ABSTRACT
Senescence of activated hepatic stellate cells (HSCs) is crucial for the regression of liver fibrosis. However, impaired immune clearance can result in the accumulation of senescent HSCs, exacerbating liver fibrosis. The activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is essential for both senescence and the innate immune response. Additionally, the specific delivery to activated HSCs is hindered by their inaccessible anatomical location, capillarization of liver sinusoidal endothelial cells (LSECs), and loss of substance exchange. Herein, we propose an antifibrotic strategy that combines prosenescence with enhanced immune clearance through targeted delivery of manganese (a cGAS-STING stimulator) via albumin-mediated transcytosis, specifically aimed at inducing senescence and eliminating activated HSCs in liver fibrosis. Our findings demonstrate that only albumin efficiently transfers manganese to activated HSCs from LSECs via transcytosis compared to liposomes, resulting in significant antifibrotic effects in vivo while exhibiting negligible toxicity.
Subject(s)
Hepatic Stellate Cells , Liver , Humans , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/pathology , Liver/pathology , Manganese , Endothelial Cells/metabolism , Liver Cirrhosis/drug therapy , Liver Cirrhosis/genetics , Albumins/metabolism , Nucleotidyltransferases/metabolismABSTRACT
Because number of matured muscle fibers in poultry does not increase after birth, the meat yield is mainly determined during embryogenesis. We previously indicated breast muscle grew rapidly from 18th day after hatching (E18) to E27, and almost stopped from E27 to E34 of Jiaji ducks, while the mechanism is unclear. This study utilized RNA-seq to explore the related genes of muscle development and their relationship with small molecule metabolites at E18, E27 and E34 of Jiaji ducks. Several thousand differentially expressed genes (DEGs) were detected among E18, E27 and E34. DEGs expression profiles included 8 trend maps, among which trend 1 was opposite to and trend 6 was consistent with breast muscle development trend of Jiaji ducks. Through joint analysis between trend 1 of DEGs and trend 1 of differential metabolites (DEMs), protein digestion and absorption pathway stood out. The decrease of COL8A2 gene expression will lead to the decrease of arginine content, which will inhibit the development of breast muscle in embryonic Jiaji duck. Similarly, joint analysis between trend 6 of DEGs and trend 6 of DEMs indicated the increase of GAMT gene expression will cause the increase of proline content, and then promote the development of breast muscle of Jiaji duck in embryonic period. These results will be helpful for further understanding the mechanism of muscle yields of Jiaji ducks.
Subject(s)
Ducks , Metabolomics , Animals , Ducks/metabolism , Ducks/genetics , Ducks/embryology , Metabolomics/methods , Gene Expression Profiling , Transcriptome , Muscle, Skeletal/metabolism , Gene Expression Regulation, DevelopmentalABSTRACT
The Muscovy duck (Cairina moschata) is an economically important poultry species, which is susceptible to fatty liver. Thus, the Muscovy duck may serve as an excellent candidate animal model of non-alcoholic fatty liver disease. However, the mechanisms underlying fatty liver development in this species are poorly understood. In this study, we report a chromosome-level genome assembly of the Muscovy duck, with a contig N50 of 11.8 Mb and scaffold N50 of 83.16 Mb. The susceptibility of Muscovy duck to fatty liver was mainly attributed to weak lipid catabolism capabilities (fatty acid ß-oxidation and lipolysis). Furthermore, conserved noncoding elements (CNEs) showing accelerated evolution contributed to fatty liver formation by down-regulating the expression of genes involved in hepatic lipid catabolism. We propose that the susceptibility of Muscovy duck to fatty liver is an evolutionary by-product. In conclusion, this study revealed the potential mechanisms underlying the susceptibility of Muscovy duck to fatty liver.
Subject(s)
Fatty Liver , Humans , Fatty Liver/genetics , Fatty Liver/veterinary , Chromosomes , LipidsABSTRACT
BACKGROUND: Schizophrenia is a psychiatric disorder including multiple clinical symptoms such as severe psychosis and cognitive dysfunction. DHF-7 is a novel dihydroflavanone derivative that was designed and synthesized to treat schizophrenia. This study aimed to investigate the effects and mechanisms of DHF-7 in a mouse model of schizophrenia induced by a combination of cuprizone and MK-801. METHODS: After intragastric administration of DHF-7 for 7 weeks, open field, Y-maze, and novel object recognition tests were performed to detect behavioral changes in the mouse model. White matter lesions and myelin loss were determined using transmission electron microscopy and oil red O staining. Western blotting and immunohistochemistry were used to detect the expression of the related proteins. RESULTS: The results showed that DHF-7 treatment significantly improved cognitive impairment and positive symptoms in the model mice. Moreover, DHF-7 alleviated white matter lesions and demyelination and promoted the differentiation and maturation of oligodendrocytes for remyelination in the corpus callosum of model mice. The mechanistic study showed that DHF-7 increased the expression of brain-derived neurotrophic factor and phosphorylated Fyn, thus activating the tyrosine kinase receptor B (Trk B)/Fyn/N-methyl-D-aspartate receptor subunit 2 B (NMDAR2B) and Raf/mitogen-activated protein kinase (MEK)/ extracellular signal-related kinase (ERK) signaling pathways. CONCLUSIONS: Our results provide an experimental basis for the development of DHF-7 as a novel therapeutic agent for schizophrenia.
Subject(s)
Brain-Derived Neurotrophic Factor , Proto-Oncogene Proteins c-fyn , Schizophrenia , White Matter , Animals , Brain-Derived Neurotrophic Factor/metabolism , Cuprizone/toxicity , Disease Models, Animal , Dizocilpine Maleate/toxicity , Humans , Mice , Mice, Inbred C57BL , Proto-Oncogene Proteins c-fyn/metabolism , Schizophrenia/chemically induced , Schizophrenia/drug therapy , Schizophrenia/metabolism , White Matter/metabolismABSTRACT
BACKGROUND AND AIMS: Risk stratification to identify patients with high risk of variceal rebleeding is particularly important in patients with decompensated cirrhosis. In clinical practice, eliminating gastroesphageal varices thoroughly after sequential endoscopic treatment reduces the rebleeding rate, however, no simple method has been build to predict high risk of variceal rebleeding. We conducted this study to explore the value of the number of endoscopic sessions required to eradicate gastroesphageal varices in identifying high risk of rebleeding. PATIENTS AND METHODS: Consecutive cirrhotic patients received sequential endoscopic therapy between January 2015 and March 2020 were enrolled. Endoscopic treatment was performed every 1-4 weeks until the eradication of varices. The primary endpoint was variceal rebleeding. RESULTS: A total of 146 patients were included of which 60 patients received standard therapy and 86 patients underwent sequential endoscopic treatment alone. The cut-off value of the number of sequential endoscopic sessions is 3.5 times. Variceal rebleeding was significant higher in patients with endoscopic sessions > 3 times versus ≤ 3 times (61.5% vs. 17.5%, p < 0.001). Variceal rebleeding of patients with endoscopic sessions ≤ 3 times was significant lower than patients with > 3 times in group of standard therapy (19.6% vs. 88.9%, p < 0.001) and endoscopic therapy (15.9% vs. 47.1%, p = 0.028) respectively. CONCLUSION: The number of sequential endoscopic sessions required to eradicate the varices is related to the risk of variceal rebleeding in patients with cirrhosis. If three times of endoscopic treatment can not eradicate the varices, a more aggressive treatment such as TIPS should be seriously considered.
Subject(s)
Esophageal and Gastric Varices , Varicose Veins , Esophageal and Gastric Varices/etiology , Esophageal and Gastric Varices/therapy , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/prevention & control , Humans , Liver Cirrhosis/complications , Sclerotherapy/methods , Varicose Veins/etiologyABSTRACT
Dermacoccus abyssi strain HZAU 226 is a spoilage bacterium isolated from eggs. So far, there are still few genomic resources available on the Dermacoccus abyssi. Here, we reported the complete genome sequence of Dermacoccus abyssi strain HZAU 226. High-quality DNA was extracted using the Qiagen kit, then single-molecule sequencing was performed by GridION sequencer. The raw data was quality-controlled and assembled to obtain the final genome, which consisted of a complete genome of 2,992,060 bp circular chromosome and a 64,524 bp plasmid. The structural and functional annotations of the genome were achieved through the analysis of different available databases, including antibiotic resistance genes, secondary metabolite synthesis genes and stress-related genes. Meanwhile, comparative genomic analyses of the strains were also performed. This is the first report on the complete genome of Dermacoccus abyssi, which will provide genomic resources for the study of spoilage bacteria in eggs.
Subject(s)
Actinobacteria/genetics , Eggs/microbiology , Genome, Bacterial , Actinobacteria/drug effects , Actinobacteria/isolation & purification , Actinobacteria/pathogenicity , Animals , Drug Resistance, Bacterial , Eggs/standards , Molecular Sequence Annotation , Poultry/microbiology , Whole Genome SequencingABSTRACT
BACKGROUND: The number of myofiber is determined during the embryonic stage and does not increase during the postnatal period for birds, including goose. Thus, muscle production of adult goose is pre-determined during embryogenesis. Previous studies show N6-methyladenosine (m6A) is an important regulator for skeletal muscle development of birds and miRNAs play as a co-regulator for the skeletal muscle development in birds. Herein, we sequenced m6A and miRNA transcriptomes to investigate the profiles of m6A and their potential mechanism of regulating breast muscle development in Dingan Goose. RESULTS: We selected embryonic 21th day (E21) and embryonic 30th day (E30) to investigate the roles of transcriptome-wide m6A modification combining with mRNAs and miRNAs in goose breast muscle development. In this study, m6A peaks were mainly enriched in coding sequence (CDS) and start codon and397 genes were identified as differentially methylated genes (DMGs). GO and KEGG analysis showed that DMGs were highly related to cellular and metabolic process and that most DMGs were enriched in muscle-related pathways including Wnt signaling pathway, mTOR signaling and FoxO signaling pathway. Interestingly, a negative correlation between m6A methylation level and mRNA abundance was found through the analysis of m6A-RNA and RNA-seq data. Besides, we found 26 muscle-related genes in 397 DMGs. We also detected 228 differentially expressed miRNAs (DEMs), and further found 329 genes shared by the target genes of DEMs and DMGs (m6A-miRNA-genes), suggesting a tightly relationship between DEMs and DMGs. Among the m6A-miRNA-genes, we found 10 genes are related to breast muscle development. We further picked out an m6A-miRNA-gene, PDK3, from the 10 genes to visualize it and the result showed differentially methylated peaks on the mRNA transcript consistent with our m6A-seq results. CONCLUSION: GO and KEGG of DMGs between E21 and E30 showed most DMGs were muscle-related. In total, 228 DEMs were found, and the majority of DMGs were overlapped with the targets of DEGs. The differentially methylated peaks along with an m6A-miRNA-gene, PDK3, showed the similar results with m6A-seq results. Taken together, the results presented here provide a reference for further investigation of embryonic skeletal muscle development mechanism in goose.
Subject(s)
Geese , Transcriptome , Animals , Embryonic Development , Geese/genetics , Gene Expression Profiling , Gene Expression Regulation, Developmental , Muscle Development/geneticsABSTRACT
BACKGROUND: Liver fibrosis is a common pathological change caused by a variety of etiologies. Early diagnosis and timely treatment can reverse or delay disease progression and improve the prognosis. This study aimed to assess the potential utility of two-dimensional shear wave elastography and texture analysis in dynamic monitoring of the progression of liver fibrosis in rat model. METHODS: Twenty rats were divided into control group (n = 4) and experimental groups (n = 4 per group) with carbon tetrachloride administration for 2, 3, 4, and 6 weeks. The liver stiffness measurement was performed by two-dimensional shear wave elastography, while the optimal texture analysis subsets to distinguish fibrosis stage were generated by MaZda. The results of elastography and texture analysis were validated through comparing with histopathology. RESULTS: Liver stiffness measurement was 6.09 ± 0.31 kPa in the control group and 7.10 ± 0.41 kPa, 7.80 ± 0.93 kPa, 8.64 ± 0.93 kPa, 9.91 ± 1.13 kPa in the carbon tetrachloride induced groups for 2, 3, 4, 6 weeks, respectively (P < 0.05). By texture analysis, histogram and co-occurrence matrix had the most frequency texture parameters in staging liver fibrosis. Receiver operating characteristic curve of liver elasticity showed that the sensitivity and specificity were 95.0% and 92.5% to discriminate liver fibrosis and non-fibrosis, respectively. In texture analysis, five optimal parameters were selected to classify liver fibrosis and non-fibrosis. CONCLUSIONS: Two-dimensional shear wave elastography showed potential applications for noninvasive monitoring of the progression of hepatic fibrosis, even in mild fibrosis. Texture analysis can further extract and quantify the texture features in ultrasonic image, which was a supplementary to further visual information and acquired high diagnostic accuracy for severe fibrosis.
Subject(s)
Elasticity Imaging Techniques/statistics & numerical data , Liver Cirrhosis/diagnosis , Liver/diagnostic imaging , Animals , Disease Models, Animal , Disease Progression , Male , ROC Curve , Rats , Reproducibility of Results , Severity of Illness IndexABSTRACT
BACKGROUND: To investigate the role of two-dimensional shear wave elastography (2D-SWE) in the preoperative evaluation of pediatric patients with biliary atresia awaiting liver transplantation. METHODS: Among a total of 152 pediatric patients enrolled in this single-institution prospective study between March 2018 and August 2019, 143 patients (age range, 4-97 months; median age, 7 months; 84 males, 59 females) who underwent successful routine ultrasound examination, SWE examination, and blood test before liver transplantation were included in the final analysis. The values of liver stiffness measured by SWE were compared with ultrasound and blood test parameters by Spearman's correlation analysis. RESULTS: The overall median liver stiffness with 2D-SWE was 29.0 ± 10.9 kPa, with a range of 9.0-53.3 kPa. The success rate of 2D-SWE measurements was 98.0% (149/152). Liver stiffness measurement (LSMs) had no significant correlation with gender, age, weight, and height of the pediatric recipients. LSMs were correlated with ultrasound parameters including portal vein (PV) maximum velocity, PV direction, hepatic artery resistance index (HARI), spleen diameter, ascites, and blood test parameters (albumin level, platelet count level, and international normalized ratio). In the pediatric recipients with hepatofugal PV flow, high HARI (HARI ⧠0.90), and ascites, or without Kasai operation, LSMs were significantly higher (P < .05). CONCLUSIONS: SWE is feasible and valuable for assessing liver damage in children with biliary atresia awaiting liver transplantation and might be used as selection criteria for children in need of priority access to liver transplantation.
Subject(s)
Biliary Atresia/diagnostic imaging , Biliary Atresia/surgery , Elasticity Imaging Techniques/methods , Liver Transplantation , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Patient Selection , Prospective StudiesABSTRACT
BACKGROUND: The aim of this study was to explore the value of SMI compared with conventional ultrasonography for assessing hepatic arterial blood flow after pediatric liver transplantation. METHODS: From March 2018 to November 2018, a total of 105 pediatric recipients with biliary atresia underwent liver transplantation in our hospital. Ultrasound examinations were performed at the bedside in the intensive care unit to check the patency of the blood flow in the hepatic allograft. CDI, PDI, cSMI, and mSMI were performed to assess the display, orientation, and distribution of the graft hepatic artery. Ultrasound examinations were performed by one radiologist, and the images were judged by two observers. RESULTS: The median age, weight, and height of the recipients were 6.97 (5.92, 9.58) months, 6.50 (6.00, 7.80) kg, and 64.00 (62.00, 68.00) cm, respectively. The measure of kappa agreement was 0.902, 0.889, 0.882, and 0.882 for CDI, PDI, cSMI, and mSMI, respectively. HAT occurred in 7 pediatric recipients and was confirmed by CTA (computed tomography angiography) and surgery. The diagnostic performance of sensitivity, specificity, PPV (positive predictive value), NPV (negative predictive value), and accuracy were 100%, 92.86%, 50%, 100%, and 93.33% for CDI and 100%, 98.98%, 87.50%, 100%, and 99.05% for SMI. CONCLUSIONS: As an additional method to CDI, SMI can clearly show the distribution of hepatic arterial blood flow and provide more details, thereby markedly improving the diagnostic performance of postoperative HAT.
Subject(s)
Blood Flow Velocity/physiology , Hepatic Artery/physiopathology , Liver/blood supply , Microvessels/diagnostic imaging , Transplant Recipients , Ultrasonography, Doppler/methods , Child, Preschool , Female , Follow-Up Studies , Hepatic Artery/diagnostic imaging , Humans , Infant , Liver/diagnostic imaging , Male , Microvessels/physiopathology , Reproducibility of Results , Retrospective StudiesABSTRACT
Microcystins (MCs), as the most dominant bloom-forming strains in eutrophic surface water, can induce hepatotoxicity by oxidative stress. Alpha-lipoic acid (α-LA) is a super antioxidant that can induce the synthesis of antioxidants, such as glutathione (GSH), by nuclear factor erythroid 2-related factor 2 (Nrf2). However, the potential molecular mechanism of α-LA regeneration of GSH remains unclear. The present study aimed to investigate whether α-LA could reduce the toxicity of MCs induced in human hepatoma (HepG2), Bel7420 cells, and BALB/c mice by activating Nrf2 to regenerate GSH. Results showed that exposure to 10 µM microcystin-leucine arginine (MC-LR) reduced viability of HepG2 and Bel7402 cells and promoted the formation of reactive oxygen species (ROS) compared with untreated cells. Moreover, the protection of α-LA included reducing the level of ROS, increasing superoxide dismutase activity, and decreasing malondialdehyde. Levels of reduced glutathione (rGSH) and rGSH/oxidized glutathione were significantly increased in cells cotreated with α-LA and MC-LR compared to those treated with MC-LR alone, indicating an ability of α-LA to attenuate oxidative stress and MC-LR-induced cytotoxicity by increasing the amount of rGSH. α-LA can mediate GSH regeneration through the Nrf2 pathway under the action of glutathione reductase in MC-LR cell lines. Furthermore, the data also showed that α-LA-induced cytoprotection against MC-LR is associated with Nrf2 mediate pathway in vivo. These findings demonstrated the potential of α-LA to resist MC-LR-induced oxidative damage of liver.
Subject(s)
Antioxidants/pharmacology , Chemical and Drug Induced Liver Injury/prevention & control , Glutathione/metabolism , Microcystins/toxicity , NF-E2-Related Factor 2/metabolism , Thioctic Acid/pharmacology , Animals , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Glutathione Reductase/metabolism , Hep G2 Cells , Humans , Malondialdehyde/metabolism , Marine Toxins , Mice , Mice, Inbred BALB C , Oxidation-Reduction , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolismABSTRACT
BACKGROUND: The reconstruction of hepatic artery is a challenging part of the pediatric liver transplantation procedure. Hepatic artery thrombosis (HAT) and stenosis are complications which may result in ischemic biliary injury, causing early graft lost and even death. METHODS: Two hundred and fifty-nine patients underwent liver transplantation in 2017 in a single liver transplantation group. Among them, 225 patients were living donor liver transplantation (LDLT) and 34 deceased donor liver transplantation (DDLT). RESULTS: In LDLT all reconstructions of hepatic artery were microsurgical, while in DDLT either microsurgical reconstruction or traditional continuous suture technique was done depending on different conditions. There were five (1.9%) HATs: four (4/34, 11.8%) in DDLT (all whole liver grafts) and one (1/225, 0.4%) in LDLT (P = 0.001). Four HATs were managed conservatively using anticoagulation, and 1 accepted salvage surgery with re-anastomosis. Until now, 3 HAT patients remain in good condition, whereas two developed biliary complications. One of them needed to be re-transplanted, and the other patient died due to biliary complications. CONCLUSIONS: Microsurgical technique significantly improves the reconstruction of hepatic artery in pediatric liver transplantation. The risk for arterial complications is higher in DDLT. Conservative therapy can achieve good outcome in selected HAT cases.
Subject(s)
End Stage Liver Disease/surgery , Hepatic Artery/surgery , Liver Transplantation , Vascular Surgical Procedures/methods , Adolescent , Anastomosis, Surgical/adverse effects , Child , Child, Preschool , Constriction, Pathologic/etiology , Female , Humans , Infant , Liver Transplantation/adverse effects , Liver Transplantation/methods , Male , Microsurgery , Plastic Surgery Procedures/adverse effects , Plastic Surgery Procedures/methods , Retrospective Studies , Thrombosis/etiology , Treatment Outcome , Vascular Surgical Procedures/adverse effectsABSTRACT
A stenotic or hypoplastic portal vein (PV) represents a challenge for PV reconstruction in pediatric living donor liver transplantation (LDLT). Several PV venoplastic techniques have been developed. However, we still seek improved venoplastic techniques with better efficacy and compatibility. From June 2016 to July 2017, 271 LDLT procedures were performed at the Department of Liver Surgery, Renji Hospital. A total of 16 consecutive children with stenotic and sclerotic PVs underwent a novel technique-the autogenous PV patch plastic technique. Vessel patches were procured from the left branch (LB), or the bifurcation of the right branch and LB of the PV in the native liver. Then, the PVs were enlarged by suturing the patches along the longitudinal axis from the confluence of the PV and coronary vein (CV). In this series, 15/16 achieved good intraoperational PV flow, and 1 showed low PV flow but was treated with stent placement. Within a median follow-up of 11 months (1-18 months), 15 patients were alive and had normal graft function, whereas 1 child died from lung infection 1 month after transplantation. No PV complications were detected. In conclusion, the autogenous patch venoplasty technique using the PV-CV confluence is simple and safe. This novel venoplastic reconstruction technique could serve as a surgical option to achieve satisfactory outcomes, especially those with stenotic PV (<4.5 mm) and dilated CV (>3.0 mm). Liver Transplantation 2018 AASLD.
Subject(s)
Biliary Atresia/surgery , Liver Transplantation/methods , Living Donors , Portal Vein/transplantation , Vascular Grafting/methods , Adolescent , Adult , Anastomosis, Surgical/methods , Autografts/transplantation , Biliary Atresia/complications , Child , Child, Preschool , Constriction, Pathologic/etiology , Constriction, Pathologic/surgery , Feasibility Studies , Female , Follow-Up Studies , Humans , Infant , Liver Transplantation/adverse effects , Male , Middle Aged , Portal Vein/pathology , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Transplantation, Autologous/adverse effects , Transplantation, Autologous/methods , Treatment Outcome , Vascular Grafting/adverse effects , Young AdultABSTRACT
Doppler ultrasonography is useful in monitoring intra-operative PV flow in LDLT. A retrospective cohort study included 550 pediatric recipients (<18 years) who underwent LDLT from October 2006 to August 2016 in our hospital. A total of 33 recipients (incidence 6%) were found to have insufficient intra-operative PV flow after PV reperfusion. The treatments included intra-operative stent placement (n=25), anticoagulation (n=3), thrombectomy and re-anastomosis (n=2), graft repositioning (n=1), collateral ligation (n=1), and replaced PV (n=1). The peak PV velocity, HAPSV, HARI, and HV velocity before and after the interventions were significantly improved 0(0,5.5) cm/s vs. 37.36±15.30 cm/s, 38.68±8.92 cm/s vs. 62.30±16.97 cm/s, 0.55±0.08 vs. 0.76±0.10, and 32.37±10.33 cm/s vs. 40.94±15.01 cm/s, respectively (P<.01). Insufficient PV flow and decreased HARI are two significant criteria indicating need for intra-operative PV management. Dramatic changes in the hepatic hemodynamics were detected after proper treatment. Immediate resolution of PV flow is feasible in pediatric LDLT.
Subject(s)
Hemodynamics , Intraoperative Care/methods , Liver Transplantation/methods , Living Donors , Portal Vein/diagnostic imaging , Portal Vein/physiopathology , Ultrasonography, Doppler , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Outcome Assessment, Health Care , Retrospective StudiesABSTRACT
BACKGROUND AND AIM: Polypoid lesions of the gallbladder may be neoplastic or non-neoplastic. Correct diagnosis would help reduce unnecessary cholecystectomies. This study aimed to determine the predictive value of individual ultrasound characteristics for diagnosis of neoplastic polyps and to build a scoring system based on these characteristics. METHODS: A total of 109 patients with gallbladder polyps ≥ 6 mm underwent conventional ultrasound examination and received finally diagnosis by pathological examination. All images were analyzed to determine characteristics of the lesions. Univariate and multivariate analyses were used to identify the predictors of neoplastic polyps, and a scoring system was built based on multivariate analysis. RESULTS: Maximum diameter, height/width ratio, base width, presence of hyper-echoic spots, and intralesional blood flow were statistically significant (P = 0.011, P = 0.016, P = 0.003, P = 0.031, and P = 0.022, respectively) predictors of neoplastic lesions. The total score = (Maximum diameter, ≥ 13.9 mm = 1, < 13.9 = 0) + (Base width, ≥ 3.5 mm = 1, < 3.4 = 0) + (Height/width ratio, ≤ 1.05 = 1, > 1.05 = 0) + (Hyper-echoic spots, presence = 0, absence = 1) + (Blood flow, presence = 1, absence = 0). Receiver operating characteristic curve showed that the sensitivity, specificity, and accuracy for the risk of neoplastic polyps with scores of 3 or higher were 81.6%, 86.7%, and 84.4%, respectively. CONCLUSION: This ultrasound-based scoring system could be a useful means for differentiating between neoplastic and non-neoplastic gallbladder polyps in the clinic.
Subject(s)
Gallbladder Diseases/diagnostic imaging , Gallbladder Neoplasms/diagnostic imaging , Polyps/diagnostic imaging , Ultrasonography/methods , Adult , Aged , Analysis of Variance , Diagnosis, Differential , Female , Gallbladder Diseases/pathology , Gallbladder Neoplasms/pathology , Humans , Male , Middle Aged , Polyps/pathology , ROC Curve , Sensitivity and Specificity , Young AdultABSTRACT
Despite similar components, the heterogeneity of skin characteristics across the human body is enormous. It is classically believed that site-specific fibroblasts in the dermis control postnatal skin identity by modulating the behavior of the surface-overlying keratinocytes in the epidermis. To begin testing this hypothesis, we characterized the gene expression differences between volar (ventral; palmoplantar) and nonvolar (dorsal) human skin. We show that KERATIN 9 (KRT9) is the most uniquely enriched transcript in volar skin, consistent with its etiology in genetic diseases of the palms and soles. In addition, ectopic KRT9 expression is selectively activated by volar fibroblasts. However, KRT9 expression occurs in the absence of all fibroblasts, although not to the maximal levels induced by fibroblasts. Through gain-of-function and loss-of-function experiments, we demonstrate that the mechanism is through overlapping paracrine or autocrine canonical WNT-ß-catenin signaling in each respective context. Finally, as an in vivo example of ectopic expression of KRT9 independent of volar fibroblasts, we demonstrate that in the human skin disease lichen simplex chronicus, WNT5a and KRT9 are robustly activated outside of volar sites. These results highlight the complexities of site-specific gene expression and its disruption in skin disease.
Subject(s)
Foot Dermatoses/metabolism , Hand Dermatoses/metabolism , Keratin-9/metabolism , Skin/metabolism , Wnt Signaling Pathway/physiology , Animals , Cell Differentiation/physiology , Female , Fibroblasts/physiology , Fluorescent Antibody Technique , Gene Expression/physiology , Gene Knockdown Techniques , Humans , Keratin-5/metabolism , Keratin-9/genetics , Keratinocytes/physiology , Male , Mice, Inbred C57BL , Neurodermatitis/metabolism , Psoriasis/metabolism , RNA, Messenger/metabolism , Wnt Signaling Pathway/genetics , Wnt-5a Protein/metabolism , beta Catenin/physiologyABSTRACT
BACKGROUND: Early hepatic artery thrombosis (eHAT) has been recognized as an important cause of graft loss and mortality. However, the incidence, etiology and outcome are not clear, especially for children. The present study was to investigate the formation of collateral artery flow after irreversible eHAT and its impact on patient's prognosis. METHODS: We analyzed eHAT after liver transplantation in children from October 2006 to April 2015 in our center, illustrated the formation of collateral hepatic artery flow after irreversible eHAT and explored the diagnosis, complications, treatment and prognosis. The basic and follow-up ultrasonographic images were also compared. RESULTS: Of the 330 pediatric liver recipients, 22 (6.67%) developed eHAT within 1 month. Revascularization attempts including surgical thrombectomy, interventional radiology and conservational treatment (thrombolysis) were successful in 5 patients. Among the 17 patients who had irreversible eHAT, follow-up ultrasonography revealed that collateral artery flow was developed as early as 2 weeks after eHAT. Liver abscess and bile duct complication occurred secondary to eHAT in variable time. CONCLUSIONS: Collateral arterial formation is a compensatory adaptation to eHAT to supply blood to liver grafts. However, the severe bile duct damage secondary to eHAT is irreversible and retransplantation is unavoidable.
Subject(s)
Arterial Occlusive Diseases/etiology , Collateral Circulation , Hepatic Artery/physiopathology , Liver Circulation , Liver Transplantation/adverse effects , Thrombosis/etiology , Age Factors , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/physiopathology , Arterial Occlusive Diseases/therapy , Bile Duct Diseases/etiology , Bile Duct Diseases/physiopathology , Child , Child, Preschool , Female , Hepatic Artery/diagnostic imaging , Humans , Infant , Male , Reoperation , Retrospective Studies , Risk Factors , Thrombosis/diagnostic imaging , Thrombosis/physiopathology , Thrombosis/therapy , Time Factors , Treatment Outcome , Ultrasonography, DopplerABSTRACT
We used Doppler US to evaluate the changes in hepatic arterial hemodynamics that occur following LDLT in pediatric recipients, with a view to assessing the utility of these parameters in predicting early HAT. A retrospective review of 144 pediatric recipients (73 males, 71 females) who underwent routine Doppler US in the first week after LDLT was undertaken, and changes in hepatic arterial hemodynamics were assessed. The HARI and HAPSV were compared in patients with early HAT (defined as occurring in the first postoperative week) and a control group, and the utility of these parameters in predicting early HAT after LDLT was determined. A total of 11 pediatric recipients experienced early HAT, being diagnosed on average four and a half days after LDLT. HARI and HAPSV values were significantly different between the early HAT group and controls. HARI values <0.6 on the day before the onset of early HAT were able to predict HAT development with a sensitivity of 81.8% and specificity of 95.2%. This provides evidence for routine Doppler US examination in these patients and supports consideration of more intensive anticoagulation in these high-risk patients.
Subject(s)
Hepatic Artery/pathology , Liver Failure/surgery , Liver Transplantation/methods , Liver/blood supply , Thrombosis/diagnosis , Child, Preschool , Female , Graft Survival , Hemodynamics , Humans , Infant , Liver/diagnostic imaging , Living Donors , Male , ROC Curve , Retrospective Studies , Risk , Sensitivity and Specificity , Thrombosis/pathology , Time Factors , Treatment Outcome , Ultrasonography, DopplerABSTRACT
OBJECTIVES: The purpose of this study was to evaluate the usefulness of real-time contrast-enhanced sonography and microvascular imaging for differential diagnosis of neoplastic and non-neoplastic polypoid lesions of the gallbladder. METHODS: Real-time contrast-enhanced sonography and microvascular imaging were performed in 128 patients with polypoid lesions of the gallbladder larger than 6 mm in diameter. The enhancement patterns, microvascular imaging types, and kinetic parameters were analyzed on contrast-enhanced sonography. The maximum diameters of the lesions measured by conventional and contrast-enhanced sonography were also recorded and subjected to a comparative analysis. RESULTS: Among the 128 patients, histologic diagnoses were obtained in 83 (27 neoplastic lesions and 56 non-neoplastic lesions), which constituted the study group. On contrast-enhanced sonography, mild enhancement and absence of contrast were more easily found in non-neoplastic lesions (12 [21.4%]), whereas all neoplastic lesions showed marked enhancement (27 [100%]; P = .006). Of the 27 neoplastic lesions, 6 malignant tumors showed a perfusion defect on contrast-enhanced sonography, whereas none of the non-neoplastic lesions showed a perfusion defect (P = .003). The microvascular architecture of the lesions was categorized into 4 types: spotty, linear, branched, and spinous, and there were significant differences between the groups (P< .001). In a kinetic evaluation, none of the parameters reached statistical significance (all P> .05). There was a discrepancy in maximum diameters between conventional and contrast-enhanced sonography in both groups but the discrepancy was significantly greater in the non-neoplastic group (P = .026). CONCLUSIONS: Contrast-enhanced sonography is a useful imaging technique and an adjunct to conventional sonography for differential diagnosis of neoplastic and non-neoplastic polypoid lesions of the gallbladder.
Subject(s)
Gallbladder Diseases/diagnostic imaging , Gallbladder Neoplasms/diagnostic imaging , Polyps/diagnostic imaging , Adult , Aged , Contrast Media , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Prospective Studies , Ultrasonography/methodsABSTRACT
BACKGROUND: Portal vein thrombosis (PVT) is one of the main vascular complications after liver transplantation (LT), especially in pediatric patients with biliary atresia (BA). This study aimed to assess the preoperative hepatic hemodynamics in pediatric patients with BA using Doppler ultrasound and determine whether ultrasonographic parameters may predict early PVT after LT. METHODS: One hundred and twenty-eight pediatric patients with BA younger than 3 years of age underwent Doppler ultrasound within seven days before LT, between October 2006 and June 2013. The preoperative hepatic hemodynamic parameters were then compared between patients with early PVT (within 1 month following LT) and those without PVT. Receiver operating characteristic analysis was performed to determine the optimal cutoff value for predicting early PVT. RESULTS: Of the 128 transplant recipients, 41 (32.03%) had a hypoplastic portal vein (PV), 52 (40.63%) had hepatofugal PV flow and 40 (31.25%) had a high hepatic artery resistance index (HARI) of ≥1. Nine cases (7.03%) experienced early PVT. A PV diameter ≤4 mm (sensitivity 88.89%, specificity 72.27%), and a hepatofugal PV flow (sensitivity 77.78%, specificity 62.18%) with a high HARI ≥1 (sensitivity 77.78%, specificity 72.27%) were hepatic hemodynamic risk factors for early PVT. CONCLUSIONS: Hepatic hemodynamic disturbances in pediatric recipients with BA were more common. Small PV diameter (≤4 mm) and hepatofugal PV flow combined with high HARI (≥1) are strong warning signs of early PVT after LT in pediatric patients with BA. Intense monitoring of vascular patency and prophylactic thrombolytic therapy should be considered in pediatric patients undergoing LT for BA.