摘要：Adequate oxygen supply is essential for maintaining the body's normal physiological function.In chronic inflammatory conditions such as inflammatory bowel disease(IBD),insufficient oxygen reaching the intestine triggers the regulatory system in response to environmental changes.However,the pathogenesis of IBD is still under investigation.Recent research has highlighted the significant role of hypoxia in IBD,particularly the involvement of hypoxia-inducible factors(HIF)and their regulatory mechanisms,making them promising therapeutic targets for IBD.This review will delve into the role of hypoxia,HIF,and the associated hypoxia-inflammatory microenvironment in the context of IBD.Potential interventions for addressing these challenging gastrointestinal inflammatory diseases will also be discussed within this framework.

摘要：Alcohol-associated liver disease(ALD)is a significant global health challenge,encompassing a spectrum from steatotic liver disease to cirrhosis and alcohol-associated hepatitis,and contributed to 25%of global cirrhosis deaths in 2019.The identification of both modifiable(e.g.heavy drinking,metabolic syndromes)and non-modifiable risk factors(e.g.genetic predispositions)is crucial for effective disease management.Alcohol use assessment and treatment,by using both behavioral therapy and pharmacotherapeutic modalities,nutrition support,and optimization of liver disease modifiers,form the cornerstone of management.Advances in medical therapies,such as fecal microbiota transplantation and novel agents such as IL-22,are being explored for their therapeutic potential.A unifying theme in ALD care is the need for a personalized approach to management,accounting for the spectrum of the disease and individual patient character-istics,to tailor interventions effectively.Finally,it is essential to address the challenges to effective ALD treatment,including socioeco-nomic,logistical,and stigma-related barriers,to improve patient outcomes.This review discusses the current knowledge on ALD,including epidemiology,pathophysiology,risk factors,and management strategies,highlighting the critical role of integrated care models.

摘要：The low incidence of combined hepatocellular cholangiocarcinoma(cHCC-CCA)is an important factor limiting research progression.Our study extensively included nearly three decades of relevant literature and assembled the most comprehensive database com-prising 5,742 patients with cHCC-CCA.We summarized the characteristics,tumor markers,and clinical features of these patients.Additionally,we present the evolution of cHCC-CCA classification and explain the underlying rationale for these classification stand-ards.We reviewed cHCC-CCA diagnostic advances using imaging features,tumor markers,and postoperative pathology,as well as treatment options such as surgical,adjuvant,and immune-targeted therapies.In addition,recent advances in more effective chemo-therapeutic regimens and immune-targeted therapies were explored.Furthermore,we described the molecular mutation features and potential specific markers of cHCC-CCA.The prognostic value of Nestin has been proven,and we speculate that Nestin will also play a role in classification and diagnosis.However,further research is needed.Moreover,we believe that the possibility of using machine learning liquid biopsy for preoperative diagnosis and establishing a scoring system are directions for future research.

摘要：Background:The oncological safety of transanal total mesorectal excision(taTME)remains uncertain,and its special surgical approach may contribute to tumor cell dissemination.Thus,we conducted a study to investigate the impact of surgical approach on circulating tumor cell(CTC)counts and phenotypes in rectal cancer. Methods:This is a prospective randomized controlled study(ClinicalTrials:NCT05109130).The patients were randomized to either the taTME(n¼49)or laparoscopic TME(laTME)(n¼48)groups.Blood samples were collected from the central vein to measure CTC counts and phenotypes at three time points:preoperative(t1),immediately post-tumor removal(t2),and one week post-surgery(t3).The effect of surgical procedure on CTCs at each time point was analyzed,with the primary endpoint being the change in CTC counts from t1 to t3 for each surgical approach.This study adheres to Consolidated Standards of Reporting Trials Guidelines. Results:The baseline clinicopathologic characteristics of the laTME and taTME groups were balanced.The change in CTC count from t1 to t3 was 1.81±5.66 in the laTME group and 2.18±5.53 in the taTME group.The taTME surgery was non-inferior to laTME in terms of changing CTC counts(mean difference[MD]:-0.371;95%confidence interval[CI]:-2.626 to 1.883,upper-sided 95%CI of 1.883<2,non-inferiority boundary value).Compared with that at t1,the CTC count at t2 did not change significantly.However,higher CTC counts were detected at t3 than at t2 in the taTME(P¼0.032)and laTME(P¼0.003)groups.From t1 to t3,CTC counts significantly in-creased in both the taTME(P¼0.008)and laTME(P¼0.031)groups.There were no significant differences in CTC phenotype changes between the two groups from t1 to t3. Conclusions:Compared with laTME,taTME did not affect CTC counts and phenotypes.Our findings indicate that taTME is not infe-rior to laTME in terms of CTC changes from an oncological perspective.

摘要：Background:Tumor regression grade(TRG)is evaluated by calculating the proportion of residual tumor to stromal fibrosis,which can reflect the tumor response to neoadjuvant chemoradiotherapy(NCRT)in patients with locally advanced rectal cancer(LARC).Overall,patients with TRG1 show good sensitivity to NCRT but the long-term survival for these patients remains different.This study aimed to assess the prognostic factors in patients with TRG1. Methods:LARC patients who underwent NCRT and radical surgery were included.TRG was evaluated according to the National Comprehensive Cancer Network guidelines.The association between clinicopathological factors and survival outcomes was assessed in patients with TRG1.Overall survival(OS)and disease-free survival(DFS)were evaluated using both Kaplan-Meier analyses and Cox proportional hazards models. Results:Of the 393 LARC patients,104(26.5%)were diagnosed with TRG1.The 5-year OS rates and 5-year DFS rates of patients with TRG1 were 90.9%and 72.2%,respectively.In patients with TRG1,the tumor regression pattern(P¼0.001),pathologic tumor node metastasis(TNM)stage(P¼0.002),neoadjuvant rectal score(P¼0.024),T downstaging(P¼0.022),and baseline carcinoembryonic antigen level(P¼0.038)were associated with DFS in univariate analysis.Only the tumor regression pattern showed prognostic significance for DFS in multivariate analysis(P¼0.003).The group with tumor shrinkage had a higher OS rate than the tumor fragmentation group but the differ-ence in the OS rates between the two groups was not significant(P¼0.196). Conclusions:TRG could be a prognostic variable for LARC patients receiving NCRT.In patients with TRG1,the tumor regression pattern may represent another useful prognostic factor to better individualize the prognosis.

摘要：Introduction Endoscopic submucosal dissection(ESD)has evolved into a viable treatment modality for early esophageal cancer,with a distinct advantage of the ability to perform en-bloc resection and accu-rate histopathological assessment.The most common adverse events of ESD in the esophagus include perforation and stricture.In this report,we present a case of a rare complication of esopha-geal ESD,which happened during the procedure and was re-solved successfully based on our experience.

摘要：Background:Biliary tract infection is a common complication of choledocholithiasis.This study aimed to analyse the distribution of pathogenic bacteria in bile cultures from patients with choledocholithiasis combined with biliary tract infection to guide clinical application of antimicrobials and reduce the emergence of drug resistance. Methods:A total of 880 patients were enrolled in this retrospective study from 30 March 2017 to 31 August 2022 at the Affiliated Hospital of Qingdao University in China.Bile specimens were extracted for microbiological culture under aseptic conditions using en-doscopic retrograde cholangiopancreatography.Bacterial culture,strain identification,and antimicrobial susceptibility testing were conducted according to the standard protocol.Baseline data were retrieved from patient files. Results:Overall,90.34%(795/880)of bile samples showed positive microbiological results and 37.50%(330/880)demonstrated polymi-crobial infections.Among the 795 bile specimens with positive culture results,1,216 pathogenic bacteria were detected,with gram-negative bacilli accounting for 56.33%,gram-positive cocci for 41.86%,and fungi for 1.81%.The predominant gram-negative bacilli in the bile cultures were Escherichia coli(30.43%)and Klebsiella pneumoniae(13.98%),whereas the main gram-positive cocci were Enterococcus faecium(14.04%)and E.casseliflavus(4.28%).The annual trend analysis revealed a gradual decrease in the proportion of gram-negative bacilli and a gradual increase in the proportion of gram-positive cocci,with a concomitant decrease in the dominance of E.coli.Both E.faecium and E.coli showed high resistance to conventional antibiotics but high sensitivity to piperacillin/tazobactam,carbapenems,amikacin,and vancomycin. Conclusions:A significant change has occurred in the bile bacterial spectrum in patients with choledocholithiasis and biliary tract infection.The incidence of gram-positive cocci infections has increased annually,while that of gram-negative bacilli and E.coli infec-tions has decreased.Antibiotic administration should be tailored based on the local bacterial profile.

摘要：Introduction Anal cancer is a rare cancer accounting for?2％of all gastroin-testinal tract malignancies[1].Among anal cancers,squamous cell cancer(SCC)is the most common and lymphoma is one of the least frequent.The gastrointestinal tract is the most common site for extranodal non-Hodgkin's lymphoma(NHL),and diffuse large B-cell lymphoma(DLBCL)is the most common histologic subtype.

摘要：Background:KRAS/BRAF mutations(mutKRAS/mutBRAF)are unfavorable prognostic factors for colorectal cancer(CRC)metastases to the liver and lungs.However,their effects on the prognosis for patients with synchronous peritoneal metastasis(S-PM)of CRC after cytoreductive surgery(CRS)and hyperthermic intraperitoneal chemotherapy(HIPEC)are controversial.In the study,we aimed to de-termine the effects of mutKRAS/mutBRAF on the prognosis for patients with S-PM who received CRS. Methods:A total of 142 patients diagnosed with S-PM between July 2007 and July 2019 were included in this study.The demo-graphics,mutKRAS/mutBRAF status,overall survival(OS),and progression-free survival(PFS)of the patients were evaluated.The Kaplan-Meier method and log-rank test were used to estimate the difference in survival between groups. Results:Among 142 patients,68(47.9%)showed mutKRAS and 42(29.5%)showed mutBRAF.The median OS values were 8.4 and 34.3 months for patients with mutBRAF and BRAF wild-type,respectively(P<0.01).However,KRAS status was not significantly associ-ated with median OS(P=0.76).Multivariate analysis revealed carcinoembryonic antigen,CRS,HIPEC,and mutBRAF as independent predictors for OS.Based on these findings,a nomogram was constructed.The C-index was 0.789(95%confidence interval,0.742-0.836),indicating good predictive ability of the model.Furthermore,the 1-and 2-year survival calibration plots showed good agreement be-tween the predicted and actual OS rates.The area under curves of the 1-and 2-year survival predictions based on the nomogram were 0.807 and 0.682,respectively.Additionally,mutBRAF was significantly associated with lower PFS(P<0.001). Conclusions:mutBRAF is an independent prognostic risk factor for S-PM.The established nomogram predicted the OS of patients with CRC having S-PM with high accuracy,indicating its usefulness as a valuable prognostic tool for the designated patient cohort.

摘要：Cirrhosis with complications of liver decompensation and hepatocellular carcinoma(HCC)constitute a leading cause of morbidity and mortality worldwide.Portal hypertension is central to the progression of liver disease and decompensation.The most recent Baveno VII guidance included revision of the nomenclature for chronic liver disease,termed compensated advanced chronic liver disease,and leveraged the use of liver stiffness measurement to categorize the degree of portal hypertension.Additionally,non-selective beta blockers,especially carvedilol,can improve portal hypertension and may even have a survival benefit.Procedural techniques with interventional radiology have become more advanced in the management of refractory ascites and variceal bleed-ing,leading to improved prognosis in patients with decompensated liver disease.While lactulose and rifaximin are the preferred treatments for hepatic encephalopathy,many alternative treatment options may be used in refractory cases and even procedural interventions such as shunt embolization may be of benefit.The approval of terlipressin for the treatment of hepatorenal syndrome(HRS)in the USA has improved the way in which HRS is managed and will be discussed in detail.Malnutrition,frailty,and sarcopenia lead to poorer outcomes in patients with decompensated liver disease and should be addressed in this patient population.Palliative care interventions can lead to improved quality of life and clinical outcomes.Lastly,the investigation of systemic therapies,in partic-ular immunotherapy,has revolutionized the management of HCC.These topics will be discussed in detail in this review.

摘要：Background:The efficacy of adjuvant chemotherapy(AC)on survival outcomes of patients with stage Ⅰ gastric cancer(GC)after curative resection remains controversial.We aimed to determine whether these patients would benefit from AC. Methods:This retrospective study included patients with pathologically confirmed stage Ⅰ GC who underwent curative resection between November 2010 and December 2020.Patients were divided into AC and non-AC groups,then a 1∶1 propensity score matching(PSM)analysis was performed to minimize the selection bias.Potential risk factors including age,pN stage,pT stage,lymphovascular invasion,perineural invasion,tumor size,histological type,and carcinoembryonic antigen level were used as matching covariates.The recurrence-free survival(RFS)and disease-specific survival(DSS)were compared between groups using the Kaplan-Meier method. Results:A total of 902 consecutive patients were enrolled and 174(19.3％)patients were treated with AC.PSM created 123 pairs of patients.Before PSM,patients receiving AC had lower 10-year RFS rates(90％ vs 94.6％,P=0.035)than those who did not receive AC;the two groups had similar 10-year DSS rates(93.8％ vs 95.0％,P=0.240).After PSM,there were no statistical differences in the 10-year RFS(90.9％ vs 93.0％,P=0.507)or DSS rates(93.5％ vs 93.6％,P=0.811)between the two groups.Similar results were found in the stage ⅠA and ⅠB subgroups.Moreover,these findings were not affected by AC cycles. Conclusions:The addition of AC could not provide survival benefits for patients with stage Ⅰ GC after surgery and follow-up is thus recommended.However,large-scale randomized clinical trials are required.

摘要：Introduction Small intestinal diseases cannot be accurately located by using imaging,so small intestinal endoscopic ultrasound(SIEUS)is needed to evaluate submucosal changes,invasion degree,and extent of submucosal lesions.As double balloon enteroscopy(DBE)is extensively employed,small intestinal diseases are fre-quently detected,and enteroscopy-guided treatments(e.g.enteroscopy-guided small intestinal polypectomy)are increas-ingly available[1].Although enteroscopy enables direct observa-tion of small intestinal lesions,it does not enable observation of the deep-seated layers of the intestinal wall.Based on entero-scopy combined with SIEUS,the histological characteristics of various layers of the intestinal lumen and endoscopic ultrasound images of peripheral and neighboring organs can be obtained to observe the layers from which small intestinal lesions originate.

摘要：The landscape of liver disease management continues to evolve,with notable advancements in non-invasive diagnostics,understand-ing of perioperative risk,new therapies for cirrhotic complications,metabolic dysfunction-associated steatotic liver disease(MASLD),and alcohol-associated liver disease(ALD),as well as screening for hepatocellular carcinoma(HCC)and the management of special populations such as mothers with hepatitis B.In this Special Issue of Gastroenterology Report,we have compiled a collection of review articles that discuss practical approaches to managing common liver diseases,including HCC screening,non-invasive assessment of fibro-sis,multifaceted approaches to perioperative care and cirrhotic com-plications,and postpartum hepatitis flare in mothers with hepatitis B.Additionally,this issue provides concise reviews on the immune mechanisms in MASLD,highlighting critical findings and paving the way for future research directions.

摘要：Achieving a sustained virologic response(SVR)through direct-acting antivirals for hepatitis C virus(HCV)infection significantly reduces the long-term risk of hepatocellular carcinoma(HCC),particularly in patients with advanced fibrosis(F3)or cirrhosis(F4).However,despite this improvement,the risks associated with HCC and the optimal surveillance strategies for patients who have achieved SVR remain topics of debate.This controversy is compounded by challenges in reliably staging liver fibrosis non-invasively,especially at advanced fibrosis(F3),and the unclear cost-effectiveness,modality,frequency,and duration of HCC surveillance in indi-viduals with SVR but without cirrhosis.These factors contribute to significant variations in surveillance guidelines recommended by different professional societies.Therefore,there is a pressing need for an optimal surveillance strategy that is both simplified and cost-effective to facilitate wider adoption by clinicians.This review article evaluates the existing data,addresses ongoing controver-sies,and aims to provide new perspectives on HCC surveillance strategies for patients who have achieved SVR from HCV.

摘要：Background:Accumulating researchers have recognized mitophagy as a key player in tumors,but few studies have investigated its role in the tumor microenvironment(TME).Advances in the technology of single-cell RNA sequencing(scRNA-seq)have allowed unveiling the concealed features of the TME at cellular resolution.This study aimed to elucidate the role of mitophagy within the TME of colorectal cancer(CRC)and to establish a mitophagy-mediated risk model. Methods:We assessed mitophagy-related pathway activities at both single-cell and tissue levels.Subsequently,an unsupervised clustering algorithm was employed to identify mitophagy-mediated subtypes.Furthermore,we developed a mitophagy-mediated risk signature(MMRS)using least absolute shrinkage and selection operator(LASSO)Cox analysis and constructed a MMRS model incorporating the risk score and clinical variables.Subsequently,we used quantitative reverse transcription polymerase chain reac-tion analysis to verify the expression of the screened genes. Results:We retrieved and annotated a total of 14,719 cells from eight samples in the scRNA-seq GSE132465 data set.The activities of mitophagy-related pathways were uniformly upregulated in cancer cells.Integrating with bulk RNA-seq data,we identified two mitophagy-mediated clusters(C1 and C2)with distinct characteristics and prognoses.C2 was identified as a mitophagy-high cluster.Then,we developed a five-gene MMRS via LASSO Cox analysis in The Cancer Genome Atlas(TCGA)cohort.We utilized the GSE39582 cohort to validate the efficacy of our model.The expression of CX3CL1 and INHBB was upregulated in CRC tissues. Conclusions:The present study identified two mitophagy-mediated CRC subtypes with distinct features.Our MMRS may provide potential therapeutic strategies for CRC.The findings of our work offer novel insights into the involvement of mitophagy in CRC.

摘要：Inflammatory bowel disease(IBD)research often relies on animal models to study the etiology,pathophysiology,and management of IBD.Among these models,rats and mice are frequently employed due to their practicality and genetic manipulability.However,for studies aiming to closely mimic human pathology,non-human primates such as monkeys and dogs offer valuable physiological parallels.Guinea pigs,while less commonly used,present unique advantages for investigating the intricate interplay between neurological and immunological factors in IBD.Additionally,New Zealand rabbits excel in endoscopic biopsy techniques,providing insights into mucosal inflammation and healing processes.Pigs,with their physiological similarities to humans,serve as ideal models for exploring the complex relationships between nutrition,metabolism,and immunity in IBD.Beyond mammals,non-mammalian organisms including zebrafish,Drosophila melanogaster,and nematodes offer specialized insights into specific aspects of IBD pathology,highlighting the diverse array of model systems available for advancing our understanding of this multifaceted disease.In this review,we conduct a thorough analysis of various animal models employed in IBD research,detailing their applications and essential experimental parameters.These include clinical observation,Disease Activity Index score,pathological assessment,intestinal barrier integrity,fibrosis,inflammatory markers,intestinal microbiome,and other critical parameters that are crucial for evaluating modeling success and drug efficacy in experimental mammalian studies.Overall,this review will serve as a valuable resource for researchers in the field of IBD,offering insights into the diverse array of animal models available and their respective applications in studying IBD.

摘要：Introduction Lynch syndrome(LS)is an autosomal dominant condition caused by pathogenic variants in mismatch repair(MMR)genes.LS is as-sociated with an 80％lifetime risk for colorectal cancer(CRC);it is also characterized by extracolonic tumors,including endome-trial,stomach,or ovarian cancer[1,2].

摘要：Background:Non-alcoholic fatty liver disease(NAFLD)is a major contributor to liver diseases globally,yet there are limited studies investigating the impact of diet and lifestyle factors on its development.This study aimed to examine the association between the prevalence of NAFLD and predicted pro-inflammatory high-sensitivity C-reactive protein(hs-CRP)score. Methods:We included 1,076 Korean adults who underwent a medical examination at the Seoul National University Hospital Gangnam Healthcare Center in Korea between May and December 2011 and updated in 2021.The predicted pro-inflammatory hs-CRP score was derived from pro-inflammatory demographic,lifestyle,dietary,and anthropometric factors,and NAFLD was diagnosed using liver ultrasound.Multivariable-adjusted odds ratios(ORs)and 95％confidence intervals(CIs)of NAFLD odds accord-ing to predicted pro-inflammatory hs-CRP score were estimated using logistic regression at a two-sided P＜0.05. Results:Among the 1,076 participants,320 had NAFLD.The multivariable-adjusted ORs and 95％CIs for NAFLD by tertiles of predicted pro-inflammatory hs-CRP score were 1.00,3.30(2.06,5.30),18.25(10.47,31.81;P＜0.0001)in men and women combined,1.00,1.77(1.10,2.84),and 3.26(2.02,5.28;P＜0.0001)among men only,and 1.00,3.03(1.39,6.62),and 16.71(7.05,39.63;P＜0.0001)among women only. Conclusions:Predicted pro-inflammatory hs-CRP score was associated with higher odds of NAFLD.Adopting dietary and lifestyle changes related to lower inflammation might be a valuable strategy for preventing NAFLD.

摘要：Introduction Chronic intestinal pseudo-obstruction(CIPO),defined as chronic constipation without mechanical obstruction of the gastrointesti-nal tract[1,2],often presents with a truly chameleon-like symp-tomatology including irregular defecation,abdominal pain and distension,nausea,vomiting,and sometimes fluid/electrolyte imbalance.Although diarrhea was found in ≤17％of CIPO cases,its nature,however,has not been precisely described.Serious deviations of electrolyte and acid-base status,to the best of our knowledge,have not been reported.

摘要：Introduction Cholestatic jaundice in infancy occurs in～1 in 2,500 term infants and 25％of cases are genetically determined[1].An accurate diag-nosis is crucial for clinicians to provide timely and personalized management.Despite the increasing application of whole-exome sequencing(WES),the genetic diagnosis of some patients remains unclear.