With increasing evidence,the biliary tract and the gallbladder mucosa are no longer considered sterile environments devoid of bacteria.Rather a profound biofilm of resident bacterial flora is associated with the mucos...With increasing evidence,the biliary tract and the gallbladder mucosa are no longer considered sterile environments devoid of bacteria.Rather a profound biofilm of resident bacterial flora is associated with the mucosal surface.The bile too harbors a resident flora.It is when a dysbiotic process ensues,that this bac-terial flora either becomes opportunist or is replaced by a pathogenic one that has a strong ability to survive the challenges of the biliary environment.Although once believed a metabolic problem,recent evidence indicates a complex intera-ction between different species of bacteria and gallbladder mucosa and bile which may culminate in calculus formation.The resident microbiota and its several enzymes dictate the type of gallstone by the mere interplay of the constituting type of bacteria in the biofilm,even without any evidence of infection.Dysbiosis is often mediated by either intestinal dysbiosis or less probably by oral dysbiosis.The gallstones,in turn,provide a haven for the resident microbiota in which they can form their own defined niche enriched with the biofilm that can resist the biliary defense mechanisms and survive the hostile biliary environment in the background of biliary stasis and local infection.However,this process of silent friendship is more complex than said,and further research is needed to define the relationship between the two.展开更多
Objective:To investigate the efficacy of laparoscopic cholecystectomy in the treatment of patients with gallstones and its effect on the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-a).Methods:A total...Objective:To investigate the efficacy of laparoscopic cholecystectomy in the treatment of patients with gallstones and its effect on the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-a).Methods:A total of 82 patients with gallstones admitted from July 2020 to July 2023 were recruited and allocated into control and observation groups using the random number table method,with 41 cases in each group.The patients were treated with laparoscopic cholecystectomy,with the anterior triangle anatomical approach to the gallbladder in the control group and the posterior triangle anatomical approach to the gallbladder in the observation group.The treatment effect and inflammatory factor levels of both groups were observed and compared.Results:When comparing the clinical outcomes of both patient groups,the key parameters evaluated included time to mobilization,duration of surgery,extubation time,and intraoperative bleeding.The observation group exhibited a significant advantage in these parameters compared to the control group(P<0.05).Regarding the levels of inflammatory factors between the two groups before and after treatment,there was no significant difference in values before treatment.However,following treatment,patients in the observation group showed significantly lower levels of IL-6,TNF-α,and C-reactive protein(CRP)compared to the control group(P<0.05).Conclusion:Patients undergoing laparoscopic cholecystectomy for gallstones can benefit from the implementation of the posterior triangular anatomical approach to the gallbladder,which not only enhances therapeutic efficacy but also offers significant advantages in reducing levels of IL-6,TNF-α,and CRP.Therefore,it is recommended for the widespread adoption of this treatment approach in clinical practice.展开更多
Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and...Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and cholesterol gallstones(CGS).To date,there is neither systematic study on BAs profile of CGP or CGS,nor the relationship between them.To explore the metabolomics profile of plasma BAs in healthy volunteers,CGP and CGS patients,an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human plasma.The developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma samples.The results show that,compared to healthy volunteers,CGP and CGS were both characterized by the significant decrease in plasma BAs pool size,furthermore CGP and CGS shared aberrant BAs metabolic characteristics.Chenodeoxycholic acid,glycochenodeoxycholic acid,l-muricholic acid,deoxycholic acid,and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder diseases.Subsequent analysis showed that clinical characteristics including cysteine,ornithine and body mass index might be closely related to metabolisms of certain BA modules.This work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.展开更多
Gallstones occur in about one third of the patients having liver cirrhosis.Pigment gallstones are the most frequent type,while cholesterol stones represent about15%of all stones in cirrhotics.Increased secretion of un...Gallstones occur in about one third of the patients having liver cirrhosis.Pigment gallstones are the most frequent type,while cholesterol stones represent about15%of all stones in cirrhotics.Increased secretion of unconjugated bilirubin,increased hydrolysis of conjugated bilirubin in the bile,reduced secretion of bile acids and phospholipds in bile favor pigment lithogenesis in cirrhotics.Gallbladder hypomotility also contributes to lithogenesis.The most recent data regarding risk factors for gallstones are presented.Gallstone prevalence increases with age,with a ratio male/female higher than in the general population.Chronic alcoholism,viral C cirrhosis,and non-alcoholic fatty liver disease are the underlying liver diseases most often associated with gallstones.Gallstones are often asymptomatic,and discovered incidentally.If asymptomatic,expectant management is recommended,as for asymptomatic gallstones in the general population.However,a closer follow-up of these patients is necessary in order to earlier treat symptoms or complications.For symptomatic stones,laparoscopic cholecystectomy has become the therapy of choice.Child-Pugh class and MELD score are the best predictors of outcome after cholecystectomy.Patients with severe liver disease are at highest surgical risk,therefore gallstone complications should be treated using noninvasive or minimally invasive procedures,until stabilization of the patient condition.展开更多
with a complex and multifactorial etiology.Declined gallbladder motility reportedly contributes to CG pathogenesis.Furthermore,interstitial Cajal-like cells(ICLCs)are reportedly present in human and guinea pig gallbla...with a complex and multifactorial etiology.Declined gallbladder motility reportedly contributes to CG pathogenesis.Furthermore,interstitial Cajal-like cells(ICLCs)are reportedly present in human and guinea pig gallbladder tissue.ICLCs potentially contribute to the regulation of gallbladder motility,and aberrant conditions involving the loss of ICLCs and/or a reduction in its pacing potential and reactivity to cholecystokinin may promote CG pathogenesis.This review discusses the association between ICLCs and CG pathogenesis and provides a basis for further studies on the functions of ICLCs and the etiologies of CG.展开更多
AIM:To evaluate the safety and effectiveness of twostage vs single-stage management for concomitant gallstones and common bile duct stones.METHODS:Four databases,including PubMed,Embase,the Cochrane Central Register o...AIM:To evaluate the safety and effectiveness of twostage vs single-stage management for concomitant gallstones and common bile duct stones.METHODS:Four databases,including PubMed,Embase,the Cochrane Central Register of Controlled Trials and the Science Citation Index up to September 2011,were searched to identify all randomized controlled trials(RCTs).Data were extracted from the studies by two independent reviewers.The primary outcomes were stone clearance from the common bile duct,postoperative morbidity and mortality.The secondary outcomes were conversion to other procedures,number of procedures per patient,length of hospital stay,total operative time,hospitalization charges,patient acceptance and quality of life scores.RESULTS:Seven eligible RCTs [five trials(n = 621) comparing preoperative endoscopic retrograde cholangiopancreatography(ERCP)/endoscopic sphincterotomy(EST) + laparoscopic cholecystectomy(LC) with LC + laparoscopic common bile duct exploration(LCBDE);two trials(n = 166) comparing postoperative ERCP/EST + LC with LC + LCBDE],composed of 787 patients in total,were included in the final analysis.The metaanalysis detected no statistically significant difference between the two groups in stone clearance from the common bile duct [risk ratios(RR) =-0.10,95% confidence intervals(CI):-0.24 to 0.04,P = 0.17],postoperative morbidity(RR = 0.79,95% CI:0.58 to 1.10,P = 0.16),mortality(RR = 2.19,95% CI:0.33 to 14.67,P = 0.42),conversion to other procedures(RR = 1.21,95% CI:0.54 to 2.70,P = 0.39),length of hospital stay(MD = 0.99,95% CI:-1.59 to 3.57,P = 0.45),total operative time(MD = 12.14,95% CI:-1.83 to 26.10,P = 0.09).Two-stage(LC + ERCP/EST) management clearly required more procedures per patient than single-stage(LC + LCBDE) management.CONCLUSION:Single-stage management is equivalent to two-stage management but requires fewer procedures.However,patient's condition,operator's expertise and local resources should be taken into account in making treatment decisions.展开更多
AIM:To perform a single-centre survey of the prevalence of and possible risk factors for gallstones in Uighur and Han Chinese.METHODS:Complete medical data for 9455 patients were collected from the medical centre of o...AIM:To perform a single-centre survey of the prevalence of and possible risk factors for gallstones in Uighur and Han Chinese.METHODS:Complete medical data for 9455 patients were collected from the medical centre of our hospital,and the overall prevalence of gallstones as well as the prevalence in different ethnic groups was studied.The risk factors for gallstones in different ethnic groups were identified in a univariate analysis,and variables with statistical significance were analysed by unconditional multiple logistic regression,to primarily explore the similarities and differences in gallstone risk factors between different ethnic groups.RESULTS:The prevalence of gallstones was significantly higher in the Uighur population than in the Hanpopulation(22.87%vs 11.64%,P<0.05).Further analysis of risk factors for gallstones based on the different ethnic areas revealed that age was a risk factor for gallstones in both groups;triglycerides,body-mass index(BMI)and high-density lipoprotein were risk factors for gallstones in the Han population,while total cholesterol(TC),gender and fatty liver were risk factors in the Uighur population.The Uighur patients were older than the Han patients,and had higher BMI,TC,low-density lipoprotein,female rate and fatty liver rate,while the incidence of hypertension was lower than that in the Han patients.CONCLUSION:The prevalence of and risk factors for gallstones differ between the Uighur and Han populations.展开更多
AIM To evaluate the effectiveness and safety of combined ursodeoxycholic acid and percutaneous transhepatic balloon dilation for management of gallstones after expulsion of common bile duct(CBD) stones.METHODS From Ap...AIM To evaluate the effectiveness and safety of combined ursodeoxycholic acid and percutaneous transhepatic balloon dilation for management of gallstones after expulsion of common bile duct(CBD) stones.METHODS From April 2014 to May 2016, 15 consecutive patients(6 men and 9 women) aged 45-86(mean, 69.07 ± 9.91) years suffering from CBD stones associated with gallstones were evaluated. Good gallbladder contraction function was confirmed by type B ultrasonography. Dilation of the CBD and cystic duct was detected. Percutaneous transhepatic balloon dilation of the papilla was performed, ursodeoxycholic acid was administered, and all patients had a high-fat diet. All subjects underwent repeated cholangiography, and percutaneous transhepatic removal was carried out in patients with secondary CBD stones originating from the gallbladder. RESULTS All patients underwent percutaneous transhepatic balloon dilation with a primary success rate of 100%. The combined therapy was successful in 86.7% of patients with concomitant CBD stones and gallstones. No remaining stones were detected in the gallbladder. Transient adverse events include abdominal pain(n = 1), abdominal distension(n = 1), and fever(n = 1). Complications were treated successfully via nonsurgical management without long-term complications. No procedure-related mortality occurred. CONCLUSION For patients with concomitant CBD stones and gallstones, after percutaneous transhepatic removal of primary CBD stones, oral ursodeoxycholic acid and a high-fat diet followed by percutaneous transhepatic removal of secondary CBD stones appear to be a feasible and effective option for management of gallstones.展开更多
AIM: To evaluate carotid intima-media thickening (IMT) and plaques, gallstone disease (GD) and fatty liver (FL) as a function of age. METHODS: In 449 subjects, FL and carotid disease were assessed ultrasonographically...AIM: To evaluate carotid intima-media thickening (IMT) and plaques, gallstone disease (GD) and fatty liver (FL) as a function of age. METHODS: In 449 subjects, FL and carotid disease were assessed ultrasonographically. In a subgroup of 65/449 patients with non-alcoholic fatty liver disease (NAFLD), carotid disease, GD and associated factors were determined. RESULTS: FL of unspecified etiology was more common in younger and GD in older individuals. FL subjects had an increased prevalence of IMT and a decreased prevalence of plaques and manifested carotid disease earlier. Plaques were more common in subjects with GD. Age was an independent predictor of carotid disease outcome and FL was a protective factor for plaques. In NAFLD, there was an inverse correlation between body weight and age and the latter independently predicted carotid findings. CONCLUSION: Cardiovascular risk in patients with FL and NAFLD needs to be assessed as a function of age and body weight.展开更多
AIM: To elucidate the prevalence and risk factors for gallstones, primarily focusing on Helicobacter pylori(H. pylori) infection. METHODS: A total of 10016 Chinese subjects, who had undergone physical examination, fas...AIM: To elucidate the prevalence and risk factors for gallstones, primarily focusing on Helicobacter pylori(H. pylori) infection. METHODS: A total of 10016 Chinese subjects, who had undergone physical examination, fasting 13 C urea breath test and abdominal ultrasonography, had sufficient blood test data, and had finished a questionnaire, were included in this cross-sectional study. Participants(n = 1122) who had previous eradication of H. pylori were studied separately. RESULTS: Gallstones were discovered in 9.10% of men and 8.58% of women, with no significant sex difference. Multivariate analyses displayed that age, aspartate aminotransferase, total cholesterol, H. pylori infection, hepatitis C virus(HCV) infection, and fattyliver had a significant association with gallstones(P < 0.05). Successive multiple logistic regression analysis including index of odds ratio(OR) and standardized coefficient(β) indicated that older age(OR/β = 1.056/0.055), H. pylori infection(OR/β = 1.454/0.109), HCV infection(OR/β = 1.871/0.123), and fatty liver(OR/β = 1.947/0.189) had a significant positive association with gallstones. After age stratification, H. pylori infection and fatty liver still had a significant positive association with gallstones in any age-specific groups, whereas HCV infection had a significant positive association in patients aged > 40 years. The prevalence of gallstones among H. pylori-positive, H. pylori-eradicated, and H. pylori-negative subjects was 9.47%, 9.02%, and 8.46%, respectively. The matched analysis showed that gallstones among H. pylori eradicated subjects was significantly lower compared with H. pylori-positive subjects(P < 0.05).CONCLUSION: H. pylori infection and fatty liver have a significant positive association with gallstones. H. pylori eradication may lead to prevention of gallstones.展开更多
Background:Cholesterol gallstones account for over 80%of gallstones,and the pathogenesis of gallstone formation involves genetic and environmental factors.However,data on the evolution of cholesterol gallstones with v...Background:Cholesterol gallstones account for over 80%of gallstones,and the pathogenesis of gallstone formation involves genetic and environmental factors.However,data on the evolution of cholesterol gallstones with various densities are limited.This study aimed to determine the roles of microbiota and mucins on the formation of calcified cholesterol gallstones in patients with cholelithiasis.Methods:Paired gallbladder tissues and bile specimens were obtained from cholelithiasis patients who were categorized into the isodense group and calcified group according to the density of gallstones.The relative abundance of microbiota in gallbladder tissues was detected.Immunohistochemistry and enzyme-linked immunosorbent assay were performed to detect the expression levels of MUC1,MUC2,MUC3a,MUC3b,MUC4,MUC5ac and MUC5b in gallbladder tissues and bile.The correlation of microbiota abundance with MUC4 expression was evaluated by linear regression.Results:A total of 23 patients with gallbladder stones were included.The density of gallstones in the isodense group was significantly lower than that of the calcified group(34.20±1.50 vs.109.40±3.84 HU,P<0.0001).Compared to the isodense group,the calcified group showed a higher abundance of gram-positive bacteria at the fundus,in the body and neck of gallbladder tissues.The concentrations of MUC1,MUC2,MUC3a,MUC3b,MUC5ac and MUC5b in the epithelial cells of gallbladder tissues showed no difference between the two groups,while the concentrations of MUC4 were significantly higher in the calcified group than that in the isodense group at the fundus(15.49±0.69 vs.10.23±0.54 ng/mL,P<0.05),in the body(14.54±0.94 vs.11.87±0.85 ng/mL,P<0.05)as well as in the neck(14.77±1.04 vs.10.85±0.72 ng/mL,P<0.05)of gallbladder tissues.Moreover,the abundance of bacteria was positively correlated with the expression of MUC4(r=0.569,P<0.05)in the calcified group.Conclusions:This study showed the potential clinical relevance among biliary microbiota,mucins and calcified gallstones in patients with gallstones.Gram-positive microbiota and MUC4 may be positively associated with the calcification of cholesterol gallstones.展开更多
AIM To evaluate the value of blood testing after elective laparoscopic cholecystectomy and its association with procedure related complications.METHODS Charts of all patients undergoing elective laparoscopic cholecyst...AIM To evaluate the value of blood testing after elective laparoscopic cholecystectomy and its association with procedure related complications.METHODS Charts of all patients undergoing elective laparoscopic cholecystectomy from January 2013 through December2014 were reviewed retrospectively for demographics,indication for surgery,operative course and outcome.In our institution the decision to perform postoperative blood analysis is left for the discretion of the surgeon,therefore we had the possibility to compare the results of those who had blood analyses results to those who did not.Analysis was performed to identify variables associated with the decision to perform postoperative blood tests.Subsequently a univariate and multivariate analyses was performed comparing the two cohorts.Secondary subgroup analysis was performed to identify factors associated with procedure related complications.RESULTS Five hundred and thirty-two elective laparoscopic cholecystectomies for symptomatic gallstones were performed during the study period.Sixty-four percent of the patients(n=340)had blood tests taken post operatively.Patients that had laboratory tests taken were older(P=0.006,OR=1.01),had longer surgery(P<0.001,OR=3.22)had more drains placed(P<0.001,OR=3.2)and stayed longer in the hospital(P<0.001,OR=1.2).A subgroup analysis of the patients who experienced complications revealed longer stay in the hospital(P<0.001),higher body mass index(BMI)(P=0.04,OR=1.08),increased rates of drain placement(P=0.006,OR=3.1)and higher conversion rates(P=0.01,OR=14.6).Postoperative blood tests withdrawals were not associated with complications(P=0.44).On Multivariate analysis BMI and drain placement were independently associated with complications.CONCLUSION The current study indicate that routine postoperative blood tests after elective laparoscopic cholecystectomy for symptomatic gallstones does not predict complications and may have an added benefit in diagnosis and management of cases were the surgeon encountered true technical difficulty during surgery.展开更多
AIM:To facilitate translational research on cholelithiasis,we have developed a rat model of human gallstones by exploiting the unique biliopancreatic features of this species.METHODS:Under anesthesia,16 adult rats of ...AIM:To facilitate translational research on cholelithiasis,we have developed a rat model of human gallstones by exploiting the unique biliopancreatic features of this species.METHODS:Under anesthesia,16 adult rats of equal genders underwent two times of abdominal surgery.First,their common bile duct(CBD)was ligated to cause cholestasis by total biliary obstruction(TBO).On day 0,1,3,7,14,21 and 28 after TBO,magnetic resonance imaging(MRI)was conducted to monitor the dilatation of the CBD,and blood was sampled to analyze total serum bilirubin(TSB).Secondly,on day 30,the abdomen was re-opened and gallstone(s)collected from human patients were implanted in the dilated CBD asa virtual gallbladder(VGB),which was closed by suture ligation.This rat cholelithiasis model was examined by MRI,clinical observation,microcholangiography and histology.RESULTS:All rats survived two laparotomies.After ligation,the CBD was dilated to a stable size of 4 to30 mm in diameter on day 21-28,which became a VGB.The rats initially showed signs of jaundice that diminished over time,which paralleled with the evolving TSB levels from 0.6±0.3 mg/d L before ligation,through a peak of 10.9±1.9 mg/dL on day 14,until a nearly normalized value after day 28.The dilated CBD with thickened wall allowed an incision for implantation of human gallstones of 1-10 mm in diameter.The rat cholelithiasis was proven by in vivo MRI and postmortem microcholangiography and histomorphology.CONCLUSION:A rat model cholelithiasis with human gallstones has been established,which proves feasible,safe,reliable,nontoxic and cost-effective.Given the gallstones of human origin,applications of this model may be of help in translational research such as optical detection and lysis of gallstones by systemic drug administration.展开更多
The appropriate management of gallstones and gallbladder disease in patients undergoing gastric bypass remains unknown.Several therapeutic modalities are used and include performing cholecystectomy on all patients at ...The appropriate management of gallstones and gallbladder disease in patients undergoing gastric bypass remains unknown.Several therapeutic modalities are used and include performing cholecystectomy on all patients at the time of gastric bypass,performing concomitant cholecystectomy only when patients have gallstones and performing cholecystectomy only in the presence of both symptoms and gallstones.Some groups administer ursodeoxycholic acid for gallstone prevention in the postoperative period.All treatment modalities are analyzed and their results and rationality are discussed.展开更多
Obesity is associated with insulin resistance, nonalcoholic fatty liver disease (NAFLD) and gallstones. High fat diets (unsaturated fats) rich in cholesterol have been demonstrated to produce not only gallstones but a...Obesity is associated with insulin resistance, nonalcoholic fatty liver disease (NAFLD) and gallstones. High fat diets (unsaturated fats) rich in cholesterol have been demonstrated to produce not only gallstones but also NAFLD and insulin resistance. Interestingly, a high incidence of gallstones is being reported in association with insulin resistance and NAFLD. Laparoscopic cholecystectomy is the best definitive therapy for symptomatic gallbladder disease. Ezetimibe is a drug that inhibits the absorption of both dietary and biliary cholesterol in the small intestine. Importantly, ezetimibe showed potential benefit not only in treating and preventing gallstones but also in insulin resistance and NAFLD. Further studies are required before the use of ezetimibe for the treatment of gallstones can be advocated.展开更多
Cholesterol gallstones are very common in hepatobiliary surgery and have been studied to a certain extent by doctors worldwide for decades.However,the mechanism of cholesterol gallstone formation is not fully understo...Cholesterol gallstones are very common in hepatobiliary surgery and have been studied to a certain extent by doctors worldwide for decades.However,the mechanism of cholesterol gallstone formation is not fully understood,so there is currently no completely effective drug for the treatment and prevention of cholesterol gallstones.The formation and development of cholesterol gallstones are caused by a variety of genetic and environmental factors,among which genetic susceptibility,intestinal microflora disorders,impaired gallbladder motility,and immune disorders are important in the pathogenesis of cholesterol gallstones.This review focuses on recent advances in these mechanisms.We also discuss some new targets that may be effective in the treatment and prevention of cholesterol gallstones,which may be hot areas in the future.展开更多
BACKGROUND Octreotide is widely used for the treatment of acromegaly,neuroendocrine tumors,and secretory diarrhea.However,long-term octreotide treatment can increase the incidence of gallstones.Vicarious contrast medi...BACKGROUND Octreotide is widely used for the treatment of acromegaly,neuroendocrine tumors,and secretory diarrhea.However,long-term octreotide treatment can increase the incidence of gallstones.Vicarious contrast medium excretion(VCME)through the hepatobiliary system is well known.However,few studies have reported octreotide-induced acute gallstones following VCME.CASE SUMMARY A 69-year-old man presented with left lower back pain and hematuria caused by a fall.The patient had a history of polycystic kidney disease.VCME occurred following renal artery embolization for a ruptured polycystic kidney.After 5 d of treatment with octreotide,the patient developed acute gallstones and intrahepatic cholestasis which further induced pancreatitis and cholangitis.He was discharged after hemodialysis,antibiotics,and supportive treatments.CONCLUSION For patients with a high-risk of VCME,octreotide should be cautiously administered and carefully monitored.展开更多
AIM: To explore the feasibility of using hypericin as an optical imaging probe with affinity for cholesterol for differential fluorescent detection of human gallstones.METHODS: Cholesterol, mixed and pigment stones fr...AIM: To explore the feasibility of using hypericin as an optical imaging probe with affinity for cholesterol for differential fluorescent detection of human gallstones.METHODS: Cholesterol, mixed and pigment stones from cholecystectomy patients were incubated with hypericin or solvent. After 72 h, the stones were analysed for fluorescence(365 nm) and treated with 2-propanol/dimethyl sulfoxide for high performance liquid chromatography(HPLC) analysis. Rats with virtual gallbladder containing human cholesterol, mixed or pigment gallstones(VGHG) received 5 mg/kg hypericin or solvent and VGHG rats with cholesterol stones were given different hypericin doses(5-15 mg/kg). Twelve hours later, the stones were analysed at 365 nm. Biliary excretion and metabolites of hypericin were assessed in common bile duct(CBD) cannulated rats for 9 h using fluorospectrometry, HPLC and matrixassisted laser desorption/ionization-time-of-flight mass spectrometry(MALDI-TOF MS).RESULTS: Homogeneous high fluorescence was seen on cholesterol stones either pre-incubated with hypericin or extracted from VGHG rats receiving hypericin. Mixed stones showed a dotted fluorescent pattern, whereas pigment and solvent-treated ones lacked fluorescence. HPLC showed 7.68, 6.65 and 0.08 × 10^(-3) M of cholesterol in extracts from cholesterol, mixed, and pigment gallstones, respectively. Hypericin accounted for 2.0, 0.5 and 0.2 × 10-6 M in that order. On cholesterol stones from VGHG rats receiving different hypericin doses, a positive correlation was observed between dose and fluorescence. In the bile from CBD-cannulated rats, fluorescence represented 20% of the injected dose with two peaks in 9 h. HPLC analysis revealed that hypericin conjugates reached 60% of the peak area. By MALDI-TOF MS, hypericinglucuronide was detected. CONCLUSION: This study proves the potential use of hypericin for differential fluorescent detection of human gallstones regarding their chemical composition.展开更多
Biliary cholesterol may contribute to the formation of cholesterol gallstones, regulation of these levels could be a useful therapeutic strategy for gallstones disease. Piperine (PA) is a potential cholesterol lower...Biliary cholesterol may contribute to the formation of cholesterol gallstones, regulation of these levels could be a useful therapeutic strategy for gallstones disease. Piperine (PA) is a potential cholesterol lowering a- gent. In this study, we assessed the effect and mechanism of PA in preventing cholesterol gallstones formation in- duced by feeding lithogenic diet containing high cholesterol levels to mice. C57BL/6 inbred mice were fed lithogen- ic or chow diets for 10 weeks, with or without PA ( 15, 30 and 60 mg ~ kg-1 ) or ursodeoxycholic acid ( UDCA, 60 mg ~ kg-1) administration. Cholesterol, phospholipids and crystals in bile, the lipid in serum, pathological chan- ges and proteins expression in liver were analyzed. The results showed that PA could decrease the cholesterol poten- cy and crystals in bile, reduce total cholesterol (TC), triglycerides (TG) and increase high-density lipoprotein / low-density lipoprotein (HDL/LDL) levels in serum. Furthermore, PA treatment reduced liver lipid peroxidation and protected hepatobiliary cells from liver injury by decreasing malondialdehyde (MDA) and increasing superoxide dismutase (SOD). In addition, PA inhibited the expression of ATP-binding cassette transporters G5/8 (ABCG5/ 8 ) and liver X receptor (LXR) in liver, and reduced cholesterol transport from the hepatocytes to the gallbladder. It may be the mechanism of PA in preventing cholesterol gallstones formation. PA as a potential drug for prevention cholesterol gallstones merits further investigation.展开更多
IM To seek effective drugs to dissolve bilirubin, glycoprotein and black stones and better lithotriptics for cholesterol stones, and study the amino acid constituents of gallstones.METHODS According to the character...IM To seek effective drugs to dissolve bilirubin, glycoprotein and black stones and better lithotriptics for cholesterol stones, and study the amino acid constituents of gallstones.METHODS According to the characteristics of infrared spectrum and the contents of bilirubin tested by semiquantitative chemical analysis, 30 of 148 cases of gallstones were selected and divided into 5 groups. Amino acids of the 30 cases were detected by high speed chromatography.RESULTS The quantity of amino acids in black stones was the highest (2269mg/g) and that of pure cholesterol stones was the lowest, only 14mg/g in a case. In five groups of gallstones, the contents of amino acids were: black stone > mixed bilirubin stone and glucoprotein stone > mixed cholesterol stone > pure cholesterol stone. The proportions were: 9595∶2902 and 2805∶578∶1. Aliphatic amino acids accounted for about 50% of the total amino acids in gallstones and glycine 153% of the total amount of 17 kinds of amino acids.CONCLUSION In mixed stones, the higher level of bilirubin, the higher contents of amino acids. The acidic amino acids of bilirubin stones were relatively higher than those of cholesterol stones.展开更多
文摘With increasing evidence,the biliary tract and the gallbladder mucosa are no longer considered sterile environments devoid of bacteria.Rather a profound biofilm of resident bacterial flora is associated with the mucosal surface.The bile too harbors a resident flora.It is when a dysbiotic process ensues,that this bac-terial flora either becomes opportunist or is replaced by a pathogenic one that has a strong ability to survive the challenges of the biliary environment.Although once believed a metabolic problem,recent evidence indicates a complex intera-ction between different species of bacteria and gallbladder mucosa and bile which may culminate in calculus formation.The resident microbiota and its several enzymes dictate the type of gallstone by the mere interplay of the constituting type of bacteria in the biofilm,even without any evidence of infection.Dysbiosis is often mediated by either intestinal dysbiosis or less probably by oral dysbiosis.The gallstones,in turn,provide a haven for the resident microbiota in which they can form their own defined niche enriched with the biofilm that can resist the biliary defense mechanisms and survive the hostile biliary environment in the background of biliary stasis and local infection.However,this process of silent friendship is more complex than said,and further research is needed to define the relationship between the two.
文摘Objective:To investigate the efficacy of laparoscopic cholecystectomy in the treatment of patients with gallstones and its effect on the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-a).Methods:A total of 82 patients with gallstones admitted from July 2020 to July 2023 were recruited and allocated into control and observation groups using the random number table method,with 41 cases in each group.The patients were treated with laparoscopic cholecystectomy,with the anterior triangle anatomical approach to the gallbladder in the control group and the posterior triangle anatomical approach to the gallbladder in the observation group.The treatment effect and inflammatory factor levels of both groups were observed and compared.Results:When comparing the clinical outcomes of both patient groups,the key parameters evaluated included time to mobilization,duration of surgery,extubation time,and intraoperative bleeding.The observation group exhibited a significant advantage in these parameters compared to the control group(P<0.05).Regarding the levels of inflammatory factors between the two groups before and after treatment,there was no significant difference in values before treatment.However,following treatment,patients in the observation group showed significantly lower levels of IL-6,TNF-α,and C-reactive protein(CRP)compared to the control group(P<0.05).Conclusion:Patients undergoing laparoscopic cholecystectomy for gallstones can benefit from the implementation of the posterior triangular anatomical approach to the gallbladder,which not only enhances therapeutic efficacy but also offers significant advantages in reducing levels of IL-6,TNF-α,and CRP.Therefore,it is recommended for the widespread adoption of this treatment approach in clinical practice.
基金supported by the National Natural Science Foundation of China(Grant Nos.:81920108033,and 82274223).
文摘Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and cholesterol gallstones(CGS).To date,there is neither systematic study on BAs profile of CGP or CGS,nor the relationship between them.To explore the metabolomics profile of plasma BAs in healthy volunteers,CGP and CGS patients,an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human plasma.The developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma samples.The results show that,compared to healthy volunteers,CGP and CGS were both characterized by the significant decrease in plasma BAs pool size,furthermore CGP and CGS shared aberrant BAs metabolic characteristics.Chenodeoxycholic acid,glycochenodeoxycholic acid,l-muricholic acid,deoxycholic acid,and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder diseases.Subsequent analysis showed that clinical characteristics including cysteine,ornithine and body mass index might be closely related to metabolisms of certain BA modules.This work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.
文摘Gallstones occur in about one third of the patients having liver cirrhosis.Pigment gallstones are the most frequent type,while cholesterol stones represent about15%of all stones in cirrhotics.Increased secretion of unconjugated bilirubin,increased hydrolysis of conjugated bilirubin in the bile,reduced secretion of bile acids and phospholipds in bile favor pigment lithogenesis in cirrhotics.Gallbladder hypomotility also contributes to lithogenesis.The most recent data regarding risk factors for gallstones are presented.Gallstone prevalence increases with age,with a ratio male/female higher than in the general population.Chronic alcoholism,viral C cirrhosis,and non-alcoholic fatty liver disease are the underlying liver diseases most often associated with gallstones.Gallstones are often asymptomatic,and discovered incidentally.If asymptomatic,expectant management is recommended,as for asymptomatic gallstones in the general population.However,a closer follow-up of these patients is necessary in order to earlier treat symptoms or complications.For symptomatic stones,laparoscopic cholecystectomy has become the therapy of choice.Child-Pugh class and MELD score are the best predictors of outcome after cholecystectomy.Patients with severe liver disease are at highest surgical risk,therefore gallstone complications should be treated using noninvasive or minimally invasive procedures,until stabilization of the patient condition.
基金National Natural Science Foundation of China,No.81000183and Natural Science Foundation of Liaoning Province,No.20180550125.
文摘with a complex and multifactorial etiology.Declined gallbladder motility reportedly contributes to CG pathogenesis.Furthermore,interstitial Cajal-like cells(ICLCs)are reportedly present in human and guinea pig gallbladder tissue.ICLCs potentially contribute to the regulation of gallbladder motility,and aberrant conditions involving the loss of ICLCs and/or a reduction in its pacing potential and reactivity to cholecystokinin may promote CG pathogenesis.This review discusses the association between ICLCs and CG pathogenesis and provides a basis for further studies on the functions of ICLCs and the etiologies of CG.
文摘AIM:To evaluate the safety and effectiveness of twostage vs single-stage management for concomitant gallstones and common bile duct stones.METHODS:Four databases,including PubMed,Embase,the Cochrane Central Register of Controlled Trials and the Science Citation Index up to September 2011,were searched to identify all randomized controlled trials(RCTs).Data were extracted from the studies by two independent reviewers.The primary outcomes were stone clearance from the common bile duct,postoperative morbidity and mortality.The secondary outcomes were conversion to other procedures,number of procedures per patient,length of hospital stay,total operative time,hospitalization charges,patient acceptance and quality of life scores.RESULTS:Seven eligible RCTs [five trials(n = 621) comparing preoperative endoscopic retrograde cholangiopancreatography(ERCP)/endoscopic sphincterotomy(EST) + laparoscopic cholecystectomy(LC) with LC + laparoscopic common bile duct exploration(LCBDE);two trials(n = 166) comparing postoperative ERCP/EST + LC with LC + LCBDE],composed of 787 patients in total,were included in the final analysis.The metaanalysis detected no statistically significant difference between the two groups in stone clearance from the common bile duct [risk ratios(RR) =-0.10,95% confidence intervals(CI):-0.24 to 0.04,P = 0.17],postoperative morbidity(RR = 0.79,95% CI:0.58 to 1.10,P = 0.16),mortality(RR = 2.19,95% CI:0.33 to 14.67,P = 0.42),conversion to other procedures(RR = 1.21,95% CI:0.54 to 2.70,P = 0.39),length of hospital stay(MD = 0.99,95% CI:-1.59 to 3.57,P = 0.45),total operative time(MD = 12.14,95% CI:-1.83 to 26.10,P = 0.09).Two-stage(LC + ERCP/EST) management clearly required more procedures per patient than single-stage(LC + LCBDE) management.CONCLUSION:Single-stage management is equivalent to two-stage management but requires fewer procedures.However,patient's condition,operator's expertise and local resources should be taken into account in making treatment decisions.
基金Supported by Xinjiang Uygur Autonomous Region’s Natural Science Foundation,No.200821118
文摘AIM:To perform a single-centre survey of the prevalence of and possible risk factors for gallstones in Uighur and Han Chinese.METHODS:Complete medical data for 9455 patients were collected from the medical centre of our hospital,and the overall prevalence of gallstones as well as the prevalence in different ethnic groups was studied.The risk factors for gallstones in different ethnic groups were identified in a univariate analysis,and variables with statistical significance were analysed by unconditional multiple logistic regression,to primarily explore the similarities and differences in gallstone risk factors between different ethnic groups.RESULTS:The prevalence of gallstones was significantly higher in the Uighur population than in the Hanpopulation(22.87%vs 11.64%,P<0.05).Further analysis of risk factors for gallstones based on the different ethnic areas revealed that age was a risk factor for gallstones in both groups;triglycerides,body-mass index(BMI)and high-density lipoprotein were risk factors for gallstones in the Han population,while total cholesterol(TC),gender and fatty liver were risk factors in the Uighur population.The Uighur patients were older than the Han patients,and had higher BMI,TC,low-density lipoprotein,female rate and fatty liver rate,while the incidence of hypertension was lower than that in the Han patients.CONCLUSION:The prevalence of and risk factors for gallstones differ between the Uighur and Han populations.
基金Supported by the Natural Science Foundation of Shandong Province,No.ZR2014HM050the Youth Foundation of the Second Hospital of Shandong University,No.Y2014010047+1 种基金the Nature Science Foundation of Shandong Province,No.ZR2018PH032 and No.ZR2018PH033the National Natural Science Foundation of China,No.61671276
文摘AIM To evaluate the effectiveness and safety of combined ursodeoxycholic acid and percutaneous transhepatic balloon dilation for management of gallstones after expulsion of common bile duct(CBD) stones.METHODS From April 2014 to May 2016, 15 consecutive patients(6 men and 9 women) aged 45-86(mean, 69.07 ± 9.91) years suffering from CBD stones associated with gallstones were evaluated. Good gallbladder contraction function was confirmed by type B ultrasonography. Dilation of the CBD and cystic duct was detected. Percutaneous transhepatic balloon dilation of the papilla was performed, ursodeoxycholic acid was administered, and all patients had a high-fat diet. All subjects underwent repeated cholangiography, and percutaneous transhepatic removal was carried out in patients with secondary CBD stones originating from the gallbladder. RESULTS All patients underwent percutaneous transhepatic balloon dilation with a primary success rate of 100%. The combined therapy was successful in 86.7% of patients with concomitant CBD stones and gallstones. No remaining stones were detected in the gallbladder. Transient adverse events include abdominal pain(n = 1), abdominal distension(n = 1), and fever(n = 1). Complications were treated successfully via nonsurgical management without long-term complications. No procedure-related mortality occurred. CONCLUSION For patients with concomitant CBD stones and gallstones, after percutaneous transhepatic removal of primary CBD stones, oral ursodeoxycholic acid and a high-fat diet followed by percutaneous transhepatic removal of secondary CBD stones appear to be a feasible and effective option for management of gallstones.
基金Supported by grants from Miur Ministero Istruzione Università e Ricerca Scientifica-PRIN 2004061213_001
文摘AIM: To evaluate carotid intima-media thickening (IMT) and plaques, gallstone disease (GD) and fatty liver (FL) as a function of age. METHODS: In 449 subjects, FL and carotid disease were assessed ultrasonographically. In a subgroup of 65/449 patients with non-alcoholic fatty liver disease (NAFLD), carotid disease, GD and associated factors were determined. RESULTS: FL of unspecified etiology was more common in younger and GD in older individuals. FL subjects had an increased prevalence of IMT and a decreased prevalence of plaques and manifested carotid disease earlier. Plaques were more common in subjects with GD. Age was an independent predictor of carotid disease outcome and FL was a protective factor for plaques. In NAFLD, there was an inverse correlation between body weight and age and the latter independently predicted carotid findings. CONCLUSION: Cardiovascular risk in patients with FL and NAFLD needs to be assessed as a function of age and body weight.
文摘AIM: To elucidate the prevalence and risk factors for gallstones, primarily focusing on Helicobacter pylori(H. pylori) infection. METHODS: A total of 10016 Chinese subjects, who had undergone physical examination, fasting 13 C urea breath test and abdominal ultrasonography, had sufficient blood test data, and had finished a questionnaire, were included in this cross-sectional study. Participants(n = 1122) who had previous eradication of H. pylori were studied separately. RESULTS: Gallstones were discovered in 9.10% of men and 8.58% of women, with no significant sex difference. Multivariate analyses displayed that age, aspartate aminotransferase, total cholesterol, H. pylori infection, hepatitis C virus(HCV) infection, and fattyliver had a significant association with gallstones(P < 0.05). Successive multiple logistic regression analysis including index of odds ratio(OR) and standardized coefficient(β) indicated that older age(OR/β = 1.056/0.055), H. pylori infection(OR/β = 1.454/0.109), HCV infection(OR/β = 1.871/0.123), and fatty liver(OR/β = 1.947/0.189) had a significant positive association with gallstones. After age stratification, H. pylori infection and fatty liver still had a significant positive association with gallstones in any age-specific groups, whereas HCV infection had a significant positive association in patients aged > 40 years. The prevalence of gallstones among H. pylori-positive, H. pylori-eradicated, and H. pylori-negative subjects was 9.47%, 9.02%, and 8.46%, respectively. The matched analysis showed that gallstones among H. pylori eradicated subjects was significantly lower compared with H. pylori-positive subjects(P < 0.05).CONCLUSION: H. pylori infection and fatty liver have a significant positive association with gallstones. H. pylori eradication may lead to prevention of gallstones.
基金the National Natural Science Foundation of China(81870433)the International Cooperation Project of Zhejiang Province Public Technology Research Program(LGJ18H030001).
文摘Background:Cholesterol gallstones account for over 80%of gallstones,and the pathogenesis of gallstone formation involves genetic and environmental factors.However,data on the evolution of cholesterol gallstones with various densities are limited.This study aimed to determine the roles of microbiota and mucins on the formation of calcified cholesterol gallstones in patients with cholelithiasis.Methods:Paired gallbladder tissues and bile specimens were obtained from cholelithiasis patients who were categorized into the isodense group and calcified group according to the density of gallstones.The relative abundance of microbiota in gallbladder tissues was detected.Immunohistochemistry and enzyme-linked immunosorbent assay were performed to detect the expression levels of MUC1,MUC2,MUC3a,MUC3b,MUC4,MUC5ac and MUC5b in gallbladder tissues and bile.The correlation of microbiota abundance with MUC4 expression was evaluated by linear regression.Results:A total of 23 patients with gallbladder stones were included.The density of gallstones in the isodense group was significantly lower than that of the calcified group(34.20±1.50 vs.109.40±3.84 HU,P<0.0001).Compared to the isodense group,the calcified group showed a higher abundance of gram-positive bacteria at the fundus,in the body and neck of gallbladder tissues.The concentrations of MUC1,MUC2,MUC3a,MUC3b,MUC5ac and MUC5b in the epithelial cells of gallbladder tissues showed no difference between the two groups,while the concentrations of MUC4 were significantly higher in the calcified group than that in the isodense group at the fundus(15.49±0.69 vs.10.23±0.54 ng/mL,P<0.05),in the body(14.54±0.94 vs.11.87±0.85 ng/mL,P<0.05)as well as in the neck(14.77±1.04 vs.10.85±0.72 ng/mL,P<0.05)of gallbladder tissues.Moreover,the abundance of bacteria was positively correlated with the expression of MUC4(r=0.569,P<0.05)in the calcified group.Conclusions:This study showed the potential clinical relevance among biliary microbiota,mucins and calcified gallstones in patients with gallstones.Gram-positive microbiota and MUC4 may be positively associated with the calcification of cholesterol gallstones.
文摘AIM To evaluate the value of blood testing after elective laparoscopic cholecystectomy and its association with procedure related complications.METHODS Charts of all patients undergoing elective laparoscopic cholecystectomy from January 2013 through December2014 were reviewed retrospectively for demographics,indication for surgery,operative course and outcome.In our institution the decision to perform postoperative blood analysis is left for the discretion of the surgeon,therefore we had the possibility to compare the results of those who had blood analyses results to those who did not.Analysis was performed to identify variables associated with the decision to perform postoperative blood tests.Subsequently a univariate and multivariate analyses was performed comparing the two cohorts.Secondary subgroup analysis was performed to identify factors associated with procedure related complications.RESULTS Five hundred and thirty-two elective laparoscopic cholecystectomies for symptomatic gallstones were performed during the study period.Sixty-four percent of the patients(n=340)had blood tests taken post operatively.Patients that had laboratory tests taken were older(P=0.006,OR=1.01),had longer surgery(P<0.001,OR=3.22)had more drains placed(P<0.001,OR=3.2)and stayed longer in the hospital(P<0.001,OR=1.2).A subgroup analysis of the patients who experienced complications revealed longer stay in the hospital(P<0.001),higher body mass index(BMI)(P=0.04,OR=1.08),increased rates of drain placement(P=0.006,OR=3.1)and higher conversion rates(P=0.01,OR=14.6).Postoperative blood tests withdrawals were not associated with complications(P=0.44).On Multivariate analysis BMI and drain placement were independently associated with complications.CONCLUSION The current study indicate that routine postoperative blood tests after elective laparoscopic cholecystectomy for symptomatic gallstones does not predict complications and may have an added benefit in diagnosis and management of cases were the surgeon encountered true technical difficulty during surgery.
基金Supported by Flanders Research Foundation(FWO-42865)the KU Leuven Molecular Small Animal Imaging Center Mo SAIC(KUL EF/05/08)+3 种基金the center of excellence in vivo molecular imaging research(IMIR),KU Leuven projects IOFHB/08/009 and IOF-HB/12/018the European Union(AsiaLink Cf P 2006-Europe Aid/123738/C/ACT/Multi-Proposal No.128-498/111)the National Natural Science Foundation of China No.81071828Jiangsu Province Natural Science Foundation No.BK2010594
文摘AIM:To facilitate translational research on cholelithiasis,we have developed a rat model of human gallstones by exploiting the unique biliopancreatic features of this species.METHODS:Under anesthesia,16 adult rats of equal genders underwent two times of abdominal surgery.First,their common bile duct(CBD)was ligated to cause cholestasis by total biliary obstruction(TBO).On day 0,1,3,7,14,21 and 28 after TBO,magnetic resonance imaging(MRI)was conducted to monitor the dilatation of the CBD,and blood was sampled to analyze total serum bilirubin(TSB).Secondly,on day 30,the abdomen was re-opened and gallstone(s)collected from human patients were implanted in the dilated CBD asa virtual gallbladder(VGB),which was closed by suture ligation.This rat cholelithiasis model was examined by MRI,clinical observation,microcholangiography and histology.RESULTS:All rats survived two laparotomies.After ligation,the CBD was dilated to a stable size of 4 to30 mm in diameter on day 21-28,which became a VGB.The rats initially showed signs of jaundice that diminished over time,which paralleled with the evolving TSB levels from 0.6±0.3 mg/d L before ligation,through a peak of 10.9±1.9 mg/dL on day 14,until a nearly normalized value after day 28.The dilated CBD with thickened wall allowed an incision for implantation of human gallstones of 1-10 mm in diameter.The rat cholelithiasis was proven by in vivo MRI and postmortem microcholangiography and histomorphology.CONCLUSION:A rat model cholelithiasis with human gallstones has been established,which proves feasible,safe,reliable,nontoxic and cost-effective.Given the gallstones of human origin,applications of this model may be of help in translational research such as optical detection and lysis of gallstones by systemic drug administration.
文摘The appropriate management of gallstones and gallbladder disease in patients undergoing gastric bypass remains unknown.Several therapeutic modalities are used and include performing cholecystectomy on all patients at the time of gastric bypass,performing concomitant cholecystectomy only when patients have gallstones and performing cholecystectomy only in the presence of both symptoms and gallstones.Some groups administer ursodeoxycholic acid for gallstone prevention in the postoperative period.All treatment modalities are analyzed and their results and rationality are discussed.
文摘Obesity is associated with insulin resistance, nonalcoholic fatty liver disease (NAFLD) and gallstones. High fat diets (unsaturated fats) rich in cholesterol have been demonstrated to produce not only gallstones but also NAFLD and insulin resistance. Interestingly, a high incidence of gallstones is being reported in association with insulin resistance and NAFLD. Laparoscopic cholecystectomy is the best definitive therapy for symptomatic gallbladder disease. Ezetimibe is a drug that inhibits the absorption of both dietary and biliary cholesterol in the small intestine. Importantly, ezetimibe showed potential benefit not only in treating and preventing gallstones but also in insulin resistance and NAFLD. Further studies are required before the use of ezetimibe for the treatment of gallstones can be advocated.
基金Supported by the Wu Jiping Medical Foundation,No.320.6750.18396Nantong“14th Five-Year”Science and Education to Strengthen Health Project,General Surgery Medical Key Discipline.
文摘Cholesterol gallstones are very common in hepatobiliary surgery and have been studied to a certain extent by doctors worldwide for decades.However,the mechanism of cholesterol gallstone formation is not fully understood,so there is currently no completely effective drug for the treatment and prevention of cholesterol gallstones.The formation and development of cholesterol gallstones are caused by a variety of genetic and environmental factors,among which genetic susceptibility,intestinal microflora disorders,impaired gallbladder motility,and immune disorders are important in the pathogenesis of cholesterol gallstones.This review focuses on recent advances in these mechanisms.We also discuss some new targets that may be effective in the treatment and prevention of cholesterol gallstones,which may be hot areas in the future.
文摘BACKGROUND Octreotide is widely used for the treatment of acromegaly,neuroendocrine tumors,and secretory diarrhea.However,long-term octreotide treatment can increase the incidence of gallstones.Vicarious contrast medium excretion(VCME)through the hepatobiliary system is well known.However,few studies have reported octreotide-induced acute gallstones following VCME.CASE SUMMARY A 69-year-old man presented with left lower back pain and hematuria caused by a fall.The patient had a history of polycystic kidney disease.VCME occurred following renal artery embolization for a ruptured polycystic kidney.After 5 d of treatment with octreotide,the patient developed acute gallstones and intrahepatic cholestasis which further induced pancreatitis and cholangitis.He was discharged after hemodialysis,antibiotics,and supportive treatments.CONCLUSION For patients with a high-risk of VCME,octreotide should be cautiously administered and carefully monitored.
基金Supported by Research Foundation-Flanders(FWO)the KU Leuven Molecular Small Animal Imaging Center Mo SAIC,No.KUL EF/05/08+4 种基金the center of excellence in vivo molecular imaging research(IMIR)KU Leuven projects,No.IOFHB/08/009 and No.IOF-HB/12/018the European Union,AsiaLink Cf P 2006-Europe Aid/123738/C/ACT/Multi-Proposal,No128-498/111National Natural Science Foundation of China,No.81071828Jiangsu Province Natural Science Foundation,No.BK2010594
文摘AIM: To explore the feasibility of using hypericin as an optical imaging probe with affinity for cholesterol for differential fluorescent detection of human gallstones.METHODS: Cholesterol, mixed and pigment stones from cholecystectomy patients were incubated with hypericin or solvent. After 72 h, the stones were analysed for fluorescence(365 nm) and treated with 2-propanol/dimethyl sulfoxide for high performance liquid chromatography(HPLC) analysis. Rats with virtual gallbladder containing human cholesterol, mixed or pigment gallstones(VGHG) received 5 mg/kg hypericin or solvent and VGHG rats with cholesterol stones were given different hypericin doses(5-15 mg/kg). Twelve hours later, the stones were analysed at 365 nm. Biliary excretion and metabolites of hypericin were assessed in common bile duct(CBD) cannulated rats for 9 h using fluorospectrometry, HPLC and matrixassisted laser desorption/ionization-time-of-flight mass spectrometry(MALDI-TOF MS).RESULTS: Homogeneous high fluorescence was seen on cholesterol stones either pre-incubated with hypericin or extracted from VGHG rats receiving hypericin. Mixed stones showed a dotted fluorescent pattern, whereas pigment and solvent-treated ones lacked fluorescence. HPLC showed 7.68, 6.65 and 0.08 × 10^(-3) M of cholesterol in extracts from cholesterol, mixed, and pigment gallstones, respectively. Hypericin accounted for 2.0, 0.5 and 0.2 × 10-6 M in that order. On cholesterol stones from VGHG rats receiving different hypericin doses, a positive correlation was observed between dose and fluorescence. In the bile from CBD-cannulated rats, fluorescence represented 20% of the injected dose with two peaks in 9 h. HPLC analysis revealed that hypericin conjugates reached 60% of the peak area. By MALDI-TOF MS, hypericinglucuronide was detected. CONCLUSION: This study proves the potential use of hypericin for differential fluorescent detection of human gallstones regarding their chemical composition.
文摘Biliary cholesterol may contribute to the formation of cholesterol gallstones, regulation of these levels could be a useful therapeutic strategy for gallstones disease. Piperine (PA) is a potential cholesterol lowering a- gent. In this study, we assessed the effect and mechanism of PA in preventing cholesterol gallstones formation in- duced by feeding lithogenic diet containing high cholesterol levels to mice. C57BL/6 inbred mice were fed lithogen- ic or chow diets for 10 weeks, with or without PA ( 15, 30 and 60 mg ~ kg-1 ) or ursodeoxycholic acid ( UDCA, 60 mg ~ kg-1) administration. Cholesterol, phospholipids and crystals in bile, the lipid in serum, pathological chan- ges and proteins expression in liver were analyzed. The results showed that PA could decrease the cholesterol poten- cy and crystals in bile, reduce total cholesterol (TC), triglycerides (TG) and increase high-density lipoprotein / low-density lipoprotein (HDL/LDL) levels in serum. Furthermore, PA treatment reduced liver lipid peroxidation and protected hepatobiliary cells from liver injury by decreasing malondialdehyde (MDA) and increasing superoxide dismutase (SOD). In addition, PA inhibited the expression of ATP-binding cassette transporters G5/8 (ABCG5/ 8 ) and liver X receptor (LXR) in liver, and reduced cholesterol transport from the hepatocytes to the gallbladder. It may be the mechanism of PA in preventing cholesterol gallstones formation. PA as a potential drug for prevention cholesterol gallstones merits further investigation.
文摘IM To seek effective drugs to dissolve bilirubin, glycoprotein and black stones and better lithotriptics for cholesterol stones, and study the amino acid constituents of gallstones.METHODS According to the characteristics of infrared spectrum and the contents of bilirubin tested by semiquantitative chemical analysis, 30 of 148 cases of gallstones were selected and divided into 5 groups. Amino acids of the 30 cases were detected by high speed chromatography.RESULTS The quantity of amino acids in black stones was the highest (2269mg/g) and that of pure cholesterol stones was the lowest, only 14mg/g in a case. In five groups of gallstones, the contents of amino acids were: black stone > mixed bilirubin stone and glucoprotein stone > mixed cholesterol stone > pure cholesterol stone. The proportions were: 9595∶2902 and 2805∶578∶1. Aliphatic amino acids accounted for about 50% of the total amino acids in gallstones and glycine 153% of the total amount of 17 kinds of amino acids.CONCLUSION In mixed stones, the higher level of bilirubin, the higher contents of amino acids. The acidic amino acids of bilirubin stones were relatively higher than those of cholesterol stones.