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OBJECTIVES: To use T1ρ mapping to assess myocardial fibrosis and to provide a reference for future clinical application, it is necessary to understand the factors influencing T1ρ values. This study explored the influence of different spin-locking frequencies on T1ρ values under a 3.0-T MR system. METHODS: Fifty-seven healthy subjects were prospectively and consecutively included in this study, and T1ρ mapping was performed on them in 3 short-axis slices with three spin-lock frequencies at the amplitude of 300 Hz, 400 Hz, and 500 Hz, then nine T1ρ images were acquired per subject. Four T1ρ-weighted images were acquired using a spin-lock preparation pulse with varying durations (0 msec, 13.3 msec, 26.6 msec, 40 msec). T1ρ relaxation times were quantified for each slice and each myocardial segment. The results were analyzed using Student's t-test and one-way analysis of variance (ANOVA) methods. RESULTS: Mean T1ρ relaxation times were 43.5 ± 2.8 msec at 300 Hz, 44.9 ± 3.6 msec at 400 Hz, and 46.2 ± 3.1 msec at 500 Hz, showing a significant progressive increase from low to high spin-lock frequency (300 Hz vs. 400 Hz, p = 0.046; 300 Hz vs. 500 Hz, p < 0.001; 400 Hz vs. 500 Hz, p = 0.043). In addition, The T1ρ values of females were significantly higher than those of males (300 Hz, p = 0.049; 400 Hz, p = 0.01; 500 Hz, p = 0.002). CONCLUSION: In this prospective study, myocardial T1ρ values for the specific CMR setting are provided, and we found that gender and spin-lock frequency can affect the T1ρ values. CRITICAL RELEVANCE STATEMENT: T1ρ mapping could supersede late gadolinium enhancement for detection of myocardial fibrosis. Establishing reference mean values that take key technical elements into account will facilitate interpretation of data in disease states. KEY POINTS: This study established myocardial T1ρ reference values for different spin-lock frequencies. T1ρ values increased with spin-lock frequency, but numerical differences were minimal. Females had higher T1ρ values than males at all frequencies.
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BACKGROUND: Epicardial adipose tissue (EAT) is a metabolically active visceral fat linked to cardiovascular disease. Prior studies demonstrated the predictive value of EAT volume (EATV) in atrial fibrillation (AF) among hypertrophic obstructive cardiomyopathy patients. PURPOSE: To investigate the association between EATV and AF in hypertrophic cardiomyopathy (HCM). STUDY TYPE: Retrospective. POPULATION: Two hundred and twenty-four HCM patients (including 79 patients with AF and 145 patients without AF, 154 men) and 80 healthy controls (54 men). FIELD STRENGTH/SEQUENCE: 3.0 T scanner; balanced steady-state free precession (SSFP) cine sequence, gradient echo. ASSESSMENT: EAT thickness was assessed in the 4-chamber and basal short-axis planes. EAT volume was calculated by outlining the epicardial border and visceral pericardium layer on short-axis cine images. STATISTICAL TESTS: Shapiro-Wilk test, Student's t test or the Mann-Whitney U test, chi-square test or Fisher's exact test, Multivariate linear regression analyses, Multivariable binary logistic regression analysis. Intraclass correlation coefficient. Significance was determined at P < 0.05. RESULTS: EATV and EAT volume index (EATVI) were significantly greater in HCM patients with AF than those without AF (126.6 ± 25.9 mL vs. 90.5 ± 24.5 mL, and 73.0 ± 15.9 mL/m2 vs. 51.3 ± 13.4 mL/m2). EATVI was associated with AF in multivariable linear regression analysis among HCM patients (ß = 0.62). Multivariable logistic regression analysis revealed that compared to other indicators, the area under curve (AUC) of EATVI was 0.86 (cut-off, 53.9 mL/m2, 95% CI, 0.80-0.89), provided a better performance, with the sensitivity of 96.2% and specificity of 58.6%. The combined model exhibited superior association with AF presence compared to the clinical model (AUC 0.96 vs. 0.76) and the imaging model (AUC 0.96 vs. 0.93). DATA CONCLUSION: EATVI was associated with AF. EATVI was significantly correlated with incident AF, and provided a better performance in HCM patients compared to other indicators. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.
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The Self-Attention Mechanism (SAM) excels at distilling important information from the interior of data to improve the computational efficiency of models. Nevertheless, many Quantum Machine Learning (QML) models lack the ability to distinguish the intrinsic connections of information like SAM, which limits their effectiveness on massive high-dimensional quantum data. To tackle the above issue, a Quantum Kernel Self-Attention Mechanism (QKSAM) is introduced to combine the data representation merit of Quantum Kernel Methods (QKM) with the efficient information extraction capability of SAM. Further, a Quantum Kernel Self-Attention Network (QKSAN) framework is proposed based on QKSAM, which ingeniously incorporates the Deferred Measurement Principle (DMP) and conditional measurement techniques to release half of quantum resources by mid-circuit measurement, thereby bolstering both feasibility and adaptability. Simultaneously, the Quantum Kernel Self-Attention Score (QKSAS) with an exponentially large characterization space is spawned to accommodate more information and determine the measurement conditions. Eventually, four QKSAN sub-models are deployed on PennyLane and IBM Qiskit platforms to perform binary classification on MNIST and Fashion MNIST, where the QKSAS tests and correlation assessments between noise immunity and learning ability are executed on the best-performing sub-model. The paramount experimental finding is that the QKSAN subclasses possess the potential learning advantage of acquiring impressive accuracies exceeding 98.05% with far fewer parameters than classical machine learning models. Predictably, QKSAN lays the foundation for future quantum computers to perform machine learning on massive amounts of data while driving advances in areas such as quantum computer vision.
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Ectomycorrhizal fungi have huge potential value, both nutritionally and economically, but most of them cannot be cultivated artificially. To better understand the influence of abiotic and biotic factors upon the growth of ectomycorrhizal fungi, mycosphere soil and bulk soil of five ectomycorrhizal fungi (Calvatia candida, Russula brevipes, Leucopaxillus laterarius, Leucopaxillus giganteus, and Lepista panaeola) were used as research objects for this study. Illumina MiSeq sequencing technology was used to analyze the community structure of the mycosphere and bulk soil bacteria of the five ectomycorrhizal fungi, and a comprehensive analysis was conducted based on soil physicochemical properties. Our results show that the mycosphere soil bacteria of the five ectomycorrhizal fungi are slightly different. Escherichia, Usitatibacter, and Bradyrhizobium are potential mycorrhizal-helper bacteria of distinct ectomycorrhizal fungi. Soil water content, soil pH, and available potassium are the main factors shaping the soil bacterial community of the studied ectomycorrhizal fungi. Moreover, from the KEGG functional prediction and LEfSe analysis, there are significant functional differences not only between the mycosphere soil and bulk soil. 'Biosynthesis of terpenoidsand steroids', 'alpha-Linolenic acid metabolism', 'Longevity regulating pathway-multiple species', 'D-Arginine and D-ornithine metabolism', 'Nitrotoluene degradation' and other functions were significantly different in mycosphere soil. These findings have pivotal implications for the sustainable utilization of ectomycorrhizal fungi, the expansion of edible fungus cultivation in forest environments, and the enhancement of derived economic benefits.
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Neoplasias Gastrointestinales , Microambiente Tumoral , Microambiente Tumoral/inmunología , Humanos , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/terapia , Neoplasias Gastrointestinales/inmunología , Animales , Terapia Molecular DirigidaRESUMEN
Cardiac amyloidosis (CA) is characterized by the deposition of amyloid fibrils within the myocardium, resulting in a restrictive physiology. Although microvascular dysfunction is a common feature, it is difficult to assess. This study aimed to explore myocardial transit time (MyoTT) by cardiovascular magnetic resonance (CMR) as a potential novel parameter of microcirculatory dysfunction in CA. This prospective study enrolled 20 CA patients and 20 control subjects. CMR acquisition included cine imaging, pre- and post-contrast T1 mapping, and MyoTT assessment, which was calculated from the time delay in contrast agent arrival between the aortic root and coronary sinus (CS). Compared to the control group, patients with CA exhibited significantly reduced left ventricular (LV) ejection fraction and myocardial strain, an increase in LV global peak wall thickness (LVGPWT), extracellular volume fraction (ECV), and prolonged MyoTT (14.4 ± 3.8 s vs. 7.7 ± 1.5 s, p < 0.001). Moreover, patients at Mayo stage III had a significantly longer MyoTT compared to those at stage I/II. MyoTT showed a positive correlation with the ECV, LVGPWT, and LV global longitudinal strain (LV-GLS) (p < 0.05). The area under the curve (AUC) for MyoTT was 0.962, demonstrating diagnostic performance comparable to that of the ECV (AUC 0.995) and LV-GLS (AUC 0.950) in identifying CA. MyoTT is significantly prolonged in patients with CA, correlating with fibrosis markers, remodeling, and dysfunction. As a novel parameter of coronary microvascular dysfunction (CMD), MyoTT has the potential to be an integral biomarker in multiparametric CMR assessment of CA.
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INTRODUCTION: Colorectal cancer (CRC) is the second most lethal malignancy worldwide. Immune checkpoint inhibitors (ICIs) benefit only 15% of patients with mismatch repair-deficient/microsatellite instability (dMMR/MSI) CRC. The majority of patients are not suitable due to insufficient immune infiltration. Cancer vaccines are a potential approach for inducing tumor-specific immunity within the solid tumor microenvironment. AREA COVERED: In this review, we have provided an overview of the current progress in CRC vaccines over the past three years and briefly depict promising directions for further exploration. EXPERT OPINION: Cancer vaccines are certainly a promising field for the antitumor treatment against CRC. Compared to monotherapy, cancer vaccines are more appropriate as adjuvants to standard treatment, especially in combination with ICI blockade, for microsatellite stable patients. Improved vaccine construction requires neoantigens with sufficient immunogenicity, satisfactory HLA-binding affinity, and an ideal delivery platform with perfect lymph node retention and minimal off-target effects. Prophylactic vaccines that potentially prevent CRC carcinogenesis are also worth investigating. The exploration of appropriate biomarkers for cancer vaccines may benefit prognostic prediction analysis and therapeutic response prediction in patients with CRC. Although many challenges remain, CRC vaccines represent an exciting area of research that may become an effective addition to current guidelines.
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Vacunas contra el Cáncer , Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/prevención & control , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/genética , Vacunas contra el Cáncer/uso terapéutico , Vacunas contra el Cáncer/inmunología , Animales , Microambiente Tumoral/inmunologíaAsunto(s)
Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Neoplasias del Recto/patología , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Estudios Prospectivos , Ultrasonografía Intervencional , Biopsia Guiada por Imagen/métodos , Ensayos Clínicos Fase II como AsuntoRESUMEN
Importance: With the widespread use of anti-SARS-CoV-2 drugs, accumulating data have revealed potential viral load rebound after treatment. Objective: To compare COVID-19 rebound after a standard 5-day course of antiviral treatment with VV116 vs nirmatrelvir-ritonavir. Design, Setting, and Participants: This is a single-center, investigator-blinded, randomized clinical trial conducted in Shanghai, China. Adult patients with mild-to-moderate COVID-19 and within 5 days of SARS-CoV-2 infection were enrolled between December 20, 2022, and January 19, 2023, and randomly allocated to receive either VV116 or nirmatrelvir-ritonavir. Interventions: Participants in the VV116 treatment group received oral 600-mg VV116 tablets every 12 hours on day 1 and 300 mg every 12 hours on days 2 through 5. Participants in the nirmatrelvir-ritonavir treatment group received oral nirmatrelvir-ritonavir tablets with 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 hours for 5 days. Participants were followed up every other day until day 28 and every week until day 60. Main Outcomes and Measures: The primary outcome was viral load rebound (VLR), defined as a half-log increase in viral RNA copies per milliliter compared with treatment completion. Secondary outcomes included a reduction in the cycle threshold value of 1.5 or more, time until VLR, and symptom rebound, defined as an increase of more than 2 points in symptom score compared with treatment completion. The primary outcome and secondary outcomes were analyzed using the full analysis set. Sensitivity analyses were conducted using the per protocol set. Adverse events were analyzed using the safety analysis set. Results: The full analysis set included 345 participants (mean [SD] age, 53.2 [16.8] years; 175 [50.7%] were men) who received VV116 (n = 165) or nirmatrelvir-ritonavir (n = 180). Viral load rebound occurred in 33 patients (20.0%) in the VV116 group and 39 patients (21.7%) in the nirmatrelvir-ritonavir group (P = .70). Symptom rebound occurred in 41 of 160 patients (25.6%) in the VV116 group and 40 of 163 patients (24.5%) in the nirmatrelvir-ritonavir group (P = .82). Viral whole-genome sequencing of 24 rebound cases revealed the same lineage at baseline and at viral load rebound in each case. Conclusions and Relevance: In this randomized clinical trial of patients with mild-to-moderate COVID-19, viral load rebound and symptom rebound were both common after a standard 5-day course of treatment with either VV116 or nirmatrelvir-ritonavir. Prolongation of treatment duration might be investigated to reduce COVID-19 rebound. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200066811.
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Adenosina , COVID-19 , Recurrencia , Adulto , Masculino , Humanos , Persona de Mediana Edad , Femenino , Tratamiento Farmacológico de COVID-19 , China , Ritonavir , SARS-CoV-2 , Adenosina/análogos & derivadosRESUMEN
Aim: To evaluate the subclinical cardiac involvement in COVID-19 patients without clinical cardiac evidence using cardiac MR imaging. Material and methods: Participants recovered from COVID-19 without cardiac symptoms and no cardiovascular medical history were enrolled in a prospective cohort study. They underwent baseline cardiac MR and follow-up cardiac MR > 300 days after discharge (n = 20). The study also included healthy controls (n = 20). Extracellular volume fraction (ECV), native T1, and 2D strain data were assessed and compared. Results: The ECV values of participants at baseline [30.0% (28.3%-32.5%)] and at follow-up [31.0% (28.0%-32.8%)] were increased compared to the healthy control group [27.0% (25.3%-28.0%)] (both p < 0.001). However, the ECV increase from baseline cardiac MR to follow-up cardiac MR was not significant (p = 0.378). There was a statistically significant difference in global native T1 between baseline [1140 (1108.3-1192.0) ms] and follow-up [1176.0 (1113.0-1206.3) ms] (p = 0.016). However, no native T1 difference was found between the healthy controls [1160.7 (1119.6-1195.4) ms] and the baseline (p = 0.394) or follow-up group (p = 0.168). The global T2 was 41(40-42) ms at follow-up which was within the normal range. In addition, We found a recovery in 2D GLS among COVID-19 participants between baseline and follow-up [-12.4(-11.7 to -14.3)% vs. -17.2(-16.2 to -18.3)%; pï¼0.001]. Conclusion: Using cardiac MR myocardial tissue and strain imaging parameters, 35% of people without cardiac symptoms or clinical evidence of myocardial injury still had subclinical myocardial tissue characteristic abnormalities at 300 days, but 2D GLS had recovered.
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BACKGROUND: Tyrosine kinase inhibitors (TKIs) are crucial in the targeted treatment of advanced colorectal cancer (CRC). Anlotinib, a multi-target TKI, has previously been demonstrated to offer therapeutic benefits in previous studies. Circular RNAs (circRNAs) have been implicated in CRC progression and their unique structural stability serves as promising biomarkers. The detailed molecular mechanisms and specific biomarkers related to circRNAs in the era of targeted therapies, however, remain obscure. METHODS: The whole transcriptome RNA sequencing and function experiments were conducted to identify candidate anlotinib-regulated circRNAs, whose mechanism was confirmed by molecular biology experiments. CircHAS2 was profiled in a library of patient-derived CRC organoids (n = 22) and patient-derived CRC tumors in mice. Furthermore, a prospective phase II clinical study of 14 advanced CRC patients with anlotinib-based therapy was commenced to verify drug sensitivity (ClinicalTrials.gov identifier: NCT05262335). RESULTS: Anlotinib inhibits tumor growth in vitro and in vivo by downregulating circHAS2. CircHAS2 modulates CCNE2 activation by acting as a sponge for miR-1244, and binding to USP10 to facilitate p53 nuclear export as well as degradation. In parallel, circHAS2 serves as a potent biomarker predictive of anlotinib sensitivity, both in patient-derived organoids and xenograft models. Moreover, the efficacy of anlotinib inclusion into the treatment regimen yields meaningful clinical responses in patients with high levels of circHAS2. Our findings offer a promising targeted strategy for approximately 52.9% of advanced CRC patients who have high circHAS2 levels. CONCLUSIONS: CircHAS2 promotes cell proliferation via the miR-1244/CCNE2 and USP10/p53/CCNE2 bidirectional axes. Patient-derived organoids and xenograft models are employed to validate the sensitivity to anlotinib. Furthermore, our preliminary Phase II clinical study, involving advanced CRC patients treated with anlotinib, confirmed circHAS2 as a potential sensitivity marker.
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Neoplasias Colorrectales , Indoles , MicroARNs , Quinolinas , Humanos , Animales , Ratones , ARN Circular/genética , Proteína p53 Supresora de Tumor , Estudios Prospectivos , MicroARNs/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Proliferación Celular/genética , Biomarcadores , Ubiquitina Tiolesterasa/metabolismo , Ciclinas/metabolismoRESUMEN
Objective: This study aims to determine the effectiveness of T1ρ in detecting myocardial fibrosis in type 2 diabetes mellitus (T2DM) patients by comparing with native T1 and extracellular volume (ECV) fraction. Methods: T2DM patients (n = 35) and healthy controls (n = 30) underwent cardiac magnetic resonance. ECV, T1ρ, native T1, and global longitudinal strain (GLS) values were assessed. Diagnostic performance was analyzed using receiver operating curves. Results: The global ECV and T1ρ of T2DM group (ECV = 32.1 ± 3.2%, T1ρ = 51.6 ± 3.8 msec) were significantly higher than those of controls (ECV = 26.2 ± 1.6%, T1ρ = 46.8 ± 2.0 msec) (all P < 0.001), whether there was no significant difference in native T1 between T2DM and controls (P = 0.264). The GLS decreased significantly in T2DM patients compared with controls (-16.5 ± 2.4% vs. -18.3 ± 2.6%, P = 0.015). The T1ρ and native T1 were associated with ECV (Pearson's r = 0.50 and 0.25, respectively, both P < 0.001); the native T1, T1ρ, and ECV were associated with hemoglobin A1c (Pearson's r = 0.41, 0.52, and 0.61, respectively, all P < 0.05); and the ECV was associated with diabetes duration (Pearson's r = 0.41, P = 0.016). The AUC of ECV, T1ρ, GLS, and native T1 were 0.869, 0.810, 0.659, and 0.524, respectively. Conclusion: In T2DM patients, T1ρ may be a new non-contrast cardiac magnetic resonance technique for identifying myocardial diffuse fibrosis, and T1ρ may be more sensitive than native T1 in the detection of myocardial diffuse fibrosis.
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Cardiomiopatías , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Diabetes Mellitus Tipo 2/patología , Miocardio/patología , Corazón , Cardiomiopatías/patología , Fibrosis , Espectroscopía de Resonancia MagnéticaRESUMEN
The aim of this study is to assess the feasibility of compressed sensing (CS) acceleration methods compared to conventional segmented cine (Seg) cardiac magnetic resonance (CMR) for evaluating left ventricular (LV) function and strain by feature tracking (FT). In this prospective study, 45 healthy volunteers underwent CMR imaging used Seg, threefold (CS3), fourfold (CS4), and eightfold (CS8) CS acceleration. Cine images were scored for quality (1-5 scale). LV volumetric and functional parameters and global longitudinal (GLS), circumferential (GCS), and radial strains (GRS) were quantified. LV volumetric and functional parameters exhibited no differences between Seg and all CS cines (all P > 0.05). The strains were similar for Seg, CS3, and CS4 (all P > 0.05). Similarly, no significant differences were observed in GRS and GCS between Seg and CS8 (all P > 0.05), but the global longitudinal strain was significantly lower for CS8 versus Seg (P < 0.001). Image quality declined with CS acceleration, especially in long-axis views with CS8. CS cine MRI at acceleration factor 4 maintained good image quality and accurate measurements of LV function and strain, although there was a slight reduction in the quality of long-axis images and GLS with CS8. CS acceleration up to a factor of 4 enabled fast CMR evaluations, making it suitable for clinical use.
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Imagen por Resonancia Cinemagnética , Humanos , Imagen por Resonancia Cinemagnética/métodos , Masculino , Adulto , Femenino , Estudios Prospectivos , Función Ventricular Izquierda/fisiología , Persona de Mediana Edad , Interpretación de Imagen Asistida por Computador/métodos , Adulto Joven , Estudios de Factibilidad , Ventrículos Cardíacos/diagnóstico por imagenRESUMEN
RNA splicing is involved in cancer initiation and progression, but how it influences host antitumor immunity in the metabolically abnormal tumor microenvironment (TME) remains unclear. Here, we demonstrate that lactate modulates Foxp3-dependent RNA splicing to maintain the phenotypic and functional status of tumor-infiltrating regulatory T (Treg) cells via CTLA-4. RNA splicing in Treg cells was correlated with the Treg cell signatures in the TME. Ubiquitin-specific peptidase 39 (USP39), a component of the RNA splicing machinery, maintained RNA-splicing-mediated CTLA-4 expression to control Treg cell function. Mechanistically, lactate promoted USP39-mediated RNA splicing to facilitate CTLA-4 expression in a Foxp3-dependent manner. Moreover, the efficiency of CTLA-4 RNA splicing was increased in tumor-infiltrating Treg cells from patients with colorectal cancer. These findings highlight the immunological relevance of RNA splicing in Treg cells and provide important insights into the environmental mechanism governing CTLA-4 expression in Treg cells.
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Neoplasias , Linfocitos T Reguladores , Humanos , Antígeno CTLA-4 , Factores de Transcripción Forkhead/genética , Ácido Láctico/metabolismo , Linfocitos Infiltrantes de Tumor , Neoplasias/genética , Neoplasias/metabolismo , Microambiente Tumoral , Proteasas Ubiquitina-Específicas/metabolismoRESUMEN
BACKGROUND: To facilitate the clinical use of cardiac T1ρ, it is important to understand the impact of age and sex on T1ρ values of the myocardium. PURPOSE: To investigate the impact of age and gender on myocardial T1ρ values. STUDY TYPE: Cross-sectional. POPULATION: Two hundred ten healthy Han Chinese volunteers without cardiovascular risk factors (85 males, mean age 34.4 ± 12.5 years; 125 females, mean age 37.9 ± 14.8 years). FIELD STRENGTH/SEQUENCE: 1.5 T; T1ρ-prepared steady-state free precession (T1ρ mapping) sequence. ASSESSMENT: Basal, mid, and apical short-axis left ventricular T1ρ maps were acquired. T1ρ maps acquired with spin-lock frequencies of 5 and 400 Hz were subtracted to create a myocardial fibrosis index (mFI) map. T1ρ and mFI values across different age decades, sex, and slice locations were compared. STATISTICAL TESTS: Shapiro-Wilk test, Student's t test, Mann-Whitney U test, linear regression analysis, one-way analysis of variance and intraclass correlation coefficient. SIGNIFICANCE: P value <0.05. RESULTS: Women had significantly higher T1ρ and mFI values than men (50.3 ± 2.0 msec vs. 47.7 ± 2.4 msec and 4.7 ± 1.0 msec vs. 4.3 ± 1.1 msec, respectively). Additionally, in males and females combined, there was a significant positive but weak correlation between T1ρ values and age (r = 0.27), while no correlation was observed between the mFI values and age (P = 0.969). DATA CONCLUSION: We report potential reference values for cardiac T1ρ by sex, age distribution, and slice location in a Chinese population. T1ρ was significantly correlated with age and sex, while mFI was only associated with sex. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.
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OBJECTIVES: To explore the characteristics of myocardial involvement in Wilson Disease (WD) patients by cardiac magnetic resonance (CMR). METHODS: We prospectively included WD patients and age- and sex-matched healthy population. We applied CMR to analyze cardiac function, strain, T1 maps, T2 maps, extracellular volume fraction (ECV) maps, and LGE images. Subgroup analyzes were performed for patients with WD with predominantly neurologic manifestations (WD-neuro +) or only hepatic manifestations (WD-neuro -). RESULTS: Forty-one WD patients (age 27.9 ± 8.0 years) and 40 healthy controls (age 25.4 ± 2.9 years) were included in this study. Compared to controls, the T1, T2, and ECV values were significantly increased in the WD group (T1 1085.1 ± 39.1 vs. 1046.5 ± 33.1 ms, T2 54.2 ± 3.3 ms vs. 51.5 ± 2.6 ms, ECV 31.8 ± 3.6% vs. 24.3 ± 3.7%) (all p < 0.001). LGE analysis revealed that LGE in WD patients was predominantly localized to the right ventricular insertion point and interventricular septum. Furthermore, the WD-neuro + group showed more severe myocardial damage compared to WD-neuro - group. The Unified Wilson Disease Rating Scale score was significantly correlated with ECV (Pearson's r = 0.64, p < 0.001). CONCLUSIONS: CMR could detect early myocardial involvement in WD patients without overt cardiac function dysfunction. Furthermore, characteristics of myocardial involvement were different between WD-neuro + and WD-neuro - , and myocardial involvement might be more severe in WD-neuro + patients. CRITICAL RELEVANCE STATEMENT: Cardiac magnetic resonance enables early detection of myocardial involvement in Wilson disease patients, contributing to the understanding of distinct myocardial characteristics in different subgroups and potentially aiding in the assessment of disease severity. KEY POINTS: ⢠CMR detects WD myocardial involvement with increased T1, T2, ECV. ⢠WD-neuro + patients show more severe myocardial damage and correlation with ECV. ⢠Differences of myocardial characteristics exist between WD-neuro + and WD-neuro - patients.
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The outcomes and prognosis of autoimmune diseases depend on early diagnosis and effective treatments. However, symptoms of early autoimmune diseases are often remarkably similar to many inflammatory diseases, leading to difficulty in precise diagnosis. Circular RNAs (circRNAs) belong to a novel class of endogenous RNAs, functioning as microRNA (miRNA) sponges or participating in protein coding. It has been shown in many studies that patients with autoimmune diseases have aberrant circRNA expression in liquid biopsy samples (such as plasma, saliva, and urine). Thus, circRNAs are potential biomarkers for the diagnosis and prognosis of autoimmune diseases. Moreover, overexpression and depletion of target circRNAs can be utilized as possible therapeutic approaches for treating autoimmune diseases. In this review, we summarized recent progress in the roles of circRNAs in the pathogenesis of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and type 1 diabetes. We also discussed their potential as biomarkers and therapeutic targets.
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A multifunctional nanoplatform is obtained by modifying copper hexacyanoferrate (Cu-HCF) nanozyme with hyaluronic acid (HA) and further loading platinum (Pt) nanoparticles. This Cu-HCF-HA@Pt platform shows peroxidase-like and glutathione oxidase-like dual-enzyme catalytic activities and photothermal properties, enabling synergistic chemodynamic and photothermal tumor therapy. HA binds to the CD44 receptor, which is highly expressed on the exterior surface of tumor cells, endowing the nanoplatform with tumor specificity. Cu-HCF-HA@Pt catalyzes the decomposition of H2O2 to produce abundant hydroxyl radicals within tumor cells, increasing intracellular oxidative stress levels and inducing tumor cell apoptosis. Meanwhile, Cu-HCF-HA@Pt catalyzes the conversion of intracellular reduced glutathione (GSH) to oxidized glutathione, resulting in GSH exhaustion. The conversion of CuII to CuI in Cu-HCF via a Fenton-like reaction can improve the peroxidase-like property of Cu-HCF-HA@Pt. After the probe is targeted to the tumor site, irradiation by an 808 nm near-infrared laser causes local heating and brings about photothermal tumor apoptosis when reaching 45 °C. The prepared Cu-HCF-HA@Pt combines nanozyme-catalyzed therapy with photothermal therapy to induce apoptosis in tumor cells.