BACKGROUND With advancements in the development of endoscopic technologies,the endo-scopic submucosal dissection(ESD)has been one of the gold-standard therapies for early gastric cancer.AIM To investigate the efficacy...BACKGROUND With advancements in the development of endoscopic technologies,the endo-scopic submucosal dissection(ESD)has been one of the gold-standard therapies for early gastric cancer.AIM To investigate the efficacy and safety ESD in the treatment of early gastric cancer and precancerous lesions in the elderly patients.METHODS Seventy-eight elderly patients with early gastric cancer and precancerous lesions admitted to the Third Affiliated Hospital of Qiqihar Medical University were se-lected and classified into two groups according to the different surgical therapies they received between January 2021 and June 2022.Among them,39 patients treated with ESD were included in an experimental group,and 39 patients treated with endoscopic mucosal resection(EMR)were included in a control group.We compared the basic intraoperative conditions,postoperative short-term recovery,long-term recovery effects and functional status of gastric mucosa between the two groups;the basic intraoperative conditions included lesion resection,intra-operative bleeding and operation time;the postoperative short-term recovery assessment indexes were length of hospital stay and incidence of surgical complic-ations;and the long-term recovery assessment indexes were the recurrence rate at 1 year postoperatively and the survival situation at 1 year and 3 years postoper-atively;and we compared the preoperative and predischarge serum pepsinogen I(PG I)and PG II levels and PG I/PG II ratio in the two groups before surgery and discharge.RESULTS The curative resection rate and the rate of en bloc resection were higher in the experimental group than in the control group.The intraoperative bleeding volume was higher in the experimental group than in the control group.The operation time was longer in the experimental group than that in the control group,and the rate for base residual focus was lower in the experimental group than that of the control group,and the differences were all statistically significant(all P<0.05).The length of hospital stay was longer in the experi-mental group than in the control group,and the incidence of surgical complications,1-year postoperative recu-rrence rate and 3-year postoperative survival rate were lower in the experimental group than in the control group,and the differences were statistically significant(all P<0.05).However,the difference in the 1-year postoperative survival rate was not statistically significant between the two groups(P>0.05).Before discharge,PG I and PG I/PG II ratio were elevated in both groups compared with the preoperative period,and the above indexes were higher in the experimental group than those in the control group,and the differences were statistically significant(both P<0.05).Moreover,before discharge,PG II level was lower in both groups compared with the preoperative period,and the level was lower in the experimental group than in the control group,and the differences were all statistically significant(all P<0.05).CONCLUSION Compared with EMR,ESD surgery is more thorough.It reduces the rate of base residual focus,recurrence rate,surgical complications,and promotes the recovery of gastric cells and glandular function.It is safe and suitable for clinical application.展开更多
BACKGROUND Gastric cancer is a common malignant tumor of the digestive tract,and endosco-pic submucosal dissection(ESD)is the preferred treatment for early-stage gastric cancer.The analysis of the epidemiological char...BACKGROUND Gastric cancer is a common malignant tumor of the digestive tract,and endosco-pic submucosal dissection(ESD)is the preferred treatment for early-stage gastric cancer.The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD.AIM To analyze the features of gastric mucosal tumors at different differentiation levels,and to explore the prognostic factors of ESD.METHODS We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021,according to the latest Japanese guidelines(sixth edition),and divided them into low-grade intrae-pithelial neoplasia(LGIN),high-grade intraepithelial neoplasia(HGIN),and computed tomography at 3,6 and 12 months after ESD.We compared clinicopathologic characteristics,ESD efficacy,and complications with different degrees of differentiation,and analyzed the related factors associated with ESD.RESULTS HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients(P<0.001)and accounted for more 0-IIc(P<0.001),atrophic gastritis was common(P<0.001),and irregular microvascular patterns(IMVPs)and demarcation lines(DLs)were more obvious(P<0.001).There was more infiltration in the undifferentiated carcinoma tissue(P<0.001),more abnormal folds and poorer mucosal peristalsis(P<0.001),and more obvious IMVPs,irregular microsurface patterns and DLs(P<0.05)than in the LGIN and HGIN tissues.The disease-free survival rates at 2,5,and 8 years after ESD were 95.0%,90.1%,and 86.9%,respectively.Undifferen-tiated lesions(HR 5.066),white moss(HR 7.187),incomplete resection(HR 3.658),and multiple primary cancers(HR 2.462)were significantly associated with poor prognosis.CONCLUSION Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics,which are closely related to the safety and efficacy of ESD.展开更多
BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported ...BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported to play an anti-inflammatory role.However,the underlying mechanism is still unclear.AIM To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium(DSS)-induced colitis.METHODS Mice were administered 3%DSS drinking water,and disease activity index was determined to evaluate the status of colitis.Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran,and bacterial translocation was evaluated by measuring serum lipopolysaccharide.Intestinal epithelial cell ultrastructure was observed by electron microscopy.Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA,respectively.Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels.RESULTS Compared to wild-type(WT)mice,inflammation and intestinal permeability in alk-SMase knockout(KO)mice were more severe beginning 4 d after DSS induction.The mRNA and protein levels of intestinal barrier proteins,including zonula occludens-1,occludin,claudin-3,claudin-5,claudin-8,mucin 2,and secretory immunoglobulin A,were significantly reduced on 4 d after DSS treatment.Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells.Furthermore,by day 4,mitochondria appeared swollen and degenerated.Additionally,compared to WT mice,serum malondialdehyde levels in KO mice were higher,and the antioxidant capacity was significantly lower.The expression of the transcription factor nuclear factor erythroid 2-related factor 2(Nrf2)in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment.mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased.Finally,colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone,which is an Nrf2 activator.CONCLUSION Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.展开更多
In this editorial we comment on the article published in the recent issue of the World Journal of Gastrointestinal Endoscopy 2023;15(11):634-680.Gastric cancer(GC)remains the fifth most common malignancy and the fourt...In this editorial we comment on the article published in the recent issue of the World Journal of Gastrointestinal Endoscopy 2023;15(11):634-680.Gastric cancer(GC)remains the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide.The overall prevalence of GC has declined,although that of proximal GC has increased over time.Thus,a significant proportion of GC cases and deaths can be avoided if preventive interventions are taken.Early GC(EGC)is defined as GC confined to the mucosa or submucosa.Endoscopic resection is considered the most appropriate treatment for precancerous gastrointestinal lesions improving patient quality of life,with reduced rates of complications,shorter hospitalization period,and lower costs when compared to surgical resection.Endoscopic mucosal resection(EMR)and endoscopic sub-mucosal dissection(ESD)are representative endoscopic treatments for EGC and precancerous gastric lesions.Standard EMR implies injection of a saline solution into the sub-mucosal space,followed by excision of the lesion using a snare.Complete resection rates vary depending on the size and severity of the lesion.When using conventional EMR methods for lesions less than 1 cm in size,the complete resection rate is approximately 60%,whereas for lesions larger than 2 cm,the complete resection rate is low(20%-30%).ESD can be used to remove tumors exceeding 2 cm in diameter and lesions associated with ulcers or submucosal fibrosis.Compared with EMR,ESD has higher en bloc resection rates(90.2%vs 51.7%),higher complete resection rates(82.1 vs 42.2%),and lower recurrence rates(0.65%vs 6.05%).Thus,innovative techniques have been introduced.展开更多
BACKGROUND Duodenal Brunner's gland hyperplasia(BGH)is a therapeutic target when complications such as bleeding or gastrointestinal obstruction occur or when malignancy cannot be ruled out.Herein,we present a case...BACKGROUND Duodenal Brunner's gland hyperplasia(BGH)is a therapeutic target when complications such as bleeding or gastrointestinal obstruction occur or when malignancy cannot be ruled out.Herein,we present a case of large BGH treated with endoscopic mucosal resection(EMR).CASE SUMMARY An 83-year-old woman presented at our hospital with dizziness.Blood tests revealed severe anemia,esophagogastroduodenoscopy showed a 6.5 cm lesion protruding from the anterior wall of the duodenal bulb,and biopsy revealed the presence of glandular epithelium.Endoscopic ultrasonography(EUS)demonstr-ated relatively high echogenicity with a cystic component.The muscularis propria was slightly elevated at the base of the lesion.EMR was performed without complications.The formalin-fixed lesion size was 6 cm×3.5 cm×3 cm,showing nodular proliferation of non-dysplastic Brunner's glands compartmentalized by fibrous septa,confirming the diagnosis of BGH.Reports of EMR or hot snare polypectomy are rare for duodenal BGH>6 cm.In this case,the choice of EMR was made by obtaining information on the base of the lesion as well as on the internal characteristics through EUS.CONCLUSION Large duodenal lesions with good endoscopic maneuverability and no evident muscular layer involvement on EUS may be resectable via EMR.展开更多
Mucosal healing(MH)is vital in maintaining homeostasis within the gut and protecting against injury and infections.Multiple factors and signaling pathways contribute in a dynamic and coordinated manner to maintain int...Mucosal healing(MH)is vital in maintaining homeostasis within the gut and protecting against injury and infections.Multiple factors and signaling pathways contribute in a dynamic and coordinated manner to maintain intestinal homeostasis and mucosal regeneration/repair.However,when intestinal homeostasis becomes chronically disturbed and an inflammatory immune response is constitutively active due to impairment of the intestinal epithelial barrier autoimmune disease results,particularly inflammatory bowel disease(IBD).Many proteins and signaling pathways become dysregulated or impaired during these pathological conditions,with the mechanisms of regulation just beginning to be understood.Consequently,there remains a relative lack of broadly effective therapeutics that can restore MH due to the complexity of both the disease and healing processes,so tissue damage in the gastrointestinal tract of patients,even those in clinical remission,persists.With increased understanding of the molecular mechanisms of IBD and MH,tissue damage from autoimmune disease may in the future be ameliorated by developing therapeutics that enhance the body’s own healing response.In this review,we introduce the concept of mucosal healing and its relevance in IBD as well as discuss the mechanisms of IBD and potential strategies for altering these processes and inducing MH.展开更多
Ulcerative colitis(UC)is a chronic nonspecific inflammatory disease with complex causes.The main pathological changes were intestinal mucosal injury.Leucinerich repeat-containing G protein coupled receptor 5(LGR5)-lab...Ulcerative colitis(UC)is a chronic nonspecific inflammatory disease with complex causes.The main pathological changes were intestinal mucosal injury.Leucinerich repeat-containing G protein coupled receptor 5(LGR5)-labeled small intestine stem cells(ISCs)were located at the bottom of the small intestine recess and inlaid among Paneth cells.LGR5+small ISCs are active proliferative adult stem cells,and their self-renewal,proliferation and differentiation disorders are closely related to the occurrence of intestinal inflammatory diseases.The Notch signaling pathway and Wnt/β-catenin signaling pathway are important regulators of LGR5-positive ISCs and together maintain the function of LGR5-positive ISCs.More importantly,the surviving stem cells after intestinal mucosal injury accelerate division,restore the number of stem cells,multiply and differentiate into mature intestinal epithelial cells,and repair the damaged intestinal mucosa.Therefore,in-depth study of multiple pathways and transplantation of LGR5-positive ISCs may become a new target for the treatment of UC.展开更多
Background Anthocyanins(AC)showed positive effects on improving the intestinal health and alleviating intestinal pathogen infections,therefore,an experiment was conducted to explore the protective effects of supplemen...Background Anthocyanins(AC)showed positive effects on improving the intestinal health and alleviating intestinal pathogen infections,therefore,an experiment was conducted to explore the protective effects of supplemented AC on Salmonella-infected chickens.Methods A total of 240 hatchling chickens were randomly allocated to 4 treatments,each with 6 replicates.Birds were fed a basal diet supplemented with 0(CON,and ST),100(ACL)and 400(ACH)mg/kg of AC for d 60,and orally challenged with PBS(CON)or 10^(9) CFU/bird(ST,ACL,ACH)Salmonella Typhimurium at d 14 and 16.Results(1)Compared with birds in ST,AC supplementation increased the body weight(BW)at d 18 and the average daily gain(ADG)from d 1 to 18 of the Salmonella-infected chickens(P<0.05);(2)AC decreased the number of Salmonella cells in the liver and spleen,the contents of NO in plasma and inflammatory cytokines in ileal mucosa of Salmonella-infected chickens(P<0.05);(3)Salmonella infection decreased the ileal villi height,villi height to crypt depth(V/C),and the expression of zonulaoccludins-1(ZO-1),claudin-1,occludin,and mucin 2(MUC2)in ileal mucosa.AC supplementation relieved these adverse effects,and decreased ileal crypt depth(P<0.05);(4)In cecal microbiota of Salmonella-infected chickens,AC increased(P<0.05)the alpha-diversity(Chao1,Pd,Shannon and Sobs indexes)and the relative abundance of Firmicutes,and decreased(P<0.05)the relative abundance of Proteobacteria and Bacteroidota and the enrichment of drug antimicrobial resistance,infectious bacterial disease,and immune disease pathways.Conclusions Dietary AC protected chicken against Salmonella infection via inhibiting the Salmonella colonization in liver and spleen,suppressing secretion of inflammatory cytokines,up-regulating the expression of ileal barrier-related genes,and ameliorating the composition and function of cecal microbes.Under conditions here used,100 mg/kg bilberry anthocyanin was recommended.展开更多
Background Cold regions have long autumn and winter seasons and low ambient temperatures.When pigs are unable to adjust to the cold,oxidative damage and inflammation may develop.However,the differences between cold an...Background Cold regions have long autumn and winter seasons and low ambient temperatures.When pigs are unable to adjust to the cold,oxidative damage and inflammation may develop.However,the differences between cold and non-cold adaptation regarding glucose and lipid metabolism,gut microbiota and colonic mucosal immunological features in pigs are unknown.This study revealed the glucose and lipid metabolic responses and the dual role of gut microbiota in pigs during cold and non-cold adaptation.Moreover,the regulatory effects of dietary glucose supplements on glucose and lipid metabolism and the colonic mucosal barrier were evaluated in cold-exposed pigs.Results Cold and non-cold-adapted models were established by Min and Yorkshire pigs.Our results exhibited that cold exposure induced glucose overconsumption in non-cold-adapted pig models(Yorkshire pigs),decreasing plasma glucose concentrations.In this case,cold exposure enhanced the ATGL and CPT-1αexpression to promote liver lipolysis and fatty acid oxidation.Meanwhile,the two probiotics(Collinsella and Bifidobacterium)depletion and the enrichment of two pathogens(Sutterella and Escherichia-Shigella)in colonic microbiota are not conducive to colonic mucosal immunity.However,glucagon-mediated hepatic glycogenolysis in cold-adapted pig models(Min pigs)maintained the stability of glucose homeostasis during cold exposure.It contributed to the gut microbiota(including the enrichment of the Rikenellaceae RC9 gut group,[Eubacterium]coprostanoligenes group and WCHB1-41)that favored cold-adapted metabolism.Conclusions The results of both models indicate that the gut microbiota during cold adaptation contributes to the protection of the colonic mucosa.During non-cold adaptation,cold-induced glucose overconsumption promotes thermogenesis through lipolysis,but interferes with the gut microbiome and colonic mucosal immunity.Furthermore,glucagon-mediated hepatic glycogenolysis contributes to glucose homeostasis during cold exposure.展开更多
BACKGROUND While colon endoscopic mucosal resection(EMR)is an effective technique,removal of larger polyps often requires piecemeal resection,which can increase recurrence rates.Endoscopic submucosal dissection(ESD)in...BACKGROUND While colon endoscopic mucosal resection(EMR)is an effective technique,removal of larger polyps often requires piecemeal resection,which can increase recurrence rates.Endoscopic submucosal dissection(ESD)in the colon offers the ability for en bloc resection and is well-described in Asia,but there are limited studies comparing ESD vs EMR in the West.AIM To evaluate different techniques in endoscopic resection of large polyps in the colon and to identify factors for recurrence.METHODS The study is a retrospective comparison of ESD,EMR and knife-assisted endoscopic resection performed at Stanford University Medical Center and Veterans Affairs Palo Alto Health Care System between 2016 and 2020.Knife-assisted endoscopic resection was defined as use of electrosurgical knife to facilitate snare resection,such as for circumferential incision.Patients≥18 years of age undergoing colonoscopy with removal of polyp(s)≥20 mm were included.The primary outcome was recurrence on follow-up.RESULTS A total of 376 patients and 428 polyps were included.Mean polyp size was greatest in the ESD group(35.8 mm),followed by knife-assisted endoscopic resection(33.3 mm)and EMR(30.5 mm)(P<0.001).ESD achieved highest en bloc resection(90.4%)followed by knife-assisted endoscopic resection(31.1%)and EMR(20.2%)(P<0.001).A total of 287 polyps had follow-up(67.1%).On follow-up analysis,recurrence rate was lowest in knife-assisted endoscopic resection(0.0%)and ESD(1.3%)and highest in EMR(12.9%)(P=0.0017).En bloc polyp resection had significantly lower rate of recurrence(1.9%)compared to non-en bloc(12.0%,P=0.003).On multivariate analysis,ESD(in comparison to EMR)adjusted for polyp size was found to significantly reduce risk of recurrence[adjusted hazard ratio 0.06(95%CI:0.01-0.57,P=0.014)].CONCLUSION In our study,EMR had significantly higher recurrence compared to ESD and knife-assisted endoscopic resection.We found factors including resection by ESD,en bloc removal,and use of circumferential incision were associated with significantly decreased recurrence.While further studies are needed,we have demonstrated the efficacy of ESD in a Western population.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
A review of the development of the key performance metrics of endoscopic mucosal resection(EMR),learning from the experience of the establishment of widespread colonoscopy quality measurements.Potential future perform...A review of the development of the key performance metrics of endoscopic mucosal resection(EMR),learning from the experience of the establishment of widespread colonoscopy quality measurements.Potential future performance markers for both colonoscopy and EMR are also evaluated to ensure continued high quality performance is maintained with a focus service framework and predictors of patient outcome.展开更多
BACKGROUND Endoscopic mucosal resection is an innovative method for treating early gastric cancer and has been widely used in clinical practice.AIM To analyze the factors associated with the development of heterochron...BACKGROUND Endoscopic mucosal resection is an innovative method for treating early gastric cancer and has been widely used in clinical practice.AIM To analyze the factors associated with the development of heterochronic gastric cancer in patients with early gastric cancer who had undergone endoscopic mucosal dissection(EMD).METHODS A cohort of patients with early gastric cancer treated using EMD was retrospectively analyzed,and patients who developed heterochronic gastric cancer after the surgery were compared with those who did not.The effects of patient age,sex,tumor size,pathological type,and surgical technique on the development of heterochronic gastric cancer were assessed using statistical analysis.RESULTS Of the 300 patients with early gastric cancer,150 patients developed heterochronic gastric cancer after EMD.Statistical analysis revealed that patient age(P value=XX),sex(P value=XX),tumor size(P value=XX),pathological type(P value=XX),and surgical technique(P value=XX)were significantly associated with the occurrence of heterochronic gastric cancer.CONCLUSION Age,sex,tumor size,pathological type,and surgical technique are key factors influencing the occurrence of heterochronic gastric cancer after EMD in patients with early gastric cancer.To address these factors,postoperative follow-up and management should be strengthened to improve the prognosis and survival rate of patients.展开更多
BACKGROUND Acute esophageal mucosal lesions(AEMLs)are an underrecognized and largely unexplored disease.Endoscopic findings are similar,and a higher percentage of AEML could be misdiagnosed as reflux esophagitis Los A...BACKGROUND Acute esophageal mucosal lesions(AEMLs)are an underrecognized and largely unexplored disease.Endoscopic findings are similar,and a higher percentage of AEML could be misdiagnosed as reflux esophagitis Los Angeles classification grade D(RE-D).These diseases could have different pathologies and require different treatments.AIM To compare AEML and RE-D to confirm that the two diseases are different from each other and to clarify the clinical features of AEML.METHODS We selected emergency endoscopic cases of upper gastrointestinal bleeding with circumferential esophageal mucosal injury and classified them into AEML and RE-D groups according to the mucosal injury’s shape on the oral side.We examined patient background,blood sampling data,comorbidities at onset,endoscopic characteristics,and outcomes in each group.RESULTS Among the emergency cases,the AEML and RE-D groups had 105(3.1%)and 48(1.4%)cases,respectively.Multiple variables exhibited significantly different results,indicating that these two diseases are distinct.The clinical features of AEML consisted of more comorbidities[risk ratio(RR):3.10;95%confidence interval(CI):1.68–5.71;P<0.001]and less endoscopic hemostasis compared with RE-D(RR:0.25;95%CI:0.10–0.63;P<0.001).Mortality during hospitalization was higher in the AEML group(RR:3.43;95%CI:0.82–14.40;P=0.094),and stenosis developed only in the AEML group.CONCLUSION AEML and RE-D were clearly distinct diseases with different clinical features.AEML may be more common than assumed,and the potential for its presence should be taken into account in cases of upper gastrointestinal bleeding with comorbidities.展开更多
Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing.This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and th...Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing.This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve(B.breve).A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing.The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography(micro-CT).Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay(ELISA).The senescence and biological functions were tested in oral mucosal stem cells(OMSCs)treated with sunitinib.Ligated loop experiments were used to investigate the effect of oral B.breve.Neutralizing antibody for interleukin-10(IL-10)was used to prove the critical role of IL-10 in the pro-healing process derived from B.breve.Results showed that sunitinib caused oral mucosal wound healing impairment in mice.In vitro,sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation,migration,and differentiation.Oral administration of B.breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells(DCs)-derived IL-10.IL-10 reversed cellular senescence caused by sunitinib in OMSCs,and IL-10 neutralizing antibody blocked the ameliorative effect of B.breve on oral mucosal wound healing under sunitinib treatment conditions.In conclusion,sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B.breve could improve wound healing impairment via intestinal DCs-derived IL-10.展开更多
We reviewed a study that reported a comparative analysis of the effects of endoscopic mucosal resection(EMR)precutting and conventional EMR for removing non-pedunculated,10-20 mm sized colorectal polyps.We identified ...We reviewed a study that reported a comparative analysis of the effects of endoscopic mucosal resection(EMR)precutting and conventional EMR for removing non-pedunculated,10-20 mm sized colorectal polyps.We identified some statistical deficiencies in this study.In addition,we believe that the differences between the treatments failed to achieve significance,and therefore,further analysis is required.展开更多
The pathogens of most infectious diseases invade the host through mucosal sites,and immunization with mucosal vaccines is the best means of combating these infectious diseases.Oral delivery and nasal delivery are the ...The pathogens of most infectious diseases invade the host through mucosal sites,and immunization with mucosal vaccines is the best means of combating these infectious diseases.Oral delivery and nasal delivery are the most common methods of mucosal vaccination.However,the delivery process is inefficient,and mucosal vaccination is ineffective because the vaccine formulation is easily and rapidly removed and has difficulty in crossing the mucosal surface.In this paper,we investigated whether the mucosal immune response could be enhanced by ultrasound facilitation of nasal mucosal delivery of vaccine preparations.For this purpose,we used manganese dioxide(MnO2)as the vaccine carrier/adjuvant,coated with chitosan oligosaccharide(COS)to enhance mucosal adsorption,and further physically adsorbed model antigen ovalbumin(OVA)to construct a nanoparticulate vaccine formulation MnO2@COS@OVA.Ultrasound treatment was found to promote antigen delivery and recruitment of dendritic cells(DCs)and macrophages as well as T-cell infiltration in nasal mucosal tissues through nasal mucosal immunization studies.With ultrasound assistance,MnO2@COS@OVA particles promoted the maturation of DCs in vitro and in vivo and promoted the production of effector memory T cells in vivo and cytokine secretion by splenocytes in vitro.In particular,ultrasound treatment significantly increased the levels of secretory IgA antibodies in the nasal mucosa and genital tract mucosa of experimental mice.In addition,the experimental data showed that the MnO2@COS@OVA particles had good biocompatibility and caused no significant damage to the nasal mucosal and vital organ tissue.These data suggest that ultrasound treatment can promote the induction of efficient immune responses to mucosal vaccines and provide new ideas for the opening and clinical translation of mucosal vaccines.展开更多
BACKGROUND Endoscopic resection(ER)with bipolar snare,in which the electric current only passes through the tissue between the device’s two electrodes,is a prominent method used to prevent perforation due to electric...BACKGROUND Endoscopic resection(ER)with bipolar snare,in which the electric current only passes through the tissue between the device’s two electrodes,is a prominent method used to prevent perforation due to electricity potentially.ER using bipolar snare with or without submucosal injection enabled safe resection of colorectal lesions measuring 10-15 mm in an ex vivo porcine model.ER with bipolar snare is expected to have good treatment outcomes in 10-15 mm colorectal lesions,with high safety even without submucosal injection.However,no clinical reports have compared treatment outcomes with and without submucosal injection.AIM To compare the treatment outcomes of bipolar polypectomy with hot snare polypectomy(HSP)to those with endoscopic mucosal resection(EMR).METHODS In this single-centre retrospective study,we enrolled 10-15 mm nonpedunculated colorectal lesions(565 Lesions in 463 patients)diagnosed as type 2A based on the Japan Narrow-band Imaging Expert Team classification,resected by either HSP or EMR between January 2018 and June 2021 at the National Cancer Center Hospital East.Lesions were divided into HSP and EMR groups,and propensity score matching was performed.In the matched cohort,en bloc and R0 resection rates and adverse events were compared between the two groups.RESULTS Of the 565 lesions in 463 patients,117 lesions each in the HSP and EMR groups were selected after propensity score matching.In the original cohort,there was a significant difference in antithrombotic drug use(P<0.05),lesion size(P<0.01),location(P<0.01),and macroscopic type(P<0.05)between the HSP and EMR groups.In the matched cohort,the en bloc resection rates were comparable between both groups[93.2%(109/117)vs 92.3%(108/117),P=0.81],and there was no significant difference in the R0 resection rate[77.8%(91/117)vs 80.3%(94/117),P=0.64].The incidence of delayed bleeding was similar in both groups[1.7%(2/117)].Perforation occurred in the EMR group[0.9%(1/117)]but not in the HSP group.CONCLUSION Using bipolar snare,ER of nonpedunculated 10-15 mm colorectal lesions may be performed safely and effectively,even without submucosal injection.展开更多
Background:Lactic acid bacteria(LAB)participating in milk fermentation naturally release and enrich the fermented dairy product with a broad range of bioactive metabolites,which has numerous roles in the intestinal he...Background:Lactic acid bacteria(LAB)participating in milk fermentation naturally release and enrich the fermented dairy product with a broad range of bioactive metabolites,which has numerous roles in the intestinal health-promot-ing of the consumer.However,information is lacking regarding the application prospect of LAB fermented milk in the animal industry.This study investigated the effects of lactic acid bacteria-fermented formula milk(LFM)on the growth performance,intestinal immunity,microbiota composition,and transcriptomic responses in weaned piglets.A total of 24 male weaned piglets were randomly divided into the control(CON)and LFM groups.Each group consisted of 6 replicates(cages)with 2 piglets per cage.Each piglet in the LFM group were supplemented with 80 mL LFM three times a day,while the CON group was treated with the same amount of drinking water.Results:LFM significantly increased the average daily gain of piglets over the entire 14 d(P<0.01)and the average daily feed intake from 7 to 14 d(P<0.05).Compared to the CON group,ileal goblet cell count,villus-crypt ratio,sIgA,and lactate concentrations in the LFM group were significantly increased(P<0.05).Transcriptomic analysis of ileal mucosa identified 487 differentially expressed genes(DEGs)between two groups.Especially,DEGs involved in the intestinal immune network for IgA production pathways,such as polymeric immunoglobulin receptor(PIGR),were significantly up-regulated(P<0.01)by LFM supplementation.Moreover,trefoil factor 2(TFF2)in the LFM group,one of the DEGs involved in the secretory function of goblet cells,was also significantly up-regulated(P<0.01).Sequenc-ing of the 16S rRNA gene of microbiota demonstrated that LFM led to selective enrichment of lactate-producing and short-chain fatty acid(SCFA)-producing bacteria in the ileum,such as an increase in the relative abundance of Entero-coccus(P=0.09)and Acetitomaculum(P<0.05).Conclusions:LFM can improve intestinal health and immune tolerance,thus enhancing the growth performance of weaned piglets.The changes in microbiota and metabolites induced by LFM might mediate the regulation of the secretory function of goblet cells.展开更多
The numerous health benefits of olive oil are widely known,however,it also provides anti-allergic properties that have not yet been fully defined.In this study,the anti-allergic activity of olive oil was evaluated by ...The numerous health benefits of olive oil are widely known,however,it also provides anti-allergic properties that have not yet been fully defined.In this study,the anti-allergic activity of olive oil was evaluated by analyzing the clinical symptoms and immune-related factors in BALB/c mice that had ingested600 mg/(kg·day)olive oil for two weeks prior to the evaluation.An allergy model was subsequently constructed for analysis,the results of which showed that the olive oil reduced the scores of allergic symptoms in the mice,and up-regulated the hypothermia and the decline in the immune organ index.Moreover,fewer allergy-related cytokines and reduced intestinal inflammation was discovered in the olive oil-treated group.In addition,analysis of intestinal mucosal immune-related factors revealed that the olive oil promoted the expression of intestinal tight junction proteins(Claudin-1,Occludin,and ZO-1)and IL-22,and helped maintain the integrity of the intestinal epithelial physical barrier.Increased levels of mucin 2 andβ-defensin were also found in the intestinal mucus of the olive oil-treated mice.These findings suggest that the oral administration of olive oil effectively attenuated the ovalbumin-induced allergic immune response in the mice,and had a positive effect on intestinal epithelial mucosal immunity.展开更多
基金Supported by Qiqihar Scientific and Technological Plan Joint Guidance Projects,No.LSFGG-2023015.
文摘BACKGROUND With advancements in the development of endoscopic technologies,the endo-scopic submucosal dissection(ESD)has been one of the gold-standard therapies for early gastric cancer.AIM To investigate the efficacy and safety ESD in the treatment of early gastric cancer and precancerous lesions in the elderly patients.METHODS Seventy-eight elderly patients with early gastric cancer and precancerous lesions admitted to the Third Affiliated Hospital of Qiqihar Medical University were se-lected and classified into two groups according to the different surgical therapies they received between January 2021 and June 2022.Among them,39 patients treated with ESD were included in an experimental group,and 39 patients treated with endoscopic mucosal resection(EMR)were included in a control group.We compared the basic intraoperative conditions,postoperative short-term recovery,long-term recovery effects and functional status of gastric mucosa between the two groups;the basic intraoperative conditions included lesion resection,intra-operative bleeding and operation time;the postoperative short-term recovery assessment indexes were length of hospital stay and incidence of surgical complic-ations;and the long-term recovery assessment indexes were the recurrence rate at 1 year postoperatively and the survival situation at 1 year and 3 years postoper-atively;and we compared the preoperative and predischarge serum pepsinogen I(PG I)and PG II levels and PG I/PG II ratio in the two groups before surgery and discharge.RESULTS The curative resection rate and the rate of en bloc resection were higher in the experimental group than in the control group.The intraoperative bleeding volume was higher in the experimental group than in the control group.The operation time was longer in the experimental group than that in the control group,and the rate for base residual focus was lower in the experimental group than that of the control group,and the differences were all statistically significant(all P<0.05).The length of hospital stay was longer in the experi-mental group than in the control group,and the incidence of surgical complications,1-year postoperative recu-rrence rate and 3-year postoperative survival rate were lower in the experimental group than in the control group,and the differences were statistically significant(all P<0.05).However,the difference in the 1-year postoperative survival rate was not statistically significant between the two groups(P>0.05).Before discharge,PG I and PG I/PG II ratio were elevated in both groups compared with the preoperative period,and the above indexes were higher in the experimental group than those in the control group,and the differences were statistically significant(both P<0.05).Moreover,before discharge,PG II level was lower in both groups compared with the preoperative period,and the level was lower in the experimental group than in the control group,and the differences were all statistically significant(all P<0.05).CONCLUSION Compared with EMR,ESD surgery is more thorough.It reduces the rate of base residual focus,recurrence rate,surgical complications,and promotes the recovery of gastric cells and glandular function.It is safe and suitable for clinical application.
基金Supported by Development Program of Shaanxi Province,No.2021SF-221.
文摘BACKGROUND Gastric cancer is a common malignant tumor of the digestive tract,and endosco-pic submucosal dissection(ESD)is the preferred treatment for early-stage gastric cancer.The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD.AIM To analyze the features of gastric mucosal tumors at different differentiation levels,and to explore the prognostic factors of ESD.METHODS We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021,according to the latest Japanese guidelines(sixth edition),and divided them into low-grade intrae-pithelial neoplasia(LGIN),high-grade intraepithelial neoplasia(HGIN),and computed tomography at 3,6 and 12 months after ESD.We compared clinicopathologic characteristics,ESD efficacy,and complications with different degrees of differentiation,and analyzed the related factors associated with ESD.RESULTS HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients(P<0.001)and accounted for more 0-IIc(P<0.001),atrophic gastritis was common(P<0.001),and irregular microvascular patterns(IMVPs)and demarcation lines(DLs)were more obvious(P<0.001).There was more infiltration in the undifferentiated carcinoma tissue(P<0.001),more abnormal folds and poorer mucosal peristalsis(P<0.001),and more obvious IMVPs,irregular microsurface patterns and DLs(P<0.05)than in the LGIN and HGIN tissues.The disease-free survival rates at 2,5,and 8 years after ESD were 95.0%,90.1%,and 86.9%,respectively.Undifferen-tiated lesions(HR 5.066),white moss(HR 7.187),incomplete resection(HR 3.658),and multiple primary cancers(HR 2.462)were significantly associated with poor prognosis.CONCLUSION Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics,which are closely related to the safety and efficacy of ESD.
基金the Natural Science Foundation of Hainan Province,No.823MS046the Talent Program of Hainan Medical University,No.XRC2022007.
文摘BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported to play an anti-inflammatory role.However,the underlying mechanism is still unclear.AIM To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium(DSS)-induced colitis.METHODS Mice were administered 3%DSS drinking water,and disease activity index was determined to evaluate the status of colitis.Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran,and bacterial translocation was evaluated by measuring serum lipopolysaccharide.Intestinal epithelial cell ultrastructure was observed by electron microscopy.Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA,respectively.Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels.RESULTS Compared to wild-type(WT)mice,inflammation and intestinal permeability in alk-SMase knockout(KO)mice were more severe beginning 4 d after DSS induction.The mRNA and protein levels of intestinal barrier proteins,including zonula occludens-1,occludin,claudin-3,claudin-5,claudin-8,mucin 2,and secretory immunoglobulin A,were significantly reduced on 4 d after DSS treatment.Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells.Furthermore,by day 4,mitochondria appeared swollen and degenerated.Additionally,compared to WT mice,serum malondialdehyde levels in KO mice were higher,and the antioxidant capacity was significantly lower.The expression of the transcription factor nuclear factor erythroid 2-related factor 2(Nrf2)in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment.mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased.Finally,colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone,which is an Nrf2 activator.CONCLUSION Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.
文摘In this editorial we comment on the article published in the recent issue of the World Journal of Gastrointestinal Endoscopy 2023;15(11):634-680.Gastric cancer(GC)remains the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide.The overall prevalence of GC has declined,although that of proximal GC has increased over time.Thus,a significant proportion of GC cases and deaths can be avoided if preventive interventions are taken.Early GC(EGC)is defined as GC confined to the mucosa or submucosa.Endoscopic resection is considered the most appropriate treatment for precancerous gastrointestinal lesions improving patient quality of life,with reduced rates of complications,shorter hospitalization period,and lower costs when compared to surgical resection.Endoscopic mucosal resection(EMR)and endoscopic sub-mucosal dissection(ESD)are representative endoscopic treatments for EGC and precancerous gastric lesions.Standard EMR implies injection of a saline solution into the sub-mucosal space,followed by excision of the lesion using a snare.Complete resection rates vary depending on the size and severity of the lesion.When using conventional EMR methods for lesions less than 1 cm in size,the complete resection rate is approximately 60%,whereas for lesions larger than 2 cm,the complete resection rate is low(20%-30%).ESD can be used to remove tumors exceeding 2 cm in diameter and lesions associated with ulcers or submucosal fibrosis.Compared with EMR,ESD has higher en bloc resection rates(90.2%vs 51.7%),higher complete resection rates(82.1 vs 42.2%),and lower recurrence rates(0.65%vs 6.05%).Thus,innovative techniques have been introduced.
文摘BACKGROUND Duodenal Brunner's gland hyperplasia(BGH)is a therapeutic target when complications such as bleeding or gastrointestinal obstruction occur or when malignancy cannot be ruled out.Herein,we present a case of large BGH treated with endoscopic mucosal resection(EMR).CASE SUMMARY An 83-year-old woman presented at our hospital with dizziness.Blood tests revealed severe anemia,esophagogastroduodenoscopy showed a 6.5 cm lesion protruding from the anterior wall of the duodenal bulb,and biopsy revealed the presence of glandular epithelium.Endoscopic ultrasonography(EUS)demonstr-ated relatively high echogenicity with a cystic component.The muscularis propria was slightly elevated at the base of the lesion.EMR was performed without complications.The formalin-fixed lesion size was 6 cm×3.5 cm×3 cm,showing nodular proliferation of non-dysplastic Brunner's glands compartmentalized by fibrous septa,confirming the diagnosis of BGH.Reports of EMR or hot snare polypectomy are rare for duodenal BGH>6 cm.In this case,the choice of EMR was made by obtaining information on the base of the lesion as well as on the internal characteristics through EUS.CONCLUSION Large duodenal lesions with good endoscopic maneuverability and no evident muscular layer involvement on EUS may be resectable via EMR.
文摘Mucosal healing(MH)is vital in maintaining homeostasis within the gut and protecting against injury and infections.Multiple factors and signaling pathways contribute in a dynamic and coordinated manner to maintain intestinal homeostasis and mucosal regeneration/repair.However,when intestinal homeostasis becomes chronically disturbed and an inflammatory immune response is constitutively active due to impairment of the intestinal epithelial barrier autoimmune disease results,particularly inflammatory bowel disease(IBD).Many proteins and signaling pathways become dysregulated or impaired during these pathological conditions,with the mechanisms of regulation just beginning to be understood.Consequently,there remains a relative lack of broadly effective therapeutics that can restore MH due to the complexity of both the disease and healing processes,so tissue damage in the gastrointestinal tract of patients,even those in clinical remission,persists.With increased understanding of the molecular mechanisms of IBD and MH,tissue damage from autoimmune disease may in the future be ameliorated by developing therapeutics that enhance the body’s own healing response.In this review,we introduce the concept of mucosal healing and its relevance in IBD as well as discuss the mechanisms of IBD and potential strategies for altering these processes and inducing MH.
基金Supported by Shaanxi Province Natural Science Basic Research Program-General Project,No:2019JM-580Project of Shaanxi Administration of Traditional Chinese Medicine,No.2019-ZZ-JC010Key R&D Projects in Shaanxi Province,No.2021SF-314.
文摘Ulcerative colitis(UC)is a chronic nonspecific inflammatory disease with complex causes.The main pathological changes were intestinal mucosal injury.Leucinerich repeat-containing G protein coupled receptor 5(LGR5)-labeled small intestine stem cells(ISCs)were located at the bottom of the small intestine recess and inlaid among Paneth cells.LGR5+small ISCs are active proliferative adult stem cells,and their self-renewal,proliferation and differentiation disorders are closely related to the occurrence of intestinal inflammatory diseases.The Notch signaling pathway and Wnt/β-catenin signaling pathway are important regulators of LGR5-positive ISCs and together maintain the function of LGR5-positive ISCs.More importantly,the surviving stem cells after intestinal mucosal injury accelerate division,restore the number of stem cells,multiply and differentiate into mature intestinal epithelial cells,and repair the damaged intestinal mucosa.Therefore,in-depth study of multiple pathways and transplantation of LGR5-positive ISCs may become a new target for the treatment of UC.
基金financially supported by Natural Science Foundation from Guangdong Province (2021A1515010830,2021A1515012412)National Key R&D Project (2018YFD0500600,2021YFD300404)+3 种基金China Agriculture Research System of MOF and MARA (CARS-41)the Key Realm R&D Program of Guangdong Province (2020B0202090004)National Natural Science Foundation of China (31802104)the Science and Technology Program of Guangdong Academy of Agricultural Sciences (202106TD,R2019PY-QF008),P.R.China。
文摘Background Anthocyanins(AC)showed positive effects on improving the intestinal health and alleviating intestinal pathogen infections,therefore,an experiment was conducted to explore the protective effects of supplemented AC on Salmonella-infected chickens.Methods A total of 240 hatchling chickens were randomly allocated to 4 treatments,each with 6 replicates.Birds were fed a basal diet supplemented with 0(CON,and ST),100(ACL)and 400(ACH)mg/kg of AC for d 60,and orally challenged with PBS(CON)or 10^(9) CFU/bird(ST,ACL,ACH)Salmonella Typhimurium at d 14 and 16.Results(1)Compared with birds in ST,AC supplementation increased the body weight(BW)at d 18 and the average daily gain(ADG)from d 1 to 18 of the Salmonella-infected chickens(P<0.05);(2)AC decreased the number of Salmonella cells in the liver and spleen,the contents of NO in plasma and inflammatory cytokines in ileal mucosa of Salmonella-infected chickens(P<0.05);(3)Salmonella infection decreased the ileal villi height,villi height to crypt depth(V/C),and the expression of zonulaoccludins-1(ZO-1),claudin-1,occludin,and mucin 2(MUC2)in ileal mucosa.AC supplementation relieved these adverse effects,and decreased ileal crypt depth(P<0.05);(4)In cecal microbiota of Salmonella-infected chickens,AC increased(P<0.05)the alpha-diversity(Chao1,Pd,Shannon and Sobs indexes)and the relative abundance of Firmicutes,and decreased(P<0.05)the relative abundance of Proteobacteria and Bacteroidota and the enrichment of drug antimicrobial resistance,infectious bacterial disease,and immune disease pathways.Conclusions Dietary AC protected chicken against Salmonella infection via inhibiting the Salmonella colonization in liver and spleen,suppressing secretion of inflammatory cytokines,up-regulating the expression of ileal barrier-related genes,and ameliorating the composition and function of cecal microbes.Under conditions here used,100 mg/kg bilberry anthocyanin was recommended.
基金supported by the National Key R&D Program of China(2021YFD1300403)the Major Program of Heilongjiang Province of China(2021ZX12B08-02).
文摘Background Cold regions have long autumn and winter seasons and low ambient temperatures.When pigs are unable to adjust to the cold,oxidative damage and inflammation may develop.However,the differences between cold and non-cold adaptation regarding glucose and lipid metabolism,gut microbiota and colonic mucosal immunological features in pigs are unknown.This study revealed the glucose and lipid metabolic responses and the dual role of gut microbiota in pigs during cold and non-cold adaptation.Moreover,the regulatory effects of dietary glucose supplements on glucose and lipid metabolism and the colonic mucosal barrier were evaluated in cold-exposed pigs.Results Cold and non-cold-adapted models were established by Min and Yorkshire pigs.Our results exhibited that cold exposure induced glucose overconsumption in non-cold-adapted pig models(Yorkshire pigs),decreasing plasma glucose concentrations.In this case,cold exposure enhanced the ATGL and CPT-1αexpression to promote liver lipolysis and fatty acid oxidation.Meanwhile,the two probiotics(Collinsella and Bifidobacterium)depletion and the enrichment of two pathogens(Sutterella and Escherichia-Shigella)in colonic microbiota are not conducive to colonic mucosal immunity.However,glucagon-mediated hepatic glycogenolysis in cold-adapted pig models(Min pigs)maintained the stability of glucose homeostasis during cold exposure.It contributed to the gut microbiota(including the enrichment of the Rikenellaceae RC9 gut group,[Eubacterium]coprostanoligenes group and WCHB1-41)that favored cold-adapted metabolism.Conclusions The results of both models indicate that the gut microbiota during cold adaptation contributes to the protection of the colonic mucosa.During non-cold adaptation,cold-induced glucose overconsumption promotes thermogenesis through lipolysis,but interferes with the gut microbiome and colonic mucosal immunity.Furthermore,glucagon-mediated hepatic glycogenolysis contributes to glucose homeostasis during cold exposure.
文摘BACKGROUND While colon endoscopic mucosal resection(EMR)is an effective technique,removal of larger polyps often requires piecemeal resection,which can increase recurrence rates.Endoscopic submucosal dissection(ESD)in the colon offers the ability for en bloc resection and is well-described in Asia,but there are limited studies comparing ESD vs EMR in the West.AIM To evaluate different techniques in endoscopic resection of large polyps in the colon and to identify factors for recurrence.METHODS The study is a retrospective comparison of ESD,EMR and knife-assisted endoscopic resection performed at Stanford University Medical Center and Veterans Affairs Palo Alto Health Care System between 2016 and 2020.Knife-assisted endoscopic resection was defined as use of electrosurgical knife to facilitate snare resection,such as for circumferential incision.Patients≥18 years of age undergoing colonoscopy with removal of polyp(s)≥20 mm were included.The primary outcome was recurrence on follow-up.RESULTS A total of 376 patients and 428 polyps were included.Mean polyp size was greatest in the ESD group(35.8 mm),followed by knife-assisted endoscopic resection(33.3 mm)and EMR(30.5 mm)(P<0.001).ESD achieved highest en bloc resection(90.4%)followed by knife-assisted endoscopic resection(31.1%)and EMR(20.2%)(P<0.001).A total of 287 polyps had follow-up(67.1%).On follow-up analysis,recurrence rate was lowest in knife-assisted endoscopic resection(0.0%)and ESD(1.3%)and highest in EMR(12.9%)(P=0.0017).En bloc polyp resection had significantly lower rate of recurrence(1.9%)compared to non-en bloc(12.0%,P=0.003).On multivariate analysis,ESD(in comparison to EMR)adjusted for polyp size was found to significantly reduce risk of recurrence[adjusted hazard ratio 0.06(95%CI:0.01-0.57,P=0.014)].CONCLUSION In our study,EMR had significantly higher recurrence compared to ESD and knife-assisted endoscopic resection.We found factors including resection by ESD,en bloc removal,and use of circumferential incision were associated with significantly decreased recurrence.While further studies are needed,we have demonstrated the efficacy of ESD in a Western population.
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.
文摘A review of the development of the key performance metrics of endoscopic mucosal resection(EMR),learning from the experience of the establishment of widespread colonoscopy quality measurements.Potential future performance markers for both colonoscopy and EMR are also evaluated to ensure continued high quality performance is maintained with a focus service framework and predictors of patient outcome.
文摘BACKGROUND Endoscopic mucosal resection is an innovative method for treating early gastric cancer and has been widely used in clinical practice.AIM To analyze the factors associated with the development of heterochronic gastric cancer in patients with early gastric cancer who had undergone endoscopic mucosal dissection(EMD).METHODS A cohort of patients with early gastric cancer treated using EMD was retrospectively analyzed,and patients who developed heterochronic gastric cancer after the surgery were compared with those who did not.The effects of patient age,sex,tumor size,pathological type,and surgical technique on the development of heterochronic gastric cancer were assessed using statistical analysis.RESULTS Of the 300 patients with early gastric cancer,150 patients developed heterochronic gastric cancer after EMD.Statistical analysis revealed that patient age(P value=XX),sex(P value=XX),tumor size(P value=XX),pathological type(P value=XX),and surgical technique(P value=XX)were significantly associated with the occurrence of heterochronic gastric cancer.CONCLUSION Age,sex,tumor size,pathological type,and surgical technique are key factors influencing the occurrence of heterochronic gastric cancer after EMD in patients with early gastric cancer.To address these factors,postoperative follow-up and management should be strengthened to improve the prognosis and survival rate of patients.
文摘BACKGROUND Acute esophageal mucosal lesions(AEMLs)are an underrecognized and largely unexplored disease.Endoscopic findings are similar,and a higher percentage of AEML could be misdiagnosed as reflux esophagitis Los Angeles classification grade D(RE-D).These diseases could have different pathologies and require different treatments.AIM To compare AEML and RE-D to confirm that the two diseases are different from each other and to clarify the clinical features of AEML.METHODS We selected emergency endoscopic cases of upper gastrointestinal bleeding with circumferential esophageal mucosal injury and classified them into AEML and RE-D groups according to the mucosal injury’s shape on the oral side.We examined patient background,blood sampling data,comorbidities at onset,endoscopic characteristics,and outcomes in each group.RESULTS Among the emergency cases,the AEML and RE-D groups had 105(3.1%)and 48(1.4%)cases,respectively.Multiple variables exhibited significantly different results,indicating that these two diseases are distinct.The clinical features of AEML consisted of more comorbidities[risk ratio(RR):3.10;95%confidence interval(CI):1.68–5.71;P<0.001]and less endoscopic hemostasis compared with RE-D(RR:0.25;95%CI:0.10–0.63;P<0.001).Mortality during hospitalization was higher in the AEML group(RR:3.43;95%CI:0.82–14.40;P=0.094),and stenosis developed only in the AEML group.CONCLUSION AEML and RE-D were clearly distinct diseases with different clinical features.AEML may be more common than assumed,and the potential for its presence should be taken into account in cases of upper gastrointestinal bleeding with comorbidities.
基金supported by the Clinical Medicine Plus X-Young Scholars Project of Peking University of the Fundamental Research Funds for the Central Universities (PKU2023LCXQ035)the Chinese Academy of Medical Sciences Central Public-Interest Scientific Institution Basal Research Fund (2022-JKCS-27)+3 种基金the National clinical key discipline construction project (PKUSSNKP-202114)China Postdoctoral Science Foundation (2022M720289)Chinese Stomatological Association Clinical Research Fund (CSA-SIS2022-01)National Natural Science Foundation of China (82301024)
文摘Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing.This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve(B.breve).A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing.The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography(micro-CT).Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay(ELISA).The senescence and biological functions were tested in oral mucosal stem cells(OMSCs)treated with sunitinib.Ligated loop experiments were used to investigate the effect of oral B.breve.Neutralizing antibody for interleukin-10(IL-10)was used to prove the critical role of IL-10 in the pro-healing process derived from B.breve.Results showed that sunitinib caused oral mucosal wound healing impairment in mice.In vitro,sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation,migration,and differentiation.Oral administration of B.breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells(DCs)-derived IL-10.IL-10 reversed cellular senescence caused by sunitinib in OMSCs,and IL-10 neutralizing antibody blocked the ameliorative effect of B.breve on oral mucosal wound healing under sunitinib treatment conditions.In conclusion,sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B.breve could improve wound healing impairment via intestinal DCs-derived IL-10.
文摘We reviewed a study that reported a comparative analysis of the effects of endoscopic mucosal resection(EMR)precutting and conventional EMR for removing non-pedunculated,10-20 mm sized colorectal polyps.We identified some statistical deficiencies in this study.In addition,we believe that the differences between the treatments failed to achieve significance,and therefore,further analysis is required.
基金supported by the National Key R&D Program of China(No.2018YFC0311103).
文摘The pathogens of most infectious diseases invade the host through mucosal sites,and immunization with mucosal vaccines is the best means of combating these infectious diseases.Oral delivery and nasal delivery are the most common methods of mucosal vaccination.However,the delivery process is inefficient,and mucosal vaccination is ineffective because the vaccine formulation is easily and rapidly removed and has difficulty in crossing the mucosal surface.In this paper,we investigated whether the mucosal immune response could be enhanced by ultrasound facilitation of nasal mucosal delivery of vaccine preparations.For this purpose,we used manganese dioxide(MnO2)as the vaccine carrier/adjuvant,coated with chitosan oligosaccharide(COS)to enhance mucosal adsorption,and further physically adsorbed model antigen ovalbumin(OVA)to construct a nanoparticulate vaccine formulation MnO2@COS@OVA.Ultrasound treatment was found to promote antigen delivery and recruitment of dendritic cells(DCs)and macrophages as well as T-cell infiltration in nasal mucosal tissues through nasal mucosal immunization studies.With ultrasound assistance,MnO2@COS@OVA particles promoted the maturation of DCs in vitro and in vivo and promoted the production of effector memory T cells in vivo and cytokine secretion by splenocytes in vitro.In particular,ultrasound treatment significantly increased the levels of secretory IgA antibodies in the nasal mucosa and genital tract mucosa of experimental mice.In addition,the experimental data showed that the MnO2@COS@OVA particles had good biocompatibility and caused no significant damage to the nasal mucosal and vital organ tissue.These data suggest that ultrasound treatment can promote the induction of efficient immune responses to mucosal vaccines and provide new ideas for the opening and clinical translation of mucosal vaccines.
文摘BACKGROUND Endoscopic resection(ER)with bipolar snare,in which the electric current only passes through the tissue between the device’s two electrodes,is a prominent method used to prevent perforation due to electricity potentially.ER using bipolar snare with or without submucosal injection enabled safe resection of colorectal lesions measuring 10-15 mm in an ex vivo porcine model.ER with bipolar snare is expected to have good treatment outcomes in 10-15 mm colorectal lesions,with high safety even without submucosal injection.However,no clinical reports have compared treatment outcomes with and without submucosal injection.AIM To compare the treatment outcomes of bipolar polypectomy with hot snare polypectomy(HSP)to those with endoscopic mucosal resection(EMR).METHODS In this single-centre retrospective study,we enrolled 10-15 mm nonpedunculated colorectal lesions(565 Lesions in 463 patients)diagnosed as type 2A based on the Japan Narrow-band Imaging Expert Team classification,resected by either HSP or EMR between January 2018 and June 2021 at the National Cancer Center Hospital East.Lesions were divided into HSP and EMR groups,and propensity score matching was performed.In the matched cohort,en bloc and R0 resection rates and adverse events were compared between the two groups.RESULTS Of the 565 lesions in 463 patients,117 lesions each in the HSP and EMR groups were selected after propensity score matching.In the original cohort,there was a significant difference in antithrombotic drug use(P<0.05),lesion size(P<0.01),location(P<0.01),and macroscopic type(P<0.05)between the HSP and EMR groups.In the matched cohort,the en bloc resection rates were comparable between both groups[93.2%(109/117)vs 92.3%(108/117),P=0.81],and there was no significant difference in the R0 resection rate[77.8%(91/117)vs 80.3%(94/117),P=0.64].The incidence of delayed bleeding was similar in both groups[1.7%(2/117)].Perforation occurred in the EMR group[0.9%(1/117)]but not in the HSP group.CONCLUSION Using bipolar snare,ER of nonpedunculated 10-15 mm colorectal lesions may be performed safely and effectively,even without submucosal injection.
基金supported by the National Natural Science Foundation of China(31872362 and 32072688)the Agricultural Science and Technology Independent Innovation Fund Project of Jiangsu Province[CX(19)1006].
文摘Background:Lactic acid bacteria(LAB)participating in milk fermentation naturally release and enrich the fermented dairy product with a broad range of bioactive metabolites,which has numerous roles in the intestinal health-promot-ing of the consumer.However,information is lacking regarding the application prospect of LAB fermented milk in the animal industry.This study investigated the effects of lactic acid bacteria-fermented formula milk(LFM)on the growth performance,intestinal immunity,microbiota composition,and transcriptomic responses in weaned piglets.A total of 24 male weaned piglets were randomly divided into the control(CON)and LFM groups.Each group consisted of 6 replicates(cages)with 2 piglets per cage.Each piglet in the LFM group were supplemented with 80 mL LFM three times a day,while the CON group was treated with the same amount of drinking water.Results:LFM significantly increased the average daily gain of piglets over the entire 14 d(P<0.01)and the average daily feed intake from 7 to 14 d(P<0.05).Compared to the CON group,ileal goblet cell count,villus-crypt ratio,sIgA,and lactate concentrations in the LFM group were significantly increased(P<0.05).Transcriptomic analysis of ileal mucosa identified 487 differentially expressed genes(DEGs)between two groups.Especially,DEGs involved in the intestinal immune network for IgA production pathways,such as polymeric immunoglobulin receptor(PIGR),were significantly up-regulated(P<0.01)by LFM supplementation.Moreover,trefoil factor 2(TFF2)in the LFM group,one of the DEGs involved in the secretory function of goblet cells,was also significantly up-regulated(P<0.01).Sequenc-ing of the 16S rRNA gene of microbiota demonstrated that LFM led to selective enrichment of lactate-producing and short-chain fatty acid(SCFA)-producing bacteria in the ileum,such as an increase in the relative abundance of Entero-coccus(P=0.09)and Acetitomaculum(P<0.05).Conclusions:LFM can improve intestinal health and immune tolerance,thus enhancing the growth performance of weaned piglets.The changes in microbiota and metabolites induced by LFM might mediate the regulation of the secretory function of goblet cells.
基金supported by National Key Research and Development Program of China(2019YFC1605003-3)the Science and Technology Projects of Xiamen Science and Technology Bureau(3502Z20183034)。
文摘The numerous health benefits of olive oil are widely known,however,it also provides anti-allergic properties that have not yet been fully defined.In this study,the anti-allergic activity of olive oil was evaluated by analyzing the clinical symptoms and immune-related factors in BALB/c mice that had ingested600 mg/(kg·day)olive oil for two weeks prior to the evaluation.An allergy model was subsequently constructed for analysis,the results of which showed that the olive oil reduced the scores of allergic symptoms in the mice,and up-regulated the hypothermia and the decline in the immune organ index.Moreover,fewer allergy-related cytokines and reduced intestinal inflammation was discovered in the olive oil-treated group.In addition,analysis of intestinal mucosal immune-related factors revealed that the olive oil promoted the expression of intestinal tight junction proteins(Claudin-1,Occludin,and ZO-1)and IL-22,and helped maintain the integrity of the intestinal epithelial physical barrier.Increased levels of mucin 2 andβ-defensin were also found in the intestinal mucus of the olive oil-treated mice.These findings suggest that the oral administration of olive oil effectively attenuated the ovalbumin-induced allergic immune response in the mice,and had a positive effect on intestinal epithelial mucosal immunity.