC groups were 67.9%,62.7%,79.7%,77.6%and 84.2%,respectively.H.pylori infection resulted in significantly higher G-17 and PG II values and decreased PG I/PG II ratio.Both types of H.pylori induced higher G-17 level,but type I strain infection resulted in an increased PG II level and decreased PG I/PG II ratio in NAG,NAGE and CAG groups over uninfected controls.Overall PG I levels showed no difference among all disease groups and in the presence or absence of H.pylori;in stratified analysis,its level was increased in GC and PU patients in H.pylori and type I H.pylori-positive groups.CONCLUSION Type I H.pylori infection is the major form of infection in this geographic region,and a very low percentage(11.6%)of GC patients are not infected by H.pylori.Both types of H.pylori induce an increase in G-17 level,while type I H.pylori is the major strain that affects PG I and PG IIs level and PG I/PG II ratio in stepwise chronic gastric disease.The data provide insights into H.pylori infection status and indicate the necessity and urgency for bacteria eradication and disease prevention in clinical practice.展开更多
The gastrointestinal epithelium has cells with features that make them a powerful line of defense in innate mucosal immunity. Features that allow gastrointestinal epithelial cells to contribute in innate defense inclu...The gastrointestinal epithelium has cells with features that make them a powerful line of defense in innate mucosal immunity. Features that allow gastrointestinal epithelial cells to contribute in innate defense include cell barrier integrity, cell turnover, autophagy, and innate immune responses. Helicobacter pylori (H. pylori) is a spiral shape gram negative bacterium that selectively colonizes the gastric epithelium of more than half of the world’s population. The infection invariably becomes persistent due to highly specialized mechanisms that facilitate H. pylori’s avoidance of this initial line of host defense as well as adaptive immune mechanisms. The host response is thus unsuccessful in clearing the infection and as a result becomes established as a persistent infection promoting chronic inflammation. In some individuals the associated inflammation contributes to ulcerogenesis or neoplasia. H. pylori has an array of different strategies to interact intimately with epithelial cells and manipulate their cellular processes and functions. Among the multiple aspects that H. pylori affects in gastric epithelial cells are their distribution of epithelial junctions, DNA damage, apoptosis, proliferation, stimulation of cytokine production, and cell transformation. Some of these processes are initiated as a result of the activation of signaling mechanisms activated on binding of H. pylori to cell surface receptors or via soluble virulence factors that gain access to the epithelium. The multiple responses by the epithelium to the infection contribute to pathogenesis associated with H. pylori.展开更多
Helicobacter pylori (H.pylori) has co-evolved with humans to be transmitted from person to person and to colonize the stomach persistently.A well-choreographed equilibrium between the bacterial effectors and host resp...Helicobacter pylori (H.pylori) has co-evolved with humans to be transmitted from person to person and to colonize the stomach persistently.A well-choreographed equilibrium between the bacterial effectors and host responses permits microbial persistence and health of the host,but confers a risk for serious diseases including gastric cancer.During its long coexistence with humans,H.pylori has developed complex strategies to limit the degree and extent of gastric mucosal damage and in? ammation,as well as immune effector activity.The present editorial thus aims to introduce and comment on major advances in the rapidly developing area of H.pylori/human gastric mucosa interaction (and its pathological sequelae),which is the result of millennia of co-evolution of,and thus of reciprocal knowledge between,the pathogen and its human host.展开更多
Helicobacter pylori (H. pylori) is a gram negative microaerophilic bacterium which resides in the mucous linings of the stomach. It has been implicated in the causation of various gastric disorders including gastric c...Helicobacter pylori (H. pylori) is a gram negative microaerophilic bacterium which resides in the mucous linings of the stomach. It has been implicated in the causation of various gastric disorders including gastric cancer. The geographical distribution and etiology of gastric cancer differ widely in different geographical regions and H. pylori, despite being labeled as a grade I carcinogen, has not been found to be associated with gastric cancer in many areas. Studies in Asian countries such as Thailand, India, Bangladesh, Pakistan, Iran, Saudi Arabian countries, Israel and Malaysia, have reported a high frequency of H. pylori infection co-existing with a low incidence of gastric cancer. In India, a difference in the prevalence of H. pylori infection and gastric cancer has been noted even in different regions of the country leading to a puzzle when attempting to find the causes of these variations. This puzzle of H. pylori distribution and gastric cancer epidemiology is known as the Indian enigma. In this review we have attempted to explain the Indian enigma using evidence from various Indian studies and from around the globe. This review covers aspects of epidemiology, the various biological strains present in different parts of the country and within individuals, the status of different H. pylori-related diseases and the molecular pathogenesis of the bacterium.展开更多
Helicobacter pylori (H. pylori) colonize the gastric mucosa of 50% of the world's population. This infection is closely associated with the development of peptic ulcer disease and gastric cancer. The present study ...Helicobacter pylori (H. pylori) colonize the gastric mucosa of 50% of the world's population. This infection is closely associated with the development of peptic ulcer disease and gastric cancer. The present study was conducted to assess the prevalence of H, pylori infection in Moroccan population and the risk to develop gastric precancerous lesions and gastric cancer. Totally, 298 patients were enrolled, 68 of asymptomatic subjects and 230 of patients with gastric diseases. Histological examination was effected to diagnostic gastric lesions and to detect H. pylori. ELISA was used to determine H. pylori status of patients. The prevalence of H. pylori within asymptomatic and symptomatic subjects was observed higher. A significant relationship was detected between H. pylori infection and the risk of gastric diseases (p-value 〈 0.0001). A meaningful association between chronic gastritis increasing and age was observed (p-value = 0.03). The risk to develop gastric cancer among infected patients was observed elevated with rate of 9%. Our results showed a high prevalence of H. pylori in both asymptomatic and gastric diseases patients. We noticed that chronic gastric infection increases with age. We remarked also that the risk to develop gastric cancer among infected patients was elevated in our population.展开更多
Helicobacter pylori(H. pylori) has long been found to cause gastric diseases such as gastritis, gastric ulcers and gastric cancer. The transmission medium of this bacterium has yet to be determined, though several stu...Helicobacter pylori(H. pylori) has long been found to cause gastric diseases such as gastritis, gastric ulcers and gastric cancer. The transmission medium of this bacterium has yet to be determined, though several studies have speculated that the oral cavity is a reservoir for H. pylori. Others have also reported that the oral cavity may be a source of both transmission and gastric reinfection; however, such results are controversial. We reviewed the literature and selected studies that report an association among H. pylori detections in the oral cavity(dental plaque, saliva, tongue, tonsil tissue, root canals, oral mucosa) in humans and in animals, as well as in the human stomach. The oral cavity may be considered the main reservoir for H. pylori. There are a correlations between H. pylori infection in the oral cavity and periodontal disease, oral tissue inflammation, H. pylori transmission, and gastric reinfection. We believe that the mouth is a reservoir and that it plays a crucial role in both H. pylori transmission and gastric infection.展开更多
The inflammatory pattern during Helicobacter pylori(H.pylori)infection is changeable and complex.During childhood,it is possible to observe a predominantly regulatory response,evidenced by high concentrations of key c...The inflammatory pattern during Helicobacter pylori(H.pylori)infection is changeable and complex.During childhood,it is possible to observe a predominantly regulatory response,evidenced by high concentrations of key cytokines for the maintenance of Treg responses such as TGF-β1 and IL-10,in addition to high expression of the transcription factor FOXP3.On the other hand,there is a predominance of cytokines associated with the Th1 and Th17 responses among H.pylori-positive adults.In the last few years,the participation of the Th17 response in the gastric inflammation against H.pylori infection has been highlighted due to the high levels of TGF-β1 and IL-17 found in this infectious scenario,and growing evidence has supported a close relationship between this immune response profile and unfavorable outcomes related to the infection.Moreover,this cytokine profile might play a pivotal role in the effectiveness of anti-H.pylori vaccines.It is evident that age is one of the main factors influencing the gastric inflammatory pattern during the infection with H.pylori,and understanding the immune response against the bacterium can assist in the development of alternative prophylactic and therapeutic strategies against the infection as well as in the comprehension of the pathogenesis of the outcomes related to that microorganism.展开更多
Traditional medical imaging,including ultrasound,computed tomography,magnetic resonance imaging,or positron emission tomography,remains widely used diagnostic modalities for gastrointestinal diseases at present.These ...Traditional medical imaging,including ultrasound,computed tomography,magnetic resonance imaging,or positron emission tomography,remains widely used diagnostic modalities for gastrointestinal diseases at present.These modalities are used to assess changes in morphology,attenuation,signal intensity,and enhancement characteristics.Gastrointestinal tumors,especially malignant tumors,are commonly seen in clinical practice with an increasing number of deaths each year.Because the imaging manifestations of different diseases usually overlap,accurate early diagnosis of tumor lesions,noninvasive and effective evaluation of tumor staging,and prediction of prognosis remain challenging.Fortunately,traditional medical images contain a great deal of important information that cannot be recognized by human eyes but can be extracted by artificial intelligence(AI)technology,which can quantitatively assess the heterogeneity of lesions and provide valuable information,including therapeutic effects and patient prognosis.With the development of computer technology,the combination of medical imaging and AI technology is considered to represent a promising field in medical image analysis.This new emerging field is called“radiomics”,which makes big data mining and extraction from medical imagery possible and can help clinicians make effective decisions and develop personalized treatment plans.Recently,AI and radiomics have been gradually applied to lesion detection,qualitative and quantitative diagnosis,histopathological grading and staging of tumors,therapeutic efficacy assessment,and prognosis evaluation.In this minireview,we briefly introduce the basic principles and technology of radiomics.Then,we review the research and application of AI and radiomics in gastrointestinal diseases,especially diagnostic advancements of radiomics in the differential diagnosis,treatment option,assessment of therapeutic efficacy,and prognosis evaluation of esophageal,gastric,hepatic,pancreatic,and colorectal diseases.展开更多
AIM: To compare the distribution of virulence-associatedgenotypes of Helicobacter pylori(H pylori) in two areas of north China with different gastric cancer risk and furthermore probe into the pathogenicity of the bac...AIM: To compare the distribution of virulence-associatedgenotypes of Helicobacter pylori(H pylori) in two areas of north China with different gastric cancer risk and furthermore probe into the pathogenicity of the bacterium. METHODS: Gastric biopsies were taken from 355 subjects from Zhuanghe, a high risk area of gastric cancer, and 136 subjects from Shenyang, a low risk area of gastric cancer. A total of 149 H pylori strains isolated from these patients were studied by PCR for differences in the genotypes of cagA, vac A, and iceA.RESULTS: In patients with high risk for gastric cancer, higher frequencies of vacA s1 or s1m1b genotypes were found as compared to those from the low risk area. CONCLUSION: There is significantly different distribution of H pylori genotypes between Zhuanghe and Shenyang areas in north China.展开更多
AIM: To investigate age, sex, histopathology and Helicobacter pylori (H. pylori) status, as risk factors for gastroduodenal disease outcome in Brazilian dyspeptic patients.tients submitted to upper gastroscopy at Hosp...AIM: To investigate age, sex, histopathology and Helicobacter pylori (H. pylori) status, as risk factors for gastroduodenal disease outcome in Brazilian dyspeptic patients.tients submitted to upper gastroscopy at Hospital das Clinicas of Marilia, antral biopsy specimens were obtained and subjected to histopathology and H. pylori diagnosis. All patients presenting chronic gastritis (CG) and peptic ulcer (PU) disease localized in the stomach, gastric ulcer (GU) and/or duodenal ulcer (DU) were included in the study. Gastric biopsies (n = 668) positive for H. pylori by rapid urease test were investigated for vacuolating cytotoxin A (vacA ) medium (m) region mosaicism by polymerase chain reaction. Logistic regression analysis was performed to verify the association of age, sex, histopathologic alterations, H. pylori diagnosis and vacA m region mosaicism with the incidence of DU, GU and CG in patients. RESULTS: Of 1466 patients submitted to endoscopy, 1060 (72.3%) presented CG [male/female = 506/554; mean age (year) ± SD = 51.2 ± 17.81], 88 (6.0%) presented DU [male/female = 54/34; mean age (year) ± SD = 51.4 ± 17.14], and 75 (5.1%) presented GU [male/female = 54/21; mean age (year) ± SD = 51.3 ± 17.12] and were included in the comparative analysis. Sex and age showed no detectable effect on CG incidence (overall c 2 = 2.1, P = 0.3423). Sex [Odds ratios (OR) = 1.8631, P = 0.0058] but not age (OR = 0.9929, P = 0.2699) was associated with DU and both parameters had a highly significant effect on GU (overall c 2 = 30.5, P < 0.0001). The histopathological results showed a significant contribution of ageing for both atrophy (OR = 1.0297, P < 0.0001) and intestinal metaplasia (OR = 1.0520, P < 0.0001). Presence of H. pylori was significantly associated with decreasing age (OR = 0.9827, P < 0.0001) and with the incidence of DU (OR = 3.6077, P < 0.0001). The prevalence of m1 in DU was statistically significant (OR = 2.3563, P = 0.0018) but not in CG (OR = 2.678, P = 0.0863) and GU (OR = 1.520, P = 0.2863). CONCLUSION: In our population, male gender was a risk factor for PU; ageing for GU, atrophy and metapla-sia; and H. pylori of vacA m1 genotype for DU.展开更多
Atfer examining 88 gastropathic patieiits with Spleen deficiency syndrome by iJsing transmis-sion electron microscope, X-ray energy disperse analysis system, histochemical staining and radioimmunomethods, the authors ...Atfer examining 88 gastropathic patieiits with Spleen deficiency syndrome by iJsing transmis-sion electron microscope, X-ray energy disperse analysis system, histochemical staining and radioimmunomethods, the authors found that the gastric mucosa cyclic adenosine monophosphate, superoxide dismutaselevel, quantity of mitochondria and its crista, the ratio of diameter between ventricle and cavity of mitochon-dria aiid the conteiit ot zinc (Zn) , copper (Cu) of mitochondria were decreasing to certain extent which tendsto get lower and lower with different groups in the order of health coritrol group, Spleen Qi deficiency groupaiid SPIeen deficiency with Qi stagnation group; chronic superficial gastritis group, chronic atrophic gastritisgroup and gastric cancor group , complete small intestinal metaplasia (IM) group, incomplete small iM group,complete colonic iM groiJp and incomplete colonic iM group (P< 0 . 05 ̄0 . 001 ) . While tlie degeiieratiori rateof mitochondria, Cu/Zn ratio, metaplasia rate of gastric mucosa, rate of incomplete colonic IM and content ofIipid peroxide were increasing in the above order (P < 0 . 05  ̄0 . 001 ) . It is suggested that tlie comprehensiveeffect ot the degeneration of mitochoridria and the quantitative changes of its correlative factors is the phys-iopathologic base for indecing SPIeen deficiency disease, gastric mucosa iM and canceration.展开更多
基金Supported by the National Natural Science Foundation of China,No.82172336“Pioneer”and“Leading Goose”R&D Program of Zhejiang,No.2022C03118 and No.2023C03075+1 种基金Natural Science Foundation of Zhejiang Province,No.LQ23H050005Scientific Research Project of Zhejiang Provincial Education Department,No.Y202250731.
文摘Pepsinogen,secreted from the gastric mucosa,is the precursor of pepsin.It is categorized as pepsinogen 1 and pepsinogen 2 based on its immunogenicity.The pepsinogen content that can enter the blood circulation through the capillaries of the gastric mucosa is approximately 1%and remains stable all the time.The pepsinogen content in serum will change with the pathological changes of gastric mucosa.Therefore,the level of pepsinogen in serum can play a role in serologic biopsy to reflect the function and morphology of different regions of gastric mucosa and serve as an indicator of gastric disease.This study conducts relevant research on serum pepsinogen 1,pepsinogen 2,and the ratio of pepsinogen 1 to pepsinogen 2,and reviews their important value in clinical diagnosis of Helicobacter pylori infection,gastric ulcer,and even gastric carcinoma,providing ideas for other researchers.
基金Supported by the National Natural Science Foundation of China,No.81372681Key Research Development Program of Shandong Province,No.2015GGH318014
文摘AIM: To explore the correlation between Helicobacter pylori(H. pylori)-associated gastric diseases and colorectal neoplasia.METHODS: Patients included in this study underwent a colonoscopy and esophago-gastro-duodenoscopy(EGD) along with histopathological measurement between March 2012 and March 2015 at Qi-Lu Hospital of Shandong University, who also had results of H. pylori detection. A total of 233 cases were selected. Demographic data, H. pylori infection status(including results of rapid urease tests and gastric mucosa pathological examinations) and histopathological examination results of gastric and colorectal mucosa were gathered and analyzed. The statistical analysis focused on the prevalence of colorectal neoplasms among patients with various histopathological categories of the stomach. ORs and their 95%CI were calculated to describe the strengths of the associations.RESULTS: The incidence rates of colorectal adenoma without high-grade intraepithelial neoplasia(HGIEN)(OR = 2.400, 95%CI: 0.969-5.941), adenoma with HGIEN(5.333, 1.025-27.758) and adenocarcinoma(1.455, 0.382-5.543) were all higher for patients with H. pylori-associated gastritis than for those in the control group. The incidence rate of colorectal adenoma with HGIEN(3.218, 0.767-13.509) was higher in patients with intestinal metaplasia than in the control group, while the incidence rates of adenoma without HGIEN(0.874, 0.414-1.845) and adenocarcinoma(0.376, 0.096-1.470) were lower in the intestinal metaplasia group than in the control group. The incidence rate of colorectal adenoma without HGIEN(3.111, 1.248-7.753) was significantly higher in the gastric intraepithelial neoplasia group than in the control group, while the rates of adenoma with HGIEN(1.481, 0.138-15.941) and adenocarcinoma(2.020, 0.561-7.272) were higher in the gastric intraepithelial neoplasia group. Incidence rates of colorectal adenoma without HGIEN(1.067, 0.264-4.314), adenoma with HGIEN(2.667, 0.231-30.800) and adenocarcinoma(2.182, 0.450-10.585) were all higher in the gastric adenocarcinoma group than in the control group.CONCLUSION: H. pylori infection as well as H. pylori-associated gastric diseases are risk factors for colorectal neoplasia.
基金supported by the National"Tenth-Five"Key Technologies R& D Program of China(2004BA703B04-02)the Technology Project of Liaoning Province(2007408001-1)
文摘Objective: To investigate the difference in susceptibilities to allitridi of Helicobacter pylori (H.pylori) strains in different gastric diseases and the associations with different genotypes. Methods: H.pylori strains were isolated from gastric antral biopsy specimens and identified. DNA was isolated from H.pylori strains. Different genotypes were determined by polymerase chain reaction(PCR), and the allitridi MICs were determined by agar dilution methods. MIC50 was calculated. Results: The susceptibilities of H, pylori strains varied among different gastric diseases. H.pylori strains in superficial gastritis were significantly more susceptible to allitridi than those in atrophic gastritis (relative median potency was 0.49, 95% confidence interval was from 0.24 to 0.80), strains in superficial gastritis were significantly more susceptible than those in gastric cancer (relative median potency was 0.32, 95% confidence interval was from 0.06 to 0.68) and strains in atrophic gastritis were significantly more susceptible than those in gastric cancer(relative median potency was 0.16, 95% confidence interval was from 0.02 to 0.40). The susceptibilities of H.pylori strains with different genotypes varied among different gastric diseases. In atrophic gastritis, strains with vacAsl+ were significantly more susceptible to allitridi than those with vacAsl(relative median potency was 0.21, 95% confidence interval was from 0.04 to 0.73). In gastric cancer, strains with vacAmlb+ were significantly more susceptible than those with vacAmlb-(relative median potency was 0.07, 95% confidence interval was from 0.03 to 0.49). Conclusion: The vacA genotypes play an important role in the susceptibility to allitridi in different gastric diseases.
基金supported by National Natural Science Foundation of China (Grant No. 81372140, 81301688, 81272192, 81171882, 81172298)Ph.D. Programs Foundation of Ministry of Education of China (No. 20130162110050 and 20130162120093)+6 种基金Post-doctoral Foundation of Central South University (No. 131425) China Postdoctoral Science Foundation (2014M552167)Key Program for International Cooperation Projects of Hunan Province (no. 2011WK2011)Natural Science Foundation of Hunan Province (Grant No. 12JJ4088)Technology Project of Hunan Province (2012SK3229)Research foundation of Health Department of Hunan Province (B2012-100)125 Talent Project of the Third Xiangya Hospital of Central South University
文摘Altered micro RNA(mi RNA) associated with gastric cancer(GC) development and mi R-17 and mi R-106 b were differentially expressed in GC tissues. This study detected serum levels of mi R-17 and mi R-106 b expression in GC, benign gastric disease(BGD) and healthy controls to assess them as tumor markers for GC. Serum samples from 40 GC, 32 BGD(10 gastric ulcer, 14 gastric polyps, and 8 gastric ulcer with polyps) and 36 healthy individuals were subjected to quantitative reverse transcription polymerase chain reaction(q RT-PCR) analysis of mi R-17 and mi R-106 b expression. The data showed that the serum levels of mi R-17 and mi R-106 b were significantly reduced in healthy individuals and BGD patients compared to GC patients. There was a significant association of mi R-17 and mi R-106 b expression with age, but not with other clinicopathological features, such as gender, tumor differentiation, stage and lymphatic metastasis. Further analysis showed that, in discriminating GC patients from healthy controls, mi R-17 could yield a receiver-operating characteristic(ROC) area under the curve(AUC) of 0.879 with 80.6% sensitivity and 87.5% specificity and mi R-106 b could yield an AUC of 0.856 with 75.0% sensitivity and 92.5% specificity. The combined AUC of mi R-17 and mi R-106 b was 0.913 with 83.3% sensitivity and 87.5% specificity. Collectively, these data suggest that detection of serum mi R-17 and mi R-106 b levels should be further evaluated as novel non-invasive biomarkers in early GC detection and surveillance of disease progression.
基金the National Natural Science Foundation of China,No.82174309National Natural Science Foundation of China,No.81973774+1 种基金National Administration of Traditional Chinese Medicine:2019 Project of Building Evidence-Based Practice Capacity for TCM,No.ZZ13-042-2 and No.2019XZZX-XH013Shuguang Hospital Siming Foundation Research Special Project,No.SGKJ-202304.
文摘BACKGROUND Three-dimensional organoid culture systems have been established as a robust tool for elucidating mechanisms and performing drug efficacy testing.The use of gastric organoid models holds significant promise for advancing personalized medicine research.However,a comprehensive bibliometric review of this burgeoning field has not yet been published.AIM To analyze and understand the development,impact,and direction of gastric organoid research using bibliometric methods using data from the Web of Science Core Collection(WoSCC)database.METHODS This analysis encompassed literature pertaining to gastric organoids published between 2010 and 2023,as indexed in the WoSCC.CiteSpace and VOSviewer were used to depict network maps illustrating collaborations among authors,institutions and keywords related to gastric organoid.Citation,co-citation,and burst analysis methodologies were applied to assess the impact and progress of research.RESULTS A total of 656 relevant studies were evaluated.The majority of research was published in gastroenterology-focused journals.Globally,Yana Zavros,Hans Clevers,James M Wells,Sina Bartfeld,and Chen Zheng were the 5 most productive authors,while Hans Clevers,Huch Meritxell,Johan H van Es,Marc Van de Wetering,and Sato Toshiro were the foremost influential scientists in this area.Institutions from the University Medical Center Utrecht,Netherlands Institute for Developmental Biology(Utrecht),and University of Cincinnati(Cincinnati,OH,United States)made the most significant contributions.Currently,gastric organoids are used mainly in studies investigating gastric cancer(GC),Helicobacter pylori-infective gastritis,with a focus on the mechanisms of GC,and drug screening tests.CONCLUSION Key focus areas of research using gastric organoids include unraveling disease mechanisms and enhancing drug screening techniques.Major contributions from renowned academic institutions highlight this field’s dynamic growth.
基金Supported by National Natural Science Foundation of China,No.U1604174Henan Provincial Government-Health and Family Planning Commission,No.20170123+1 种基金Henan Provincial Government-Health and Family Planning Commission Research Innovative Talents Project,No.51282Henan Provincial Government-Science and Technology Bureau,No.142300410050.
文摘BACKGROUND Type I Helicobacter pylori(H.pylori)infection causes severe gastric inflammation and is a predisposing factor for gastric carcinogenesis.However,its infection status in stepwise gastric disease progression in this gastric cancer prevalent area has not been evaluated;it is also not known its impact on commonly used epidemiological gastric cancer risk markers such as gastrin-17(G-17)and pepsinogens(PGs)during clinical practice.AIM To explore the prevalence of type I and type II H.pylori infection status and their impact on G-17 and PG levels in clinical practice.METHODS Thirty-five hundred and seventy-two hospital admitted patients with upper gastrointestinal symptoms were examined,and 523 patients were enrolled in this study.H.pylori infection was confirmed by both 13C-urea breath test and serological assay.Patients were divided into non-atrophic gastritis(NAG),nonatrophic gastritis with erosion(NAGE),chronic atrophic gastritis(CAG),peptic ulcers(PU)and gastric cancer(GC)groups.Their serological G-17,PG I and PG II values and PG I/PG II ratio were also measured.RESULTS A total H.pylori infection rate of 3572 examined patients was 75.9%,the infection rate of 523 enrolled patients was 76.9%,among which type I H.pylori infection accounted for 72.4%(291/402)and type II was 27.6%;88.4%of GC patients were H.pylori positive,and 84.2%of them were type I infection,only 11.6%of GC patients were H.pylori negative.Infection rates of type I H.pylori in NAG,NAGE,CAG,PU and GC groups were 67.9%,62.7%,79.7%,77.6%and 84.2%,respectively.H.pylori infection resulted in significantly higher G-17 and PG II values and decreased PG I/PG II ratio.Both types of H.pylori induced higher G-17 level,but type I strain infection resulted in an increased PG II level and decreased PG I/PG II ratio in NAG,NAGE and CAG groups over uninfected controls.Overall PG I levels showed no difference among all disease groups and in the presence or absence of H.pylori;in stratified analysis,its level was increased in GC and PU patients in H.pylori and type I H.pylori-positive groups.CONCLUSION Type I H.pylori infection is the major form of infection in this geographic region,and a very low percentage(11.6%)of GC patients are not infected by H.pylori.Both types of H.pylori induce an increase in G-17 level,while type I H.pylori is the major strain that affects PG I and PG IIs level and PG I/PG II ratio in stepwise chronic gastric disease.The data provide insights into H.pylori infection status and indicate the necessity and urgency for bacteria eradication and disease prevention in clinical practice.
基金Supported by National Institutes of Health,No.K22AI68712,No.R56DK090090-01American Gastroenterological Association Research Scholar Award,NIH 1U54RR02614+4 种基金The University of Texas Medical Branch Clinical and Translational Sciences AwardThe American Cancer Society RSG-10-159-01-LIB,NIH 8UL1TR000041The University of New Mexico Clinical and Translational Science CenterAlzahrani S founded by Saudi Arabia’s Ministry of Higher Education,the Saudi A Cultural Mission(SACM)Lina TT funded by Sealy Centre for Vaccine Development Pre-doctoral fellowship and McLaughlin Pre-doctoral Fellowship,UTMB
文摘The gastrointestinal epithelium has cells with features that make them a powerful line of defense in innate mucosal immunity. Features that allow gastrointestinal epithelial cells to contribute in innate defense include cell barrier integrity, cell turnover, autophagy, and innate immune responses. Helicobacter pylori (H. pylori) is a spiral shape gram negative bacterium that selectively colonizes the gastric epithelium of more than half of the world’s population. The infection invariably becomes persistent due to highly specialized mechanisms that facilitate H. pylori’s avoidance of this initial line of host defense as well as adaptive immune mechanisms. The host response is thus unsuccessful in clearing the infection and as a result becomes established as a persistent infection promoting chronic inflammation. In some individuals the associated inflammation contributes to ulcerogenesis or neoplasia. H. pylori has an array of different strategies to interact intimately with epithelial cells and manipulate their cellular processes and functions. Among the multiple aspects that H. pylori affects in gastric epithelial cells are their distribution of epithelial junctions, DNA damage, apoptosis, proliferation, stimulation of cytokine production, and cell transformation. Some of these processes are initiated as a result of the activation of signaling mechanisms activated on binding of H. pylori to cell surface receptors or via soluble virulence factors that gain access to the epithelium. The multiple responses by the epithelium to the infection contribute to pathogenesis associated with H. pylori.
基金Supported by University of Pavia(Fondo d'Ateneo per la Ricercato Ricci V)+1 种基金Second University of Naples(CIRANAD to Romano M)
文摘Helicobacter pylori (H.pylori) has co-evolved with humans to be transmitted from person to person and to colonize the stomach persistently.A well-choreographed equilibrium between the bacterial effectors and host responses permits microbial persistence and health of the host,but confers a risk for serious diseases including gastric cancer.During its long coexistence with humans,H.pylori has developed complex strategies to limit the degree and extent of gastric mucosal damage and in? ammation,as well as immune effector activity.The present editorial thus aims to introduce and comment on major advances in the rapidly developing area of H.pylori/human gastric mucosa interaction (and its pathological sequelae),which is the result of millennia of co-evolution of,and thus of reciprocal knowledge between,the pathogen and its human host.
文摘Helicobacter pylori (H. pylori) is a gram negative microaerophilic bacterium which resides in the mucous linings of the stomach. It has been implicated in the causation of various gastric disorders including gastric cancer. The geographical distribution and etiology of gastric cancer differ widely in different geographical regions and H. pylori, despite being labeled as a grade I carcinogen, has not been found to be associated with gastric cancer in many areas. Studies in Asian countries such as Thailand, India, Bangladesh, Pakistan, Iran, Saudi Arabian countries, Israel and Malaysia, have reported a high frequency of H. pylori infection co-existing with a low incidence of gastric cancer. In India, a difference in the prevalence of H. pylori infection and gastric cancer has been noted even in different regions of the country leading to a puzzle when attempting to find the causes of these variations. This puzzle of H. pylori distribution and gastric cancer epidemiology is known as the Indian enigma. In this review we have attempted to explain the Indian enigma using evidence from various Indian studies and from around the globe. This review covers aspects of epidemiology, the various biological strains present in different parts of the country and within individuals, the status of different H. pylori-related diseases and the molecular pathogenesis of the bacterium.
文摘Helicobacter pylori (H. pylori) colonize the gastric mucosa of 50% of the world's population. This infection is closely associated with the development of peptic ulcer disease and gastric cancer. The present study was conducted to assess the prevalence of H, pylori infection in Moroccan population and the risk to develop gastric precancerous lesions and gastric cancer. Totally, 298 patients were enrolled, 68 of asymptomatic subjects and 230 of patients with gastric diseases. Histological examination was effected to diagnostic gastric lesions and to detect H. pylori. ELISA was used to determine H. pylori status of patients. The prevalence of H. pylori within asymptomatic and symptomatic subjects was observed higher. A significant relationship was detected between H. pylori infection and the risk of gastric diseases (p-value 〈 0.0001). A meaningful association between chronic gastritis increasing and age was observed (p-value = 0.03). The risk to develop gastric cancer among infected patients was observed elevated with rate of 9%. Our results showed a high prevalence of H. pylori in both asymptomatic and gastric diseases patients. We noticed that chronic gastric infection increases with age. We remarked also that the risk to develop gastric cancer among infected patients was elevated in our population.
基金Supported by Sao Paulo Research Foundation(FAPESP)Sacred Heart University of Bauru Marília School of Medicine,No.2012/18333-3
文摘Helicobacter pylori(H. pylori) has long been found to cause gastric diseases such as gastritis, gastric ulcers and gastric cancer. The transmission medium of this bacterium has yet to be determined, though several studies have speculated that the oral cavity is a reservoir for H. pylori. Others have also reported that the oral cavity may be a source of both transmission and gastric reinfection; however, such results are controversial. We reviewed the literature and selected studies that report an association among H. pylori detections in the oral cavity(dental plaque, saliva, tongue, tonsil tissue, root canals, oral mucosa) in humans and in animals, as well as in the human stomach. The oral cavity may be considered the main reservoir for H. pylori. There are a correlations between H. pylori infection in the oral cavity and periodontal disease, oral tissue inflammation, H. pylori transmission, and gastric reinfection. We believe that the mouth is a reservoir and that it plays a crucial role in both H. pylori transmission and gastric infection.
文摘The inflammatory pattern during Helicobacter pylori(H.pylori)infection is changeable and complex.During childhood,it is possible to observe a predominantly regulatory response,evidenced by high concentrations of key cytokines for the maintenance of Treg responses such as TGF-β1 and IL-10,in addition to high expression of the transcription factor FOXP3.On the other hand,there is a predominance of cytokines associated with the Th1 and Th17 responses among H.pylori-positive adults.In the last few years,the participation of the Th17 response in the gastric inflammation against H.pylori infection has been highlighted due to the high levels of TGF-β1 and IL-17 found in this infectious scenario,and growing evidence has supported a close relationship between this immune response profile and unfavorable outcomes related to the infection.Moreover,this cytokine profile might play a pivotal role in the effectiveness of anti-H.pylori vaccines.It is evident that age is one of the main factors influencing the gastric inflammatory pattern during the infection with H.pylori,and understanding the immune response against the bacterium can assist in the development of alternative prophylactic and therapeutic strategies against the infection as well as in the comprehension of the pathogenesis of the outcomes related to that microorganism.
文摘Traditional medical imaging,including ultrasound,computed tomography,magnetic resonance imaging,or positron emission tomography,remains widely used diagnostic modalities for gastrointestinal diseases at present.These modalities are used to assess changes in morphology,attenuation,signal intensity,and enhancement characteristics.Gastrointestinal tumors,especially malignant tumors,are commonly seen in clinical practice with an increasing number of deaths each year.Because the imaging manifestations of different diseases usually overlap,accurate early diagnosis of tumor lesions,noninvasive and effective evaluation of tumor staging,and prediction of prognosis remain challenging.Fortunately,traditional medical images contain a great deal of important information that cannot be recognized by human eyes but can be extracted by artificial intelligence(AI)technology,which can quantitatively assess the heterogeneity of lesions and provide valuable information,including therapeutic effects and patient prognosis.With the development of computer technology,the combination of medical imaging and AI technology is considered to represent a promising field in medical image analysis.This new emerging field is called“radiomics”,which makes big data mining and extraction from medical imagery possible and can help clinicians make effective decisions and develop personalized treatment plans.Recently,AI and radiomics have been gradually applied to lesion detection,qualitative and quantitative diagnosis,histopathological grading and staging of tumors,therapeutic efficacy assessment,and prognosis evaluation.In this minireview,we briefly introduce the basic principles and technology of radiomics.Then,we review the research and application of AI and radiomics in gastrointestinal diseases,especially diagnostic advancements of radiomics in the differential diagnosis,treatment option,assessment of therapeutic efficacy,and prognosis evaluation of esophageal,gastric,hepatic,pancreatic,and colorectal diseases.
基金Supported by the National Key Basic Research Program of China (G1998051203)National Key Technologies R&D Program of China during the 10th Five-year Plan Period,2001BA703B06(B)
文摘AIM: To compare the distribution of virulence-associatedgenotypes of Helicobacter pylori(H pylori) in two areas of north China with different gastric cancer risk and furthermore probe into the pathogenicity of the bacterium. METHODS: Gastric biopsies were taken from 355 subjects from Zhuanghe, a high risk area of gastric cancer, and 136 subjects from Shenyang, a low risk area of gastric cancer. A total of 149 H pylori strains isolated from these patients were studied by PCR for differences in the genotypes of cagA, vac A, and iceA.RESULTS: In patients with high risk for gastric cancer, higher frequencies of vacA s1 or s1m1b genotypes were found as compared to those from the low risk area. CONCLUSION: There is significantly different distribution of H pylori genotypes between Zhuanghe and Shenyang areas in north China.
基金Supported by Fundaao de Amparo a Pesquisa do Estado de So Paulo (FAPESP), Research Grant 06/01223-0Fellowship CGF 2001/14509-5
文摘AIM: To investigate age, sex, histopathology and Helicobacter pylori (H. pylori) status, as risk factors for gastroduodenal disease outcome in Brazilian dyspeptic patients.tients submitted to upper gastroscopy at Hospital das Clinicas of Marilia, antral biopsy specimens were obtained and subjected to histopathology and H. pylori diagnosis. All patients presenting chronic gastritis (CG) and peptic ulcer (PU) disease localized in the stomach, gastric ulcer (GU) and/or duodenal ulcer (DU) were included in the study. Gastric biopsies (n = 668) positive for H. pylori by rapid urease test were investigated for vacuolating cytotoxin A (vacA ) medium (m) region mosaicism by polymerase chain reaction. Logistic regression analysis was performed to verify the association of age, sex, histopathologic alterations, H. pylori diagnosis and vacA m region mosaicism with the incidence of DU, GU and CG in patients. RESULTS: Of 1466 patients submitted to endoscopy, 1060 (72.3%) presented CG [male/female = 506/554; mean age (year) ± SD = 51.2 ± 17.81], 88 (6.0%) presented DU [male/female = 54/34; mean age (year) ± SD = 51.4 ± 17.14], and 75 (5.1%) presented GU [male/female = 54/21; mean age (year) ± SD = 51.3 ± 17.12] and were included in the comparative analysis. Sex and age showed no detectable effect on CG incidence (overall c 2 = 2.1, P = 0.3423). Sex [Odds ratios (OR) = 1.8631, P = 0.0058] but not age (OR = 0.9929, P = 0.2699) was associated with DU and both parameters had a highly significant effect on GU (overall c 2 = 30.5, P < 0.0001). The histopathological results showed a significant contribution of ageing for both atrophy (OR = 1.0297, P < 0.0001) and intestinal metaplasia (OR = 1.0520, P < 0.0001). Presence of H. pylori was significantly associated with decreasing age (OR = 0.9827, P < 0.0001) and with the incidence of DU (OR = 3.6077, P < 0.0001). The prevalence of m1 in DU was statistically significant (OR = 2.3563, P = 0.0018) but not in CG (OR = 2.678, P = 0.0863) and GU (OR = 1.520, P = 0.2863). CONCLUSION: In our population, male gender was a risk factor for PU; ageing for GU, atrophy and metapla-sia; and H. pylori of vacA m1 genotype for DU.
文摘Atfer examining 88 gastropathic patieiits with Spleen deficiency syndrome by iJsing transmis-sion electron microscope, X-ray energy disperse analysis system, histochemical staining and radioimmunomethods, the authors found that the gastric mucosa cyclic adenosine monophosphate, superoxide dismutaselevel, quantity of mitochondria and its crista, the ratio of diameter between ventricle and cavity of mitochon-dria aiid the conteiit ot zinc (Zn) , copper (Cu) of mitochondria were decreasing to certain extent which tendsto get lower and lower with different groups in the order of health coritrol group, Spleen Qi deficiency groupaiid SPIeen deficiency with Qi stagnation group; chronic superficial gastritis group, chronic atrophic gastritisgroup and gastric cancor group , complete small intestinal metaplasia (IM) group, incomplete small iM group,complete colonic iM groiJp and incomplete colonic iM group (P< 0 . 05 ̄0 . 001 ) . While tlie degeiieratiori rateof mitochondria, Cu/Zn ratio, metaplasia rate of gastric mucosa, rate of incomplete colonic IM and content ofIipid peroxide were increasing in the above order (P < 0 . 05  ̄0 . 001 ) . It is suggested that tlie comprehensiveeffect ot the degeneration of mitochoridria and the quantitative changes of its correlative factors is the phys-iopathologic base for indecing SPIeen deficiency disease, gastric mucosa iM and canceration.