RESUMO
Cuproptosis in antitumor therapy faces challenges from copper homeostasis efflux mechanisms and high glutathione (GSH) levels in tumor cells, hindering copper accumulation and treatment efficacy. Herein, we propose a strategy of "adding fuel to the flames" for potent antitumor therapy through a self-accelerating cycle of ferroptosis-cuproptosis. Disulfiram (DSF) loaded hollow mesoporous copper-iron sulfide (HMCIS) nanoparticle with conjugation of polyethylene glycol (PEG) and folic acid (FA) (i.e., DSF@HMCIS-PEG-FA) was developed to swiftly release DSF, H2S, Cu2+, and Fe2+ in the acidic tumor microenvironment (TME). The hydrogen peroxide (H2O2) levels and acidity within tumor cells enhanced by the released H2S induce acceleration of Fenton (Fe2+) and Fenton-like (Cu2+) reactions, enabling the powerful tumor ferroptosis efficacy. The released DSF acts as a role of "fuel", intensifying catalytic effect ("flame") in tumor cells through the sustainable Fenton chemistry (i.e., "add fuel to the flames"). Robust ferroptosis in tumor cells is characterized by serious mitochondrial damage and GSH depletion, leading to excess intracellular copper that triggers cuproptosis. Cuproptosis disrupts mitochondria, compromises iron-sulfur (Fe-S) proteins, and elevates intracellular oxidative stress by releasing free Fe3+. These interconnected processes form a self-accelerating cycle of ferroptosis-cuproptosis with potent antitumor capabilities, as validated in both cancer cells and tumor-bearing mice.
Assuntos
Antineoplásicos , Cobre , Dissulfiram , Ferroptose , Ferroptose/efeitos dos fármacos , Animais , Dissulfiram/farmacologia , Dissulfiram/química , Humanos , Camundongos , Cobre/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral , Ferro/metabolismo , Ferro/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Ácido Fólico/química , Ácido Fólico/metabolismo , Polietilenoglicóis/química , Camundongos Endogâmicos BALB C , Peróxido de Hidrogênio/metabolismoRESUMO
BACKGROUND: Currently, the diagnosis of invasive pulmonary aspergillosis (IPA) mainly depends on the integration of clinical, radiological and microbiological data. Artificial intelligence (AI) has shown great advantages in dealing with data-rich biological and medical challenges, but the literature on IPA diagnosis is rare. OBJECTIVE: This study aimed to provide a non-invasive, objective and easy-to-use AI approach for the early diagnosis of IPA. METHODS: We generated a prototype diagnostic deep learning model (IPA-NET) comprising three interrelated computation modules for the automatic diagnosis of IPA. First, IPA-NET was subjected to transfer learning using 300,000 CT images of non-fungal pneumonia from an online database. Second, training and internal test sets, including clinical features and chest CT images of patients with IPA and non-fungal pneumonia in the early stage of the disease, were independently constructed for model training and internal verification. Third, the model was further validated using an external test set. RESULTS: IPA-NET showed a marked diagnostic performance for IPA as verified by the internal test set, with an accuracy of 96.8%, a sensitivity of 0.98, a specificity of 0.96 and an area under the curve (AUC) of 0.99. When further validated using the external test set, IPA-NET showed an accuracy of 89.7%, a sensitivity of 0.88, a specificity of 0.91 and an AUC of 0.95. CONCLUSION: This novel deep learning model provides a non-invasive, objective and reliable method for the early diagnosis of IPA.
Assuntos
Aprendizado Profundo , Aspergilose Pulmonar Invasiva , Pneumonia , Humanos , Aspergilose Pulmonar Invasiva/diagnóstico , Big Data , Inteligência Artificial , Sensibilidade e Especificidade , Estudos RetrospectivosRESUMO
OBJECTIVES: Noninvasive fetal electrocardiography (FECG) offers many advantages over alternative fetal monitoring techniques in evaluating fetal health conditions. However, it is difficult to extract a clean FECG signal with morphological features from an abdominal ECG recorded at the maternal abdomen; the signal is usually contaminated by the maternal ECG and various noises. The aim of the work is to extract an FECG signal that preserves the morphological features from the mother's abdominal ECG recording, which allows for accurately estimating the fetal heart rate (FHR) and analyzing the waveforms of the fetal ECG. METHODS: We propose a novel nonlinear adaptive noise cancelling framework (ANC) based on a temporal convolutional neural network (CNN) to effectively extract fetal ECG signals from mothers' abdominal ECG recordings. The proposed framework consists of a two-stage network, using the ANC architecture; one network is for the maternal ECG component elimination and the other is for the residual noise component removal of the extracted fetal ECG signal. Then, JADE (one of the blind source separation algorithms) is applied as a postprocessing step to produce a clean fetal ECG signal. RESULTS: Synthetic ECG data (FECGSYNDB) and clinical ECG data (NIFECGDB, PCDB) are used to evaluate the extraction performance of the proposed framework. The statistical and visual results demonstrate that our method outperforms the other state-of-the-art algorithms in the literature. Specifically, on the FECGSYNDB, the mean squared error (MSE), signal-to-noise ratio (SNR), correlation coefficient (R) and F1-score of our method are 0.16, 7.94, 0.95 and 98.89%, respectively. The F1-score on the NIFECGDB reaches 98.62%. The value of the F1-score on the PCDB is 98.62%. CONCLUSION: As opposed to the existing algorithms being restricted to fetal QRS complex detection, the proposed framework can preserve the morphological features of the extracted fetal ECG signal well, which could support medical diagnoses based on the morphology of the fetal ECG signal.
Assuntos
Monitorização Fetal , Processamento de Sinais Assistido por Computador , Gravidez , Feminino , Humanos , Monitorização Fetal/métodos , Eletrocardiografia/métodos , Frequência Cardíaca Fetal/fisiologia , Redes Neurais de Computação , AlgoritmosRESUMO
The present study proposes a cognitive prosthesis device for face memory impairment as a proof-of-concept for the domain-specific cognitive prosthesis. Healthy subjects (n = 6) and a patient with poor face memory were enrolled. An acquaintance face recognition test with and without the use of cognitive prosthesis for face memory impairment, face recognition tests, quality of life, neuropsychological assessments, and machine learning performance of the cognitive prosthesis were followed-up throughout four weeks of real-world device use by the patient. The healthy subjects had an accuracy of 92.38 ± 4.41% and reaction time of 1.27 ± 0.12 s in the initial attempt of the acquaintance face recognition test, which changed to 80.48 ± 6.23% (p = 0.06) and 2.11 ± 0.20 s (p < 0.01) with prosthesis use. The patient had an accuracy of 74.29% and a reaction time of 6.65 s, which improved to 94.29% and 3.28 s with prosthesis use. After four weeks, the patient's unassisted accuracy and reaction time improved to 100% and 1.23 s. Functional MRI study revealed activation of the left superior temporal lobe during face recognition task without prosthesis use and activation of the right precentral motor area with prosthesis use. The prosthesis could improve the patient's performance by bypassing the brain area inefficient for facial recognition and employing the area more efficiently for the cognitive task.
RESUMO
Metal tetrakis(1-methylpyridinium-4-yl)porphyrins were immobilized on sulfonated SBA-15 (MTMPyP-SO3-pr-SBA-15, M = Fe, Mn, Zn) for oxidative degradation of 2,4,6-tribromophenol in the presence of humic substances. The influence of the central metal of metalloporphyrins, pH, and catalyst dosage on the 2,4,6-tribromophenol degradation was investigated. FeTMPyP-SO3-pr-SBA-15 and MnTMPyP-SO3-pr-SBA-15 showed the catalytic activities. The activity of MnTMPyP-SO3-pr-SBA-15 was more strongly inhibited by humic substances than that of FeTMPyP-SO3-pr-SBA-15. Kinetic study indicated that humic substances suppressed the generation of high valent metal-oxo species in MnTMPyP-SO3-pr-SBA-15 at slightly acid condition. There was a clear linear relationship between the content of phenolic-OH and aromatic-C in humic substances and the corresponding inhibition ability. The inhibition by humic substances is probably ascribed to the coordination of humic substances with the monopersulfate species of MnTMPyP-SO3-pr-SBA-15, which prevented the formation of the reactive Mn-oxo species.
Assuntos
Substâncias Húmicas , Porfirinas , Estresse Oxidativo , Fenóis , Compostos de Piridínio , Dióxido de SilícioRESUMO
An all-inorganic zeolitic octahedral metal oxide based on cobalt tungstoselenate with porosity and hydrophilicity is successfully used to fabricate a membrane. The as-synthesized membrane and its ion-exchanged membranes exhibit extraordinary permeation flux with high salt rejection by pervaporative desalination for high-salinity brines up to 25 wt%.
Assuntos
Cobalto/química , Óxidos/química , Purificação da Água/métodos , Zeolitas/química , Interações Hidrofóbicas e Hidrofílicas , Membranas Artificiais , Porosidade , Salinidade , Sais/química , Cloreto de Sódio/química , Propriedades de Superfície , ÁguaRESUMO
OBJECTIVES: To investigate whether dosiomics can benefit to IMRT treated patient's locoregional recurrences (LR) prediction through a comparative study on prediction performance inspection between radiomics methods and that integrating dosiomics in head and neck cancer cases. MATERIALS AND METHODS: A cohort of 237 patients with head and neck cancer from four different institutions was obtained from The Cancer Imaging Archive and utilized to train and validate the radiomics-only prognostic model and integrate the dosiomics prognostic model. For radiomics, the radiomics features were initially extracted from images, including CTs and PETs, and selected on the basis of their concordance index (CI) values, then condensed via principle component analysis. Lastly, multivariate Cox proportional hazards regression models were constructed with class-imbalance adjustment as the LR prediction models by inputting those condensed features. For dosiomics integration model establishment, the initial features were similar, but with additional 3-dimensional dose distribution from radiation treatment plans. The CI and the Kaplan-Meier curves with log-rank analysis were used to assess and compare these models. RESULTS: Observed from the independent validation dataset, the CI of the model for dosiomics integration (0.66) was significantly different from that for radiomics (0.59) (Wilcoxon test, p=5.9×10-31). The integrated model successfully classified the patients into high- and low-risk groups (log-rank test, p=2.5×10-02), whereas the radiomics model was not able to provide such classification (log-rank test, p=0.37). CONCLUSION: Dosiomics can benefit in predicting the LR in IMRT-treated patients and should not be neglected for related investigations.
Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Radioterapia de Intensidade Modulada/métodos , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Recidiva Local de Neoplasia , Prognóstico , Análise de SobrevidaRESUMO
The mammography is the first choice of breast cancer screening, which has proven to be the most effective screening method. An antiscatter grid is usually employed to enhance the contrast of image by absorbing unexpected scattered signals. However, the grid pattern casts shadows and grid artifacts, which severely degrade the image quality. To solve the problem, we propose the patch based frequency signal filtering for fast grid artifacts suppressing. As opposed to whole image processing synchronously, the proposed method divides image into a number of blocks for tuning filter simultaneously, which reduces the frequency interference among image blocks and saves computation time by multithread processing. Moreover, for mitigating grid artifacts more precisely, characteristic peak detection is employed in each block automatically, which can accurately identify the location of the antiscatter grid and its motion pattern. Qualitative and quantitative studies were performed on simulation and real machine data to validate the proposed method. The results show great potential for fast suppressing grid artifacts and generating high quality of digital mammography.
Assuntos
Artefatos , Mamografia , Intensificação de Imagem Radiográfica , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Imagens de Fantasmas , Espalhamento de RadiaçãoRESUMO
OBJECTIVE: To study and design a maternal and fetal monitoring system based on the cloud computing and internet of things, which can monitor and take smart care of the mother and fetus in 24 h. METHODS: Using a new kind of wireless fetal monitoring detector and a mobile phone, thus the doctor can keep touch with hospital through internet. The mobile terminal was developed on the Android system, which accepted the data of fetal heart rate and uterine contraction transmitted from the wireless detector, exchange information with the server and display the monitoring data and the doctor's advice in real-time. RESULTS: The mobile phone displayed the fetal heart rate line and uterine contraction line in real-time, recorded the fetus' grow process. It implemented the real-time communication between the doctor and the user, through wireless communication technology. CONCLUSIONS: The system removes the constraint of traditional telephone cable for users, while the users can get remote monitoring from the medical institutions at home or in the nearest community at any time, providing health and safety guarantee for mother and fetus.
Assuntos
Monitorização Fisiológica/instrumentação , Tecnologia sem Fio , Telefone Celular , Feminino , Feto , Humanos , Internet , GravidezRESUMO
This article presents the development and design of a new type intelligent high potential therapeutic apparatus, by using Atmega1280 as its controller. The circuit transforms voltage from 220 V ac to 110 V ac and constitutes different circuits with relays. In order to get different treatment waveforms, inductance of various values is used in different circuits. The circuit generates appropriate treatment voltage with the transformer booster. Simultaneously, the corresponding control software was composed. Finally the hardware and software designs of the high potential therapeutic apparatus were completed. Result of the experiment showed that the high potential therapeutic apparatus worked steadily and the effect of treatment was satisfactory.
Assuntos
Terapia por Estimulação Elétrica/instrumentação , Desenho de Equipamento , Terapia por Estimulação Elétrica/métodos , Humanos , SoftwareRESUMO
OBJECTIVE: To evaluate the value of CT common rail technique for application in intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC). METHODS: Twenty-seven NPC patients underwent Somatom CT scans using the Siemens CTVision system prior to the commencement of the radiotherapy sessions. The acquired CT images were registered with the planning CT images using the matching function of the system to obtain the linear set-up errors of 3 directions, namely X (left to right), Y (superior to inferior), and Z (anterior to posterior). The errors were then corrected online on the moving couch. RESULTS: The 27 NPC patients underwent a total of 110 CT scans and the displacement deviations of the X, Y and Z directions were -0.16∓1.68 mm, 0.25∓1.66 mm, and 0.33∓1.09 mm, respectively. CONCLUSION: CT common rail technique can accurately and rapidly measure the space error between the posture and the target area to improve the set-up precision of intensity-modulated radiotherapy for NPC.
Assuntos
Neoplasias Nasofaríngeas/radioterapia , Posicionamento do Paciente , Radioterapia de Intensidade Modulada/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma NasofaríngeoRESUMO
We have designed a sort of multi-functional bone forceps for use as orthopedic surgical instruments to grip, bend and cut the spicula. It is labor-saving and easily installed. Its left and right clamp bodies are connected by a rivet to hold the spicula, and the pressure-regulating shank is connected with the clamp seat body at the right top of the clamp body by a rivet. It is used to curve the spicula. At an appropriate location on the pressure-regulating shank is a pin-cutting chip. On the right body rotating disc-clamp, there is a rectangular open cutting groove to be in use for cutting the specula with the role of pin-cutting chip. Being characterized by the use of mechanical leverage, the manipulations of holding and bending are less arduous. After achieving the 90-degree bend, the operator can cut off the specula successfully. The operation is easy to perform and labor-saving; the forceps can further meet the actual clinical demand.
Assuntos
Fixação Interna de Fraturas/instrumentação , Instrumentos Cirúrgicos , Desenho de Equipamento , HumanosRESUMO
This is the design of a mechanical systems for use in the balanceable system of ambulance, which can keep the medical service bed at the ambulance level, whatever the terrain is. A level detector will detect the level state of the bed and turn it to a signal. The central processing unit will use this signal to analyse and control the movement of the motor. By this design (which uses the rolling rail as a drive transmission and makes three supports of the bed go up and down), the bed will keep level. With the use of this design, the balanceable system of ambulance can counteract 35 degrees. The error is controlled within +/- 1 degree. And the response time is within 0.3 s. The method of registration can be effective for keeping the bed at the ambulance level, and for reducing the chance of making the patient get hurt on the way to hospital.
Assuntos
Ambulâncias , Robótica/métodos , Transporte de Pacientes , Desenho de Equipamento , HumanosRESUMO
OBJECTIVE: To reduce the influence of breathing movement on the location precision of the tumor target in precise radiotherapy for thoraco-abdominal tumors. METHODS: An inverse tracking system was developed to track the path of the breathing movement of the tumor target via image guiding. With this system, the displacement of the target in a given time period was tracked and quickly transformed in signals that drove the tracking couch to move inversely relative to the tumor target. CONCLUSION: This system can effectively reduce the influence of tumor target breath movement during radiotherapy. Compared with other breath movement control methods, this method avoids prolonged exposure time, allows the patient to breathe at ease and shortens the time of CT scanning.
Assuntos
Neoplasias Pulmonares/radioterapia , Movimento , Radioterapia Conformacional/instrumentação , Respiração , Feminino , Humanos , Masculino , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia Conformacional/métodosRESUMO
A new head and neck location frame for positron emission tomography (PET) and computed tomography (CT) cross-modality medical image fusion in radiotherapy was developed. The solid mark bars of N form in the old designed CT location frame were replaced by closed hollow pipes which could be filled with different developer solutions before CT or PET scan, respectively. Nine points of external marker used for registration and fusion were obtained in CT images and PET images, respectively. The locations of the two sets of nine points showed the method of registration to be effective and accurate in achieving the PET and CT image fusion. This method, based on its characteristics of simple structure and easy-to-use, can be of wide application in clinical setting.
Assuntos
Cabeça/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Pescoço/diagnóstico por imagem , Cabeça/anatomia & histologia , Humanos , Interpretação de Imagem Assistida por Computador/instrumentação , Imagem Multimodal/métodos , Pescoço/anatomia & histologia , Tomografia por Emissão de Pósitrons/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
In the end of last century, there was a leap in the technological quality of radiotherapy, which is incarnated in three new technologies: Stereotactic radiation surgery (SRS), three-dimensional conformal radiation therapy (3D-CRT) and intensity modulated radiation therapy (IMRT). However, the achievement of these technologies has a close relationship with the precise orientation of tumour. Especially, in terms of body stereotactic precise radiation therapy, its body mechanical orientation system is the kernel to guarantee the accuracy of radiotherapy. This paper presents a novel mechanical orientation system for body precise radiotherapy. It is characterized by flexible adjustment, deft removal, easy disassembly and accurate orientation using apart structure to substitute old integer structure and adopting single segment Z shape orientation marker staff. The new mechanical orientation system guarantees the effect of tumour radiotherapy, which is worthy to be recommended for clinical use.
Assuntos
Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Planejamento da Radioterapia Assistida por Computador/instrumentação , Radioterapia de Intensidade Modulada/instrumentação , Tomografia Computadorizada por Raios X/métodos , Humanos , Imagens de Fantasmas , Radiografia Intervencionista , Radioterapia Conformacional/instrumentação , Técnicas EstereotáxicasRESUMO
This paper presents a novel x-ray dose testing water tank used for the stereotactic radiation therapy system, including its constitution, structure and the method of using it. The water tank has a simple structure of inner and outer sleeves which are connected through a drowned pump and a water pipe in order to control the water level of the tank. The water tank featuring autoregulation and easy use is worthy of clinical application and popularization.
Assuntos
Radiocirurgia/instrumentação , Planejamento da Radioterapia Assistida por Computador/instrumentação , Desenho de Equipamento , Radiocirurgia/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
As a powerful global optimization approach, genetic algorithms (GA) can solve a variety of optimization problems in which the objective function is discontinuous, non-differentiable, or highly non-linear, to produce high convergence speed and vast search space. In this thesis, GA is used to optimize the beam weights of intensity modulated radiation therapy (IMRT) inverse planning, and 2D and 3D isodose contour as well as dose volume histogram (DVH) are used to evaluate the treatment plan. Also presented in this thesis are the results of calculation with discussions.
Assuntos
Algoritmos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Humanos , Modelos Teóricos , Dosagem Radioterapêutica , Radioterapia Conformacional/normasRESUMO
UNLABELLED: To study the method for dose calculation and beam weight optimization of intensity-modulated radiation therapy (IMRT). METHODS: The IMRT dose calculation model based on two-dimensional convolution was constructed, the program of dose calculation and beam weight optimization with genetic algorithm was written with Visual c#.Net, and the optimization results were analyzed. RESULTS: Genetic algorithm optimization of beam weights can produce highly conformal dose distributions within a clinically acceptable computation time. CONCLUSION: Genetic algorithm is valid and efficient in IMRT beam weight optimization, which may facilitate IMRT treatment planning.
Assuntos
Algoritmos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Humanos , Modelos Estatísticos , Modelos Teóricos , Dosagem Radioterapêutica , Radioterapia Conformacional/normasRESUMO
OBJECTIVE: To develop a new method for static intensity-modulated radiation therapy (IMRT) possible for implementation in smaller hospitals by incorporating accurate location equipments and treatment planning system in the available equipments for general radiotherapy. METHODS: Based on the techniques of conformal radiotherapy, a new split method for fabricating the three-dimensional physical compensator was developed to achieve IMRT. RESULTS: Experiment with the new method showed that the fabricated compensator could achieve good match between the high dosage shape in the target area and the dimensions of the tumor, and allowed adjustment of the dosage distribution according to the therapeutic requirement. CONCLUSION: This simple and feasible method allows cost-effect application of IMRT in smaller hospitals.