The Efficacy of Chaihu-Guizhi-Ganjiang Decoction on Chronic Non-Atrophic Gastritis with Gallbladder Heat and Spleen Cold Syndrome and Its Metabolomic Analysis: An Observational Controlled Before-After Clinical Trial.

Purpose: The aim of this study was to verify the effectiveness and explore the mechanism of Chaihu-Guizhi-Ganjiang decoction (CGGD) in the treatment of chronic non-atrophic gastritis (CNAG) with gallbladder heat and spleen cold syndrome (GHSC) by metabolomics based on UHPLC-Q-TOF/MS. Patients and Methods: An observational controlled before-after study was conducted to verify the effectiveness of CGGD in the treatment of CNAG with GHSC from January to June 2023, enrolling 27 patients, who took CGGD for 28 days. 30 healthy volunteers were enrolled as the controls. The efficacy was evaluated by comparing the traditional Chinese medicine (TCM) syndrome and CNAG scores, and clinical parameters before and after treatment. The plasma levels of hormones related to gastrointestinal function were collected by ELISA. The mechanisms of CGGD in the treatment of CNAG with GHSC were explored using a metabolomic approach based on UHPLC-Q-TOF/MS. Results: Patients treated with CGGD experienced a statistically significant improvement in TCM syndrome and CNAG scores (p < 0.01). CGGD treatment evoked the concentration alteration of 15 biomarkers, which were enriched in the glycerophospholipid metabolism, and branched-chain amino acids biosynthesis pathways. Moreover, CGGD treatment attenuated the abnormalities of the gastrointestinal hormone levels and significantly increased the pepsinogen level. Conclusion: It was the first time that this clinical trial presented detailed data on the clinical parameters that demonstrated the effectiveness of CGGD in the treatment of CNAG with GHSC patients. This study also provided supportive evidence that CNAG with GHSC patients were associated with disturbed branched-chain amino acid metabolism and glycerophospholipid levels, suggesting that CNAG treatment based on TCM syndrome scores was reasonable and also provided a potential pharmacological mechanism of action of CGGD.

Application of Data Mining Technology in the Screening for Gallbladder Stones: A Cross-Sectional Retrospective Study of Chinese Adults.

PURPOSE: The purpose of this study was to use data mining methods to establish a simple and reliable predictive model based on the risk factors related to gallbladder stones (GS) to assist in their diagnosis and reduce medical costs. MATERIALS AND METHODS: This was a retrospective cross-sectional study. A total of 4215 participants underwent annual health examinations between January 2019 and December 2019 at the Physical Examination Center of Shengjing Hospital Affiliated to China Medical University. After rigorous data screening, the records of 2105 medical examiners were included for the construction of J48, multilayer perceptron (MLP), Bayes Net, and Naïve Bayes algorithms. A ten-fold cross-validation method was used to verify the recognition model and determine the best classification algorithm for GS. RESULTS: The performance of these models was evaluated using metrics of accuracy, precision, recall, F-measure, and area under the receiver operating characteristic curve. Comparison of the F-measure for each algorithm revealed that the F-measure values for MLP and J48 (0.867 and 0.858, respectively) were not statistically significantly different (p>0.05), although they were significantly higher than the F-measure values for Bayes Net and Naïve Bayes (0.824 and 0.831, respectively; p<0.05). CONCLUSION: The results of this study showed that MLP and J48 algorithms are effective at screening individuals for the risk of GS. The key attributes of data mining can further promote the prevention of GS through targeted community intervention, improve the outcome of GS, and reduce the burden on the medical system.

Early host immune responses in a human organoid-derived gallbladder monolayer to Salmonella Typhi strains from patients with acute and chronic infections: a comparative analysis.

Salmonella enterica serovar Typhi (S. Typhi), a human-restricted pathogen, invades the host through the gut to cause typhoid fever. Recent calculations of the typhoid fever burden estimated that more than 10 million new typhoid fever cases occur in low and middle-income countries, resulting in 65,400-187,700 deaths yearly. Interestingly, if not antibiotic-treated, upon the resolution of acute disease, 1%-5% of patients become asymptomatic chronic carriers. Chronically infected hosts are not only critical reservoirs of infection that transmit the disease to naive individuals but are also predisposed to developing gallbladder carcinoma. Nevertheless, the molecular mechanisms involved in the early interactions between gallbladder epithelial cells and S. Typhi remain largely unknown. Based on our previous studies showing that closely related S. Typhi strains elicit distinct innate immune responses, we hypothesized that host molecular pathways activated by S. Typhi strains derived from acutely and chronically infected patients would differ. To test this hypothesis, we used a novel human organoid-derived polarized gallbladder monolayer model, and S. Typhi strains derived from acutely and chronically infected patients. We found that S. Typhi strains derived from acutely and chronically infected patients differentially regulate host mitogen-activated protein kinase (MAPK) and S6 transcription factors. These variations might be attributed to differential cytokine signaling, predominantly via TNF-α and IL-6 production and appear to be influenced by the duration the isolate was subjected to selective pressures in the gallbladder. These findings represent a significant leap in understanding the complexities behind chronic S. Typhi infections in the gallbladder and may uncover potential intervention targets.

Colesevelam has no acute effect on postprandial GLP-1 levels but abolishes gallbladder refilling.

OBJECTIVE: Colesevelam, a bile acid sequestrant approved for the treatment of hypercholesterolaemia, improves glycaemic control in type 2 diabetes. We hypothesised that single-dose colesevelam increases postprandial GLP-1 secretion, thus, reducing postprandial glucose excursions in individuals with type 2 diabetes. Further, we explored the effects of single-dose colesevelam on ultrasonography-assessed postprandial gallbladder motility, paracetamol absorption (proxy for gastric emptying), and circulating factors known to affect gallbladder motility. METHODS: In a randomised, double-blind, placebo-controlled crossover study, 12 individuals with type 2 diabetes (mean ± SD: age 61 ± 8.8 years; body mass index 29.8 ± 3.0 kg/m2) were subjected to 4 mixed meal tests on separate days; 2 with orally administered colesevelam (3.75 g) and 2 with placebo, with intravenous infusion of the GLP-1 receptor antagonist exendin(9-39)NH2 or saline. RESULTS: Single-dose colesevelam had no effect on postprandial concentrations of glucose (P = .786), C-peptide (P = .440), or GLP-1 (P = .729), and exendin(9-39)NH2 administration revealed no GLP-1-mediated effects of colesevelam. Colesevelam did not affect gallbladder emptying but abolished gallbladder refilling (P = .001), increased postprandial cholecystokinin (CCK) secretion (P = .010), and decreased postprandial serum concentrations of fibroblast growth factor 19 (FGF19) (P = .035) and bile acids (P = .043). CONCLUSION: Single-dose colesevelam had no effect on postprandial GLP-1 responses or glucose tolerance but disrupted postprandial gallbladder refilling by increasing CCK secretion and reducing circulating concentrations of FGF19 and bile acids. These findings leave the antidiabetic actions of colesevelam unresolved but provide mechanistic insights into its effect on gallbladder motility.

Gallbladder carcinoid in a cat.

Carcinoids are rare tumors that originate from neuroendocrine system cells. There has apparently only been 1 report in the veterinary medical literature of a cat with a gallbladder carcinoid, with no long-term follow-up information available from that case. Furthermore, apparently only 9 dogs with gallbladder carcinoids have been reported, again with no long-term follow-up. This case report describes the clinical presentation, surgical appearance, histopathologic and immunohistochemical findings, postoperative adjuvant chemotherapy treatment, and long-term outcome of a domestic longhair cat with a gallbladder carcinoid. The diagnosis of a gallbladder carcinoid in the present case was based on histologic and immunohistochemical findings. Clinical signs of a gallbladder carcinoid are nonspecific and ultrasonographic findings may not be definitive; however, it should be considered as a potential differential diagnosis in cats with lesions of the gallbladder or in the region of the gallbladder. The prognosis is poor, with a potentially high metastatic rate. In the present case, metastasis occurred 7 mo postoperatively despite adjuvant therapy, and the survival time was only 10 mo from the time of diagnosis. Key clinical message: This case report describes the clinical presentation, surgical appearance, histopathologic and immunohistochemical findings, postoperative adjuvant treatment, and long-term outcome of a cat with a gallbladder carcinoid, which should be considered as a potential differential diagnosis in cats with lesions of the gallbladder or in the region of the gallbladder.

Carcinoïde de la vésicule biliaire chez un chat. Les carcinoïdes sont des tumeurs rares qui prennent leur origine des cellules du système neuroendocrinien. Dans la littérature médicale vétérinaire il n'y aurait qu'un seul cas rapporté d'un chat avec un carcinoïde de la vésicule biliaire, sans aucune information de suivi à long terme disponible pour ce chat. Également, il y aurait 9 cas rapportés de chiens avec des carcinoïdes de la vésicule biliaire, mais encore là aucun suivi à long terme. Le cas présenté ici décrit la présentation clinique, l'apparence chirurgicale, les trouvailles histopathologiques et immunohistochimiques, le traitement post-opératoire par chimiothérapie adjuvante, et le devenir à long terme d'un chat domestique à poil court avec un carcinoïde de la vésicule biliaire. Dans le cas présent, le diagnostic de carcinoïde de la vésicule biliaire était basé sur les trouvailles histologiques et immunohistochimiques. Les signes cliniques d'un carcinoïde de la vésicule biliaire sont non-spécifiques et les trouvailles échographiques pourraient ne pas être concluantes; toutefois, il devrait être considéré comme un diagnostic différentiel possible chez des chats avec des lésions à la vésicule biliaire ou dans la région de la vésicule biliaire. Le pronostic est mauvais, avec un risque élevé de métastases. Dans le cas présent, des métastases sont apparues 7 mo post-chirurgie malgré une chimiothérapie adjuvante, et le temps de survie a été de 10 mo à compter du moment du diagnostic.Message clinique clé:Ce rapport de cas décrit la présentation clinique, l'apparence chirurgicale, les trouvaille histologiques et immunohistochimiques, la thérapie adjuvante postopératoire, et le résultat à long-terme pour un chat avec un carcinoïde de la vésicule biliaire, qui devrait être considéré comme un diagnostic différentiel potentiel chez les chats avec des lésions à la vésicule biliaire ou dans la région de la vésicule biliaire.(Traduit par Dr Serge Messier).

Analysis of the sonographic predictors of difficult laparoscopic cholecystectomy in symptomatic cholelithiasis.

BACKGROUND: Laparoscopic cholecystectomy (LC) is one of the most common laparoscopic procedures performed by young surgeons nowadays. Sometimes, LC could be challenging, especially for junior surgeons leading to serious complications. Therefore, this study aims to investigate the preoperative ultrasonographic features that could predict difficult LC. METHODS: In this prospective study, patients (n = 204) who underwent LC for symptomatic cholelithiasis from January 2020 to August 2022 were included. Preoperative parameters, including the ultrasonographic findings, were evaluated for their ability to predict difficult LC. RESULTS: The difficulty of LC was evaluated using two intraoperative scores. Among the ultrasonic parameters that were assessed preoperatively, thickened gallbladder (GB) wall, contracted GB, and impacted stone in the GB neck were associated with difficult LC. However, an impacted stone in the GB neck was the only independent predictor of difficult LC according to both difficulty scores in the multivariate analysis (odds ratio [OR] = 7.56, p = .001; OR = 8.42, p = .001). CONCLUSIONS: The impacted stone in the GB neck is an ultrasonographic sign of difficult LC. It should alert the surgeon for a more appropriate preoperative preparation, and the patient should be informed about the increased risk of complications, including conversion to open cholecystectomy.

Preoperative diagnostic criteria for scleroatrophic gallbladder: A systematic review protocol.

BACKGROUND: Although scleroatrophic gallbladder is a rare condition, it presents significant clinical challenges in diagnosis and management. More agreement is needed on this disorder's diagnostic criteria and optimal management approach. We will conduct a systematic review to summarise the scleroatrophic gallbladder's preoperative diagnostic criteria, including imaging modalities. METHODS: A systematic review will be undertaken using the PRISMA guidelines. The protocol has been registered in PROSPERO (CRD42024503701). We will search in Medline (via PubMed), Embase, SCOPUS, the Cochrane Library, and Web of Science to find original studies reporting about scleroatrophic gallbladder or synonymous. Two reviewers will independently screen the titles and abstracts following the eligibility criteria. We will include all types of studies that describe any diagnostic criteria or tools. After retrieving the full text of the selected studies, we will conduct a standardised data extraction. Finally, a narrative synthesis will be performed. The quality of the identified studies will be assessed using the Quality Assessment of Diagnostic Accuracy Studies- 2 tool. DISCUSSION: This systematic review will provide information on the preoperative diagnostic criteria of the scleroatrophic gallbladder and the value of imaging studies in its diagnosis. In addition, this work will aid doctors in the decision-making process for diagnosing scleroatrophic gallbladder and propose treatment approaches to this condition. SYSTEMATIC REVIEW REGISTRATION: The protocol has been registered in PROSPERO (CRD42024503701).

Bile salt hydrolase acyltransferase activity expands bile acid diversity.

Bile acids (BAs) are steroid detergents in bile that contribute to the absorption of fats and fat-soluble vitamins while shaping the gut microbiome because of their antimicrobial properties1-4. Here we identify the enzyme responsible for a mechanism of BA metabolism by the gut microbiota involving amino acid conjugation to the acyl-site of BAs, thus producing a diverse suite of microbially conjugated bile acids (MCBAs). We show that this transformation is mediated by acyltransferase activity of bile salt hydrolase (bile salt hydrolase/transferase, BSH/T). Clostridium perfringens BSH/T rapidly performed acyl transfer when provided various amino acids and taurocholate, glycocholate or cholate, with an optimum at pH 5.3. Amino acid conjugation by C. perfringens BSH/T was diverse, including all proteinaceous amino acids except proline and aspartate. MCBA production was widespread among gut bacteria, with strain-specific amino acid use. Species with similar BSH/T amino acid sequences had similar conjugation profiles and several bsh/t alleles correlated with increased conjugation diversity. Tertiary structure mapping of BSH/T followed by mutagenesis experiments showed that active site structure affects amino acid selectivity. These MCBA products had antimicrobial properties, where greater amino acid hydrophobicity showed greater antimicrobial activity. Inhibitory concentrations of MCBAs reached those measured natively in the mammalian gut. MCBAs fed to mice entered enterohepatic circulation, in which liver and gallbladder concentrations varied depending on the conjugated amino acid. Quantifying MCBAs in human faecal samples showed that they reach concentrations equal to or greater than secondary and primary BAs and were reduced after bariatric surgery, thus supporting MCBAs as a significant component of the BA pool that can be altered by changes in gastrointestinal physiology. In conclusion, the inherent acyltransferase activity of BSH/T greatly diversifies BA chemistry, creating a set of previously underappreciated metabolites with the potential to affect the microbiome and human health.

Ventriculo-gallbladder shunt: case series and literature review.

BACKGROUND: The ventriculoperitoneal shunt (VPS) is the gold-standard surgical technique to treat hypertensive hydrocephalus; however, it may fail in 20 to 70% of cases. The present study shows an alternative for patients with contraindications to VPS. METHODS: A case series of nine patients. The medical records of all patients under 17 years of age who underwent ventriculo-gallbladder (VGB) shunt at a pediatric hospital from January 2014 to October 2022 were reviewed. RESULTS: There were 6 (66.7%) males and 3 (33.3%) females. The average age of 73.6 months or 6.1 years at the time of surgery. They had undergone, on average, 5.1 VPS reviews before the VGB shunt. Five (55.5%) had complications of VGB shunt: infection (11.1%), atony (11.1%), hypodrainage (11.1%), and ventriculoenteric fistula (22.2%); all these patients got better at surgical reapproach, and in two of them, the VGB shunt was re-implanted. CONCLUSION: This case series shows a lower risk of death and a similar risk of complications compared to other alternative shunts. This article spotlighted VGB as a viable alternative when VPS fails or has contraindications.

Cytomorphology of metastatic dedifferentiated/undifferentiated melanoma to the gallbladder: A case report and review of literature.

Dedifferentiated/undifferentiated melanoma (DM/UM) is a distinct subtype of malignant melanoma that tends to lose all melanocytic markers of differentiation. DM/UM pose major diagnostic challenges as they could be easily confused with UM sarcoma or carcinoma, thus necessitating the use of molecular studies such as Next Generation Sequencing (NGS) for detecting melanoma-compatible mutations to confirm such diagnosis. The capability of performing NGS molecular studies on small biopsy material with confirmation of adequacy via rapid on-site evaluation (ROSE) has tremendous value in diagnosing DM/UM. Herein, we present the first reported case of metastatic DM/UM to the gall bladder arising in a 60-year-old female with a prior history of right knee melanoma. We also shed light on the cytomorphology of DM/UM, review the literature on such a challenging entity, and emphasize the crucial role of molecular testing in their diagnosis.