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Inborn errors of immunity (IEI) are a diverse group of disorders caused by defects in immune system structure or function, involving both innate and adaptive immunity. The 2022 update of the IEI classification includes 485 distinct disorders, categorized into ten major disease groups. With the rapid development of molecular biology, the specific pathogenesis of many IEI has been revealed, making gene therapy possible in preclinical and clinical research of this type of disease. This article reviews the advancements in gene therapy for IEI, aiming to increase awareness and understanding of these disorders.
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Terapia Genética , Humanos , Enfermedades del Sistema Inmune/terapia , Enfermedades del Sistema Inmune/genética , Enfermedades del Sistema Inmune/inmunología , AnimalesRESUMEN
ABSTRACT: Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive patients who were treated at Beijing Children's Hospital, Capital Medical University (Beijing, China), between January 2016 and October 2023 were retrospectively reviewed. Clinical evaluations, including physical examination, hormone examination, serum tumor marker analysis, abdominal and scrotal ultrasound, chest X-ray, and bone age measurement, were conducted before surgery and at follow-up time points. Surgical approaches were selected according to the individual conditions. Patients with an abnormal hormonal status and suspected of having central precocious puberty were referred to endocrinologists to confirm the diagnosis. Subsequently, gonadotropin-releasing hormone analog therapy was proposed. The mean patient age was 81.3 (range: 40-140) months at the time of the operation. Ten patients had peripheral precocious puberty at admission. All patients had elevated preoperative testosterone levels, whereas tumor marker levels were normal. Testis-sparing surgery was performed in eleven patients, and radical orchiectomy was performed in one patient. The follow-up duration (mean ± standard deviation) was 36.2 ± 25.3 months. Five patients had central precocious puberty, with a mean duration of 3.4 (range: 1-6) months postoperatively. Three patients were receiving gonadotropin-releasing hormone analog therapy, and good suppression of puberty was observed. No risk factors were found for secondary central precocious puberty. There was a high prevalence of central precocious puberty secondary to Leydig cell tumors in our study. Gonadotropin-releasing hormone analog therapy has satisfactory treatment effects. Larger sample sizes and long-term follow-up are needed in future studies.
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In virtual surgical training, it is crucial to achieve real-time, high-fidelity simulation of the tissue deformation. The anisotropic and nonlinear characteristics of the organ with multi-component make accurate real-time deformation simulation difficult. A localized tissue constraint progressive transfer learning method is proposed in this paper, where the base-compensated dual-output transfer learning strategy and the localized tissue constraint progressive learning architecture are developed. The proposed strategy enriches the multi-component biomechanical dataset to fully represent complex force-displacement with minimal high-quality data. Meanwhile, the proposed architecture adopts focused and progressive model to accurately describe tissues with varied biomechanical properties rather than singular homogeneous model. We made comparison with 4 state-of-the-art (SOTA) methods in simulating multi-component biomechanical deformations of organs with 100 pairs of testing data. Results show that the accuracy of our method is 50% higher than other methods in different validation matrix. And our method can stably simulate the deformations in 0.005 s per frame, which largely improves the computing efficiency.
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Fenómenos Mecánicos , Fenómenos Biomecánicos , Simulación por Computador , Factores de Tiempo , Aprendizaje Automático , HumanosRESUMEN
Soil macro-aggregates are the main location for soil organic carbon ï¼SOCï¼ sequestration, which is of great significance to improve soil fertility. This study aimed to understand the mechanisms of the organic carbon ï¼OCï¼ sequestration in macroaggregates and improve crop yield in wheat fields on the loess plateau. With the aggregate-density fractionation method, an eight-year experiment was conducted to investigate the following three factorsï¼ â the effects of long-term fertilization on OC fractions within macroaggregatesï¼ â¡ the variation characteristics of OC fractions within macroaggregates, including coarse particulate organic carbon ï¼cPOCï¼, fine particulate organic carbon ï¼fPOCï¼, intra-microaggregate particulate organic carbon ï¼iPOCï¼, free silt and clay particulate carbon ï¼s+c_fï¼, and intra-microaggregate silt and clay particulate carbon ï¼s+c_mï¼ï¼ ⢠and the relationships between them and SOC input and yield formation. The treatments included no fertilization ï¼CKï¼, farmer pattern ï¼NPï¼, optimized fertilizers pattern ï¼NPKï¼, optimized fertilizers + organic fertilizers pattern ï¼NPKMï¼, and optimized fertilizers + biological organic fertilizers pattern ï¼NPKBï¼. The results showed that the application of organic and chemical fertilizer ï¼NPKM and NPKBï¼ improved significantly the SOC content in macroaggregates compared with that in the single fertilizer treatment ï¼NP and NPKï¼, which had a greater increase in SOC content in macroaggregates than that of the soil. All fertilization treatments had a tendency to increase the content of fractions iPOC, fPOC, and iPOC in macroaggregates, but silt and clay carbon ï¼s+c_f and s+c_mï¼ contents were decreased. The application of manure combined with chemicals markedly increased the allocations of fractions cPOC, fPOC, and iPOC reserves, but it greatly decreased ï¼s+c_fï¼ reserves allocation. However, the application of chemical fertilizers only significantly increased the proportion of cPOC reserves in macroaggregates. Correlation analysis showed that there were significant positive correlations among wheat grain yield and OC fractions ï¼cPOC and fPOCï¼ contents, SOC content, the OC content of >0.25 mm macroaggregates, and SOC input, and the correlation coefficient was 0.645-0.883. In conclusion, long-term fertilization, especially combined with organic fertilizer, could promote the free silt and clay carbon fraction ï¼s+c_fï¼ to transfer into other forms of OC components through the increase in soil carbon input in the wheat field of the loess plateau. Furthermore, the OC content of macroaggregates was increased overall, providing a good soil environment for crop yield.
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Detecting coronary stenosis accurately in X-ray angiography (XRA) is important for diagnosing and treating coronary artery disease (CAD). However, challenges arise from factors like breathing and heart motion, poor imaging quality, and the complex vascular structures, making it difficult to identify stenosis fast and precisely. In this study, we proposed a Quantum Diffusion Model with Spatio-Temporal Feature Sharing to Real-time detect Stenosis (STQD-Det). Our framework consists of two modules: Sequential Quantum Noise Boxes module and spatio-temporal feature module. To evaluate the effectiveness of the method, we conducted a 4-fold cross-validation using a dataset consisting of 233 XRA sequences. Our approach achieved the F1 score of 92.39% with a real-time processing speed of 25.08 frames per second. These results outperform 17 state-of-the-art methods. The experimental results show that the proposed method can accomplish the stenosis detection quickly and accurately.
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Deep learning methods have recently achieved remarkable performance in vessel segmentation applications, yet require numerous labor-intensive labeled data. To alleviate the requirement of manual annotation, transfer learning methods can potentially be used to acquire the related knowledge of tubular structures from public large-scale labeled vessel datasets for target vessel segmentation in other anatomic sites of the human body. However, the cross-anatomy domain shift is a challenging task due to the formidable discrepancy among various vessel structures in different anatomies, resulting in the limited performance of transfer learning. Therefore, we propose a cross-anatomy transfer learning framework for 3D vessel segmentation, which first generates a pre-trained model on a public hepatic vessel dataset and then adaptively fine-tunes our target segmentation network initialized from the model for segmentation of other anatomic vessels. In the framework, the adaptive fine-tuning strategy is presented to dynamically decide on the frozen or fine-tuned filters of the target network for each input sample with a proxy network. Moreover, we develop a Gaussian-based signed distance map that explicitly encodes vessel-specific shape context. The prediction of the map is added as an auxiliary task in the segmentation network to capture geometry-aware knowledge in the fine-tuning. We demonstrate the effectiveness of our method through extensive experiments on two small-scale datasets of coronary artery and brain vessel. The results indicate the proposed method effectively overcomes the discrepancy of cross-anatomy domain shift to achieve accurate vessel segmentation for these two datasets.
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AIM: The initial decrease in estimated glomerular filtration rate (eGFR), often known as the "initial dip," associated with sodium-glucose cotransporter 2 inhibitors (SGLT2i) is typically transient but may be more pronounced in older patients. METHODS: We analyzed real-world data from 2,070 patients newly prescribed SGLT2i, tracking eGFR changes at baseline and 3, 6, 9, and 12 months after initiation. We defined a significant initial dip as over 10 % reduction in eGFR at 3 months. In addition, the 1-year change in eGFR after the initial decline was also assessed. RESULTS: Of the total patients, 34.5 % were aged 60-69 years, 21.1 % were aged 70-79 years, and 11.5 % were aged 80 years or older. About 21.4 % experienced a significant dip at 3 months. The incidence of initial dip increases with age, with the highest incidence (38.7 %) in those aged 80 + . Despite the initial decline, subsequent eGFR was stable over one year in all age groups. Factors such as age, lower hemoglobin, higher uric acid levels, and use of RAS blockers were linked to the initial dip. CONCLUSIONS: Older patients showed a more pronounced initial eGFR decline after starting SGLT2i, but it stabilized for one year without further deterioration, similar to younger patients.
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Diabetes Mellitus Tipo 2 , Tasa de Filtración Glomerular , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Tasa de Filtración Glomerular/efectos de los fármacos , Anciano , Masculino , Femenino , Persona de Mediana Edad , Anciano de 80 o más Años , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Factores de Edad , Nefropatías DiabéticasRESUMEN
BACKGROUND: Monogenic lupus is defined as systemic lupus erythematosus (SLE)/SLE-like patients with either dominantly or recessively inherited pathogenic variants in a single gene with high penetrance. However, because the clinical phenotype of monogenic SLE is extensive and overlaps with that of classical SLE, it causes a delay in diagnosis and treatment. Currently, there is a lack of early identification models for clinical practitioners to provide early clues for recognition. Our goal was to create a clinical model for the early identification of pediatric monogenic lupus, thereby facilitating early and precise diagnosis and treatment for patients. METHODS: This retrospective cohort study consisted of 41 cases of monogenic lupus treated at the Department of Pediatrics at Peking Union Medical College Hospital from June 2012 to December 2022. The control group consisted of classical SLE patients recruited at a 1:2 ratio. Patients were randomly divided into a training group and a validation group at a 7:3 ratio. A logistic regression model was established based on the least absolute shrinkage and selection operator to generate the coefficient plot. The predictive ability of the model was evaluated using receiver operator characteristic curves and the area under the curve (AUC) index. RESULTS: A total of 41 cases of monogenic lupus patients and 82 cases of classical SLE patients were included. Among the monogenic lupus cases (with a male-to-female ratio of 1:1.05 and ages of onset ranging from birth to 15 years), a total of 18 gene mutations were identified. The variables included in the coefficient plot were age of onset, recurrent infections, intracranial calcifications, growth and developmental delay, abnormal muscle tone, lymphadenopathy/hepatosplenomegaly, and chilblain-like skin rash. Our model demonstrated satisfactory diagnostic performance through internal validation, with an AUC value of 0.97 (95% confidence interval = 0.92-0.97). CONCLUSIONS: We summarized and analyzed the clinical characteristics of pediatric monogenic lupus and developed a predictive model for early identification by clinicians. Clinicians should exercise high vigilance for monogenic lupus when the score exceeds - 9.032299.
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Brown and brown-like adipose tissues have attracted significant attention for their role in metabolism and therapeutic potential in diabetes and obesity. Despite compelling evidence of an interplay between adipocytes and lymphocytes, the involvement of these tissues in immune responses remains largely unexplored. This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue. Leveraging the use of [18F]F-AraG, a mitochondrial metabolic tracer capable of tracking activated lymphocytes and adipocytes simultaneously, we demonstrate, in models of glioblastoma and multiple sclerosis, the correlation between intracerebral immune infiltration and changes in brown- and bone marrow adipose tissue. Significantly, we show initial evidence that a neuroinflammation-adipose tissue link may also exist in humans. This study proposes the concept of an intricate immuno-neuro-adipose circuit, and highlights brown- and bone marrow adipose tissue as an intermediary in the communication between the immune and nervous systems. Understanding the interconnectedness within this circuitry may lead to advancements in the treatment and management of various conditions, including cancer, neurodegenerative diseases and metabolic disorders.
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Tejido Adiposo Pardo , Enfermedades Neuroinflamatorias , Animales , Humanos , Tejido Adiposo Pardo/metabolismo , Enfermedades Neuroinflamatorias/inmunología , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/patología , Médula Ósea/metabolismo , Ratones , Masculino , Glioblastoma/patología , Glioblastoma/inmunología , Glioblastoma/metabolismo , Ratones Endogámicos C57BL , Femenino , Esclerosis Múltiple/patología , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/diagnóstico por imagen , Tomografía de Emisión de PositronesRESUMEN
The applications of polysaccharides as emulsifiers are limited due to the lack of hydrophobicity. However, traditional hydrophobic modification methods used for polysaccharides are complicated and involve significant mechanical and thermal losses. In this study, soy hull polysaccharide (SHP) and terminally aminopropylated polydimethylsiloxane (NPN) were selected to investigate the feasibility of a simple and green interfacial membrane strengthening strategy based on the interfacial polymerization of anionic polysaccharides and fat-soluble alkaline ligands. Our results show that deprotonated SHP and protonated NPN can be complexed at the water/oil (W/O) interface, reduce interfacial tension, and form a strong membrane structure. Moreover, they can quickly form a membrane at the W/O interface upon the moment of contact to produce stable all-liquid printing products with complex patterns. However, the molecular weight of NPN affects the complexation reaction. Consequently, this study has long-term implications to expanding the areas of application for anionic polysaccharides.
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Polisacáridos , Polisacáridos/química , Ligandos , Aniones/química , Membranas Artificiales , Agua/química , Dimetilpolisiloxanos/química , Glycine max/química , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
Medical image segmentation and registration are two fundamental and highly related tasks. However, current works focus on the mutual promotion between the two at the loss function level, ignoring the feature information generated by the encoder-decoder network during the task-specific feature mapping process and the potential inter-task feature relationship. This paper proposes a unified multi-task joint learning framework based on bi-fusion of structure and deformation at multi-scale, called BFM-Net, which simultaneously achieves the segmentation results and deformation field in a single-step estimation. BFM-Net consists of a segmentation subnetwork (SegNet), a registration subnetwork (RegNet), and the multi-task connection module (MTC). The MTC module is used to transfer the latent feature representation between segmentation and registration at multi-scale and link different tasks at the network architecture level, including the spatial attention fusion module (SAF), the multi-scale spatial attention fusion module (MSAF) and the velocity field fusion module (VFF). Extensive experiments on MR, CT and ultrasound images demonstrate the effectiveness of our approach. The MTC module can increase the Dice scores of segmentation and registration by 3.2%, 1.6%, 2.2%, and 6.2%, 4.5%, 3.0%, respectively. Compared with six state-of-the-art algorithms for segmentation and registration, BFM-Net can achieve superior performance in various modal images, fully demonstrating its effectiveness and generalization.
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BACKGROUND: The role of type I interferon (IFN-I) signaling in systemic lupus erythematosus (SLE) has been well established. However, unanswered questions remain regarding the applicability of these findings to pediatric-onset SLE. The aim of this review is to provide an overview of the novel discoveries on IFN-I signaling in pediatric-onset SLE. DATA SOURCES: A literature search was conducted in the PubMed database using the following keywords: "pediatric systemic lupus erythematosus" and "type I interferon". RESULTS: IFN-I signaling is increased in pediatric SLE, largely due to the presence of plasmacytoid dendritic cells and pathways such as cyclic GMP-AMP synthase-stimulator of interferon genes-TANK-binding kinase 1 and Toll-like receptor (TLR)4/TLR9. Neutrophil extracellular traps and oxidative DNA damage further stimulate IFN-I production. Genetic variants in IFN-I-related genes, such as IFN-regulatory factor 5 and tyrosine kinase 2, are linked to SLE susceptibility in pediatric patients. In addition, type I interferonopathies, characterized by sustained IFN-I activation, can mimic SLE symptoms and are thus important to distinguish. Studies on interferonopathies also contribute to exploring the pathogenesis of SLE. Measuring IFN-I activation is crucial for SLE diagnosis and stratification. Both IFN-stimulated gene expression and serum IFN-α2 levels are common indicators. Flow cytometry markers such as CD169 and galectin-9 are promising alternatives. Anti-IFN therapies, such as sifalimumab and anifrolumab, show promise in adult patients with SLE, but their efficacy in pediatric patients requires further investigation. Janus kinase inhibitors are another treatment option for severe pediatric SLE patients. CONCLUSIONS: This review presents an overview of the IFN-I pathway in pediatric SLE. Understanding the intricate relationship between IFN-I and pediatric SLE may help to identify potential diagnostic markers and targeted therapies, paving the way for improved patient care and outcomes.
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Interferón Tipo I , Lupus Eritematoso Sistémico , Transducción de Señal , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/diagnóstico , Interferón Tipo I/metabolismo , Interferón Tipo I/sangre , NiñoRESUMEN
We designed and prepared probe W-1 for the detection of H2O2. W-1 showed excellent selectivity for H2O2 and was accompanied by colorimetric signal changes. The excellent linear relationship between fluorescence intensity and H2O2 concentration (0-100 µM) provided favorable conditions for its quantitative detection. In addition, the combination of portable test strips with a smartphone platform provided great convenience for on-site visual detection of H2O2. Moreover, W-1 possessed targeting mitochondria property and could be applied to image the exogenous and endogenous H2O2 in cells to distinguish normal cells and cancer cells. Lastly, W-1 was used for monitoring the H2O2 fluctuation of the diabetic process in mice, and the results showed an increase in H2O2 levels in diabetes. Therefore, the probe provided a tool for understanding the pathological and physiological mechanisms of diabetes by imaging H2O2.
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Diabetes Mellitus Experimental , Colorantes Fluorescentes , Peróxido de Hidrógeno , Mitocondrias , Peróxido de Hidrógeno/metabolismo , Animales , Mitocondrias/metabolismo , Colorantes Fluorescentes/química , Ratones , Humanos , Colorimetría/métodos , Imagen Óptica/métodosAsunto(s)
Insuficiencia Cardíaca , Tumores Fibrosos Solitarios , Humanos , Tumores Fibrosos Solitarios/cirugía , Tumores Fibrosos Solitarios/diagnóstico por imagen , Tumores Fibrosos Solitarios/patología , Insuficiencia Cardíaca/etiología , Neoplasias Pélvicas/diagnóstico por imagen , Neoplasias Pélvicas/cirugía , Masculino , Femenino , Persona de Mediana EdadRESUMEN
BACKGROUND: The aim of this study was to establish a simple and practical grading system for evaluating the status of the sphincter of Oddi (SO) during intraoperative choledochoscopy. This system helps identify relevant variables that influence the status of the SO and provides recommendations for preventing stone recurrence. METHODS: Ninety-three patients were selected retrospectively from a total of 316 patients diagnosed with choledocholithiasis between July 2020 and June 2023. All patients underwent common bile duct (CBD) exploration surgery and intraoperative choledochoscopy. The status of the SO was assessed during choledochoscopy. According to the severity of the condition, the patients were categorized into 4 groups. Data from each group, grades 1, 2, 3, 4, was analyzed statistically. RESULTS: The number of patients in grade 1 was significantly lower than that of the other 3 groups. Except for grade 1, patients in grade 4 exhibited significant differences compared with the other 2 groups in terms of the diameter of the CBD, size of stones, presence of pneumobilia, and history of endoscopic retrograde cholangiopancreatography (ERCP) ( P <0.05). There were no significant differences between the groups in terms of sex, age, liver function, number of stones, history of gastrectomy, cholecystectomy, or CBD exploration. CONCLUSIONS: The grading system helps us classify different sphincter functions and better understand the formation of choledocholithiasis by subdividing the status of the SO. Endoscopic sphincterotomy (EST) treatment can easily result in the loss of SO function, which increases the risk of stone recurrence.
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Coledocolitiasis , Esfínter de la Ampolla Hepatopancreática , Humanos , Masculino , Femenino , Estudios Retrospectivos , Coledocolitiasis/cirugía , Persona de Mediana Edad , Esfínter de la Ampolla Hepatopancreática/cirugía , Esfínter de la Ampolla Hepatopancreática/fisiopatología , Anciano , Adulto , Cuidados Intraoperatorios/métodos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Endoscopía del Sistema Digestivo/métodos , Índice de Severidad de la Enfermedad , Esfinterotomía Endoscópica/métodosRESUMEN
Accurately reconstructing 4D critical organs contributes to the visual guidance in X-ray image-guided interventional operation. Current methods estimate intraoperative dynamic meshes by refining a static initial organ mesh from the semantic information in the single-frame X-ray images. However, these methods fall short of reconstructing an accurate and smooth organ sequence due to the distinct respiratory patterns between the initial mesh and X-ray image. To overcome this limitation, we propose a novel dual-stage complementary 4D organ reconstruction (DSC-Recon) model for recovering dynamic organ meshes by utilizing the preoperative and intraoperative data with different respiratory patterns. DSC-Recon is structured as a dual-stage framework: 1) The first stage focuses on addressing a flexible interpolation network applicable to multiple respiratory patterns, which could generate dynamic shape sequences between any pair of preoperative 3D meshes segmented from CT scans. 2) In the second stage, we present a deformation network to take the generated dynamic shape sequence as the initial prior and explore the discriminate feature (i.e., target organ areas and meaningful motion information) in the intraoperative X-ray images, predicting the deformed mesh by introducing a designed feature mapping pipeline integrated into the initialized shape refinement process. Experiments on simulated and clinical datasets demonstrate the superiority of our method over state-of-the-art methods in both quantitative and qualitative aspects.
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Nested entities and relationship extraction are two tasks for analysis of electronic medical records. However, most of existing medical information extraction models consider these tasks separately, resulting in a lack of consistency between them. In this paper, we propose a joint medical entity-relation extraction model with progressive recognition and targeted assignment (PRTA). Entities and relations share the information of sequence and word embedding layers in the joint decoding stage. They are trained simultaneously and realize information interaction by updating the shared parameters. Specifically, we design a compound triangle strategy for the nested entity recognition and an adaptive multi-space interactive strategy for relationship extraction. Then, we construct a parameter-shared information space based on semantic continuity to decode entities and relationships. Extensive experiments were conducted on the Private Liver Disease Dataset (PLDD) provided by Beijing Friendship Hospital of Capital Medical University and public datasets (NYT, ACE04 and ACE05). The results show that our method outperforms existing SOTA methods in most indicators, and effectively handles nested entities and overlapping relationships.
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Registros Electrónicos de Salud , Humanos , Minería de Datos/métodos , Algoritmos , Bases de Datos Factuales , HepatopatíasRESUMEN
Mesoporous silica microspheres (MSMs) possess poor biocompatibility. This study focuses on integrating MSMs with polymers to obtain hybrid materials with superior performance compared to the individual components and responsive release in specific environments. The synthesized MSMs were aminated, and subsequently, soybean hull polysaccharide (SHPs) was modified onto MSMs-NH2 to produce MSMs-NH2@SHPs nanoparticles. The encapsulation rate, loading rate of curcumin (Cur), and in vitro release behavior were investigated. Results indicated that the encapsulation efficiency of Cur by MSMs-NH2@SHPs nanoparticles reached 75.58%, 6.95 times that of MSMs-NH2 with a load capacity of 35.12%. It is noteworthy that these nanoparticles exhibit pH-responsive release capacity in vitro. The cumulative release rate of the three nanoparticles at pH 5.0 was higher than that at pH 7.4. MSMs-NH2@SHPs had a cumulative release rate of 56.55% at pH 7.4, increasing to 76.21% at pH 5.0. In vitro experiments have shown that MSMs-based nanoparticles have high delivery efficiency and can achieve pH-sensitive drug release, with a high release rate in a slightly acidic acid, highlighting the potential for controlled release of Cur.