Small Ducts Research Articles

Development of biotissue training models for anastomotic suturing in pancreatic surgery

BackgroundAnastomotic suturing is the Achilles heel of pancreatic surgery. Especially in laparoscopic and robotically assisted surgery, the pancreatic anastomosis should first be trained outside the operating room. Realistic training models are therefore needed. MethodsModels of the pancreas, small bowel, stomach, bile duct, and a realistic training torso were developed for training of anastomoses in pancreatic surgery. Pancreas models with soft and hard textures, small and large ducts were incrementally developed and evaluated. Experienced pancreatic surgeons (n = 44) evaluated haptic realism, rigidity, fragility of tissues, and realism of suturing and knot tying. ResultsIn the iterative development process the pancreas models showed high haptic realism and highest realism in suturing (4.6 ± 0.7 and 4.9 ± 0.5 on 1–5 Likert scale, soft pancreas). The small bowel model showed highest haptic realism (4.8 ± 0.4) and optimal wall thickness (0.1 ± 0.4 on −2 to +2 Likert scale) and suturing behavior (0.1 ± 0.4). The bile duct models showed optimal wall thickness (0.3 ± 0.8 and 0.4 ± 0.8 on −2 to +2 Likert scale) and optimal tissue fragility (0 ± 0.9 and 0.3 ± 0.7). ConclusionThe biotissue training models showed high haptic realism and realistic suturing behavior. They are suitable for realistic training of anastomoses in pancreatic surgery which may improve patient outcomes.

A large-scale plasma proteome Mendelian randomization study identifies novel causal plasma proteins related to primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a progressive chronic autoimmune cholestatic liver disease characterized by the destruction of small intrahepatic bile ducts leading to biliary cirrhosis. Liver biopsy is required in the diagnosis of Antimitochondrial antibody-negative patients. Therefore, novel biomarkers are needed for the non-invasive diagnosis of PBC. To identify novel biomarkers for PBC, we conducted large-scale plasma proteome Mendelian randomization (MR). A total of 21,593 protein quantitative trait loci (pQTLs) for 2297 circulating proteins were used and classified into four different groups. MR analyses were conducted in the four groups separately. Furthermore, the results were discovered and replicated in two different cohorts of PBC. Colocalization analysis and enrichment analysis were also conducted. Three plasma proteins (ficolin-1, CD40 and protein FAM177A1) were identified and replicated as being associated with PBC. All of them showed significant protective effects against PBC. An increase in ficolin-1 (OR=0.890 [0.843-0.941], p=3.50×10-5), CD40 (OR=0.814 [0.741-0.895], p=1.96×10-5) and protein FAM177A1 (OR=0.822 [0.754-0.897], p=9.75×10-6) reduced the incidence of PBC. Ficolin-1 (PP4 = 0.994) and protein FAM177A1 (PP4 = 0.995) colocalized with the expression of the genes FCN1 and FAM177A1 in whole blood, respectively. Furthermore, CD40 (PP4 = 0.977) and protein FAM177A1 (PP4 = 0.897) strongly colocalized with PBC. We expand the current biomarkers for PBC. In total, three (ficolin-1, CD40, and protein FAM177A1) plasma proteins were identified and replicated as being associated with PBC in MR analysis. All of them showed significant protective effects against PBC. These proteins can be potential biomarkers or drug targets for PBC.

The Genetics of Primary Biliary Cholangitis: A GWAS and Post-GWAS Update.

Primary biliary cholangitis (PBC) is a chronic, progressive cholestatic liver disease in which the small intrahepatic bile ducts are destroyed by autoimmune reactions. Among autoimmune diseases, which are polygenic complex traits caused by the combined contribution of genetic and environmental factors, PBC exhibits the strongest involvement of genetic heritability in disease development. As at December 2022, genome-wide association studies (GWASs) and associated meta-analyses identified approximately 70 PBC susceptibility gene loci in various populations, including those of European and East Asian descent. However, the molecular mechanisms through which these susceptibility loci affect the pathogenesis of PBC are not fully understood. This study provides an overview of current data regarding the genetic factors of PBC as well as post-GWAS approaches to identifying primary functional variants and effector genes in disease-susceptibility loci. Possible mechanisms of these genetic factors in the development of PBC are also discussed, focusing on four major disease pathways identified by in silico gene set analyses, namely, (1) antigen presentation by human leukocyte antigens, (2) interleukin-12-related pathways, (3) cellular responses to tumor necrosis factor, and (4) B cell activation, maturation, and differentiation pathways.

TRPS1 Is Differentially Expressed in a Variety of Malignant and Benign Cutaneous Sweat Gland Neoplasms

Neoplasms of sweat glands and the breast may be morphologically and immunophenotypically similar. A recent study showed that TRPS1 staining is a highly sensitive and specific marker for breast carcinoma. In this study, we analyzed TRPS1 expression in a spectrum of cutaneous sweat gland tumors. We stained five microcystic adnexal carcinomas (MACs), three eccrine adenocarcinomas, two syringoid eccrine carcinomas, four hidradenocarcinomas, six porocarcinomas, one eccrine carcinoma-NOS, 11 hidradenomas, nine poromas, seven cylindromas, three spiradenomas, and 10 syringomas with TRPS1 antibodies. All of the MACs and syringomas were negative. Every cylindroma and two of the three spiradenomas demonstrated intense staining in cells lining the ductular spaces, with negative to relatively weak expression in surrounding cells. Of the 16 remaining malignant entities, 13 were intermediate to high positive, one was low positive, and two were negative. From the 20 hidradenomas and poromas, intermediate to high positivity was revealed in 14 cases, low positivity in three cases, and negative staining in three cases. Our study demonstrates a very high (86%) expression of TRPS1 in malignant and benign adnexal tumors that are mainly composed of islands or nodules with polygonal cells, e.g., hidradenomas. On the other hand, tumors with small ducts or strands of cells, such as MACs, appear to be completely negative. This differential staining among types of sweat gland tumors may represent either differential cells of origin or divergent differentiation and has the potential to be used as a diagnostic tool in the future.

Natural history and prognosis of pediatric PSC with updates on management.

Natural history and prognosis of pediatric PSC with updates on management.

OP10 Proctocolectomy with permanent ileostomy is associated with better transplant-free survival in patients with primary sclerosing cholangitis: a retrospective cohort study

Abstract Background Inflammatory bowel disease (IBD) is the strongest known risk factor for primary sclerosing cholangitis (PSC) and seems associated with a worse prognosis. After liver transplantation, colectomy is associated with decreased rates of recurrent PSC and better graft survival.1 At the same time, the effect of colectomy on the disease course of PSC remains unclear.2 Available evidence depends either on small patient numbers, may be confounded by unobserved risk factors or colectomy was not considered as time-depending covariate. The aim of our study is to estimate the effect of colectomy on the disease course of PSC by taking time dependency and known risk factors into account. Methods We conducted a retrospective cohort study between January 1st 2008 and December 31st 2021 based on the Dutch population-based EpiPSC2 cohort. Transplant-free survival was defined as liver transplantation or PSC-related death (excluding colorectal carcinoma). The effect of colectomy was determined as time depending variable via Cox proportional hazards regression and was corrected for the following known risk factors; sex, age at diagnosis, large or small duct PSC, features of auto-immune hepatitis, time depending IBD status (i.e. no IBD, ulcerative colitis (UC), Crohn’s disease (CD) or IBD Unspecified (IBD-U)), and tertiary centre inclusion. Effect of colectomy was stratified for extent (i.e. hemi-, subtotal, or proctocolectomy with pouch or ileostomy). Indication of colectomy (i.e. active disease, dysplasia and colorectal carcinoma or other) was also considered as predictor variable. Events in the first year after colectomy were censored due to a presumed delayed effect of colectomy on disease course. Results Of the 1341 patients included, 912(68%) were diagnosed with IBD and 187(14%) had undergone a colectomy. During a total follow-up of 14,393 patient years, 370(28%) patients underwent liver transplantation and 318(24%) patients died due to a PSC-related cause. Median transplant-free survival time was 20 years. Hazard ratio (HR) was significantly decreased in patients who had undergone proctocolectomy with ileostomy (HR 0.47(0.24-0.93)) compared to patients without colectomy. This effect was absent in the group with any other type of colectomy (HR 0.90(0.67-1.19)). Indication of colectomy had no apparent effect. Presence of UC, CD or IBD-U was not associated with a worse prognosis compared to absence of IBD (HR 0.99(0.81-1.21), HR 0.85(0.64-1.13), HR 0.75(0.43-1.29)). Conclusion Our data suggest that proctocolectomy with ileostomy confers protection for liver transplantation and PSC-related death. This points towards the putative pathophysiologic role of the colonic microbiota in PSC and may open avenues to a better understanding of the aetiology of PSC.

Reply: Insurance should cover vancomycin for primary sclerosing cholangitis.

Ali and colleagues raise issues of insurance coverage for oral vancomycin (OV) for the treatment of primary sclerosing cholangitis (PSC); however, the purpose of AASLD guidance statements is to help clinicians understand and implement the most recent evidence (https://www.aasld.org/practice-guidelines). The writing group, Practice Guidance Committee, and AASLD Governing Board and supported the final statement that there is insufficient evidence to recommend the use of OV which is consistent with the 2022 European Association for the Study of the Liver guidelines.1 The meta-analysis referred to included only 2 randomized controlled trials of OV.2. The largest study randomized 29 patients to OV or placebo for 12 weeks and reported an improvement in Mayo Risk Score, though total bilirubin did not change. The other randomized controlled trials was not placebo-controlled and included 8 and 9 patients who received low or high doses of OV, respectively, for 12 weeks. Compared with baseline, alkaline phosphatase decreased in both groups, and Mayo Risk Score decreased only in the low-dose group, but without change in total bilirubin. A third study was open-labeled and reported on 30 enrolled subjects and 29 patients treated outside protocol, 25 (42%) of whom had small duct PSC, and several previously treated with OV.3 The methods used to support the claims of imprvements in histology and cholangiograms were not reported. In contrast, a retrospective study of 264 patients found that neither OV nor ursodiol were associated with clinical improvements compared with observation in pediatric patients with PSC.4 Thus, the data supporting the use of OV in PSC is not “robust” and the statements Ali an colleagues made about OV are not supported by current evidence. More concerning is the suggestion that OV might be a substitute for biologics for treating inflammatory bowel disease. Management of PSC-associated inflammatory bowel disease was outside the scope of the Guidance, but multiple society guidelines do not recommend vancomycin for acute severe ulcerative colitis. All stakeholders desire a safe and effective treatment for PSC. Ali and colleagues believe that OV is that treatment, but current evidence does not support this belief.

Localization and Laparoscopic Excision of Gastric Heterotopic Pancreas in a Child by Endoscopic SPOT® Tattooing

Heterotopic pancreas (HP) is defined as pancreatic tissue lacking vascular or anatomic connection with the normal pancreas. Surgical resection is often indicated for symptomatic gastric HP. However, intraoperative identification of gastric HP is often difficult during laparoscopic surgery. Herein, we describe a patient with gastric HP, which was marked with SPOT® dye (GI Supply, Camp Hill, PA, USA). The dye was seen clearly laparoscopically facilitating total excision of the lesion. The final pathology report confirmed the presence of heterotopic pancreatic tissue including pancreatic acini, small pancreatic ducts tissue with islets of Langerhans in the deep gastric submucosal area. There were no postoperative complications, and the patient was symptom-free. To the best of our knowledge, this was the first case report in the literature in which endoscopic tattooing of gastric HP before laparoscopic resection was performed. This method of localization was simple and reliable in children.

Integrative analysis of multiple genomic data from intrahepatic cholangiocarcinoma organoids enables tumor subtyping

As genomic analysis technology has advanced, it has become possible to sub-classify intrahepatic cholangiocarcinoma (ICC) at the histological or molecular level. Here, we verify the recently suggested two subgroups of ICC in the organoids model, compare the characteristics between types. ICC patients are subclassified into small-duct (SD) and large-duct (LD) subtype according to histological characteristics. ICC organoids are established, and unsupervised principal component analysis clustering separates each type of ICC. Differential gene expression reveals enrichment on KRAS, TGFβ and ERBB2 signaling pathways in LD-type compared with SD-type (P < 0.05). Gene set enrichment analysis demonstrates that the cholangiocarcinoma class 2 signature, defined by Andersen et al., is enriched in the LD-type (enrichment Score = 2.19, P < 0.001). A protein-protein interaction network analysis identifies ZNF217 as a significant hub protein (odds ratio = 4.96, P = 0.0105). We perform prospective modeling of histological subtype using patient-derived organoids. Moreover, gene expression profiling of ICC organoids enables identification of type-specific targetable pathways.

A duct-to-mucosa pancreaticojejunostomy for small main pancreatic duct and soft pancreas in minimally invasive pancreaticoduodenectomy

BackgroundPostoperative pancreatic fistula (POPF) is often associated with significant morbidity and mortality after the Whipple operation. Patient-related factors associated with POPF include soft pancreatic texture and a small main pancreatic duct (MPD). The traditional duct-to-mucosa anastomosis was modified to be easily performed. The aim of the study was to evaluate the simplified pancreaticojejunostomy (PJ) method in the prevention of POPF after minimally invasive pancreaticoduodenectomy (PD).MethodsNinety-eight patients who underwent laparoscopic pancreaticoduodenectomy (LPD) and robotic pancreaticoduodenectomy (RPD) with a simplified PJ procedure containing only two duct-to-mucosa sutures and four penetrating-sutures to anastomose the pancreatic parenchyma and jejunal seromuscular layer in our center were retrospectively studied. Demographics and clinical short-term safety were assessed.ResultsAll LPD and RPD procedures were successfully performed. The median time of PJ was 17 min, and the median blood loss was 60 mL, with only one patient requiring transfusion. Four patients (4.1%) suffered from clinically relevant POPF (CR-POPF), including four grade B cases and no grade C cases. For patients with an MPD diameter of 3 mm or less, POPF was noted in two (4%) of the fifty patients, with all cases being grade B. Of the patients with a soft pancreas, only two (4.5%) patients suffered from grade B POPF. One patient (1.0%) experienced a 90-day mortality. Neither the main pancreatic diameter nor pancreatic texture had an impact on postoperative outcomes.ConclusionsOur technique is a simple, safe and efficient alternative to prevent POPF after LPD and RPD. This method is suitable for almost all pancreatic conditions, including cases with a small main pancreatic duct and soft pancreas, and has the potential to become the preferred procedure in low-volume pancreatic surgery centers.Graphical abstractOur modified duct-to-mucosa PJ, which contains only two duct-to-mucosa sutures and four penetrating-sutures to anastomose the pancreatic parenchyma and jejunal seromuscular layer, is ideal for small MPD and soft pancreas when performing minimally invasive PD and has a low rate of POPF. PJ pancreaticojejunostomy, MPD main pancreatic diameter, PD pancreaticoduodenectomy, POPF postoperative pancreatic fistula

Selective use of pancreatic duct occlusion during pancreaticoduodenectomy in patients with a small-size duct and atrophic parenchyma in the distal pancreas: A retrospective study.

Despite the advancements in surgical techniques, postoperative pancreatic fistula (POPF) remains a potentially life-threatening complication of pancreaticoduodenectomy (PD). Pancreatic duct occlusion (PDO) without anastomosis has also been proposed to alleviate the clinical consequences of POPF in selected patients after PD. To assess the safety and effectiveness of PDO with mechanical closure after PD in patients with an atrophic pancreatic body-tail and a small pancreatic duct. We retrospectively identified two female and two male patients from April 2019 to October 2020 through preoperative computed tomography of the abdomen. Among them, three patients underwent PDO with mechanical closure after PD, and one underwent PDO after pylorus-preserving PD. In addition, patients' medical records and medium-and long-term follow-up data were analyzed. Postoperative histological examination revealed a solid pseudopapillary tumor in two patients, pancreatic ductal adenocarcinoma in one patient, and chronic pancreatitis with pancreatic duct stones in one patient. However, none of the patients developed biochemical or clinically relevant POPF, with no postpancreatectomy hemorrhage, biliary leakage, delayed gastric emptying, intra-abdominal abscess, or chyle leakage. Among the four patients, three developed new-onset diabetes mellitus, and one had impaired glucose tolerance. Furthermore, three patients received pancreatic enzyme supplementation at a dose of 90,000 Ph. Eur. units/d, and one was prescribed a higher dose of 120,000 Ph. Eur. units/d. PDO with mechanical closure is an alternative approach for patients with an atrophic pancreatic body-tail and a small pancreatic duct after PD. Therefore, further evidence should evaluate the potential benefits of selective PDO in these patients.

INVESTIGATION ON IMPACTS OF ELLIPTICAL DUCTS ON MACROSCOPIC SPRAY CHARACTERISTICS OF DUCTED FUEL INJECTION

To study the influence of ducts other than circular shapes on spray characteristics of ducted fuel injection (DFI), experimental and simulation methods were used to study the impacts of elliptical ducts on DFI macroscopic spray characteristics. Two elliptical ducts, small and large, were used, with a circular duct for comparison. The small elliptical duct had the same hole cross-sectional area as the circular duct, and the large elliptical duct had a larger cross-sectional area. The DFI spray configuration with the elliptical duct promoted the axial dispersion and weakened the radial dispersion of spray with respect to free spray. Different spray-duct interactions caused differences in spray characteristics, manifested in changes in velocity field and pressure field. The spray velocity field of the circular duct had the best effect on promoting spray dispersion, followed by the small elliptical duct, and finally by the large elliptical duct compared to that of free spray. Furthermore, the pumping effect caused by the pressure differences between inside and outside the duct promoted the thorough mixing of spray and ambient gas inside the duct. From the radial velocity of ambient gas flowing to spray around the duct inlet, the pumping effect of the circular duct was the strongest, followed by the small elliptical duct and finally by the large elliptical duct.

Clinical and Laboratory Characteristics in Children with Alagille Syndrome: Experience of a Single Center.

This study aimed to explore the clinical predictors of Alagille syndrome (ALGS) in children and to provide a basis for early diagnosis. We retrospectively analyzed the clinical data of 14 children diagnosed with ALGS at the First People's Hospital of Lianyungang City from March 2016 to March 2021 and followed up the children. Among the 14 patients, 9 (64.28%) had cholestasis, 12 (85.71%) had heart malformations, 13 (92.85%) had characteristic facial features, 2 (14.28%) had pruritus, and 2 (14.28%) had a positive family history. Among the 13 patients who were examined by pediatric ophthalmologists, 3 patients had ocular lesions. Among the 13 patients who underwent spine radiography, 2 had typical butterfly vertebrae. Among the 6 patients with hepatic pathology, 2 had intracellular cholestasis, 2 had reduced or no small bile duct in the portal area, 2 had small bile duct hyperplasia with massive fibrous hyperplasia and extensive inflammatory cell infiltration, and 2 underwent biliary tract exploration. Genetic testing of 12 children with ALGS revealed JAG1 gene mutations in 7 cases and NOTCH2 gene mutations in 2 cases. The abovementioned two mutant genes were not detected in any of the 3 cases. Among the 12 followed-up patients, 7 were in stable condition, 5 underwent liver transplantation, and 1 died of severe pneumonia. Cholestatic liver disease, cardiac malformations, and abnormal facial development are predictors of ALGS in children and can be definitively diagnosed by genetic testing.

CLINICAL COURSE OF MEDICALLY MANAGED PATIENTS WITH LARGE AND SMALL DUCT CHRONIC PANCREATITIS.

Pancreatic duct obstruction is the primary indication for endoscopic and/or surgical therapy in patients with chronic pancreatitis (CP). However, the clinical course of medically managed patients in relation to pancreatic duct obstruction is largely unknown. This was a retrospective cohort study of medically managed CP patients. We classified patients based on pancreatic duct obstruction from a stricture or stone using cross-sectional imaging (i.e., large vs small duct CP). We compared prevalence of diabetes and exocrine insufficiency (EPI) between subgroups at inclusion and investigated risk of new onset diabetes, EPI, and all-cause mortality over a follow-up period of 5 years. Changes in pancreatic morphology were studied in patients who underwent follow-up imaging. A total of 198 patients (mean age 58 ± 12 years, 70% male, 60% alcoholic aetiology, 38% large duct CP) were evaluated. At inclusion, patients with large vs small duct CP had a higher prevalence of both diabetes (43% vs 24%, P=0.004) and EPI (47% vs 28%, P=0.007). There was an increased risk of new onset EPI in patients with large duct CP (hazard ratio 1.72; 95% CI [1.05-2.80], P=0.031) and higher rates of pancreatic atrophy (P<0.001). No differences between groups were observed for new onset diabetes and all-cause mortality. Conversion from small to large duct CP or vice versa during follow-up was observed in 14% of patients. In a medically managed cohort of patients, large duct CP was associated with increased risk of EPI and pancreatic atrophy compared to small duct CP.

Endoscopic retrograde cholangiopancreatography versus conservative treatment of biliary leakage due to injury of Luschka duct during laparoscopic cholecystectomy

Background Gallstones remain the most common disease of gastrointestinal tract in the world. Laparoscopic cholecystectomy is one of the most common performed surgical operations. Bile leaks remain a significant cause of morbidity for patients undergoing laparoscopic cholecystectomy and these occur in 0.3–0.8% of cases. The ducts of Luschka, or subvesical ducts, are small ducts originate from the right hepatic lobe, course along the gallbladder bed, and usually drain into the extrahepatic bile ducts. Injury of these ducts is the second most frequent cause of postcholecystectomy bile leakage after cystic duct leak. Aim The aim of this study is to compare between conservative and endoscopic retrograde cholangiopancreatography (ERCP) treatment of leaked injured Luschka duct as regarding outcomes, effectiveness, and cost. Patients and methods Retrospective study included patients with postcholecystectomy biliary leakage due to Luschka duct injury from June 2015 to December 2022. Results A total of 20 patients were included in this study and classified into two groups: group A with conservative treatment was successful in eight cases within 2–3 weeks and two cases reoperated, one with relaparoscopy with drainage and one cases reoperated with open exploration and ligation of leaked duct while group B with 10 cases treated with ERCP, all patients treated successfully with ERCP sphincterotomy and stent placement and leaks stopped and discharged within third or fourth day without any morbidity, no mortality in both groups. Conclusion Treatment of biliary leakage due to injured Luschka (subvesical duct) with ERCP sphincterotomy and stent placement is safe and effective without any morbidity or mortality.

Molecular and radiopathologic spectrum between HCC and intrahepatic cholangiocarcinoma.

Primary liver cancers (LCs), including HCC and intrahepatic cholangiocarcinoma (iCCA), are derived from a common developmental lineage, conferring a molecular spectrum between them. To elucidate the molecular spectrum, we performed an integrative analysis of transcriptome profiles associated with patients' radiopathologic features. We identified four LC subtypes (LC1-LC4) from RNA-sequencing profiles, revealing intermediate subtypes between HCC and iCCA. LC1 is a typical HCC characterized by active bile acid metabolism, telomerase reverse transcriptase promoter mutations, and high uptake of gadoxetic acid in MRI. LC2 is an iCCA-like HCC characterized by expression of the progenitor cell-like trait, tumor protein p53 mutations, and rim arterial-phase hyperenhancement in MRI. LC3 is an HCC-like iCCA, mainly small duct (SD) type, associated with HCC-related etiologic factors. LC4 is further subclassified into LC4-SD and LC4-large duct iCCAs according to the pathological features, which exhibited distinct genetic variations (e.g., KRAS , isocitrate dehydrogenase 1/2 mutation, and FGF receptor 2 fusion), stromal type, and prognostic outcomes. Our integrated view of the molecular spectrum of LCs can identify subtypes associated with transcriptomic, genomic, and radiopathologic features, providing mechanistic insights into heterogeneous LC progression.

Pathology of Cholangiocarcinomas.

Cholangiocarcinomas (CCA) are heterogeneous tumors that arise from epithelial cells of the biliary tract. They represent the second primary liver malignancy, after hepatocellular carcinoma. Recent epidemiological data show an increased incidence of intrahepatic CCA without any identified causes. According to their location on the biliary tract, intrahepatic, perihilar (p) and distal (d) CCA can be individualized. Intrahepatic CCA (iCCA) are subdivided into small duct type iCCA and large duct type iCCA, according to the level or size of the biliary duct affected. These two subgroups are characterized by distinct risk factors, gross aspect, histopathological and molecular features, and therapeutic management. The role of biopsy in iCCA is to confirm the diagnosis and to eliminate various differential diagnostics, in particular, metastases. In p/d CCA, biopsy requires more invasive approaches, and tissue samples are difficult to obtain, leading to a high rate of false negatives. In this review, we will discuss the different classifications of CCA (anatomical and macroscopic). We will describe the various microscopic and phenotypic subtypes of CCA. Finally, we will deal with their mode of extension, the role of biopsy and pre-neoplastic lesions.

Apoptotic biliary epithelial cells and gut dysbiosis in the induction of murine primary biliary cholangitis

Primary biliary cholangitis (PBC) is a female-predominant liver autoimmune disease characterized by the specific immune-mediated destruction of the intrahepatic small bile duct. Although apoptosis of biliary epithelial cells (BECs) and alterations in gut microbiota are observed in patients with PBC, it is still unclear whether these events happen in the early stage and cause the breakdown of tolerance in PBC. In this study, we examined the early events in the loss of tolerance in our well-defined 2-OA-OVA-induced murine autoimmune cholangitis (AIC) model. We report herein that apoptosis of BECs was notable in the early stage of murine AIC. An altered gut microbiota, in particular, an increased percentage of gram-positive Firmicutes in AIC mice was also observed. BECs in AIC mice expressed adhesion molecule ICAM-1, cytokines/chemokines TNF-α, CCL2, CXCL9, CXCL10, and toll-like receptor (TLR) 2. Moreover, BECs treated with TLR2 ligand had elevated apoptosis and CXCL10 production. These data collectively suggest a new mechanism of tolerance breakdown in AIC. Altered gut microbiota induces apoptosis of BECs through TLR2 signaling. BECs secrete chemokines to recruit CD8 T cells to damage BECs further.

Influence of wire spacing and plate spacing on electrostatic precipitation of nanoparticles: An approach involving electrostatic shielding and diffusion charging

Electrostatic precipitation is a process widely used as gas cleaning device, to removal particles from gas flows. However, in a conventional and well-sized precipitator, the collection efficiency decreases for ultrafine particles, making it difficult to employ this equipment for controlling nanoparticle pollution. This paper investigates the influence of plate spacing (4 and 6.5 cm) and wire spacing (4, 6, and 12 cm) on the electric current and nanoparticle collection efficiency, considering the effect of diffusion charging and electrostatic shielding. Two laboratory-scale dry wire-plate electrostatic precipitators with different plate spacings were tested for the collection of nanoparticles (6.15–241.4 nm) at three air velocities (1.9, 2.9, and 3.9 cm/s). The results demonstrated the effectiveness of the equipment in removing nanoparticles (99.9%) under the highest electric fields. Higher values of the wire spacing led to increases in the current and the collection efficiency. This was associated with reduced electrostatic shielding, which is more evident in smaller ducts with a higher density of field lines. It is expected that the findings should improve knowledge on electrostatic precipitation of nanoparticles, enabling optimization of collection efficiency by considering the effects of geometric parameters.

CFD Simulations of the Effect of Equalizing Duct Configurations on Cavitating Flow around a Propeller

This study presented the results of a computational study of cavitating flows of a marine propeller with energy saving equalizing ducts. The main purpose of the study was to estimate the cavitating flows around a propeller with a duct, and to investigate the interaction between a duct and a propeller in cavitating flows. The INSEAN E779A propeller was used as a baseline model. Validation studies were conducted for non-cavitating and cavitating flows around a hydrofoil and a propeller. A comparison with the experimental data showed good agreement in terms of sheet cavity patterns and propulsion performances of the propeller. Various duct configurations have been presented, and it was found that a duct in front of the propeller had effects on the propeller’s cavitation and propulsion performance. Higher angles of attack of the duct showed a significant effect on the propeller’s cavitation behavior, especially with a small duct. The small duct lowered the cavitation inception radius with increase in angle of attack of the duct, while the large duct had more effect on the tip cavitation. The propeller with large duct gave higher thrust, however, the higher torque loading affected the propeller efficiency. Overall, it was found that the propeller with small duct provided a higher propeller efficiency