Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 179
Filtrar
1.
Cell Rep Med ; 5(9): 101716, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39241773

RESUMO

Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer that presents significant challenges for early detection. This study introduces the GlyExo-Capture method for isolating fucosylated extracellular vesicles (Fu-EVs) from serum. We analyze microRNA (miRNA) profiles from Fu-EVs in 88 HCC patients and 179 non-HCC controls using next-generation sequencing (NGS) and identify five miRNAs (hsa-let-7a, hsa-miR-21, hsa-miR-125a, hsa-miR-200a, and hsa-miR-150) as biomarkers for HCC diagnosis. The five-miRNA panel demonstrates exceptional HCC diagnostic performance, with a sensitivity of 0.90 and specificity of 0.92 in a combined cohort of 194 HCC and 412 non-HCC controls, significantly surpassing the performance of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP). Notably, the miRNA model achieves recall rates of 85.7% and 90.8% for stage 0 and stage A early-stage HCC, respectively, identifies 88.1% of AFP-negative HCC cases, and effectively differentiates HCC from other cancers. This study provides a high-throughput, rapid, and non-invasive approach for early HCC detection.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular , Vesículas Extracelulares , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , MicroRNAs/genética , MicroRNAs/sangue , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Fucose/metabolismo , Idoso , Sequenciamento de Nucleotídeos em Larga Escala/métodos , alfa-Fetoproteínas/metabolismo , alfa-Fetoproteínas/genética
2.
Materials (Basel) ; 17(17)2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39274812

RESUMO

(111)-oriented nanotwinned Cu ((111)nt-Cu) has shown its high surface diffusion rate and better oxidation resistance over common polycrystalline Cu (C-Cu). The application of (111)nt-Cu as an interface metallization layer in Ag-sintered technology under the role of oxygen was investigated in this work, and its connecting behavior was further clarified by comparing it with C-Cu. As the sintering temperature decreasing from 300 to 200 °C, the shear strength on the (111)nt-Cu substrate was still greater than 55 MPa after sintering for 10 min. The fracture surface correspondingly changed from the interface of Ag/die to mixed fracture mode, involving the interface of the Ag/Cu substrate and Ag/die. The existence of copper oxide provided a tight connection between Ag and the (111)nt-Cu substrate at all of the studied temperatures. Although lots of small dispersed voids were seen at the interface between copper oxide and (111)nt-Cu at 300 °C, these impurity-induced voids would not necessarily be a failure position and could be improved by adjusting the sintering temperature and time; for example, 200 °C/10 min or heating to 300 °C, and then start cooling at the same time. The microstructure of Ag-Cu joint on (111)nt-Cu behaved better than that on C-Cu. The thinner copper oxide layer and the higher connection ratio of the interface between copper oxide and Ag were still found on the (111)nt-Cu connection's structure. The poor connection between copper oxide and Ag on C-Cu easily became the failure interface. By controlling the thickness of copper oxide and the content of impurity-induced voids, the use of (111)nt-Cu in advanced-packaging could be improved to a new level.

3.
Signal Transduct Target Ther ; 9(1): 242, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39271680

RESUMO

Over the past two decades, mesenchymal stem/stromal cell (MSC) therapy has made substantial strides, transitioning from experimental clinical applications to commercial products. MSC therapies hold considerable promise for treating refractory and critical conditions such as acute graft-versus-host disease, amyotrophic lateral sclerosis, and acute respiratory distress syndrome. Despite recent successes in clinical and commercial applications, MSC therapy still faces challenges when used as a commercial product. Current detection methods have limitations, leaving the dynamic biodistribution, persistence in injured tissues, and ultimate fate of MSCs in patients unclear. Clarifying the relationship between the pharmacokinetic characteristics of MSCs and their therapeutic effects is crucial for patient stratification and the formulation of precise therapeutic regimens. Moreover, the development of advanced imaging and tracking technologies is essential to address these clinical challenges. This review provides a comprehensive analysis of the kinetic properties, key regulatory molecules, different fates, and detection methods relevant to MSCs and discusses concerns in evaluating MSC druggability from the perspective of integrating pharmacokinetics and efficacy. A better understanding of these challenges could improve MSC clinical efficacy and speed up the introduction of MSC therapy products to the market.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Doença Enxerto-Hospedeiro/terapia , Pesquisa Translacional Biomédica , Esclerose Lateral Amiotrófica/terapia
4.
Nature ; 632(8025): 686-694, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39112701

RESUMO

The dopamine transporter has a crucial role in regulation of dopaminergic neurotransmission by uptake of dopamine into neurons and contributes to the abuse potential of psychomotor stimulants1-3. Despite decades of study, the structure, substrate binding, conformational transitions and drug-binding poses of human dopamine transporter remain unknown. Here we report structures of the human dopamine transporter in its apo state, and in complex with the substrate dopamine, the attention deficit hyperactivity disorder drug methylphenidate, and the dopamine-uptake inhibitors GBR12909 and benztropine. The dopamine-bound structure in the occluded state precisely illustrates the binding position of dopamine and associated ions. The structures bound to drugs are captured in outward-facing or inward-facing states, illuminating distinct binding modes and conformational transitions during substrate transport. Unlike the outward-facing state, which is stabilized by cocaine, GBR12909 and benztropine stabilize the dopamine transporter in the inward-facing state, revealing previously unseen drug-binding poses and providing insights into how they counteract the effects of cocaine. This study establishes a framework for understanding the functioning of the human dopamine transporter and developing therapeutic interventions for dopamine transporter-related disorders and cocaine addiction.


Assuntos
Benzotropina , Proteínas da Membrana Plasmática de Transporte de Dopamina , Inibidores da Captação de Dopamina , Dopamina , Humanos , Apoproteínas/metabolismo , Apoproteínas/química , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Benzotropina/metabolismo , Benzotropina/farmacologia , Sítios de Ligação , Cocaína/farmacologia , Cocaína/metabolismo , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/antagonistas & inibidores , Proteínas da Membrana Plasmática de Transporte de Dopamina/química , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Inibidores da Captação de Dopamina/metabolismo , Inibidores da Captação de Dopamina/farmacologia , Metilfenidato/metabolismo , Metilfenidato/farmacologia , Modelos Moleculares , Piperazinas/metabolismo , Piperazinas/farmacologia , Ligação Proteica , Conformação Proteica
5.
Front Bioeng Biotechnol ; 12: 1399689, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39045537

RESUMO

Extracellular vesicles (EVs) are pivotal in intercellular communication, disease mechanisms. Despite numerous methods for EVs isolation, challenges persist in yield, purity, reproducibility, cost, time, and automation. We introduce a EVs isolation technique using Fe3O4@ZrO2 beads, leveraging ZrO2-phosphate interaction. The results indicated that EVs were efficiently separated from large volumes of samples in 30 minutes without preconcentration. Our method demonstrated capture efficiency (74%-78%) compared to ultracentrifugation, purity (97%), and reproducibility (0.3%-0.5%), with excellent linearity (R2 > 0.99). EVs from urine samples showed altered expression of miRNAs. The logistic regression model achieved an AUC of 0.961, sensitivity of 0.92, and specificity of 0.94. With potential for automation, this magnetic bead-based method holds promise for clinical applications, offering an efficient and reliable tool for EVs research and clinical studies.

6.
Sensors (Basel) ; 24(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732958

RESUMO

Ensuring source location privacy is crucial for the security of underwater acoustic sensor networks amid the growing use of marine environmental monitoring. However, the traditional source location privacy scheme overlooks multi-attacker cooperation strategies and also has the problem of high communication overhead. This paper addresses the aforementioned limitations by proposing an underwater source location privacy protection scheme based on game theory under the scenario of multiple cooperating attackers (SLP-MACGT). First, a transformation method of a virtual coordinate system is proposed to conceal the real position of nodes to a certain extent. Second, through using the relay node selection strategy, the diversity of transmission paths is increased, passive attacks by adversaries are resisted, and the privacy of source nodes is protected. Additionally, a secure data transmission technique utilizing fountain codes is employed to resist active attacks by adversaries, ensuring data integrity and enhancing data transmission stability. Finally, Nash equilibrium could be achieved after the multi-round evolutionary game theory of source node and multiple attackers adopting their respective strategies. Simulation experiments and performance evaluation verify the effectiveness and reliability of SLP-MACGT regarding aspects of the packet forwarding success rate, security time, delay and energy consumption: the packet delivery rate average increases by 30%, security time is extended by at least 85%, and the delay is reduced by at least 90% compared with SSLP, PP-LSPP, and MRGSLP.

8.
World J Clin Cases ; 12(14): 2350-2358, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38765753

RESUMO

BACKGROUND: This study presents an evaluation of the computed tomography lymphangiography (CTL) features of lymphatic plastic bronchitis (PB) and primary chylothorax to improve the diagnostic accuracy for these two diseases. AIM: To improve the diagnosis of lymphatic PB or primary chylothorax, a retrospective analysis of the clinical features and CTL characteristics of 71 patients diagnosed with lymphatic PB or primary chylothorax was performed. METHODS: The clinical and CTL data of 71 patients (20 with lymphatic PB, 41 with primary chylothorax, and 10 with lymphatic PB with primary chylothorax) were collected retrospectively. CTL was performed in all patients. The clinical manifestations, CTL findings, and conventional chest CT findings of the three groups of patients were compared. The chi-square test or Fisher's exact test was used to compare the differences among the three groups. A difference was considered to be statistically significant when P < 0.05. RESULTS: (1) The percentages of abnormal contrast medium deposits on CTL in the three groups were as follows: Thoracic duct outlet in 14 (70.0%), 33 (80.5%) and 8 (80.0%) patients; peritracheal region in 18 (90.0%), 15 (36.6%) and 8 (80.0%) patients; pleura in 6 (30.0%), 33 (80.5%) and 9 (90.0%) patients; pericardium in 6 (30.0%), 6 (14.6%) and 4 (40.0%) patients; and hilum in 16 (80.0%), 11 (26.8%) and 7 (70.0%) patients; and (2) the abnormalities on conventional chest CT in the three groups were as follows: Ground-glass opacity in 19 (95.0%), 18 (43.9%) and 8 (80.0%) patients; atelectasis in 4 (20.0%), 26 (63.4%) and 7 (70.0%) patients; interlobular septal thickening in 12 (60.0%), 11 (26.8%) and 3 (30.0%) patients; bronchovascular bundle thickening in 14 (70.0%), 6 (14.6%) and 4 (40.0%) patients; localized mediastinal changes in 14 (70.0%), 14 (34.1%), and 7 (70.0%) patients; diffuse mediastinal changes in 6 (30.0%), 5 (12.2%), and 3 (30.0%) patients; cystic lesions in the axilla in 2 (10.0%), 6 (14.6%), and 2 (20.0%) patients; and cystic lesions in the chest wall in 0 (0%), 2 (4.9%), and 2 (4.9%) patients. CONCLUSION: CTL is well suited to clarify the characteristics of lymphatic PB and primary chylothorax. This method is an excellent tool for diagnosing these two diseases.

9.
Cancer Manag Res ; 16: 395-402, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707744

RESUMO

Background: Lymphoepithelioma-like carcinoma of the liver is a rare primary malignancy of the liver. The identification of lymphoepithelioma-like cholangiocarcinoma is very limited as there are currently very few reports of such cases. Although previous studies have reported the lymphoepithelioma-like cholangiocarcinoma pathologic features, few studies have revealed the clinic features, imaging characteristics, and clinical course and outcomes. This study was analyzed from multiple aspects such as contrast-enhanced ultrasound, magnetic resonance imaging, and pathological characteristics, aiming to improve the comprehensive understanding of this rare subtype of disease. Case Presentation: A 43-year-old female with a history of hepatitis B for over 20 years presented with a lesion found in the right lobe of her liver. After discussion by a multidisciplinary team (MDT), malignant tumors cannot be excluded based on contrast-enhanced ultrasound and MRI. Thus, we decided to perform surgery for the patient. Postoperative pathology confirmed lymphoepithelioma-like intrahepatic cholangiocarcinoma. After 3 months of follow-up, the patient was still alive and no recurrence was observed. Conclusion: The purpose of this article is to describe a rare case of lymphoepithelioma-like intrahepatic cholangiocarcinoma and analyze its contrast-enhanced ultrasound and contrast-enhanced MRI features, which will be helpful for physicians in diagnosing this disease. From the perspective of CEUS, the wedge-shaped highly enhanced area around the lesion in the arterial phase appears to be inflammatory but looks malignant based on the extremely fast washout. The lesion showed a low signal on T1WI, a high signal on T2WI and DWI, and an abnormal perfusion shadow can be seen behind the lesion. In particular, this subtype of cholangiocarcinoma has a good prognosis, the clinician should improve the recognition of the disease to strive for early diagnosis and therapy.

10.
J Vasc Surg Venous Lymphat Disord ; 12(5): 101890, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38636733

RESUMO

PURPOSE: The dermal rim sign (DRS) on nonenhanced magnetic resonance imaging has been shown to predict dermal backflow (DBF) in patients with secondary upper limb lymphedema. However, whether the DRS has the same effects on primary lower extremity lymphedema (PLEL) has not been clearly reported. Therefore, this study aimed to explore whether the DRS can be used to diagnose DBF on lymphoscintigraphy in patients with PLEL. METHODS: A total of 94 patients who were diagnosed with PLEL were recruited for this retrospective study from January 2022 to December 2023. All the patients were divided into two groups according to the lymphoscintigraphy findings: no DBF and DBF. The magnetic resonance imaging data of the two groups were recorded and statistically compared for the following indicators: range of lymphedema involvement (left, right, whole lower limbs, only thigh, only calf and ankle), signs of lymphedema (notable thickening of skin, parallel line sign, grid sign, honeycomb sign, band sign, lymph lake sign, crescent sign, DRS), and lymphedema measurement (skin thickness, band width). The DRS is characterized by notable thickening of the skin plus the grid sign and/or honeycomb sign, plus the band sign. RESULTS: The following statistically significant differences in the following indicators were found between the two groups (P < .05): notable skin thickening, parallel line sign, grid sign, honeycomb sign, band sign, DRS, skin thickness, and band width. The sensitivity, specificity, and accuracy for predicting for DBF with the DRS was 82%, 64%, and 77%, respectively. CONCLUSIONS: This study confirmed good consistency between the DRS and DBF from the perspective of imaging. This tool is suitable for children, adolescents, and patients with contraindications to lymphoscintigraphy. The DRS has important value in assessing the severity of PLEL. The DRS is suggested for the clinical use of combined surgical treatment of PLEL.


Assuntos
Extremidade Inferior , Linfedema , Linfocintigrafia , Imageamento por Ressonância Magnética , Valor Preditivo dos Testes , Humanos , Linfedema/diagnóstico por imagem , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Extremidade Inferior/irrigação sanguínea , Adulto , Idoso , Reprodutibilidade dos Testes , Adulto Jovem , Pele/diagnóstico por imagem , Pele/irrigação sanguínea , Adolescente
11.
Anal Chem ; 96(16): 6158-6169, 2024 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-38602477

RESUMO

Raman spectroscopy has been widely used for label-free biomolecular analysis of cells and tissues for pathological diagnosis in vitro and in vivo. AI technology facilitates disease diagnosis based on Raman spectroscopy, including machine learning (PCA and SVM), manifold learning (UMAP), and deep learning (ResNet and AlexNet). However, it is not clear how to optimize the appropriate AI classification model for different types of Raman spectral data. Here, we selected five representative Raman spectral data sets, including endometrial carcinoma, hepatoma extracellular vesicles, bacteria, melanoma cell, diabetic skin, with different characteristics regarding sample size, spectral data size, Raman shift range, tissue sites, Kullback-Leibler (KL) divergence, and significant Raman shifts (i.e., wavenumbers with significant differences between groups), to explore the performance of different AI models (e.g., PCA-SVM, SVM, UMAP-SVM, ResNet or AlexNet). For data set of large spectral data size, Resnet performed better than PCA-SVM and UMAP. By building data characteristic-assisted AI classification model, we optimized the network parameters (e.g., principal components, activation function, and loss function) of AI model based on data size and KL divergence etc. The accuracy improved from 85.1 to 94.6% for endometrial carcinoma grading, from 77.1 to 90.7% for hepatoma extracellular vesicles detection, from 89.3 to 99.7% for melanoma cell detection, from 88.1 to 97.9% for bacterial identification, from 53.7 to 85.5% for diabetic skin screening, and mean time expense of 5 s.


Assuntos
Análise Espectral Raman , Análise Espectral Raman/métodos , Humanos , Feminino , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/química , Aprendizado de Máquina , Melanoma/patologia , Melanoma/diagnóstico , Melanoma/classificação , Vesículas Extracelulares/química , Máquina de Vetores de Suporte , Bactérias/classificação , Bactérias/isolamento & purificação , Inteligência Artificial
13.
Stem Cell Rev Rep ; 20(4): 1093-1105, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38457059

RESUMO

Breast cancer, the most prevalent malignancy in women, often progresses to bone metastases, especially in older individuals. Dormancy, a critical aspect of bone-metastasized breast cancer cells (BCCs), enables them to evade treatment and recur. This dormant state is regulated by bone marrow mesenchymal stem cells (BMMSCs) through the secretion of various factors, including those associated with senescence. However, the specific mechanisms by which BMMSCs induce dormancy in BCCs remain unclear. To address this gap, a bone-specific senescence-accelerated murine model, SAMP6, was utilized to minimize confounding systemic age-related factors. Confirming senescence-accelerated osteoporosis, distinct BMMSC phenotypes were observed in SAMP6 mice compared to SAMR1 counterparts. Notably, SAMP6-BMMSCs exhibited premature senescence primarily due to telomerase activity loss and activation of the p21 signaling pathway. Furthermore, the effects of conditioned medium (CM) derived from SAMP6-BMMSCs versus SAMR1-BMMSCs on BCC proliferation were examined. Intriguingly, only CM from SAMP6-BMMSCs inhibited BCC proliferation by upregulating p21 expression in both MCF-7 and MDA-MB-231 cells. These findings suggest that the senescence-associated secretory phenotype (SASP) of BMMSCs suppresses BCC viability by inducing p21, a pivotal cell cycle inhibitor and tumor suppressor. This highlights a heightened susceptibility of BCCs to dormancy in a senescent microenvironment, potentially contributing to the increased incidence of breast cancer bone metastasis and recurrence observed with aging.


Assuntos
Neoplasias da Mama , Células-Tronco Mesenquimais , Fenótipo Secretor Associado à Senescência , Células-Tronco Mesenquimais/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Feminino , Humanos , Animais , Camundongos , Proliferação de Células , Sobrevivência Celular , Senescência Celular , Meios de Cultivo Condicionados/farmacologia , Células da Medula Óssea/metabolismo , Células da Medula Óssea/citologia , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Células MCF-7
15.
Sensors (Basel) ; 24(3)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38339576

RESUMO

Ship detection is vital for maritime safety and vessel monitoring, but challenges like false and missed detections persist, particularly in complex backgrounds, multiple scales, and adverse weather conditions. This paper presents YOLO-Vessel, a ship detection model built upon YOLOv7, which incorporates several innovations to improve its performance. First, we devised a novel backbone network structure called Efficient Layer Aggregation Networks and Omni-Dimensional Dynamic Convolution (ELAN-ODConv). This architecture effectively addresses the complex background interference commonly encountered in maritime ship images, thereby improving the model's feature extraction capabilities. Additionally, we introduce the space-to-depth structure in the head network, which can solve the problem of small ship targets in images that are difficult to detect. Furthermore, we introduced ASFFPredict, a predictive network structure addressing scale variation among ship types, bolstering multiscale ship target detection. Experimental results demonstrate YOLO-Vessel's effectiveness, achieving a 78.3% mean average precision (mAP), surpassing YOLOv7 by 2.3% and Faster R-CNN by 11.6%. It maintains real-time detection at 8.0 ms/frame, meeting real-time ship detection needs. Evaluation in adverse weather conditions confirms YOLO-Vessel's superiority in ship detection, offering a robust solution to maritime challenges and enhancing marine safety and vessel monitoring.

16.
Heliyon ; 10(1): e23739, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38192817

RESUMO

Reactive oxygen species (ROS) play multiple roles in synaptic transmission, and estrogen-related receptor α (ERRα) is involved in regulating ROS production. The purpose of our study was to explore the underlying effect of ERRα on ROS production, neurite formation and synaptic transmission. Our results revealed that knocking down ERRα expression affected the formation of neuronal neurites and dendritic spines, which are the basic structures of synaptic transmission and play important roles in learning, memory and neuronal plasticity; moreover, the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) were decreased. These abnormalities were reversed by overexpression of human ERRα. Additionally, we also found that knocking down ERRα expression increased intracellular ROS levels in neurons. ROS inhibitor PBN rescued the changes in neurite formation and synaptic transmission induced by ERRα knockdown. These results indicate a new possible cellular mechanism by which ERRα affects intracellular ROS levels, which in turn regulate neurite and dendritic spine formation and synaptic transmission.

17.
J Vasc Surg Venous Lymphat Disord ; 12(2): 101746, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38158121

RESUMO

OBJECTIVE: Currently, the focus on limb lymphedema (LE) is on classification and staging. However, few scholars have conducted staging for Klippel-Trenaunay syndrome complicated LE (KTS-LE). This study aimed to investigate the value of the short time inversion recovery sequence of magnetic resonance imaging (MRI) in the staging of KTS-LE. METHODS: Forty-six patients who were diagnosed with KTS-LE were recruited for this retrospective study from July 2011 to November 2022. Referring to the clinical staging standard of lower extremity LE of the International Society of Lymphology in 2020, all patients were divided into three groups: stages I, II, and III. The MRI indicators of the three groups were recorded and statistically compared: LE range (unilateral bilateral, lower limbs, only thighs, only calves and ankles), abnormal parts (skin thickening, abnormal subcutaneous fat signal, abnormal muscle signal, muscle hypertrophy or contraction, abnormal bone signal, hyperostosis), and subcutaneous soft tissue signs (parallel line sign, grid sign, band sign, honeycomb sign, lymph lake sign, crescent sign, and nebula sign). RESULTS: There was a significant difference in the honeycomb sign among the three periods (P = .028). There was a significant difference between stage II and stage I disease (P < .05). There was a significant difference between stage II and stage III disease (P < .05). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the honeycomb sign in diagnosing KTS-LE of stage II were 87.5%, 63.2%, 33.3%, 96.0%, and 67.4%, respectively. In contrast, the other signs were not statistically significant among the three periods. CONCLUSIONS: The short time inversion recovery sequence of MRI is of great value in KTS-LE. The honeycomb sign is an important imaging indicator for the diagnosis of stage II disease. It is necessary to evaluate the severity of edema with MRI for KTS-LE, which is very important for therapeutic options.


Assuntos
Síndrome de Klippel-Trenaunay-Weber , Linfedema , Humanos , Síndrome de Klippel-Trenaunay-Weber/complicações , Síndrome de Klippel-Trenaunay-Weber/diagnóstico por imagem , Estudos Retrospectivos , Linfedema/etiologia , Linfedema/complicações , Imageamento por Ressonância Magnética/métodos , Extremidade Inferior
18.
Pharm Res ; 41(2): 247-262, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38148384

RESUMO

OBJECTIVE: Antineoplastic agent-induced systolic dysfunction is a major reason for interruption of anticancer treatment. Although targeted anticancer agents infrequently cause systolic dysfunction, their combinations with chemotherapies remarkably increase the incidence. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide a potent in vitro model to assess cardiovascular safety. However, quantitatively predicting the reduction of ejection fraction based on hiPSC-CMs is challenging due to the absence of the body's regulatory response to cardiomyocyte injury. METHODS: Here, we developed and validated an in vitro-in vivo translational platform to assess the reduction of ejection fraction induced by antineoplastic drugs based on hiPSC-CMs. The translational platform integrates drug exposure, drug-cardiomyocyte interaction, and systemic response. The drug-cardiomyocyte interaction was implemented as a mechanism-based toxicodynamic (TD) model, which was then integrated into a quantitative system pharmacology-physiological-based pharmacokinetics (QSP-PBPK) model to form a complete translational platform. The platform was validated by comparing the model-predicted and clinically observed incidence of doxorubicin and trastuzumab-induced systolic dysfunction. RESULTS: A total of 33,418 virtual patients were incorporated to receive doxorubicin and trastuzumab alone or in combination. For doxorubicin, the QSP-PBPK-TD model successfully captured the overall trend of systolic dysfunction incidences against the cumulative doses. For trastuzumab, the predicted incidence interval was 0.31-2.7% for single-agent treatment and 0.15-10% for trastuzumab-doxorubicin sequential treatment, covering the observations in clinical reports (0.50-1.0% and 1.5-8.3%, respectively). CONCLUSIONS: In conclusion, the in vitro-in vivo translational platform is capable of predicting systolic dysfunction incidence almost merely depend on hiPSC-CMs, which could facilitate optimizing the treatment protocol of antineoplastic agents.


Assuntos
Antineoplásicos , Células-Tronco Pluripotentes Induzidas , Humanos , Cardiotoxicidade/etiologia , Miócitos Cardíacos/patologia , Células Cultivadas , Doxorrubicina/toxicidade , Antineoplásicos/toxicidade , Trastuzumab/efeitos adversos , Combinação de Medicamentos
19.
Zhongguo Zhong Yao Za Zhi ; 48(20): 5404-5409, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-38114134

RESUMO

Accurate assessment of the risks associated with traditional Chinese medicine(TCM), such as the potential to induce serious cardiovascular adverse reactions including cardiac arrhythmias, is crucial. This article introduced the pharmacological evaluation strategies for cardiac safety and the progress in cardiac organ research, with a focus on discussing the application prospects of human induced pluripotent stem cells(hiPSCs) and organoids in assessing the risks of TCM-induced cardiac arrhythmias. Compared with traditional animal models, hiPSCs and organoid models provide better reference and predictive capabilities, allowing for more accurate simulation of human cardiac responses. Researchers have successfully generated various cardiac tissue models that mimic the structure and function of the heart to evaluate the effects of TCM on the heart. The hiPSCs model, by reprogramming adult cells into pluripotent stem cells and differentiating them into cardiac cells, enables the generation of personalized cardiac tissue, which better reflects individual differences and drug responses. This provides guidance for the assessment of TCM cardiac toxicity risks. By combining organoid model with cardiac safety pharmacology strategies such as electrocardiogram monitoring and ion channel function assessment, the impact of TCM on the heart can be comprehensively evaluated. In addition, the application of the Comprehensive in Vitro Proarrhythmia Assay(CiPA) approach improves the accuracy of evaluation. Applying the CiPA approach to TCM research reveals potential risks and provides a scientific basis for the clinical application and industrial development of TCM. In conclusion, organoid model and cardiac safety pharmacology evaluation strategies provide important tools for assessing the cardiac toxicity risks of TCM. The combination of hiPSCs model, comprehensive assessment methods, and the CiPA strategy enables an accurate assessment of the risks of TCM-induced cardiac arrhythmias, thus providing a scientific basis for the safe use and international recognition of TCM in clinical practice. This contributes to ensuring the safety and efficacy of TCM and promoting its clinical application and global acceptance.


Assuntos
Medicamentos de Ervas Chinesas , Células-Tronco Pluripotentes Induzidas , Animais , Humanos , Medicina Tradicional Chinesa/efeitos adversos , Cardiotoxicidade , Arritmias Cardíacas/induzido quimicamente , Miócitos Cardíacos , Organoides , Medicamentos de Ervas Chinesas/efeitos adversos
20.
Math Biosci Eng ; 20(9): 15568-15602, 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37919981

RESUMO

Aiming at the problems of the basic ant colony algorithm in path planning, such as long convergence time, poor global path quality and not being suitable for dynamic environments and unknown environments, this paper proposes a path planning method for mobile robots in complex environments based on an improved ant colony (CBIACO) algorithm. First, a new probability transfer function is designed for an ant colony algorithm, the weights of each component in the function are adaptively adjusted to optimize the convergence speed of the algorithm, and the global path is re-optimized by using the detection and optimization mechanism of diagonal obstacles. Second, a new unknown environment path exploration strategy (UPES) is designed to solve the problem of poor path exploration ability of the ant colony algorithm in unknown environment. Finally, a collision classification model is proposed for a dynamic environment, and the corresponding dynamic obstacle avoidance strategy is given. The experimental results show that CBIACO algorithm can not only rapidly generate high-quality global paths in known environments but also enable mobile robots to reach the specified target points safely and quickly in a variety of unknown environments. The new dynamic obstacle avoidance strategy enables the mobile robot to avoid dynamic obstacles in different directions at a lower cost.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA