Therapeutic uses of animal biles in traditional Chinese medicine:An ethnopharmacological,biophysical chemical and medicinal review

Forty-four different animal biles obtained from both invertebrates and vertebrates (including human bile) have been used for centuries for a host of maladies in traditional Chinese medicine (TCM) beginning with dog, ox and common carp biles approximately in the Zhou dynasty (c. 1046-256 BCE). Overall, different animal biles were prescribed principally for the treatment of liver, biliary, skin (including burns), gynecological and heart diseases, as well as diseases of the eyes, ears, nose, mouth and throat. We present an informed opinion of the clinical efficacy of the medicinal uses of the different animal biles based on their presently known principal chemical components which are mostly steroidal detergent-like molecules and the membrane lipids such as unesterified cholesterol and mixed phosphatidylcholines and sometimes sphingomyelin, as well as containing lipopigments derived from heme principally bilirubin glucuronides. All of the available information on the ethnopharmacological uses of biles in TCM were collated from the rich collection of ancient Chinese books on materia medica held in libraries in China and United States and the composition of various animal biles was based on rigorous separatory and advanced chemical identification techniques published since the mid-20th century collected via library (Harvard’s Countway Library) and electronic searches (PubMed and Google Scholar). Our analysis of ethnomedical data and information on biliary chemistry shows that specific bile salts, as well as the common bile pigment bilirubin and its glucuronides plus the minor components of bile such as vitamins A, D, E, K, as well as melatonin (N-acetyl-5-methoxytryptamine) are salutary in improving liver function, dissolving gallstones, inhibiting bacterial and viral multiplication, promoting cardiac chronotropsim, as well as exhibiting anti-inflammatory, anti-pyretic, anti-oxidant, sedative, anti-convulsive, anti-allergic, anti-congestive, anti-diabetic and anti-spasmodic effects. Pig, wild boar and human biles diluted with alcohol were shown to form an artificial skin for burns and wounds one thousand years ago in the Tang dynasty (618-907 CE). Although various animal biles exhibit several generic effects in common, a number of biles appear to be advantageous for specific therapeutic indications. We attempt to understand these effects based on the pharmacology of individual components of bile as well as attempting to identify a variety of future research needs.

Quantitative Analysis of Elements in Gallstones and Biles from Chinese and Japanese Patients

The concentration of 26 elements in biles and gallstones from Chi-nese patients and the concentration of 10 elements from Japanese patients withgallstones were determined by inductively coupled plasma atomic emission spec-trometry (ICAP). Comparison of the level of elements between cholesterol andpigment gallstones revealed that Ca, Na, Fe, Cu, S, and Zn were higher inpigment gallstones than those in the cholesterol gallstones. Cholesterol stones aredivided into three subtypes: pure, mixed and combinated cholesterol stone.There were no significant difference among element contents. The levels of Ca,P, S, Li, and Ba in gallbladder biles were obviously higher in control groupthan in gallstone group. The element composition in gallbladder bile were similarto those in common bile duct bile. The former were 2～3 time high than the lat-ter.

A comparison study on structure-function relationship of polysaccharides obtained from sea buckthorn berries using different methods:antioxidant and bile acid-binding capacity

In this study,the structural characters,antioxidant activities and bile acid-binding ability of sea buckthorn polysaccharides(HRPs)obtained by the commonly used hot water(HRP-W),pressurized hot water(HRP-H),ultrasonic(HRP-U),acid(HRP-C)and alkali(HRP-A)assisted extraction methods were investigated.The results demonstrated that extraction methods had significant effects on extraction yield,monosaccharide composition,molecular weight,particle size,triple-helical structure,and surface morphology of HRPs except for the major linkage bands.Thermogravimetric analysis showed that HRP-U with filamentous reticular microstructure exhibited better thermal stability.The HRP-A with the lowest molecular weight and highest arabinose content possessed the best antioxidant activities.Moreover,the rheological analysis indicated that HRPs with higher galacturonic acid content and molecular weight showed higher viscosity and stronger crosslinking network(HRP-C,HRP-W and HRP-U),which exhibited stronger bile acid binding capacity.The present findings provide scientific evidence in the preparation technology of sea buckthorn polysaccharides with good antioxidant and bile acid binding capacity which are related to the structure affected by the extraction methods.

Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

Response letter to “Acute cholangitis: Does malignant biliary obstruction vs choledocholithiasis etiology change the outcomes?” with imaging aspects

Radiological imaging findings may contribute to the differentiation of malignant biliary obstruction from choledocholithiasis in the etiology of acute cholangitis.

Percutaneous transhepatic cholangioscopy-assisted biliary polypectomy for local palliative treatment of intraductal papillary neoplasm of the bile duct

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a premalignant biliarytype epithelial neoplasm with intraductal papillary or villous growth.Currently reported local palliative therapeutic modalities,including endoscopic nasobiliary drainage,stenting and biliary curettage,endoscopic biliary polypectomy,percutaneous biliary drainage,laser ablation,argon plasma coagulation,photodynamic therapy,and radiofrequency ablation to relieve mechanical obstruction are limited with weaknesses and disadvantages.We have applied percutaneous transhepatic cholangioscopy(PTCS)-assisted biliary polypectomy(PTCS-BP)technique for the management of IPNB including mucin-hypersecreting cast-like and polypoid type tumors since 2010.AIM To assess the technical feasibility,efficacy,and safety of PTCS-BP for local palliative treatment of IPNB.METHODS Patients with mucin-hypersecreting cast-like or polypoid type IPNB and receiving PTCS-BP between September 2010 and December 2019 were included.PTCS-BP was performed by using a half-moon type snare with a soft stainless-steel wire,and the tumor was snared and resected with electrocautery.The primary outcome was its feasibility,indicated by technical success.The secondary outcomes were efficacy,including therapeutic success,curative resection,and clinical success,and safety.RESULTS Five patients(four with mucin-hypersecreting cast-like type and one with polypoid type IPNB)were included.Low-and high-grade intraepithelial neoplasia(HGIN)and recurrent IPNB with invasive carcinoma were observed in one,two,and two patients,respectively.Repeated cholangitis and/or obstructive jaundice were presented in all four patients with mucin-hypersecreting cast-like type IPNB.All five patients achieved technical success of PTCS-BP.Four patients(three with mucin-hypersecreting cast-like type and one with polypoid type IPNB)obtained therapeutic success;one with mucin-hypersecreting cast-like type tumors in the intrahepatic small bile duct and HGIN had residual tumors.All four patients with mucin-hypersecreting IPNB achieved clinical success.The patient with polypoid type IPNB achieved curative resection.There were no PTCS-BP-related serious adverse events.CONCLUSION PTCS-BP appears to be feasible,efficacious,and safe for local palliative treatment of both mucin-hypersecreting cast-like and polypoid type IPNB.

Removal of intrahepatic bile duct stone could reduce the risk of cholangiocarcinoma: A single-center retrospective study in South Korea

BACKGROUND Intrahepatic duct(IHD)stones are among the most important risk factors for cholangiocarcinoma(CCC).Approximately 10%of patients with IHD stones develop CCC;however,there are limited studies regarding the effect of IHD stone removal on CCC development.AIM To investigate the association between IHD stone removal and CCC development.METHODS We retrospectively analyzed 397 patients with IHD stones at a tertiary referral center between January 2011 and December 2020.RESULTS CCC occurred in 36 of the 397 enrolled patients.In univariate analysis,chronic hepatitis B infection(11.1%vs 3.0%,P=0.03),carbohydrate antigen 19-9(CA19-9,176.00 vs 11.96 II/mL,P=0.010),stone located in left or both lobes(86.1%vs 70.1%,P=0.042),focal atrophy(52.8%vs 26.9%,P=0.001),duct stricture(47.2%vs 24.9%,P=0.004),and removal status of IHD stone(33.3%vs 63.2%,P<0.001)were significantly different between IHD stone patients with and without CCC.In the multivariate analysis,CA19-9>upper normal limit,carcinoembryonic antigen>upper normal limit,stones located in the left or both lobes,focal atrophy,and complete removal of IHD stones without recurrence were independent factors influencing CCC development.However,the type of removal method was not associated with CCC risk.CONCLUSION Complete removal of IHD stones without recurrence could reduce CCC risk.

Analysis of the Effectiveness of Biling Weitong Granules Combined with Trimethoprim and Vonoprazan in The Treatment of Reflux Esophagitis

Objective:To analyze the effectiveness of Biling Weitong Granules(BLWTG)combined with trimethoprim and vonoprazan in treating reflux esophagitis.Methods:Sixty patients with reflux esophagitis admitted to our hospital from March 2020 to March 2023 were selected as study subjects and randomly divided into a control group and an experimental group,with 30 cases in each group.The control group received only the combination treatment of trimethoprim and vonoprazan,while the experimental group was treated with BLWTG based on the control group.The acid reflux and heartburn symptom scores,quality-of-life scores,clinical efficacy,Chinese medicine symptom incidences,and the occurrence of adverse reactions before and after treatment in the two groups were compared.Results:After treatment,the acid reflux and heartburn symptom scores of patients in the experimental group were lower than those of the treatment control group,and the quality-of-life scores were higher than those of the treatment control group(P<0.05).The total clinical efficacy of the experimental group was 96.66%,which was significantly higher than that of the control group(73.33%,P<0.05).After treatment,the incidence of Chinese medicine symptoms,such as nausea and vomiting,abdominal distension and abdominal pain,and loss of appetite of the patients in the experimental group were significantly lower than those of the control group(P<0.05).During the treatment period,there was no significant difference in the incidence of adverse reactions between the two groups,which indicated that the safety of the two treatments was comparable(P>0.05).Conclusion:BLWTG combined with trimethoprim and vonoprazan was safe and reliable in treating reflux esophagitis,effectively relieving the symptoms and improving its clinical efficacy.This treatment is worthy of popularization.

Diseases of bile duct in children

Several diseases originate from bile duct pathology.Despite studies on these diseases,certain etiologies of some of them still cannot be concluded.The most common disease of the bile duct in newborns is biliary atresia,whose prognosis varies according to the age of surgical correction.Other diseases such as Alagille syndrome,inspissated bile duct syndrome,and choledochal cysts are also time-sensitive because they can cause severe liver damage due to obstruction.The majority of these diseases present with cholestatic jaundice in the newborn or infant period,which is quite difficult to differentiate regarding clinical acumen and initial investigations.Intraoperative cholangiography is potentially necessary to make an accurate diagnosis,and further treatment will be performed synchronously or planned as findings suggest.This article provides a concise review of bile duct diseases,with interesting cases.

Influence of gut microbiome composition on effect variations of anti-cholesterol treatment among individual mice

This study investigated if the variation in the effect of anti-cholesterol(AC)treatment on individual mice are related to gut microbiome composition.The bile salt hydrolase(BSH)activity of 23 commercial fermented milk products was examined to select a fermented milk product for AC treatment.Mice were fed to different diets for 6 weeks:high-fat(60%of total calories from fat;D1),high-dietary fibre(20%cellulose;D2),and low-fat(17.2%of total calories from fat;D3)diets to change their gut microbiomes.Subsequently,faecal microbiome was transplanted(FMT)into mice treated with high cholesterol diet contained 2%cholesterol,followed by AC or non-AC(sterile tap water,STW)treatments.Control groups with normal(NC)and highcholesterol diets(PC)were prepared for both AC and STW treatment.All experimental groups were subjected to serum and liver cholesterol,cholesterol metabolism-related(CMR)gene expression,and intestinal microbiome analyses.D3-FMT mice showed the most significant enhancements in cholesterol ratio and decreased hepatic cholesterol levels with AC treatment.Moreover,upregulation of the Cyp7a1 gene expression was observed in this group.Furthermore,the intestinal microbiome analysis indicated higher abundances of BSH-producing Eubacterium,Bifidobacterium,and Parabacteroides in the D3-FMT+AC group compare to others,potentially contributing to increased bile acid synthesis.

The Therapeutic Effect of Biling Weitong Granules Combined with Oryz-Aspergillus Enzyme and Pancreatin Tablet on Reflux Esophagitis with Functional Dyspepsia

Objective:To investigate the therapeutic effect of Biling Weitong Granules combined with oryz-aspergillus enzyme and pancreatin tablets on patients with reflux esophagitis with functional dyspepsia.Methods:Sixty patients diagnosed with reflux esophagitis with functional dyspepsia who were admitted to the Affiliated Hospital of Hebei University between June 2020 and June 2023 were selected and divided into two groups:the control group and the observation group,each consisting of 30 cases.The control group received oryz-aspergillus enzyme and pancreatin tablets only,while the observation group received Biling Weitong Granules in addition to the tablets.The clinical efficacy,Chinese medicine syndrome points,esophageal kinetic indexes,gastrointestinal hormone levels,and therapeutic safety of both groups were evaluated.Results:The total efficiency of the observation group reached 93.33%,significantly higher than the 73.33%of the control group(P<0.05).After treatment,patients in the observation group exhibited significantly lower scores for Chinese medicine symptoms such as early satiety,belching,abdominal distension,abdominal pain,and loss of appetite compared to the control group(P<0.05).Furthermore,the observation group showed significantly higher upper esophageal sphincter pressure,lower esophageal sphincter pressure,and distal esophageal contraction scores compared to the control group(P<0.05).Additionally,levels of gastric motility hormone,vasoactive intestinal peptide,and gastrin were significantly higher in the observation group compared to the control group(P<0.05).Throughout the treatment period,there was no significant difference in the incidence of adverse reactions between the two groups,indicating comparable safety of the two treatment modalities(P>0.05).Conclusion:The combination of Biling Weitong Granules with oryz-aspergillus enzyme and pancreatin tablets demonstrates significant efficacy in the treatment of reflux esophagitis with functional dyspepsia,with a better safety profile.This finding warrants further clinical promotion.

Bioactivities,Mechanisms,Production,and Potential Application of Bile Acids in Preventing and Treating Infectious Diseases

Infectious diseases are a global public health problem,with emerging and re-emerging infectious diseases on the rise worldwide.Therefore,their prevention and treatment are still major challenges.Bile acids are common metabolites in both hosts and microorganisms that play a significant role in controlling the metabolism of lipids,glucose,and energy.Bile acids have historically been utilized as first-line,valuable therapeutic agents for related metabolic and hepatobiliary diseases.Notably,bile acids are the major active ingredients of cow bezoar and bear bile,which are commonly used traditional Chinese medicines(TCMs)with the therapeutic effects of clearing heat,detoxification,and relieving wind and spasm.In recent years,the promising performance of bile acids against infectious diseases has attracted attention from the scientific community.This paper reviews for the first time the biological activities,possible mechanisms,production routes,and potential applications of bile acids in the treatment and prevention of infectious diseases.Compared with previous reviews,we comprehensively summarize existing studies on the use of bile acids against infectious diseases caused by pathogenic microorganisms that are leading causes of global morbidity and mortality.In addition,to ensure a stable supply of bile acids at affordable prices,it is necessary to clarify the biosynthesis of bile acids in vivo,which will assist scientists in elucidating the accumulation of bile acids and discovering how to engineer various bile acids by means of chemosynthesis,biosynthesis,and chemoenzymatic synthesis.Finally,we explore the current challenges in the field and recommend a development strategy for bile-acid-based drugs and the sustainable production of bile acids.The presented studies suggest that bile acids are potential novel therapeutic agents for managing infectious diseases and can be artificially synthesized in a sustainable way.

Aberrant bile duct communicating with the cystic duct:From early detection to management of late surgical complications

The aberrant hepatic duct is classified by Huang et al.[1]into type A(right intrahepatic duct variant)and type B(left intrahepatic duct variant).Type A and B are further classified into 5(A1-5)and 6(B1-6)subtypes,respectively.The variation of cystic duct involves only in type A.Type A1 or classic arrangement refers to the formation of the common hepatic duct(CHD)by the left hepatic duct(LHD)and the right hepatic duct(RHD).The RHD has two tributaries composed of the right anterior hepatic duct(RAHD)and the right posterior hepatic duct(RPHD).Then,the common bile duct(CBD)is formed when the cystic duct joins with the CHD(Fig.1).Type A2 refers to the RAHD and RPHD joining with LHD at hepatic hilum,and the absence of the RHD.Type A3 refers to the RAHD or RPHD directly draining to the LHD.Type A4 refers to the RAHD or RPHD directly draining to the CHD.Type A5 refers to the RAHD,RPHD or RHD directly draining to the cystic duct(or aberrant bile duct communicating with the cystic duct,ACC)(Fig.1)[1].

Tri-modal death distribution towards personalized management of intraductal papillary neoplasm of the bile duct patients:Every story has its own conclusion

The concept of intraductal papillary neoplasm of the bile duct(IPNB)has gained recognition as a discrete entity[1,2],possessing many features including multiplicity[3,4],mucin production[3],slow progression[3,5],various morphology[6,7],easy sloughing and seeding[8],and having unique risk factors[2,9-11].We have previously proposed a morphologic classification[6]and a progression model of IPNB[12].

Two intestinal microbiota-derived metabolites, deoxycholic acid and butyrate, synergize to enhance host defense peptide synthesis and alleviate necrotic enteritis

Background Necrotic enteritis(NE)is a major enteric disease in poultry,yet effective mitigation strategies remain elusive.Deoxycholic acid(DCA)and butyrate,two major metabolites derived from the intestinal microbiota,have independently been shown to induce host defense peptide(HDP)synthesis.However,the potential synergy between these two compounds remains unexplored.Methods To investigate the possible synergistic effect between DCA and butyrate in regulating HDP synthesis and barrier function,we treated chicken HD11 macrophage cells and jejunal explants with DCA and sodium butyrate(NaB),either individually or in combination,for 24 h.Subsequently,we performed RNA isolation and reverse transcrip-tion-quantitative PCR to analyze HDP genes as well as the major genes associated with barrier function.To further determine the synergy between DCA and NaB in enhancing NE resistance,we conducted two independent trials with Cobb broiler chicks.In each trial,the diet was supplemented with DCA or NaB on the day-of-hatch,followed by NE induction through sequential challenges with Eimeria maxima and Clostridium perfringens on d 10 and 14,respectively.We recorded animal mortality after infection and assessed intestinal lesions on d 17.The impact of DCA and NaB on the microbiota in the ileum and cecum was evaluated through bacterial 16S rRNA gene sequencing.Results We found that the combination of DCA and NaB synergistically induced multiple HDP genes in both chicken HD11 cells and jejunal explants.Additionally,the gene for claudin-1,a major tight junction protein,also exhibited synergistic induction in response to DCA and NaB.Furthermore,dietary supplementation with a combination of 0.75 g/kg DCA and 1 g/kg NaB led to a significant improvement in animal survival and a reduction in intestinal lesions compared to either compound alone in a chicken model of NE.Notably,the cecal microbiota of NE-infected chickens showed a marked decrease in SCFA-producing bacteria such as Bacteroides,Faecalibacterium,and Cuneatibacter,with lactobacilli becoming the most dominant species.However,supplementation with DCA and NaB largely restored the intestinal microbiota to healthy levels.Conclusions DCA synergizes with NaB to induce HDP and claudin-1 expression and enhance NE resistance,with potential for further development as cost-effective antibiotic alternatives.

Enhancing milk quality and modulating rectal microbiota of dairy goats in starch‑rich diet:the role of bile acid supplementation

Background Diets rich in starch have been shown to increase a risk of reducing milk fat content in dairy goats.While bile acids(BAs)have been used as a lipid emulsifier in monogastric and aquatic animals,their effect on ruminants is not well understood.This study aimed to investigate the impact of BAs supplementation on various aspects of dairy goat physiology,including milk composition,rumen fermentation,gut microbiota,and BA metabolism.Results We randomly divided eighteen healthy primiparity lactating dairy goats(days in milk=100±6 d)into two groups and supplemented them with 0 or 4 g/d of BAs undergoing 5 weeks of feeding on a starch-rich diet.The results showed that BAs supplementation positively influenced milk yield and improved the quality of fatty acids in goat milk.BAs supplementation led to a reduction in saturated fatty acids(C16:0)and an increase in monounsaturated fatty acids(cis-9 C18:1),resulting in a healthier milk fatty acid profile.We observed a significant increase in plasma total bile acid concentration while the proportion of rumen short-chain fatty acids was not affected.Furthermore,BAs supplementation induced significant changes in the composition of the gut microbiota,favoring the enrichment of specific bacterial groups and altering the balance of microbial populations.Correlation analysis revealed associations between specific bacterial groups(Bacillus and Christensenellaceae R-7 group)and BA types,suggesting a role for the gut microbiota in BA metabolism.Functional prediction analysis revealed notable changes in pathways associated with lipid metabolism,suggesting that BAs supplementation has the potential to modulate lipid-related processes.Conclusion These findings highlight the potential benefits of BAs supplementation in enhancing milk production,improving milk quality,and influencing metabolic pathways in dairy goats.Further research is warranted to elucidate the underlying mechanisms and explore the broader implications of these findings.

Undifferentiated high-grade pleomorphic sarcoma of the common bile duct:A case report and review of literature

BACKGROUND Undifferentiated pleomorphic sarcoma(UPS)is a rare malignant mesenchymal tumor with a poor prognosis.It mainly occurs in the extremities,trunk,head and neck,and retroperitoneum regions.Owing to the lack of specific clinical manifestations and imaging features,UPS diagnosis mainly depends on pathological and immunohistochemical examinations for exclusive diagnosis.Here we report an extremely rare case of high-grade UPS in the common bile duct(CBD).There are limited available data on such cases.CASE SUMMARY A 70-year-old woman was admitted to our department with yellow eyes and urine accompanied by upper abdominal distending pain for 2 wk.Her laboratory data suggested significantly elevated hepatorenal function levels.The imaging data revealed calculous cholecystitis,intrahepatic and extrahepatic bile duct dilation with extrahepatic bile duct calculi,and a space-occupying lesion at the distal CBD.After endoscopic biliary stenting and symptomatic support therapy,CBD exploration and biopsy were performed.The frozen section indicated malignant spindle cell tumor of the CBD mass,and further radical pancreaticoduodenectomy was performed.Finally,the neoplasm was diagnosed as a high-grade UPS combined with the light-microscopic morphology and immunohistochemical results.CONCLUSION This extremely rare case highlighted the need for increasing physicians'vigilance,reducing the odds of misdiagnosis,and providing appropriate treatment strategies.

Artificial Bear Bile:A Novel Approach to Balancing Medical Requirements and Animal Welfare

Bear bile has been a valuable and effective medicinal material in traditional Chinese medicine(TCM)for over 13 centuries.However,the current practice of obtaining it through bear farming is under scrutiny for its adverse impact on bear welfare.Here,we present a new approach for creating artificial bear bile(ABB)as a high-quality and sustainable alternative to natural bear bile.This study addresses the scientific challenges of creating bear bile alternatives through interdisciplinary collaborations across various fields,including resources,chemistry,biology,medicine,pharmacology,and TCM.A comprehensive efficacy assessment system that bridges the gap between TCM and modern medical terminology has been established,allowing for the systematic screening of therapeutic constituents.Through the utilization of chemical synthesis and enzyme engineering technologies,our research has achieved the environmentally friendly,large-scale production of bear bile therapeutic compounds,as well as the optimization and recomposition of ABB formulations.The resulting ABB not only closely resembles natural bear bile in its composition but also offers advantages such as consistent product quality,availability of raw materials,and independence from threatened or wild resources.Comprehensive preclinical efficacy evaluations have demonstrated the equivalence of the therapeutic effects from ABB and those from commercially available drained bear bile(DBB).Furthermore,preclinical toxicological assessment and phase I clinical trials show that the safety of ABB is on par with that of the currently used DBB.This innovative strategy can serve as a new research paradigm for developing alternatives for other endangered TCMs,thereby strengthening the integrity and sustainability of TCM.

Mirizzi syndrome:Problems and strategies

Mirizzi syndrome is a serious complication of gallstone disease.It is caused by the impacted stones in the gallbladder neck or cystic duct.One of the features of Mirizzi syndrome is severe inflammation or dense fibrosis at the Calot’s triangle.In our clinical practice,bile duct,branches of right hepatic artery and right portal vein clinging to gallbladder infundibulum are often observed due to gallbladder infundibulum adhered to right hepatic hilum.The intraoperative damage of branches of right hepatic artery occurs more easily than that of bile duct,all of which are hidden pitfalls for surgeons.Magnetic resonance cholangiopancreatography(MRCP)and endoscopic retrograde cholangiopancreatography(ERCP)are the preferable tools for the diagnosis of Mirizzi syndrome.Anterograde cholecystectomy in Mirizzi syndrome is easy to damage branches of right hepatic artery and bile duct due to gallbladder infundibulum adhered to right hepatic hilum.Subtotal cholecystectomy is an easy,safe and definitive approach to Mirizzi syndrome.When combined with the application of ERCP,a laparoscopic management of Mirizzi syndrome by well-trained surgeons is feasible and safe.The objective of this review was to highlight its existing problems:(1)low preoperative diagnostic rate,(2)easy to damage bile duct and branches of right hepatic artery,and(3)high concomitant gallbladder carcinoma.Meanwhile,the review aimed to discuss the possible therapeutic strategies:(1)to enhance its preoperative recognition by imaging findings,and(2)to avoid potential pitfalls during surgery.

Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling

Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.