Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling res...Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling results in mucosal impairment and the initiation of cancer.Banxia Xiexin Decoction(BXD),a well-known formula in traditional Chinese medicine(TCM),shows promise in treating gastric disorders,but its mechanisms in gastric restoration remain unclear.Methods:Using MNNG-induced CAG and PLGC rat models,BXD was administered for 12 weeks.Gastric mucosal pathology was assessed via hematoxylin-eosin staining.Proliferation(Ki-67)and angiogenesis(VEGFA)markers were evaluated by immunohistochemistry.Network pharmacology identified BXD’s targets and pathways.Notch pathway components(Notch1,Jagged1,Dll4,Hes1)were analyzed via qPCR,Western blot,and immunohistochemistry.Results:BXD significantly ameliorated mucosal atrophy,glandular structural disorder,and dysplasia in CAG and PLGC rats.Network pharmacology revealed 323 overlapping targets between BXD and PLGC,with Notch signaling as a central pathway.BXD downregulated Notch1,Jagged1,Dll4,and Hes1 expression at transcriptional and protein levels,suppressed Ki-67(proliferation)and VEGFA(angiogenesis)overexpression,and restored gastric mucosal integrity.Conclusion:BXD inhibits Notch signaling,reduces aberrant proliferation and angiogenesis,and interrupts Correa’s gastric carcinogenesis cascade.This study provides mechanistic evidence supporting BXD as a TCM-based intervention for gastric precancerous lesions.展开更多
Gastric precancerous lesions(GPL)represent a crucial stage in the complex process of gastric carcinogenesis that leads to gastric cancer(GC),one of the most prevalent cancers and a major source of cancer mortality wor...Gastric precancerous lesions(GPL)represent a crucial stage in the complex process of gastric carcinogenesis that leads to gastric cancer(GC),one of the most prevalent cancers and a major source of cancer mortality worldwide.Many studies have identified the gastrointestinal microbiota,or gut microbiota,as an important contributor to both the pathogenesis and treatment of GPL and GC,thus understanding its role in this transition is crucial.The purpose of this literature review is to introduce the current landscape of microbiota research associated with GPL and GC,with an emphasis on Helicobacter pylori(H.pylori)driven microbial dysbiosis and its modulation through Western medicine and traditional Chinese medicine(TCM)approaches.By elucidating the underlying mechanisms of H.pylori colonization,patterns,and interactions among microbiota,as well as the influence of microbial metabolites,this review highlights crucial driving factors of gastric carcinogenesis.The role of microbiota in conventional interventions,including H.pylori eradication,immunotherapy,as well as TCM herbal decoctions,is also discussed to provide a detailed understanding of the complex interactions between therapy and microbiota and how it could be potentially targeted for effective management of GPL and GC.Ultimately,microbiota-targeting therapeutics may represent a new path toward early detection,targeted treatment,improved prognosis,and potentially reduced incidence of GPL and GC.展开更多
BACKGROUND Precancerous lesions of gastric cancer(PLGC)represent a critical pathological stage in the development of intestinal gastric cancer.Early detection and diagnosis are key to reducing the incidence of gastric...BACKGROUND Precancerous lesions of gastric cancer(PLGC)represent a critical pathological stage in the development of intestinal gastric cancer.Early detection and diagnosis are key to reducing the incidence of gastric cancer.Substantial advancements have been made in PLGC research in recent years,making it necessary to provide updated reviews using bibliometric methods.We hypothesize that this review will identify emerging trends,key research areas,and gaps in PLGC research,providing insights that could guide future studies and enhance prevention strategies.AIM To comprehensively review the current state of research on PLGC,examining development trends and research hotspots.METHODS We conducted a bibliometric analysis of PLGC-related studies published between 2004 and 2023 using the Web of Science Core Collection database.We employed Software,including VOSviewer,CiteSpace,R software,and SCImago Graphica,to map scientific networks and visualize knowledge trends in terms of publication volume,countries/regions,institutions,journals,authors,and keywords.RESULTS A total of 4097 articles were included,and overall publication volume showed an increasing trend.Over the past two decades,China published the most articles,followed by the United States,Japan,South Korea,and Italy.Among the top 10 contributors,the United States ranked highest in institutions,authors,and citations and demonstrated the strongest international collaboration.Research keywords in this field were clustered into three main categories:Risk factors,pathogenesis,and diagnosis and treatment.Pathogenesis and molecular biomarkers remain key areas of focus.Future research should explore the mechanisms of gut microbiota,immune microenvironment,metabolic reprogramming,and epigenetics.Advanced technologies,including single-cell sequencing,spatially resolved analysis,multi-omics approaches,artificial intelligence,and machine learning,will likely accelerate in-depth investigations of PLGC.CONCLUSION PLGC research has rapidly developed in recent years,gaining considerable attention.This bibliometric analysis reveals research state and emerging trends over the past 20 years,providing insights for future studies.展开更多
Precancerous lesions of gastric cancer(PLGC)are crucial for the progression to gastric cancer,and early intervention in PLGC is pivotal in preventing its development into gastric cancer.In order to illustrate the mole...Precancerous lesions of gastric cancer(PLGC)are crucial for the progression to gastric cancer,and early intervention in PLGC is pivotal in preventing its development into gastric cancer.In order to illustrate the molecular mechanisms underlying PLGC and the roles of associated genes within these lesions,genetically engineered mouse models(GEMMs)have been developed.We systematically summarize the current GEMMs,and highlight the principal pathological mechanisms involved,including gastrin/gastric acid balance,inflammatory factors,the interplay between cancer-promoting and cancer-suppressing genes,and apoptotic pathways.We further discuss the mechanisms involved in the existing GEMMs of PLGC.展开更多
BACKGROUND As a minimally invasive technique,endoscopic submucosal dissection(ESD)is widely used in treating early colorectal cancer(ECRC)and precancerous lesions(PCLs).However,a common postoperative complication-dela...BACKGROUND As a minimally invasive technique,endoscopic submucosal dissection(ESD)is widely used in treating early colorectal cancer(ECRC)and precancerous lesions(PCLs).However,a common postoperative complication-delayed postoperative bleeding(DPOB)-can significantly hinder patient recovery.AIM To build and validate a predictive model for assessing post-ESD DPOB risk in ECRC and PCL patients,utilizing logistic regression methodology.METHODS A retrospective review was conducted on ECRC/PCL 302 patients who received ESD at our hospital between July 2021 and July 2024.The cohort was stratified based on the incidence of DPOB following ESD,forming DPOB and non-DPOB groups.Through allocation,they were further allocated into model and validation cohorts.Clinical variables from both cohorts were collated and subjected to univariate analysis to determine potential factors associated with post-ESD DPOB.Subsequently,we constructed a predictive model for DPOB risk employing logistic regression analysis.Model performance assessment used receiver operating characteristic curves in both the training and validation cohorts,with internal validation accomplished via 10-fold cross-validation.RESULTS The occurrence rate of DPOB was 9.93%.Univariate analysis revealed that the number of lesions,lesion size,lesion location,degree of submucosal fibrosis,and intraoperative bleeding were significantly associated with DPOB.Binary logistic regression analysis identified the number of lesions,lesion size,lesion location,and degree of submucosal fibrosis as independent DPOB determinants.A nomogram that was developed to quantify the DPOB risk exhibited that an increment in the total score corresponded to an increased risk.The model achieved area under the curve values of 0.831 and 0.821 in the model and validation groups,respectively,with P values of 0.853 and 0.203 in the Hosmer-Lemeshow test.The model demonstrated robust discriminative performance,with an average area under the curve of 0.795(95%confidence interval:0.702-0.887)in 10-fold cross-validation.CONCLUSION Collectively,the presence of multiple lesions,lesion size of≥3 cm,lesion localization in the rectum,and severe fibrosis are significant independent predictors of DPOB in patients undergoing surgery for ECRC or PCLs.The proposed risk prediction model,which integrates these factors,demonstrates excellent predictive accuracy and clinical utility,thereby providing a valuable tool for risk stratification and postoperative management in this patient population.展开更多
BACKGROUND Early gastric cancer(EGC)or precancerous lesions(PCLs)are generally small tumors and carry a diminished chance of nodal infiltration.Thus far,very few studies have examined how endoscopic submucosal dissect...BACKGROUND Early gastric cancer(EGC)or precancerous lesions(PCLs)are generally small tumors and carry a diminished chance of nodal infiltration.Thus far,very few studies have examined how endoscopic submucosal dissection(ESD)affects postoperative recovery and complications in such patients.AIM To evaluate the influence of ESD on postoperative recovery and complications in patients with EGC or PCL.METHODS The study population included patients with EGC and PCL admitted to The First People’s Hospital of Fuyang District between December 2022 and December 2024,who were divided into the research(n=65)and control(n=55)groups if they underwent ESD and laparoscopic radical gastrectomy,respectively.Therapeutic outcomes(en bloc and curative resection rates),surgical parameters(incision length,intraoperative bleeding,and operative duration),postoperative recovery indices(time to first ambulation/flatus/first oral intake,and hospital stay duration),complications(infection,outflow obstruction,bleeding,and perforation),and tumor markers[carcinoembryonic antigen(CEA)and carbohydrate antigen(CA)125/19-9]were comparatively evaluated.RESULTS Compared with the control group,the research group achieved a significantly higher en bloc resection rate but a notably lower curative resection rate.Additionally,the research group demonstrated shorter incision lengths,reduced intraoperative bleeding,and shorter operative duration.Regarding postoperative recovery,the research group demonstrated earlier ambulation,faster bowel function restoration,quicker oral intake resumption,and shorter hospital stays.Furthermore,an evidently lower overall complication rate was recorded in the research group,as well as markedly reduced postoperative CEA,CA125,and CA19-9 concentrations.CONCLUSION When performed for EGC and PCLs,ESD demonstrates advantages such as higher en bloc resection(although lower curative resection rates),surgical trauma minimization,shortened operative duration,and faster recovery.Moreover,it is effective in reducing serum tumor marker levels while maintaining favorable safety.展开更多
BACKGROUND Tumor progression in patients with esophageal precancerous lesions(EPLs)or early esophageal carcinoma(EEC)is typically confined in both extent and location.Prompt and effective intervention significantly im...BACKGROUND Tumor progression in patients with esophageal precancerous lesions(EPLs)or early esophageal carcinoma(EEC)is typically confined in both extent and location.Prompt and effective intervention significantly improves treatment outcomes and prognosis for these individuals.AIM To determine the effect of endoscopic submucosal dissection(ESD)on efficacy,serum tumor markers(STMs),and 6-month postoperative recurrence rate in patients with either EPL or EEC.METHODS This study initially enrolled 120 patients with EPL or EEC,who were admitted from April 2021 to April 2024.Participants were divided into the control group(60 cases),which underwent thoracotomy,and the research group(60 cases)which received ESD treatment.The comparative analysis involved information regarding the efficacy(dissection area and resection rate per unit time),complications(delayed bleeding,wound infection,esophageal reflux,and postoperative esophageal stenosis),surgery-related parameters(bleeding volume,operation duration,and hospital length of stay),STMs[carcinoembryonic antigen(CEA),carbohydrate antigen 724(CA724),and tumor-specific growth factor(TSGF)],and the 6-month postoperative recurrence rate of the two groups.RESULTS Data indicated statistically higher dissection area and resection rate per unit of time in the research group than in the control group.Meanwhile,the research group demonstrated a notably lower overall incidence rate of complications,bleeding volume,operation duration,and hospital length of stay.Further,the CEA,CA724,and TSGF were markedly reduced in the research group after treatment,which were statistically lower compared to the baseline and those of the control group.Finally,during the follow-up,a comparable 6-month postoperative recurrence rate was determined in the two groups.CONCLUSION ESD is clinically effective and safe for EPL and EEC and can significantly restore abnormally increased levels of STMs.展开更多
BACKGROUND Detecting gastric precancerous lesions(GPLs)is critical for the early diagnosis and treatment of gastric cancer.Endoscopy combined with tissue examination is an important method for detecting GPLs.However,n...BACKGROUND Detecting gastric precancerous lesions(GPLs)is critical for the early diagnosis and treatment of gastric cancer.Endoscopy combined with tissue examination is an important method for detecting GPLs.However,negative biopsy results often increase patients’risks,economic burdens,and lead to additional healthcare costs.Improving the detection rate of GPLs and reducing the rate of negative biopsies is currently a key focus in endoscopic quality control.AIM To explore the relationships between the endoscopist biopsy rate(EBR),qualifications of endoscopists and endoscopic assistants,and detection rate of GPLs.METHODS EBR,endoscopists,and endoscopic assistants were divided into four groups:Low,moderate,high,and very high levels.Multivariable logistic regression analysis was used to analyze the relationships between EBR and the qualifications of endoscopists with respect to the detection rate of positive lesions.Pearson and Spearman correlation analyses were used to evaluate the correlation between EBR,endoscopist or endoscopic assistant qualifications,and the detection rate of positive lesions.RESULTS Compared with those in the low EBR group,the odds ratio(OR)values for detecting positive lesions in the moderate,high,and very high EBR groups were 1.12[95%confidence interval(CI):1.06-1.19,P<0.001],1.22(95%CI:1.14-1.31,P<0.001),and 1.38(95%CI:1.29-1.47,P<0.001),respectively.EBR was positively correlated with the detection rate of gastric precancerous conditions(atrophic gastritis/intestinal metaplasia)(ρ=0.465,P=0.004).In contrast,the qualifications of the endoscopists were positively correlated with GPLs detection(ρ=0.448,P=0.005).Compared to endoscopists with low qualification levels,those with moderate,high,and very high qualification levels endoscopists demonstrated increased detection rates of GPLs by 13%(OR=1.13,95%CI:0.98-1.31),20%(OR=1.20,95%CI:1.03-1.39),and 32%(OR=1.32,95%CI:1.15-1.52),respectively.Further analysis revealed that the qualifications of endoscopists were positively correlated with the detection rates of GPLs in the cardia(ρ=0.350,P=0.034),angularis(ρ=0.396,P=0.015)and gastric body(ρ=0.453,P=0.005)but not in the antrum(ρ=0.292,P=0.079).Moreover,the experience of endoscopic assistants was positively correlated with the detection rate of precancerous lesions by endoscopists with low or moderate qualifications(ρ=0.427,P=0.015).CONCLUSION Endoscopists and endoscopic assistants with high/very high qualifications,but not EBR,can improve the detection rate of GPLs.These results provide reliable evidence for the development of gastroscopic quality control indicators.展开更多
AIM： To evaluate whether celecoxib, a selective cyclooxygenase 2 （COX-2） inhibitor, could reduce the severity of gastric precancerous lesions following Hel/cobacter pylori （H pylorl） eradication. METHODS： H pylo...AIM： To evaluate whether celecoxib, a selective cyclooxygenase 2 （COX-2） inhibitor, could reduce the severity of gastric precancerous lesions following Hel/cobacter pylori （H pylorl） eradication. METHODS： H pylori-eradicated patients with gastric precancerous lesions randomly received either celecoxib （n = 30） or placebo （n = 30） for up to 3 mo. COX-2 expression and activity was determined by immunostaining and prostaglandin E2 （PGE2） assay, cell proliferation by Ki-67 immunostaining, apoptosis by TUNEL staining and angiogenesis by microvascular density （MVD） assay using CD31 staining.RESULTS： COX-2 protein expression was significantly increased in gastric precancerous lesions （atrophy, intestinal metaplasia and dysplasia, respectively） compared with chronic gastritis, and was concomitant with an increase in cell proliferation and angiogenesis. A significant improvement in precancerous lesions was observed in patients who received celecoxib compared with those who received placebo （P 〈 0.001）. Of these three changes, 84.6% of sites with dysplasia regressed in patients treated with celecoxib （P = 0.002） compared with 60% in the placebo group, suggesting that celecoxib was effective on the regression of dysplasia. COX-2 protein expression （P 〈 0.001） and COX-2 activity （P 〈 0.001） in the gastric tissues were consistently lower in celecoxib-treated patients compared with the placebo-treated subjects. Moreover, it was also shown that celecoxib suppressed cell proliferation （P 〈 0.01）, induced cell apoptosis （P 〈 0.01） and inhibited angiogenesis with decreased MVD （P 〈 0.001）. However, all of these effects were not seen in placebo-treated subjects. Furthermore, COX-2 inhibition resulted in the up-regulation of PPARy expression, a protective molecule with anti-neoplastic effects. CONCLUSION： H pylori eradication therapy followed by celecoxib treatment improves gastric precancerous lesions by inhibiting COX-2 activity, inducing apoptosis, and suppressing cell proliferation and angiogenesis.展开更多
AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gast...AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gastric cancer, intestinal metaplasia, atrophic gastritis, and atypical hyperplasia were analyzed for PTEN LOH and mutations within the entire coding region of PTEN gene by PCR-SSCP denaturing PAGE gel electrophoresis, and PTEN mutation was detected by PCR-SSCP sequencing followed by silver staining. RESULTS: LOH rate found in respectively atrophic gastritis was 10% (3/30), intestinal metaplasia 10% (3/30), atypical hyperplasia 13.3% (4/30), early stage gastric cancer 20% (6/30), and advanced stage gastric cancer 33.3% (9/30), None of the precancerous lesions and early stage gastric cancer showed PTEN mutations, but 10% (3/30) of the advanced stage gastric cancers, which were all positive for LOH, showed PTEN mutation. CONCLUSION: LOH of PTEN gene appears in precancerous lesions, and PTEN mutations are restricted to advanced gastric cancer, LOH and mutation of PTEN gene are closely related to the infiltration and metastasis of gastric cancer.展开更多
AIM:To explore the relationship between Cripto-1 (CR-1) and tyrosine phosphorylation STAT3 (p-STAT3) expressions in gastric cancer (GC) and gastric carcinogensis and metastasis.METHODS: The PV9000 immunohistochemical ...AIM:To explore the relationship between Cripto-1 (CR-1) and tyrosine phosphorylation STAT3 (p-STAT3) expressions in gastric cancer (GC) and gastric carcinogensis and metastasis.METHODS: The PV9000 immunohistochemical method was used to detect the expression of CR-1 and p-STAT3 in 178 cases of GC, 95 matched normal gastric mucosa, 40 chronic atrophic gastritis (CAG), 48 intestinal meta-plasia (IM) and 25 dysplasia (DYS). RESULTS: The positive rates of CR-1 and p-STAT3 expression were significantly higher in CAG (65.0% and 60.0%), in IM (83.3% and 77.1%), DYS (80.0% and 68%) and GC (71.3% and 60.1%) than in normal gastric mucosa (43.2% and 41.1%, P < 0.05), respectively. The expressions of CR-1 and p-STAT3 (78.3% and 66.7%) were signifi cantly higher in GC with lymphnode metastasis than in those without metastasis (53.1% and 42.9%, P < 0.05). CR-1 expression was also related to histological and Lauren's types of GC (P < 0.001). Furthermore, there was positive relation-ship between CR-1 and p-STAT3 expressions in GC (rk = 0.189, P = 0.002).CONCLUSION: The up-regulation of CR-1 and p-STAT3 may play important roles in gastric carcinogenesis and lymph node metastasis. CR-1 and p-STAT3 expression in GC was positively correlated, and the relevant molecular mechanism requires further investigations.展开更多
Hepatocarcinogenesis in human chronic liver diseases is a multi-step process in which hepatic precancerous lesions progress into early hepatocellular carcinoma(HCC) and progressed HCC, and the close surveillance and t...Hepatocarcinogenesis in human chronic liver diseases is a multi-step process in which hepatic precancerous lesions progress into early hepatocellular carcinoma(HCC) and progressed HCC, and the close surveillance and treatment of these lesions will help improve the survival rates of patients with HCC. The rapid development and extensive application of imaging technology have facilitated the discovery of nodular lesions of ambiguous significance, such as dysplastic nodules. Further investigations showed that these nodules may be hepatic precancerous lesions, and they often appear in patients with liver cirrhosis. Although the morphology of these nodules is not sufficient to support a diagnosis of malignant tumor, these nodules are closely correlated with the occurrence of HCC, as indicated by long-term follow-up studies. In recent years, the rapid development and wide application of pathology, molecular genetics and imaging technology have elucidated the characteristics of precancerous lesions. Based on our extensive review of the relevant literature, this article focuses on evidence indicating that high-grade dysplastic nodules are more likely to transform into HCC than low-grade dysplastic nodules based on clinical, pathological, molecular genetic and radiological assessments. In addition, evidence supporting the precancerous nature of large cell change in hepatitis B virus-related HCC is discussed.展开更多
Gastric cancer(GC)is a common gastrointestinal tumor.Gastric precancerous lesions(GPL)are the last pathological stage before normal gastric mucosa transforms into GC.However,preventing the transformation from GPL to G...Gastric cancer(GC)is a common gastrointestinal tumor.Gastric precancerous lesions(GPL)are the last pathological stage before normal gastric mucosa transforms into GC.However,preventing the transformation from GPL to GC remains a challenge.Traditional Chinese medicine(TCM)has been used to treat gastric disease for millennia.A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL.This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC,especially focusing on antiinflammatory,anti-angiogenesis,proliferation,and apoptosis.This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.展开更多
BACKGROUND Gastric precancerous lesions(GPL)precede the development of gastric cancer(GC).They are characterized by gastric mucosal intestinal metaplasia and dysplasia caused by various factors such as inflammation,ba...BACKGROUND Gastric precancerous lesions(GPL)precede the development of gastric cancer(GC).They are characterized by gastric mucosal intestinal metaplasia and dysplasia caused by various factors such as inflammation,bacterial infection,and injury.Abnormalities in autophagy and glycolysis affect GPL progression,and their effective regulation can aid in GPL treatment and GC prevention.Xiaojianzhong decoction(XJZ)is a classic compound for the treatment of digestive system diseases in ancient China which can inhibit the progression of GPL.However,its specific mechanism of action is still unclear.AIM To investigate the therapeutic effects of XJZ decoction on a rat GPL model and the mechanisms underlying its effects on autophagy and glycolysis regulation in GPLs.METHODS Wistar rats were randomly divided into six groups of five rats each and all groups except the control group were subjected to GPL model construction for 18 wk.The rats’body weight was monitored every 2 wk starting from the beginning of modeling.Gastric histopathology was examined using hematoxylin-eosin staining and Alcian blue-periodic acid-Schiff staining.Autophagy was observed using transmission electron microscopy.The expressions of autophagy,hypoxia,and glycolysis related proteins in gastric mucosa were detected using immunohistochemistry and immunofluorescence.The expressions of the following proteins in gastric tissues:B cell lymphoma/Leukemia-2 and adenovirus E1B19000 interacting protein 3(Bnip-3),microtubule associated protein 1 light chain 3(LC-3),moesin-like BCL2-interacting protein 1(Beclin-1),phosphatidylinositol 3-kimase(PI3K),protein kinase B(AKT),mammalian target of rapamycin(mTOR),p53,AMP-activated protein kinase(AMPK),and Unc-51 like kinase 1(ULK1)were detected using western blot.The relative expressions of autophagy,hypoxia,and glycolysis related mRNA in gastric tissues was detected using reverse transcription-polymerase chain reaction.RESULTS Treatment with XJZ increased the rats’body weight and improved GPL-related histopathological manifestations.It also decreased autophagosome and autolysosome formation in gastric tissues and reduced Bnip-3,Beclin-1,and LC-3II expressions,resulting in inhibition of autophagy.Moreover,XJZ down-regulated glycolysis-related monocarboxylate transporter(MCT1),MCT4,and CD147 expressions.XJZ prevented the increase of autophagy level by decreasing gastric mucosal hypoxia,activating the PI3K/AKT/mTOR pathway,inhibiting the p53/AMPK pathway activation and ULK1 Ser-317 and Ser-555 phosphorylation.In addition,XJZ improved abnormal gastric mucosal glucose metabolism by ameliorating gastric mucosal hypoxia and inhibiting ULK1 expression.CONCLUSION This study demonstrates that XJZ may inhibit autophagy and glycolysis in GPL gastric mucosal cells by improving gastric mucosal hypoxia and regulating PI3K/AKT/mTOR and p53/AMPK/ULK1 signaling pathways,providing a feasible strategy for the GPL treatment.展开更多
AIM： To observe the curative effect of Weiansan （WAS） on gastric precancerous lesions （GPL） and H pylori elimination. METHODS： Seventy-six patients with GPL were randomly divided into two groups： WAS group （n ...AIM： To observe the curative effect of Weiansan （WAS） on gastric precancerous lesions （GPL） and H pylori elimination. METHODS： Seventy-six patients with GPL were randomly divided into two groups： WAS group （n = 42） and Weifuchun （WFC） group （n = 34）. The patients in the WAS group were administered 5 g WAS 3 times a day, and the patients in the WFC group took WFC （4 tablets） 3 times a day. To monitor inflammation of gastric mucosa, degree of glandular atrophy （GA）, intestinal metaplasia （IM） and dysplasia, and H pylori infection, all patients underwent gastroscopy and biopsy with pathological examination before and after treatment. Fifty male Sprague-Dawley （SD） rats were used in animal experiments. Of these, 10 served as the control group （n = 10）, 40 were given ranitidine combined with N-methyl- N^1-nitro-N-nitrosoguanidine （MNNG） for 12 wk and divided into 4 groups randomly： model group （n = 10）, high-dose WAS group （n = 10）, low-close WAS group （n = 10） and WFC group （n = 10）. Twelve weeks later, all rats were killed and a 2 cm ×1 cm tissue was taken from the lesser curvature of the gastric antrum. H pylori infection was determined by the fast urease method. RESULTS： The curative effect in WAS groups was similar to that in WFC groups. There was no statistical difference in degree of GA, IM and dysplasia between WAS and WFC groups. The rate of Hpylori infection in the model group （positive/negative： 9/1） was significantly higher than that in the control group （positive/negative： 1/9） （P 〈 0.01）. H pylori elimination in the high-dose WAS group （positive/negative： 4/6） and low-dose WAS group （positive/negative： 6/4） was similar to that in the WFC group （positive/negative： 4/6） （P 〉 0.05）.CONCLUSION： WAS improves clinical symptoms by suppressing GA, IM and dysplasia and eliminating H pylori.展开更多
China has a high incidence of gastric cancer. Secondary prevention of gastric cancer is a major public health problem that must be solved urgently. Modern medicine focuses on the pathogenesis of precancerous lesions o...China has a high incidence of gastric cancer. Secondary prevention of gastric cancer is a major public health problem that must be solved urgently. Modern medicine focuses on the pathogenesis of precancerous lesions of gastric cancer(PLGC), and it has been found that there are a variety of abnormal gene expression patterns in PLGC. This study summarizes recent advances in our understanding of the therapeutic mechanisms of PLGC from various clinical studies;this will provide a reference for studying the therapeutic mechanisms of Traditional Chinese Medicine in the treatment of PLGC from the combined points of view of Traditional Chinese and Conventional medicine.展开更多
BACKGROUND Helicobacter pylori(H.pylori)infects about 50%of the world population and is the major cause of chronic gastritis,peptic ulcers,and gastric cancer.Chronic H.pylori infection induces gastric mucosal precance...BACKGROUND Helicobacter pylori(H.pylori)infects about 50%of the world population and is the major cause of chronic gastritis,peptic ulcers,and gastric cancer.Chronic H.pylori infection induces gastric mucosal precancerous lesions mostly in adulthood,and it is debatable whether these pathological conditions can occur in childhood and adolescents as well.Since this is a critical issue to determine if intervention should be offered for this population group,we investigated the gastric mucosal precancerous lesions in pediatric patients in an area in central China with a high prevalence of H.pylori and gastric cancer.AIM To investigate the relationship of H.pylori infection and gastric mucosal precancerous lesions in children and adolescents in central China.METHODS We screened 4258 ward-admitted children and adolescent patients with upper gastrointestinal symptoms,and finally enrolled 1015 pediatric patients with H.pylori infection and endoscopic and histological data.H.pylori infection status was determined by rapid urease test and histopathological examination.Both clinical and pathological data were collected and analyzed retrospectively.Occurrence of gastric mucosal precancerous lesions,inflammatory activity and degree of inflammatory cell infiltration between H.pylori-positive and-negative groups were compared.RESULTS Among the 1015 eligible children and adolescents,the overall H.pylori infection rate was 84.14%(854/1015).The infection rate increased with age.The incidence of gastric mucosal precancerous lesions in H.pylori-infected children was 4.33%(37/854),which included atrophic gastritis(17 cases),intestinal metaplasia(11 cases)and dysplasia(9 cases).In H.pylori-negative patients,only 1 atrophic gastritis case[0.62%,(1/161)]was found(P<0.05).Active inflammation in H.pyloriinfected patients was significantly higher than that in non-infected patients,and the H.pyloriinfected group showed more severe lymphocyte and neutrophil granulocyte infiltration(P<0.001).In addition,endoscopy revealed that the most common findings in H.pylori-positive patients were antral nodularity,but in H.pylori-negative patients only superficial gastritis was observed.CONCLUSION In children and adolescents,gastric mucosal precancerous lesions occurred in 4.33%of H.pyloriinfected patients in central China.These cases included atrophic gastritis,intestinal metaplasia,and dysplasia.The data revealed an obvious critical issue requiring future investigation and intervention for this population group.展开更多
BACKGROUND In recent years,two new narrow-band imaging(NBI)classifications have been proposed:The NBI international colorectal endoscopic(NICE)classification and Japanese NBI expert team(JNET)classification.Most valid...BACKGROUND In recent years,two new narrow-band imaging(NBI)classifications have been proposed:The NBI international colorectal endoscopic(NICE)classification and Japanese NBI expert team(JNET)classification.Most validation studies of the two new NBI classifications were conducted in classification setting units by experienced endoscopists,and the application of use in different centers among endoscopists with different endoscopy skills remains unknown.AIM To evaluate clinical application and possible problems of NICE and JNET classification for the differential diagnosis of colorectal cancer and precancerous lesions.METHODS Six endoscopists with varying levels of experience participated in this study.Eighty-seven consecutive patients with a total of 125 lesions were photographed during non-magnifying conventional white-light colonoscopy,non-magnifying NBI,and magnifying NBI.The three groups of endoscopic pictures of each lesion were evaluated by the six endoscopists in randomized order using the NICE and JENT classifications separately.Then we calculated the six endoscopists’sensitivity,specificity,accuracy,positive predictive value,and negative predictive value for each category of the two classifications.RESULTS The sensitivity,specificity,and accuracy of JNET classification type 1 and 3 were similar to NICE classification type 1 and 3 in both the highly experienced endoscopist(HEE)and less-experienced endoscopist(LEE)groups.The specificity of JNET classification type 1 and 3 and NICE classification type 3 in both the HEE and LEE groups was>95%,and the overall interobserver agreement was good in both groups.The sensitivity of NICE classification type 3 lesions for diagnosis of SM-d carcinoma in the HEE group was significantly superior to that in the LEE group(91.7%vs 83.3%;P=0.042).The sensitivity of JNET classification type 2B lesions for the diagnosis of high-grade dysplasia or superficial submucosal invasive carcinoma in the HEE and LEE groups was 53.8%and 51.3%,respectively.Compared with other types of JNET classification,the diagnostic ability of type 2B was the weakest.CONCLUSION The treatment strategy of the two classification type 1 and 3 lesions can be based on the results of endoscopic examination.JNET type 2B lesions need further examination.展开更多
Upper gastrointestinal(GI)cancers are the leading cause of cancer-related deaths worldwide.Early identification of precancerous lesions has been shown to minimize the incidence of GI cancers and substantiate the vital...Upper gastrointestinal(GI)cancers are the leading cause of cancer-related deaths worldwide.Early identification of precancerous lesions has been shown to minimize the incidence of GI cancers and substantiate the vital role of screening endoscopy.However,unlike GI cancers,precancerous lesions in the upper GI tract can be subtle and difficult to detect.Artificial intelligence techniques,especially deep learning algorithms with convolutional neural networks,might help endoscopists identify the precancerous lesions and reduce interobserver variability.In this review,a systematic literature search was undertaken of the Web of Science,PubMed,Cochrane Library and Embase,with an emphasis on the deep learning-based diagnosis of precancerous lesions in the upper GI tract.The status of deep learning algorithms in upper GI precancerous lesions has been systematically summarized.The challenges and recommendations targeting this field are comprehensively analyzed for future research.展开更多
Objective： To investigate potential therapeutic effects and mechanism of Weining granule in the treatment of gastric precancerous lesions. Methods： Sixty rats were randomly assigned to a blank group or a model group...Objective： To investigate potential therapeutic effects and mechanism of Weining granule in the treatment of gastric precancerous lesions. Methods： Sixty rats were randomly assigned to a blank group or a model group or to receive retinoic acid or high-, medium- or low- dose of Weining granule. General conditions of the animals were observed before and after treatment. Changes in gastric mucosal pathohistology, telomerase activity, proliferation index （PI） and apoptosis index （AI） were measured. Results： General conditions, including activity and eating, were improved in all Weining-granule-treated groups with the numbers of rats having intestinal metaplasia （IM）, atypical hyperplasia （ATP） or positive telomerase activity being significantly lower than those in the model group （P 〈 0.05 or P 〈 0.01）. Compared with the model group, all doses of Weining granule significantly decreased PI （P 〈 0.01） and increased AI （P 〈 0.05）. Conclusion： Weining granule may provide a therapeutic benefit for the treatment of gastric precancerous lesions by inhibiting telomerase activity and proliferation of gastric cancer cells and by accelerating their apoptosis.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82274442)the Key Research Project in Traditional Chinese Medicine of Tianjin Municipal Health Commission(Grant No.202007)the Integrated Traditional Chinese and Western Medicine Research Project of Tianjin Municipal Health Commission(Grant No.2023134).
文摘Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling results in mucosal impairment and the initiation of cancer.Banxia Xiexin Decoction(BXD),a well-known formula in traditional Chinese medicine(TCM),shows promise in treating gastric disorders,but its mechanisms in gastric restoration remain unclear.Methods:Using MNNG-induced CAG and PLGC rat models,BXD was administered for 12 weeks.Gastric mucosal pathology was assessed via hematoxylin-eosin staining.Proliferation(Ki-67)and angiogenesis(VEGFA)markers were evaluated by immunohistochemistry.Network pharmacology identified BXD’s targets and pathways.Notch pathway components(Notch1,Jagged1,Dll4,Hes1)were analyzed via qPCR,Western blot,and immunohistochemistry.Results:BXD significantly ameliorated mucosal atrophy,glandular structural disorder,and dysplasia in CAG and PLGC rats.Network pharmacology revealed 323 overlapping targets between BXD and PLGC,with Notch signaling as a central pathway.BXD downregulated Notch1,Jagged1,Dll4,and Hes1 expression at transcriptional and protein levels,suppressed Ki-67(proliferation)and VEGFA(angiogenesis)overexpression,and restored gastric mucosal integrity.Conclusion:BXD inhibits Notch signaling,reduces aberrant proliferation and angiogenesis,and interrupts Correa’s gastric carcinogenesis cascade.This study provides mechanistic evidence supporting BXD as a TCM-based intervention for gastric precancerous lesions.
文摘Gastric precancerous lesions(GPL)represent a crucial stage in the complex process of gastric carcinogenesis that leads to gastric cancer(GC),one of the most prevalent cancers and a major source of cancer mortality worldwide.Many studies have identified the gastrointestinal microbiota,or gut microbiota,as an important contributor to both the pathogenesis and treatment of GPL and GC,thus understanding its role in this transition is crucial.The purpose of this literature review is to introduce the current landscape of microbiota research associated with GPL and GC,with an emphasis on Helicobacter pylori(H.pylori)driven microbial dysbiosis and its modulation through Western medicine and traditional Chinese medicine(TCM)approaches.By elucidating the underlying mechanisms of H.pylori colonization,patterns,and interactions among microbiota,as well as the influence of microbial metabolites,this review highlights crucial driving factors of gastric carcinogenesis.The role of microbiota in conventional interventions,including H.pylori eradication,immunotherapy,as well as TCM herbal decoctions,is also discussed to provide a detailed understanding of the complex interactions between therapy and microbiota and how it could be potentially targeted for effective management of GPL and GC.Ultimately,microbiota-targeting therapeutics may represent a new path toward early detection,targeted treatment,improved prognosis,and potentially reduced incidence of GPL and GC.
基金the National Natural Science Foundation of China,No.82374292,82205095,and 82305179the Horizontal Development Foundation of Beijing University of Chinese Medicine,No.BUCM-2021-JS-KF-065the China Postdoctoral Science Foundation Grant,No.2022M720520.
文摘BACKGROUND Precancerous lesions of gastric cancer(PLGC)represent a critical pathological stage in the development of intestinal gastric cancer.Early detection and diagnosis are key to reducing the incidence of gastric cancer.Substantial advancements have been made in PLGC research in recent years,making it necessary to provide updated reviews using bibliometric methods.We hypothesize that this review will identify emerging trends,key research areas,and gaps in PLGC research,providing insights that could guide future studies and enhance prevention strategies.AIM To comprehensively review the current state of research on PLGC,examining development trends and research hotspots.METHODS We conducted a bibliometric analysis of PLGC-related studies published between 2004 and 2023 using the Web of Science Core Collection database.We employed Software,including VOSviewer,CiteSpace,R software,and SCImago Graphica,to map scientific networks and visualize knowledge trends in terms of publication volume,countries/regions,institutions,journals,authors,and keywords.RESULTS A total of 4097 articles were included,and overall publication volume showed an increasing trend.Over the past two decades,China published the most articles,followed by the United States,Japan,South Korea,and Italy.Among the top 10 contributors,the United States ranked highest in institutions,authors,and citations and demonstrated the strongest international collaboration.Research keywords in this field were clustered into three main categories:Risk factors,pathogenesis,and diagnosis and treatment.Pathogenesis and molecular biomarkers remain key areas of focus.Future research should explore the mechanisms of gut microbiota,immune microenvironment,metabolic reprogramming,and epigenetics.Advanced technologies,including single-cell sequencing,spatially resolved analysis,multi-omics approaches,artificial intelligence,and machine learning,will likely accelerate in-depth investigations of PLGC.CONCLUSION PLGC research has rapidly developed in recent years,gaining considerable attention.This bibliometric analysis reveals research state and emerging trends over the past 20 years,providing insights for future studies.
基金Supported by the National Administration of Traditional Chinese Medicine National Superior Specialty Project of Traditional Chinese Medicine,No.[2024]90Shanghai Municipal Administrator of Traditional Chinese Medicine Policy Letter[2024],No.20+1 种基金Science and Technology Development Fund of Shanghai University of Traditional Chinese Medicine,No.23KFL102Shuguang Hospital Siming Foundation Research Special Project,No.SGKJ-202304。
文摘Precancerous lesions of gastric cancer(PLGC)are crucial for the progression to gastric cancer,and early intervention in PLGC is pivotal in preventing its development into gastric cancer.In order to illustrate the molecular mechanisms underlying PLGC and the roles of associated genes within these lesions,genetically engineered mouse models(GEMMs)have been developed.We systematically summarize the current GEMMs,and highlight the principal pathological mechanisms involved,including gastrin/gastric acid balance,inflammatory factors,the interplay between cancer-promoting and cancer-suppressing genes,and apoptotic pathways.We further discuss the mechanisms involved in the existing GEMMs of PLGC.
文摘BACKGROUND As a minimally invasive technique,endoscopic submucosal dissection(ESD)is widely used in treating early colorectal cancer(ECRC)and precancerous lesions(PCLs).However,a common postoperative complication-delayed postoperative bleeding(DPOB)-can significantly hinder patient recovery.AIM To build and validate a predictive model for assessing post-ESD DPOB risk in ECRC and PCL patients,utilizing logistic regression methodology.METHODS A retrospective review was conducted on ECRC/PCL 302 patients who received ESD at our hospital between July 2021 and July 2024.The cohort was stratified based on the incidence of DPOB following ESD,forming DPOB and non-DPOB groups.Through allocation,they were further allocated into model and validation cohorts.Clinical variables from both cohorts were collated and subjected to univariate analysis to determine potential factors associated with post-ESD DPOB.Subsequently,we constructed a predictive model for DPOB risk employing logistic regression analysis.Model performance assessment used receiver operating characteristic curves in both the training and validation cohorts,with internal validation accomplished via 10-fold cross-validation.RESULTS The occurrence rate of DPOB was 9.93%.Univariate analysis revealed that the number of lesions,lesion size,lesion location,degree of submucosal fibrosis,and intraoperative bleeding were significantly associated with DPOB.Binary logistic regression analysis identified the number of lesions,lesion size,lesion location,and degree of submucosal fibrosis as independent DPOB determinants.A nomogram that was developed to quantify the DPOB risk exhibited that an increment in the total score corresponded to an increased risk.The model achieved area under the curve values of 0.831 and 0.821 in the model and validation groups,respectively,with P values of 0.853 and 0.203 in the Hosmer-Lemeshow test.The model demonstrated robust discriminative performance,with an average area under the curve of 0.795(95%confidence interval:0.702-0.887)in 10-fold cross-validation.CONCLUSION Collectively,the presence of multiple lesions,lesion size of≥3 cm,lesion localization in the rectum,and severe fibrosis are significant independent predictors of DPOB in patients undergoing surgery for ECRC or PCLs.The proposed risk prediction model,which integrates these factors,demonstrates excellent predictive accuracy and clinical utility,thereby providing a valuable tool for risk stratification and postoperative management in this patient population.
文摘BACKGROUND Early gastric cancer(EGC)or precancerous lesions(PCLs)are generally small tumors and carry a diminished chance of nodal infiltration.Thus far,very few studies have examined how endoscopic submucosal dissection(ESD)affects postoperative recovery and complications in such patients.AIM To evaluate the influence of ESD on postoperative recovery and complications in patients with EGC or PCL.METHODS The study population included patients with EGC and PCL admitted to The First People’s Hospital of Fuyang District between December 2022 and December 2024,who were divided into the research(n=65)and control(n=55)groups if they underwent ESD and laparoscopic radical gastrectomy,respectively.Therapeutic outcomes(en bloc and curative resection rates),surgical parameters(incision length,intraoperative bleeding,and operative duration),postoperative recovery indices(time to first ambulation/flatus/first oral intake,and hospital stay duration),complications(infection,outflow obstruction,bleeding,and perforation),and tumor markers[carcinoembryonic antigen(CEA)and carbohydrate antigen(CA)125/19-9]were comparatively evaluated.RESULTS Compared with the control group,the research group achieved a significantly higher en bloc resection rate but a notably lower curative resection rate.Additionally,the research group demonstrated shorter incision lengths,reduced intraoperative bleeding,and shorter operative duration.Regarding postoperative recovery,the research group demonstrated earlier ambulation,faster bowel function restoration,quicker oral intake resumption,and shorter hospital stays.Furthermore,an evidently lower overall complication rate was recorded in the research group,as well as markedly reduced postoperative CEA,CA125,and CA19-9 concentrations.CONCLUSION When performed for EGC and PCLs,ESD demonstrates advantages such as higher en bloc resection(although lower curative resection rates),surgical trauma minimization,shortened operative duration,and faster recovery.Moreover,it is effective in reducing serum tumor marker levels while maintaining favorable safety.
文摘BACKGROUND Tumor progression in patients with esophageal precancerous lesions(EPLs)or early esophageal carcinoma(EEC)is typically confined in both extent and location.Prompt and effective intervention significantly improves treatment outcomes and prognosis for these individuals.AIM To determine the effect of endoscopic submucosal dissection(ESD)on efficacy,serum tumor markers(STMs),and 6-month postoperative recurrence rate in patients with either EPL or EEC.METHODS This study initially enrolled 120 patients with EPL or EEC,who were admitted from April 2021 to April 2024.Participants were divided into the control group(60 cases),which underwent thoracotomy,and the research group(60 cases)which received ESD treatment.The comparative analysis involved information regarding the efficacy(dissection area and resection rate per unit time),complications(delayed bleeding,wound infection,esophageal reflux,and postoperative esophageal stenosis),surgery-related parameters(bleeding volume,operation duration,and hospital length of stay),STMs[carcinoembryonic antigen(CEA),carbohydrate antigen 724(CA724),and tumor-specific growth factor(TSGF)],and the 6-month postoperative recurrence rate of the two groups.RESULTS Data indicated statistically higher dissection area and resection rate per unit of time in the research group than in the control group.Meanwhile,the research group demonstrated a notably lower overall incidence rate of complications,bleeding volume,operation duration,and hospital length of stay.Further,the CEA,CA724,and TSGF were markedly reduced in the research group after treatment,which were statistically lower compared to the baseline and those of the control group.Finally,during the follow-up,a comparable 6-month postoperative recurrence rate was determined in the two groups.CONCLUSION ESD is clinically effective and safe for EPL and EEC and can significantly restore abnormally increased levels of STMs.
基金Supported by Jiangsu Science and Technology Project,No.BK20211039the Top Talent Support Program for Young and Middle-Aged People of the Wuxi Health Committee,No.BJ2023008+3 种基金the Major Program of Wuxi Medical Center,Nanjing Medical University,No.WMCM202305the Cohort and Clinical Research Program of Wuxi Medical Center,Nanjing Medical University,No.WMCC202302the Scientific Research Program of Wuxi Health Commission,No.Z202208Wuxi Municipal Health and Health Commission Precision Medicine Project,No.J202104.
文摘BACKGROUND Detecting gastric precancerous lesions(GPLs)is critical for the early diagnosis and treatment of gastric cancer.Endoscopy combined with tissue examination is an important method for detecting GPLs.However,negative biopsy results often increase patients’risks,economic burdens,and lead to additional healthcare costs.Improving the detection rate of GPLs and reducing the rate of negative biopsies is currently a key focus in endoscopic quality control.AIM To explore the relationships between the endoscopist biopsy rate(EBR),qualifications of endoscopists and endoscopic assistants,and detection rate of GPLs.METHODS EBR,endoscopists,and endoscopic assistants were divided into four groups:Low,moderate,high,and very high levels.Multivariable logistic regression analysis was used to analyze the relationships between EBR and the qualifications of endoscopists with respect to the detection rate of positive lesions.Pearson and Spearman correlation analyses were used to evaluate the correlation between EBR,endoscopist or endoscopic assistant qualifications,and the detection rate of positive lesions.RESULTS Compared with those in the low EBR group,the odds ratio(OR)values for detecting positive lesions in the moderate,high,and very high EBR groups were 1.12[95%confidence interval(CI):1.06-1.19,P<0.001],1.22(95%CI:1.14-1.31,P<0.001),and 1.38(95%CI:1.29-1.47,P<0.001),respectively.EBR was positively correlated with the detection rate of gastric precancerous conditions(atrophic gastritis/intestinal metaplasia)(ρ=0.465,P=0.004).In contrast,the qualifications of the endoscopists were positively correlated with GPLs detection(ρ=0.448,P=0.005).Compared to endoscopists with low qualification levels,those with moderate,high,and very high qualification levels endoscopists demonstrated increased detection rates of GPLs by 13%(OR=1.13,95%CI:0.98-1.31),20%(OR=1.20,95%CI:1.03-1.39),and 32%(OR=1.32,95%CI:1.15-1.52),respectively.Further analysis revealed that the qualifications of endoscopists were positively correlated with the detection rates of GPLs in the cardia(ρ=0.350,P=0.034),angularis(ρ=0.396,P=0.015)and gastric body(ρ=0.453,P=0.005)but not in the antrum(ρ=0.292,P=0.079).Moreover,the experience of endoscopic assistants was positively correlated with the detection rate of precancerous lesions by endoscopists with low or moderate qualifications(ρ=0.427,P=0.015).CONCLUSION Endoscopists and endoscopic assistants with high/very high qualifications,but not EBR,can improve the detection rate of GPLs.These results provide reliable evidence for the development of gastroscopic quality control indicators.
基金Support by The National Natural Science Foundation of China, No. 30370637
文摘AIM： To evaluate whether celecoxib, a selective cyclooxygenase 2 （COX-2） inhibitor, could reduce the severity of gastric precancerous lesions following Hel/cobacter pylori （H pylorl） eradication. METHODS： H pylori-eradicated patients with gastric precancerous lesions randomly received either celecoxib （n = 30） or placebo （n = 30） for up to 3 mo. COX-2 expression and activity was determined by immunostaining and prostaglandin E2 （PGE2） assay, cell proliferation by Ki-67 immunostaining, apoptosis by TUNEL staining and angiogenesis by microvascular density （MVD） assay using CD31 staining.RESULTS： COX-2 protein expression was significantly increased in gastric precancerous lesions （atrophy, intestinal metaplasia and dysplasia, respectively） compared with chronic gastritis, and was concomitant with an increase in cell proliferation and angiogenesis. A significant improvement in precancerous lesions was observed in patients who received celecoxib compared with those who received placebo （P 〈 0.001）. Of these three changes, 84.6% of sites with dysplasia regressed in patients treated with celecoxib （P = 0.002） compared with 60% in the placebo group, suggesting that celecoxib was effective on the regression of dysplasia. COX-2 protein expression （P 〈 0.001） and COX-2 activity （P 〈 0.001） in the gastric tissues were consistently lower in celecoxib-treated patients compared with the placebo-treated subjects. Moreover, it was also shown that celecoxib suppressed cell proliferation （P 〈 0.01）, induced cell apoptosis （P 〈 0.01） and inhibited angiogenesis with decreased MVD （P 〈 0.001）. However, all of these effects were not seen in placebo-treated subjects. Furthermore, COX-2 inhibition resulted in the up-regulation of PPARy expression, a protective molecule with anti-neoplastic effects. CONCLUSION： H pylori eradication therapy followed by celecoxib treatment improves gastric precancerous lesions by inhibiting COX-2 activity, inducing apoptosis, and suppressing cell proliferation and angiogenesis.
基金Supported by the National Natural Science Foundation of China,No. 30070845
文摘AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gastric cancer, intestinal metaplasia, atrophic gastritis, and atypical hyperplasia were analyzed for PTEN LOH and mutations within the entire coding region of PTEN gene by PCR-SSCP denaturing PAGE gel electrophoresis, and PTEN mutation was detected by PCR-SSCP sequencing followed by silver staining. RESULTS: LOH rate found in respectively atrophic gastritis was 10% (3/30), intestinal metaplasia 10% (3/30), atypical hyperplasia 13.3% (4/30), early stage gastric cancer 20% (6/30), and advanced stage gastric cancer 33.3% (9/30), None of the precancerous lesions and early stage gastric cancer showed PTEN mutations, but 10% (3/30) of the advanced stage gastric cancers, which were all positive for LOH, showed PTEN mutation. CONCLUSION: LOH of PTEN gene appears in precancerous lesions, and PTEN mutations are restricted to advanced gastric cancer, LOH and mutation of PTEN gene are closely related to the infiltration and metastasis of gastric cancer.
基金Supported by National Natural Science Foundation of China, No.30973503Special Fund for Climbing Scholars of Universities in Liaoning Province, China, 2009-2010
文摘AIM:To explore the relationship between Cripto-1 (CR-1) and tyrosine phosphorylation STAT3 (p-STAT3) expressions in gastric cancer (GC) and gastric carcinogensis and metastasis.METHODS: The PV9000 immunohistochemical method was used to detect the expression of CR-1 and p-STAT3 in 178 cases of GC, 95 matched normal gastric mucosa, 40 chronic atrophic gastritis (CAG), 48 intestinal meta-plasia (IM) and 25 dysplasia (DYS). RESULTS: The positive rates of CR-1 and p-STAT3 expression were significantly higher in CAG (65.0% and 60.0%), in IM (83.3% and 77.1%), DYS (80.0% and 68%) and GC (71.3% and 60.1%) than in normal gastric mucosa (43.2% and 41.1%, P < 0.05), respectively. The expressions of CR-1 and p-STAT3 (78.3% and 66.7%) were signifi cantly higher in GC with lymphnode metastasis than in those without metastasis (53.1% and 42.9%, P < 0.05). CR-1 expression was also related to histological and Lauren's types of GC (P < 0.001). Furthermore, there was positive relation-ship between CR-1 and p-STAT3 expressions in GC (rk = 0.189, P = 0.002).CONCLUSION: The up-regulation of CR-1 and p-STAT3 may play important roles in gastric carcinogenesis and lymph node metastasis. CR-1 and p-STAT3 expression in GC was positively correlated, and the relevant molecular mechanism requires further investigations.
文摘Hepatocarcinogenesis in human chronic liver diseases is a multi-step process in which hepatic precancerous lesions progress into early hepatocellular carcinoma(HCC) and progressed HCC, and the close surveillance and treatment of these lesions will help improve the survival rates of patients with HCC. The rapid development and extensive application of imaging technology have facilitated the discovery of nodular lesions of ambiguous significance, such as dysplastic nodules. Further investigations showed that these nodules may be hepatic precancerous lesions, and they often appear in patients with liver cirrhosis. Although the morphology of these nodules is not sufficient to support a diagnosis of malignant tumor, these nodules are closely correlated with the occurrence of HCC, as indicated by long-term follow-up studies. In recent years, the rapid development and wide application of pathology, molecular genetics and imaging technology have elucidated the characteristics of precancerous lesions. Based on our extensive review of the relevant literature, this article focuses on evidence indicating that high-grade dysplastic nodules are more likely to transform into HCC than low-grade dysplastic nodules based on clinical, pathological, molecular genetic and radiological assessments. In addition, evidence supporting the precancerous nature of large cell change in hepatitis B virus-related HCC is discussed.
基金Supported by the National Natural Science Foundation of China,No.81904064Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences,No.CI2021A03804 and No.CI2021A05052Fundamental Research Funds for the Central Public Welfare Research Institutes,No.ZZ14-YQ-023,No.ZXKT21017,and No.ZXKT21024.
文摘Gastric cancer(GC)is a common gastrointestinal tumor.Gastric precancerous lesions(GPL)are the last pathological stage before normal gastric mucosa transforms into GC.However,preventing the transformation from GPL to GC remains a challenge.Traditional Chinese medicine(TCM)has been used to treat gastric disease for millennia.A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL.This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC,especially focusing on antiinflammatory,anti-angiogenesis,proliferation,and apoptosis.This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.
基金Supported by the Shaanxi Science and Technology overall Planning and Innovation Project,No.2016KTTSSF01-05Key R&D projects in Shaanxi Province,No.2022ZDLSF05-10Shaanxi University of Chinese Medicine Discipline Innovation Team Construction Project,No.2019-YL-05.
文摘BACKGROUND Gastric precancerous lesions(GPL)precede the development of gastric cancer(GC).They are characterized by gastric mucosal intestinal metaplasia and dysplasia caused by various factors such as inflammation,bacterial infection,and injury.Abnormalities in autophagy and glycolysis affect GPL progression,and their effective regulation can aid in GPL treatment and GC prevention.Xiaojianzhong decoction(XJZ)is a classic compound for the treatment of digestive system diseases in ancient China which can inhibit the progression of GPL.However,its specific mechanism of action is still unclear.AIM To investigate the therapeutic effects of XJZ decoction on a rat GPL model and the mechanisms underlying its effects on autophagy and glycolysis regulation in GPLs.METHODS Wistar rats were randomly divided into six groups of five rats each and all groups except the control group were subjected to GPL model construction for 18 wk.The rats’body weight was monitored every 2 wk starting from the beginning of modeling.Gastric histopathology was examined using hematoxylin-eosin staining and Alcian blue-periodic acid-Schiff staining.Autophagy was observed using transmission electron microscopy.The expressions of autophagy,hypoxia,and glycolysis related proteins in gastric mucosa were detected using immunohistochemistry and immunofluorescence.The expressions of the following proteins in gastric tissues:B cell lymphoma/Leukemia-2 and adenovirus E1B19000 interacting protein 3(Bnip-3),microtubule associated protein 1 light chain 3(LC-3),moesin-like BCL2-interacting protein 1(Beclin-1),phosphatidylinositol 3-kimase(PI3K),protein kinase B(AKT),mammalian target of rapamycin(mTOR),p53,AMP-activated protein kinase(AMPK),and Unc-51 like kinase 1(ULK1)were detected using western blot.The relative expressions of autophagy,hypoxia,and glycolysis related mRNA in gastric tissues was detected using reverse transcription-polymerase chain reaction.RESULTS Treatment with XJZ increased the rats’body weight and improved GPL-related histopathological manifestations.It also decreased autophagosome and autolysosome formation in gastric tissues and reduced Bnip-3,Beclin-1,and LC-3II expressions,resulting in inhibition of autophagy.Moreover,XJZ down-regulated glycolysis-related monocarboxylate transporter(MCT1),MCT4,and CD147 expressions.XJZ prevented the increase of autophagy level by decreasing gastric mucosal hypoxia,activating the PI3K/AKT/mTOR pathway,inhibiting the p53/AMPK pathway activation and ULK1 Ser-317 and Ser-555 phosphorylation.In addition,XJZ improved abnormal gastric mucosal glucose metabolism by ameliorating gastric mucosal hypoxia and inhibiting ULK1 expression.CONCLUSION This study demonstrates that XJZ may inhibit autophagy and glycolysis in GPL gastric mucosal cells by improving gastric mucosal hypoxia and regulating PI3K/AKT/mTOR and p53/AMPK/ULK1 signaling pathways,providing a feasible strategy for the GPL treatment.
基金Supported by Tianjin Education Committee Foundation, No.020334
文摘AIM： To observe the curative effect of Weiansan （WAS） on gastric precancerous lesions （GPL） and H pylori elimination. METHODS： Seventy-six patients with GPL were randomly divided into two groups： WAS group （n = 42） and Weifuchun （WFC） group （n = 34）. The patients in the WAS group were administered 5 g WAS 3 times a day, and the patients in the WFC group took WFC （4 tablets） 3 times a day. To monitor inflammation of gastric mucosa, degree of glandular atrophy （GA）, intestinal metaplasia （IM） and dysplasia, and H pylori infection, all patients underwent gastroscopy and biopsy with pathological examination before and after treatment. Fifty male Sprague-Dawley （SD） rats were used in animal experiments. Of these, 10 served as the control group （n = 10）, 40 were given ranitidine combined with N-methyl- N^1-nitro-N-nitrosoguanidine （MNNG） for 12 wk and divided into 4 groups randomly： model group （n = 10）, high-dose WAS group （n = 10）, low-close WAS group （n = 10） and WFC group （n = 10）. Twelve weeks later, all rats were killed and a 2 cm ×1 cm tissue was taken from the lesser curvature of the gastric antrum. H pylori infection was determined by the fast urease method. RESULTS： The curative effect in WAS groups was similar to that in WFC groups. There was no statistical difference in degree of GA, IM and dysplasia between WAS and WFC groups. The rate of Hpylori infection in the model group （positive/negative： 9/1） was significantly higher than that in the control group （positive/negative： 1/9） （P 〈 0.01）. H pylori elimination in the high-dose WAS group （positive/negative： 4/6） and low-dose WAS group （positive/negative： 6/4） was similar to that in the WFC group （positive/negative： 4/6） （P 〉 0.05）.CONCLUSION： WAS improves clinical symptoms by suppressing GA, IM and dysplasia and eliminating H pylori.
基金Supported by National Key Technology R&D Program during the 13th Five-Year Plan Period Evidence-based evaluation and efficacy mechanism of Jianpi-Huoxue principle in the treatment of gastric precancerous lesions (No. 2017YFC1700601)Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences:Screening of miRNAs in different pathological stages of gastric mucosal “inflammation-cancer” transformation and its correlation with symptom patterns (No. CI2021A01005)。
文摘China has a high incidence of gastric cancer. Secondary prevention of gastric cancer is a major public health problem that must be solved urgently. Modern medicine focuses on the pathogenesis of precancerous lesions of gastric cancer(PLGC), and it has been found that there are a variety of abnormal gene expression patterns in PLGC. This study summarizes recent advances in our understanding of the therapeutic mechanisms of PLGC from various clinical studies;this will provide a reference for studying the therapeutic mechanisms of Traditional Chinese Medicine in the treatment of PLGC from the combined points of view of Traditional Chinese and Conventional medicine.
基金Supported by the National Natural Science Foundation of China,No.U1604174Henan Provincial Government-Health and Family Planning Commission,No.20170123 and No.SBGJ202002004Henan Provincial Government-Health and Family Planning Commission Research Innovative Talents Project,No.51282。
文摘BACKGROUND Helicobacter pylori(H.pylori)infects about 50%of the world population and is the major cause of chronic gastritis,peptic ulcers,and gastric cancer.Chronic H.pylori infection induces gastric mucosal precancerous lesions mostly in adulthood,and it is debatable whether these pathological conditions can occur in childhood and adolescents as well.Since this is a critical issue to determine if intervention should be offered for this population group,we investigated the gastric mucosal precancerous lesions in pediatric patients in an area in central China with a high prevalence of H.pylori and gastric cancer.AIM To investigate the relationship of H.pylori infection and gastric mucosal precancerous lesions in children and adolescents in central China.METHODS We screened 4258 ward-admitted children and adolescent patients with upper gastrointestinal symptoms,and finally enrolled 1015 pediatric patients with H.pylori infection and endoscopic and histological data.H.pylori infection status was determined by rapid urease test and histopathological examination.Both clinical and pathological data were collected and analyzed retrospectively.Occurrence of gastric mucosal precancerous lesions,inflammatory activity and degree of inflammatory cell infiltration between H.pylori-positive and-negative groups were compared.RESULTS Among the 1015 eligible children and adolescents,the overall H.pylori infection rate was 84.14%(854/1015).The infection rate increased with age.The incidence of gastric mucosal precancerous lesions in H.pylori-infected children was 4.33%(37/854),which included atrophic gastritis(17 cases),intestinal metaplasia(11 cases)and dysplasia(9 cases).In H.pylori-negative patients,only 1 atrophic gastritis case[0.62%,(1/161)]was found(P<0.05).Active inflammation in H.pyloriinfected patients was significantly higher than that in non-infected patients,and the H.pyloriinfected group showed more severe lymphocyte and neutrophil granulocyte infiltration(P<0.001).In addition,endoscopy revealed that the most common findings in H.pylori-positive patients were antral nodularity,but in H.pylori-negative patients only superficial gastritis was observed.CONCLUSION In children and adolescents,gastric mucosal precancerous lesions occurred in 4.33%of H.pyloriinfected patients in central China.These cases included atrophic gastritis,intestinal metaplasia,and dysplasia.The data revealed an obvious critical issue requiring future investigation and intervention for this population group.
基金Supported by Digestive Medical Coordinated Development Center of Beijing Hospitals Authority,No.XXZ015Capital Citizens Health Cultivation Project of Beijing Municipal Science&Technology Commission,No.Z161100000116084+1 种基金Medical and Health Public Foundation of Beijing,No.YWJKJJHKYJJ-B17262-067Science and Technology Development Project of China State Railway Group,No.N2019Z004.
文摘BACKGROUND In recent years,two new narrow-band imaging(NBI)classifications have been proposed:The NBI international colorectal endoscopic(NICE)classification and Japanese NBI expert team(JNET)classification.Most validation studies of the two new NBI classifications were conducted in classification setting units by experienced endoscopists,and the application of use in different centers among endoscopists with different endoscopy skills remains unknown.AIM To evaluate clinical application and possible problems of NICE and JNET classification for the differential diagnosis of colorectal cancer and precancerous lesions.METHODS Six endoscopists with varying levels of experience participated in this study.Eighty-seven consecutive patients with a total of 125 lesions were photographed during non-magnifying conventional white-light colonoscopy,non-magnifying NBI,and magnifying NBI.The three groups of endoscopic pictures of each lesion were evaluated by the six endoscopists in randomized order using the NICE and JENT classifications separately.Then we calculated the six endoscopists’sensitivity,specificity,accuracy,positive predictive value,and negative predictive value for each category of the two classifications.RESULTS The sensitivity,specificity,and accuracy of JNET classification type 1 and 3 were similar to NICE classification type 1 and 3 in both the highly experienced endoscopist(HEE)and less-experienced endoscopist(LEE)groups.The specificity of JNET classification type 1 and 3 and NICE classification type 3 in both the HEE and LEE groups was>95%,and the overall interobserver agreement was good in both groups.The sensitivity of NICE classification type 3 lesions for diagnosis of SM-d carcinoma in the HEE group was significantly superior to that in the LEE group(91.7%vs 83.3%;P=0.042).The sensitivity of JNET classification type 2B lesions for the diagnosis of high-grade dysplasia or superficial submucosal invasive carcinoma in the HEE and LEE groups was 53.8%and 51.3%,respectively.Compared with other types of JNET classification,the diagnostic ability of type 2B was the weakest.CONCLUSION The treatment strategy of the two classification type 1 and 3 lesions can be based on the results of endoscopic examination.JNET type 2B lesions need further examination.
基金The Science and Technology Development Fund,Macao SAR,No.0021/2019/A.
文摘Upper gastrointestinal(GI)cancers are the leading cause of cancer-related deaths worldwide.Early identification of precancerous lesions has been shown to minimize the incidence of GI cancers and substantiate the vital role of screening endoscopy.However,unlike GI cancers,precancerous lesions in the upper GI tract can be subtle and difficult to detect.Artificial intelligence techniques,especially deep learning algorithms with convolutional neural networks,might help endoscopists identify the precancerous lesions and reduce interobserver variability.In this review,a systematic literature search was undertaken of the Web of Science,PubMed,Cochrane Library and Embase,with an emphasis on the deep learning-based diagnosis of precancerous lesions in the upper GI tract.The status of deep learning algorithms in upper GI precancerous lesions has been systematically summarized.The challenges and recommendations targeting this field are comprehensively analyzed for future research.
文摘Objective： To investigate potential therapeutic effects and mechanism of Weining granule in the treatment of gastric precancerous lesions. Methods： Sixty rats were randomly assigned to a blank group or a model group or to receive retinoic acid or high-, medium- or low- dose of Weining granule. General conditions of the animals were observed before and after treatment. Changes in gastric mucosal pathohistology, telomerase activity, proliferation index （PI） and apoptosis index （AI） were measured. Results： General conditions, including activity and eating, were improved in all Weining-granule-treated groups with the numbers of rats having intestinal metaplasia （IM）, atypical hyperplasia （ATP） or positive telomerase activity being significantly lower than those in the model group （P 〈 0.05 or P 〈 0.01）. Compared with the model group, all doses of Weining granule significantly decreased PI （P 〈 0.01） and increased AI （P 〈 0.05）. Conclusion： Weining granule may provide a therapeutic benefit for the treatment of gastric precancerous lesions by inhibiting telomerase activity and proliferation of gastric cancer cells and by accelerating their apoptosis.
