-
Hepatology Communications Jul 2024The incidence of gallbladder diseases is as high as 20%, but whether gallbladder diseases contribute to hepatic disorders remains unknown.
BACKGROUND
The incidence of gallbladder diseases is as high as 20%, but whether gallbladder diseases contribute to hepatic disorders remains unknown.
METHODS
Here, we established an animal model of gallbladder dysfunction and assessed the role of a diseased gallbladder in cholestasis-induced hepatic fibrosis (CIHF).
RESULTS
Mice with smooth muscle-specific deletion of Mypt1, the gene encoding the main regulatory subunit of myosin light chain phosphatase (myosin phosphatase target subunit 1 [MYPT1]), had apparent dysfunction of gallbladder motility. This dysfunction was evidenced by abnormal contractile responses, namely, inhibited cholecystokinin 8-mediated contraction and nitric oxide-resistant relaxation. As a consequence, the gallbladder displayed impaired bile filling and biliary tract dilation comparable to the alterations in CIHF. Interestingly, the mutant animals also displayed CIHF features, including necrotic loci by the age of 1 month and subsequently exhibited progressive fibrosis and hyperplastic/dilated bile ducts. This pathological progression was similar to the phenotypes of the animal model with bile duct ligation and patients with CIHF. The characteristic biomarker of CIHF, serum alkaline phosphatase activity, was also elevated in the mice. Moreover, we observed that the myosin phosphatase target subunit 1 protein level was able to be regulated by several reagents, including lipopolysaccharide, exemplifying the risk factors for gallbladder dysfunction and hence CIHF.
CONCLUSIONS
We propose that gallbladder dysfunction caused by myosin phosphatase target subunit 1 ablation is sufficient to induce CIHF in mice, resulting in impairment of the bile transport system.
Topics: Animals; Myosin-Light-Chain Phosphatase; Mice; Disease Models, Animal; Liver Cirrhosis; Cholestasis; Gallbladder Diseases; Gallbladder; Male; Mice, Knockout
PubMed: 38934703
DOI: 10.1097/HC9.0000000000000473 -
MSystems Jun 2024Cholestasis is a common morbid state that may occur in different phases; however, a comprehensive evaluation of the long-term effect post-recovery is still lacking. In...
UNLABELLED
Cholestasis is a common morbid state that may occur in different phases; however, a comprehensive evaluation of the long-term effect post-recovery is still lacking. In the hepatic cholestasis mouse model, which was induced by a temporary complete blockage of the bile duct, the stasis of bile acids and liver damage typically recovered within a short period. However, we found that the temporary hepatic cholestasis had a long-term effect on gut microbiota dysbiosis, including overgrowth of small intestinal bacteria, decreased diversity of the gut microbiota, and an overall imbalance in its composition accompanied by an elevated inflammation level. Additionally, we observed an increase in (represented by ASV136078), rich in virulence factors, in both small and large intestines following cholestasis. To confirm the causal role of dysregulated gut microbiota in promoting hepatic inflammation and injury, we conducted gut microbiota transplantation into germ-free mice. We found that recipient mice transplanted with feces from cholestasis mice exhibited liver inflammation, damage, and accumulation of hepatic bile acids. In conclusion, our study demonstrates that cholestasis disrupts the overall load and structural composition of the gut microbiota in mice, and these adverse effects persist after recovery from cholestatic liver injury. This finding suggests the importance of monitoring the structural composition of the gut microbiota in patients with cholestasis and during their recovery.
IMPORTANCE
Our pre-clinical study using a mouse model of cholestasis underscores that cholestasis not only disrupts the equilibrium and structural configuration of the gut microbiota but also emphasizes the persistence of these adverse effects even after bile stasis restoration. This suggests the need of monitoring and initiating interventions for gut microbiota structural restoration in patients with cholestasis during and after recovery. We believe that our study contributes to novel and better understanding of the intricate interplay among bile acid homeostasis, gut microbiota, and cholestasis-associated complications. Our pre-clinical findings may provide implications for the clinical management of patients with cholestasis.
PubMed: 38934542
DOI: 10.1128/msystems.00127-24 -
Tidsskrift For Den Norske Laegeforening... Jun 2024Vulvar leiomyoma is rare and is often misdiagnosed as a cyst or abscess in the Bartholin's glands. Other causes of benign tumours of the vulva are Gartner's duct cysts,...
Vulvar leiomyoma is rare and is often misdiagnosed as a cyst or abscess in the Bartholin's glands. Other causes of benign tumours of the vulva are Gartner's duct cysts, fibromas, fibroadenomas, lipomas and hamartomas. Adenoma was the tentative diagnosis is this case history, but the histology showed a benign leiomyoma.
Topics: Humans; Female; Vulvar Neoplasms; Leiomyoma; Adult; Middle Aged; Diagnosis, Differential
PubMed: 38934324
DOI: 10.4045/tidsskr.23.0818 -
Medicina (Kaunas, Lithuania) May 2024Hepatobiliary ascariasis is caused by the entry of the nematode from the duodenum into the biliary duct. We report a case of an -induced extrahepatic biliary tract... (Review)
Review
Hepatobiliary ascariasis is caused by the entry of the nematode from the duodenum into the biliary duct. We report a case of an -induced extrahepatic biliary tract obstruction in a pediatric patient admitted to the hospital due to a wide spectrum of symptoms of biliary disease, which included abdominal pain in the upper abdominal quadrants, vomiting, and jaundice. Imaging tests-including ultrasound, magnetic resonance cholangiopancreatography (MRCP), and endoscopic retrograde cholangiopancreatography (ERCP)-were performed to confirm the diagnosis of biliary ascariasis. The tests did, in fact, demonstrate signs of this disease. Nevertheless, during the ERCP, only the remains of parasites in the form of tissue fragments were extracted. We also aim to discuss the prevalence of ascariasis in children, the causes of migration of parasites into the bile ducts, together with its clinical manifestations, as well as the diagnostic and treatment methods of this disease.
Topics: Humans; Ascariasis; Lithuania; Cholangiopancreatography, Endoscopic Retrograde; Child; Animals; Male; Ascaris lumbricoides; Cholangiopancreatography, Magnetic Resonance; Female
PubMed: 38929533
DOI: 10.3390/medicina60060916 -
Animals : An Open Access Journal From... Jun 2024Yanshan Cashmere bucks are seasonal breeding animals and an important national genetic resource. This study aimed to investigate the involvement of prolactin (PRL) in...
Yanshan Cashmere bucks are seasonal breeding animals and an important national genetic resource. This study aimed to investigate the involvement of prolactin (PRL) in the epididymal function of bucks. Twenty eleven-month-old Cashmere bucks were randomly divided into a control (CON) group and a bromocriptine (BCR, a prolactin inhibitor, 0.06 mg/kg body weight (BW)) treatment group. The experiment was conducted from September to October 2020 in Qinhuangdao City, China, and lasted for 30 days. Blood was collected on the last day before the BCR treatment (day 0) and on the 15th and 30th days after the BCR treatment (days 15 and 30). On the 30th day, all bucks were transported to the local slaughterhouse, where epididymal samples were collected immediately after slaughter. The left epididymis was preserved in 4% paraformaldehyde for histological observation, and the right epididymis was immediately preserved in liquid nitrogen for RNA sequencing (RNA-seq). The results show that the PRL inhibitor reduced the serum PRL and estradiol (E2) concentrations ( < 0.05) and tended to decrease luteinizing hormone (LH) concentrations ( = 0.052) by the 30th day, but no differences ( > 0.05) occurred by either day 0 or 15. There were no differences ( > 0.05) observed in the follicle-stimulating hormone (FSH), testosterone (T), and dihydrotestosterone (DHT) concentrations between the two groups. The PRL receptor (PRLR) protein was mainly located in the cytoplasm and intercellular substance of the epididymal epithelial cells. The PRL inhibitor decreased ( < 0.05) the expression of the PRLR protein in the epididymis. In the BCR group, the height of the epididymal epithelium in the caput and cauda increased, as did the diameter of the epididymal duct in the caput ( < 0.05). However, the diameter of the cauda epididymal duct decreased ( < 0.05). Thereafter, a total of 358 differentially expressed genes (DEGs) were identified in the epididymal tissues, among which 191 were upregulated and 167 were downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that , , , , and were mainly enriched in the estrogen signaling pathway, steroid binding, calcium ion binding, the GnRH signaling pathway, the cAMP signaling pathway, and the chemical carcinogenesis-reactive oxygen species pathway, which are related to epididymal function. In conclusion, the inhibition of PRL may affect the structure of the epididymis by reducing the expression of the PRLR protein and the secretion of E2. , , , , and could be the key genes of PRL in its regulation of epididymal reproductive function.
PubMed: 38929397
DOI: 10.3390/ani14121778 -
Animals : An Open Access Journal From... Jun 2024Ringed seals are consumed in Greenland and are therefore included as a key biomonitoring species with the focus on pollution exposure and health effects. Ringed seals in...
Ringed seals are consumed in Greenland and are therefore included as a key biomonitoring species with the focus on pollution exposure and health effects. Ringed seals in Central West Greenland (Qeqertarsuaq) and in North West Greenland (Qaanaaq) were analyzed for metal concentrations in the liver and histological changes in the liver and kidney. The mean liver concentration of mercury in Qaanaaq was 3.73 ± 5.01 µg/g ww (range: 0.28-23.29 µg/g ww), and the mean cadmium concentration was 7.80 ± 8.95 µg/g ww (range: 0.013-38.79 µg/g ww). For Qeqertarsuaq, the liver concentration of mercury was 1.78 ± 1.70 µg/g ww (range: 0.45-8.00 µg/g ww) and the mean cadmium concentration was 11.58 ± 6.32 µg/g ww (range: 0.11-25.45 µg/g ww). Age had a positive effect on the liver concentrations of metals, while no effect was found for sex or histological changes. The prevalence of histological changes in liver tissue decreased in the following order: random pattern mononuclear cell infiltration (92.1%), portal cell infiltration (68.4%), hepatic intracellular fat (18.4%), portal fibrosis (7.9%), focal hepatic fibrosis (7.9%), bile duct hyperplasia/fibrosis (7.9%) and lipid granuloma (2.6%). For kidney tissue, the prevalence of histological changes decreased in the following order: glomerular mesangial deposits (54.1%) > glomerular basement membrane thickening (45.9%) > THD (40%) > tubular hyaline casts (14.0%) > glomerular atrophy (13.5%) > dilated tubules (13.5%) > glomerular hyper-cellularity (10.8%) > mononuclear cell infiltrations (8.1%).
PubMed: 38929358
DOI: 10.3390/ani14121739 -
Animals : An Open Access Journal From... Jun 2024Ventricular septal defects (VSDs) can lead to congestive heart failure and pulmonary hypertension, particularly in patients with large shunts. However, no surgical...
Ventricular septal defects (VSDs) can lead to congestive heart failure and pulmonary hypertension, particularly in patients with large shunts. However, no surgical treatment for feline VSD has been reported. Here, we elucidated the first surgical correction of an infundibular muscular VSD in a one-year-old Ragdoll cat, atypically located and classified under the Soto classification rather than the standard Kirklin classification, through cardiac arrest using cardiopulmonary bypass-a method rarely used in feline cardiac surgery. Detailed echocardiography revealed that the defect required intervention owing to left heart and main pulmonary artery enlargement. Despite the VSD being located on the contralateral side, as anticipated in the preoperative examinations, the choice of median sternotomy allowed for the successful closure of the defect. Conversely, the insertion of two cannulas into the ascending aorta resulted in damage to the adjacent thoracic duct, causing transient chylothorax, which was resolved with conservative treatment. Cardiac arrest induced by a cardioplegic solution facilitated the surgical procedure, although it leads to anemia in cats. However, on postoperative day 490, the patient exhibited only minor residual shunting, with normalized heart size, and remained healthy. This technique appears to be a viable treatment option for congenital heart disease in cats.
PubMed: 38929355
DOI: 10.3390/ani14121736 -
Diagnostics (Basel, Switzerland) Jun 2024This paper introduces a novel one-dimensional convolutional neural network that utilizes clinical data to accurately detect choledocholithiasis, where gallstones...
This paper introduces a novel one-dimensional convolutional neural network that utilizes clinical data to accurately detect choledocholithiasis, where gallstones obstruct the common bile duct. Swift and precise detection of this condition is critical to preventing severe complications, such as biliary colic, jaundice, and pancreatitis. This cutting-edge model was rigorously compared with other machine learning methods commonly used in similar problems, such as logistic regression, linear discriminant analysis, and a state-of-the-art random forest, using a dataset derived from endoscopic retrograde cholangiopancreatography scans performed at Olive View-University of California, Los Angeles Medical Center. The one-dimensional convolutional neural network model demonstrated exceptional performance, achieving 90.77% accuracy and 92.86% specificity, with an area under the curve of 0.9270. While the paper acknowledges potential areas for improvement, it emphasizes the effectiveness of the one-dimensional convolutional neural network architecture. The results suggest that this one-dimensional convolutional neural network approach could serve as a plausible alternative to endoscopic retrograde cholangiopancreatography, considering its disadvantages, such as the need for specialized equipment and skilled personnel and the risk of postoperative complications. The potential of the one-dimensional convolutional neural network model to significantly advance the clinical diagnosis of this gallstone-related condition is notable, offering a less invasive, potentially safer, and more accessible alternative.
PubMed: 38928692
DOI: 10.3390/diagnostics14121278 -
Diagnostics (Basel, Switzerland) Jun 2024Metastatic pancreatic lesions (MPLs) are relatively uncommon, constituting 2 to 5% of all pancreatic tumors. They often manifest as solitary lesions without distinct...
BACKGROUND
Metastatic pancreatic lesions (MPLs) are relatively uncommon, constituting 2 to 5% of all pancreatic tumors. They often manifest as solitary lesions without distinct clinical symptoms, usually identified incidentally during radiologic imaging for the surveillance of prior malignancies. Differentiating these lesions from primary pancreatic tumors presents a significant challenge due to their nonspecific presentation.
METHODS
We aimed to prospectively assess the effectiveness of endoscopic ultrasound (EUS) and EUS-guided fine needle aspiration/biopsy (EUS-FNA/B) in diagnosing MPLs in a carefully selected cohort of patients presenting with pancreatic masses. Additionally, we sought to examine the relevance of specific EUS findings in supporting the initial diagnosis of MPLs and their agreement with the definitive cytological diagnosis. This study retrospectively analyzed data from 41 patients diagnosed with MPLs between 2013 and 2023, focusing on their clinical and pathological characteristics, the echogenic features of the pancreatic lesions, and the techniques used for tissue acquisition.
RESULTS
The incidence of MPLs in our cohort was 3.53%, with the most frequent primary tumors originating in the kidney (43.90%), colorectum (9.76%), lung (9.76%), lymphoma (9.76%), and breast (4.88%). MPLs typically presented as hypoechoic, oval-shaped lesions with well-defined borders and were predominantly hypervascular. Interestingly, 68.29% of the cases were discovered incidentally during follow-up of the primary tumors, while the involvement of the common bile duct was uncommon (19.51%).
CONCLUSIONS
EUS and EUS-FNA/B have been validated as valuable diagnostic tools for identifying MPLs. While our findings are promising, further multicenter studies are necessary to corroborate these results and elucidate the predictive value of specific EUS characteristics in determining the metastatic origin of pancreatic lesions.
PubMed: 38928665
DOI: 10.3390/diagnostics14121250 -
Biomedicines Jun 2024This article addresses the semantic segmentation of laparoscopic surgery images, placing special emphasis on the segmentation of structures with a smaller number of...
This article addresses the semantic segmentation of laparoscopic surgery images, placing special emphasis on the segmentation of structures with a smaller number of observations. As a result of this study, adjustment parameters are proposed for deep neural network architectures, enabling a robust segmentation of all structures in the surgical scene. The U-Net architecture with five encoder-decoders (U-Net5ed), SegNet-VGG19, and DeepLabv3+ employing different backbones are implemented. Three main experiments are conducted, working with Rectified Linear Unit (ReLU), Gaussian Error Linear Unit (GELU), and Swish activation functions. The applied loss functions include Cross Entropy (CE), Focal Loss (FL), Tversky Loss (TL), Dice Loss (DiL), Cross Entropy Dice Loss (CEDL), and Cross Entropy Tversky Loss (CETL). The performance of Stochastic Gradient Descent with momentum (SGDM) and Adaptive Moment Estimation (Adam) optimizers is compared. It is qualitatively and quantitatively confirmed that DeepLabv3+ and U-Net5ed architectures yield the best results. The DeepLabv3+ architecture with the ResNet-50 backbone, Swish activation function, and CETL loss function reports a Mean Accuracy (MAcc) of 0.976 and Mean Intersection over Union (MIoU) of 0.977. The semantic segmentation of structures with a smaller number of observations, such as the hepatic vein, cystic duct, Liver Ligament, and blood, verifies that the obtained results are very competitive and promising compared to the consulted literature. The proposed selected parameters were validated in the YOLOv9 architecture, which showed an improvement in semantic segmentation compared to the results obtained with the original architecture.
PubMed: 38927516
DOI: 10.3390/biomedicines12061309