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BACKGROUND: Both individuals and society bear a considerable burden from ischemic stroke (IS), not only do patients continue suffering from motor dysfunction after discharge from hospital, but their caregivers also undertake the principal responsibility of assisting them in reintegrating into the family and society. To better improve the IS patients' limb function and daily life activities, their caregivers should also be involved in the training of the motor function rehabilitation during the period transitioning from hospital back home. This study mainly aims to investigate the effects of a nurse-led training for IS patients and their family caregivers on the improvement of the patients' physical function and the burden of caregivers. METHODS/DESIGN: A randomized controlled trial with blind assessment will be conducted in hospitals and during the follow-ups at home. Fifty-eight pairs of adults diagnosed with ischemic stroke and their primary caregivers will be included. Participants will be randomly given with (1) a nurse-led, home-based motor rehabilitation training participated by caregivers (intervention group) or (2) routine self-care (control group). Both groups will receive assessment and health guidance on the day of discharge, and the intervention group will receive an additional home-based training program and supervision. These two groups will be followed up every week after discharge. The primary results are drawn from the evaluation of physical function and caregiver-related burden, and the secondary results derived from statistics of the modified Barthel index, stroke-specific quality of life, and National Institutes of Health Stroke Scale. Differences between the two groups will be measured by two-way repeated measures ANOVA, considering the data at baseline and at 1-week and 4-week follow-up after training. DISCUSSION: Results may provide novel and valuable information on the effects of this culturally appropriate, caregiver-involved, and home-based rehabilitation training on the physical function of IS patients and caregiver-related burden. TRIAL REGISTRATION: Chinese Clinical Trial Registry (chictr.org.cn) ChiCTR2300078798. Registered on December 19, 2023.
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Cuidadores , Accidente Cerebrovascular Isquémico , Ensayos Clínicos Controlados Aleatorios como Asunto , Recuperación de la Función , Rehabilitación de Accidente Cerebrovascular , Humanos , Rehabilitación de Accidente Cerebrovascular/métodos , Cuidadores/educación , Accidente Cerebrovascular Isquémico/rehabilitación , Accidente Cerebrovascular Isquémico/enfermería , Accidente Cerebrovascular Isquémico/fisiopatología , Femenino , Persona de Mediana Edad , Masculino , Carga del Cuidador , Factores de Tiempo , Resultado del Tratamiento , China , Adulto , Actividades Cotidianas , Anciano , Actividad Motora , Calidad de Vida , Estado FuncionalRESUMEN
Reperfusion after myocardial ischemia would aggravate myocardial structural and functional damage, known as myocardial ischemia-reperfusion (MI/R) injury. Cinnamamide derivatives have been reported to exert cardioprotective effects, and we have previously reported that compound 7 played a role in cardioprotection against MI/R via anti-inflammatory effect. However, exact mechanism underlying such beneficial action of compound 7 is still unclear. The protective effect of compound 7 was determined in H9c2 cells under H2O2 stimulation with or without nigerin (NLRP3 activator). Electrocardiogram, echocardiography, myocardial infarction size, histopathology and serum biochemical assay were performed in MI/R rats. Metabolomics in vivo and mRNA or protein levels of NLRP3, ASC, cleaved caspase-1 and its downstream IL-18 and IL-1ß were detected both in vitro and in vivo. Compound 7 significantly ameliorate H2O2-induced cardiomyocyte damage, which was supported by in vivo data determined by improved left ventricular systolic function and histopathological changes, reduced myocardial infarction area and cellular apoptosis in heart tissue. Cardiac differential metabolites demonstrated that compound 7 indeed altered the cardiac reprogramming of inflammation-related metabolites, which was evidenced by down-regulated cardiac inflammation by compound 7. Additionally, compound 7 alleviated myocardial injury by inhibiting the NLRP3 pathway rather than other members of the inflammasome both in vitro and in vivo, which was further evidenced by CETSA assay. Whereas, nigerin blocked the inhibitory activity of compound 7 against NLRP3. Cinnamamide derivative compound 7 ameliorated MI/R injury by inhibiting inflammation via NLRP3.
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Antiinflamatorios , Daño por Reperfusión Miocárdica , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Masculino , Ratas , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Línea Celular , Cinamatos/farmacología , Cinamatos/uso terapéutico , Ratas Sprague-Dawley , Peróxido de Hidrógeno/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Miocitos Cardíacos/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/patología , Apoptosis/efectos de los fármacos , Inflamasomas/metabolismo , Modelos Animales de EnfermedadRESUMEN
Retinal microvascular disease has caused serious visual impairment widely in the world, which can be hopefully prevented via early and precision microvascular hemodynamic diagnosis. Due to artifacts from choroidal microvessels and tiny movements, current fundus microvascular imaging techniques including fundus fluorescein angiography (FFA) precisely identify retinal microvascular microstructural damage and abnormal hemodynamic changes difficulty, especially in the early stage. Therefore, this study proposes an FFA-based multi-parametric retinal microvascular functional perfusion imaging (RM-FPI) scheme to assess the microstructural damage and quantify its hemodynamic distribution precisely. Herein, a spatiotemporal filter based on singular value decomposition combined with a lognormal fitting model was used to remove the above artifacts. Dynamic FFAs of patients (n = 7) were collected first. The retinal time fluorescence intensity curves were extracted and the corresponding perfusion parameters were estimated after decomposition filtering and model fitting. Compared with in vivo results without filtering and fitting, the signal-to-clutter ratio of retinal perfusion curves, average contrast, and resolution of RM-FPI were up to 7.32 ± 0.43 dB, 14.34 ± 0.24 dB, and 11.0 ± 2.0 µm, respectively. RM-FPI imaged retinal microvascular distribution and quantified its spatial hemodynamic changes, which further characterized the parabolic distribution of local blood flow within diameters ranging from 9 to 400 µm. Finally, RM-FPI was used to quantify, visualize, and diagnose the retinal hemodynamics of retinal vein occlusion from mild to severe. Therefore, this study provided a scheme for early and precision diagnosis of retinal microvascular disease, which might be beneficial in preventing its development.
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BACKGROUND: Breast tumor is a fatal threat to the health of women. Ultrasound (US) is a common and economical method for the diagnosis of breast cancer. Breast imaging reporting and data system (BI-RADS) category 4 has the highest false-positive value of about 30% among five categories. The classification task in BI-RADS category 4 is challenging and has not been fully studied. PURPOSE: This work aimed to use convolutional neural networks (CNNs) for breast tumor classification using B-mode images in category 4 to overcome the dependence on operator and artifacts. Additionally, this work intends to take full advantage of morphological and textural features in breast tumor US images to improve classification accuracy. METHODS: First, original US images coming directly from the hospital were cropped and resized. In 1385 B-mode US BI-RADS category 4 images, the biopsy eliminated 503 samples of benign tumor and left 882 of malignant. Then, K-means clustering algorithm and entropy of sliding windows of US images were conducted. Considering the diversity of different characteristic information of malignant and benign represented by original B-mode images, K-means clustering images and entropy images, they are fused in a three-channel form multi-feature fusion images dataset. The training, validation, and test sets are 969, 277, and 139. With transfer learning, 11 CNN models including DenseNet and ResNet were investigated. Finally, by comparing accuracy, precision, recall, F1-score, and area under curve (AUC) of the results, models which had better performance were selected. The normality of data was assessed by Shapiro-Wilk test. DeLong test and independent t-test were used to evaluate the significant difference of AUC and other values. False discovery rate was utilized to ultimately evaluate the advantages of CNN with highest evaluation metrics. In addition, the study of anti-log compression was conducted but no improvement has shown in CNNs classification results. RESULTS: With multi-feature fusion images, DenseNet121 has highest accuracy of 80.22 ± 1.45% compared to other CNNs, precision of 77.97 ± 2.89% and AUC of 0.82 ± 0.01. Multi-feature fusion improved accuracy of DenseNet121 by 1.87% from classification of original B-mode images (p < 0.05). CONCLUSION: The CNNs with multi-feature fusion show a good potential of reducing the false-positive rate within category 4. The work illustrated that CNNs and fusion images have the potential to reduce false-positive rate in breast tumor within US BI-RADS category 4, and make the diagnosis of category 4 breast tumors to be more accurate and precise.
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Neoplasias de la Mama , Procesamiento de Imagen Asistido por Computador , Redes Neurales de la Computación , Neoplasias de la Mama/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Femenino , Ultrasonografía/métodos , Ultrasonografía Mamaria/métodosRESUMEN
In the pathogenesis of age-related macular degeneration, long non-coding RNAs have become important regulators. This study aimed to investigate the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the progression of choroidal neovascularization (CNV) and the underlying mechanisms. The in vivo and in vitro model of CNV was established using laser-induced mouse CNV model and human choroidal vascular endothelial cells (HCVECs) exposed to hypoxia respectively. We explore the role of MALAT1 in the pathogenesis of CNV by using the small interference RNA both in vivo and in vitro. MALAT1 expression was found to be upregulated in the retinal pigment epithelial-choroidal complexes. MALAT1 knockdown inhibited CNV development and leakage in vivo and decreased HCVECs proliferation, migration, and tube formation in vitro. MALAT1 performed the task as a miR-17-5p sponge to regulate the expression of vascular endothelial growth factor A (VEGFA) and E26 transformation specific-1 (ETS1). This study provides a new perspective on the pathogenesis of CNV and suggests that the axis MALAT/miR-17-5p/VEGFA or ETS1 may be an effective therapeutic target for CNV.
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In underwater acoustic (UWA) communications, channels often exhibit a clustered-sparse structure, wherein most of the channel impulse responses are near zero, and only a small number of nonzero taps assemble to form clusters. Several algorithms have used the time-domain sparse characteristic of UWA channels to reduce the complexity of channel estimation and improve the accuracy. Employing the clustered structure to enhance channel estimation performance provides another promising research direction. In this work, a deep learning-based channel estimation method for UWA orthogonal frequency division multiplexing (OFDM) systems is proposed that leverages the clustered structure information. First, a cluster detection model based on convolutional neural networks is introduced to detect the cluster of UWA channels. This method outperforms the traditional Page test algorithm with better accuracy and robustness, particularly in low signal-to-noise ratio conditions. Based on the cluster detection model, a cluster-aware distributed compressed sensing channel estimation method is proposed, which reduces the noise-induced errors by exploiting the joint sparsity between adjacent OFDM symbols and limiting the search space of channel delay spread. Numerical simulation and sea trial results are provided to illustrate the superior performance of the proposed approach in comparison with existing sparse UWA channel estimation methods.
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Objective. Three-dimensional (3D) ultrasound (US) is needed to provide sonographers with a more intuitive panoramic view of the complex anatomical structure, especially the musculoskeletal system. In actual scanning, sonographers may perform fast scanning using a one-dimensional (1D) array probe .at random angles to gain rapid feedback, which leads to a large US image interval and missing regions in the reconstructed volume.Approach.In this study, a 3D residual network (3D-ResNet) modified by a 3D global residual branch (3D-GRB) and two 3D local residual branches (3D-LRBs) was proposed to retain detail and reconstruct high-quality 3D US volumes with high efficiency using only sparse two-dimensional (2D) US images. The feasibility and performance of the proposed algorithm were evaluated onex vivoandin vivosets.Main results. High-quality 3D US volumes in the fingers, radial and ulnar bones, and metacarpophalangeal joints were obtained by the 3D-ResNet, respectively. Their axial, coronal, and sagittal slices exhibited rich texture and speckle details. Compared with kernel regression, voxel nearest-neighborhood, squared distance weighted methods, and a 3D convolution neural network in the ablation study, the mean peak-signal-to-noise ratio and mean structure similarity of the 3D-ResNet were up to 28.53 ± 1.29 dB and 0.98 ± 0.01, respectively, and the corresponding mean absolute error dropped to 0.023 ± 0.003 with a better resolution gain of 1.22 ± 0.19 and shorter reconstruction time.Significance.These results illustrate that the proposed algorithm can rapidly reconstruct high-quality 3D US volumes in the musculoskeletal system in cases of a large amount of data loss. This suggests that the proposed algorithm has the potential to provide rapid feedback and precise analysis of stereoscopic details in complex and meticulous musculoskeletal system scanning with a less limited scanning speed and pose variations for the 1D array probe.
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Imagenología Tridimensional , Sistema Musculoesquelético , Imagenología Tridimensional/métodos , Ultrasonografía , Algoritmos , Sistema Musculoesquelético/diagnóstico por imagen , Redes Neurales de la Computación , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
As increasing number of people migrated to high altitude, highland encephalopathy and hypoxia-induced cognitive impairment arouse public attention. Yet, its underlying mechanisms remain unclear. Emerging evidence has implied neuroinflammation and neuronal loss may be involved. In the present study, we investigated the neuroinflammation and neuronal loss in mice after hypoxic insult. Our reports showed hypobaric hypoxia exposure for 3 weeks led to impaired spatial exploration and short-term memory in mice, concomitant with neuron loss. In addition, hypoxia induced neuroinflammation and NLRP3 inflammasome activation. Besides, to explore the role of the inflammasome in hypoxia-induced cognitive dysfunction, NLRP3 knockout mice were applied and the results showed that NLRP3 could negatively regulate GPX4 to modify antioxidant capacity. In summary, our work demonstrated that hypoxia exposure led to neuroinflammation and neuronal-deletion, which may be the key events in the process of hypoxia induced cognitive impairment. NLRP3 inflammasome promoted antioxidant deficiency by negatively regulating GPX4.
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Disfunción Cognitiva , Inflamasomas , Ratones , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Enfermedades Neuroinflamatorias , Antioxidantes , Ratones Noqueados , Disfunción Cognitiva/etiología , HipoxiaRESUMEN
A defining feature of successful vaccination is the ability to induce long-lived antigen-specific memory cells. T follicular helper (Tfh) cells specialize in providing help to B cells in mounting protective humoral immunity in infection and after vaccination. Memory Tfh cells that retain the CXCR5 expression can confer protection through enhancing humoral response upon antigen re-exposure but how they are maintained is poorly understood. CXCR5+ memory Tfh cells in human blood are divided into Tfh1, Tfh2, and Tfh17 cells by the expression of chemokine receptors CXCR3 and CCR6 associated with Th1 and Th17, respectively. Here, we developed a new method to induce Tfh1, Tfh2, and Tfh17-like (iTfh1, iTfh2, and iTfh17) mouse cells in vitro. Although all three iTfh subsets efficiently support antibody responses in recipient mice with immediate immunization, iTfh17 cells are superior to iTfh1 and iTfh2 cells in supporting antibody response to a later immunization after extended resting in vivo to mimic memory maintenance. Notably, the counterpart human Tfh17 cells are selectively enriched in CCR7+ central memory Tfh cells with survival and proliferative advantages. Furthermore, the analysis of multiple human cohorts that received different vaccines for HBV, influenza virus, tetanus toxin or measles revealed that vaccine-specific Tfh17 cells outcompete Tfh1 or Tfh2 cells for the persistence in memory phase. Therefore, the complementary mouse and human results showing the advantage of Tfh17 cells in maintenance and memory function supports the notion that Tfh17-induced immunization might be preferable in vaccine development to confer long-term protection.
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Memoria Inmunológica , Células T Auxiliares Foliculares , Humanos , Animales , Ratones , Células Th17/metabolismo , Linfocitos B , Linfocitos T Colaboradores-InductoresRESUMEN
High-frame-rate plane wave (PW) imaging suffers from unsatisfactory image quality due to the absence of focus in transmission. Although coherent compounding from tens of PWs can improve PW image quality, it in turn results in a decreased frame rate, which is limited for tracking fast moving tissues. To overcome the trade-off between frame rate and image quality, we propose a progressively dual reconstruction network (PDRN) to achieve adaptive beamforming and enhance the image quality via both supervised and transfer learning in the condition of single or a few PWs transmission. Specifically, the proposed model contains a progressive network and a dual network to form a close loop and provide collaborative supervision for model optimization. The progressive network takes the channel delay of each spatial point as input and progressively learns coherent compounding beamformed data with increased numbers of steered PWs step by step. The dual network learns the downsampling process and reconstructs the beamformed data with decreased numbers of steered PWs, which reduces the space of the possible learning functions and improves the model's discriminative ability. In addition, the dual network is leveraged to perform transfer learning for the training data without sufficient steered PWs. The simulated, in vivo, vocal cords (VCs), and public available CUBDL dataset are collected for model evaluation.
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Procesamiento de Imagen Asistido por Computador , Procesamiento de Imagen Asistido por Computador/métodos , Fantasmas de Imagen , Ultrasonografía/métodosRESUMEN
Numerous studies have examined the effects of lead (Pb) on cognitive ability. It is essential for the brain to maintain its functions through the differentiation of neural stem cells into various types of cells. Despite this, it remains unclear how Pb exposure affects neural stem cells and how it does, so the Pb-exposed mice were treated with the Notch inhibitor DAPT after we established the Pb exposure models. Neuronal stem cells and autophagy were assessed by immunofluorescence staining and western blot. The microbiota of the feces was also analyzed using the 16S rRNA amplicon sequencing technique. In this study, we found that Pb exposure caused neural injuries and deficits in neural stem cells, whereas DAPT rescued the damage. With DAPT, Pb-induced autophagy was partially reversed. Exposure to Pb also reduced inflammation and damaged gut barrier function. Furthermore, Pb exposure led to low bacterial diversity, an increase in pathogen abundance, and an unusual mode of interaction. Taken together, this study revealed that damages in neural stem cells contributed largely to cognitive impairment during Pb exposure, and this process was partially dependent on the Notch pathway and gut dysbiosis.
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Plomo , Células-Madre Neurales , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Animales , Eje Cerebro-Intestino , Plomo/toxicidad , Ratones , Células-Madre Neurales/metabolismo , Inhibidores de Agregación Plaquetaria/farmacología , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Transducción de SeñalRESUMEN
Lead exposure may weaken the ability of learning and memory in the nervous system through mitochondrial paramorphia and dysfunction. However, the underlying mechanism has not been fully elucidated. In our works, with SD rats, primary culture of hippocampal neuron and PC12 cell line model were built up and behavioral tests were performed to determine the learning and memory insults; Western blot, immunological staining, and electron microscope were then conducted to determine endoplasmic reticulum stress and mitochondrial paramorphia and dysfunction. Co-immunoprecipitation were performed to investigate potential protein-protein interaction. The results show that lead exposure may cripple rats' learning and memory capability by inducing endoplasmic reticulum stress and mitochondrial paramorphia and dysfunction. Furthermore, we clarify that enhanced MFN2 ubiquitination degradation mediated by PINK1 may account for mitochondrial paramorphia and endoplasmic reticulum stress. Our work may provide important clues for research on the mechanism of how Pb exposure leads to nervous system damage.
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Plomo , Síndromes de Neurotoxicidad , Animales , Apoptosis , Estrés del Retículo Endoplásmico , Plomo/metabolismo , Plomo/toxicidad , Mitocondrias/metabolismo , Síndromes de Neurotoxicidad/metabolismo , Proteínas Quinasas/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Objective myocardial contractility assessment during stress tests aims to improve the diagnosis of myocardial ischemia. Tissue Doppler imaging (TDI) or optical flow (OF) speckle tracking echocardiography (STE) has been used to quantify myocardial contractility at rest. However, this is more challenging during stress tests due to image decorrelation at high heart rates. Moreover, stress tests imply a high frame rate which leads to a limited lateral field of view. Therefore, a large lateral field-of-view robust ultrafast myocardial regularized OF-TDI principal strain estimator has been developed for high-frame-rate echocardiography of coherently compounded transmitted diverging waves. The feasibility and accuracy of the proposed estimator were validated in vitro (using sonomicrometry as the gold standard) and in vivo stress experiments. Compared with OF strain imaging, the proposed estimator improved the accuracy of principal major and minor strains during stress tests, with an average contrast-to-noise ratio improvement of 4.4 ± 2.7 dB ( p -value < 0.01). Moreover, there was a significant correlation and a very close agreement between the proposed estimator and sonomicrometry for tested heart rates between 60 and 180 beats per minute (bpm). The averages ± standard deviations (STD) of R2 and biases ± STD between them were 0.96 ± 0.04 ( p -value < 0.01) and 0.01 ± 0.03% in the axial direction, respectively; and 0.94 ± 0.02 ( p -value < 0.01) and 0.04 ± 0.06% in the lateral direction, respectively. These results suggest that the proposed estimator could be useful clinically to provide an accurate and quantitative 2-D large lateral field-of-view myocardial strain assessment at high heart rates during stress echocardiography.
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Diagnóstico por Imagen de Elasticidad , Humanos , Ecocardiografía/métodos , Ecocardiografía de Estrés/métodos , Diagnóstico por Imagen de Elasticidad/métodos , Estudios de FactibilidadRESUMEN
AIM: To investigate the synergetic regulatory effect of miR-22 on HIF-1α and NLRP3, subsequently regulating the production of the NLRP3/CASP1 inflammasome pathway-mediated proinflammatory cytokines IL-1ß and IL-18 in human dental pulp fibroblasts (HDPFs) during the progression of pulpitis. METHODOLOGY: Fluorescence in situ hybridization (FISH) and immunofluorescence (IF) were performed to determine the localization of miR-22-3p, NLRP3 and HIF-1α in human dental pulp tissues (HDPTs). The miR-22 mimics and inhibitor or plasmid of NLRP3 or HIF-1α were used to upregulate or downregulate miR-22 or NLRP3 or HIF-1α in HDPFs, respectively. Computational prediction via TargetScan 5.1 and a luciferase reporter assay were conducted to confirm target association. The mRNA and protein expression of HIF-1α, NLRP3, caspase-1, IL-1ß and IL-18 were determined by qRT-PCR and western blotting, respectively. The release of IL-1ß and IL-18 was analysed by ELISA. The significance of the differences between the experimental and control groups was determined by one-way analysis of variance, p < .05 indicated statistical significance. RESULTS: A decrease in miR-22 and an increase in HIF-1α and NLRP3 in HDPTs occurred during the transformation of reversible pulpitis into irreversible pulpitis compared with that in the healthy pulp tissues (p < .05). In the normal HDPTs, miR-22-3p was extensively expressed in dental pulp cells. HIF-1α and NLRP3 were mainly expressed in the odontoblasts and vascular endothelial cells. Whereas in the inflamed HDPTs, the odontoblast layers were disrupted. HDPFs were positive for miR-22-3p, HIF-1α and NLRP3. Computational prediction via TargetScan 5.1 and luciferase reporter assays confirmed that both NLRP3 and HIF-1α were direct targets of miR-22 in HDPFs. The miR-22 inhibitor further promoted the activation of NLRP3/CASP1 inflammasome pathway induced by ATP plus LPS and hypoxia (p < .05). In contrast, the miR-22 mimic significantly inhibited the NLRP3/CASP1 inflammasome pathway activation induced by ATP plus LPS and hypoxia (p < .05). CONCLUSION: MiR-22, as a synergetic negative regulator, is involved in controlling the secretion of proinflammatory cytokines mediated by the NLRP3/CASP1 inflammasome pathway by targeting NLRP3 and HIF-1α. These results provide a novel function and mechanism of miR-22-HIF-1α-NLRP3 signalling in the control of proinflammatory cytokine secretion, thus indicating a potential therapeutic strategy for future endodontic treatment.
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MicroARNs , Pulpitis , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/farmacología , Caspasa 1/metabolismo , Citocinas/metabolismo , Pulpa Dental , Células Endoteliales/metabolismo , Fibroblastos , Humanos , Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Hibridación Fluorescente in Situ , Inflamasomas/metabolismo , Interleucina-18/genética , Interleucina-18/metabolismo , Interleucina-18/farmacología , Lipopolisacáridos/farmacología , MicroARNs/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Pulpitis/metabolismo , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Early-life Pb exposure can cause behavioral and cognitive problems and induce symptoms of hyperactivity, impulsivity, and inattention in children. Studies showed that blood lead levels were highly correlated with neuropsychiatric disorders, and effects of neurotoxicity might persist and affect the incidence of neurodegenerative diseases, for example Alzheimer's disease (AD). OBJECTIVE: To explore possible mechanisms of developmental Pb-induced neuropsychiatric dysfunctions. METHODS: Children were divided into low blood lead level (BLL) group (0-50.00µg/L) and high BLL group (>â50.00µg/L) and blood samples were collected. miRNA array was used to testify miRNA expression landscape between two groups. Correlation analysis and real-time PCR were applied to find miRNAs that altered in Pb and neuropsychiatric diseases. Animal models and cell experiments were used to confirm the effect of miRNAs in response to Pb, and siRNA and luciferase experiments were conducted to examine their effect on neural functions. RESULTS: miRNA array data and correlation analysis showed that miR-34b was the most relevant miRNA among Pb neurotoxicity and neuropsychiatric disorders, and synapse-associated membrane protein 2 (VAMP2) was the target gene regulating synapse function. In vivo and in vitro studies showed Pb exposure injured rats' cognitive abilities and induced upregulation of miR-34b and downregulation of VAMP2, resulting in decreases of hippocampal synaptic vesicles. Blockage of miR-34b mitigated Pb's effects on VAMP2 in vitro. CONCLUSION: Early-life Pb exposure might exert synapse-toxic effects via inhibiting VAMP2 mediated by upregulation of miR-34b and shed a light on the underlying relationship between Pb neurotoxicity and developmental neuropsychiatric disorders.
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Plomo , MicroARNs , Animales , Humanos , Plomo/metabolismo , Plomo/toxicidad , MicroARNs/metabolismo , Ratas , Sinapsis/metabolismo , Regulación hacia Arriba , Proteína 2 de Membrana Asociada a Vesículas/genética , Proteína 2 de Membrana Asociada a Vesículas/metabolismoRESUMEN
PURPOSE: Owing to acoustic-pressure dependence, amplitudes of backscattered-echoes of encapsulated microbubbles (MBs) are unavoidably regulated by an uneven acoustic field, resulting in the misestimation of hemodynamics in conventional amplitude-coding dynamic contrast-enhanced ultrasound (DCEUS) with focused pulse transmission. This study aimed to investigate the feasibility and performance of Nakagami statistical-feature parametric imaging to recover the above misestimation. METHODS: Logarithmic Nakagami parameter (m)-coding DCEUS scheme was investigated via simulation and in vitro MB phantoms as well as in vivo kidney-perfusion experiments of four rabbits in the uneven acoustic fields with two different focal depths. In vivo tissue artifacts for m estimation were suppressed by pulse-inversion second-harmonic imaging and its robustness was enhanced by multiscale moment-estimation strategy. Time-Nakagami-m curves and the corresponding perfusion metrics of intensity and volume were calculated from the logarithmic m-coding DCEUS images within the prefocal and focal regions. These curves and metrics were further compared with the perfusion curves and metrics estimated from the conventional amplitude-coding images within the same regions. RESULTS: Compared with amplitudes of nonlinear scattering MB echoes, their logarithmic m values were relatively independent of the changes in acoustics pressures. Compared with the fixed-scale moment-estimation, the perfusion intensity estimated from logarithmic m-coding DCEUS scheme using multiscale statistical moment-estimation had smaller differences between the prefocal and focal regions. The differences of perfusion intensity induced by an uneven acoustic field decreased to 3.47% ± 1.58 %. The differences decreased by the logarithmic m-coding DCEUS scheme were further regulated by threshold values of m estimation. CONCLUSIONS: The logarithmic m-coding DCEUS scheme could recover the underestimated MB backscattered-echoes and the misestimated perfusion intensity induced by the uneven acoustic field. The scheme had the potential to weaken the limitation of microvasculature identification and hemodynamic characterization marked by MBs within tissues or tumors in the uneven acoustic field.
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Acústica , Benchmarking , Animales , Estudios de Factibilidad , Perfusión , Conejos , Ultrasonografía/métodosRESUMEN
BACKGROUND: Noninvasive vascular strain imaging under conventional line-by-line scanning has a low frame rate and lateral resolution and depends on the coordinate system. It is thus affected by high deformations due to image decorrelation between frames. PURPOSE: To develop an ultrafast time-ensemble regularized tissue-Doppler optical-flow principal strain estimator for aorta deformability assessment in a long-axis view. METHODS: This approach alleviated the impact of lateral resolution using image compounding and that of the coordinate system dependency using principal strain. Accuracy and feasibility were evaluated in two aorta-mimicking phantoms first, and then in four age-matched individuals with either a normal aorta or a pathological ascending thoracic aorta aneurysm (TAA). RESULTS: Instantaneous aortic maximum and minimum principal strain maps and regional accumulated strains during each cardiac cycle were estimated at systolic and diastolic phases to characterize the normal aorta and TAA. In vitro, principal strain results matched sonomicrometry measurements. In vivo, a significant decrease in maximum and minimum principal strains was observed in TAA cases, whose range was respectively 7.9 ± 6.4% and 8.2 ± 2.6% smaller than in normal aortas. CONCLUSIONS: The proposed principal strain estimator showed an ability to potentially assess TAA deformability, which may provide an individualized and reliable evaluation method for TAA rupture risk assessment.
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Aorta Torácica , Aneurisma de la Aorta Torácica , Aorta/diagnóstico por imagen , Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Estudios de Factibilidad , Humanos , UltrasonografíaRESUMEN
BACKGROUND: Immune checkpoint inhibitors (ICIs) -induced adverse events (AEs) have been reported affecting almost all human organs. However, studies about ocular AEs are few. A meta-analysis was performed to evaluate the risks of ICI-related ophthalmic AEs compare to chemotherapy.Methods: Eligible studies were selected from phase II/III randomized controlled trials investigating ICIs. The data were analyzed by R software and Stata. RESULTS: Odds ratio of treatment-related AE (trAEs) and nonspecific ophthalmic trAEs (NS-trAEs) were lower for PD-1/PD-L1 inhibitors than chemotherapy (OR 0.44, p < .05; OR 0.28, p < .001; OR 0.18, p < . 05; OR: 0.18, p < .001respectively). Compared with monotherapy, PD-1 plus CTLA-4 inhibitors increased the risks of immune-related AEs (irAEs) (OR 4.52, p < .01); ICIs plus chemotherapy increased the risks of trAEs and irAEs (OR 2.82, p < .001; OR 3.63, p < .05 respectively). CONCLUSIONS: PD-L1/PD-1 inhibitors had lower risks of trAEs and NS-trAEs than chemotherapy; Compared with monotherapy, combination therapy had higher risks of ophthalmic trAEs and irAEs. ABBREVIATION: PD-1: programmed cell death protein 1; PD-L1: programmed cell death protein ligand 1; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; ICI: immune checkpoint inhibitor; AE: adverse event; trAE: treatment-related adverse event;irAE: immune-related adverse events; NS-trAE: nonspecific ophthalmic treatment-related adverse event; RCT: randomized controlled trials; PFS: progression-free survival; OS: overall survival; ORR: objective response rate; MM: melanoma; NSCLC: non-small cell lung cancer; SCLC: small cell lung cancer; HNSCC: head-neck squamous cell carcinoma; PICOL: patient, intervention, comparison, and outcome; Versus: VS; Chem: chemotherapy; 95%CI: 95% confidence interval; FEM: fixed-effects model; REM: random-effects model; NA: not applicable; MeSH: medical subject heading.
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Antineoplásicos Inmunológicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Receptor de Muerte Celular Programada 1 , Antígeno B7-H1/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Antineoplásicos Inmunológicos/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológicoRESUMEN
BACKGROUND: Neuroinflammation induced by lead exposure (Pb) is a major cause of neurotoxicity of Pb in the central nervous system (CNS). The NLR family, domain of pyrin containing 3 (NLRP3) involves in various neurological diseases, while the question of whether NLRP3 plays a role in lead-induced neuroinflammation has not yet been reported. METHODS: Developmental and knockout (KO) NLRP3 mice were used to establish two in vivo models, and BV2 cells were used to establish an in vitro model. Behavioral and electrophysiologic tests were used to assess the neurotoxicity of Pb, and immunofluorescence staining was used to assess neuroinflammation. Real-time PCR and western blot were performed to examine the mRNA and protein levels of inflammatory cytokines and NLRP3 inflammasomes. siRNA technology was used to block NLRP3 expression. RESULTS: Pb exposure led to neural injure and microglial activation in the hippocampus region, while minocycline intervention attenuated Pb-induced neurotoxicity by inhibiting neuroinflammation. Pb increased the expression of NLRP3 and promoted cleavage of caspase-1 in mRNA and protein levels, and minocycline partially reversed the effects of Pb on NLRP3 inflammasomes. Blocking of NLRP3 by KO mice or siRNA attenuated neural alterations induced by Pb, weakened microglial activation in vivo and in vitro as well, without affecting the accumulation of Pb. Pb increased autophagic protein levels and phosphorylation of NF-κB, while suppressing autophagy or NF-κB inhibited Pb's effects on NLRP3. CONCLUSIONS: NLRP3 is involved in the regulation of Pb-induced neurotoxicity. These findings expand mechanism research of Pb neurotoxicity and may help establish new prevention strategies for Pb neurotoxicity.
Asunto(s)
Microglía , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Citocinas , Inflamasomas , Ratones , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR/genéticaRESUMEN
OBJECTIVE: Changes in ultrasound backscatter energy (CBE) imaging can monitor thermal therapy. Catheter-based ultrasound (CBUS) can treat deep tumors with precise spatial control of energy deposition and ablation zones, of which CBE estimation can be limited by low contrast and robustness due to small or inconsistent changes in ultrasound data. This study develops a multi-spatiotemporal compounding CBE (MST-CBE) imaging approach for monitoring specific to CBUS thermal therapy. METHODS: Ex vivo thermal ablations were performed with stereotactic positioning of a 180° directional CBUS applicator, temperature monitoring probes, endorectal US probe, and subsequent lesion sectioning and measurement. Five frames of raw radiofrequency data were acquired throughout in 15s intervals. Using window-by-window estimation methods, absolute and positive components of MST-CBE images at each point were obtained by the compounding ratio of squared envelope data within an increasing spatial size in each short-time window. RESULTS: Compared with conventional US, Nakagami, and CBE imaging, the detection contrast and robustness quantified by tissue-modification-ratio improved by 37.2 ± 4.7 (p < 0.001), 37.5 ± 5.2 (p < 0.001), and 6.4 ± 4.0 dB (p < 0.05) in the MST-CBE imaging, respectively. Correlation coefficient and bias between cross-sectional dimensions of the ablation zones measured in tissue sections and estimated from MST-CBE were up to 0.91 (p < 0.001) and -0.02 mm2, respectively. CONCLUSION: The MST-CBE approach can monitor the detailed changes within target tissues and effectively characterize the dimensions of the ablation zone during CBUS energy deposition. SIGNIFICANCE: The MST-CBE approach could be practical for improved accuracy and contrast of monitoring and evaluation for CBUS thermal therapy.