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The dysregulation of Angiotensin-converting enzyme 2 (ACE2) in central nervous system is believed associates with COVID-19 induced cognitive dysfunction. However, the detailed mechanism remains largely unknown. In this study, we performed a comprehensive system genetics analysis on hippocampal ACE2 based on BXD mice panel. Expression quantitative trait loci (eQTLs) mapping showed that Ace2 was strongly trans-regulated, and the elevation of Ace2 expression level was significantly correlated with impaired cognitive functions. Further Gene co-expression analysis showed that Ace2 may be correlated with the membrane proteins in Calcium signaling pathway. Further, qRT-PCR confirmed that SARS-CoV-2 spike S1 protein upregulated ACE2 expression together with eight membrane proteins in Calcium Signaling pathway. Moreover, such elevation can be attenuated by recombinant ACE2. Collectively, our findings revealed a potential mechanism of Ace2 in cognitive dysfunction, which could be beneficial for COVID-19-induced cognitive dysfunction prevention and potential treatment.
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The kagome spin ice can host frustrated magnetic excitations by flipping its local spin. Under an inelastic tunneling condition, the tip in a scanning tunneling microscope can flip the local spin, and we apply this technique to kagome metal HoAgGe with a long-range ordered spin ice ground state. Away from defects, we discover a pair of pronounced dips in the local tunneling spectrum at symmetrical bias voltages with negative intensity values, serving as a striking inelastic tunneling signal. This signal disappears above the spin ice formation temperature and has a dependence on the magnetic fields, demonstrating its intimate relation with the spin ice magnetism. We provide a two-level spin-flip model to explain the tunneling dips considering the spin ice magnetism under spin-orbit coupling. Our results uncover a local emergent excitation of spin ice magnetism in a kagome metal, suggesting that local electrical field induced spin flip climbs over a barrier caused by spin-orbital locking.
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BACKGROUND: Adverse drug reactions (ADRs) refer to an unintended harmful reaction that occurs after the administration of a medication for therapeutic purposes, which is unrelated to the intended pharmacological action of the drug. In the United States, ADRs account for 6% of all hospital admissions annually. The cost of ADR-related illnesses in 2016 was estimated at USD 528.4 billion. Increasing the awareness of ADRs is an effective measure to prevent them. Assessing suspected drugs in adverse events helps to enhance the awareness of ADRs. METHODS: In this study, a suspect drug assisted judgment model (SDAJM) is designed to identify suspected drugs in adverse events. This framework utilizes the graph isomorphism network (GIN) and an attention mechanism to extract features based on patients' demographic information, drug information, and ADR information. RESULTS: By comparing it with other models, the results of various tests show that this model performs well in predicting the suspected drugs in adverse reaction events. ADR signal detection was conducted on a group of cardiovascular system drugs, and case analyses were performed on two classic drugs, Mexiletine and Captopril, as well as on two classic antithyroid drugs. The results indicate that the model can accomplish the task of predicting drug ADRs. Validation using benchmark datasets from ten drug discovery domains shows that the model is applicable to classification tasks on the Tox21 and SIDER datasets. CONCLUSIONS: This study applies deep learning methods to construct the SDAJM model for three purposes: (1) identifying drugs suspected to cause adverse drug events (ADEs), (2) predicting the ADRs of drugs, and (3) other drug discovery tasks. The results indicate that this method can offer new directions for research in the field of ADRs.
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Classical swine fever (CSF) is caused by the classical swine fever virus (CSFV), which poses a threat to swine production. The activation of host innate immunity through linker proteins such as tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) is crucial for the induction of the NF-κB pathway. Recent research has revealed the involvement of mitochondrial antiviral-signaling protein (MAVS) in the interaction with TRAF2, 3, 5, and 6 to activate both the NF-κB and IRF3 pathways. This study revealed that CSFV infection led to the upregulation of TRAF1 mRNA and protein levels; moreover, TRAF1 overexpression inhibited CSFV replication, while TRAF1 knockdown promoted replication, highlighting its importance in the host response to CSFV infection. Additionally, the expression of RIG-I, MAVS, TRAF1, IRF1, and ISG15 were detected in PK-15 cells infected with CSFV, revealing that TRAF1 plays a role in regulating IRF1 and ISG15 within the RIG-I pathway. Furthermore, Co-IP, GST pull-down, and IFA analyses demonstrated that TRAF1 interacted with MAVS and co-localized in the cytoplasm during CSFV infection. Ultimately, TRAF1 acted as a novel member of the TRAF family, bound to MAVS as a linker molecule, and functioned as a mediator downstream of MAVS in the RIG-I/MAVS pathway against CSFV replication.
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Proteínas Adaptadoras de Transdução de Sinal , Vírus da Febre Suína Clássica , Fator Regulador 1 de Interferon , Fator 1 Associado a Receptor de TNF , Regulação para Cima , Animais , Vírus da Febre Suína Clássica/fisiologia , Fator 1 Associado a Receptor de TNF/metabolismo , Fator 1 Associado a Receptor de TNF/genética , Suínos , Regulação para Cima/genética , Fator Regulador 1 de Interferon/metabolismo , Fator Regulador 1 de Interferon/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Transdução de Sinais , Peste Suína Clássica/virologia , Peste Suína Clássica/metabolismo , Peste Suína Clássica/genética , Replicação Viral , Linhagem Celular , Citocinas/metabolismo , Ligação ProteicaRESUMO
Objective: The prognosis of malignant tumors with peritoneal metastases and cancerous ascites has generally been poor, with limited treatment options. The PRaG regimen, which comprised of hypofractionated radiotherapy, programmed cell death-1 (PD-1) inhibitor, and granulocyte-macrophage colony-stimulating factor (GM-CSF), showed a survival advantage in patients with advanced solid tumors who failed at least the first line of standard systemic treatment. Intraperitoneal infusion of PD-1 inhibitors may be a novel therapeutic strategy for managing malignant ascites. Integrating the PRaG regimen with intraperitoneal perfusion of a PD-1 inhibitor might control malignant ascites and provide further survival benefits in these patients. This proposed study aims to investigate the safety and efficacy of intraperitoneal infusion of serplulimab in combination with the PRaG regimen in patients with simultaneous advanced solid tumors and cancerous ascites who fail at least the first-line treatment. Methods: This proposed study is a prospective, single-arm, open-label, multicenter clinical trial. All eligible patients will receive 2 cycles of intensive treatment, a combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor. The patients who are beneficially treated with intensive treatment will receive consolidation treatment every 2 weeks until ascites disappear, disease progression occurs, intolerable toxicity occurs, or for up to 1 year. Phase I of this study will be conducted using a modified 3 + 3 design. The dose of intraperitoneal infusion of PD-1 inhibitor for phase II will be determined according to dose-limiting toxicity evaluation in the phase I study. Conclusion: This prospective, open-label, multicenter study will potentially lead to intraperitoneal perfusion of a PD-1 inhibitor being a new strategy for malignant ascites patients and provide a meaningful efficacy and safety of the combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor for these patients.
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Ascite , Inibidores de Checkpoint Imunológico , Infusões Parenterais , Neoplasias , Humanos , Ascite/etiologia , Ascite/tratamento farmacológico , Ascite/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Neoplasias/patologia , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Idoso , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Resultado do Tratamento , Estudos ProspectivosRESUMO
In this work, a sea urchin gold nanoparticles-zearalenone aptamer- tetramethylrhodamine sensor was constructed. Sea urchin gold nanoparticles, prepared using the seed-mediated growth method, were used as Raman substrates. Nucleic acid aptamers were mainly used as specific recognition molecules. Zearalenone detection in miscellaneous beans was accomplished using the principle of conformational change in aptamer. In addition, we evaluated the linear range, sensitivity, and selectivity of our sensor. We observed that at the displacement of 814 cm-1, for Zearalenone concentrations of 0.01-60 ng/mL, the Raman signal intensity linearly correlated with the zearalenone concentration, with a limit of detection of 0.01 ng/mL, and recoveries of 91.7% to 108.3%. The optimum detection time was 30 min. Thus, our sensor exhibited great potential in zearalenone detection in food products.
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Neuropathic pain (NP) is a common type of chronic pain caused by a lesion or disease of the somatosensory nervous system. This condition imposes a considerable economic burden on society and patients. Daphnetin (DAP) is a natural product isolated from a Chinese medicinal herb with various pharmacological activities, such as anti-inflammatory and analgesic properties. However, the underlying mechanisms of these effects are not fully understood. In the present study, we aimed to investigate DAP's anti-inflammatory and analgesic effects and explore the underlying mechanisms of action. The NP model was established as chronic constrictive injury (CCI) of the sciatic nerve, and pain sensitivity was evaluated by measuring the mechanical withdrawal threshold (MWT) and thermal withdrawal threshold (TWT). The activation of microglia in the spinal dorsal horn was measured via immunofluorescence staining. Protein levels were measured using a western blot assay. Using a mass-spectrometry proteomics platform and an LC-MS/MS-based metabolomics platform, proteins and metabolites in spinal cord tissues were extracted and analyzed. DAP treatment ameliorated the MWT and TWT in CCI rats. The expression of IL-1ß, IL-6, and TNF-α was inhibited by DAP treatment in the spinal cords of CCI rats. Moreover, the activation of microglia was suppressed after DAP treatment. The elevation in the levels of P2X4, IRF8, IRF5, BDNF, and p-P38/P38 in the spinal cord caused by CCI was inhibited by DAP. Proteomics and metabolomics results indicated that DAP ameliorated the imbalance of glycerophospholipid metabolism in the spinal cords of CCI rats. DAP can potentially ameliorate NP by regulating microglial responses and glycerophospholipid metabolism in the CCI model. This study provides a pharmacological justification for using DAP in the management of NP.
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Rapeseed (Brassica napus) silique is the major carbohydrate source for seed development, and the final silique length has attracted great attention from breeders. However, no studies had focused on the dynamic character of silique elongation length (SEL). Here, the dynamic SEL investigation in a natural population including 588 lines over two years indicate that dynamic SEL during 0-20 days after flowering was the most essential stage associated with seed number per silique (SPS) and thousand seed weight (TSW). Then, nine loci were identified to be associated with SEL based on GWAS analysis, among which five SNPs (over 50%) distributed on the A02 chromosome within 6.08 to 6.48 Mb. Subsequently, we screened 5078 differentially expressed genes between two extreme materials. An unknown protein, BnaA02.SE, was identified combining with GWAS and RNA-Seq analysis. Subcellular localization and expression profiles analysis demonstrated that BnaA02.SE is a chloroplast- and nucleus-localized protein mainly expressed in pericarps and leaves. Furthermore, transgenic verification and dynamic cytological observation reveal that overexpressed BnaA02.SE can promote silique elongation by regulating JA and IAA contents, affecting cell proliferation and expansion, respectively, and finally enhance seed yield by influencing SPS and TSW. Haplotype analysis reveal that the homologs of BnaA02.SE may also be involved in silique elongation regulation. Our findings provided comprehensive insights into a newly SEL trait, and cloned the first gene (BnaA02.SE) controlling silique elongation in B. napus. The identified BnaA02.SE and its homologs can offer a valuable target for improving B. napus yield.
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The maintenance of normal vascular function and homeostasis is largely dependent on the signaling mechanisms that occur within and between cells of the vasculature. TGF-ß-activated kinase 1 (TAK1), a multifaceted signaling molecule, has been shown to play critical roles in various tissue types. Although the precise function of TAK1 in the vasculature remains largely unknown, emerging evidence suggests its potential involvement in both physiological and pathological processes. A comprehensive search strategy was employed to identify relevant studies, PubMed, Web of Science, and other relevant databases were systematically searched using keywords related to TAK1, TABs and MAP3K7.In this review, we discussed the role of TAK1 in vascular signaling, with a focus on its function, activation, and related signaling pathways. Specifically, we highlight the TA1-TABs complex is a key factor, regulating vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) involved in the processes of inflammation, vascular proliferation and angiogenesis. This mini review aims to elucidate the evidence supporting TAK1 signaling in the vasculature, in order to better comprehend its beneficial and potential harmful effects upon TAK1 activation in vascular tissue.
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INTRODUCTION: This study explored the feasibility of a supporting catheter combined with modified end-to-side anastomosis in the operation of radio-cephalic arteriovenous fistula (RC-AVF) and evaluated the clinical application value of this technique. METHODS: Sixty patients underwent RC-AVF operations in our hospital from January 2022 to June 2022. All the patients were treated with modified end-to-side AVF anastomosis and divided into the control group or the test group depending on whether a supporting catheter was applied. The clinical data of 60 cases were analysed retrospectively. Intraoperative related indices, the first time the fistula was used, the success rate of first puncture, the blood flow of first dialysis, the maturity condition of fistula, the size of anastomosis, the diameter of radial artery and drainage vein, the blood flow of brachial artery 8 weeks after operation and the incidence of complications within 6 months after operation were compared between the two groups. RESULTS: Compared with that in the control group, the time spent on the vascular anastomosis in the test group was significantly shortened (p<0.05). The blood flow of the first dialysis, the size of the anastomosis, the diameter of the drainage vein, the blood flow of the brachial artery 8 weeks after the operation and the incidence of complications within 6 months after operation were significantly different between the two groups (p<0.05). CONCLUSION: In the RC-AVF operation, using a supporting catheter can not only increase operation efficiency by reducing surgical injury and difficulty of vascular anastomosis, but also improve postoperative prognosis. RC-AVF is worth promoting in clinical practice.
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The objective of this experiment was to investigate the effects of Lactobacillus plantarum and molasses on the nutrient composition, fermentation quality, bacterial count, aerobic stability, and microflora of alfalfa silage in sandy grasslands. The experimental treatments included control (CK), 106 CFU/g Lactobacillus plantarum (L), 5% molasses (M), and 106 CFU/g Lactobacillus plantarum + 5% molasses (LM). The nutrient composition, fermentation quality, bacterial count, aerobic stability, and microflora were determined after 14 days and 56 days of ensiling, respectively. The results showed that the addition of L, M, and LM reduced dry matter loss (DM), neutral detergent fiber (NDF), and acid detergent fiber (ADF) content, and increased water-soluble carbohydrates (WSC) and ether extract (EE) content, compared to the CK group. Meanwhile, more lactic acid (LA) and accelerated fermentation were observed, causing the pH value to drop below 4.5 in the L, M, and LM groups after 56 days of ensiling. The addition of L, M, and LM promoted lactic acid bacteria (LAB), and inhibited yeast. The addition of L significantly increased the content of acetic acid (AA). In terms of microflora, the addition of L, M, and LM made Firmicutes become the dominant bacterial phylum earlier, while Lactobacillus, Weissella, and Pediococcus had a higher abundance. According to the result of Pearson's correlation, there is a very significant negative correlation between pH value and Lactobacillus (P < 0.01) and a very significant positive correlation between pH value and Lactococcus, Enterobacter, Enterococcus, and Leuconostoc (P < 0.01), which may be inhibited by Lactobacillus under the decreased pH value. The results of the prediction of microbial genes indicated that the addition of M could enhance the carbohydrate metabolism and membrane transport metabolism, which may contribute to LA production by LAB metabolism. In general, L, M and LM all improved the fermentation quality and reduced the loss of nutrients to varying degrees, but considering the fermentation quality, the overall effects of M and LM were better than L. M and LM are recommended to be used as silage additives in the process of alfalfa silage in sandy grasslands to improve the quality.
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Local cells can actively create reverse bending (evagination) in invaginated epithelia, which plays a crucial role in the formation of elaborate organisms. However, the precise physical mechanism driving the evagination remains elusive. Here, we present a three-dimensional vertex model, incorporating the intrinsic cell polarity, to explore the complex morphogenesis induced by local mechanical modulations. We find that invaginated tissues can spontaneously generate local reverse bending due to the shift of the apicobasal polarity. Their exact shapes can be analytically determined by the local apicobasal differential tension and the internal stress. Our continuum theory exhibits three regions in a phase diagram controlled by these two parameters, showing curvature transitions from ordered to disordered states. Additionally, we delve into epithelial curvature transition induced by the nucleus repositioning, revealing its active contribution to the apicobasal force generation. The uncovered mechanical principles could potentially guide more studies on epithelial folding in diverse systems.
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Polaridade Celular , Epitélio/fisiologia , Polaridade Celular/fisiologia , Células Epiteliais/citologia , Modelos Biológicos , Morfogênese , Estresse Mecânico , Animais , HumanosRESUMO
OBJECTIVE: Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs. MATERIALS AND METHODS: The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis. RESULTS: According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2-3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level. CONCLUSION: In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.
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Braquiterapia , Craniofaringioma , Neoplasias Hipofisárias , Humanos , Braquiterapia/métodos , Braquiterapia/efeitos adversos , Craniofaringioma/radioterapia , Seguimentos , Neoplasias Hipofisárias/radioterapia , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
Lymphocytes, which are highly sensitive to radiation, play a crucial role in the body's defense against tumors. Radiation-induced lymphopenia has been associated with poorer outcomes in different cancer types. Despite being the largest secondary lymphoid organ, the spleen has not been officially designated as an organ at risk. This study hypothesizes a connection between spleen irradiation and lymphopenia and seeks to establish evidence-based dosage limits for the spleen. We retrospectively analyzed data from 96 patients with locally advanced gastric cancer who received postoperative chemoradiotherapy (CRT) between May 2010 and May 2017. Complete blood counts were collected before, during and after CRT. We established a model for predicting the minimum absolute lymphocyte count (Min ALC) and to investigate potential associations between spleen dosimetric variables and Min ALC. The median follow-up was 60 months. The 5-year overall survival (OS) and disease-free survival (DFS) were 65.2% and 56.8%, respectively. The median values of pre-treatment ALC, Min ALC and post-treatment ALC were 1.40 × 109, 0.23 × 109 and 0.28 × 109/L, respectively. Regression analysis confirmed that the primary tumor location, number of fractions and spleen V5 were significant predictors of Min ALC during radiation therapy. Changes in ALC (ΔALC) were identified as an independent predictor of both OS and DFS. Spleen V5 is an independent predictor for Min ALC, and the maximum dose of the spleen is associated with an increased risk of severe lymphopenia. Therefore, these doses should be restricted in clinical practice. Additionally, ΔALC can serve as a prognostic indicator for adjuvant radiotherapy in gastric cancer.
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Linfopenia , Baço , Neoplasias Gástricas , Humanos , Linfopenia/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Baço/efeitos da radiação , Baço/patologia , Idoso , Neoplasias Gástricas/radioterapia , Neoplasias Gástricas/patologia , Adulto , Relação Dose-Resposta à Radiação , Contagem de Linfócitos , Intervalo Livre de Doença , Estudos Retrospectivos , Quimiorradioterapia , Dosagem Radioterapêutica , Idoso de 80 Anos ou maisRESUMO
Glioma, particularly glioblastomas (GBM), is incurable brain tumor. The most targeted receptor tyrosine kinase (RTKs) drugs did not bring benefit to GBM patients. The mechanism of glioma growth continues to be explored to find more effective treatment. Here, we reported that Ser/Thr protein kinase YANK2 (yet another kinase 2) is upregulated in glioma tissues and promotes the growth and proliferation of glioma in vitro and in vivo. Further, we confirmed that oncogene Fyn directly activated YANK2 through phosphorylation its Y110, and Fyn-mediated YANK2 phosphorylation at Y110 site promotes glioma growth by increasing its stability. Finally, YANK2 was proved to be a novel upstream kinase of p70S6K and promotes glioma growth by directly phosphorylating p70S6K at T389. Taken together, we found a new mTOR-independent p70S6K activation pathway, Fyn-YANK2-p70S6K, which promotes glioma growth, and YANK2 is a potential oncogene and serves as a novel therapeutic target for glioma.
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Proliferação de Células , Glioma , Proteínas Proto-Oncogênicas c-fyn , Proteínas Quinases S6 Ribossômicas 70-kDa , Transdução de Sinais , Serina-Treonina Quinases TOR , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Humanos , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Proteínas Proto-Oncogênicas c-fyn/genética , Serina-Treonina Quinases TOR/metabolismo , Glioma/metabolismo , Glioma/patologia , Glioma/genética , Animais , Linhagem Celular Tumoral , Fosforilação , Carcinogênese/genética , Carcinogênese/metabolismo , Camundongos , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Camundongos Nus , Regulação Neoplásica da Expressão GênicaRESUMO
Preterm birth represents a multifaceted syndrome with intricacies still present in our comprehension of its etiology. In the context of a semi-allograft, the prosperity from implantation to pregnancy to delivery hinges on the establishment of a favorable maternal-fetal immune microenvironment and a successful trilogy of immune activation, immune tolerance and then immune activation transitions. The occurrence of spontaneous preterm birth could be related to abnormalities within the immune trilogy, stemming from deviation in maternal and fetal immunity. These immune deviations, characterized by insufficient immune tolerance and early immune activation, ultimately culminated in an unsustainable pregnancy. In this review, we accentuated the role of both innate and adaptive immune reason in promoting spontaneous preterm birth, reviewed the risk of preterm birth from vaginal microbiome mediated by immune changes and the potential of vaginal microbiomes and metabolites as a new predictive marker, and discuss the changes in the role of progesterone and its interaction with immune cells in a preterm birth population. Our objective was to contribute to the growing body of knowledge in the field, shedding light on the immunologic reason of spontaneous preterm birth and effective biomarkers for early prediction, providing a roadmap for forthcoming investigations.
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BACKGROUND: The pathway by which drugs are injected subcutaneously behind the ear to act on the inner ear has not been fully elucidated. OBJECTIVES: To compare the uptake of gadopentetate dimeglumine (Gd-DTPA) and dexamethasone (Dex) in the cochlea and facial nerve of rats following different administrations. MATERIALS AND METHODS: Magnetic resonance imaging was applied to observe the distribution of Gd-DTPA in the facial nerve and inner ear. We observed the uptake of Dex after it was injected with different methods. RESULTS: Images of the intravenous (IV) and intramuscular (IM) groups showed that the bilateral cochlea of the rat was visualized almost simultaneously. While in the left post-auricular (PA) injection group, it was asynchronous. The maximum accumulation (Cmax) of the Gd in the left facial nerve of the PA group (35.406 ± 5.32) was substantially higher than that of the IV group (16.765 ± 3.7542) (p < .01). CONCLUSIONS: Compared with systemic administration, PA has the advantages of long Gd and Dex action time and high accumulation concentration to treat facial nerve diseases. SIGNIFICANCE: The distribution of Gd and Dex in the inner ear and facial nerve of rats following PA injection might be unique.
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Meios de Contraste , Dexametasona , Nervo Facial , Gadolínio DTPA , Imageamento por Ressonância Magnética , Animais , Dexametasona/farmacocinética , Dexametasona/administração & dosagem , Gadolínio DTPA/farmacocinética , Gadolínio DTPA/administração & dosagem , Meios de Contraste/farmacocinética , Meios de Contraste/administração & dosagem , Nervo Facial/metabolismo , Nervo Facial/efeitos dos fármacos , Ratos , Masculino , Ratos Sprague-Dawley , Orelha Interna/metabolismo , Orelha Interna/efeitos dos fármacos , Orelha Interna/diagnóstico por imagem , Injeções IntramuscularesRESUMO
BACKGROUND: To investigate the value of a nomogram model based on the combination of clinical-CT features and multiphasic enhanced CT radiomics for the preoperative prediction of the microsatellite instability (MSI) status in colorectal cancer (CRC) patients. METHODS: A total of 347 patients with a pathological diagnosis of colorectal adenocarcinoma, including 276 microsatellite stabilized (MSS) patients and 71 MSI patients (243 training and 104 testing), were included. Univariate and multivariate regression analyses were used to identify the clinical-CT features of CRC patients linked with MSI status to build a clinical model. Radiomics features were extracted from arterial phase (AP), venous phase (VP), and delayed phase (DP) CT images. Different radiomics models for the single phase and multiphase (three-phase combination) were developed to determine the optimal phase. A nomogram model that combines clinical-CT features and the optimal phasic radscore was also created. RESULTS: Platelet (PLT), systemic immune inflammation index (SII), tumour location, enhancement pattern, and AP contrast ratio (ACR) were independent predictors of MSI status in CRC patients. Among the AP, VP, DP, and three-phase combination models, the three-phase combination model was selected as the best radiomics model. The best MSI prediction efficacy was demonstrated by the nomogram model built from the combination of clinical-CT features and the three-phase combination model, with AUCs of 0.894 and 0.839 in the training and testing datasets, respectively. CONCLUSION: The nomogram model based on the combination of clinical-CT features and three-phase combination radiomics features can be used as an auxiliary tool for the preoperative prediction of the MSI status in CRC patients.
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Neoplasias Colorretais , Nomogramas , Humanos , Instabilidade de Microssatélites , Radiômica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgiaRESUMO
Hypersynchronous (HYP) seizure onset is one of the frequently observed seizure-onset patterns in temporal lobe epileptic animals and patients, often accompanied by hippocampal sclerosis. However, the exact mechanisms and ion dynamics of the transition to HYP seizures remain unclear. Transcranial magneto-acoustic stimulation (TMAS) has recently been proposed as a novel non-invasive brain therapy method to modulate neurological disorders. Therefore, we propose a biophysical computational hippocampal network model to explore the evolution of HYP seizure caused by changes in crucial physiological parameters and design an effective TMAS strategy to modulate HYP seizure onset. We find that the cooperative effects of abnormal glial uptake strength of potassium and excessive bath potassium concentration could produce multiple discharge patterns and result in transitions from the normal state to the HYP seizure state and ultimately to the depolarization block state. Moreover, we find that the pyramidal neuron and the PV+ interneuron in HYP seizure-onset state exhibit saddle-node-on-invariant-circle/saddle homoclinic (SH) and saddle-node/SH at onset/offset bifurcation pairs, respectively. Furthermore, the response of neuronal activities to TMAS of different ultrasonic waveforms revealed that lower sine wave stimulation can increase the latency of HYP seizures and even completely suppress seizures. More importantly, we propose an ultrasonic parameter area that not only effectively regulates epileptic rhythms but also is within the safety limits of ultrasound neuromodulation therapy. Our results may offer a more comprehensive understanding of the mechanisms of HYP seizure and provide a theoretical basis for the application of TMAS in treating specific types of seizures.