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1.
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.

2.
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.

3.
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.

5.
Anal Chem ; 96(16): 6158-6169, 2024 Apr 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
6.
J Vasc Surg Venous Lymphat Disord ; : 101890, 2024 Apr 16.
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.

7.
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
10.
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.

11.
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.

12.
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
13.
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
14.
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
15.
Int J Ophthalmol ; 16(11): 1773-1781, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38028512

RESUMO

AIM: To compare the postoperative binocular visual performance with an iTrace analyzer following femtosecond laser-assisted cataract surgery (FLACS) combined with bilateral implantation of two different types of diffractive trifocal intraocular lenses (IOL). METHODS: During this retrospective observational study, patients who received bilateral FLACS combined with implantation of two different types of diffractive trifocal IOLs were evaluated. According to the IOLs' different types and design, the patients were divided into AT LISA tri839MP group (tri839 group) and AcrySof PanOptix TFNT00 group (TFNT group). Study parameters included preoperative and postoperative uncorrected distance visual acuity (UDVA) at 5 m, uncorrected near visual acuity (UNVA) at 30 cm and 40 cm, uncorrected intermediate visual acuity (UIVA) at 60 cm and 80 cm, postoperative refractive status, objective visual qualities and total high order aberrations (HOAs) postoperatively. The postoperative complications were also recorded. RESULTS: Totally 56 eyes of 28 patients (tri839 group, n=26; TFNT group, n=30) were included. Preoperative baseline characteristics between groups were not statistically significantly different. UDVA was not significantly different between groups except for 1wk follow-up due to the postoperative corneal edema. TFNT group showed statistically significant better UNIA at 60 cm than tri839 group at the 1wk (0.05±0.19 vs 0.15±0.10 logMAR, P=0.013), 1mo (0.05±0.12 vs 0.15±0.09 logMAR, P=0.001) and 3mo (0.04±0.12 vs 0.15±0.11 logMAR, P=0.001) follow-up, while tri839 group showed statistically significant better UNIA at 80 cm than TFNT group at the 1d (0.14±0.15 vs 0.20±0.14 logMAR, P=0.041) and 1mo (0.09±0.07 vs 0.14±0.10 logMAR, P=0.042) follow-up. Postoperative refractive status showed stable at every visit. Modulated transfer function (MTF) values and strehl ratio (SR) values were improved and HOAs were lower significantly after surgery. CONCLUSION: FLACS with bilateral implantations of both tri839 and TFNT00 can achieve satisfactory natural whole-course vision, high postoperative refractive stability and good visual quality but without significantly difference. iTrace aberration instrument can accurately evaluate the visual quality under different status.

16.
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.

17.
Pharmaceutics ; 15(9)2023 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-37765243

RESUMO

Despite the recent advances in this field, there are limited methods for translating organoid-based study results to clinical response. The goal of this study was to develop a pharmacokinetic/pharmacodynamic (PK/PD) model to facilitate the translation, using oxaliplatin and irinotecan treatments with colorectal cancer (CRC) as examples. The PK models were developed using qualified oxaliplatin and irinotecan PK data from the literature. The PD models were developed based on antitumor efficacy data of SN-38 and oxaliplatin evaluated in vitro using tumor organoids. To predict the clinical response, translational scaling of the models was established by incorporating predicted ultrafiltration platinum in plasma or SN-38 in tumors to PD models as the driver of efficacy. The final PK/PD model can predict PK profiles and responses following treatments with oxaliplatin or irinotecan. After generation of virtual patient cohorts, this model simulated their tumor shrinkages following treatments, which were used in analyzing the efficacies of the two treatments. Consistent with the published clinical trials, the model simulation suggested similar patient responses following the treatments of oxaliplatin and irinotecan with regards to the probabilities of progression-free survival (HR = 1.05, 95%CI [0.97;1.15]) and the objective response rate (OR = 1.15, 95%CI [1.00;1.32]). This proposed translational PK/PD modeling approach provides a significant tool for predicting clinical responses of different agents, which may help decision-making in drug development and guide clinical trial design.

18.
iScience ; 26(9): 107455, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37680481

RESUMO

Type H vessels couple angiogenesis with osteogenesis, while sympathetic cues regulate vascular and skeletal function. The crosstalk between sympathetic nerves and type H vessels in bone remains unclear. Here, we first identify close spatial connections between sympathetic nerves and type H vessels in bone, particularly in metaphysis. Sympathoexcitation, mimicked by isoproterenol (ISO) injection, reduces type H vessels and bone mass. Conversely, beta-2-adrenergic receptor (ADRB2) deficiency maintains type H vessels and bone mass in the physiological condition. In vitro experiments reveal indirect sympathetic modulation of angiogenesis via paracrine effects of mesenchymal stem cells (MSCs), which alter the transcription of multiple angiogenic genes in endothelial cells (ECs). Furthermore, Notch signaling in ECs underlies sympathoexcitation-regulated type H vessel formation, impacting osteogenesis and bone mass. Finally, propranolol (PRO) inhibits beta-adrenergic activity and protects type H vessels and bone mass against estrogen deficiency. These findings unravel the specialized neurovascular coupling in bone homeostasis and regeneration.

19.
EJNMMI Res ; 13(1): 72, 2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37535169

RESUMO

BACKGROUND: Chylothorax is a condition that can be challenging to diagnose due to its nonspecific clinical presentation. Several biochemical parameters of chylous pleural effusion have been identified as important indicators for the diagnosis of chylothorax. Lymphoscintigraphy is utilized to assess chylothorax and determine the location of chyle leakage. The present study aimed to evaluate the correlation between the biochemical parameters of chylous pleural effusion and 99mTc-dextran (99mTc-DX) lymphoscintigraphy in diagnosing chylothorax. MATERIAL AND METHODS: A total of 120 patients were enrolled in the study, 83 of the patients with unilateral chylothorax, and 37 with bilateral chylothorax. All patients underwent both 99mTc-DX lymphoscintigraphy and pleural effusion laboratory analysis. The 99mTc-DX lymphoscintigraphy images were categorized as positive or negative groups based on the presence or absence of abnormal radioactive tracer accumulation in the thorax, respectively. The biochemical parameters of the two groups were subsequently compared. RESULTS: Among these patients, 101 (84.17%) had exudative effusions, while 19 (15.83%) had transudative effusions, as determined by the levels of pleural effusion protein, lactate dehydrogenase and cholesterol. Abnormal tracer accumulation in thorax was observed in 82 patients (68.33%). Our findings indicated that lymphoscintigraphy results were not associated with exudative and transudative chylothorax (P = 0.597). The lymphoscintigraphy positive group displayed significantly higher levels of pleural effusion triglyceride and pleural effusion triglyceride/serum triglyceride ratio in all biochemical parameters, compared to the negative group (P = 0.000 and P = 0.005). We identified cutoff values of 2.870 mmol/L for pleural effusion triglycerides and 4.625 for pleural effusion triglyceride/serum triglyceride ratio, respectively, which can facilitate differentiating the positive and negative cases on lymphoscintigraphy. CONCLUSION: Lymphoscintigraphy technique is a dependable diagnostic tool for the qualitative assessment of chylous pleural effusion. Higher pleural effusion triglyceride level and pleural effusion triglyceride/serum triglyceride ratio indicate a positive result in patients with chylothorax on lymphoscintigraphy, with the cutoff values of 2.870 mmol/L and 4.625 aiding in the diagnosis.

20.
Quant Imaging Med Surg ; 13(8): 4839-4851, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37581039

RESUMO

Background: The staging of primary lower extremity lymphedema (LEL) is difficult yet vital in clinical work, and magnetic resonance imaging (MRI) can be used for quantitative assessment of primary LEL due to its high resolution for soft tissues. In this study, we evaluated the value of MRI-based soft tissue area measurements for staging primary LEL. Methods: A total of 90 consecutive patients with clinically diagnosed primary lower limb lymphoedema from January 2017 to December 2019 in Beijing Shijitan Hospital were enrolled retrospectively. Short time inversion recovery (STIR) sequence was applied to measure the total, muscle, bone, and subcutaneous areas in the upper 1/3 level of the bilateral lower calf. The difference between the affected and unaffected calf regarding the subcutaneous area was obtained, and (subcutaneous area)/(bone area) and (subcutaneous area)/(muscle area) were calculated. According to the International Society of Lymphology (ISL) clinical staging standard established in 2020, all patients were divided into stages I, II, and III, accordingly. Statistical analysis was performed to determine the validity of MRI measurements in staging LEL. Results: There were 33 patients classified as stage I clinically, 44 patients as stage II, and 13 patients as stage III. There were significant differences in total, subcutaneous, the difference in subcutaneous area of limbs, subcutaneous/bone (S/B), and subcutaneous/muscle (S/M) between stage I and II as well as between stage I and III (P<0.001), but not between stage II and III (P=0.706, 0.329, and 0.229, respectively). A positive correlation was detected between the clinical stage and difference in subcutaneous area of limbs (rho =0.752, P<0.001), S/B (rho =0.747, P<0.001), S/M (rho =0.709, P<0.001), and subcutaneous (rho =0.723, P<0.001). For staging primary LEL, receiver operating characteristic (ROC) curves indicated that the difference in subcutaneous area of limbs had the best discrimination ability among parameters [area under the ROC curve (AUC) =0.950; 95% confidence interval (CI): 0.875-0.987; sensitivity: 95.45%; specificity: 84.85%], followed by S/B (AUC =0.930; 95% CI: 0.848-0.975; sensitivity: 77.27%; specificity: 93.94%) and S/M (AUC =0.895; 95% CI: 0.804-0.953; sensitivity: 77.27%; specificity: 90.91%). The ROC curves indicated that subcutaneous area (AUC =0.927; 95% CI: 0.844-0.974; sensitivity: 84.09%, specificity: 90.91%) and total (AUC =0.852; 95% CI: 0.753-0.923; sensitivity: 70.45%; specificity: 90.91%) also had discrimination ability between stage I and II. Conclusions: The measurement of the soft tissue area of the calf may be used as an auxiliary method for staging primary LEL. For patients with unilateral primary LEL, the difference in subcutaneous area of limbs could be a specific indicator to distinguish clinical stage I from II.

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