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Fibroblast activation protein-α (FAP) plays a crucial role in various physiological and pathological processes, making it a key target for cancer diagnostics and therapeutics. However, in vivo detection of FAP activity with fluorogenic probes remains challenging due to the rapid diffusion and clearance of fluorescent products from the target. Herein, we developed a self-immobilizing near-infrared (NIR) fluorogenic probe, Hcy-CF2H-PG, by introducing a difluoromethyl group to FAP substrate-caged NIR fluorophore. Upon selective activation by FAP, the fluorescence of Hcy-CF2H-PG was triggered, followed by the covalent labelling of FAP. Hcy-CF2H-PG demonstrated significantly improved sensitivity, selectivity, and long-lasting labelling capacity for FAP both in vitro and in vivo, compared to that of non-immobilized probes. This represents a noteworthy advancement in FAP detection and cancer diagnostics within complex physiological systems.
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Endopeptidasas , Colorantes Fluorescentes , Gelatinasas , Proteínas de la Membrana , Serina Endopeptidasas , Colorantes Fluorescentes/química , Animales , Humanos , Proteínas de la Membrana/análisis , Proteínas de la Membrana/metabolismo , Gelatinasas/metabolismo , Endopeptidasas/metabolismo , Serina Endopeptidasas/metabolismo , Serina Endopeptidasas/análisis , Rayos Infrarrojos , Ratones , Imagen ÓpticaRESUMEN
Terminally ill patients face multiple difficulties in home care.Home-based palliative care adhering to the concept of whole-person,whole-family,whole-team,and whole-course care is able to meet the needs of terminally ill patients and their families.In this paper,we reported the care history and home-based palliative care process of a patient with end-stage breast tumor and summarized the experience,aiming to provide reference for the future work of home-based palliative care.
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Cuidados Paliativos , HumanosRESUMEN
AIM: To compare the surgical outcomes of glaucoma drainage device implantation (GDI) and trans-scleral neodymium:YAG cyclophotocoagulation (CPC) in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty (DSAEK). METHODS: This retrospective study on observational case series enrolled 29 patients who underwent DSAEK and posterior anti-glaucoma surgery (15 with GDI and 14 with CPC). The main outcome measures were intraocular pressure (IOP), glaucoma surgery success rate (defined as IOP of 6-21 mm Hg without additional anti-glaucoma operation), number of glaucoma medications, endothelial graft status, and best-corrected visual acuity (BCVA). RESULTS: The mean follow-up time was 34.1 and 21.0mo for DSAEK or glaucoma surgeries, both for the GDI and CPC groups. Both groups showed significant IOP reduction after glaucoma surgery. The GDI group presented a significantly higher success rate in IOP control than the CPC group (60% vs 21.4%, P=0.03). Both procedures significantly decreased the number of glaucoma medications (P=0.03). Forty percent and 57% of cases in the GDI and the CPC group, respectively, experienced endothelial graft failure during follow-up (P=0.36). Significantly worse BCVA after surgery was observed in the CPC group but not in the GDI group. CONCLUSION: Both GDI and CPC significantly decrease IOP in eyes with glaucoma after DSAEK. GDI is preferable to CPC in refractory glaucoma cases after DSAEK, as it manifests a significantly higher success rate for IOP control, similar endothelial graft failure rate, and relatively preserves BCVA than CPC.
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It is generally believed that mycorrhiza is a microecosystem composed of mycorrhizal fungi, host plants and other microscopic organisms. The mycorrhiza of Rhododendron dauricum is more complex and the diverse morphology of our investigated results displays both typical ericoid mycorrhizal characteristics and ectomycorrhizal traits. The characteristics of ectendoomycorrhiza, where mycelial invade from the outside into the root cells, have also been observed. In order to further clarify the mycorrhizal fungi members and other fungal communities of R. dauricum mycorrhiza, and explore the effects of vegetation and soil biological factors on their community structure, we selected two woodlands in the northeast of China as samples-one is a mixed forest of R. dauricum and Quercus mongolica, and the other a mixed forest of R. dauricum, Q. mongolica, and Pinus densiflor. The sampling time was during the local growing season, from June to September. High-throughput sequencing yielded a total of 3020 fungal amplicon sequence variants (ASVs), which were based on sequencing of the internal transcribed spacer ribosomal RNA (ITS rRNA) via the Illumina NovaSeq platform. In the different habitats of R. dauricum, there are differences in the diversity of fungi obtained from mycorrhizal niches, and specifically the mycorrhizal fungal community structure in the complex vegetation of mixed forests, where R. dauricum is found, exhibits greater stability, with relatively minor changes over time. Soil fungi are identified as the primary source of fungi within the mycorrhizal niche, and the abundance of mycorrhizal fungi from mycorrhizal niches in R. dauricum is significantly influenced by soil pH, organic matter, and available nitrogen. The relationship between soil fungi and mycorrhizal fungi from mycorrhizal niches is simultaneously found to be intricate, while the genus Hydnellum emerges as a central genus among mycorrhizal fungi from mycorrhizal niches. However, there is currently a substantial gap in the foundational research of this genus, including the fact that mycorrhizal fungi from mycorrhizal niches have, compared to fungi present in the soil, proven to be more sensitive to changes in soil moisture.
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OBJECTIVE: Microvascular invasion (MVI) is an independent risk factor for the early recurrence and poor survival of hepatocellular carcinoma (HCC). This study aims to investigate the potential clinical value of dynamic contrast-enhanced ultrasound (DCE-ultrasound)-Sonazoid in pre-operatively assessing MVI in HCC. METHODS AND MATERIALS: This single centre prospective study included 140 patients with histopathologically confirmed single HCC lesions. Patients were classified according to the post-operative pathological information presence of MVI: MVI+ group (n = 32) and MVI- group (n = 108). All patients underwent DCE-ultrasound within 1 week before surgery. The quantitative perfusion parameters of HCC lesions, margins of HCC lesions, and distal liver parenchyma were obtained and analyzed. RESULTS: Clinicopathological (serum alpha-fetoprotein, Des-gamma-carboxyprothrombin, and pathological grade) and grayscale imaging features (tumor size) were significantly different between the MVI+ and MVI- groups (p < 0.05). Further quantitative analysis showed that when comparing the MVI+ and MVI- groups, half-decrease time and wash-out rate of HCC lesions and peak enhancement in the arterial phase of difference between the margin area of HCC and distal liver parenchyma were significantly different (p = 0.045, p = 0.035, and p = 0.023, respectively). Combining the above three quantitative parameters, the accuracy, sensitivity, specificity, positive-predictive value, and negative-predictive value were 69.3% (97/140), 37.8% (17/45), 84.3% (80/95), 53.1% (17/32), 74.1% (80/108), respectively. CONCLUSION: DCE-ultrasound with quantitative perfusion analysis has the potential to predict MVI in HCC lesions. ADVANCES IN KNOWLEDGE: DCE-ultrasound with quantitative perfusion analysis has the potential to predict MVI in HCC lesions.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Estudios Prospectivos , Estudios Retrospectivos , Invasividad Neoplásica , Ultrasonografía/métodosRESUMEN
Optical imaging holds great promise for monitoring bacterial infectious processes and drug resistance with high temporal-spatial resolution. Currently, the diagnosis of deep-seated bacterial infections in vivo with fluorescence imaging, including near-infrared (NIR) fluorescence imaging technology, remains a significant challenge due to its limited tissue penetration depth. In this study, we developed a highly specific targeting probe, Cy7-Neo-NO2, by conjugating a bacterial 16S rRNA-targeted moiety, neomycin, with a bacterial nitroreductase (NTR)-activated NIR photoacoustic (PA) scaffold using our previously developed caged photoinduced electron transfer (a-PeT) approach. This conjugation effectively resolved probe aggregation issues in physiological conditions and substantially enhanced its reactivity toward bacterial NTR. Notably, Cy7-Neo-NO2 enabled the first in situ photoacoustic imaging of pneumonia induced by methicillin-resistant Staphylococcus aureus (MRSA), as well as the detection of bacteria within tumors. Furthermore, upon NIR irradiation, Cy7-Neo-NO2 successfully inhibited MRSA growth through a synergistic effect combining photothermal therapy and photodynamic therapy. Our results provided an effective tool for obtaining exceptional PA agents for accurate diagnosis, therapeutic evaluation of deep-seated bacterial infections in vivo, and intratumoral bacteria-specific recognition.
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Continuously recording the dynamic changes of circulating tumor cells (CTCs) is crucial for tumor metastasis. This paper creates a continuous magnetic separation microfluidic chip that enables rapid and continuous in vivo cell detection. The chip shows its potential to study tumor cell circulation in the blood, offering a new platform for studying the cellular mechanism of tumor metastasis.
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MicroRNAs (miRNAs) are a class of non-coding single-stranded RNA molecules about 22 nucleotides in length and are encoded by endogenous genes, and are involved in the regulation of post-transcriptional gene expression in animals and plants. Many studies have shown that microRNAs regulate the development of skeletal muscle, mainly manifested in the activation of muscle satellite cells and biological processes such as proliferation, differentiation, and formation of muscle tubes. In this study, miRNA sequencing screening of longissimus dorsi (LD, mainly fast-twitch fibers) and soleus muscle (Sol, dominated by slow-twitch fibers) identified the miR-196b-5p as a differentially expressed and highly conserved sequence in different skeletal muscles. Studies of miR-196b-5p in skeletal muscle have not been reported. In this study, miR-196b-5p mimics and inhibitor were used in miR-196b-5p overexpression and interference experiments in C2C12 cells. The effect of miR-196b-5p on myoblast proliferation and differentiation was analyzed by western blotting, real-time quantitative RT-PCR, flow cytometry, immunofluorescence staining, and the target gene of miR-196b-5p was identified by bioinformatics prediction and analyzed by dual luciferase reporter assays. The results showed that overexpression of miR-196b-5p could significantly increase the mRNA and protein expression of Cyclin B, Cyclin D and Cyclin E (P<0.05); Cell cycle analysis showed that overexpression of miR-196b-5p significantly increased the proportion of cells in the S phase (P<0.05), indicating that miR-196b-5p could accelerate cell cycle progress. Results of EdU staining showed that overexpression of miR-196b-5p significantly promoted cell proliferation. Conversely, inhibition of miR-196b-5p expression could significantly reduce the proliferation capacity of myoblasts. Further, overexpression of miR-196b-5p could significantly increase the expression levels of myogenic marker genes MyoD, MoyG and MyHC (P<0.05), thereby promoting myoblast fusion and accelerating C2C12 cell differentiation. Bioinformatics predictions and dual luciferase experiments demonstrated that miR-196b-5p could target and inhibit the expression of the Sirt1 gene. Altering the Sirt1 expression could not rescue the effects of miR-196b-5p on the cell cycle, but could weaken the promoting effects of miR-196b-5p on myoblast differentiation, suggesting that miR-196b-5p promoted myoblast differentiation by targeting Sirt1.
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Diferenciación Celular , Proliferación Celular , Mioblastos , Animales , Ratones , Línea Celular , MicroARNs/genética , Mioblastos/citología , Mioblastos/metabolismoRESUMEN
Damage to peritubular capillaries is a key process that contributes to acute kidney injury (AKI) progression. Vascular endothelial growth factor A (VEGFA) plays a critical role in maintaining the renal microvasculature. However, the physiological role of VEGFA in various AKI durations remains unclear. A severe unilateral ischemiaâreperfusion injury model was established to provide an overview of VEGFA expression and the peritubular microvascular density from acute to chronic injury in mouse kidneys. Therapeutic strategies involving early VEGFA supplementation protecting against acute injury and late anti-VEGFA treatment for fibrosis alleviation were analyzed. A proteomic analysis was conducted to determine the potential mechanism of renal fibrosis alleviation by anti-VEGFA. The results showed that two peaks of extraglomerular VEGFA expression were observed during AKI progression: one occurred at the early phase of AKI, and the other occurred during the transition to chronic kidney disease (CKD). Capillary rarefaction progressed despite the high expression of VEGFA at the CKD stage, and VEGFA was associated with interstitial fibrosis. Early VEGFA supplementation protected against renal injury by preserving microvessel structures and counteracting secondary tubular hypoxic insults, whereas late anti-VEGFA treatment attenuated renal fibrosis progression. The proteomic analysis highlighted an array of biological processes related to fibrosis alleviation by anti-VEGFA, which included regulation of supramolecular fiber organization, cell-matrix adhesion, fibroblast migration, and vasculogenesis. These findings establish the landscape of VEGFA expression and its dual roles during AKI progression, which provides the possibility for the orderly regulation of VEGFA to alleviate early acute injury and late fibrosis.
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Lesión Renal Aguda , Insuficiencia Renal Crónica , Ratones , Animales , Factor A de Crecimiento Endotelial Vascular , Proteómica , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , FibrosisRESUMEN
Fluorescence-guided surgery (FGS) with tumor-targeted imaging agents, particularly those using the near-infrared wavelength, has emerged as a real-time technique to highlight the tumor location and margins during a surgical procedure. For accurate visualization of prostate cancer (PCa) boundary and lymphatic metastasis, we developed a new approach involving an efficient self-quenched near-infrared fluorescence probe, Cy-KUE-OA, with dual PCa-membrane affinity. Cy-KUE-OA specifically targeted the prostate-specific membrane antigen (PSMA), anchored into the phospholipids of the cell membrane of PCa cells and consequently showed a strong Cy7-de-quenching effect. This dual-membrane-targeting probe allowed us to detect PSMA-expressing PCa cells both in vitro and in vivo and enabled clear visualization of the tumor boundary during fluorescence-guided laparoscopic surgery in PCa mouse models. Furthermore, the high PCa preference of Cy-KUE-OA was confirmed on surgically resected patient specimens of healthy tissues, PCa, and lymph node metastases. Taken together, our results serve as a bridge between preclinical and clinical research in FGS of PCa and lay a solid foundation for further clinical research.
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BACKGROUND: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is still under investigation as adjuvant treatment for early-stage disease. Here, we performed a meta-analysis to evaluate the efficacy of adjuvant EGFR-TKI versus non-EGFR-TKI treatment in patients with completely resected non-small cell lung cancer (NSCLC) harboring EGFR mutation. METHODS: Two investigators independently extracted data from databases. A meta-analysis was performed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The protocol was registered in PROSPERO (ID: CRD42022316481). The primary outcome was disease-free survival (DFS) in patients with EGFR mutation, measured as the hazard ratio (HR). Other outcomes (of subgroup analyses) included overall survival (OS) and DFS. RESULTS: After the systematic screening, eight studies with a total of 3098 patients with stage IB-IIIA NSCLC were included. The results show that in patients with EGFR mutation, the DFS in the adjuvant EGFR-TKI group was significantly superior to that in the control group, with a HR of 0.47 (95% confidence interval [CI]: 0.30-0.74; P = 0.001). In subgroup analyses of DFS, the benefit was observed in the EGFR-TKI group versus the chemotherapy group (HR 0.50, 95% CI 0.30-0.84; P = 0.009), the EGFR-TKI combined with chemotherapy group versus the chemotherapy group (HR 0.37, 95% CI 0.16-0.85; P = 0.02), and in stage IIA-IIIA NSCLC (HR 0.45, 95% CI 0.27-0.74; P = 0.002). However, the benefit of DFS did not translate into improved OS in the whole population (HR 0.79, 95% CI 0.54-1.14; P = 0.20). CONCLUSION: EGFR-TKIs prolonged DFS but not OS in patients with completely resected stage II-IIIA NSCLC harboring EGFR mutation. Longer follow-ups and new clinical trials that can result in changes in clinical practice are needed.
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Humanos , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Receptores ErbB/antagonistas & inhibidores , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Mutación , Ensayos Clínicos Controlados Aleatorios como Asunto , /uso terapéuticoRESUMEN
The use of efficient and clean methods for the recycling of waste circuit boards is an ongoing challenge. In this research, the effect of microwave pretreatment on the leaching and enrichment of copper from waste print circuit board (WPCB) was studied. The morphology and chemical structure of WPCB particles before and after microwave pretreatment were analyzed by SEM/EDS and Fourier infrared spectroscopy. Leaching experiments and copper enrichment tests were designed to investigate the effect of different microwave irradiation powers and microwave irradiation times on the copper leaching rate and copper enrichment rate in WPCB. The leaching experiment results showed that microwave pretreatment can effectively improve the leaching rate of WPCB. When the microwave irradiation power was 700 W, the irradiation time was 120 s, and the leaching time was 15 min, the copper leaching rate in WPCB was 57.01%, which was 24.34% higher than that in the untreated condition. The results of copper enrichment experiment show that microwave pretreatment can effectively improve the copper enrichment of WPCB. After microwave pretreatment, copper was effectively enriched in the 4-2 and 2-1 mm particle sizes. When the microwave irradiation time was 120 s, the copper enrichment rates in the 4-2 and 2-1 mm particle sizes were 1.74 and 1.66, which increased by 0.63 and 0.32, respectively, compared to the untreated condition. Microwave pretreatment enables the effective separation of metallic copper from non-metallic components in WPCB, increasing the exposure area of copper and promoting the monomer separation of copper, thus improving the leaching and enrichment of copper.
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BACKGROUND: It is found that there are great differences in the efficacy of quetiapine at the same dose in many patients with bipolar disorders. Therefore, therapeutic drug monitoring (TDM) is a valuable tool for guiding treatment with quetiapine. The aims of this study were to assess the relationship between serum concentration and clinical response of quetiapine in adolescents and adults with bipolar disorders in acute stage. METHODS: The study design was prospective and observational. Within the naturalistic setting of a routine TDM service at the First Affiliated Hospital, Zhejiang University School of Medicine. Psychiatric symptoms were assessed using the HAMD (Hamilton Depression Scale), YRMS (Young manic rating scale) and CUDOS-M (Clinically Useful Depression Outcome Scale-Mixed Subscale). The decline of HAMD and YMRS scores was were used to assess clinical outcome of bipolar disorders respectively. RESULTS: 169 inpatients (23.7 % male, 76.3 % female) were enrolled in the study. We found that there was a strong correlation between quetiapine serum concentrations and clinical outcomes (rs = 0.702, p < 0.001). While, quetiapine daily dose was not correlated with clinical outcome. We found that when the quetiapine serum level is >146.85 ng/ml in depression episodes patients could obtain a satisfactory treatment effect after 2 weeks of hospitalization. CONCLUSIONS: We found a significant positive relationship between serum concentration and clinical outcome, and also determined the serum concentration of quetiapine for the treatment of bipolar depression.
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Antipsicóticos , Trastorno Bipolar , Humanos , Masculino , Adulto , Femenino , Adolescente , Fumarato de Quetiapina/uso terapéutico , Trastorno Bipolar/psicología , Antipsicóticos/uso terapéutico , Estudios Prospectivos , Dibenzotiazepinas/uso terapéutico , Resultado del Tratamiento , Método Doble Ciego , Escalas de Valoración PsiquiátricaRESUMEN
Acute kidney injury (AKI) refers to a group of common clinical syndromes characterized by acute renal dysfunction, which may lead to chronic kidney disease (CKD), and this process is called the AKI-CKD transition. The transcriptional coactivator YAP can promote the AKI-CKD transition by regulating the expression of profibrotic factors, and 14-3-3 protein zeta (14-3-3ζ), an important regulatory protein of YAP, may prevent the AKI-CKD transition. We established an AKI-CKD model in mice by unilateral renal ischemia-reperfusion injury and overexpressed 14-3-3ζ in mice using a fluid dynamics-based gene transfection technique. We also overexpressed and knocked down 14-3-3ζ in vitro. In AKI-CKD model mice, 14-3-3ζ expression was significantly increased at the AKI stage. During the development of chronic disease, the expression of 14-3-3ζ tended to decrease, whereas active YAP was consistently overexpressed. In vitro, we found that 14-3-3ζ can combine with YAP, promote the phosphorylation of YAP, inhibit YAP nuclear translocation, and reduce the expression of fibrosis-related proteins. In an in vivo intervention experiment, we found that the overexpression of 14-3-3ζ slowed the process of renal fibrosis in a mouse model of AKI-CKD. These findings suggest that 14-3-3ζ can affect the expression of fibrosis-related proteins by regulating YAP, inhibit the maladaptive repair of renal tubular epithelial cells, and prevent the AKI-CKD transition.
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Lesión Renal Aguda , Insuficiencia Renal Crónica , Daño por Reperfusión , Ratones , Animales , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo , Riñón/patología , Insuficiencia Renal Crónica/metabolismo , Lesión Renal Aguda/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Fibrosis , Daño por Reperfusión/patologíaRESUMEN
BACKGROUND: Patients with pancreatic cancer-caused biliary obstruction (PC-BO) have poor prognosis, but we lack of tools to predict survival for clinical decision-making. This study aims to establish a model for survival prediction among patients with PC-BO. METHODS: A total of 172 patients with PC-BO treated with percutaneous biliary drainage were randomly divided into a training group (n = 120) and a validation group (n = 52). The independent risk factors for overall survival were selected to develop a Cox model. The predictive performance of M stage, hepatic metastases, cancer antigen 199, and the Cox model was determined. Naples prognostic score (NPS), the prognostic nutritional index (PNI), and the controlling nutritional status (CONUT) for 1-month mortality risk were compared with the Cox model. RESULTS: The Cox model was developed based on total cholesterol, direct bilirubin, hepatic metastases, cancer antigen 199, stenosis type, and preprocedural infection (all P < 0.05), which named "COMBO-PaS." The COMBO-PaS model had the highest area under the curves (AUC) (0.801-0.933) comparing with other predictors (0.506-0.740) for 1-, 3-, and 6-month survival prediction. For 1-month mortality risk prediction, the COMBO-PaS model had the highest AUC of 0.829 comparing with NPS, PNI, and CONUT. CONCLUSION: The COMBO-PaS model was useful for survival prediction among patients with PC-BO.
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Colestasis , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Pronóstico , Neoplasias Pancreáticas/complicaciones , Colestasis/etiología , Colestasis/cirugía , Neoplasias Hepáticas/complicaciones , Drenaje/efectos adversos , Estudios Retrospectivos , Neoplasias PancreáticasRESUMEN
The aim of this prospective study was to compare the diagnostic accuracy of oral contrast-enhanced transabdominal ultrasound imaging (OCTU) with that of contrast-enhanced computed tomography (CT) for the pre-operative tumor staging of gastric cancer, with post-operative pathology as the standard. We included 108 cases of gastric cancer with simultaneous OCTU and enhanced CT pre-operative tumor staging diagnoses. Results were compared with post-operative pathology based on the eighth edition of the American Joint Committee on Cancer tumor-node-metastasis staging guidelines for gastric cancer. The accuracy of each tumor stage was obtained by comparing OCTU and enhanced CT diagnoses with post-operative pathology. The McNemar test was used to compare the overall accuracy of the two methods. There was no statistical difference in accuracy between OCTU (72.2%) and enhanced CT (75.9%, p = 0.644) for overall pre-operative tumor staging diagnosis. For stages T1 to T4, the accuracy rates of OCTU were 84.2%, 81.8%, 69.4% and 65.5%, respectively, and those for enhanced CT were 52.6%, 72.7%, 87.8% and 72.4%, respectively. OCTU is comparable to enhanced CT in the preoperative overall T-stage diagnosis of gastric cancer.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/cirugía , Estadificación de Neoplasias , Estudios Prospectivos , Tomografía Computarizada por Rayos X/métodos , UltrasonografíaRESUMEN
Synaptic plasticity enhances or reduces connections between neurons, affecting learning and memory. Postsynaptic AMPARs mediate greater than 90% of the rapid excitatory synaptic transmission in glutamatergic neurons. The number and subunit composition of AMPARs are fundamental to synaptic plasticity and the formation of entire neural networks. Accordingly, the insertion and functionalization of AMPARs at the postsynaptic membrane have become a core issue related to neural circuit formation and information processing in the central nervous system. In this review, we summarize current knowledge regarding the related mechanisms of AMPAR expression and trafficking. The proteins related to AMPAR trafficking are discussed in detail, including vesicle-related proteins, cytoskeletal proteins, synaptic proteins, and protein kinases. Furthermore, significant emphasis was placed on the pivotal role of the actin cytoskeleton, which spans throughout the entire transport process in AMPAR transport, indicating that the actin cytoskeleton may serve as a fundamental basis for AMPAR trafficking. Additionally, we summarize the proteases involved in AMPAR post-translational modifications. Moreover, we provide an overview of AMPAR transport and localization to the postsynaptic membrane. Understanding the assembly, trafficking, and dynamic synaptic expression mechanisms of AMPAR may provide valuable insights into the cognitive decline associated with neurodegenerative diseases.
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Depresores del Sistema Nervioso Central , Receptores AMPA , Sistema Nervioso Central , Neuronas , Cognición , AprendizajeRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. AIM: To predict early recurrence (ER) and overall survival (OS) in patients with HCC after radical resection using deep learning-based radiomics (DLR). METHODS: A total of 414 consecutive patients with HCC who underwent surgical resection with available preoperative grayscale and contrast-enhanced ultrasound images were enrolled. The clinical, DLR, and clinical + DLR models were then designed to predict ER and OS. RESULTS: The DLR model for predicting ER showed satisfactory clinical benefits [area under the curve (AUC)] = 0.819 and 0.568 in the training and testing cohorts, respectively), similar to the clinical model (AUC = 0.580 and 0.520 in the training and testing cohorts, respectively; P > 0.05). The C-index of the clinical + DLR model in the prediction of OS in the training and testing cohorts was 0.800 and 0.759, respectively. The clinical + DLR model and the DLR model outperformed the clinical model in the training and testing cohorts (P < 0.001 for all). We divided patients into four categories by dichotomizing predicted ER and OS. For patients in class 1 (high ER rate and low risk of OS), retreatment (microwave ablation) after recurrence was associated with improved survival (hazard ratio = 7.895, P = 0.005). CONCLUSION: Compared to the clinical model, the clinical + DLR model significantly improves the accuracy of predicting OS in HCC patients after radical resection.
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The prevalence of neurodevelopment disorders (NDDs) among children has been on the rise. This has affected the health and social life of children. This condition has also imposed a huge economic burden on families and health care systems. Currently, it is difficult to perform early diagnosis of NDDs, which results in delayed intervention. For this reason, patients with NDDs have a prognosis. In recent years, machine learning (ML) technology, which integrates artificial intelligence technology and medicine, has been applied in the early detection and prediction of diseases based on data mining. This paper reviews the progress made in the application of ML in the diagnosis and treatment of NDDs in children based on supervised and unsupervised learning tools. The data reviewed here provide new perspectives on early diagnosis and treatment of NDDs.
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AIM: To compare the ciliary body thickness between eyes with primary angle closure (PAC) and primary angle-closure glaucoma (PACG) with the normal eyes, and to investigate the association between ciliary body thickness and ciliary processes situation. METHODS: In this cross-sectional study, 57 patients with PAC/PACG were matched to 57 normal subjects after propensity score matching (PSM) adjusting for age and gender. All subjects underwent conventional ocular examinations and ultrasound biomicroscopy (UBM) examination, among which the patients with PAC/PACG performed the examinations one month after laser peripheral iridotomy (LPI). Quantitative parameters were measured, which included ciliary body thickness at the position of 1 mm posterior to the scleral spur (CBT1), trabecular-ciliary process distance (TCPD) and trabecular-ciliary process angle (TCA). RESULTS: Eyes with PAC/PACG presented significantly thinner CBT1, shorter TCPD and smaller TCA (P<0.001) than the normal eyes, both in comparison of the means of four quadrants and in comparisons of each quadrant. After removing images with peripheral anterior synechia (PAS), the same results were also found in comparisons between the two groups. Significant correlations were found between TCPD (R 2=0.537, P<0.001) and TCA (R 2=0.517, P<0.001) with CBT1. CONCLUSION: Eyes with PAC/PACG have thinner ciliary body thickness and more anteriorly situated ciliary processes. Thinner ciliary body thickness is associated with anterior situation of the ciliary processes.