BACKGROUND Bile spillage occurs more frequently in patients with incidental gallbladder carcinoma(iGBC)and may be associated with poor survival due to presumed high risk of peritoneal seeding.AIM To investigate the im...BACKGROUND Bile spillage occurs more frequently in patients with incidental gallbladder carcinoma(iGBC)and may be associated with poor survival due to presumed high risk of peritoneal seeding.AIM To investigate the impact of bile spillage during primary surgery on the survival of patients with iGBC.METHODS Medical records of patients with iGBC diagnosed between 2000 and 2019 in 27 Dutch secondary centers and 5 tertiary centers were retrospectively reviewed.Patient medical records were assessed.Predictors for overall survival(OS)were determined using multivariable Cox regression.RESULTS Of the 346 included patients with iGBC,138(39.9%)had bile spillage,which was associated with higher American Society of Anesthesiologists classification(P=0.020),cholecystitis(P<0.001),higher tumor stage(P=0.005),and non-radical resection(P<0.001).Bile spillage was associated with poor OS[hazard ratio=1.97,95%confidence interval(CI):1.48-2.63,P<0.001]with a median OS of 12 months(95%CI:7-18 months)vs 34 months(95%CI:14-55 months,P<0.001).In multivariable analysis,spillage was not an independent prognostic factor for survival(hazard ratio=1.21,95%CI:0.84-1.74,P=0.313).CONCLUSION Although bile spillage correlates with prognostic factors,it lacks independent prognostic significance for survival.Patients with an indication for additional treatment should be promptly referred to a specialized hepatopancreatobiliary center,irrespective of whether bile spillage has occurred.展开更多
BACKGROUND At present,there are few studies on the risk factors for bile leakage after laparoscopic common bile duct exploration(LCBDE)for older patients with choledocholithiasis.AIM To identify the potential risk fac...BACKGROUND At present,there are few studies on the risk factors for bile leakage after laparoscopic common bile duct exploration(LCBDE)for older patients with choledocholithiasis.AIM To identify the potential risk factors for bile leakage after LCBDE in older patients.METHODS A retrospective,single-center observational analysis was performed on patients aged≥70 years with choledocholithiasis treated by LCBDE who were admitted to our center between January 2011 and August 2022.The included patients were divided into non-bile leakage and bile leakage groups.Risk factors were determined by analyzing the observation indicators.RESULTS Seventy older patients with choledocholithiasis who underwent LCBDE were included.Univariate analysis showed that positive culture of bile bacteria was a risk factor for bile leakage after LCBDE(P<0.05).We further analyzed the bile bacteria,and univariate analysis showed that Enterococcus faecalis(E.faecalis)(P<0.05)and Pseudomonas aeruginosa(P<0.05)were associated with an increased risk of postoperative bile leakage in older patients(P<0.05).Multivariate analysis showed that E. faecalis was an independent risk factor for postoperative bile leakage in older patients (P < 0.05). Theresults of antibiotic sensitivity analysis showed that E. faecalis had 100% susceptibility to penicillin, ampicillin,linezolid, vancomycin, and furantoin.CONCLUSIONE. faecalis-associated biliary tract infection is an independent risk factor for bile leakage after LCBDE in olderpatients with choledocholithiasis. We suggest coverage with antibiotics to which E. faecalis is sensitive.展开更多
BACKGROUND Barrett esophagus(BE),a metaplastic adaptive process to gastrointestinal reflux,is associated with a higher risk of developing esophageal adenocarcinoma.However,the factors and mechanism that drive the mali...BACKGROUND Barrett esophagus(BE),a metaplastic adaptive process to gastrointestinal reflux,is associated with a higher risk of developing esophageal adenocarcinoma.However,the factors and mechanism that drive the malignant progression of BE is not well understood.AIM To investigate the role of bile acids,a component of the reflux fluid,in the malignant progression of BE.METHODS Using engineered green fluorescent protein-labeled adult tissue-resident stem cells isolated from BE clinical biopsies(BE-ASCs)as the target,we studied the effect of hydrophobic deoxycholic acid(DCA)and hydrophilic tetrahydroxylated bile acids(THBA)on cell viability by fluorescence intensity analysis,mucin production by dark density measurement,tissue structure by pathology analysis,expression of different pro-inflammatory factors gene by quantitative polymerase chain reaction and proteins by Western blot.RESULTS We found that hydrophobic DCA has cytotoxic and proinflammatory effects through activation of interleukin-1β(IL-1β)-nuclear factor kappa-B(NF-κB)inflammatory pathway on BE-ASCs.This action results in impaired cell viability,tissue intactness,reduced mucin production,and increased transition to disorganized atypical cells without intestinal features.In contrast,co-culture with hydrophilic THBA inhibited the IL-1β-NF-κB inflammatory pathway with maintenance of mature intestinal type cellular and histomorphology.CONCLUSION Our data indicates that the hydrophilic bile acid THBA can counteract the cytotoxic and proinflammatory effect of hydrophobic DCA and prevent the malignant progression of BE by inhibiting the IL-1β-NF-κB pathway.展开更多
BACKGROUND Complex hepatolithiasis has a high perioperative risk and recurrence rate.Currently,standardized treatment protocols and reliable anatomical landmarks remain undefined,posing considerable challenges for lap...BACKGROUND Complex hepatolithiasis has a high perioperative risk and recurrence rate.Currently,standardized treatment protocols and reliable anatomical landmarks remain undefined,posing considerable challenges for laparoscopic hepatectomy in these cases.Achieving complete stone clearance and addressing hilar bile duct stenosis are critical determinants of surgical efficacy in hepatolithiasis management.CASE SUMMARY We present the case of a woman with intrahepatic and extrahepatic bile duct stones and chronic cholangitis who underwent laparoscopic hepatectomy.Hepatic segments I,II,III,IV,VI,and VII of the diseased bile duct tree and bile duct cyst were resected according to the preoperative plan,plastic repair of the hilar bile duct was performed,and the repaired bile duct was anastomosed with the jejunum.The patient achieved a favorable prognosis and long-term survival.CONCLUSION Based on segmental/subsegmental diseased bile duct tree territory hepatectomy and hilar stenosis relief,laparoscopic hepatectomy for complex hepatolithiasis can be safely performed guided by double landmarks(diseased bile duct/hepatic vein).展开更多
BACKGROUND The pathogenesis of hepatic encephalopathy(HE)remains unclear,and the classical theory of ammonia toxicity lacks sufficient justification.AIM To investigate the potential of bile acids as intervention targe...BACKGROUND The pathogenesis of hepatic encephalopathy(HE)remains unclear,and the classical theory of ammonia toxicity lacks sufficient justification.AIM To investigate the potential of bile acids as intervention targets for HE.METHODS This study employed 42 wild-type male SD rats weighing 200±20 g.Using a random number table method,two rats were randomly selected to undergo common bile duct ligation(BDL).The remaining 40 rats were randomly assigned to four groups serving as controls:The vehicle+control diet(VC)group,the thioacetamide(TAA)group,the TAA+total bile acids(TAAT)group,and the TAA+cholestyramine(TAAC)group.Except for the VC group,all rats were intraperitoneally injected with 100 mg/kg TAA solution once daily for ten consecutive days to establish a HE model.Simultaneously,the TAAT and TAAC groups were administered a diet containing 0.3%bile acids(derived from BDL rats)and 2%cholestyramine,respectively,by gavage for ten days.For the BDL rat model group,the common BDL procedure was performed following the aforementioned protocol.After four weeks,laparotomy revealed swollen bile ducts at the ligation site,and bile was collected.Following successful modeling,behavioral tests,including the elevated plus maze and open field test,were conducted to assess the HE status of the rats.Peripheral blood,liver,and cerebral cortex tissue samples were collected,and the total bile acid content in the serum and cerebral cortex was measured using an enzyme cycling method.The levels of inflammatory factors in the serum and cerebral cortex were analyzed using enzyme-linked immunosorbent assay.Liver histological examination was performed using the hematoxylin-eosin double-labeling method.Reverse transcription polymerase chain reaction,western blot,immunohistochemistry,and other techniques were employed to observe the expression of microglial activation marker ionized calcium-binding adaptor molecule-1 and Takeda G protein-coupled receptor 5(TGR5)protein.RESULTS Compared to the VC group,the TAA group exhibited an exacerbation of HE in rats.The total bile acid content,proinflammatory factors[interleukin-1β(IL-1β),IL-6],and the anti-inflammatory factor IL-10 in both the serum and cerebral cortex were significantly elevated.Similarly,the expression of the TGR5 receptor in the cerebral cortex was upregulated.To investigate the impact of total bile acids on HE in rats,comparisons were made with the TAA group.In the TAAT group,the severity of HE was further aggravated,accompanied by increased total bile acid content in the serum and cerebral cortex,elevated pro-inflammatory factors(IL-1β,IL-6),reduced levels of the antiinflammatory factor IL-10,and decreased expression of the TGR5 receptor in the cerebral cortex.In the TAAC group,the severity of HE was alleviated.This group showed reductions in total bile acid content in the serum and cerebral cortex,decreased pro-inflammatory factors(IL-1β,IL-6),increased levels of the anti-inflammatory factor IL-10,and enhanced expression of the TGR5 receptor in the cerebral cortex.CONCLUSION This study demonstrated that the total bile acid content in the serum and cerebral cortex of TAA-induced liver cirrhosis rats was elevated.Furthermore,total bile acids exacerbate the progression of HE in rats.This effect may be attributed to bile acids’involvement in the development of neurological dysfunction by mediating TGR5 expression and regulating neuroinflammation.展开更多
BACKGROUND Intraoperative and postoperative biliary injuries remain significant complications of laparoscopic common bile duct exploration(LCBDE).Indocyanine green(ICG)has been shown to significantly reduce injuries c...BACKGROUND Intraoperative and postoperative biliary injuries remain significant complications of laparoscopic common bile duct exploration(LCBDE).Indocyanine green(ICG)has been shown to significantly reduce injuries caused by intraoperative operational errors.We found that the J-tube can reduce postoperative strictures and injuries to the common bile duct.At this moment,we aim to analyze and compare the complications,efficacy,short-term outcomes,and feasibility of these two adjunctive tools for LCBDE.AIM To evaluate the efficacy of ICG fluorescence imaging In LCBDE and J-tube drainage for patients with common bile duct stones.METHODS We retrospectively collected the clinical case data of patients who were treated at the Hepatobiliary Surgery Department of the Third People’s Hospital of Nantong,affiliated with Nantong University,from January 2016 to January 2021 due to gallbladder stones with choledocholithiasis and who underwent LCBDE combined with a primary suture and either J-tube or T-tube drainage.The patients were divided into groups:Traditional white-light laparoscopy+T-tube group(WL+T-tube),traditional WL+J-tube group,fluorescent laparoscopy+T-tube group(ICG+T-tube)and fluorescent laparoscopy+J-tube group(ICG+J-tube).The preoperative and postoperative clinical case data,laboratory examination data,and intraoperative and postoperative complications(including postoperative bile leakage,electrolyte disturbances,biliary peritonitis,and postoperative infections)and other relevant indicators were compared.RESULTS A total of 198 patients(112 males and 86 females)were included in the study,with 74 patients in the WL+T-tube,47 in the WL+J-tube,42 in the ICG+T-tube,and 35 in the ICG+J-tube.Compared with the other groups,the ICG+J had significantly shorter operation time(114 minutes,P=0.001),less blood loss(42 mL,P=0.02),shorter postoperative hospital stays(7 days,P=0.038),and lower surgical costs(China yuan 30178,P=0.001).Furthermore,patients were subdivided into two groups based on whether a T-tube or J-tube was placed during the surgery.By the third postoperative day,the aspartate transaminase,glutamic pyruvic transaminase,total bilirubin,and direct bilirubin levels were lower in the J-tube group than in the T-tube group(P<0.001).At last,follow-up observations showed that the incidence of biliary strictures at three months postoperatively was significantly lower in the J-tube group than in the T-tube group(P=0.002).CONCLUSION ICG fluorescence imaging in laparoscopic cholecystectomy with common bile duct exploration and J-tube drainage facilitates rapid identification of biliary anatomy and variations,reducing intraoperative bile duct injury,blood loss,surgery duration,and postoperative bile duct stenosis rates,supporting its clinical adoption.展开更多
The liver is a central metabolic organ that regulates numerous physiological processes,including glucose and lipid metabolism,detoxification,and the synthesis of essential proteins and bile.Bile acids(BAs),synthesized...The liver is a central metabolic organ that regulates numerous physiological processes,including glucose and lipid metabolism,detoxification,and the synthesis of essential proteins and bile.Bile acids(BAs),synthesized from cholesterol in hepatocytes,not only facilitate the emulsification and absorption of dietary fats but also act as potent signaling molecules through receptors such as the farnesoid X receptor(FXR)and Takeda G-protein-coupled receptor 5.Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally,closely linked with obesity,insulin resis-tance,and other components of metabolic syndrome.In MASLD,the metabolism of BAs is markedly disrupted,resulting in alterations in their synthesis,compo-sition,and signaling activity.These changes contribute to hepatic steatosis,inflammation,and fibrosis,thereby exacerbating metabolic dysfunction and liver damage.The altered profiles and signaling activity of BAs in MASLD patients suggest that BAs act not only as biomarkers of disease severity,but also as active mediators of its pathogenesis.Modulators of BA signaling pathways,especially FXR agonists,are the focus of intense research for their potential to beneficially influence liver steatosis and inflammation in MASLD.Recent research has yielded promising results,indicating potential therapeutic application and the introduction of novel agents aimed at modulating BA homeostasis and function.This minireview outlines the physiological roles of BAs,seeks to advance the elucidation of the mechanisms by which their dysregulation contributes to MASLD progression,and highlights current and emerging therapeutic approa-ches.A deeper understanding of these complex interactions is essential for improving the diagnosis,prognosis and treatment of MASLD.展开更多
BACKGROUND Bile leakage is a common complication following laparoscopic common bile duct exploration(LCBDE)with primary duct closure(PDC).Identifying and analyzing the risk factors associated with bile leakage is cruc...BACKGROUND Bile leakage is a common complication following laparoscopic common bile duct exploration(LCBDE)with primary duct closure(PDC).Identifying and analyzing the risk factors associated with bile leakage is crucial for improving surgical outcomes.AIM To explore the value analysis of common risk factors for bile leakage after LCBDE and PDC,with a focus on strict adherence to indications.METHODS Clinical data of 106 cases undergoing LCBDE+PDC in the Hepatobiliary and Pancreatic Surgery Department(Division 1)of Chuzhou First People’s Hospital from April 2019 to March 2024 were collected.Retrospective and multiple factor regression analysis were conducted on common risk factors for bile leakage.The change in surgical time was analyzed using the cumulative summation(CUSUM)method,and the minimum number of cases required to complete the learning curve for PDC was obtained based on the proposed fitting curve by identifying the CUSUM maximum value.RESULTS Multifactor logistic regression analysis showed that fibrinous inflammation and direct bilirubin/indirect bilirubin were significant independent high-risk factors for postoperative bile leakage(P<0.05).The time to drain removal and length of hospital stay in cases without bile leakage were significantly shorter than in cases with bile leakage(P<0.05),with statistical significance.The CUSUM method indicated that a minimum of 51 cases were required for the surgeon to complete the learning curve(P=0.023).CONCLUSION With a good assessment of duodenal papilla sphincter function,unobstructed bile-pancreatic duct convergence,exact stone clearance,and sufficient surgical experience to complete the learning curve,PDC remains the preferred method for bile duct closure and is worthy of clinical promotion.展开更多
While endoscopic retrograde cholangiopancreatography(ERCP)remains the primary treatment modality for common bile duct stones(CBDS)or choledocho-lithiasis due to advancements in instruments,surgical intervention,known ...While endoscopic retrograde cholangiopancreatography(ERCP)remains the primary treatment modality for common bile duct stones(CBDS)or choledocho-lithiasis due to advancements in instruments,surgical intervention,known as common bile duct exploration(CBDE),is still necessary in cases of difficult CBDS,failed endoscopic treatment,or altered anatomy.Recent evidence also supports CBDE in patients requesting single-step cholecystectomy and bile duct stone removal with comparable outcomes.This review elucidates relevant clinical anatomy,selection indications,and outcomes to enhance surgical understanding.The selection between trans-cystic(TC)vs trans-choledochal(TD)approaches is described,along with stone removal techniques and ductal closure.Detailed surgical techniques and strategies for both the TC and TD approaches,including instrument selection,is also provided.Additionally,this review comprehensively addresses operation-specific complications such as bile leakage,stricture,and entrapment,and focuses on preventive measures and treatment strategies.This review aims to optimize the management of CBDS through laparoscopic CBDE,with the goal of improving patient outcomes and minimizing risks.展开更多
BACKGROUND Proximal bile duct injury(BDI),which often occurs after laparoscopic cholecystectomy(LC),can lead to complex biliary stricture and recurrent cholangitis.This case report presented a 39-year-old woman who ex...BACKGROUND Proximal bile duct injury(BDI),which often occurs after laparoscopic cholecystectomy(LC),can lead to complex biliary stricture and recurrent cholangitis.This case report presented a 39-year-old woman who experienced proximal BDI during LC in 2017,leading to multiple episodes of cholangitis and subsequent hepaticojejunostomy in 2018.Despite these interventions,persistent biliary complications necessitated repeated hospital admissions and antibiotic treatment.Imaging studies revealed persistent stricture at the site of hepaticojejunostomy,prompting a series of percutaneous procedures,including balloon dilatation and biliary drainage.In August 2024,she underwent biodegradable biliary stenting,which significantly improved her condition.Subsequently,she remained clinically stable for 5 months without further episodes of cholangitis and had improved liver function tests.This case highlighted the complexities of managing postinjury biliary stricture,underscored the potential of biodegradable stents as an effective treatment option,and emphasized the need for a multidisciplinary approach in managing such complications.Long-term follow-up is essential for monitoring treatment effectiveness and preventing recurrence.CASE SUMMARY A 39-year-old female had a routine LC in 2017.The patient sustained a proximal BDI during the surgery.In the months that followed,recurrent bouts of cholangitis occurred.A hepaticojejunostomy biliary reconstruction was performed in 2018.However,hepatic cholangitis persisted.In 2021 and 2022,MRCP scans revealed biliary stasis,duct dilation,and a stricture at the hepaticojejunostomy site.A subsequent percutaneous transhepatic cholangiography(PTC)confirmed these findings and led to drain placement.The treatment included internal and external biliary drain placements,repeated balloon dilations of the stricture,percutaneous transhepatic cholangioscopy to extract intrahepatic lithiasis,and insertion of a biodegradable biliary stent.Since the first PTC intervention,there have been no hospital admissions for cholangitis.Liver function tests showed improvement,and for five months following the biodegradable stenting,the condition remained stable.Long-term surveillance with regular imaging and blood work has been emphasized.The final diagnosis is recurrent biliary stricture secondary to proximal BDI.Treatment,including hepaticojejunostomy,repeated PTC with balloon dilation,and biodegradable biliary stenting,has led to complete drainage of the biliary system.Ongoing follow-up remains crucial for monitoring the patient's progress and maintaining their health.CONCLUSION This case demonstrated how strictures and recurrent cholangitis complicate the management of BDI after LC.A customized and multidisciplinary approach to control chronic biliary disease was proven effective,as shown by the patient’s good outcome.This was achieved by integrating balloon dilatation sessions,biliary drainage,stone clearing,and biodegradable stent placement.Long-term follow-up and continued monitoring remain essential to ensure patient stability and prevent further complications.展开更多
BACKGROUND Pancreaticobiliary maljunction(PBM)is a rare congenital abnormality in pancreaticobiliary duct development.PBM is commonly found in children,and it often leads to acute pancreatitis and other diseases as a ...BACKGROUND Pancreaticobiliary maljunction(PBM)is a rare congenital abnormality in pancreaticobiliary duct development.PBM is commonly found in children,and it often leads to acute pancreatitis and other diseases as a result of pancreaticobiliary reflux.Roux-en-Y choledochojejunostomy is a common surgical method for the treatment of PBM,but there are several associated complications that may occur after this operation.CASE SUMMARY The patient,a 12-year-old female,was hospitalized nearly 20 times in 2021 for recurrent acute pancreatitis.In 2022,she was diagnosed with PBM and underwent laparoscopic common bile duct resection and Roux-en-Y choledochojejunostomy in a tertiary hospital.In the first year after surgery,the patient had more than 10 recurrent acute pancreatitis episodes.After undergoing abdominal computed tomography and other examinations,she was diagnosed with“residual bile duct stones and recurrent acute pancreatitis”.On January 30,2024,the patient was admitted to our hospital due to recurrent upper abdominal pain and was cured through endoscopic retrograde cholangiopancreatography.CONCLUSION This article reports a case of a child with distal residual common bile duct stones and recurrent acute pancreatitis after Roux-en-Y choledochojejunostomy for PBM.The patient was cured through endoscopic retrograde cholangiopancreatography.展开更多
Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic ...Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic liver disease,is still unknown,treatment remains symptomatic.Knowledge of the physicochemical properties of various bile acids and the adaptive responses of cholangiocytes and hepatocytes to them has provided an important basis for the development of relatively effective drugs based on hydrophilic bile acids that can potentially slow the progression of the disease.Advances in the use of hydrophilic bile acids for the treatment of PBC are also associated with the discovery of pathogenetic mechanisms of the development of cholangiocyte damage and the appearance of the first signs of this disease.For 35 years,ursodeoxycholic acid(UDCA)has been the unique drug of choice for the treatment of patients with PBC.In recent years,the list of hydrophilic bile acids used to treat cholestatic liver diseases,including PBC,has expanded.In addition to UDCA,the use of obeticholic acid,tauroursodeoxycholic acid and norursodeoxycholic acid as drugs is discussed.The pathogenetic rationale for treatment of PBC with various bile acid drugs is discussed in this review.Emphasis is made on the mechanisms explaining the beneficial therapeutic effects and potential of each of the bile acid as a drug,based on the understanding of the pathogenesis of the initial stages of PBC.展开更多
Bile reflux gastritis (BRG) is a gastro-intestinal condition especially characterized by the reflux of bile into the stomach, further leading to mucosal inflammation along with various other clinical manifestations. D...Bile reflux gastritis (BRG) is a gastro-intestinal condition especially characterized by the reflux of bile into the stomach, further leading to mucosal inflammation along with various other clinical manifestations. Despite its increasing recognition, BRG remains understudied, with limited understanding of its epidemiology, pathophysiology, and optimal therapeutic strategies. Present narrative review aimed to comprehensively examine the available literature on BRG, focusing on its prevalence, risk factors, pathophysiology, clinical presentation, diagnostic modalities, and available therapeutic strategies. A comprehensive literature search was conducted using PubMed, Embase, Google Scholar and Cochrane databases. Relevant studies were included based on predefined inclusion and exclusion criteria. A narrative synthesis was conducted to summarize and interpret the findings. The prevalence of BRG remains uncertain due to diagnostic challenges. Risk factors include impaired gastrointestinal motility, sphincteric dysfunction (pyloric sphincter and the lower oesophageal sphincter), biliary tract disease, and certain medications. The pathophysiology involves bile acid-induced mucosal injury, inflammation, and impaired gastric defence mechanisms. Clinical manifestations are often nonspecific. Diagnostic modalities primarily include endoscopy and bile acid reflux testing. Management strategies encompass lifestyle modifications, medical therapy, and in severe cases, surgery. BRG is a complex condition with significant clinical implications. Further research is needed to refine diagnostic criteria, elucidate pathophysiological mechanisms, and develop effective therapeutic interventions. Addressing knowledge gaps in epidemiology, risk factors, and long-term outcomes is crucial for improving patient care.展开更多
BACKGROUND Although an association between gut microbiota and cholestatic liver disease(CLD)has been reported,the precise functional roles of these microbes in CLD pathogenesis remain largely unknown.AIM To explore th...BACKGROUND Although an association between gut microbiota and cholestatic liver disease(CLD)has been reported,the precise functional roles of these microbes in CLD pathogenesis remain largely unknown.AIM To explore the function of gut microbes in CLD pathogenesis and the effects of gut microbiota on intestinal barrier and bile acid(BA)metabolism in CLD.METHODS Male C57BL/6J mice were fed a 0.05%3,5-diethoxycarbonyl-1,4-dihydrocollidine diet for 2 weeks to induce CLD.The sterile liver tissues of mice were then meticulously harvested,and bacteria in homogenates were identified through culture methods.Furthermore,16S ribosomal DNA sequencing was employed to analyze sterile liver samples collected from eight patients with primary biliary cholangitis(PBC)and three control individuals with hepatic cysts.The functional roles of the identified bacteria in CLD pathogenesis were assessed through microbiota transfer experiments,involving the evaluation of changes in intestinal permeability and BA dynamics.RESULTS Ligilactobacillus murinus(L.murinus)and Lactococcus garvieae(L.garvieae)were isolated from the bacterial culture of livers from CLD mice.L.murinus was prevalently detected in PBC patients and controls,whereas L.garvieae was detected only in patients with PBC but not in controls.Mice inoculated with L.garvieae exhibited increased susceptibility to experimental CLD,with both in vitro and in vivo indicating that L.garvieae disrupted the intestinal barrier function by down-regulating the expression of occludin and zonula occludens-1.Moreover,L.garvieae administration significantly upregulated the expression of the apical sodium-dependent BA transporter in the terminal ileum and increased serum BA levels.CONCLUSION L.garvieae contributes to excessive BA-induced hepatobiliary injury and liver fibrosis by increasing intestinal permeability and enhancing BA reabsorption.展开更多
Background Aflatoxins have been reported as a significant pollutant in feed,capable of causing harm to the liver,gastrointestinal tract and kidneys of piglets.However,research on the interactions among aflatoxin B1(AF...Background Aflatoxins have been reported as a significant pollutant in feed,capable of causing harm to the liver,gastrointestinal tract and kidneys of piglets.However,research on the interactions among aflatoxin B1(AFB1),bile acid(BA)metabolism and gut microbiota is limited.Methods In this study,piglets were treated with AFB1 and antibiotics(ABX)to evaluate the interaction between AFB1 and gut microbiota.Subsequently,the roles of the farnesoid X receptor(FXR)and sterol 12α-hydroxylase(CYP8B1)in AFB1 absorption were studied by using FXR agonists obeticholic acid(OCA)and Cyp8b1-knockout(KO)mice,respectively.Result AFB1 inhibited bile salt hydrolase(BSH)activity in ileal microbiota,downregulated ileal FXR expression,and upregulated CYP8B1 expression in liver,increasing the proportion of 12α-OH BAs and potentially enhancing AFB1 absorption.ABX treatment reduced AFB1 absorption and liver damage,and unexpectedly increased BSH activity,counteracting the AFB1-induced downregulation of FXR and upregulation of CYP8B1.OCA reactivated ileal FXR,reduced AFB1 absorption,and alleviated liver damage.Furthermore,Cyp8b1-KO mice showed increased resistance to AFB1-induced liver damage by lowering AFB1 absorption.Conclusions These results underscore the significance of gut microbiota and BAs in AFB1 absorption,suggesting new strategies to mitigate health risks from AFB1 in piglets.展开更多
BACKGROUND Endoscopic retrograde cholangiopancreatography is a challenging procedure involving bile duct cannulation.Despite the development of several cannulation devices,none have effectively facilitated the procedu...BACKGROUND Endoscopic retrograde cholangiopancreatography is a challenging procedure involving bile duct cannulation.Despite the development of several cannulation devices,none have effectively facilitated the procedure.AIM To evaluate the efficacy of a recently developed catheter for bile duct cannulation.METHODS We retrospectively examined 342 patients who underwent initial cholangiopan-creatography.We compared the success rate of bile duct cannulation and the incidence of complications between the groups using existing and novel catheters.RESULTS The overall success rates of bile duct cannulation were 98.3%and 99.1%in the existing and novel catheter groups,respectively(P=0.47).The bile duct cannulation rate using the standard technique was 73.0%and 82.1%in the existing and novel catheter groups,respectively(P=0.042).Furthermore,when catheterization was performed by expert physicians,the bile duct cannulation rate was significantly higher in the novel catheter group(81.3%)than in the existing catheter group(65.2%)(P=0.017).The incidence of difficult cannulation was also significantly lower in the novel catheter group(17.4%)than in the existing catheter group(33.0%)(P=0.019).CONCLUSION The novel catheter improved the bile duct cannulation rate using the standard technique and reduced the frequency of difficult cannulation cases,valuable tool in endoscopic retrograde cholangiopancreatography procedures performed by experts.展开更多
The association between dietary fat types and obesity is controversial,and the underlying mechanism remains unclear.This study aimed to evaluate the effect of different dietary fat sources(lard,corn oil or canola oil)...The association between dietary fat types and obesity is controversial,and the underlying mechanism remains unclear.This study aimed to evaluate the effect of different dietary fat sources(lard,corn oil or canola oil)on obesity in mice.The results revealed that lard-fed mice showed a lean phenotype,as well as lower serum cholesterol level compared with mice fed corn oil or canola oil.The 16S rRNA gene sequencing showed that the lard-fed mice had higherα-diversity of gut microbiota.In addition,the lard group had similar relative abundance of Lactobacillus,unclassified_f_Lachnospiraceae and Bacteroides compared with the control group.Targeted metabolomics analysis of caecal bile acid(BA)profile suggested the levels of chenodeoxycholic acid,lithocholic acid,deoxycholic acid and cholic acid in the lard group were higher than those in the corn oil and canola oil groups.Meanwhile,the levels of BA receptor farnesoid X receptor(Fxr)gene in lard-fed mice were higher than vegetable oil groups.These results suggested that lard could reduce the risk of obesity compared with corn oil and canola oil,which may be associated with more balanced gut microbiota and BA composition as well as activated FXR signaling.展开更多
Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucid...Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucidate the effects of milk replacer(MR)feeding on growth,lipid metabolism,colonic epithelial gene expression,colonic microbiota composition and systemic metabolism in goat kids compared to breast milk(BM)feeding,addressing a critical knowledge gap in early life nutrition.Methods Ten female goat kids were divided into 2 groups:those fed breast milk(BM group)and those fed a milk replacer(MR group).Over a period of 28 d,body weight was monitored and blood and tissue samples were collected for biochemical,transcriptomic and metabolomic analyses.Profiling of the colonial microbiota was performed using 16S rRNA gene sequencing.Intestinal microbiota transplantation(IMT)experiments in gnotobiotic mice were per-formed to validate causality.Results MR-fed pups exhibited reduced daily body-weight gain due to impaired lipid metabolism as evidenced by lower serum and liver total cholesterol(TC)and non-esterified fatty acid(NEFA)concentrations.Transcriptomic analysis of the colonic epithelium revealed upregulated genes involved in negative regulation of lipid metabolism,concomitant with microbiota shifts characterized by a decrease in Firmicutes and an increase in Actinobacteria.Specifically,genera such as Bifidobacterium and Prevotella were enriched in the MR group,while Clostridium and Fae-calibacterium were depleted.Metabolomics analyses confirmed alterations in bile acid and fatty acid metabolic path-ways.IMT experiments in mice recapitulated the metabolic phenotype observed in MR-fed goats,confirming the role of the microbiota in modulating host lipid metabolism.Conclusions Milk replacer feeding in goat kids disrupts lipid metabolism and gut microbiota dynamics,result-ing in reduced growth rates and metabolic alterations.These findings highlight the importance of early nutritional intervention on metabolic programming and suggest that modulation of the gut microbiota may be a target for improving growth and metabolic health in ruminants.This study contributes to the understanding of nutritional management strategies in livestock and their impact on animal health and productivity.展开更多
Background Salmonella Typhimurium(S.Typhimurium)is a common pathogenic microorganism and poses a threat to the efficiency of poultry farms.As signaling molecules regulating the interaction between the host and gut mic...Background Salmonella Typhimurium(S.Typhimurium)is a common pathogenic microorganism and poses a threat to the efficiency of poultry farms.As signaling molecules regulating the interaction between the host and gut microbiota,bile acids(BAs)play a protective role in maintaining gut homeostasis.However,the antibacterial effect of BAs on Salmonella infection in broilers has remained unexplored.Therefore,the aim of this study was to investigate the potential role of feeding BAs in protecting against S.Typhimurium infection in broilers.Methods A total of 1441-day-old Arbor Acres male broilers were randomly assigned to 4 groups,including non-challenged birds fed a basal diet(CON),S.Typhimurium-challenged birds(ST),S.Typhimurium-challenged birds treated with 0.15 g/kg antibiotic after infection(ST-ANT),and S.Typhimurium-challenged birds fed a basal diet supplemented with 350 mg/kg of BAs(ST-BA).Results BAs supplementation ameliorated weight loss induced by S.Typhimurium infection and reduced the colonization of Salmonella in the liver and small intestine in broilers(P<0.05).Compared to the ST group,broilers in ST-BA group had a higher ileal mucosal thickness and villus height,and BAs also ameliorated the increase of diamine oxidase(DAO)level in serum(P<0.05).It was observed that the mucus layer thickness and the number of villous and cryptic goblet cells(GCs)were increased in the ST-BA group,consistent with the upregulation of MUC2 gene expression in the ileal mucosa(P<0.05).Moreover,the m RNA expressions of Toll-like receptor 5(TLR5),Toll-like receptor 4(TLR4),and interleukin 1 beta(IL1b)were downregulated in the ileum by BAs treatment(P<0.05).16S rDNA sequencing analysis revealed that,compared to ST group,BAs ameliorated the decreases in Bacteroidota,Bacteroidaceae and Bacteroides abundances,which were negatively correlated with serum DAO activity,and the increases in Campylobacterota,Campylobacteraceae and Campylobacter abundances,which were negatively correlated with body weight but positively correlated with serum D-lactic acid(D-LA)levels(P<0.05).Conclusions Dietary BAs supplementation strengthens the intestinal mucosal barrier and reverses dysbiosis of gut microbiota,which eventually relieves the damage to the intestinal barrier and weight loss induced by S.Typhimurium infection in broilers.展开更多
Calycosin,Astragali Radix most prominent ingredient,has drawn more attention as a result of its ability to treat atherosclerosis(AS).However,the mechanism of action has not been fully elucidated.We investigated the ef...Calycosin,Astragali Radix most prominent ingredient,has drawn more attention as a result of its ability to treat atherosclerosis(AS).However,the mechanism of action has not been fully elucidated.We investigated the effects of calycosin on bile acid(BA)metabolism and gut microbiome in ApoE^(-/-)mice fed a high-fat diet(HFD).The data showed that the aorta of ApoE^(-/-)mice treated with HFD showed significant atheromatous plaque formation and lipid accumulation,and the levels of total cholesterol(TC),triglycerides(TG)and low-density lipoprotein cholesterol(LDL-C)were significantly increased,while the levels of high-density lipoprotein cholesterol(HDL-C)were significantly decreased.Calycosin can substantially regulate lipid levels,thereby alleviating liver lipid deposition induced by atherosclerosis.In addition,16S rRNA sequencing showed that calycosin treatment has reshaped the gut microbiota disturbed by HFD,in particular,increasing the ratio of Bacteroidetes/Firmicutes,and improving the relative abundance of Bilophila,Desulfovibrio,Bacteroides,Lactobacillus,etc.Meanwhile,targeted metabolomics analysis showed that calycosin treatment significantly modulated glycodeoxycholic acid(CDCA),taurocholic acids(TCA),lithocholic acid(LCA),deoxycholic acid(DCA),taurodeoxycholic acid(TDCA)and BA pool composition,which were associated with atherosclerotic plaque areas.In addition,calycosin treatment also down-regulated farnesoid X receptor(FXR)protein levels and up-regulated cytochrome P450 family 7 subfamily A member 1(CYP7A1)protein levels in the hepatic.At the same time,calycosin inhibits the ileum FXR/TGR5 signaling pathway,inhibits BA reabsorption,promotes BA excretion,and reduces hepatic cholesterol accumulation by enterohepatic circulation.In addition,we found that calycosin significantly promoted the expression of hepatic ATP-binding cassette transporter A1(ABCA1)and ABCG1 to mediate cholesterol efflux.Meanwhile,calycosin regulates gut microbiota,and Bacteroides,Alistipes,Desulfovibrio,Lactobacillus,Bilophila and Odoribacter are closely related to specific BAs.This enables us to further understand the relationship between BA metabolism and gut microbiota.Calycosin may reduce high-fat diet-induced hepatic cholesterol accumulation in ApoE^(-/-)mice through gut microbiota and BA metabolism,and play a role in treating AS.Finally,we confirmed that calycosin-altered gut microbiota by fecal microbiota transplantation was sufficient to alleviate atherosclerosis.Taken together,our findings provide important insights into the pharmacological mechanisms underlying the efficacy of calycosin on atherosclerosis.展开更多
文摘BACKGROUND Bile spillage occurs more frequently in patients with incidental gallbladder carcinoma(iGBC)and may be associated with poor survival due to presumed high risk of peritoneal seeding.AIM To investigate the impact of bile spillage during primary surgery on the survival of patients with iGBC.METHODS Medical records of patients with iGBC diagnosed between 2000 and 2019 in 27 Dutch secondary centers and 5 tertiary centers were retrospectively reviewed.Patient medical records were assessed.Predictors for overall survival(OS)were determined using multivariable Cox regression.RESULTS Of the 346 included patients with iGBC,138(39.9%)had bile spillage,which was associated with higher American Society of Anesthesiologists classification(P=0.020),cholecystitis(P<0.001),higher tumor stage(P=0.005),and non-radical resection(P<0.001).Bile spillage was associated with poor OS[hazard ratio=1.97,95%confidence interval(CI):1.48-2.63,P<0.001]with a median OS of 12 months(95%CI:7-18 months)vs 34 months(95%CI:14-55 months,P<0.001).In multivariable analysis,spillage was not an independent prognostic factor for survival(hazard ratio=1.21,95%CI:0.84-1.74,P=0.313).CONCLUSION Although bile spillage correlates with prognostic factors,it lacks independent prognostic significance for survival.Patients with an indication for additional treatment should be promptly referred to a specialized hepatopancreatobiliary center,irrespective of whether bile spillage has occurred.
基金Supported by the Ke Qiao Science and Technology Plan Projects,No.2022KZ70.
文摘BACKGROUND At present,there are few studies on the risk factors for bile leakage after laparoscopic common bile duct exploration(LCBDE)for older patients with choledocholithiasis.AIM To identify the potential risk factors for bile leakage after LCBDE in older patients.METHODS A retrospective,single-center observational analysis was performed on patients aged≥70 years with choledocholithiasis treated by LCBDE who were admitted to our center between January 2011 and August 2022.The included patients were divided into non-bile leakage and bile leakage groups.Risk factors were determined by analyzing the observation indicators.RESULTS Seventy older patients with choledocholithiasis who underwent LCBDE were included.Univariate analysis showed that positive culture of bile bacteria was a risk factor for bile leakage after LCBDE(P<0.05).We further analyzed the bile bacteria,and univariate analysis showed that Enterococcus faecalis(E.faecalis)(P<0.05)and Pseudomonas aeruginosa(P<0.05)were associated with an increased risk of postoperative bile leakage in older patients(P<0.05).Multivariate analysis showed that E. faecalis was an independent risk factor for postoperative bile leakage in older patients (P < 0.05). Theresults of antibiotic sensitivity analysis showed that E. faecalis had 100% susceptibility to penicillin, ampicillin,linezolid, vancomycin, and furantoin.CONCLUSIONE. faecalis-associated biliary tract infection is an independent risk factor for bile leakage after LCBDE in olderpatients with choledocholithiasis. We suggest coverage with antibiotics to which E. faecalis is sensitive.
文摘BACKGROUND Barrett esophagus(BE),a metaplastic adaptive process to gastrointestinal reflux,is associated with a higher risk of developing esophageal adenocarcinoma.However,the factors and mechanism that drive the malignant progression of BE is not well understood.AIM To investigate the role of bile acids,a component of the reflux fluid,in the malignant progression of BE.METHODS Using engineered green fluorescent protein-labeled adult tissue-resident stem cells isolated from BE clinical biopsies(BE-ASCs)as the target,we studied the effect of hydrophobic deoxycholic acid(DCA)and hydrophilic tetrahydroxylated bile acids(THBA)on cell viability by fluorescence intensity analysis,mucin production by dark density measurement,tissue structure by pathology analysis,expression of different pro-inflammatory factors gene by quantitative polymerase chain reaction and proteins by Western blot.RESULTS We found that hydrophobic DCA has cytotoxic and proinflammatory effects through activation of interleukin-1β(IL-1β)-nuclear factor kappa-B(NF-κB)inflammatory pathway on BE-ASCs.This action results in impaired cell viability,tissue intactness,reduced mucin production,and increased transition to disorganized atypical cells without intestinal features.In contrast,co-culture with hydrophilic THBA inhibited the IL-1β-NF-κB inflammatory pathway with maintenance of mature intestinal type cellular and histomorphology.CONCLUSION Our data indicates that the hydrophilic bile acid THBA can counteract the cytotoxic and proinflammatory effect of hydrophobic DCA and prevent the malignant progression of BE by inhibiting the IL-1β-NF-κB pathway.
基金Supported by Education Project of Yunnan Province,No.2024J1628and Project of Qujing Medical College in 2024,No.2024XQ002.
文摘BACKGROUND Complex hepatolithiasis has a high perioperative risk and recurrence rate.Currently,standardized treatment protocols and reliable anatomical landmarks remain undefined,posing considerable challenges for laparoscopic hepatectomy in these cases.Achieving complete stone clearance and addressing hilar bile duct stenosis are critical determinants of surgical efficacy in hepatolithiasis management.CASE SUMMARY We present the case of a woman with intrahepatic and extrahepatic bile duct stones and chronic cholangitis who underwent laparoscopic hepatectomy.Hepatic segments I,II,III,IV,VI,and VII of the diseased bile duct tree and bile duct cyst were resected according to the preoperative plan,plastic repair of the hilar bile duct was performed,and the repaired bile duct was anastomosed with the jejunum.The patient achieved a favorable prognosis and long-term survival.CONCLUSION Based on segmental/subsegmental diseased bile duct tree territory hepatectomy and hilar stenosis relief,laparoscopic hepatectomy for complex hepatolithiasis can be safely performed guided by double landmarks(diseased bile duct/hepatic vein).
基金Supported by the National Natural Science Foundation of China,No.82200650the Key Research and Development Projects of Shanxi Province,No.202102130501014the Natural Science Foundation of Shanxi Province,No.202203021211021,No.202203021212046,and No.20210302123258.
文摘BACKGROUND The pathogenesis of hepatic encephalopathy(HE)remains unclear,and the classical theory of ammonia toxicity lacks sufficient justification.AIM To investigate the potential of bile acids as intervention targets for HE.METHODS This study employed 42 wild-type male SD rats weighing 200±20 g.Using a random number table method,two rats were randomly selected to undergo common bile duct ligation(BDL).The remaining 40 rats were randomly assigned to four groups serving as controls:The vehicle+control diet(VC)group,the thioacetamide(TAA)group,the TAA+total bile acids(TAAT)group,and the TAA+cholestyramine(TAAC)group.Except for the VC group,all rats were intraperitoneally injected with 100 mg/kg TAA solution once daily for ten consecutive days to establish a HE model.Simultaneously,the TAAT and TAAC groups were administered a diet containing 0.3%bile acids(derived from BDL rats)and 2%cholestyramine,respectively,by gavage for ten days.For the BDL rat model group,the common BDL procedure was performed following the aforementioned protocol.After four weeks,laparotomy revealed swollen bile ducts at the ligation site,and bile was collected.Following successful modeling,behavioral tests,including the elevated plus maze and open field test,were conducted to assess the HE status of the rats.Peripheral blood,liver,and cerebral cortex tissue samples were collected,and the total bile acid content in the serum and cerebral cortex was measured using an enzyme cycling method.The levels of inflammatory factors in the serum and cerebral cortex were analyzed using enzyme-linked immunosorbent assay.Liver histological examination was performed using the hematoxylin-eosin double-labeling method.Reverse transcription polymerase chain reaction,western blot,immunohistochemistry,and other techniques were employed to observe the expression of microglial activation marker ionized calcium-binding adaptor molecule-1 and Takeda G protein-coupled receptor 5(TGR5)protein.RESULTS Compared to the VC group,the TAA group exhibited an exacerbation of HE in rats.The total bile acid content,proinflammatory factors[interleukin-1β(IL-1β),IL-6],and the anti-inflammatory factor IL-10 in both the serum and cerebral cortex were significantly elevated.Similarly,the expression of the TGR5 receptor in the cerebral cortex was upregulated.To investigate the impact of total bile acids on HE in rats,comparisons were made with the TAA group.In the TAAT group,the severity of HE was further aggravated,accompanied by increased total bile acid content in the serum and cerebral cortex,elevated pro-inflammatory factors(IL-1β,IL-6),reduced levels of the antiinflammatory factor IL-10,and decreased expression of the TGR5 receptor in the cerebral cortex.In the TAAC group,the severity of HE was alleviated.This group showed reductions in total bile acid content in the serum and cerebral cortex,decreased pro-inflammatory factors(IL-1β,IL-6),increased levels of the anti-inflammatory factor IL-10,and enhanced expression of the TGR5 receptor in the cerebral cortex.CONCLUSION This study demonstrated that the total bile acid content in the serum and cerebral cortex of TAA-induced liver cirrhosis rats was elevated.Furthermore,total bile acids exacerbate the progression of HE in rats.This effect may be attributed to bile acids’involvement in the development of neurological dysfunction by mediating TGR5 expression and regulating neuroinflammation.
文摘BACKGROUND Intraoperative and postoperative biliary injuries remain significant complications of laparoscopic common bile duct exploration(LCBDE).Indocyanine green(ICG)has been shown to significantly reduce injuries caused by intraoperative operational errors.We found that the J-tube can reduce postoperative strictures and injuries to the common bile duct.At this moment,we aim to analyze and compare the complications,efficacy,short-term outcomes,and feasibility of these two adjunctive tools for LCBDE.AIM To evaluate the efficacy of ICG fluorescence imaging In LCBDE and J-tube drainage for patients with common bile duct stones.METHODS We retrospectively collected the clinical case data of patients who were treated at the Hepatobiliary Surgery Department of the Third People’s Hospital of Nantong,affiliated with Nantong University,from January 2016 to January 2021 due to gallbladder stones with choledocholithiasis and who underwent LCBDE combined with a primary suture and either J-tube or T-tube drainage.The patients were divided into groups:Traditional white-light laparoscopy+T-tube group(WL+T-tube),traditional WL+J-tube group,fluorescent laparoscopy+T-tube group(ICG+T-tube)and fluorescent laparoscopy+J-tube group(ICG+J-tube).The preoperative and postoperative clinical case data,laboratory examination data,and intraoperative and postoperative complications(including postoperative bile leakage,electrolyte disturbances,biliary peritonitis,and postoperative infections)and other relevant indicators were compared.RESULTS A total of 198 patients(112 males and 86 females)were included in the study,with 74 patients in the WL+T-tube,47 in the WL+J-tube,42 in the ICG+T-tube,and 35 in the ICG+J-tube.Compared with the other groups,the ICG+J had significantly shorter operation time(114 minutes,P=0.001),less blood loss(42 mL,P=0.02),shorter postoperative hospital stays(7 days,P=0.038),and lower surgical costs(China yuan 30178,P=0.001).Furthermore,patients were subdivided into two groups based on whether a T-tube or J-tube was placed during the surgery.By the third postoperative day,the aspartate transaminase,glutamic pyruvic transaminase,total bilirubin,and direct bilirubin levels were lower in the J-tube group than in the T-tube group(P<0.001).At last,follow-up observations showed that the incidence of biliary strictures at three months postoperatively was significantly lower in the J-tube group than in the T-tube group(P=0.002).CONCLUSION ICG fluorescence imaging in laparoscopic cholecystectomy with common bile duct exploration and J-tube drainage facilitates rapid identification of biliary anatomy and variations,reducing intraoperative bile duct injury,blood loss,surgery duration,and postoperative bile duct stenosis rates,supporting its clinical adoption.
文摘The liver is a central metabolic organ that regulates numerous physiological processes,including glucose and lipid metabolism,detoxification,and the synthesis of essential proteins and bile.Bile acids(BAs),synthesized from cholesterol in hepatocytes,not only facilitate the emulsification and absorption of dietary fats but also act as potent signaling molecules through receptors such as the farnesoid X receptor(FXR)and Takeda G-protein-coupled receptor 5.Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally,closely linked with obesity,insulin resis-tance,and other components of metabolic syndrome.In MASLD,the metabolism of BAs is markedly disrupted,resulting in alterations in their synthesis,compo-sition,and signaling activity.These changes contribute to hepatic steatosis,inflammation,and fibrosis,thereby exacerbating metabolic dysfunction and liver damage.The altered profiles and signaling activity of BAs in MASLD patients suggest that BAs act not only as biomarkers of disease severity,but also as active mediators of its pathogenesis.Modulators of BA signaling pathways,especially FXR agonists,are the focus of intense research for their potential to beneficially influence liver steatosis and inflammation in MASLD.Recent research has yielded promising results,indicating potential therapeutic application and the introduction of novel agents aimed at modulating BA homeostasis and function.This minireview outlines the physiological roles of BAs,seeks to advance the elucidation of the mechanisms by which their dysregulation contributes to MASLD progression,and highlights current and emerging therapeutic approa-ches.A deeper understanding of these complex interactions is essential for improving the diagnosis,prognosis and treatment of MASLD.
基金Supported by the Wannan Medical College Teaching Hospital Special Application for Scientific Research,No.WK2023JXYY036the Anhui Provincial Translational Clinical Medical Research Special Application,No.202204295107020062.
文摘BACKGROUND Bile leakage is a common complication following laparoscopic common bile duct exploration(LCBDE)with primary duct closure(PDC).Identifying and analyzing the risk factors associated with bile leakage is crucial for improving surgical outcomes.AIM To explore the value analysis of common risk factors for bile leakage after LCBDE and PDC,with a focus on strict adherence to indications.METHODS Clinical data of 106 cases undergoing LCBDE+PDC in the Hepatobiliary and Pancreatic Surgery Department(Division 1)of Chuzhou First People’s Hospital from April 2019 to March 2024 were collected.Retrospective and multiple factor regression analysis were conducted on common risk factors for bile leakage.The change in surgical time was analyzed using the cumulative summation(CUSUM)method,and the minimum number of cases required to complete the learning curve for PDC was obtained based on the proposed fitting curve by identifying the CUSUM maximum value.RESULTS Multifactor logistic regression analysis showed that fibrinous inflammation and direct bilirubin/indirect bilirubin were significant independent high-risk factors for postoperative bile leakage(P<0.05).The time to drain removal and length of hospital stay in cases without bile leakage were significantly shorter than in cases with bile leakage(P<0.05),with statistical significance.The CUSUM method indicated that a minimum of 51 cases were required for the surgeon to complete the learning curve(P=0.023).CONCLUSION With a good assessment of duodenal papilla sphincter function,unobstructed bile-pancreatic duct convergence,exact stone clearance,and sufficient surgical experience to complete the learning curve,PDC remains the preferred method for bile duct closure and is worthy of clinical promotion.
文摘While endoscopic retrograde cholangiopancreatography(ERCP)remains the primary treatment modality for common bile duct stones(CBDS)or choledocho-lithiasis due to advancements in instruments,surgical intervention,known as common bile duct exploration(CBDE),is still necessary in cases of difficult CBDS,failed endoscopic treatment,or altered anatomy.Recent evidence also supports CBDE in patients requesting single-step cholecystectomy and bile duct stone removal with comparable outcomes.This review elucidates relevant clinical anatomy,selection indications,and outcomes to enhance surgical understanding.The selection between trans-cystic(TC)vs trans-choledochal(TD)approaches is described,along with stone removal techniques and ductal closure.Detailed surgical techniques and strategies for both the TC and TD approaches,including instrument selection,is also provided.Additionally,this review comprehensively addresses operation-specific complications such as bile leakage,stricture,and entrapment,and focuses on preventive measures and treatment strategies.This review aims to optimize the management of CBDS through laparoscopic CBDE,with the goal of improving patient outcomes and minimizing risks.
文摘BACKGROUND Proximal bile duct injury(BDI),which often occurs after laparoscopic cholecystectomy(LC),can lead to complex biliary stricture and recurrent cholangitis.This case report presented a 39-year-old woman who experienced proximal BDI during LC in 2017,leading to multiple episodes of cholangitis and subsequent hepaticojejunostomy in 2018.Despite these interventions,persistent biliary complications necessitated repeated hospital admissions and antibiotic treatment.Imaging studies revealed persistent stricture at the site of hepaticojejunostomy,prompting a series of percutaneous procedures,including balloon dilatation and biliary drainage.In August 2024,she underwent biodegradable biliary stenting,which significantly improved her condition.Subsequently,she remained clinically stable for 5 months without further episodes of cholangitis and had improved liver function tests.This case highlighted the complexities of managing postinjury biliary stricture,underscored the potential of biodegradable stents as an effective treatment option,and emphasized the need for a multidisciplinary approach in managing such complications.Long-term follow-up is essential for monitoring treatment effectiveness and preventing recurrence.CASE SUMMARY A 39-year-old female had a routine LC in 2017.The patient sustained a proximal BDI during the surgery.In the months that followed,recurrent bouts of cholangitis occurred.A hepaticojejunostomy biliary reconstruction was performed in 2018.However,hepatic cholangitis persisted.In 2021 and 2022,MRCP scans revealed biliary stasis,duct dilation,and a stricture at the hepaticojejunostomy site.A subsequent percutaneous transhepatic cholangiography(PTC)confirmed these findings and led to drain placement.The treatment included internal and external biliary drain placements,repeated balloon dilations of the stricture,percutaneous transhepatic cholangioscopy to extract intrahepatic lithiasis,and insertion of a biodegradable biliary stent.Since the first PTC intervention,there have been no hospital admissions for cholangitis.Liver function tests showed improvement,and for five months following the biodegradable stenting,the condition remained stable.Long-term surveillance with regular imaging and blood work has been emphasized.The final diagnosis is recurrent biliary stricture secondary to proximal BDI.Treatment,including hepaticojejunostomy,repeated PTC with balloon dilation,and biodegradable biliary stenting,has led to complete drainage of the biliary system.Ongoing follow-up remains crucial for monitoring the patient's progress and maintaining their health.CONCLUSION This case demonstrated how strictures and recurrent cholangitis complicate the management of BDI after LC.A customized and multidisciplinary approach to control chronic biliary disease was proven effective,as shown by the patient’s good outcome.This was achieved by integrating balloon dilatation sessions,biliary drainage,stone clearing,and biodegradable stent placement.Long-term follow-up and continued monitoring remain essential to ensure patient stability and prevent further complications.
文摘BACKGROUND Pancreaticobiliary maljunction(PBM)is a rare congenital abnormality in pancreaticobiliary duct development.PBM is commonly found in children,and it often leads to acute pancreatitis and other diseases as a result of pancreaticobiliary reflux.Roux-en-Y choledochojejunostomy is a common surgical method for the treatment of PBM,but there are several associated complications that may occur after this operation.CASE SUMMARY The patient,a 12-year-old female,was hospitalized nearly 20 times in 2021 for recurrent acute pancreatitis.In 2022,she was diagnosed with PBM and underwent laparoscopic common bile duct resection and Roux-en-Y choledochojejunostomy in a tertiary hospital.In the first year after surgery,the patient had more than 10 recurrent acute pancreatitis episodes.After undergoing abdominal computed tomography and other examinations,she was diagnosed with“residual bile duct stones and recurrent acute pancreatitis”.On January 30,2024,the patient was admitted to our hospital due to recurrent upper abdominal pain and was cured through endoscopic retrograde cholangiopancreatography.CONCLUSION This article reports a case of a child with distal residual common bile duct stones and recurrent acute pancreatitis after Roux-en-Y choledochojejunostomy for PBM.The patient was cured through endoscopic retrograde cholangiopancreatography.
文摘Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic liver disease,is still unknown,treatment remains symptomatic.Knowledge of the physicochemical properties of various bile acids and the adaptive responses of cholangiocytes and hepatocytes to them has provided an important basis for the development of relatively effective drugs based on hydrophilic bile acids that can potentially slow the progression of the disease.Advances in the use of hydrophilic bile acids for the treatment of PBC are also associated with the discovery of pathogenetic mechanisms of the development of cholangiocyte damage and the appearance of the first signs of this disease.For 35 years,ursodeoxycholic acid(UDCA)has been the unique drug of choice for the treatment of patients with PBC.In recent years,the list of hydrophilic bile acids used to treat cholestatic liver diseases,including PBC,has expanded.In addition to UDCA,the use of obeticholic acid,tauroursodeoxycholic acid and norursodeoxycholic acid as drugs is discussed.The pathogenetic rationale for treatment of PBC with various bile acid drugs is discussed in this review.Emphasis is made on the mechanisms explaining the beneficial therapeutic effects and potential of each of the bile acid as a drug,based on the understanding of the pathogenesis of the initial stages of PBC.
文摘Bile reflux gastritis (BRG) is a gastro-intestinal condition especially characterized by the reflux of bile into the stomach, further leading to mucosal inflammation along with various other clinical manifestations. Despite its increasing recognition, BRG remains understudied, with limited understanding of its epidemiology, pathophysiology, and optimal therapeutic strategies. Present narrative review aimed to comprehensively examine the available literature on BRG, focusing on its prevalence, risk factors, pathophysiology, clinical presentation, diagnostic modalities, and available therapeutic strategies. A comprehensive literature search was conducted using PubMed, Embase, Google Scholar and Cochrane databases. Relevant studies were included based on predefined inclusion and exclusion criteria. A narrative synthesis was conducted to summarize and interpret the findings. The prevalence of BRG remains uncertain due to diagnostic challenges. Risk factors include impaired gastrointestinal motility, sphincteric dysfunction (pyloric sphincter and the lower oesophageal sphincter), biliary tract disease, and certain medications. The pathophysiology involves bile acid-induced mucosal injury, inflammation, and impaired gastric defence mechanisms. Clinical manifestations are often nonspecific. Diagnostic modalities primarily include endoscopy and bile acid reflux testing. Management strategies encompass lifestyle modifications, medical therapy, and in severe cases, surgery. BRG is a complex condition with significant clinical implications. Further research is needed to refine diagnostic criteria, elucidate pathophysiological mechanisms, and develop effective therapeutic interventions. Addressing knowledge gaps in epidemiology, risk factors, and long-term outcomes is crucial for improving patient care.
基金Supported by Tianjin Health Research Project,No.TJWJ2024QN005Beijing iGandan Public Welfare Foundation Artificial Liver Special Fund,No.iGandanF-1082024-RGG122.
文摘BACKGROUND Although an association between gut microbiota and cholestatic liver disease(CLD)has been reported,the precise functional roles of these microbes in CLD pathogenesis remain largely unknown.AIM To explore the function of gut microbes in CLD pathogenesis and the effects of gut microbiota on intestinal barrier and bile acid(BA)metabolism in CLD.METHODS Male C57BL/6J mice were fed a 0.05%3,5-diethoxycarbonyl-1,4-dihydrocollidine diet for 2 weeks to induce CLD.The sterile liver tissues of mice were then meticulously harvested,and bacteria in homogenates were identified through culture methods.Furthermore,16S ribosomal DNA sequencing was employed to analyze sterile liver samples collected from eight patients with primary biliary cholangitis(PBC)and three control individuals with hepatic cysts.The functional roles of the identified bacteria in CLD pathogenesis were assessed through microbiota transfer experiments,involving the evaluation of changes in intestinal permeability and BA dynamics.RESULTS Ligilactobacillus murinus(L.murinus)and Lactococcus garvieae(L.garvieae)were isolated from the bacterial culture of livers from CLD mice.L.murinus was prevalently detected in PBC patients and controls,whereas L.garvieae was detected only in patients with PBC but not in controls.Mice inoculated with L.garvieae exhibited increased susceptibility to experimental CLD,with both in vitro and in vivo indicating that L.garvieae disrupted the intestinal barrier function by down-regulating the expression of occludin and zonula occludens-1.Moreover,L.garvieae administration significantly upregulated the expression of the apical sodium-dependent BA transporter in the terminal ileum and increased serum BA levels.CONCLUSION L.garvieae contributes to excessive BA-induced hepatobiliary injury and liver fibrosis by increasing intestinal permeability and enhancing BA reabsorption.
基金supported by grant from the Science and Technology Program of Zhejiang Province 2022C04034(to Jinzhi Zhang,Junli Zhu and Haifeng Wang)the Key Research and Development Program of China 2022YFD1300602(to Haifeng Wang)。
文摘Background Aflatoxins have been reported as a significant pollutant in feed,capable of causing harm to the liver,gastrointestinal tract and kidneys of piglets.However,research on the interactions among aflatoxin B1(AFB1),bile acid(BA)metabolism and gut microbiota is limited.Methods In this study,piglets were treated with AFB1 and antibiotics(ABX)to evaluate the interaction between AFB1 and gut microbiota.Subsequently,the roles of the farnesoid X receptor(FXR)and sterol 12α-hydroxylase(CYP8B1)in AFB1 absorption were studied by using FXR agonists obeticholic acid(OCA)and Cyp8b1-knockout(KO)mice,respectively.Result AFB1 inhibited bile salt hydrolase(BSH)activity in ileal microbiota,downregulated ileal FXR expression,and upregulated CYP8B1 expression in liver,increasing the proportion of 12α-OH BAs and potentially enhancing AFB1 absorption.ABX treatment reduced AFB1 absorption and liver damage,and unexpectedly increased BSH activity,counteracting the AFB1-induced downregulation of FXR and upregulation of CYP8B1.OCA reactivated ileal FXR,reduced AFB1 absorption,and alleviated liver damage.Furthermore,Cyp8b1-KO mice showed increased resistance to AFB1-induced liver damage by lowering AFB1 absorption.Conclusions These results underscore the significance of gut microbiota and BAs in AFB1 absorption,suggesting new strategies to mitigate health risks from AFB1 in piglets.
文摘BACKGROUND Endoscopic retrograde cholangiopancreatography is a challenging procedure involving bile duct cannulation.Despite the development of several cannulation devices,none have effectively facilitated the procedure.AIM To evaluate the efficacy of a recently developed catheter for bile duct cannulation.METHODS We retrospectively examined 342 patients who underwent initial cholangiopan-creatography.We compared the success rate of bile duct cannulation and the incidence of complications between the groups using existing and novel catheters.RESULTS The overall success rates of bile duct cannulation were 98.3%and 99.1%in the existing and novel catheter groups,respectively(P=0.47).The bile duct cannulation rate using the standard technique was 73.0%and 82.1%in the existing and novel catheter groups,respectively(P=0.042).Furthermore,when catheterization was performed by expert physicians,the bile duct cannulation rate was significantly higher in the novel catheter group(81.3%)than in the existing catheter group(65.2%)(P=0.017).The incidence of difficult cannulation was also significantly lower in the novel catheter group(17.4%)than in the existing catheter group(33.0%)(P=0.019).CONCLUSION The novel catheter improved the bile duct cannulation rate using the standard technique and reduced the frequency of difficult cannulation cases,valuable tool in endoscopic retrograde cholangiopancreatography procedures performed by experts.
基金funded by Basic Research Fund of Chinese Academy of Agricultural Sciences(CAAS)(1610072021001)the China Agriculture Research System(CARS-35)the Agricultural Science and Technology Innovation Program of CAAS。
文摘The association between dietary fat types and obesity is controversial,and the underlying mechanism remains unclear.This study aimed to evaluate the effect of different dietary fat sources(lard,corn oil or canola oil)on obesity in mice.The results revealed that lard-fed mice showed a lean phenotype,as well as lower serum cholesterol level compared with mice fed corn oil or canola oil.The 16S rRNA gene sequencing showed that the lard-fed mice had higherα-diversity of gut microbiota.In addition,the lard group had similar relative abundance of Lactobacillus,unclassified_f_Lachnospiraceae and Bacteroides compared with the control group.Targeted metabolomics analysis of caecal bile acid(BA)profile suggested the levels of chenodeoxycholic acid,lithocholic acid,deoxycholic acid and cholic acid in the lard group were higher than those in the corn oil and canola oil groups.Meanwhile,the levels of BA receptor farnesoid X receptor(Fxr)gene in lard-fed mice were higher than vegetable oil groups.These results suggested that lard could reduce the risk of obesity compared with corn oil and canola oil,which may be associated with more balanced gut microbiota and BA composition as well as activated FXR signaling.
基金financially supported by National Natural Science Foundation of China (32160801)China Agriculture Research System (CARS-39-12)+1 种基金Young Talent Fund of Association for Science and Technology in Shaanxi, China (2023-6-2-1)“Double-chain” project on livestock breeding (2022GDTSLD-46)
文摘Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucidate the effects of milk replacer(MR)feeding on growth,lipid metabolism,colonic epithelial gene expression,colonic microbiota composition and systemic metabolism in goat kids compared to breast milk(BM)feeding,addressing a critical knowledge gap in early life nutrition.Methods Ten female goat kids were divided into 2 groups:those fed breast milk(BM group)and those fed a milk replacer(MR group).Over a period of 28 d,body weight was monitored and blood and tissue samples were collected for biochemical,transcriptomic and metabolomic analyses.Profiling of the colonial microbiota was performed using 16S rRNA gene sequencing.Intestinal microbiota transplantation(IMT)experiments in gnotobiotic mice were per-formed to validate causality.Results MR-fed pups exhibited reduced daily body-weight gain due to impaired lipid metabolism as evidenced by lower serum and liver total cholesterol(TC)and non-esterified fatty acid(NEFA)concentrations.Transcriptomic analysis of the colonic epithelium revealed upregulated genes involved in negative regulation of lipid metabolism,concomitant with microbiota shifts characterized by a decrease in Firmicutes and an increase in Actinobacteria.Specifically,genera such as Bifidobacterium and Prevotella were enriched in the MR group,while Clostridium and Fae-calibacterium were depleted.Metabolomics analyses confirmed alterations in bile acid and fatty acid metabolic path-ways.IMT experiments in mice recapitulated the metabolic phenotype observed in MR-fed goats,confirming the role of the microbiota in modulating host lipid metabolism.Conclusions Milk replacer feeding in goat kids disrupts lipid metabolism and gut microbiota dynamics,result-ing in reduced growth rates and metabolic alterations.These findings highlight the importance of early nutritional intervention on metabolic programming and suggest that modulation of the gut microbiota may be a target for improving growth and metabolic health in ruminants.This study contributes to the understanding of nutritional management strategies in livestock and their impact on animal health and productivity.
基金The National Key R&D Program of China(2023YFD2000802)provided financial contributions。
文摘Background Salmonella Typhimurium(S.Typhimurium)is a common pathogenic microorganism and poses a threat to the efficiency of poultry farms.As signaling molecules regulating the interaction between the host and gut microbiota,bile acids(BAs)play a protective role in maintaining gut homeostasis.However,the antibacterial effect of BAs on Salmonella infection in broilers has remained unexplored.Therefore,the aim of this study was to investigate the potential role of feeding BAs in protecting against S.Typhimurium infection in broilers.Methods A total of 1441-day-old Arbor Acres male broilers were randomly assigned to 4 groups,including non-challenged birds fed a basal diet(CON),S.Typhimurium-challenged birds(ST),S.Typhimurium-challenged birds treated with 0.15 g/kg antibiotic after infection(ST-ANT),and S.Typhimurium-challenged birds fed a basal diet supplemented with 350 mg/kg of BAs(ST-BA).Results BAs supplementation ameliorated weight loss induced by S.Typhimurium infection and reduced the colonization of Salmonella in the liver and small intestine in broilers(P<0.05).Compared to the ST group,broilers in ST-BA group had a higher ileal mucosal thickness and villus height,and BAs also ameliorated the increase of diamine oxidase(DAO)level in serum(P<0.05).It was observed that the mucus layer thickness and the number of villous and cryptic goblet cells(GCs)were increased in the ST-BA group,consistent with the upregulation of MUC2 gene expression in the ileal mucosa(P<0.05).Moreover,the m RNA expressions of Toll-like receptor 5(TLR5),Toll-like receptor 4(TLR4),and interleukin 1 beta(IL1b)were downregulated in the ileum by BAs treatment(P<0.05).16S rDNA sequencing analysis revealed that,compared to ST group,BAs ameliorated the decreases in Bacteroidota,Bacteroidaceae and Bacteroides abundances,which were negatively correlated with serum DAO activity,and the increases in Campylobacterota,Campylobacteraceae and Campylobacter abundances,which were negatively correlated with body weight but positively correlated with serum D-lactic acid(D-LA)levels(P<0.05).Conclusions Dietary BAs supplementation strengthens the intestinal mucosal barrier and reverses dysbiosis of gut microbiota,which eventually relieves the damage to the intestinal barrier and weight loss induced by S.Typhimurium infection in broilers.
基金supported by Heilongjiang Postdoctoral Program(ZHY2022-114)General program of Heilongjiang Province(LBHZ22251)Young Elite Scientists Sponsorship Program(2022-QNRC1-27)。
文摘Calycosin,Astragali Radix most prominent ingredient,has drawn more attention as a result of its ability to treat atherosclerosis(AS).However,the mechanism of action has not been fully elucidated.We investigated the effects of calycosin on bile acid(BA)metabolism and gut microbiome in ApoE^(-/-)mice fed a high-fat diet(HFD).The data showed that the aorta of ApoE^(-/-)mice treated with HFD showed significant atheromatous plaque formation and lipid accumulation,and the levels of total cholesterol(TC),triglycerides(TG)and low-density lipoprotein cholesterol(LDL-C)were significantly increased,while the levels of high-density lipoprotein cholesterol(HDL-C)were significantly decreased.Calycosin can substantially regulate lipid levels,thereby alleviating liver lipid deposition induced by atherosclerosis.In addition,16S rRNA sequencing showed that calycosin treatment has reshaped the gut microbiota disturbed by HFD,in particular,increasing the ratio of Bacteroidetes/Firmicutes,and improving the relative abundance of Bilophila,Desulfovibrio,Bacteroides,Lactobacillus,etc.Meanwhile,targeted metabolomics analysis showed that calycosin treatment significantly modulated glycodeoxycholic acid(CDCA),taurocholic acids(TCA),lithocholic acid(LCA),deoxycholic acid(DCA),taurodeoxycholic acid(TDCA)and BA pool composition,which were associated with atherosclerotic plaque areas.In addition,calycosin treatment also down-regulated farnesoid X receptor(FXR)protein levels and up-regulated cytochrome P450 family 7 subfamily A member 1(CYP7A1)protein levels in the hepatic.At the same time,calycosin inhibits the ileum FXR/TGR5 signaling pathway,inhibits BA reabsorption,promotes BA excretion,and reduces hepatic cholesterol accumulation by enterohepatic circulation.In addition,we found that calycosin significantly promoted the expression of hepatic ATP-binding cassette transporter A1(ABCA1)and ABCG1 to mediate cholesterol efflux.Meanwhile,calycosin regulates gut microbiota,and Bacteroides,Alistipes,Desulfovibrio,Lactobacillus,Bilophila and Odoribacter are closely related to specific BAs.This enables us to further understand the relationship between BA metabolism and gut microbiota.Calycosin may reduce high-fat diet-induced hepatic cholesterol accumulation in ApoE^(-/-)mice through gut microbiota and BA metabolism,and play a role in treating AS.Finally,we confirmed that calycosin-altered gut microbiota by fecal microbiota transplantation was sufficient to alleviate atherosclerosis.Taken together,our findings provide important insights into the pharmacological mechanisms underlying the efficacy of calycosin on atherosclerosis.
