RESUMEN

Bile infarct is a pivotal characteristic of obstructive biliary disease, but its evolution during the disease progression remains unclear. Our objective, therefore, is to explore morphological alterations of the bile infarct in the disease course by means of multiscale X-ray phase-contrast CT. Bile duct ligation is performed in mice to mimic the obstructive biliary disease. Intact liver lobes of the mice are scanned by phase-contrast CT at various resolution scales. Phase-contrast CT clearly presents three-dimensional (3D) images of the bile infarcts down to the submicron level with good correlation with histological images. The CT data illustrates that the infarct first appears on day 1 post-BDL, while a microchannel between the infarct and hepatic sinusoids is identified, the number of which increases with the disease progression. A 3D model of hepatic acinus is proposed, in which the infarct starts around the portal veins (zone I) and gradually progresses towards the central veins (zone III) during the disease process. Multiscale phase-contrast CT offers the comprehensive analysis of the evolutionary features of the bile infarct in obstructive biliary disease. During the course of the disease, the bile infarcts develop infarct-sinusoidal microchannels and gradually occupy the whole liver, promoting the disease progression.

Asunto(s)

RESUMEN

Introduction: Diabetic kidney disease (DKD), one of the leading causes of end-stage renal disease, has complex pathogenic mechanisms and few effective clinical therapies. DKD progression is accompanied by the loss of renal resident cells, followed by chronic inflammation and extracellular matrix deposition. Necroptosis is a newly discovered form of regulated cell death and is a major form of intrinsic cell loss in certain diabetic complications such as cardiomyopathy, intestinal disease, and retinal neuropathy; however, its significance in DKD is largely unknown. Methods: In this study, the expression of necroptosis marker phosphorylated MLKL (p-MLKL) in renal biopsy tissues of patients with DKD was detected using immunofluorescence and semiquantified using immunohistochemistry. The effects of different disease-causing factors on necroptosis activation in human HK-2 cells were evaluated using immunofluorescence and Western blotting. db/db diabetic mice were fed a high-fat diet to establish an animal model of DKD with significant renal tubule damage. Mice were treated with the RIPK1 inhibitor RIPA-56 to evaluate its renal protective effects. mRNA transcriptome sequencing was used to explore the changes in signaling pathways after RIPA-56 treatment. Oil red O staining and electron macroscopy were used to observe lipid droplet accumulation in renal biopsy tissues and mouse kidney tissues. Results: Immunostaining of phosphorylated RIPK1/RIPK3/MLKL verified the occurrence of necroptosis in renal tubular epithelial cells of patients with DKD. The level of the necroptosis marker p-MLKL correlated positively with the severity of renal functional, pathological damages, and lipid droplet accumulation in patients with DKD. High glucose and fatty acids were the main factors causing necroptosis in human renal tubular HK-2 cells. Renal function deterioration and renal pathological injury were accelerated, and the necroptosis pathway was activated in db/db mice fed a high-fat diet. Application of RIPA-56 effectively reduced the degree of renal injury, inhibited the necroptosis pathway activation, and reduced necroinflammation and lipid droplet accumulation in the renal tissues of db/db mice fed a high-fat diet. Conclusion: The present study revealed the role of necroptosis in the progression of DKD and might provide a new therapeutic target for the treatment of DKD.

RESUMEN

BACKGROUND: Since most infants are usually discharged before age 48-72 hours, peak bilirubin levels will almost always occur after discharge. Parents may be the first to observe the onset of jaundice after discharge, but visual assessment is unreliable. The jaundice colour card (JCard) is a low-cost icterometer designed for the assessment of neonatal jaundice. The objective of this study was to evaluate parental use of JCard to detect jaundice in neonates. METHODS: We conducted a multicentre, prospective, observational cohort study in nine sites across China. A total of 1161 newborns ≥35 weeks of gestation were enrolled in the study. Measurements of total serum bilirubin (TSB) levels were based on clinical indications. The JCard measurements by parents and paediatricians were compared with the TSB. RESULTS: JCard values of parents and paediatricians were correlated with TSB (r=0.754 and 0.788, respectively). The parents' and paediatricians' JCard values 9 had sensitivities of 95.2% vs 97.6% and specificities of 84.5% vs 71.7% for identifying neonates with TSB ≥153.9 µmol/L. The parents' and paediatricians' JCard values 15 had sensitivities of 79.9% vs 89.0% and specificities of 66.7% vs 64.9% for identifying neonates with TSB ≥256.5 µmol/L. Areas under the receiver operating characteristic curves of parents for identifying TSB ≥119.7, ≥153.9, ≥205.2, and ≥256.5 µmol/L were 0.967, 0.960, 0.915, and 0.813, respectively, and those of paediatricians were 0.966, 0.961, 0.926 and 0.840, respectively. The intraclass correlation coefficient was 0.933 between parents and paediatricians. CONCLUSION: The JCard can be used to classify different levels of bilirubin, but it is less accurate with high bilirubin levels. The JCard diagnostic performance of parents was slightly lower than that of paediatricians.

Asunto(s)

RESUMEN

OBJECTIVE: Mounting evidence has linked microbiome and metabolome to systemic autoimmunity and cardiovascular diseases (CVDs). Takayasu arteritis (TAK) is a rare disease that shares features of immune-related inflammatory diseases and CVDs, about which there is relatively limited information. This study was undertaken to characterize gut microbial dysbiosis and its crosstalk with phenotypes in TAK. METHODS: To address the discriminatory signatures, we performed shotgun sequencing of fecal metagenome across a discovery cohort (n = 97) and an independent validation cohort (n = 75) including TAK patients, healthy controls, and controls with Behçet's disease (BD). Interrogation of untargeted metabolomics and lipidomics profiling of plasma and fecal samples were also used to refine features mediating associations between microorganisms and TAK phenotypes. RESULTS: A combined model of bacterial species, including unclassified Escherichia, Veillonella parvula, Streptococcus parasanguinis, Dorea formicigenerans, Bifidobacterium adolescentis, Lachnospiraceae bacterium 7 1 58FAA, Escherichia coli, Streptococcus salivarius, Klebsiella pneumoniae, Bifidobacterium longum, and Lachnospiraceae Bacterium 5 1 63FAA, distinguished TAK patients from controls with areas under the curve (AUCs) of 87.8%, 85.9%, 81.1%, and 71.1% in training, test, and validation sets including healthy or BD controls, respectively. Diagnostic species were directly or indirectly (via metabolites or lipids) correlated with TAK phenotypes of vascular involvement, inflammation, discharge medication, and prognosis. External validation against publicly metagenomic studies (n = 184) on hypertension, atrial fibrillation, and healthy controls, confirmed the diagnostic accuracy of the model for TAK. CONCLUSION: This study first identifies the discriminatory gut microbes in TAK. Dysbiotic microbes are also linked to TAK phenotypes directly or indirectly via metabolic and lipid modules. Further explorations of the microbiome-metagenome interface in TAK subtype prediction and pathogenesis are suggested.

Asunto(s)

RESUMEN

OBJECTIVES: To investigate microvascular alterations in the Glisson system of biliary atresia (BA) patients after Kasai portoenterostomy (KP) using three-dimensional (3D) virtual histopathology based on X-ray phase-contrast CT (PCCT). METHODS: Liver explants from BA patients were imaged using PCCT, and 32 subjects were included and divided into two groups: KP (n = 16) and non-KP (n = 16). Combined with histological analysis and 3D visualization technology, 3D virtual histopathological assessment of the biliary, arterial, and portal venous systems was performed. According to loop volume ratio, 3D spatial density, relative surface area, tortuosity, and other parameters, pathological changes of microvasculature in the Glisson system were investigated. RESULTS: In the non-KP group, bile ducts mostly manifested as radial multifurcated hyperplasia and twisted into loops. In the KP group, the bile duct hyperplasia was less, and the loop volume ratio of bile ducts decreased by 13.89%. Simultaneously, the arterial and portal venous systems presented adaptive alterations in response to degrees of bile duct hyperplasia. Compared with the non-KP group, the 3D spatial density of arteries in the KP group decreased by 3.53%, and the relative surface area decreased from 0.088 ± 0.035 to 0.039 ± 0.015 (p < .01). Deformed portal branches gradually recovered after KP, with a 2.93% increase in 3D spatial density and a decrease in tortuosity from 1.17 ± 0.06 to 1.14 ± 0.04 (p < .01) compared to the non-KP group. CONCLUSION: 3D virtual histopathology via PCCT clearly reveals the microvascular structures in the Glisson system of BA patients and provides key insights into the morphological mechanism of microvascular adaptation induced by biliary tract dredging after KP in BA disease. KEY POINTS: • 3D virtual histopathology via X-ray phase-contrast computed tomography clearly presented the morphological structures and pathological changes of microvasculature in the Glisson system of biliary atresia patients. • The morphological alterations of microvasculature in the Glisson system followed the competitive occupancy mechanism in the process of biliary atresia.

Asunto(s)

RESUMEN

Objective: To analyze the clinical manifestations and imaging features of a hospitalized patient with intermittent headache who was finally diagnosed with von Hippel-Lindau (VHL) syndrome and to perform whole-exon gene detection to improve the understanding of the diagnosis and treatment strategies of the disease. Methods: A case of suspected VHL syndrome in Shanxi Provincial People's Hospital was analyzed. Proband DNA was also extracted for whole exome sequencing and screened for causative mutation sites, which were validated by Sanger sequencing. The literature about VHL gene mutations in Chinese patients in the past 10 years were also reviewed. Results: There is a heterozygous mutation site c.499C > G on the VHL gene on the short arm of chromosome 3 of the patient, which is a missense mutation. The mutation results in the substitution of arginine with glycine at amino acid 167 of the encoded protein, which may be primarily responsible for the disease in the patient with VHL syndrome. However, the mutation did not occur in other family members. Conclusion: Early recognition and treatment of VHL syndrome can be available with genetic testing technology. Strengthening the understanding of this complex genetic disease and improving the diagnostic rate of VHL syndrome are helpful for the precise treatment of patients with this disease, which may help prolong the survival time of patients to a certain extent and improve their quality of life.

RESUMEN

Background: Dysbiosis of the gut microbiota is closely related to chronic systemic inflammation and autoimmunity, playing an essential role in the pathogenesis of primary Sjögren's syndrome (pSS). Abnormalities in the proportions of blood T lymphocyte subtype, that is Th17/Treg, were detected in pSS patients. We aimed to determine the associations between gut microbiota and Th17/Treg in pSS. Method: 98 pSS patients and 105 healthy controls (NC) were enrolled between Dec 1, 2018, and Aug 31, 2019. The baseline information and clinical parameters on pSS patients and healthy controls were collected. 16S rRNA sequencing was performed to characterize the gut microbiome and identify gut microbes that are differentially abundant between patients and healthy controls. Lastly, associations between relative abundances of specific bacterial taxa in the gut and clinical outcome parameters were evaluated. Results: Patients with pSS show decreased gut microbial diversity and richness, decreased abundance of butyrate producing bacteria, such as Roseburia and Coprococcus, and increased abundance of other taxa, such as Eubacterium rectale and Roseburia inulinivorans. These bacteria are enriched with functions related to glycolytic and lipogenic, energy, substance, galactose, pentose metabolism pathways and glucuronate interconversions, decreased with functions related to peptidoglycan biosynthesis, pyrimidine metabolism pathways. An integrative analysis identified pSS-related specific bacterial taxa in the gut, for which the abundance of Eubacterium rectale is negatively correlated with Th17/Treg. Furthermore, the pathways of biosynthesis of secondary metabolites, biosynthesis of amino acids, peptidoglycan biosynthesis and pyrimidine, galactose, pentose, microbial metabolism in diverse environments, glyoxylate and dicarboxylate metabolism are associated with Treg or Th17/Treg. Conclusions: Primary Sjögren's syndrome could lead to decreased gut microbial diversity and richness of intestinal flora in patients. The proportions of Th17 and Treg cells induced by microbiota were predictive pSS manifestations and accounted for the pSS severity.

Asunto(s)

RESUMEN

Long non-coding RNAs (lncRNAs) play important roles in many biological processes. Knocking out or knocking down some lncRNAs will lead to lethality or infertility. These lncRNAs are called essential lncRNAs. Knowledges of essential lncRNAs are important in establishing minimal genomes of living cells, developing drug therapies and early diagnostic approaches for complex diseases. However, existing databases focus on collecting essential coding genes. Essential non-coding gene records are rare in existing databases. A comprehensive collection of essential non-coding genes, particularly essential lncRNA genes, is demanded. We manually curated 207 essential lncRNAs from literatures for establishing a database on essential lncRNAs, which is named as dbEssLnc (Database of essential lncRNAs). The dbEssLnc database has a web-based user-friendly interface for the users to browse, to search, to visualize and to blast search records in the database. The dbEssLnc database is freely accessible at https://esslnc.pufengdu.org. All data and source codes for mirroring the dbEssLnc database have been deposited in GitHub (https://github.com/yyZhang14/dbEssLnc).

RESUMEN

Objective: Establishment of an efficient method of preparing human kidney single cell suspension, using a very small amount of tissue puncture. Methods: Samples of human kidney tissue puncture were cut into pieces, and then 80 µL of the digestive enzyme were added to each punctured tissue to induce enzymatic digestion. The enzyme combination is composed of collagenases, DNase and hyaluronidase and the sample was incubated 20 min at 37°C. The obtained cell suspension was filtered through a 70 µm cell strainer, centrifuged at 300 g for 5 min and the supernatant was removed, then the pellet was resuspended in 3 ml of DMEM (Dulbecco's Modified Eagle's Medium). Cell suspension was sorted and purified by flow sorting to remove dead cells and obtain a cell suspension with higher viability rate. Results: We found that 1) diverse single cells of human kidney can be obtained by the digestive enzyme, as observed under the light microscope, with different sizes, normal cell morphology and good dispersion. 2) (2-3) × 106 single cells can be extracted from one fresh punctured kidney tissue of about 10 mg, with a cell viability rate of more than 80%. Conclusion: In this work we generated a comprehensive and high-resolution single-cell method, which is simple and efficient for preparing single cell suspension from a minimal amount of human kidney tissue. This method can facilitate the study of renal cell biology and the pathogenesis of kidney diseases.

RESUMEN

Long noncoding RNAs (lncRNAs) play important roles in a variety of biological processes. Knocking out or knocking down some lncRNA genes can lead to death or infertility. These lncRNAs are called essential lncRNAs. Identifying the essential lncRNA is of importance for complex disease diagnosis and treatments. However, experimental methods for identifying essential lncRNAs are always costly and time consuming. Therefore, computational methods can be considered as an alternative approach. We propose a method to identify essential lncRNAs by combining network centrality measures and lncRNA sequence information. By constructing a lncRNA-protein-protein interaction network, we measure the essentiality of lncRNAs from their role in the network and their sequence together. We name our method as the systematic gene importance index (SGII). As far as we can tell, this is the first attempt to identify essential lncRNAs by combining sequence and network information together. The results of our method indicated that essential lncRNAs have similar roles in the LPPI network as the essential coding genes in the PPI network. Another encouraging observation is that the network information can significantly boost the predictive performance of sequence-based method. All source code and dataset of SGII have been deposited in a GitHub repository (https://github.com/ninglolo/SGII).

RESUMEN

MicroRNAs (miRNAs) play vital roles in gene expression regulations. Identification of essential miRNAs is of fundamental importance in understanding their cellular functions. Experimental methods for identifying essential miRNAs are always costly and time-consuming. Therefore, computational methods are considered as alternative approaches. Currently, only a handful of studies are focused on predicting essential miRNAs. In this work, we proposed to predict essential miRNAs using the XGBoost framework with CART (Classification and Regression Trees) on various types of sequence-based features. We named this method as XGEM (XGBoost for essential miRNAs). The prediction performance of XGEM is promising. In comparison with other state-of-the-art methods, XGEM performed the best, indicating its potential in identifying essential miRNAs.

RESUMEN

BACKGROUND: Vascular changes in liver fibrosis can result in increased intrahepatic vascular resistance and impaired blood circulation. This can hinder the recovery from fibrosis and may eventually lead to portal hypertension, a major cirrhosis complication. This report proposed a volume-averaged Murray's deviation method to characterize intrahepatic circulation in the liver during fibrosis and its subsequent regression via X-ray phase-contrast computed tomography (PCCT). METHODS: Liver fibrosis was induced in 24 Sprague-Dawley rats by exposure to carbon tetrachloride (CCl4) for up to 10 weeks, after which, spontaneous regression commenced and continued until week 30. High-resolution three-dimensional (3D) imaging of the livers was performed with PCCT. The values of Murray's deviation based on the volume-averaged and the conventional diameter-based methods were compared. After that, the intrahepatic circulation at different stages of fibrosis was evaluated using the volume-averaged method. The increase in collagen during liver fibrosis was assessed by pathological analyses. RESULTS: A comparison of the 2 methods showed that with an increase in the number of diameter measurements, the value of Murrary's deviation obtained using the diameter-based method gradually approaches those of the volume-averaged method, with minimal variations. The value of Murray's deviation increased with the development of fibrosis. After reversal, the value rapidly decreased and approached that of the normal state in both the main branches (1.05±0.17, 1.17±0.21, 1.34±0.18, and 1.17±0.19 in the normal, moderate, severe, and regressive groups, respectively; P<0.05 between the severe group and other groups) and the small branches (1.05±0.09, 1.42±0.48, 1.79±0.57, and 1.18±0.28 in the normal, moderate, severe, and regressive group, respectively; P<0.05 between adjacent groups). An analysis of Murray's deviation and the pathological results showed that the vascular circulation in this disease model was consistent with the progression and recovery from fibrosis. CONCLUSIONS: This study showed the validity of the volume-averaged method for calculating Murray's deviation and demonstrated that it could accurately evaluate the blood circulation state of the liver during fibrosis and its subsequent regression. Thus, the volume-averaged method of calculating Murray's deviation may be an objective and valuable staging criterion to evaluate intrahepatic circulation during liver fibrosis.

RESUMEN

PURPOSE: Differentiating the intrahepatic vascular type is essential for the early diagnosis of liver fibrosis. X-ray phase-contrast computed tomography (PCCT) is a label-free, high-resolution imaging modality for imaging vascular networks in a whole liver lobe. This study explores the use of three-dimensional (3D) branching geometry to differentiate between the hepatic vein (HV) and portal vein (PV) in early-stage liver fibrosis with PCCT. METHOD: Bile duct ligation surgery was conducted in mice to induce early-stage liver fibrosis. The individual liver lobes of mice were imaged using PCCT, and morphological characteristics, including vascular diameter, cross-sectional area, eccentricity, branch angle, bifurcation index, area ratio and junction exponent, were investigated in 3D modality. These characteristics were used to differentiate the HV from the PV, and their performance was evaluated through receiver operating characteristic (ROC) curve analysis. RESULTS: PCCT revealed a 3D vascular structure of the liver lobes. For intact lobes, the differentiation method between the HV and PV using the junction exponent had an AUC of 0.99 (95% CI: 0.98-1.00). Moreover, the AUCs of the junction exponent for 15, 10, and 5 branches in dissected lobes for differentiation were 0.98 (95% CI: 0.94-1.00), 0.86 (95% CI: 0.73-0.99) and 0.82 (95% CI: 0.67-0.97), respectively. CONCLUSION: The method of 3D branching geometry using the junction exponent could differentiate the HV from PV in early-stage liver fibrosis via the PCCT, which provides the foundation for further analysis of liver fibrosis.

Asunto(s)

RESUMEN

PURPOSE: High-resolution synchrotron radiation X-ray phase contrast microtomography (PC-µCT) images often suffer from severe ring artifacts, which are mainly caused by undesirable responses of detector elements. In the medical imaging field, the existence of ring artifacts can lead to degraded visual quality and can directly affect diagnosis accuracy. Thus, removing or at least effectively reducing ring artifacts is indispensable. METHOD: The existing ring artifacts removal algorithms mainly focus on two-dimensional (matrix-based) priors, and these algorithms fail to consider correlations hidden in sequential computed tomography (CT) images. This paper proposed a novel three-dimensional (tensor-based) ring artifacts removal algorithm for synchrotron radiation X-ray PC-µCT images. In the sinogram domain, ring artifacts manifest as vertical stripe artifacts. From an image decomposition perspective, a degraded sinogram can be decomposed into a stripe artifacts component and an underlying clean sinogram component. The proposed algorithm is designed to detect and remove stripe artifacts from a degraded sinogram by fully identifying the characteristics of the two components. Specifically, for the stripe artifacts component, tensor Tucker decomposition is used to describe its low-rank character. For the underlying clean sinogram component, spatial-sequential total variation regularization is adopted to enhance the piecewise smoothness. Moreover, the Frobenius norm term is further used to model Gaussian noise. An efficient augmented Lagrange multiplier method is designed to solve the proposed optimization model. RESULTS: The proposed method is evaluated utilizing both simulations and real data containing different ring artifacts patterns. In the simulations, the human chest CT images are used for evaluating the proposed method. We compare the peak signal-to-noise ratio (PSNR), structural similarity (SSIM), and mean absolute error (MAE) results of our algorithm with the Naghia's method, the RRRTV method, the wavelet-FFT method, and the SDRSD-GIF method. The proposed method was also evaluated on real data from rat liver samples and rat tooth samples. Our proposed method outperforms the competing methods in terms of both qualitative and quantitative evaluation results. Additionally, the 3D visualization results were presented to make the ring artifacts removal effect more intuitive. CONCLUSION: The experimental results on simulations and real data clearly demonstrated that the proposed algorithm can significantly improve the quality of PC-µCT images compared with the existing popular algorithms, and it has great potential to promote the application of high-resolution imaging for visualizing biological tissues.

Asunto(s)

RESUMEN

Heat shock protein 40 (Hsp40), a member of Heat shock proteins (Hsps) family, plays a crucial role in regulation of cell proliferation, survival and apoptosis in mammals. In this study, Hsp40, EcHsp40, was identified from Epinephelus coioides, an economically important marine-cultured fish in China and Southeast Asian counties. The full length of EcHsp40 was 2236 bp in length containing a 1026 bp open reading frame (ORF) encoding 341 amino acids, with a molecular mass of 37.88 kDa and a theoretical pI of 9.09. EcHsp40 has two conserved domains DnaJ and DnaJ_C. EcHsp40 mRNA was detected in all tissues examined, and the expression was significantly up-regulated response to challenged with Vibrio alginolyticus or Singapore grouper iridovirus (SGIV), one of the important pathogens of marine fish. EcHsp40 was distributed in both the cytoplasm and nucleus, over-expression of EcHsp40 can inhibit the activity of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), significantly promote SGIV-induced apoptosis, intracellular caspase-3 activity and viral replication, suggesting that the EcHsp40 may play an important role in pathogenic stimulation.

Asunto(s)

RESUMEN

Propagation-based X-ray phase-contrast computed tomography (PB-PCCT) can serve as an effective tool for studying organ function and pathologies. However, it usually suffers from a high radiation dose due to the long scan time. To alleviate this problem, we propose a deep learning reconstruction framework for PB-PCCT with sparse-view projections. The framework consists of dual-path deep neural networks, where the edge detection, edge guidance, and artifact removal models are incorporated into two subnetworks. It is worth noting that the framework has the ability to achieve excellent performance by exploiting the data-based knowledge of the sample material characteristics and the model-based knowledge of PB-PCCT. To evaluate the effectiveness and capability of the proposed framework, simulations and real experiments were performed. The results demonstrated that the proposed framework could significantly suppress streaking artifacts and produce high-contrast and high-resolution computed tomography images.

RESUMEN

In-line X-ray phase-contrast computed tomography (IL-PCCT) can produce high-contrast and high-resolution images of biological samples, and it has a great advantage with regard to imaging the microstructures and morphologies of fibrous biological tissues (FBTs). Filtered back projection (FBP) is widely used in ILPCCT. However, it requires long scanning times and high radiation doses to produce high-quality CT images, and this restricts its applicability in biomedical and preclinical studies on FBTs. To solve this problem, a novel IL-PCCT reconstruction algorithm is proposed to decrease the radiation dose by reducing the number of projections and reconstruct high-quality CT images of FBTs. The proposed algorithm incorporates the FBP method into the iterative reconstruction framework. Considering the area types and anisotropic edge properties of FBTs, a discriminant adaptive-weighted total variation model is introduced to optimize the intermediate reconstructed images. A fibrous phantom simulation and real experiment were performed to assess the performance of the proposed algorithm. Simulation and experimental results demonstrated that the proposed algorithm is an effective IL-PCCT reconstruction method for FBTs with incomplete projection data, and it has a great ability to suppress artifacts and preserve the edges of fibrous structures.

RESUMEN

AIM: As a specialized intraparenchymal vascular conduit, hepatic sinusoids play a key role in liver microcirculation. This study aimed to explore the three-dimensional (3D) morphological changes of cirrhotic sinusoids by serial histological sections. METHODS: Cirrhosis was induced by tail vein injection of albumin in Wistar rats with a positive antibody. A total of 356 serial histological sections were prepared from liver tissue blocks of normal and cirrhotic rats. The optical microscope images were registered and reconstructed, and 3D reconstructions of the fine structures of fibrous tissues and sinusoids were subsequently visualized. RESULTS: The fibrosis area of the cirrhotic sample was 6-16 times that of the normal sample (P<0.001). Cirrhosis led to obvious changes in the distribution and morphology of sinusoids, which were mainly manifested as dilation, increased quantity and disordered distribution. Compared with normal liver, cirrhotic liver has a significantly increased volume ratio, number and volume of sinusoids (1.63-, 0.53-, and 1.75-fold, respectively, P<0.001). Furthermore, the samples were further divided into three zones according to the oxygen supply, and there were significant differences in the morphology of the sinusoids in the normal and cirrhotic samples (P<0.05). In particular, morphological parameters of the cirrhotic sinusoids near the portal area were obviously greater than those in the normal liver (P<0.05). CONCLUSION: 3D morphological structures of hepatic sinusoids were reconstructed, and the adaptive microstructure changes of cirrhotic sinusoids were accurately measured, which has an important implications for the study of hepatic microcirculation and pathological changes of cirrhosis.

Asunto(s)

RESUMEN

Autoantibodies against M-type phospholipase A2 receptor (PLA2R) serve as specific biomarkers for idiopathic membranous nephropathy (IMN), and its quantification helps monitor disease activity. In this study, we describe a rapid and highly sensitive quantum dots-based immunochromatography assay (QD-ICA) for quantifying PLA2R autoantibodies. Serum samples from 135 biopsy-confirmed patients with nephrotic syndrome were analyzed for PLA2R autoantibodies using the novel QD-ICA as well as commercialized enzyme-linked immunosorbent assay (ELISA). Areas under the receiver operating characteristic curve (AUC-ROC) of QD-ICA were significantly greater than those of ELISA (91.1% [95% CI 85.9-96.3%] and 83.9% [95% CI 76.5-91.2%] respectively; p < 0.01). The detection sensitivity and specificity of QD-ICA (80.9% [95% CI 69.2-89.0%] and 100% [95% CI 93.2-100.0%], respectively) exceeded those of ELISA (72.1% [95% CI 59.7-81.9%] and 98.5% [95% CI 90.9-100.0%], respectively). The optimum cut-off value of QD-ICA was 18.18 relative units (RU)/mL, and the limit of detection was 2.86 RU/mL. The novel QD-ICA outperforms ELISA in detecting PLA2R autoantibodies, with shorter detection time, fewer steps, smaller equipment size, and broader testing application, suggesting its capability to improve IMN diagnosis and monitor patient response to treatment.

Asunto(s)

RESUMEN

Propagation-based x-ray phase-contrast computed tomography (PB-PCCT) images often suffer from severe ring artifacts. Ring artifacts are mainly caused by the nonuniform response of detector elements, and they can degrade image quality and affect the subsequent image processing and quantitative analyses. To remove ring artifacts in PB-PCCT images, a novel method combined sparse-domain regularized stripe decomposition (SDRSD) method with guided image filtering (GIF) was proposed. In this method, polar coordinate transformation was utilized to convert the ring artifacts to stripe artifacts. And then considering the directional and sparse properties of the stripe artifacts and the continuity characteristics of the sample, the SDRSD method was designed to remove stripe artifacts. However, for the SDRSD method, the presence of noise may destroy the edges of the stripe artifacts and lead to incomplete decomposition. Hence, a simple and efficient smoothing technique, namely GIF, was employed to overcome this issue. The simulations and real experiments demonstrated that the proposed method could effectively remove ring artifacts as well as preserve the structures and edges of the samples. In conclusion, the proposed method can serve as an effective tool to remove ring artifacts in PB-PCCT images, and it has high potential for promoting the biomedical and preclinical applications of PB-PCCT.

Asunto(s)