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PURPOSE: Accurately and early detection of intestinal fibrosis in Crohn's disease (CD) is crucial for clinical management yet remains an unmet need. Fibroblast activation protein inhibitor (FAPI) PET/CT has emerged as a promising tool to assess fibrosis. We aimed to investigate the diagnostic capability of [18F]F-FAPI PET/CT in detecting intestinal fibrosis and compared it with[18F]F-FDG PET/CT and magnetization transfer MR imaging (MTI). METHODS: Twenty-two rats underwent TNBS treatment to simulate fibrosis development, followed by three quantitative imaging sessions within one week. Mean and maximum standardized uptake values (SUVmean and SUVmax) were calculated on[18F]F-FAPI and [18F]F-FDG PET/CT, along with normalized magnetization transfer ratio on MTI. Intestinal fibrosis was assessed pathologically, with MTI serving as imaging standard for fibrosis. The diagnostic efficacy of imaging parameters in fibrosis was compared using pathological and imaging standards. Ten patients with 34 bowel strictures were prospectively recruited to validate their diagnostic performance, using the identical imaging protocol. RESULTS: In CD patients, the accuracy of FAPI uptake (both AUCs = 0.87, both P ≤ 0.01) in distinguishing non-to-mild from moderate-to-severe fibrosis was higher than FDG uptake (both AUCs = 0.82, P ≤ 0.01) and comparable to MTI (AUCs = 0.90, P ≤ 0.001). In rats, FAPI uptake responded earlier to fibrosis development than FDG and MTI; consistently, during early phase, FAPI uptake showed a stronger correlation (SUVmean: R = 0.69) with pathological fibrosis than FDG (SUVmean: R = 0.17) and MTI (R = 0.52). CONCLUSION: The diagnostic efficacy of [18F]F-FAPI PET/CT in detecting CD fibrosis is superior to [18F]F-FDG PET/CT and comparable to MTI, exhibiting great potential for early detection of intestinal fibrosis.
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Enfermedad de Crohn , Modelos Animales de Enfermedad , Fibrosis , Fluorodesoxiglucosa F18 , Intestinos , Imagen por Resonancia Magnética , Tomografía Computarizada por Tomografía de Emisión de Positrones , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/complicaciones , Animales , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Ratas , Fibrosis/diagnóstico por imagen , Humanos , Masculino , Femenino , Adulto , Intestinos/diagnóstico por imagen , Intestinos/patología , Estudios Prospectivos , Persona de Mediana EdadRESUMEN
Celiac disease (CD), triggered by exposure to gluten in genetically susceptible individuals, is an immune-mediated small bowel disease affecting about 1% of the population worldwide. But the prevalence of CD varies with age, sex, and location. A strict gluten-free diet remains the primary treatment for CD, currently. Most of patients with CD respond well to gluten-free diet with good prognosis, while some patients fail to get symptomatic relief or histological remission (e.g., nonresponsive or refractory CD). Because of heterogeneous clinical appearance, the diagnosis of CD is difficult. Moreover, malignant complications and poor outcomes accompanied with refractory CD present great challenges in disease management. Over the past three decades, cross-sectional imaging techniques (computed tomography [CT] and magnetic resonance imaging [MRI]) play an important role in small bowel inflammatory and neoplastic diseases. Compared with endoscopic techniques, cross-sectional imaging permits clearly presentation of both intraluminal and extraluminal abnormalities. It provides vascular and functional information, thus improving the possibility as diagnostic and follow-up tool. The value of cross-sectional imaging for patients with suspected or confirmed CD has been gradually demonstrated. Studies revealed that certain features suggested by cross-sectional imaging could help to establish the early diagnosis of CD. Besides, the potential contributions of cross-sectional imaging may lie in the evaluation of disease activity and severity, which helps guiding management strategies. The purpose of this review is to provide current overviews and future directions of cross-sectional imaging in adult CD, thus facilitating the understanding and application in clinical practice. CLINICAL RELEVANCE STATEMENT: In this review, we systematically summarized the existing knowledge of cross-sectional imaging in adult CD and analyzed their possible roles in clinical practice, including disease diagnosis, complication identification, treatment evaluation, and prognostic prediction. KEY POINTS: ⢠Regarding a condition described as "celiac iceberg", celiac disease remains underdiagnosed and undertreated. ⢠Cross-sectional imaging is helpful in clinical management of celiac disease, including disease diagnosis, complication identification, treatment evaluation, and prognostic prediction. ⢠Cross-sectional imaging should be considered as the valuable examination in patients suspected from celiac disease.
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Enfermedad Celíaca , Humanos , Adulto , Enfermedad Celíaca/diagnóstico por imagen , Enfermedad Celíaca/complicaciones , Glútenes/efectos adversos , Dieta Sin Gluten , Intestino Delgado/diagnóstico por imagen , PronósticoRESUMEN
Optical soliton molecules exhibiting behaviors analogous to matter molecules have been the hotspot in the dissipative system for decades. Based on the dispersion Fourier transformation technique, the real-time spectral interferometry has become the popular method to reveal the internal dynamics of soliton molecules. The rising degrees of freedom in pace with the increased constitutes of soliton molecules yield more intriguing sights into the internal motions. Yet the soliton molecules with three or more pulses are rarely investigated owing to the exponentially growing complexity. Here, we present both experimental and theoretical studies on the soliton molecules containing three solitons. Different assemblies of the constitutes are categorized as different types of soliton triplet akin to the geometric isomer, including equally-spaced triplet and unequally-spaced triplet. Typical soliton triplets with different dynamics including regular internal motions, hybrid phase dynamics and complex dynamics involving separation evolution are experimentally analyzed and theoretically simulated. Specifically, the energy difference which remains elusive in experiments are uncovered through the simulation of diverse triplets with plentiful dynamics. Moreover, the multi-dimensional interaction space is proposed to visualize the internal motions in connection with the energy exchange, which play significant roles in the interplays among the solitons. Both the experimental and numerical simulations on the isomeric soliton triplets would release a larger number of degrees of freedom and motivate the potentially artificial configuration of soliton molecules for various ultrafast applications, such as all-optical buffering and multiple encoding for telecommunications.
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OBJECTIVES: Differences in clinical adverse outcomes (CAO) based on different intestinal stricturing definitions in Crohn's disease (CD) are poorly documented. This study aims to compare CAO between radiological strictures (RS) and endoscopic strictures (ES) in ileal CD and explore the significance of upstream dilatation in RS. METHODS: This retrospective double-center study included 199 patients (derivation cohort, n = 157; validation cohort, n = 42) with bowel strictures who simultaneously underwent endoscopic and radiologic examinations. RS was defined as a luminal narrowing with wall thickening relative to the normal gut on cross-sectional imaging (group 1 (G1)), which further divided into G1a (without upstream dilatation) and G1b (with upstream dilatation). ES was defined as an endoscopic non-passable stricture (group 2 (G2)). Strictures met the definitions of RS (with or without upstream dilatation) and ES were categorized as group 3 (G3). CAO referred to stricture-related surgery or penetrating disease. RESULTS: In the derivation cohort, G1b (93.3%) had the highest CAO occurrence rate, followed by G3 (32.6%), G1a (3.2%), and G2 (0%) (p < 0.0001); the same order was found in the validation cohort. The CAO-free survival time was significantly different among the four groups (p < 0.0001). Upstream dilatation (hazard ratio, 1.126) was a risk factor for predicting CAO in RS. Furthermore, when upstream dilatation was added to diagnose RS, 17.6% of high-risk strictures were neglected. CONCLUSIONS: CAO differs significantly between RS and ES, and clinicians should pay more attention to strictures in G1b and G3. Upstream dilatation has an important impact on the clinical outcome of RS but may not be an essential factor for RS diagnosis. CLINICAL RELEVANCE STATEMENT: This study explored the definition of intestinal stricture with the greatest significance for the clinical diagnosis and prognosis of patients with CD, and consequently provided effective auxiliary information for clinicians to formulate strategies for the treatment of CD intestinal strictures. KEY POINTS: ⢠The retrospective double-center study showed that clinical adverse outcome is different between radiological strictures and endoscopic strictures in CD. ⢠Upstream dilatation has an important impact on the clinical outcome of radiological strictures but may not be an essential factor for diagnosis of radiological strictures. ⢠Radiological stricture with upstream dilatation and simultaneous radiological and endoscopic stricture were at increased risk for clinical adverse outcomes; thus, closer monitoring should be considered.
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Enfermedad de Crohn , Obstrucción Intestinal , Humanos , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico por imagen , Constricción Patológica/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Endoscopía/métodos , Obstrucción Intestinal/diagnóstico por imagen , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Dilatación/métodos , Endoscopía Gastrointestinal/métodosRESUMEN
BACKGROUND & AIMS: No reliable method for evaluating intestinal fibrosis in Crohn's disease (CD) exists; therefore, we developed a computed-tomography enterography (CTE)-based radiomic model (RM) for characterizing intestinal fibrosis in CD. METHODS: This retrospective multicenter study included 167 CD patients with 212 bowel lesions (training, 98 lesions; test, 114 lesions) who underwent preoperative CTE and bowel resection at 1 of the 3 tertiary referral centers from January 2014 through June 2020. Bowel fibrosis was histologically classified as none-mild or moderate-severe. In the training cohort, 1454 radiomic features were extracted from venous-phase CTE and a machine learning-based RM was developed based on the reproducible features using logistic regression. The RM was validated in an independent external test cohort recruited from 3 centers. The diagnostic performance of RM was compared with 2 radiologists' visual interpretation of CTE using receiver operating characteristic (ROC) curve analysis. RESULTS: In the training cohort, the area under the ROC curve (AUC) of RM for distinguishing moderate-severe from none-mild intestinal fibrosis was 0.888 (95% confidence interval [CI], 0.818-0.957). In the test cohort, the RM showed robust performance across 3 centers with an AUC of 0.816 (95% CI, 0.706-0.926), 0.724 (95% CI, 0.526-0.923), and 0.750 (95% CI, 0.560-0.940), respectively. Moreover, the RM was more accurate than visual interpretations by either radiologist (radiologist 1, AUC = 0.554; radiologist 2, AUC = 0.598; both, P < .001) in the test cohort. Decision curve analysis showed that the RM provided a better net benefit to predicting intestinal fibrosis than the radiologists. CONCLUSIONS: A CTE-based RM allows for accurate characterization of intestinal fibrosis in CD.
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Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/patología , Intestinos/diagnóstico por imagen , Intestinos/patología , Tomografía Computarizada por Rayos X/normas , Adulto , Enfermedad de Crohn/complicaciones , Femenino , Fibrosis , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Reproducibilidad de los Resultados , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X/métodosRESUMEN
Long non-coding RNAs (lncRNAs) have been reported to play an important role in cardiovascular diseases. The present study aimed to investigate the levels of lncRNA H19 in patients with coronary artery disease (CAD) and the genetic association of lncRNA H19 rs217727 and rs4929984 polymorphisms with CAD susceptibility. We detected an upregulated expression of lncRNA H19 in the peripheral blood of CAD patients compared with healthy controls, and the area under the receiver operating characteristic curve of lncRNA H19 for CAD diagnosis was 0.918. In addition, rs4929984 was associated with the susceptibility of Han Chinese females to CAD, as shown in the additive and dominant models, and the significant association remained after adjusting for age and Bonferroni correction. The A allele carriers of rs4929984 were correlated with females' susceptibility to CAD compared with the C allele, and the A-G haplotype of rs4929984-rs217727 was associated with females' susceptibility to CAD. Furthermore, rs217727 and rs4929984 were associated with the levels of clinicopathological parameters of CAD cases. We suggest that lncRNA H19 has a potential to be a diagnostic biomarker for CAD; rs4929984 polymorphism is associated with females' susceptibility to CAD in the Han Chinese population, and lncRNA H19 variants may influence lipid metabolism, inflammation, and coagulation function of CAD patients.
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Enfermedad de la Arteria Coronaria , ARN Largo no Codificante , Estudios de Casos y Controles , China , Enfermedad de la Arteria Coronaria/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Polimorfismo de Nucleótido Simple , ARN Largo no Codificante/genéticaRESUMEN
OBJECTIVES: Identifying inflammation- or fibrosis-predominant strictures in Crohn's disease (CD) is crucial for treatment strategies. We evaluated the additive value of magnetisation transfer (MT) to conventional MRI for differentiating CD strictures using surgical histopathology as a reference standard. METHODS: Twenty-eight consecutive CD patients who underwent MRI preoperatively were recruited. MRI parameters included T2-weighted imaging (T2WI) hyperintensity, bowel wall thickness, enhancement pattern changes over time, enhancement pattern and gain ratio in dynamic contrast-enhanced phases, and MT ratio. Correlation analysis was performed using Spearman's rank test. Receiver operating characteristic curve analysis and Cohen's κ were used. A model with combined MRI variables characterising intestinal strictures was proposed and validated in 14 additional CD patients. RESULTS: Significant correlations with histological inflammation scores were shown for wall thickness (r = 0.361, p = 0.001) and T2WI hyperintensity (r = 0.396, p < 0.001), whereas histological fibrosis scores were significantly correlated with MT ratio (r = 0.681, p < 0.001) and wall thickness (r = 0.461, p < 0.001). T2WI hyperintensity could differentiate mild from moderate-to-severe inflammation with a sensitivity of 0.871 and a specificity of 0.800. MT ratio could discriminate mild from moderate-to-severe fibrosis with a sensitivity and a specificity of 0.913 and 0.923, respectively. Combining MT ratio and T2WI hyperintensity, the MRI classification moderately agreed with the pathological stricture classification (p < 0.01, κ = 0.549). In the validation set, the diagnostic accuracy of T2WI hyperintensity and MT ratio were 86% and 89%, with good agreement between MRI and histopathological classification (p < 0.01, κ = 0.665). CONCLUSIONS: MT ratio combined with conventional MRI improves the differentiation of fibrotic from inflammatory components of small-bowel strictures in CD patients. KEY POINTS: ⢠MT ratio from magnetisation transfer imaging combined with T2WI from conventional MRI can simultaneously characterise bowel fibrosis and inflammation in adult Crohn's disease.
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Enfermedad de Crohn/diagnóstico , Obstrucción Intestinal/diagnóstico , Intestino Delgado/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Adulto , Diagnóstico Diferencial , Femenino , Fibrosis/diagnóstico , Humanos , Masculino , Curva ROCRESUMEN
OBJECTIVES: Although diffusion-weighted imaging (DWI) is reported to be accurate in detecting bowel inflammation in Crohn's disease (CD), its ability to assess bowel fibrosis remains unclear. This study assessed the role of DWI in the characterization of bowel fibrosis using surgical histopathology as the reference standard. METHODS: Abdominal DWI was performed before elective surgery in 30 consecutive patients with CD. The apparent diffusion coefficients (ADCs) in pathologic bowel walls were calculated. Region-by-region correlations between DWI and the surgical specimens were performed to determine the histologic degrees of bowel fibrosis and inflammation. RESULTS: ADCs correlated negatively with bowel inflammation (r = - 0.499, p < 0.001) and fibrosis (r = - 0.464, p < 0.001) in 90 specimens; the ADCs in regions of nonfibrosis and mild fibrosis were significantly higher than those in regions of moderate-severe fibrosis (p = 0.008). However, there was a significant correlation between the ADCs and bowel fibrosis (r = - 0.641, p = 0.001) in mildly inflamed segments but not in moderately (r = - 0.274, p = 0.255) or severely (r = - 0.225, p = 0.120) inflamed segments. In the mildly inflamed segments, the ADCs had good accuracy with an area under the receiver-operating characteristic curve of 0.867 (p = 0.004) for distinguishing nonfibrosis and mild fibrosis from moderate-severe fibrosis. CONCLUSIONS: ADC can be used to assess bowel inflammation in patients with CD. However, it only enables the accurate detection of the degree of bowel fibrosis in mildly inflamed bowel walls. Therefore, caution is advised when using ADC to predict the degree of intestinal fibrosis. KEY POINTS: ⢠Diffusion-weighted imaging was used to assess bowel inflammation in patients with Crohn's disease. ⢠The ability of diffusion-weighted imaging to evaluate bowel fibrosis decreased with increasing bowel inflammation. ⢠Diffusion-weighted imaging enabled accurate detection of the degree of fibrosis only in mildly inflamed bowel walls.
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Enfermedad de Crohn/diagnóstico , Imagen de Difusión por Resonancia Magnética/métodos , Inflamación/diagnóstico por imagen , Intestinos/diagnóstico por imagen , Adulto , Femenino , Fibrosis/diagnóstico , Humanos , Masculino , Estudios Prospectivos , Curva ROCRESUMEN
OBJECTIVES: Intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (MRI) provides information on both perfusion and diffusion and has been used to evaluate Crohn's disease (CD) activity and fibrosis in children; however, there are no reports on its use in adults. We aimed to determine its value for detecting and grading intestinal fibrosis in adults with CD compared with contrast-enhanced imaging and traditional diffusion-weighted imaging using surgical histopathology as a reference standard. METHODS: Twenty-four adults with CD underwent preoperative IVIM, traditional diffusion-weighted, and contrast-enhanced imaging. Region-by-region correlations between MRI findings and histologic findings of the surgical specimens were performed. Imaging parameters including fractional perfusion, perfusion coefficient, and diffusion coefficient for IVIM and apparent diffusion coefficient value for traditional diffusion-weighted imaging and contrast-enhanced parameter of 95 bowel lesions were measured. Intestinal fibrosis was histologically scored from 0 to 3. RESULTS: The fractional perfusion (r = - 0.629, p < 0.001) and apparent diffusion coefficient values (r = - 0.495, p < 0.001) were significantly correlated with fibrosis scores. Fractional perfusion decreased following increases in fibrosis severity from mild, to moderate, to severe (p < 0.001). The area under the receiver operating characteristic curve for distinguishing moderate-severe from mild fibrosis was 0.876 (p < 0.001) for fractional perfusion, followed by 0.802 for apparent diffusion coefficient value (p < 0.001). Perfusion coefficient, diffusion coefficient, and contrast-enhanced parameter were uncorrelated with histological fibrosis. CONCLUSIONS: IVIM diffusion-weighted magnetic resonance imaging outperforms traditional diffusion-weighted and contrast-enhanced imaging in grading bowel fibrosis, and fractional perfusion may be a promising biomarker for fibrosis severity in adults with CD. KEY POINTS: ⢠Intravoxel incoherent motion diffusion-weighted MRI outperforms contrast-enhanced imaging and traditional diffusion-weighted MRI for detecting and grading intestinal fibrosis in adult Crohn's disease. ⢠The parameter fractional perfusion, a promising biomarker for fibrosis severity, may be beneficial for treatment planning and monitoring of bowel fibrosis in adult Crohn's disease. ⢠Perfusion coefficient, diffusion coefficient, and the percentage of enhancement gain between 70 s and 7 min were uncorrelated with histological fibrosis.
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Enfermedad de Crohn/diagnóstico por imagen , Intestinos/patología , Adolescente , Adulto , Niño , Enfermedad de Crohn/complicaciones , Difusión , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Fibrosis , Humanos , Aumento de la Imagen/métodos , Intestinos/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Perfusión , Curva ROC , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: A validated histopathological tool to precisely evaluate bowel fibrosis in patients with Crohn's disease is lacking. We attempted to establish a new index to quantify the severity of bowel fibrosis in patients with Crohn's disease-associated fibrostenosis. METHODS: We analyzed the histopathological data of 31 patients with Crohn's disease strictures undergoing surgical resection. The most representative sections of resected strictured segments were stained with Masson trichrome to manifest bowel fibrosis. The collagen area fraction and histological fibrosis score were simultaneously calculated for the same section to evaluate the severity of bowel fibrosis. RESULTS: Collagen area fraction strongly correlated with histological fibrosis scores (r = 0.733, P < 0.001). It showed a stronger correlation (r = 0.561, P < 0.001) with the degree of bowel strictures than the histological fibrosis score did (r = 0.468, P < 0.001). It was also shown to be more accurate for diagnosing Crohn's disease strictures (area under the receiver operating characteristic curve = 0.815, P < 0.001) compared with the histological fibrosis score (area under the curve = 0.771, P < 0.001). High repeatability was observed for the collagen area fraction, with an intraclass correlation coefficient of 0.915 (P < 0.001). CONCLUSIONS: Collagen area fraction is a simple and reliable index to quantify the severity of bowel fibrosis in patients with Crohn's disease-associated fibrostenosis.
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Colágeno/análisis , Enfermedad de Crohn , Intestinos/patología , Adulto , Constricción Patológica/etiología , Constricción Patológica/patología , Correlación de Datos , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/metabolismo , Enfermedad de Crohn/patología , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Femenino , Fibrosis , Humanos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/patología , Obstrucción Intestinal/cirugía , Masculino , Proyectos de Investigación , Índice de Severidad de la EnfermedadRESUMEN
Stroke is the leading cause of death in China. Previous studies have demonstrated that long noncoding RNAs play important roles in ischemic stroke (IS). This study aimed to investigate long noncoding RNA H19 (lncRNA H19) expression in IS cases and the association between lncRNA H19 variants and IS risk and IS-related risk factors. A total of 550 IS cases and 550 controls were recruited for this study. LncRNA H19 expression was detected using quantitative real-time polymerase chain reaction. Genotyping was conducted by the Sequenom MassARRAY technology. LncRNA H19 level in peripheral blood of IS cases was significantly upregulated compared with healthy controls (P = 0.046). No significant association was observed between lncRNA H19 rs217727 and rs4929984 polymorphisms with IS risk in all genetic models, and rs217727-rs4929984 haplotypes are not associated with IS susceptibility. Further meta-analysis also implied that the rs217727 and rs4929984 polymorphisms were not associated with IS in Chinese population. However, rs4929984 is significantly associated with the diastolic blood pressure level of IS patients (additive model: Padj = 0.007; dominant model: Padj = 0.013), whereas rs217727 is associated with international normalized ratio (additive model: Padj = 0.019; recessive model: Padj = 0.004), prothrombin time activity level (additive model: Padj = 0.026; recessive model: Padj = 0.004), and homocysteine level (recessive model: Padj = 0.048) in patients with IS. Our findings suggest that lncRNA H19 level may affect the occurrence of IS, and lncRNA H19 variants may influence blood pressure, coagulation function, and homocysteine metabolism of patients with IS in the southern Chinese Han population.
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Isquemia Encefálica/genética , Predisposición Genética a la Enfermedad , ARN Largo no Codificante/genética , Accidente Cerebrovascular/genética , Anciano , Alelos , Estudios de Casos y Controles , China , Femenino , Estudios de Asociación Genética , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND/AIMS: Long non-coding RNAs (lncRNAs) are potential biomarkers of tumors, cardiac disease, and cerebral disease because of their interaction with coding RNAs. This work focused on ischemic stroke (IS) and aimed to identify novel lncRNA biomarkers and construct lncRNA-related networks in IS. METHODS: Differentially expressed lncRNAs were identified using Arraystar Human LncRNA Microarray v4.0, and validated with qRT-PCR. A lncRNA-mRNA co-expression network and a lncRNA-miRNA-mRNA regulatory network were constructed. Functional and pathway analyses were then performed. RESULTS: In total, 560 up-regulated and 690 down-regulated differentially expressed lncRNAs were found (P < 0.05, false discovery rate < 0.05, absolute fold change ≥ 2). qRT-PCR results confirmed that lncRNA-ENST00000568297, lncRNA-ENST00000568243, and lncRNA-NR_046084 exhibited significant differential expression between IS and controls (all P < 0.05). Areas under the curves (AUCs) for these lncRNAs were 0.733, 0.743, and 0.690, respectively, and the combined AUC was 0.843. A coding-noncoding co-expression (CNC) network was constructed based on Pearson's correlation coefficient. A specific lncRNA-miRNA-mRNA regulatory network of ENST00000568297, ENST00000568243, and NR_046084 was also constructed. Functional annotation of the up- and down-regulated mRNAs was performed. Pathway analysis enriched IS-related pathways with mRNAs in the lncRNA-miRNA-mRNA regulatory network. CONCLUSION: LncRNA and mRNA expression profiles in human peripheral blood were altered after IS. ENST00000568297, ENST00000568243, and NR_046084 were identified as novel potential diagnostic biomarkers of IS. Analysis of the CNC network and lncRNA-miRNA-mRNA regulatory network suggested that lncRNAs may participate in IS pathophysiology by regulating pivotal miRNAs, mRNAs, or IS-related pathways.
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Pueblo Asiatico/genética , Biomarcadores/metabolismo , Redes Reguladoras de Genes/genética , ARN Largo no Codificante/metabolismo , Accidente Cerebrovascular/patología , Anciano , Área Bajo la Curva , Estudios de Casos y Controles , China , Femenino , Humanos , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/metabolismo , Curva ROC , Accidente Cerebrovascular/genética , TranscriptomaRESUMEN
Purpose To evaluate the role of magnetization transfer (MT) magnetic resonance (MR) imaging for the characterization of intestinal fibrosis compared with contrast material-enhanced and diffusion-weighted MR imaging and its capability for differentiating fibrotic from inflammatory strictures in humans with Crohn disease (CD) by using surgical histopathologic analysis as the reference standard. Materials and Methods Institutional review board approval and informed consent were obtained for this prospective study. Abdominal MT imaging, contrast-enhanced imaging, and diffusion-weighted imaging of 31 consecutive patients with CD were analyzed before elective surgery. The bowel wall MT ratio normalized to skeletal muscle, the apparent diffusion coefficient (ADC), and the percentage of enhancement gain were calculated; region-by-region correlations with the surgical specimen were performed to determine the histologic degree of fibrosis and inflammation. The performance of MT imaging was validated in five new patients. One-way analysis of variance test, Spearman rank correlation, and receiver operating characteristic curve were used for statistical analysis. Results Normalized MT ratios strongly correlated with fibrosis scores (r = 0.769; P = .000) but did not correlate with inflammation scores (r = -0.034; P = .740). Significant differences (F = 49.002; P = .000) in normalized MT ratios were found among nonfibrotic, mildly, moderately, and severely fibrotic walls. The normalized MT ratios of mixed fibrotic and inflammatory bowel walls were significantly higher than those of bowel walls with only inflammation present (t = -8.52; P = .000). A high accuracy of normalized MT ratios was shown with an area under the receiver operating characteristic curve (AUC) of 0.919 (P = .000) for differentiating moderately to severely fibrotic bowel walls from nonfibrotic and mildly fibrotic bowel walls, followed by ADC (AUC, 0.747; P = .001) and the percentage of enhancement gain (AUC, 0.592; P = .209). The sensitivity, specificity, and AUC of MT imaging for diagnosing moderate to severe fibrosis in the validation data set were 80% (12 of 15), 100% (three of three), and 0.9 (P = .033), respectively. Conclusion MT imaging outperforms ADC and contrast-enhanced imaging in detecting and distinguishing varying degrees of bowel fibrosis with or without coexisting inflammation. MT imaging could potentially be used as a method to differentiate fibrotic from inflammatory intestinal strictures in patients with CD. © RSNA, 2018 Online supplemental material is available for this article.
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Enfermedad de Crohn/patología , Fibrosis/patología , Interpretación de Imagen Asistida por Computador , Obstrucción Intestinal/patología , Imagen por Resonancia Magnética , Adulto , Área Bajo la Curva , Medios de Contraste/administración & dosificación , Enfermedad de Crohn/diagnóstico por imagen , Progresión de la Enfermedad , Femenino , Fibrosis/diagnóstico por imagen , Humanos , Aumento de la Imagen , Obstrucción Intestinal/diagnóstico por imagen , Masculino , Estudios Prospectivos , Estándares de Referencia , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: To assess the efficacy of diffusion kurtosis imaging (DKI) and to compare DKI-derived parameters with that of conventional diffusion-weighted imaging (DWI) for grading the inflammatory activity of Crohn's disease (CD). MATERIALS AND METHODS: In all, 38 patients with CD underwent 3T magnetic resonance enterography (MRE) with DKI (b values of 0-2000 s/mm2 ). The inflammatory activity of the bowel segments was graded by magnetic resonance index of activity (MaRIA) as inactive (<7), mild (≥7 and <11), or moderate-severe (≥11). Apparent diffusion for non-Gaussian distribution (Dapp ) and apparent kurtosis coefficient (Kapp ) on DKI as well as apparent diffusion coefficient (ADC) on DWI were compared. RESULTS: In all, 86 bowel segments including inactive (20), mild (19), and moderate-severe (47) CD were analyzed. The differences in Kapp , Dapp , and ADC among inactive, mild, and moderate-severe CD were significant (all P < 0.05). Kapp (r = 0.862), Dapp (r = -0.755), and ADC (r = -0.713) correlated well with MaRIA in all segments. Stronger correlation with MaRIA in moderate-severe CD was found for Kapp (r = 0.647) than that of Dapp (r = -0.414) and ADC (r = -0.580). Receiver operating characteristic (ROC) curve analysis showed high accuracy of Kapp , Dapp , and ADC for differentiating active from inactive CD (AUC: 0.953 for Kapp , 0.944 for Dapp , 0.907 for ADC) as well as differentiating inactive-mild from moderate-severe CD (AUC: 0.946 for Kapp , 0.887 for Dapp , 0.846 for ADC). The threshold Kapp of 0.731 allowed differentiation of active from inactive CD with 89.4% sensitivity and 95% specificity. CONCLUSION: DKI of CD is clinically feasible and might be superior to conventional DWI for grading the inflammatory activity of CD. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:702-709.
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Enfermedad de Crohn/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Tracto Gastrointestinal/diagnóstico por imagen , Adolescente , Adulto , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: Assessing bowel fibrosis in patients with Crohn's disease (CD) has important therapeutic implications. PURPOSE: To determine the utility of T2* mapping versus that of contrast enhanced (CE) imaging in grading intestinal fibrosis in patients with CD using surgical pathology as the reference standard. STUDY TYPE: Prospective. SPECIMENS: 102 specimens from 27 patients with CD. FIELD STRENGTH/SEQUENCE: 3.0T; T2WI; T1WI; T2*WI. ASSESSMENT: The T2*WI values of the bowel wall targeted for resection were measured by two radiologists by drawing regions of interest on the thickened bowel wall. The resected bowel specimens with pathological fibrosis and type I collagen were classified into four severity grades (0-3) by a pathologist using a semi-quantitative scoring system. STATISTICAL TESTS: The differences in the T2*WI values among the different histological grades were analyzed using one-way analysis of variance or the Kruskal-Wallis test, and their correlations were analyzed. The ability of the T2*WI values to discriminate between various degrees of fibrosis was assessed using a receiver operating characteristic (ROC) curve. RESULTS: Significant differences were observed in the T2* values of mild (23.56 ± 1.60 ms), moderate (16.19 ± 0.55 ms), and severe (13.59 ± 0.53 ms) fibrosis types (F = 35.84; P < 0.001). T2* values were moderately associated with histological fibrosis (r = -0.627; P < 0.001) and type I collagen scores (r = -0.588; P < 0.001). T2* values were highly accurate, with an area under the ROC curve (AUC) of 0.951 (P < 0.001) for differentiating moderate-to-severe fibrosis from nonfibrosis and mild fibrosis, followed by an AUC of 0.508 for the percentage of enhancement gain (P = 0.908). A threshold T2* value of 18.06 ms was recommended for diagnosing moderate-to-severe fibrosis with 94.7% sensitivity and 78.3% specificity. DATA CONCLUSION: MRI T2* mapping outperforms CE parameters in distinction of various degrees of bowel fibrosis in CD. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.
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OBJECTIVE: The objective of this study was to assess the efficacy and clinical value of 64-slice computed tomography angiography (CTA) with image fusion for demonstrating the perigastric venous anatomy. METHODS: Twenty-six patients with gastric cancer underwent abdominal CTA examinations. Computed tomography angiography of stomach and perigastric veins and arteries were reconstructed and fused using volume-rendering technique. The inflow and courses of perigastric veins as well as the spatial relationship among the perigastric veins, arteries, and stomach were compared with surgery. RESULTS: Compared with surgical findings, the visualization rate of the 7 perigastric veins on CTA was 90.9% to 100%. There was a statistically significant decrease in number of short gastric veins identified on CTA compared with surgery (P = 0.004). There was no statistically significant difference between the 2 modalities in detecting other perigastric veins including the left gastric vein, right gastric vein, right gastroepiploic vein, left gastroepiploic vein, posterior gastric vein, and gastrocolic trunk (P = 0.317, P = 0.157, P = 1, P = 1, P = 0.317, P = 1, respectively). CONCLUSIONS: Sixty-four-slice CTA with image fusion clearly depicts most of perigastric veins and their relationship with the stomach and perigastric arteries. It can facilitate gastrectomy.
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Angiografía/métodos , Neoplasias Gástricas/diagnóstico por imagen , Estómago/irrigación sanguínea , Estómago/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Medios de Contraste , Femenino , Gastrectomía , Humanos , Yohexol/análogos & derivados , Masculino , Persona de Mediana Edad , Interpretación de Imagen Radiográfica Asistida por Computador , Estadísticas no Paramétricas , Estómago/cirugía , Neoplasias Gástricas/cirugíaRESUMEN
Self-assembly of particle-like dissipative solitons, in the presence of mutual interactions, emphasizes the vibrant concept of soliton molecules in varieties of laser resonators. Controllable manipulation of the molecular patterns, held by the degrees of freedom of internal motions, still remains challenging to explore more efficient and subtle tailoring approaches for the increasing demands. Here, we report a new phase-tailored quaternary encoding format based on the controllable internal assembly of dissipative soliton molecules. Artificial manipulation of the energy exchange of soliton-molecular elements stimulates the deterministic harnessing of the assemblies of internal dynamics. Self-assembled soliton molecules are tailored into four phase-defined regimes, thus constituting the phase-tailored quaternary encoding format. Such phase-tailored streams are endowed with great robustness and are resistant to significant timing jitter. All these results experimentally demonstrate the programmable phase tailoring and exemplify the application of the phase-tailored quaternary encoding, prospectively promoting high-capacity all-optical storage.
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BACKGROUND: More than half of patients with Crohn's disease (CD) require at least one surgery for symptom management; however, approximately half of the patients may experience postoperative anastomotic recurrence (PAR). OBJECTIVES: This study aims to develop and validate a preoperative computed tomography enterography (CTE)-based radiomics signature to predict early PAR in CD. DESIGN: A total of 186 patients with CD (training cohort, n = 134; test cohort, n = 52) who underwent preoperative CTE and surgery between January 2014 and June 2020 were included in this retrospective multi-centre study. METHODS: 106 radiomic features were initially extracted from intestinal lesions and peri-intestinal mesenteric fat, respectively; significant radiomic features were selected from them and then used to develop intestinal or mesenteric radiomics signatures, using the least absolute shrinkage and selection operator and a Cox regression model. A radiomics-based nomogram incorporating these signatures with clinical-radiological factors was created for comparison with a model based on clinical-radiological features alone. RESULTS: 68 of 134 patients in training cohort and 16 of 52 patients in test cohort suffered from PAR. The intestinal radiomic signature (hazard ratio [HR]: 2.17; 95% confidence interval [CI]: 1.32-3.58; P = 0.002) and mesenteric radiomic signature (HR: 2.19; 95% CI: 1.14-4.19; P = 0.018) were independent risk factors for PAR in the training cohort as per a multivariate analysis. The radiomics-based nomogram (C-index: 0.710; 95% CI: 0.672-0.748) yielded superior predictive performance than the clinical-radiological model (C-index, 0.607; 95% CI: 0.582-0.632) in the test cohort. Decision curve analysis demonstrated that the radiomics-based nomogram outperformed the clinical-radiological model in terms of clinical usefulness. CONCLUSIONS: Preoperative mesenteric and intestinal CTE radiomics signatures are potential non-invasive predictors of PAR in postoperative patients with CD.
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Enfermedad de Crohn , Humanos , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/cirugía , Tomografía Computarizada por Rayos X/métodos , Nomogramas , Radiografía , Estudios RetrospectivosRESUMEN
BACKGROUND: Calmodulin 1 (CALM1) mutations are involved in the development of coronary artery disease (CAD). However, the relationship of CALM1 rs3179089 polymorphism with CAD is unknown. OBJECTIVE: This study aimed to identify the relationship of CALM1 rs3179089 polymorphism with CAD susceptibility, CALM1 expression, blood pressure, blood glucose, blood coagulation and serum lipid levels of CAD patients. METHODS: 550 CAD patients and 550 control subjects were genotyped for CALM1 using Sequenom MassARRAY technology. CALM1 expression level was measured by quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: CALM1 mRNA expression was higher in CAD patients than that in control subjects (P < 0.001). CAD patients with CC genotype had higher CALM1 mRNA expression level than control subjects with CC genotype (P = 0.006). Genotypic frequency of rs3179089 was different between male patients of CAD and control subjects (P = 0.045). Rs3179089 polymorphism was related to CAD risk of males in recessive model (P = 0.039). Moreover, rs3179089 polymorphism was associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), and D-Dimer (D-D) level of patients with CAD in recessive model (P = 0.013 for SBP; P = 0.034 for DBP; P = 0.004 for FPG; P = 0.046 for D-D). In addition, rs3179089 polymorphism was correlated with low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) serum levels of patients with CAD in both addictive (P = 0.025 for LDL-C; P = 0.001 for TC) and recessive models (P = 0.001 for LDL-C; P = 0.001 for TC). CONCLUSION: CALM1 expression is associated with development of CAD. CALM1 rs3179089 polymorphism affects CAD susceptibility in males, and blood pressure, blood glucose, blood coagulation and serum lipid of CAD patients.
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Calmodulina , Enfermedad de la Arteria Coronaria , Calmodulina/genética , Estudios de Casos y Controles , China , LDL-Colesterol/genética , Enfermedad de la Arteria Coronaria/genética , Glucosa , Humanos , Masculino , Polimorfismo de Nucleótido Simple , ARN Mensajero , Factores de RiesgoRESUMEN
Background: While the grading of intestinal fibrosis is closely related to the therapeutic strategy of patients with Crohn's disease (CD), it has not yet been well resolved. Mesenteric abnormalities are inextricably linked to intestinal fibrosis. Objectives: We aimed to establish an optimal model for assessing intestinal fibrosis using computed tomography enterography (CTE) and clinical markers. Design: A total of 174 patients with CD between January 2014 and June 2020 were included in this retrospective multicentre study. Methods: All patients underwent CTE within 3 months prior to surgery. Intestinal fibrosis was pathologically scored as non-mild or moderate-to-severe. Selected imaging of the intestinal walls and mesentery and/or clinical factors were used to develop the diagnostic models. The area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the discrimination performance of the models. A decision curve analysis was performed to evaluate the clinical usefulness of the models. Results: One-, two-, and three-variable models were identified as possible diagnostic models. Model 1 [mesenteric creeping fat index (MCFI)], Model 2 (mesenteric oedema and MCFI), and Model 3 (mesenteric oedema, MCFI, and disease duration) were established. The AUCs of Model 1 in training and test cohorts 1 and 2 were 0.799, 0.859, and 0.693, respectively; Model 2 was 0.851, 0.833, and 0.757, respectively; and Model 3 was 0.832, 0.821, and 0.850, respectively. We did not observe any significant difference in diagnostic performance between the training and total test cohorts in any model (all p > 0.05). The decision curves showed that Model 3 had the highest net clinical benefit in test cohort 2. The nomogram of this optimal model was constructed by considering the favourable and robust performance of Model 3. Conclusion: A nomogram integrating mesenteric abnormalities on CTE with a clinical marker was optimal for differentiating between non-mild and moderate-to-severe fibrosis in patients with CD.