The presence of positive bile culture during intraoperative procedures has been associated with elevated morbidity and mortality rates in hepatobiliopancreatic surgeries, contributing to increased healthcare expenditures. However, the precise impact of bactobilia on the development of postoperative complications remains uncertain due to existing disparities in the published literature. In this retrospective cohort study, we assessed 137 patients who underwent major hepatobiliopancreatic surgery to examine the relationship between intraoperative bile culture outcomes and subsequent postoperative infectious complications. Among patients with bactobilia, a significant 35.1% exhibited systemic or local infectious complications, whereas only 11.1% of those with negative culture results experienced any infectious complications (p = 0.002). Similarly, a notable difference was observed in the incidence of surgical site infections, with 24.3% in the bactobilia group compared to 7.9% in the negative culture group (p = 0.01). A total of 74 monomicrobial cultures with microbiological growth were isolated, predominantly featuring Gram-negative microorganisms, primarily Enterobacteriaceae in 49 cultures. Escherichia coli was identified in 37.8% of positive cultures, while Klebsiella pneumoniae was evident in 21.6%. Gram-positive microorganisms were present in 10 cultures, with Enterococcus emerging as the prevailing species. The logistic regression model identified a positive bile culture as an independent factor significantly associated with infection development (OR: 2.26; 95% confidence interval: 1.23-11; p = 0.02). Considering the limitations of the study, these findings underscore the critical importance of conducting bile cultures during the intraoperative phase to enable vigilant monitoring and prompt management of infectious complications.

Scutellariae Radix extract is one of the important components in Shuganning Injection. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method was established for simultaneously determining five components in Shuganning Injection and Scutellariae Radix extract in bile, urine, and feces of rats, so as to reveal the difference in the excretion process of Shuganning Injection and Scutellariae Radix extract in rats and explore the law of the excretion process of the five components in vivo before and after the compatibility of Scutellariae Radix. Rats were injected with Shuganning Injection and Scutellariae Radix extract(4.2 mL·kg~(-1)), respectively, and the excretion of baicalin, baicalein, oroxylin A, oroxylin A-7-O-β-D-glucuronide, and scutellarin in bile, urine, and feces of rats in 24 h was observed. The results showed that except for baicalin, the other four index components were excreted as prototype components in a high proportion after intravenous injection of Shuganning Injection and Scutellariae Radix extract in rats, respectively. The excretion of each component was relatively high in urine and less in feces and bile. After the compatibility of Scutellariae Radix extract, the accumulative excretion of five index components in rats all decreased. Among them, the cumulative excretion of baicalein in bile, urine, and feces significantly decreased by 26.67%, 48.11%, and 31.01%. The cumulative excretion of baicalin in bile, urine, and feces decreased significantly by 70.69%, 19.43%, and 31.22%. The result showed that the five index components in Scutellariae Radix extract were mainly excreted by the kidneys, and other components in Shuganning Injection delayed the excretion process and prolonged the residence time. This study is of great significance for elucidating the compatibility rationality of Shuganning Injection.

Lectins are carbohydrate-binding proteins with specific affinity to glycoconjugates expressed in various tissues. Lectins are of substantial utility as research, histochemical, and diagnostic tools in mammalian systems. Reactivity of 12 commonly used plant-based lectins was studied in zebrafish liver. Four lectins, tomato lectin (TL), wheat germ agglutinin, concanavalin A, and Jacalin showed strong reactivity to hepatic parenchymal structures. Importantly, TL reacted to glycoconjugates within segments of the larval and adult intrahepatic biliary network, from canaliculi to bile ducts. We provide evidence that lectins can serve as important histochemical tools to investigate the structural and functional characteristics of the zebrafish liver.

BACKGROUND: Perforation is one of the most serious complications of endoscopic retrograde cholangiopancreatography (ERCP). Conventional nonsurgical endoscopic treatments including intravenous antibiotic administration and plastic endoscopic biliary drainage are generally approved for the treatment of ERCP-related Stapfer type II perforation (perivaterian type). Biliary covered metal stent placement has recently been reported to have favorable outcomes in ERCP-related Stapfer type II perforations. We aimed to compare the outcomes of conventional endoscopic bile drainage and biliary covered self-expandable metal stent (SEMS) insertion in patients with Stapfer type II perforation.
METHODS: Medical records of patients who underwent ERCP at Kyungpook National University Hospital in Daegu from 2011 to 2022 were retrospectively reviewed.
RESULTS: A total of 8,402 ERCP procedures were performed in our hospital. Sixty-six ERCP-related perforations (0.78%) were identified. Among them, 37 patients (56.1%) who had Stapfer type II perforations were enrolled. Thirteen and twenty-four patients received biliary covered SEMS insertion and conventional endoscopic bile drainage treatments, respectively. No significant differences were observed in the clinical success rate (92.3% vs. 91.7%, p = 1.000), hospital stay (9.46 ± 5.97 vs. 13.9 ± 13.2 days, p = 0.258), and post-ERCP-related fasting time (5.4 ± 3.4 vs 4.3 ± 3.0 days, p = 0.305). Complications including bleeding, post-ERCP pancreatitis, fever, and death were not significantly different between the two groups. The conventional endoscopic bile drainage group took less time for ERCP than the SEMS group (11.5 ± 5.2 vs. 18.5 ± 11.2 min, p = 0.013).
CONCLUSIONS: Compared with the conventional endoscopic bile drainage treatment method, biliary covered SEMS did not improve patient outcomes in ERCP-related Stapfer type II perforations.

OBJECTIVE: To investigate the digestive enzymes and biomarkers in the saliva of patients with laryngopharyngeal reflux (LPR) and asymptomatic individuals.
METHODS: Prospective controlled study.
METHODS: Multicenter study.
METHODS: Patients with LPR at the hypopharyngeal-esophageal impedance-pH monitoring (HEMII-pH) and asymptomatic individuals were consecutively recruited from January 2020 to April 2023 from 2 University Hospitals. The saliva of patients (off PPIs) and asymptomatic individuals was collected to measure pH, elastase, bile salts, cholesterol, gastric, and pancreatic lipases. Anxiety, symptoms, and findings were studied through perceived stress scale (PSS), reflux symptom score (RSS), and reflux sign assessment (RSA).
RESULTS: Sixty-seven LPR patients and 57 asymptomatic individuals completed the evaluations. LPR patients reported higher PSS, RSS, and RSA than asymptomatic individuals. The mean saliva pH was more alkaline in LPR patients (7.23: 95% confidence interval [CI]: 7.08, 7.38) compared to controls (6.13; 95% CI: 5.95, 6.31; P = .001). The mean concentration of elastase was higher in patients (51.65 µg/mL; 95% CI: 44.47, 58.83 µg/mL) versus asymptomatic individuals (25.18 µg/mL; 95% CI: 21.64, 28.72 µg/mL; P = .001). The saliva cholesterol reported higher concentration in healthy individuals (3.43 mg/dL; 95% CI: 3.21, 3.65 mg/dL) compared to patients (1.16 mg/dL; 95% CI: 1.05, 1.27 mg/dL; P = .001). The saliva pH, and elastase concentration were significantly associated with the baseline RSS, while saliva cholesterol was negatively associated with the severity of RSS and RSA.
CONCLUSIONS: Cholesterol, bile salts, and elastase are biomarkers of LPR and should be considered to develop future non-invasive saliva device for the detection of LPR.

Endoscopic Retrograde Cholangio-Pancreatography (ERCP) with biliary stenting is a minimally invasive medical procedure employed to address both malignant and benign obstructions within the biliary tract. Benign biliary strictures (BBSs), typically arising from surgical interventions such as liver transplants and cholecystectomy, as well as chronic inflammatory conditions, present a common clinical challenge. The current gold standard for treating BBSs involves the periodic insertion of plastic stents at intervals of 3-4 months, spanning a course of approximately one year. Unfortunately, stent occlusion emerges as a prevalent issue within this treatment paradigm, leading to the recurrence of symptoms and necessitating repeated ERCPs. In response to this clinical concern, we initiated a pilot study, delving into the microbial composition present in bile and on the inner surfaces of plastic stents. This investigation encompassed 22 patients afflicted by BBSs who had previously undergone ERCP with plastic stent placement. Our preliminary findings offered promising insights into the microbial culprits behind stent occlusion, with Enterobacter and Lactobacillus spp. standing out as prominent bacterial species known for their biofilm-forming tendencies on stent surfaces. These revelations hold promise for potential interventions, including targeted antimicrobial therapies aimed at curtailing bacterial growth on stents and the development of advanced stent materials boasting anti-biofilm properties.

Secondary bile acids (SBAs), the products of bacterial metabolism, are ligands of the nuclear farnesoid X receptor (FXR) and have been implicated in cardiovascular health. Diet can modulate gut microbiota composition and bile acid metabolism.
We aimed to examine the associations of circulating SBAs and their receptor polymorphisms with the risk of incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D).
A total of 1234 participants with newly diagnosed T2D without CVD or cancer were included from the Dongfeng-Tongji Cohort study in China. Circulating SBAs and their conjugated forms were quantified using liquid chromatography-tandem mass spectrometry. Fifteen single-nucleotide polymorphisms in genes encoding bile acid receptors were genotyped.
During a median follow-up of 5.7 y, 259 incident CVD cases were documented. After multivariable adjustment, higher levels of unconjugated SBAs [sum of deoxycholic acid (DCA), lithocholic acid, and ursodeoxycholic acid] and DCA were significantly associated with a higher risk of CVD among people with T2D, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.62 (1.12, 2.35) and 1.46 (1.04, 2.06) comparing the extreme quartile of SBAs and DCA, respectively. Restricted cubic spline regression suggested a linear relationship of unconjugated SBAs and DCA with an elevated risk of CVD, and per standard deviation, an increment in natural log-transformed unconjugated SBAs and DCA was associated with an 18% (95% CI: 4%, 34%) and 16% (95% CI: 2%, 33%) higher risk of CVD, respectively. Moreover, genetic variants in FXR (rs56163822 TT compared with GG, and rs17030295 TT compared with CC) were significantly associated with a 121%-129% higher risk of CVD among individuals with T2D.
A higher proportion of unconjugated SBAs, especially DCA, is linearly associated with a higher risk of CVD among people with newly diagnosed T2D. Our findings support the potential role of gut microbiota-derived SBAs in cardiovascular health in individuals with T2D.

Flonoltinib Maleate (FM) is a dual-target inhibitor that selectively suppresses Janus kinase 2/FMS-like tyrosine kinase 3 (JAK2/FLT3), which is currently in phase I/IIa clinical trial in China for the treatment of myeloproliferative neoplasms (MPNs). In this research, we used [14C]-labeled FM (14C-FM) to investigate the distribution, metabolism, and excretion of FM in rats using High-Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry/Radioactivity Monitoring (HPLC-HRMS/RAM) and liquid scintillation counter. The results revealed that FM displayed widespread distribution in rats. Furthermore, FM demonstrated rapid clearance without any observed risk of organ toxicity attributed to accumulation. Profiling of FM metabolites in rat plasma, feces, urine, and bile identified a total of 17 distinct metabolites, comprising 7 phase I metabolites and 10 phase II metabolites. The major metabolic reactions involved oxygenation, dealkylation, methylation, sulfation, glucuronidation and glutathione conjugation. Based on these findings, a putative metabolic pathway of FM in rats was proposed. The overall recovery rate in the excretion experiment ranged from 93.04 % to 94.74 %. The results indicated that FM undergoes extensive hepatic metabolism in SD rats, with the majority being excreted through bile as metabolites and ultimately eliminated via feces. A minor fraction of FM (<10 %) was excreted through renal excretion in the form of urine. Integration of the current results with previous pharmacokinetic investigations of FM in rats and dogs enables a comprehensive elucidation of the in vivo ADME processes and characteristics of FM, thereby establishing a solid foundation for subsequent clinical investigations of FM.

BACKGROUND: The relationship between adenomyomatous hyperplasia of the Vaterian system(AV) and cancer is unclear, some reports suggest that AV is often combined with mucosal glandular dysplasia, but it is not clear whether mucosal glandular dysplasia is a risk factor for carcinogenesis of AV. The aim of this study was to retrospective analysis of role of ductal glandular dysplasia as a risk factor in the development of carcinoma in AV.
METHODS: A total of 328 cases who underwent surgery with a final pathological diagnosis of adenomyomatous hyperplasia (AH) in the Chinese PLA General Hospital in BeiJing, China, between January 2005 and December 2021 were retrospectively collected. There were Seventeen cases(5%) in which the lesions were located in the common bile duct as well as the ampulla of Vater, and their clinical (age, sex, etc.), imaging (cholelithiasis, etc.) and pathological data (mucosal glandular dysplasia, etc.) were collected. Clinical data and pathological features of AV with or without mucosal glandular dysplasia were analyzed.
RESULTS: There were 17 out of 328 cases of AH occurring in the Vaterian system (5%). Three of seventeen AV cases were associated with carcinoma (18%). Of three cases, two (12%) with the tumor lesions in the mucosal glands adjacent to the AH (biliary tract cancer and ampullary cancer), and one (6%) with carcinoma developed from AH itself in the ampulla of Vater. All carcinomas had adenomyomatous hyperplasia with nearby mucosal glandular dysplasia (MGD). The percentage of BTC or AC was higher in patients with concurrent AH and MGD compared to AH patients without MGD. The results show tendency toward statistical significance (P = 0.082). This difference was more obvious among AH with severe dysplasia compared to adenomyomatous hyperplasia with mild-moderate dysplasia (P = 0.018).
CONCLUSIONS: This study is the first to find that AV is associated with biliary tract cancer and ampullary cancer. In AV, the mucosal glandular dysplasia may be a risk factor for the development of malignancy. The underlying mechanism for carcinogenesis of AV could be AH itself or its secretions stimulating mucosal glands hyperplasia, then mucosal glands dysplasia. AV may be a precancerous lesion.

Pancreatic ductal adenocarcinoma (PDAC) has a very poor survival. The intra-tumoural microbiome can influence pancreatic tumourigenesis and chemoresistance and, therefore, patient survival. The role played by bile microbiota in PDAC is unknown. We aimed to define bile microbiome signatures that can effectively distinguish malignant from benign tumours in patients presenting with obstructive jaundice caused by benign and malignant pancreaticobiliary disease. Prospective bile samples were obtained from 31 patients who underwent either Endoscopic Retrograde Cholangiopancreatography (ERCP) or Percutaneous Transhepatic Cholangiogram (PTC). Variable regions (V3-V4) of the 16S rRNA genes of microorganisms present in the samples were amplified by Polymerase Chain Reaction (PCR) and sequenced. The cohort consisted of 12 PDAC, 10 choledocholithiasis, seven gallstone pancreatitis and two primary sclerosing cholangitis patients. Using the 16S rRNA method, we identified a total of 135 genera from 29 individuals (12 PDAC and 17 benign). The bile microbial beta diversity significantly differed between patients with PDAC vs. benign disease (Permanova p = 0.0173). The separation of PDAC from benign samples is clearly seen through unsupervised clustering of Aitchison distance. We found three genera to be of significantly lower abundance among PDAC samples vs. benign, adjusting for false discovery rate (FDR). These were Escherichia (FDR = 0.002) and two unclassified genera, one from Proteobacteria (FDR = 0.002) and one from Enterobacteriaceae (FDR = 0.011). In the same samples, the genus Streptococcus (FDR = 0.033) was found to be of increased abundance in the PDAC group. We show that patients with obstructive jaundice caused by PDAC have an altered microbiome composition in the bile compared to those with benign disease. These bile-based microbes could be developed into potential diagnostic and prognostic biomarkers for PDAC and warrant further investigation.