Cav-1 regulates the bile salt export pump on the canalicular membrane of hepatocytes by PKCα-associated signalling under cholesterol stimulation.

BACKGROUND AND AIMS: The secretion of bile salts transported by the bile salt export pump (BSEP) is the primary driving force for the generation of bile flow; thus, it is closely related to the formation of cholesterol stones. Caveolin-1 (Cav-1), an essential player in cell signalling and endocytosis, is known to co-localize with cholesterol-rich membrane domains. This study illustrates the role of Cav-1 and BSEP in cholesterol stone formation. METHODS: Adult male C57BL/6 mice were used as an animal model. HepG2 cells were cultured under different cholesterol concentrations and BSEP, Cav-1, p-PKCα and Hax-1 expression levels were determined via Western blotting. Expression levels of BSEP and Cav-1 mRNA were detected using real-time PCR. Immunofluorescence and immunoprecipitation assays were performed to study BSEP and Hax-1 distribution. Finally, an ATPase activity assay was performed to detect BSEP transport activity under different cholesterol concentrations in cells. RESULTS: Under low-concentration stimulation with cholesterol, Cav-1 and BSEP protein and mRNA expression levels significantly increased, PKCα phosphorylation significantly decreased, BSEP binding capacity to Hax-1 weakened, and BSEP function increased. Under high-concentration stimulation with cholesterol, Cav-1 and BSEP protein and mRNA expression levels decreased, PKCα phosphorylation increased, BSEP binding capacity to Hax-1 rose, and BSEP function decreased. CONCLUSION: Cav-1 regulates the bile salt export pump on the canalicular membrane of hepatocytes via PKCα-associated signalling under cholesterol stimulation.

Resistance to Cholesterol Gallstone Disease: Hepatic Cholesterol Metabolism.

Cholesterol gallstone disease (CGD) is one of the most common digestive diseases, and it is closely associated with hepatic cholesterol metabolism. Cholesterol gallstones may be caused by abnormal hepatic cholesterol metabolism, such as excessive cholesterol biosynthesis within the liver, interfering with the uptake or export of cholesterol in the liver, and abnormal hepatic cholesterol esterification. In this review, we begin with a brief overview of the clinical diagnosis and treatment of gallstone disease (GSD). Then, we briefly describe the major processes of hepatic cholesterol metabolism and summarize the key molecular expression changes of hepatic cholesterol metabolism in patients with gallstones. We review and analyze the recent advances in elucidating the relationships between these key molecules and CGD, and some targets significantly impacting on CGD via hepatic cholesterol metabolism are also listed. We also provide a significant discussion on the relationship between CGD and nonalcoholic fatty liver disease (NAFLD). Finally, the new discoveries of some therapeutic strategies associated with hepatic cholesterol metabolism to prevent and treat CGD are summarized.

CHMP3 promotes the progression of hepatocellular carcinoma by inhibiting caspase­1­dependent pyroptosis.

Charged multivesicular body protein 3 (CHMP3) is an elemental constituent of the endosomal sorting complex required for transport (ESCRT) III, whose function as a tumor susceptibility gene in the development of liver cancer remains unclear. CHMP3 was found to be associated with pyroptosis by bioinformatics analysis of data from patients with hepatocellular carcinoma (HCC) in The Cancer Genome Atlas database. It was aimed to explore the role and potential mechanisms of CHMP3 in the development of liver cancer. The expression of CHMP3 at the tissue level was examined using immunohistochemistry and western blot analysis. Subsequently, HepG2 and Huh­7 cells were transfected with small interfering RNA and overexpression plasmids to change CHMP3 expression. The proliferative capacity of cells was examined using colony formation and Cell Counting Kit­8 assays. Wound healing and Transwell assays were used to examine the migratory and invasive abilities of the cells. Transmission electron microscopy was used to observe changes in cell morphology. Western blotting was used to examine the expression of caspase­1 signaling pathway related proteins, a classic pathway of pyroptosis. In addition, a xenograft tumor model was used to examine the tumorigenic ability of CHMP3 in vivo. The results demonstrated that CHMP3 expression was upregulated in HCC and was associated with poor prognosis. Knockdown or overexpression of CHMP3 inhibited or promoted the proliferation, migration and invasion of liver cancer cells. Knockdown of Huh­7 showed changes in cell membrane integrity as well as cytoplasmic leakage. Furthermore, knockdown of CHMP3 may activate the caspase­1 pyroptosis signaling pathway which in turn inhibits the progression of liver cancer, and this effect can be reversed by the caspase­1 inhibitor AYC. In conclusion, CHMP3 may affect the development of liver cancer through the caspase­1­mediated pyroptosis pathway.

Causal association between serum total bilirubin and cholelithiasis: a bidirectional two-sample Mendelian randomization study.

Background: Observational studies about the association between serum total bilirubin and cholelithiasis are inconsistent. Hence, it is essential to reevaluate the association between serum total bilirubin and cholelithiasis and to verify whether such association is causal or not. Methods: We selected single-nucleotide polymorphisms (SNPs) that are strongly associated with exposure as instrumental variable and conducted a bidirectional two-sample Mendelian randomization (MR) study to explore the causal association between serum total bilirubin and cholelithiasis. We implemented the inverse-variance weighted approach as a primary analysis to combine the Wald ratio estimates. Four additional analyses, namely, MR-Egger regression, weighted median, weighted mode, and MR-pleiotropy residual sum and outlier (PRESSO), were utilized to investigate the causal association and the influence of potential pleiotropy. Results: A total of 116 SNPs were selected as valid instrumental variables to estimate the causal association of serum total bilirubin on cholelithiasis, and causal association between genetically determined serum total bilirubin and cholelithiasis was demonstrated [beta = 0.10; 95% confident interval (CI), 0.07 to 0.14; p < 0.001]. Likewise, the other methods, namely, the weighted median (beta = 0.12; 95% CI, 0.08 to 0.15; p < 0.001), MR-Egger (beta = 0.11; 95% CI, 0.08 to 0.15; p < 0.001), weighted mode (beta = 0.11; 95% CI, 0.08 to 0.15; p < 0.001), and MR-PRESSO approaches, further confirmed that this result (p = 0.054) indicates similar results. In addition, seven SNPs were selected as instrumental variable to estimate causal association of cholelithiasis on serum total bilirubin, and the result supported the causal effect of cholelithiasis to serum total bilirubin (beta = 0.12; 95% CI, 0.09 to 0.15; p < 0.001). At the same time, the other methods, namely, the weighted median (beta = 0.10; 95% CI, 0.06 to 0.13; p < 0.001), MR-Egger (beta = 0.12; 95% CI, 0.07 to 0.18; p = 0.007), weighted mode (beta = 0.09; 95% CI, 0.03 to 0.14, p = 0.019), and MR-PRESSO methods, further confirmed this result (p < 0.001). Conclusion: Our MR study revealed that the serum total bilirubin was causally associated with the risk of cholelithiasis, and the genetic predisposition to cholelithiasis was causally associated with the increased serum total bilirubin levels.

Effectiveness and safety of central pancreatectomy in benign or low-grade malignant pancreatic body lesions: a systematic review and meta-analysis.

BACKGROUND: The best approach for treating benign or low-grade malignant lesions localized in the pancreatic neck or body remains debatable. Conventional pancreatoduodenectomy and distal pancreatectomy (DP) are associated with a risk of impairment of pancreatic function at long-term follow-up. With advances in technology and surgical skills, the use of central pancreatectomy (CP) has gradually increased. OBJECTIVES: The objective was to compare the safety, feasibility, and short-term and long-term clinical benefits of CP and DP in matched cases. METHODS: The PubMed, MEDLINE, Web of Science, Cochrane, and EMBASE databases were systematically searched to identify studies published from database inception to February 2022 that compared CP and DP. This meta-analysis was performed using R software. RESULTS: Twenty-six studies matched the selection criteria, including 774 CP and 1713 DP cases. CP was significantly associated with longer operative time ( P <0.0001), less blood loss ( P <0.01), overall and clinically relevant pancreatic fistula ( P <0.0001), postoperative hemorrhage ( P <0.0001), reoperation ( P =0.0196), delayed gastric emptying ( P =0.0096), increased hospital stay ( P =0.0002), intra-abdominal abscess or effusion ( P =0.0161), higher morbidity ( P <0.0001) and severe morbidity ( P <0.0001) but with a significantly lower incidence of overall endocrine and exocrine insufficiency ( P <0.01), and new-onset and worsening diabetes mellitus ( P <0.0001) than DP. CONCLUSIONS: CP should be considered as an alternative to DP in selected cases such as without pancreatic disease, length of the residual distal pancreas is more than 5 cm, branch-duct intraductal papillary mucinous neoplasms, and a low risk of postoperative pancreatic fistula after adequate evaluation.

Comparison of Efficacy and Safety between Endoscopic Retrograde Cholangiopancreatography and Percutaneous Transhepatic Cholangial Drainage for the Treatment of Malignant Obstructive Jaundice: A Systematic Review and Meta-Analysis.

BACKGROUND: At present, endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangial drainage (PTCD) are frequently used for reducing malignant obstructive jaundice (MOJ). However, it is controversial as to which method is superior in terms of efficacy and safety. OBJECTIVES: The aim of this study was to compare the safety, feasibility, and clinical benefits of ERCP and PTCD in matched cases of MOJ. METHODS: The Web of Science, Cochrane, PubMed, and CNKI databases were searched systematically to identify studies published between January 2000 and December 2019, without language restrictions, that compared ERCP and PTCD in patients with MOJ. The primary outcome was the success rate for each procedure. The secondary outcomes were the technical success rate, serum total bilirubin level, length of hospital stay, hospital expense, complication rate, and survival. This meta-analysis was performed using Review Manager 5.3. RESULTS: Sixteen studies met the inclusion criteria, including 1,143 cases of ERCP and 854 cases of PTCD. The analysis demonstrated that jaundice remission in PTCD was equal to that in ERCP (mean difference [MD], 1.19; 95% confidence interval [CI]: -0.56 to -2.93; p = 0.18). However, the length of hospital stay in the ERCP group was 3.03 days shorter than that in the PTCD group (MD, -2.41; 95% CI: -4.61 to -0.22; p = 0.03). ERCP had a lower rate of postoperative complications (odds ratio, 0.66; 95% CI: 0.42-1.05); however, the difference was not significant (p = 0.08). ERCP was also more cost-efficient (MD, -5.42; 95% CI: -5.52 to -5.32; p < 0.01). Further, we calculated the absolute mean of hospital stay (ERCP:PTCD = 8.73:12.95 days), hospital expenses (ERCP:PTCD = 5,104.13:5,866.75 RMB), and postoperative complications (ERCP:PTCD = 11.2%:9.1%) in both groups. CONCLUSION: For remission of MOJ, PTCD and ERCP had similar clinical efficacy. Each method has its own strengths and weaknesses. Considering that ERCP had a lower rate of postoperative complications, shorter hospital stay, and higher cost efficiency, ERCP may be a superior initial treatment choice for MOJ.

Macrophages and derived-TNF-α promote lipopolysaccharide-induced upregulation of endogenous ß-glucuronidase in the epithelial cells of the bile duct: A possible facilitator of hepatolithiasis formation.

BACKGROUND: Hepatolithiasis is prevalent in Southeast Asian regions, and the role of endogenous ß-glucuronidase (ß-GD) in the formation of hepatolithiasis is being gradually recognised. Revealing the regulation mechanism of the expression of endogenous ß-GD will provide new therapeutic strategies for intervening in the formation of hepatolithiasis. METHODS: Liver specimens from patients with hepatolithiasis were examined by immunohistochemistry to assess the expression of macrophage markers including CD68, CD80, and CD206, as well as that of TNF-α and endogenous ß-GD, compared with that in normal liver samples. HiBEpiC cells were co-cultured directly or indirectly with induced M2 macrophages or directly stimulated with TNF-α, and the expression of the endogenous ß-GD was examined. A PKC inhibitor, chelerythrine, and an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), were used to elucidate the possible regulation mechanism. RESULTS: The expression of macrophage markers including CD68 and CD206, as well as that of TNF-α and endogenous ß-GD significantly increased in liver specimens from patients with hepatolithiasis compared with that in normal liver samples. The expression of CD68, CD206 and TNF-α was positively correlated with that of endogenous ß-GD. When HiBEpiC cells were co-cultured directly or indirectly with M2 macrophages, following stimulation with lipopolysaccharide (LPS), the expression of endogenous ß-GD was significantly higher in the indirect co-culture group than that in the direct co-culture group, or in HiBEpiC cells or M2 macrophages cultured alone. Further experiments revealed that following stimulation with LPS, TNF-α secretion increased in both the indirect and direct co-culture groups compared with that in HiBEpiC cells cultured alone. TNF-α increased the expression of endogenous ß-GD in HiBEpiC cells, in a dose- and time-dependent manner. In addition, TNF-α significantly increased the expression levels of p-P65 and proliferating cell nuclear antigen (PCNA), and PDTC effectively inhibited the TNF-α-induced expression of PCNA and ß-GD. CONCLUSIONS: Infiltration of macrophages, especially M2 macrophages, may be involved in the hepatolithiasis formation. LPS activates the macrophages, inducing the secretion of TNF-α, which can further increase the expression of endogenous ß-GD in the epithelial cells of the bile duct, possibly via the NF-κB/PCNA signalling cascade.

Laparoscopic surgery for gallstones or common bile duct stones: A stably safe and feasible surgical strategy for patients with a history of upper abdominal surgery.

Backgrounds/Aims: A history of upper abdominal surgery has been identified as a relative contraindication for laparoscopy. This study aimed to compare the clinical efficacy and safety of laparoscopic cholecystectomy (LC) and laparoscopic common bile duct exploration (LCBDE) in patients with and without previous upper abdominal surgery. Methods: In total, 131 patients with previous upper abdominal surgery and 64 without upper abdominal surgery underwent LC or LCBDE between September 2017 and September 2021 at the Shengjing Hospital of China Medical University. Patients with previous upper abdominal surgery were divided into four groups: group A included patients with previous right upper abdominal surgery who underwent LC (n = 17), group B included patients with previous other upper abdominal surgery who underwent LC (n = 66), group C included patients with previous right upper abdominal surgery who underwent LCBDE (n = 30), and group D included patients with previous other upper abdominal surgery who underwent LCBDE (n = 18). Patient demographics and perioperative outcomes were retrospectively analyzed. Results: The preoperative liver function indexes showed no significant difference between the observation and control groups. For patients who underwent LC, groups A and B had more abdominal adhesions than the control group. One case was converted to open surgery in each of groups A and B. There was no statistical difference in operation time, estimated blood loss, postoperative hospital stay, and drainage volume. For patients who underwent LCBDE, groups C and D had more estimated blood loss than the control group (group C, 41.33 ± 50.84 vs. 18.97 ± 13.12 ml, p = 0.026; group D, 66.11 ± 87.46 vs. 18.97 ± 13.12 ml, p = 0.036). Compared with the control group, group C exhibited longer operative time (173.87 ± 60.91 vs. 138.38 ± 57.38 min, p = 0.025), higher drainage volume (296.83 ± 282.97 vs. 150.83 ± 127.04 ml, p = 0.015), and longer postoperative hospital stay (7.97 ± 3.68 vs. 6.17 ± 1.63 days, p = 0.021). There was no mortality in all groups. Conclusions: LC or LCBDE is a safe and feasible procedure for experienced laparoscopic surgeons to perform on patients with previous upper abdominal surgery.

Developments in the Diagnosis and Management of Cholecystoenteric Fistula.

Background: Cholecystoenteric fistula (CEF) is a rare complication of cholelithiasis. CEF refers to one or more pathological perforations between the gallbladder and the adjacent gastrointestinal tract, first described by Bartholin in 1645. The aim of this review is to examine the etiology, symptoms, diagnosis, and treatment of CEF.Methods: A literature search was conducted according to a set of criteria in PubMed for historical and current peer-reviewed studies regarding CEF.Results: Clinical manifestations of CEF are always latent. Despite modern imaging studies and diagnostic methods, it is still very difficult to definitively diagnose CEF preoperatively. Instead, CEF is often accidentally discovered in the perioperative period or via intraoperative exploration.Conclusions: Without appropriate preoperative preparation, gastrointestinal injury and intraoperative bleeding often occur. CEF often goes unreported, and its diagnosis and treatment are still controversial. Early diagnosis of CEF is essential for effective treatment and improved outcome.

Osthole: An up-to-date review of its anticancer potential and mechanisms of action.

With its high incidence and mortality rates, cancer is one of the largest health problems worldwide. Investigating various cancer treatment options has been the focus of many domestic and international researchers, and significant progress has been made in the study of the anticancer effects of traditional Chinese medicines. Osthole, a coumarin compound extracted from Cnidium monnieri (L.) Cuss., has become a new research hotspot. There have been many reports on its anticancer effects, and recent studies have elucidated that its underlying mechanism of action mainly involves inhibiting cancer cell proliferation, inducing cancer cell apoptosis, inhibiting invasion and migration of cancer cells, inhibiting cancer angiogenesis, increasing sensitivity to chemotherapy drugs, and reversing multidrug resistance of cancer cells. This mini-review summarizes the research progress on the anticancer effects of osthole in recent years.

The safety and feasibility of laparoscopic approach for the management of intrahepatic and extrahepatic bile duct stones in patients with prior biliary tract surgical interventions.

The purpose of this study was to compare the efficacy and safety of laparoscopic and open reoperation for intrahepatic and extrahepatic bile duct stones patients with previous biliary tract surgical procedures. The clinical data were retrospectively analyzed of intrahepatic and extrahepatic bile duct stones patients with previous biliary tract surgical procedures who underwent reoperation in the Second General Surgery Department of China Medical University from January 2012 to February 2018. 44 eligible cases were selected. In accordance with the surgical procedures, they were divided into a laparoscopy group (n = 23) and an open surgery group (n = 21). No statistically significant differences were found in the preoperative general clinical data between the two group. Two patients in the laparoscopy group were converted to open surgery. Comparisons between the two groups showed that the intraoperative blood loss [90.87 ± 62.95 (ml) vs. 152.38 ± 118.82 (ml)], the proportion of postoperative analgesia [10/23 (43.5%) vs. 16/21 (76.2%)], and the length of stay [7.19 ± 5.32 (d) vs. 11.00 ± 4.66 (d)] in the laparoscopy group were significantly lower than those in the open surgery group (P < 0.05). Laparoscopic biliary reoperation for intrahepatic and extrahepatic bile duct stones was feasible. Compared with open surgery, laparoscopic surgery has the advantages of less bleeding, a shorter postoperative length of stay, and a lower rate of additional postoperative analgesia.

Endoscopic nasobiliary drainage-based saline-injection ultrasound: an imaging technique for remnant stone detection after retrograde cholangiopancreatography.

BACKGROUND: The purpose of this retrospective study aimed to assess the accuracy of detection of remnant common bile duct (CBD) stones by injecting saline through endoscopic nasobiliary drainage (ENBD) tubes under transabdominal ultrasound (US) guidance. METHOD: Stone extraction and ENBD are regularly achieved through endoscopic retrograde cholangiopancreatography (ERCP) in patients with CBD stones. At 1-3  days thereafter, routine US studies were performed and repeated, using ENBD tubal saline injections (20-100  mL). RESULTS: A total of 302 patients underwent standard ERCP stone extractions in conjunction with occlusion cholangiograms, routine US testing, and ENBD-based saline-injection US exams. By occlusion cholangiogram, remnant stones were suspected in 31 (10.3%) patients in total of 302, and 26 (83.8%) were verified as true positives (sensitivity, 50.9%; specificity, 98.0%). Routine US studies proved suspicious in 13 (4.3%) patients in total of 302, and 12 (92.3%) were verified as true positives (sensitivity, 23.5%; specificity, 99.6%). Using ENBD-based saline-injection US, suspected stones were identified in 50 (16.6%) patients in total of 302, and 46 (92%) were verified as true positives (sensitivity, 90.1%; specificity, 98.4%). The sensitivity of ENBD-based saline-injection US significantly surpassed that of occlusion cholangiogram (p < 0.001) and routine US (p < 0.001). CONCLUSION: Detection of remnant CBD stones via ENBD-based saline-injection US is a valid, inexpensive, and repeatable means of patient screening that is non-invasive, radiation-free, and dynamically informative. This may help improve the accuracy of detecting remnant CBD stones after ERCP.

Advances in the Study of Acute Acalculous Cholecystitis: A Comprehensive Review.

BACKGROUND: Acute acalculous cholecystitis (AAC) is characterized by acute necrotizing inflammation with no calculi and is diagnosed based on imaging, intraoperative, and pathological examinations. KEY MESSAGE: Although AAC has been studied clinically for a long time, it remains difficult to diagnose and treat. The pathogenesis of AAC is still not fully understood, and it is often regarded as a relatively independent clinical disease that is different from acute calculous cholecystitis (ACC). Pathological studies suggest that AAC is the manifestation of a critical systemic disease, while ACC is a local disease of the gallbladder. SUMMARY: Concerning the pathogenesis, diagnosis, and treatment of AAC, we reviewed the research progress of AAC, which will enhance the understanding of the early diagnosis and treatment of AAC.

Role of caveolin-1 in human organ function and disease: friend or foe?

Caveolin-1 (Cav-1) is a structural protein component of caveolae, which are invaginations of the plasma membrane involved in various cellular processes, including endocytosis, extracellular matrix organization, cholesterol distribution, cell migration and signaling. Mounting evidence over the last 10-15 years has demonstrated a central role of Cav-1 in many diseases, such as cancer, diabetes and fibrosis. Cav-1 plays positive and negative roles in various diseases through its different regulation pathways. Here, we review the current knowledge on Cav-1 in different diseases and discuss the role of this protein in human organs and diseases.

MUC2 and related bacterial factors: Therapeutic targets for ulcerative colitis.

The mucin2 (MUC2) mucus barrier acts as the first barrier that prevents direct contact between intestinal bacteria and colonic epithelial cells. Bacterial factors related to the MUC2 mucus barrier play important roles in the response to changes in dietary patterns, MUC2 mucus barrier dysfunction, contact stimulation with colonic epithelial cells, and mucosal and submucosal inflammation during the occurrence and development of ulcerative colitis (UC). In this review, these underlying mechanisms are summarized and updated, and related interventions for treating UC, such as dietary adjustment, exogenous repair of the mucus barrier, microbiota transplantation and targeted elimination of pathogenic bacteria, are suggested. Such interventions are likely to induce and maintain a long and stable remission period and reduce or even avoid the recurrence of UC. A better mechanistic understanding of the MUC2 mucus barrier and its related bacterial factors may help researchers and clinicians to develop novel approaches for treating UC.

Role of Forkhead Box O Proteins in Hepatocellular Carcinoma Biology and Progression (Review).

Hepatocellular carcinoma (HCC), the most common type of malignant tumor of the digestive system, is associated with high morbidity and mortality. The main treatment for HCC is surgical resection. Advanced disease, recurrence, and metastasis are the main factors affecting prognosis. Chemotherapy and radiotherapy are not sufficiently efficacious for the treatment of primary and metastatic HCC; therefore, optimizing targeted therapy is essential for improving outcomes. Forkhead box O (FOXO) proteins are widely expressed in cells and function to integrate a variety of growth factors, oxidative stress signals, and other stimulatory signals, thereby inducing the specific expression of downstream signal factors and regulation of the cell cycle, senescence, apoptosis, oxidative stress, HCC development, and chemotherapy sensitivity. Accordingly, FOXO proteins are considered multifunctional targets of cancer treatment. The current review discusses the roles of FOXO proteins, particularly FOXO1, FOXO3, FOXO4, and FOXO6, in HCC and establishes a theoretical basis for the potential targeted therapy of HCC.

Cholesterol gallstones: Focusing on the role of interstitial Cajal-like cells.

Cholesterol gallstone (CG) is a common, frequent biliary system disease in China, 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.

Biliary Microbiota in Choledocholithiasis and Correlation With Duodenal Microbiota.

Background: The pathogenesis of choledocholithiasis is closely related to the role of bacteria. However, little is known about the predictive role of bile bacteria in clinical conditions of patients and the compositional and functional characteristics of biliary microbiota in choledocholithiasis. Methods: To investigate the predictive value of biliary bacteria, clinical data of 488 patients with choledocholithiasis were collected. The predictive value of common bile bacteria to patients' clinical conditions was analyzed by logistic regression. Samples of bile and corresponding duodenal juice from 10 selected patients with choledocholithiasis were obtained, and the composition and function of microbial communities were analyzed based on 16S rRNA sequencing and Tax4Fun. Results: The clinical conditions of patients with choledocholithiasis, such as recurrence, the severity of acute cholangitis, and duration of hospital stay were closely related to different species of bile bacteria as well as antimicrobial-resistant bacteria. Employing 16S rRNA sequencing, the dominant phyla of biliary and duodenal microbiota were Proteobacteria and Firmicutes. The top three core microbiota at the genus level were Escherichia-Shigella, Fusobacterium, and Enterococcus. Escherichia coli accounted for the most abundant annotated species in both. Differences in composition between biliary and duodenal microbiota were not significant according to the alpha and beta diversities. Differential abundant features were not found in biliary microbiota indicated by A linear discriminant analysis effective size algorithm. The major pathways identified in biliary and duodenal microbiota were related to membrane transport, translation, replication and repair, carbohydrate and amino acid metabolism. However, no significant difference in those major pathways, as well as antimicrobial-resistance patterns, was observed between biliary and duodenal microbiota. Conclusion: Our study first demonstrates the predictive contribution of biliary bacteria to the clinical conditions of patients with choledocholithiasis, and then it offers new insights into the compositional and functional features of biliary and duodenal microbiota. Similarities between biliary and duodenal microbiota support the theory of bacterial duodenal-biliary reflux in patients with choledocholithiasis. Meanwhile, when it is impracticable to obtain a bile sample, duodenal juice may be used as an alternative for bacterial culture and susceptibility tests.

Diagnosis and Treatment of Male Accessory Breast Cancer: A Comprehensive Systematic Review.

BACKGROUND: Accessory breast cancer is extremely rare, especially in male patients, and only a few cases have been reported in the literature. To date, no specific guidelines regarding its diagnosis and treatment are available. OBJECTIVES: This study aimed to investigate the guidelines for the diagnosis and treatment of male accessory breast cancer by reviewing the available literature on this disease. METHODS: The Web of Science, Cochrane, PubMed, and CNKI databases were systematically searched (last search: 30 November 2020) to identify studies on male axillary accessory breast cancer. The following data were extracted: author names, number of patients, country, patient age, tumor location, tumor size, pathologic diagnosis, and treatment. RESULTS: There were 16 studies included (6 in Chinese and 10 in English), corresponding to 16 cases of male axillary accessory breast cancer. Primary surgical resection is currently the main procedure, followed by comprehensive treatment including chemotherapy, radiotherapy, and endocrine therapy. Patient age ranged from 51-87 years, and the average age was 67.1 years. The main clinical features of the patients were pain, the portion of the skin covering the mass was either reddish or purplish, and the mass could show swelling and erosion on the surface, with purulent exudate. CONCLUSIONS: Once male accessory breast cancer is diagnosed, we can follow the latest guidelines for the diagnosis and treatment of breast cancer. Tumor biopsy and resection seems the treatment of first choice, combined with comprehensive treatment including chemotherapy, radiotherapy, and endocrine therapy.

Regulatory mechanisms of the bile salt export pump (BSEP/ABCB11) and its role in related diseases.

The bile salt export pump (BSEP/ABCB11) is located on the apical membrane and mediates the secretion of bile salts from hepatocytes into the bile. BSEP-mediated bile salt efflux is the rate-limiting step of bile salt secretion and the main driving force of bile flow. BSEP drives and maintains the enterohepatic circulation of bile salts. In recent years, research efforts have been focused on understanding the physiological and pathological functions and regulatory mechanisms of BSEP. These studies elucidated the roles of farnesoid X receptor (FXR), AMP-activated protein kinase (AMPK), liver receptor homolog-1(LRH-1) and nuclear factor erythroid 2-related factor 2 (Nrf-2) in BSEP expression and discovered some regulatory factors which participate in its post-transcriptional regulation. A series of liver diseases have also been shown to be related to BSEP expression and dysfunction, such as cholestasis, drug-induced liver injury, and gallstones. Here, we systematically review and summarize recent literature on BSEP structure, physiological functions, regulatory mechanisms, and related diseases.