RESUMO
Dysbiosis of gut microbiota may account for pathobiology in simple fatty liver (SFL), metabolic dysfunction-associated steatohepatitis (MASH), fibrotic progression, and transformation to MASH-associated hepatocellular carcinoma (MASH-HCC). The aim of the present study is to investigate gut dysbiosis in this progression. Fecal microbial rRNA-16S sequencing, absolute quantification, histopathologic, and biochemical tests were performed in mice fed high fat/calorie diet plus high fructose and glucose in drinking water (HFCD-HF/G) or control diet (CD) for 2, 16 weeks, or 14 months. Histopathologic examination verified an early stage of SFL, MASH, fibrotic, or MASH-HCC progression with disturbance of lipid metabolism, liver injury, and impaired gut mucosal barrier as indicated by loss of occludin in ileum mucosa. Gut dysbiosis occurred as early as 2 weeks with reduced α diversity, expansion of Kineothrix, Lactococcus, Akkermansia; and shrinkage in Bifidobacterium, Lactobacillus, etc., at a genus level. Dysbiosis was found as early as MAHS initiation, and was much more profound through the MASH-fibrotic and oncogenic progression. Moreover, the expansion of specific species, such as Lactobacillus johnsonii and Kineothrix alysoides, was confirmed by an optimized method for absolute quantification. Dynamic alterations of gut microbiota were characterized in three stages of early SFL, MASH, and its HCC transformation. The findings suggest that the extent of dysbiosis was accompanied with MASH progression and its transformation to HCC, and the shrinking or emerging of specific microbial species may account at least in part for pathologic, metabolic, and immunologic alterations in fibrogenic progression and malignant transition in the liver.
Assuntos
Carcinoma Hepatocelular , Disbiose , Microbioma Gastrointestinal , Neoplasias Hepáticas , Camundongos Endogâmicos C57BL , Animais , Camundongos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/microbiologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/microbiologia , Neoplasias Hepáticas/etiologia , Disbiose/microbiologia , Masculino , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado Gorduroso/microbiologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Progressão da Doença , Metabolismo dos Lipídeos , Fígado/metabolismo , Fígado/patologiaRESUMO
OBJECTIVE: To compare the ability of gadolinium ethoxybenzyl dimeglumine (Gd-EOB-DTPA) and gadobenate dimeglumine (Gd-BOPTA) to display the 3 major features recommended by the Liver Imaging Reporting and Data System (LI-RADS 2018v) for diagnosing hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In this retrospective study, we included 98 HCC lesions that were scanned with either Gd-EOB-DTPA-MR or Gd-BOPTA-M.For each lesion, we collected multiple variables, including size and enhancement pattern in the arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). The lesion-to-liver contrast (LLC) was measured and calculated for each phase and then compared between the 2 contrast agents. A P value < .05 was considered statistically significant. The display efficiency of the LLC between Gd-BOPTA and Gd-EOB-DTPA for HCC features was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Between Gd-BOPTA and Gd-EOB-DTPA, significant differences were observed regarding the display efficiency for capsule enhancement and the LLC in the AP/PVP/DP (P < .05), but there was no significant difference regarding the LLC in the TP/HBP. Both Gd-BOPTA and Gd-EOB-DTPA had good display efficiency in each phase (AUCmin > 0.750). When conducting a total evaluation of the combined data across the 5 phases, the display efficiency was excellent (AUC > 0.950). CONCLUSION: Gd-BOPTA and Gd-EOB-DTPA are liver-specific contrast agents widely used in clinical practice. They have their own characteristics in displaying the 3 main signs of HCC. For accurate noninvasive diagnosis, the choice of agent should be made according to the specific situation.
Assuntos
Carcinoma Hepatocelular , Meios de Contraste , Gadolínio DTPA , Neoplasias Hepáticas , Imageamento por Ressonância Magnética , Meglumina , Compostos Organometálicos , Curva ROC , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Feminino , Meglumina/análogos & derivados , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Adulto , Aumento da Imagem/métodos , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: To compare the ability to depict MRI features of hepatobiliary agents in microvascular infiltration (MVI) of hepatocellular carcinoma (HCC) during different stages of dynamic enhancement MRI. MATERIALS AND METHODS: A retrospective study included 111 HCC lesions scanned with either Gd-EOB-DTPA or Gd-BOPTA. All cases underwent multiphase dynamic contrast-enhanced scanning before surgery, including arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). Two abdominal radiologists independently evaluated MRI features of MVI in HCC, such as peritumoral hyperenhancement, incomplete capsule, non-smooth tumor margins, and peritumoral hypointensity. Finally, the results were reviewed by the third senior abdominal radiologist. Chi-square (χ2) Inspection for comparison between groups. P < 0.05 is considered statistically significant. Receiver operating characteristic (ROC) curve was used to evaluate correlation with pathology, and the area under the curve (AUC) and 95% confidence interval (95% CI) were calculated. RESULTS: Among the four MVI evaluation signs, Gd-BOPTA showed significant differences in displaying two signs in the HBP (P < 0.05:0.000, 0.000), while Gd-EOB-DTPA exhibited significant differences in displaying all four signs (P < 0.05:0.005, 0.006, 0.000, 0.002). The results of the evaluations of the two contrast agents in the DP phase with incomplete capsulation showed the highest correlation with pathology (AUC: 0.843, 0.761). By combining the four MRI features, Gd-BOPTA and Gd-EOB-DTPA have correlated significantly with pathology, and Gd-BOPTA is better (AUC: 0.9312vs0.8712). CONCLUSION: The four features of hepatobiliary agent dynamic enhancement MRI demonstrate a good correlation with histopathological findings in the evaluation of MVI in HCC, and have certain clinical significance.
Assuntos
Carcinoma Hepatocelular , Meios de Contraste , Gadolínio DTPA , Neoplasias Hepáticas , Imageamento por Ressonância Magnética , Meglumina , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Feminino , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Idoso , Meglumina/análogos & derivados , Compostos Organometálicos , Adulto , Microvasos/diagnóstico por imagem , Microvasos/patologia , Aumento da Imagem/métodosRESUMO
BACKGROUND AND AIMS: Liver regeneration retardation post partial hepatectomy (PH) is a common clinical problem after liver transplantation. Identification of key regulators in liver regeneration post PH may be beneficial for clinically improving the prognosis of patients after liver transplantation. This study aimed to clarify the function of junctional protein-associated with coronary artery disease (JCAD) in liver regeneration post PH and to reveal the underlying mechanisms. METHODS: JCAD knockout (JCAD-KO), liver-specific JCAD-KO (Jcadâ³Hep) mice and their control group were subjected to 70% PH. RNA sequencing was conducted to unravel the related signalling pathways. Primary hepatocytes from KO mice were treated with epidermal growth factor (EGF) to evaluate DNA replication. Fluorescent ubiquitination-based cell cycle indicator (FUCCI) live-imaging system was used to visualise the phases of cell cycle. RESULTS: Both global and liver-specific JCAD deficiency postponed liver regeneration after PH as indicated by reduced gene expression of cell cycle transition and DNA replication. Prolonged retention in G1 phase and failure to transition over the cell cycle checkpoint in JCAD-KO cell line was indicated by a FUCCI live-imaging system as well as pharmacologic blockage. JCAD replenishment by adenovirus reversed the impaired DNA synthesis in JCAD-KO primary hepatocyte in exposure to EGF, which was abrogated by a Yes-associated protein (YAP) inhibitor, verteporfin. Mechanistically, JCAD competed with large tumour suppressor 2 (LATS2) for WWC1 interaction, leading to LATS2 inhibition and thereafter YAP activation, and enhanced expression of cell cycle-associated genes. CONCLUSION: JCAD deficiency led to delayed regeneration after PH as a result of blockage in cell cycle progression through the Hippo-YAP signalling pathway. These findings uncovered novel functions of JCAD and suggested a potential strategy for improving graft growth and function post liver transplantation. KEY POINTS: JCAD deficiency leads to an impaired liver growth after PH due to cell division blockage. JCAD competes with LATS2 for WWC1 interaction, resulting in LATS2 inhibition, YAP activation and enhanced expression of cell cycle-associated genes. Delineation of JCADHippoYAP signalling pathway would facilitate to improve prognosis of acute liver failure and graft growth in living-donor liver transplantation.
Assuntos
Moléculas de Adesão Celular , Regeneração Hepática , Transplante de Fígado , Animais , Humanos , Camundongos , Fator de Crescimento Epidérmico/genética , Fator de Crescimento Epidérmico/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fígado/metabolismo , Regeneração Hepática/genética , Doadores Vivos , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Moléculas de Adesão Celular/metabolismoRESUMO
The vertical groundwater circulation well (GCW) is a commonly used technique in contaminated sites to remove secondary contaminants from low permeable zones. Early GCW studies often used simple subsurface hydraulic properties, such as anisotropic homogeneous aquifers or low conductivity lens/blocks, to mimic the complex subsurface heterogeneity. Although studies based on simplified representations of aquifer heterogeneity provide straightforward flow and transport information for engineering design of a GCW, they may over- or under-estimate contaminant fate and transport in the field. The objective of this study is to identify key heterogeneity factors that control the capture zone extension and to examine the extent to which the accuracy of estimated heterogeneity spatial distributions influences the prediction of remedial reagent transport. To achieve these objectives, we utilized Monte Carlo simulation to investigate the extension of the circulation zone in heterogeneous aquifers and to identify the key factors that contribute most to the variability of the circulation zone. Three commonly used geostatistical approaches (equivalent homogeneous, kriging, and highly parameterized methods) were employed to estimate the spatial distributions of key factors. The reliabilities of these estimated fields were evaluated through their remedial reagent transport predictability. The key factor analysis revealed that the mean porosity value, the variance of lnK, and the correlation length of lnK profoundly influence the lateral expansion of the capture zone. Neglecting the aquifer hydraulic conductivity heterogeneity underestimates the extension of the circulation zone and the spread of remedial reagent. Additionally, utilizing a highly parameterized approach to estimate the high-resolution K field can accurately reproduce the key remedial reagent distributions. The concentration arrival time and peak concentration are significantly improved compared to those predictions based on the equivalent homogeneous and kriged K fields.
RESUMO
BACKGROUND/AIMS: Cholestatic liver diseases including primary biliary cholangitis (PBC) are associated with active hepatic fibrogenesis, which ultimately progresses to cirrhosis. Activated hepatic stellate cells (HSCs) are the main fibrogenic effectors in response to cholangiocyte damage. JCAD regulates cell proliferation and malignant transformation in nonalcoholic steatoheaptitis-associated hepatocellular carcinoma (NASH-HCC). However, its participation in cholestatic fibrosis has not been explored yet. METHODS: Serial sections of liver tissue of PBC patients were stained with immunofluorescence. Hepatic fibrosis was induced by bile duct ligation (BDL) in wild-type (WT), global JCAD knockout mice (JCAD-KO) and HSC-specific JCAD knockout mice (HSC-JCAD-KO), and evaluated by histopathology and biochemical tests. In situ-activated HSCs isolated from BDL mice were used to determine effects of JCAD on HSC activation. RESULTS: In consistence with staining of liver sections from PBC patients, immunofluorescent staining revealed that JCAD expression was identified in smooth muscle α-actin (α-SMA)-positive fibroblast-like cells and was significantly up-regulated in WT mice with BDL. JCAD deficiency remarkably ameliorated BDL-induced hepatic injury and fibrosis, as documented by liver hydroxyproline content, when compared to WT mice with BDL. Histopathologically, collagen deposition was dramatically reduced in both JCAD-KO and HSC-JCAD-KO mice compared to WT mice, as visualized by Trichrome staining and semi-quantitative scores. Moreover, JCAD deprivation significantly attenuated in situ HSC activation and reduced expression of fibrotic genes after BDL. CONCLUSION: JCAD deficiency effectively suppressed hepatic fibrosis induced by BDL in mice, and the underlying mechanisms are largely through suppressed Hippo-YAP signaling activity in HSCs.
Assuntos
Carcinoma Hepatocelular , Moléculas de Adesão Celular , Colestase , Neoplasias Hepáticas , Animais , Humanos , Camundongos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Colestase/complicações , Colestase/metabolismo , Colestase/patologia , Células Estreladas do Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/patologia , Camundongos Knockout , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismoRESUMO
Purpose: The global fight against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has led to widespread vaccination efforts, yet the optimal dosing schedule for SARS-CoV-2 vaccines remains a subject of ongoing research. This study aims to investigate the effectiveness of administering two booster doses as the third and fourth doses at different intervals to enhance vaccine protection. Materials and Methods: This study was conducted at a military regional hospital operated by the Ministry of National Defense in Taiwan. A cohort of vaccinated individuals was selected, and their vaccine potency was assessed at various time intervals following their initial vaccine administration. The study participants received booster doses as the third and fourth doses, with differing time intervals between them. The study monitored neutralizing antibody titers and other relevant parameters to assess vaccine efficacy. Results: Our findings revealed that the potency of the SARS-CoV-2 vaccine exhibited a significant decline 80 days after the initial vaccine administration. However, a longer interval of 175 days between booster injections resulted in significantly higher neutralizing antibody titers. The individuals who received the extended interval boosters exhibited a more robust immune response, suggesting that a vaccine schedule with a 175-day interval between injections may provide superior protection against SARS-CoV-2. Conclusion: This study underscores the importance of optimizing vaccine booster dosing schedules to maximize protection against SARS-CoV-2. The results indicate that a longer interval of 175 days between the third and fourth doses of the vaccine can significantly enhance the neutralizing antibody response, potentially offering improved protection against the virus. These findings have important implications for vaccine distribution and administration strategies in the ongoing battle against the SARS-CoV-2 pandemic. Further research and large-scale trials are needed to confirm and extend these findings for broader public health implications.
RESUMO
BACKGROUND: Dental panoramic imaging plays a pivotal role in dentistry for diagnosis and treatment planning. However, correctly positioning patients can be challenging for technicians due to the complexity of the imaging equipment and variations in patient anatomy, leading to positioning errors. These errors can compromise image quality and potentially result in misdiagnoses. OBJECTIVE: This research aims to develop and validate a deep learning model capable of accurately and efficiently identifying multiple positioning errors in dental panoramic imaging. METHODS AND MATERIALS: This retrospective study used 552 panoramic images selected from a hospital Picture Archiving and Communication System (PACS). We defined six types of errors (E1-E6) namely, (1) slumped position, (2) chin tipped low, (3) open lip, (4) head turned to one side, (5) head tilted to one side, and (6) tongue against the palate. First, six Convolutional Neural Network (CNN) models were employed to extract image features, which were then fused using transfer learning. Next, a Support Vector Machine (SVM) was applied to create a classifier for multiple positioning errors, using the fused image features. Finally, the classifier performance was evaluated using 3 indices of precision, recall rate, and accuracy. RESULTS: Experimental results show that the fusion of image features with six binary SVM classifiers yielded high accuracy, recall rates, and precision. Specifically, the classifier achieved an accuracy of 0.832 for identifying multiple positioning errors. CONCLUSIONS: This study demonstrates that six SVM classifiers effectively identify multiple positioning errors in dental panoramic imaging. The fusion of extracted image features and the employment of SVM classifiers improve diagnostic precision, suggesting potential enhancements in dental imaging efficiency and diagnostic accuracy. Future research should consider larger datasets and explore real-time clinical application.
Assuntos
Aprendizado Profundo , Sistemas de Informação em Radiologia , Humanos , Estudos Retrospectivos , Diagnóstico por Imagem , Redes Neurais de ComputaçãoRESUMO
OBJECTIVE: To investigate the incidence of air embolism (AE) related to CT-guided localization of pulmonary ground-glass nodules (GGNs) prior to video-assisted thoracoscopic surgery (VATS). METHODS: The data of all patients who received CT-guided localization of GGNs before VATS from May 2020 to October 2021 were retrospectively analyzed. RESULTS: A total of 1395 consecutive patients with 1553 GGNs were enrolled. AEs occurred in seven patients (0.5%). In four of the seven patients with AE, the embolism was detected before the patients left the CT table and emergency treatments were carried out. Among them, one patient had chest tightness and unilateral limb dyskinesia, one patient had convulsions and transient loss of consciousness, and two patients had no definite clinical symptoms. After a short-term high-flow oxygen inhalation, the clinical symptoms of two patients with symptomatic AE disappeared and two patients with asymptomatic AE did not show any symptoms. In the remaining three patients with AE, the embolism were detected retrospectively when evaluating the images in the PACS for this study. Fortunately, these three patients never developed clinical symptoms related to AE. All seven patients with AE underwent VATS on the day of localization and all GGNs were successfully removed under the guidance of markers. CONCLUSION: The incidence of AE related to CT-guided localization of GGNs was 0.5%, which was significantly higher than expected. Post-localization whole thoracic CT should be performed and observed carefully so as to avoid missed AE and delayed treatment. ADVANCES IN KNOWLEDGE: The incidence of AE related to CT-guided localization of GGNs was 0.5%. In order to timely detect AE, whole thoracic CT scan rather than local CT in the lesion area should be performed after localization. A small amount of AE may be missed if the post- localization CT images are not carefully observed.
Assuntos
Embolia Aérea , Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Neoplasias Pulmonares/patologia , Embolia Aérea/diagnóstico por imagem , Embolia Aérea/etiologia , Estudos Retrospectivos , Nódulo Pulmonar Solitário/cirurgia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Tomografia Computadorizada por Raios X/métodosRESUMO
Although the important role of cell intercalation within a collective has long been recognized particularly for morphogenesis, the underlying mechanism remains poorly understood. Here we investigate the possibility that cellular responses to cyclic stretching play a major role in this process. By applying synchronized imaging and cyclic stretching to epithelial cells cultured on micropatterned polyacrylamide (PAA) substrates, we discovered that uniaxial cyclic stretching induces cell intercalation along with cell shape change and cell-cell interfacial remodeling. The process involved intermediate steps as previously reported for cell intercalation during embryonic morphogenesis, including the appearance of cell vertices, anisotropic vertex resolution, and directional expansion of cell-cell interface. Using mathematical modeling, we further found that cell shape change in conjunction with dynamic cell-cell adhesions was sufficient to account for the observations. Further investigation with small-molecule inhibitors indicated that disruption of myosin II activities suppressed cyclic stretching-induced intercalation while inhibiting the appearance of oriented vertices. Inhibition of Wnt signaling did not suppress stretch-induced cell shape change but disrupted cell intercalation and vertex resolution. Our results suggest that cyclic stretching, by inducing cell shape change and reorientation in the presence of dynamic cell-cell adhesions, can induce at least some aspects of cell intercalation and that this process is dependent in distinct ways on myosin II activities and Wnt signaling.
Assuntos
Células Epiteliais , Miosina Tipo II , Adesão Celular , Morfogênese , Miosina Tipo II/metabolismo , Estresse MecânicoRESUMO
BACKGROUND: Pancreatic segmental portal hypertension (PSPH) is the only type of portal hypertension that can be completely cured. However, it can easily cause varicose veins in the esophagus and stomach and hemorrhage in the digestive tract. AIM: To explore the application of computed tomography (CT) to examine the characteristics of PSPH and assess the risk level. METHODS: This was a retrospective analysis of CT images of 22 patients diagnosed with PSPH at our center. Spearman correlation analysis was performed using the range of esophageal and gastric varices (measured by the vertical gastric wall), the ratio of the width of the splenic portal vein to that of the compression site (S/C ratio), the degree of splenomegaly, and the stage determined by gastroscopy. This study examined whether patients experienced gastrointestinal bleeding within 2 wk and combined CT and gastroscopy to explore the connection between bleeding and CT findings. RESULTS: The range of esophageal and gastric varices showed the best correlation in the diagnosis of PSPH (P < 0.001), and the S/C ratio (P = 0.007) was correlated with the degree of splenomegaly (P = 0.021) and PSPH (P < 0.05). This study revealed that male patients were more likely than females to progress to grade 2 or grade 3 as determined by gastroscopy. CT demonstrated excellent performance, with an area under the curve of 0.879. CONCLUSION: CT can be used to effectively analyze the imaging signs of PSPH, and CT combined with gastroscopy can effectively predict the risk level of gastrointestinal bleeding.
RESUMO
Morinda officinalis oligosaccharides (MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. Here, we show that oral MOO acted on tryptophan â 5-hydroxytryptophan (5-HTP) â serotonin (5-HT) metabolic pathway in the gut microbiota. MOO could increase tryptophan hydroxylase levels in the gut microbiota which accelerated 5-HTP production from tryptophan; meanwhile, MOO inhibited 5-hydroxytryptophan decarboxylase activity, thus reduced 5-HT generation, and accumulated 5-HTP. The raised 5-HTP from the gut microbiota was absorbed to the blood, and then passed across the blood-brain barrier to improve 5-HT levels in the brain. Additionally, pentasaccharide, as one of the main components in MOO, exerted the significant anti-depressant effect through a mechanism identical to that of MOO. This study reveals for the first time that MOO can alleviate depression via increasing 5-HTP in the gut microbiota.
RESUMO
BACKGROUND: Metabolic disorder increases the risk of abdominal aortic aneurysm (AAA). NRs (nuclear receptors) have been increasingly recognized as important regulators of cell metabolism. However, the role of NRs in AAA development remains largely unknown. METHODS: We analyzed the expression profile of the NR superfamily in AAA tissues and identified NR1D1 (NR subfamily 1 group D member 1) as the most highly upregulated NR in AAA tissues. To examine the role of NR1D1 in AAA formation, we used vascular smooth muscle cell (VSMC)-specific, endothelial cell-specific, and myeloid cell-specific conditional Nr1d1 knockout mice in both AngII (angiotensin II)- and CaPO4-induced AAA models. RESULTS: Nr1d1 gene expression exhibited the highest fold change among all 49 NRs in AAA tissues, and NR1D1 protein was upregulated in both human and murine VSMCs from AAA tissues. The knockout of Nr1d1 in VSMCs but not endothelial cells and myeloid cells inhibited AAA formation in both AngII- and CaPO4-induced AAA models. Mechanistic studies identified ACO2 (aconitase-2), a key enzyme of the mitochondrial tricarboxylic acid cycle, as a direct target trans-repressed by NR1D1 that mediated the regulatory effects of NR1D1 on mitochondrial metabolism. NR1D1 deficiency restored the ACO2 dysregulation and mitochondrial dysfunction at the early stage of AngII infusion before AAA formation. Supplementation with αKG (α-ketoglutarate, a downstream metabolite of ACO2) was beneficial in preventing and treating AAA in mice in a manner that required NR1D1 in VSMCs. CONCLUSIONS: Our data define a previously unrecognized role of nuclear receptor NR1D1 in AAA pathogenesis and an undescribed NR1D1-ACO2 axis involved in regulating mitochondrial metabolism in VSMCs. It is important that our findings suggest αKG supplementation as an effective therapeutic approach for AAA treatment.
Assuntos
Aneurisma da Aorta Abdominal , Humanos , Camundongos , Animais , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/prevenção & controle , Aorta Abdominal/patologia , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo , Músculo Liso Vascular/metabolismo , Ciclo do Ácido Cítrico , Miócitos de Músculo Liso/metabolismo , Angiotensina II/efeitos adversos , Camundongos Knockout , Aconitato Hidratase/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BLRESUMO
Background: Gliomas are more malignant and invasive than meningiomas. Objective: To distinguish meningiomas from low-grade/high-grade gliomas (LGGs/HGGs) using amide proton transfer imaging (APT) combined with conventional magnetic resonance imaging (MRI) and to explore the application of APT in evaluating brain tumour invasiveness. Materials and Methods: The imaging data of 50 brain tumors confirmed by pathology in patients who underwent APT scanning in our centre were retrospectively analysed. Of these tumors, 25 were meningiomas, 10 were LGGs, and 15 were HGGs. The extent of the tumour-induced range was measured on APT images, T2-weighted imaging (T2WI), and MRI enhancement; additionally, and the degree of enhancement was graded. Ratios (RAPT/T2 and RAPT/E) were obtained by dividing the range of changes observed by APT by the range of changes observed via T2WI and MR enhancement, respectively, and APTmean values were measured. The Mann-Whitney U test was used to compare the above measured values with the pathological results obtained for gliomas and meningiomas, the Kruskal-Wallis test was used to compare LGGs, HGGs and meningiomas, and Dunn's test was used for pairwise comparisons. In addition, receiver operating characteristic (ROC) curves were drawn. Results: The Mann-Whitney U test showed that APTmean (p=0.005), RAPT/T2 (p<0.001), and RAPT/E (p<0.001) values were statistically significant in the identification of meningioma and glioma. The Kruskal-Wallis test showed that the parameters APTmean, RAPT/T2, RAPT/E and the degree of enhancement are statistically significant. Dunn's test revealed that RAPT/T2 (p=0.004) and RAPT/E (p=0.008) could be used for the identification of LGGs and meningiomas. APTmean (p<0.001), RAPT/T2 (p<0.001), and RAPT/E (p<0.001) could be used for the identification of HGGs and meningiomas. APTmean (p<0.001) was statistically significant in the comparison of LGGs and HGGs. ROC curves showed that RAPT/T2 (area under the curve (AUC)=0.947) and RAPT/E (AUC=0.919) could be used to distinguish gliomas from meningiomas. Conclusion: APT can be used for the differential diagnosis of meningioma and glioma, but APTmean values can only be used for the differential diagnosis of HGGs and meningiomas or HGGs and LGGs. Gliomas exhibit more obvious changes than meningiomas in APT images of brain tissue; this outcome may be caused by brain infiltration.
RESUMO
OBJECTIVES: To evaluate the efficacy and safety of marking ground glass nodules (GGNs) with pulmonary nodules localization needle (PNLN) prior to video-assisted thoracoscopic surgery (VATS). MATERIALS AND METHODS: From June 2020 to February 2021, all patients with GGNs who received CT-guided localization using PNLN before VATS were enrolled. Clinical and imaging data were retrospectively analyzed. RESULTS: A total of 352 consecutive patients with 395 GGNs were included in the study. The mean diameter of GGNs was 0.95 ± 0.48 cm, and the shortest distance from nodules to the pleura was 1.73 ± 0.96 cm. All 395 GGNs were marked using PNLNs. The time required for marking was 7.8 ± 2.2 min. The marking success rate was 99.0% (391/395). The marking failure of four nodules was all due to the unsatisfactory position of PNLNs. No marker dislocation occurred. Marking-related complications included pneumothorax in 63 cases (17.9%), hemorrhage in 34 cases (9.7%), and hemoptysis in 6 cases (1.7%). All the complications were minor and did not need special treatment. Localization and VATS were performed on the same day in 95 cases and on different days in 257 cases. All GGNs were successfully removed by VATS. No patient converted to thoracotomy. Histopathological examination revealed 74 (18.7%) benign nodules and 321 (81.3%) malignant nodules. CONCLUSIONS: It is safe and reliable to perform preoperative localization of GGNs using PNLNs, which can effectively guide VATS to remove GGNs. KEY POINTS: ⢠Preoperative localization of GGNs could effectively guide VATS to remove GGNs. ⢠PNLN was based on the marking principle of hook-wire, through the improvement of its material, specially designed to mark pulmonary nodules. ⢠The application of PNLN to mark GGNs had high success rate, good patient tolerance, and no dislocation. Meanwhile, VATS could be performed 2 to 3 days after marking GGNs with PNLN.
Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Estudos Retrospectivos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/cirurgia , Cirurgia Torácica Vídeoassistida/métodosRESUMO
BACKGROUND: Compared with traditional computed tomography (CT), dual-layer spectral detector CT (SDCT) shows significant improvement in imaging soft tissues of the digestive tract. This work aimed to explore the application of SDCT to evaluate the expression of the molecular marker Ki-67 in colorectal cancer. METHODS: We retrospectively analyzed the imaging data of the SDCT (IQon Spectral CT; Philips Healthcare) of 45 patients with colorectal cancer in our centre. We used Spearman's test for the imaging parameters (reconstruction of 40, 70, and 100 keV virtual monoenergetic images [VMIs] and the slope of the Hounsfield unit attenuation plot [VMI Slope] based on venous phase CT images, the arterial phase iodine concentration [AP-IC] and venous phase iodine concentration [VP-IC], and the effective atomic number [Z effect]) and correlation analysis for the Ki-67 index. Multivariate logistic regression was used to eliminate confounding factors. We evaluated the expression level of Ki-67 and drew the receiver operating characteristic curve. RESULTS: The 40-keV VMI, VMI Slope, and AP-IC were found to better reflect the Ki-67 index in patients with colorectal cancer with statistical significance. The 40-keV VMI (r = -0.612, p < 0.001) and VMI Slope (r = -0.523, p < 0.001) were negatively correlated with the Ki-67 index, and AP-IC (r = 0.378, p = 0.010) was positively correlated with the Ki-67 index. The other indexes (p > 0.05) were not statistically significant. The SDCT parameters demonstrated good performance, with area under curves of 0.785 for 40-keV VMI and 0.752 for AP-IC. CONCLUSION: The SDCT parameters 40-keV VMI and AP-IC can be used for preliminary evaluation of the Ki-67 index in colorectal cancer.
Assuntos
Neoplasias Colorretais , Iodo , Neoplasias Colorretais/diagnóstico por imagem , Humanos , Antígeno Ki-67 , Estudos Retrospectivos , Razão Sinal-Ruído , Tomografia Computadorizada por Raios X/métodosRESUMO
This study aimed to add two functional components-antibacterial 45S5BGs particles and AIE nanoparticles (TPE-NIM+) with bioprobe characteristics-to the guided tissue regeneration (GTR) membrane, to optimize the performance. The PLGA/BG/TPE-NIM+ membrane was synthesized. The static water contact angle, morphologies, and surface element analysis of the membrane were then characterized. In vitro biocompatibility was tested with MC3T3-E1 cells using CCK-8 assay, and antibacterial property was evaluated with Streptococcus mutans and Porphyromonas gingivalis by the LIVE/DEAD bacterial staining and dilution plating procedure. The fluorescence staining of bacteria was observed by Laser Scanning Confocal Microscope. The results showed that the average water contact angle was 46°. In the cytotoxicity test, except for the positive control group, there was no significant difference among the groups (p > 0.05). The antibacterial effect in the PLGA/BG/TPE-NIM+ group was significantly (p < 0.01), while the sterilization rate was 99.99%, better than that in the PLGA/BG group (98.62%) (p < 0.01). Confocal images showed that the membrane efficiently distinguished G+ bacteria from G- bacteria. This study demonstrated that the PLGA/BG/TPE-NIM+ membrane showed good biocompatibility, efficient sterilization performance, and surface mineralization ability and could be used to detect pathogens in a simple, fast, and wash-free protocol.
RESUMO
Groundwater responses measured from multiple wells at different depths are essential for delineating the aquifer heterogeneity using hydraulic tomography (HT). In general, conducting HT requires many wells because traditional well monitoring is usually partially open at a specific depth interval or is fully penetrating. Accordingly, conducting an HT survey is typically costly and time-consuming. To tackle these issues, a new multi-level monitoring system (MLMS) for the HT survey was developed using the fiber Bragg grating (FBG) technique. This FBG MLMS could collect the depth-discrete groundwater observations from a fully penetrated 2-inch well. Three field campaigns were conducted to validate the capability of the FBG MLMS for HT surveys. The results show that the accuracy and stability of this MLMS are reliable and that FBG MLMS is beneficial for conducting an HT survey. Specifically, compared to the traditional monitoring well in an injection event, this FBG MLMS can concurrently cause an increase in the number of cross-hole tests several times and collect many more head observations than the standard methods, resulting in the observed flow fields efficiently reaching ergodic conditions and effectively improving the accuracy of the estimated hydraulic heterogeneity. Therefore, the FBG MLMS could be an alternative MLMS for efficiently and economically conducting an HT survey.
Assuntos
Água Subterrânea , Tomografia , Tomografia Computadorizada por Raios X , Poços de ÁguaRESUMO
Background and objectives: Pheochromocytoma and adrenal adenoma are common space-occupying lesions of the adrenal gland, and incorrect surgery may lead to adrenal crisis. We used a new method, dual-energy spectral detector computed tomography (SDCT), to differentiate between the two. Materials and methods: We analysed the imaging images of patients with SDCT scans and pathologically confirmed adrenal adenomas (n=70) and pheochromocytomas (n=15). The 40, 70, and 100 KeV virtual monoenergetic images (VMIs) were reconstructed based on the SCDT arterial phase, and the correlation between the arterial/venous phase iodine concentration (AP-IC/VP-IC), the effective atomic number (Z-effect), the slope of the Hounsfield unit attenuation plot (VMI slope) and the pathological results was tested. The Shapiro-Wilk test was used to determine whether the above data conformed to a normal distribution. For parameters with P greater than 0.05, Student's t test was used, and the Mann-Whitney test was used for the remaining parameters. A ROC curve was drawn based on the results. Results: Student's t test showed that the 40 KeV VMI and the VMI slope were both statistically significant (P<0.01). The Mann-Whitney U test showed that ID-A was statistically significant (P=0.004). ROC curve analysis showed that 40 keV VMI (AUC=0.818), AP-IC (AUC=0.736), difference (AUC=0.817) and VMI-Slope (0.817) could be used to differentiate adrenal adenoma from pheochromocytoma. Conclusion: The effect of lipid components on SDCT parameters can be used to differentiate adrenal adenoma from pheochromocytoma.