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Background: The contrasted-enhanced ultrasound thyroid imaging reporting and data system (CEUS TI-RADS) is the first international risk stratification system for thyroid nodules based on conventional ultrasound (US) and CEUS. This study aimed to evaluate the diagnostic efficacy of CEUS TI-RADS for benign and malignant thyroid nodules and to assess the related interobserver agreement. Methods: The study recruited 433 patients who underwent thyroid US and CEUS between January 2019 and June 2023 at the Affiliated Hospital of Guangdong Medical University. A retrospective analysis of 467 thyroid nodules confirmed by fine-needle aspiration (FNA) and/or surgery was performed. Further, a CEUS TI-RADS classification was assigned to each thyroid nodule based on the CEUS TI-RADS scoring criteria for the US and CEUS features of the nodule. The nodules were grouped based on their sizes as follows: size ≤1 cm, group A; size >1 and ≤4 cm, group B; and size >4 cm, group C. Multivariate logistic regression was used to analyze independent risk factors for malignant thyroid nodules. Pathological assessment was the reference standard for establishing the sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) of CEUS TI-RADS in diagnosing malignant thyroid nodules. The area under the curve (AUC) in the receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic efficacy of the scoring system in predicting malignancy in three groups of nodules. The intragroup correlation coefficient (ICC) was adopted to assess the interobserver agreement of the CEUS TI-RADS score. Results: Out of the 467 thyroid nodules, 262 were malignant and 205 were benign. Logistic regression analysis revealed that the independent risk factors for malignant thyroid nodules included punctate echogenic foci (P<0.001), taller-than-wide shape (P=0.015), extrathyroidal invasion (P=0.020), irregular margins/lobulation (P=0.036), hypoechoicity on US (P=0.038), and hypoenhancement on CEUS (P<0.001). The AUC for the CEUS TI-RADS in diagnosing malignant thyroid nodules was 0.898 for all nodules, 0.795 for group A, 0.949 for group B, and 0.801 for group C, with the optimal cutoff values of the CEUS TI-RADS being 5 points, 6 points, 5 points, and 5 points, respectively. Among these groups of nodules, group B had the highest AUC, with the SEN, SPE, ACC, PPV, and NPV for diagnosing malignant nodules being 95.9%, 88.1%, 92.8%, 92.6%, and 93.2%, respectively. The ICC of the CEUS TI-RADS classification between senior and junior physicians was 0.862 (P<0.001). Conclusions: In summary, CEUS TI-RADS demonstrated significant efficacy in distinguishing thyroid nodules. Nonetheless, there were variations in its capacity to detect malignant nodules across diverse sizes, and it demonstrate optimal performance in 1- to 4-cm nodules. These findings may serve as important insights for clinical diagnoses.
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Mechanical stretching is commonly used for mesogen alignment which is essential for the muscle-like actuations of liquid crystal elastomers (LCEs). Despite the simplicity of the method, the mesogens are typically aligned in the stretching direction, limiting exclusively the LCE to an actuation mode of cooling-induced elongation. Here, we design an interpenetrating double network consisting of an LCE network and an elastomer network, with one polymerized network stretched before the polymerization of the other network. Depending on the polymerization sequence of the two networks, the double network shows two opposite actuation modes, namely, the conventional cooling-induced elongation or an unusual cooling-induced contraction. Strategic integration of the two opposite behaviors into the same LCE leads to sophisticated actuation difficult to achieve with a conventional LCE design. Coupled with 3D printing, geometrically complexed LCEs with diverse multimodal four-dimensional actuation behaviors are illustrated. Our work expands the design scope of LCE actuators and their potential device applications.
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Electrochemical water splitting is regarded as an emerging green and sustainable hydrogen production technology because of its zero-carbon process. However, the overall cost of anode materials in a proton exchange membrane water electrolyzer (PEMWE) is high due to the use of noble metal Ir. It has been proved that introducing carrier materials to reduce the content of Ir element is a feasible cost-reduction program. Here, the Ir/TiO2 composite material was prepared by the polyol method and used to catalyze the oxygen evolution reaction, which could effectively reduce the load amount of Ir in the membrane electrode assembly (MEA). In addition, the theoretical load of Ir was obtained by model calculation and the polarization curve test and electrochemical impedance spectroscopy (EIS) were used to discuss the relationship between Ir load in MEA and voltage loss and conductivity. The results show that MEA has lower voltage loss and better conductivity as the Ir load is in the range of 0.204-0.304 mgIr/cm2. Altogether, an effective method to reduce the Ir load of PEMWE anode was proposed under the premise comprehensive consideration of both catalyst design and MEA preparation in this work.
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Faults play a crucial role in shaping the formation and damage patterns of landslides in the mountainous region, particularly in Qinling-Daba (Qinba) area in China. On 6 October 2022, following a 4-day rainfall event totaling 221.5 mm, a landslide occurred in Hanwang Town, Shaanxi Province. The left boundary of the landslide coincided with a fault, which influence the formation and movement development of the landslide. To further understand and quantified the formation process and damage mechanism of the landslide, a comprehensive study was conducted, incorporating field investigations, local rainfall data, and various methods including unmanned aerial vehicles (UAVs), numerical simulations, and laboratory test. The results indicate that fault dictate the formation of the Lijiaping landslide by influencing the mechanical strength of the rock mass and the catchment topography in the landslide area. Due to fault, the rock mass in the landslide area is high fragmentation, with a softening coefficient of about 0.52. Weathering resulted in numerous residual and slope sediments in the landslide area, providing ample material for the landslide. Meanwhile, the fault activity led to a wedge-shaped topography in the landslide area, with an average Terrain Wetness Index (TWI) of 3.43, significantly higher than the Hanwang Township average of 1.47. This creates a hydrogeological structure favorable for landslides. Numerical simulations revealed that the maximum velocity of the landslide reached 5.05 m/s and the maximum displacement was 53.18 m, both occurring in the central part of the landslide. These findings offer crucial scientific insights for understanding and preventing similar geological hazards.
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Immune checkpoint therapy has limited efficacy for patients with bone-metastatic castration-resistant prostate cancer (bmCRPC). To improve immunotherapy for bmCRPC, we aimed to identify the mechanism of bmCRPC-induced changes in the immune microenvironment. Among bmCRPC patients, higher levels of a 32-gene M2-like macrophage signature in bone metastasis samples correlated with shorter overall survival. Immunohistochemistry showed that CD206-positive (CD206+) macrophages were enriched in bmCRPC bone biopsy specimens compared with primary tumors or lymph node metastases. In preclinical osteogenic prostate cancer (Pca) xenograft models, CD206+ macrophages were recruited to areas with tumor-induced bone. RNA sequencing (RNAseq) analysis showed higher expression of an M2-like gene signature, with activated canonical and noncanonical Wnt pathways, in tumor-associated macrophages isolated from osteogenic tumors (bone-TAMs) than in TAMs isolated from nonosteogenic tumors (ctrl-TAMs). Mechanistic studies showed that endothelial cells (ECs) that had undergone EC-to-osteoblast (EC-to-OSB) transition, the precursors of tumor-induced OSBs, produced paracrine factors, including Wnts, CXCL14, and lysyl oxidase, which induced M2 polarization and recruited M2-like TAMs to the bone-tumor microenvironment (bone-TME). Bone-TAMs suppressed CD8+ T cells' proliferation and cytolytic activity, and these effects were partially reversed by treating bone-TAMs with Wnt inhibitors. Genetic or pharmacological inhibition of Pca-induced EC-to-OSB transition reduced the levels of M2-like macrophages in osteogenic tumors. Our study demonstrates that Pca-induced EC-to-OSB transition drives immunosuppression in the bone-TME, suggesting that therapies that reduce Pca-induced bone formation may improve immunotherapeutic outcomes for bmCRPC.
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Neoplasias Óseas , Células Endoteliales , Macrófagos , Osteoblastos , Microambiente Tumoral , Vía de Señalización Wnt , Masculino , Microambiente Tumoral/inmunología , Humanos , Neoplasias Óseas/inmunología , Neoplasias Óseas/secundario , Neoplasias Óseas/patología , Neoplasias Óseas/metabolismo , Animales , Ratones , Macrófagos/metabolismo , Macrófagos/inmunología , Células Endoteliales/metabolismo , Células Endoteliales/inmunología , Osteoblastos/metabolismo , Osteoblastos/inmunología , Neoplasias de la Próstata Resistentes a la Castración/inmunología , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Línea Celular Tumoral , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/metabolismo , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunologíaRESUMEN
Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) still lacks efficient therapeutic drugs. This study aimed to systematically evaluate the effects of Huangqi Guizhi Wuwu Decoction (HGWD) alone or combined with positive drugs on CIPN prevention and treatment. Methods: The PubMed, Embase, Web of Science, Cochrane, China National Knowledge Infrastructure (CNKI), Wan Fang Data, China Science and Technology Journal (VIP) and Chinese Biomedical (CBM) databases were searched for randomized controlled trials (RCTs) of HGWD for CIPN prevention and treatment. The search time ranged from database establishment to October 17, 2023. The Cochrane risk-of-bias assessment tool was used for quality assessment, Review Manager 5.3 and STATA 12.0 were used for meta-analysis, and GRADEprofiler was used for evidence level assessment. Results: A total of 32 RCTs involving 1987 patients were included. The meta-analysis results revealed the following: 1. In terms of the total CIPN incidence, that in the HGWD group was lower than that in the blank control group. The incidence in both the HGWD and HGWD+positive drug groups was lower than that in the monotherapy-positive drug group. 2. In terms of the incidence of severe CIPN, that in the HGWD group was lower than that in the blank control and positive drug groups. There was no statistically significant difference between the HGWD+positive drug and positive drug groups. Sensitivity analysis revealed that the results of severe incidence in the HGWD group was lower than that in the positive drug group were unstable 3. HGWD did not increase the number of chemotherapy-related adverse events. Conclusion: HGWD can safely and effectively prevent CIPN, reduce symptoms, improve quality of life and reduce the impact of chemotherapy drugs on sensory nerve conduction. However, more high-quality RCTs are needed to compare the efficacy of HGWD with that of positive control drugs in preventing severe CIPN.
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Atherosclerosis (AS) is a chronic inflammatory disorder characterized by arterial intimal lipid plaques. Small interfering ribonucleic acid (siRNA)-based therapies, with their ability to suppress specific genes with high targeting precision and minimal side effects, have shown great potential for AS treatment. However, targets of siRNA therapies based on macrophages for AS treatment are still limited. Olfactory receptor 2 (Olfr2), a potential target for plaque formation, was discovered recently. Herein, anti-Olfr2 siRNA (si-Olfr2) targeting macrophages was designed, and the theranostic platform encapsulating si-Olfr2 to target macrophages within atherosclerotic lesions was also developed, with the aim of downregulating Olfr2, as well as diagnosing AS through photoacoustic imaging (PAI) in the second near-infrared (NIR-II) window with high resolution. By utilization of a reactive oxygen species (ROS)-responsive nanocarrier system, the expression of Olfr2 on macrophages within atherosclerotic plaques was effectively downregulated, leading to the inhibition of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and interleukin-1 ß (IL-1ß) secretion, thereby reducing the formation of atherosclerotic plaques. As manifested by decreased Olfr2 expression, the lesions exhibited a significantly alleviated inflammatory response that led to reduced lipid deposition, macrophage apoptosis, and a noticeable decrease in the necrotic areas. This study provides a proof of concept for evaluating the theranostic nanoplatform to specifically deliver si-Olfr2 to lesional macrophages for AS diagnosis and treatment.
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BACKGROUND: Dysphagia, as a geriatric syndrome, is prevalent in the intensive care unit (ICU). Malnutrition resulting from swallowing disorders is likely to correlate with adverse ICU outcomes, including delirium, thereby escalating the costs of care and hospitalization. However, malnutrition has not received the attention it deserves in ICU clinical nursing practice. As two preventable and correctable conditions-malnutrition and delirium-the advantages of early identification and intervention are substantial. Exploring the relationship between malnutrition and delirium, starting from the high-risk group of elderly patients with swallowing difficulties in the ICU, will aid us in managing patients promptly and effectively. AIM: To investigate the relationship between malnutrition and the incidence of delirium in elderly patients with dysphagia in the ICU. SUDY DESIGN: This is a retrospective study. Data for this study were obtained from the Medical Information Mart for Intensive Care-IV. All 2273 patients included were dysphagia older patients over 65 years of age admitted to the ICU, and logistic regression was used to explore the relationship between malnutrition and delirium. We also used propensity score matching (PSM) for sensitivity analysis. RESULTS: Among the included patients with swallowing difficulties, 13% individuals (297/2273) exhibited malnutrition, with a delirium incidence rate of 55.9% (166/297). In the non-malnutrition group (1976/2273), the delirium incidence rate is 35.6% (704/1976). After adjusting for 31 covariates, multifactorial logistic regression showed that malnutrition was significantly positively associated with the incidence of delirium in elderly dysphagic patients in the ICU (adjusted odds ratio (OR) = 1.96, 95% confidence interval (CI) = 1.47-2.62). The results remained stable after analysis by PSM. CONCLUSION: Malnutrition was significantly positively associated with the incidence of delirium in elderly dysphagic patients in the ICU. Malnutrition should be given adequate attention in the ICU. RELEVANCE TO CLINICAL PRACTICE: ICU nurses should pay particular attention to malnutrition, especially among the high-prevalence group of patients with dysphagia. Early identification and nutritional intervention for these patients may help reduce the costs of care and health care expenditures.
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Malignant peritoneal mesothelioma (MPM) is a rare and invasive tumor, and some patients will develop paraneoplastic syndrome (PS) during the course of the disease. This review summarizes PS associated with MPM, focusing on the clinical characteristics and treatment progress in hematological, endocrine, rheumatic, neurological, urinary, and other systems to decrease missed diagnosis and misdiagnosis, help early diagnosis and prompt treatment, and provide guidance for the clinical decision-making of this kind of patients.
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BACKGROUND: Subarachnoid hemorrhage (SAH) is a severe stroke subtype that lacks effective treatment. Exosomes derived from human dental pulp stem cells (DPSCs) are a promising acellular therapeutic strategy for neurological diseases. However, the therapeutic effects of DPSC-derived exosomes (DPSC-Exos) on SAH remain unknown. In this study, we investigated the therapeutic effects and mechanisms of action of DPSC-Exos in SAH. MATERIALS AND METHODS: SAH was established using 120 male Sprague-Dawley rats. One hour after SAH induction, DPSC-Exos were administered via tail vein injection. To investigate the effect of DPSC-Exos, SAH grading, short-term and long-term neurobehavioral assessments, brain water content, western blot (WB), immunofluorescence staining, Nissl staining, and HE staining were performed. The role of miR-197-3p/FOXO3 in regulating pyroptosis was demonstrated through miRNA sequencing, bioinformatics analysis, and rescue experiments. The SAH model in vitro was established by stimulating BV2 cells with hemoglobin (Hb) and the underlying mechanism of DPSC-Exos was investigated through WB and Hoechst/PI staining. RESULTS: The expressions of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) were increased after SAH. DPSC-Exos alleviated brain edema and neuroinflammation by inhibiting the expression of FOXO3 and reducing NLRP3 inflammasome activation, leading to improved neurobehavioral functions at 24 h after SAH. In vitro, the expression of the NLRP3 inflammasome components (NLRP3 and caspase1-p20), GSDMD-N, and IL-18 was inhibited in BV2 cells pretreated with DPSC-Exos. Importantly, DPSC-Exos overexpressing miR-197-3p had a more obvious protective effect than those from NC-transfected DPSCs, while those from DPSCs transfected with the miR-197-3p inhibitor had a weaker protective effect. Functional studies indicated that miR-197-3p bound to the 3'-untranslated region of FOXO3, inhibiting its transcription. Furthermore, the overexpression of FOXO3 reversed the protective effects of miR-197-3p. CONCLUSIONS: DPSC-Exos inhibited activation of the NLRP3 inflammasome and related cytokine release via the miR-197-3p/FOXO3 pathway, alleviated neuroinflammation, and inhibited microglial pyroptosis. These findings suggest that using DPSC-Exos is a promising therapeutic strategy for SAH.
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Pulpa Dental , Exosomas , Proteína Forkhead Box O3 , Células Madre Mesenquimatosas , MicroARNs , Microglía , Enfermedades Neuroinflamatorias , Piroptosis , Ratas Sprague-Dawley , Hemorragia Subaracnoidea , Animales , Exosomas/metabolismo , MicroARNs/metabolismo , MicroARNs/genética , Proteína Forkhead Box O3/metabolismo , Masculino , Células Madre Mesenquimatosas/metabolismo , Ratas , Pulpa Dental/citología , Pulpa Dental/metabolismo , Hemorragia Subaracnoidea/metabolismo , Hemorragia Subaracnoidea/terapia , Humanos , Enfermedades Neuroinflamatorias/metabolismo , Microglía/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratones , Modelos Animales de EnfermedadRESUMEN
Hydrogen peroxide (H2O2) as a reactive oxygen species produced by cellular metabolism can be used in antitumor therapy. However, the concentration of intracellular H2O2 limits its application. Some materials could enhance the concentration of intracellular H2O2 to strengthen antitumor therapy. In this review, the recent advances in H2O2-supplying materials in terms of promoting intracellular H2O2 production and exogenous H2O2 supply are summarized. Then the mechanism of H2O2-supplying materials for tumor therapy is discussed from three aspects: reconstruction of the tumor hypoxia microenvironment, enhancement of oxidative stress, and the intrinsic anti-tumor ability of H2O2-supplying materials. In addition, the application of H2O2-supplying materials for tumor therapy is discussed. Finally, the future of H2O2-supplying materials is presented. This review aims to provide a novel idea for the application of H2O2-supplying materials in tumor therapy.
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Peróxido de Hidrógeno , Neoplasias , Microambiente Tumoral , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/farmacología , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Microambiente Tumoral/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Antineoplásicos/farmacología , Antineoplásicos/química , Especies Reactivas de Oxígeno/metabolismo , Hipoxia Tumoral/efectos de los fármacosRESUMEN
OBJECTIVE: Multitargeted tyrosine kinase inhibitors (TKIs) have been approved as second-line therapy in refractory sarcoma, prolonging progression-free survival (PFS) but with short-lived duration of disease control. Fruquintinib is a TKI that specifically inhibits vascular endothelial growth factor receptor-1,2,3 with no metabolism by liver enzymes. In this retrospective study, we assessed the efficacy and safety of fruquintinib-based treatment in patients with refractory sarcoma after developing several lines of TKI resistance. METHODS: We retrospectively analyzed the clinical data of patients with refractory sarcoma after they had developed several lines of resistance to TKIs and who received fruquintinib-based treatment from November 2021 to August 2023. The primary endpoint was the progression-free survival rate at 4 months (4m-PFSR). Secondary endpoints were the median PFS, overall survival (OS), objective response rate, disease control rate, and adverse effects (AEs). PFS and OS were estimated using the Kaplan-Meier method. A log-rank test was used to compare survival curves between different clinical and pathological factors. Cox proportional hazards analysis was performed to identify PFS-related prognostic factors. RESULTS: We included 124 patients: 56 (45.2%) with osteosarcoma, 28 (22.6%) with Ewing sarcoma, seven (5.6%) with chondrosarcoma, and 33 (26.6%) with soft tissue sarcomas (STS). Only 18 (14.5%) patients received monotherapy with fruquintinib. With a median follow-up time of 6.8 (interquartile range [IQR], 4.6-9.4) months, 22 (17.7%) patients had partial response and 78 (62.9%) had stable disease. The 4m-PFSR was 58.4% (95% confidence interval [CI], 49.6%-67.1%). The median PFS and OS were 4.4 (95% CI, 3.9-5.0) months and 11.4 (95% CI, 10.3-12.5) months. In multivariate analysis, a high hazard ratio for progression was associated with target lesions located outside the lung and bone with 1.79 (95% CI, 1.10-2.93; p = 0.020). Eighty-eight AEs were recorded in 47 (37.9%) patients; the most common were pneumothorax (18/124, 14.5%), diarrhea (8/124, 6.5%), oral mucositis (7/124, 5.6%), and thrombocytopenia (7/124, 5.6%). CONCLUSIONS: Fruquintinib may be a potential option for patients with refractory sarcoma after developing several lines of TKI resistance, with a satisfactory efficacy and safety profile in combination therapy. However, the degree of contribution of fruquintinib to results is unclear when combined with other effective substances. Additional prospective trials of fruquintinib should be conducted, especially involving different pathological types and combination regimens.
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Purpose: The crosstalk between hepatocellular carcinoma (HCC) cells and hepatic stellate cells (HSCs) is one of the important mechanisms of liver cancer metastasis. The relationship between liver cancer metastasis and glycolysis has been extensively studied recently. However, the role of von Willebrand factor (vWF) mediated glycolysis mechanism in liver cancer metastasis is currently unknown. Methods: Western blot was used to verify the expression of vWF in HCC cells. PAS staining, glycogen and L-lactate content assays were used to reflect cellular glycolysis levels. The ability of cell migration was explored by Wound-healing and Transwell assays. Besides, the effect of vWF on the progression of HCC in vivo was also studied using subcutaneous xenograft model. Results: vWF derived from HCC cells promoted tumor migration by mediating glycolysis. Besides, vWF participated in the crosstalk between HCC cells and HSCs. HCC cells activated HSCs through vWF-mediated TGFB1 expression and secretion, and activated HSCs upregulated vWF expression in HCC cells through IL-6 secretion feedback. Further, in vitro and in vivo experiments also confirmed the importance of the JAK1/vWF/TGFB1 axis in regulating HSCs-derived IL-6 mediated HCC migration and growth. Conclusion: In summary, this article demonstrated that IL-6 released from hepatic stellate cells enhanced glycolysis and migration ability of liver cancer cells by activating JAK1/vWF/TGFB1 axis which may also be a potential target for inhibiting liver cancer metastasis.
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Glycomics, an emerging "omics" technology that was developed after genomics and proteomics, is a discipline that studies the composition, structure, and functions of glycomes in cells, tissues, and organisms. Glycomics plays key roles in understanding the laws of major life activities, disease prevention and treatment, and drug quality control and development. At present, the structural analysis of glycans relies mainly on mass spectrometry. However, glycans have low abundance in biological samples. In addition, factors such as variable monosaccharide compositions, differences in glycosidic bond positions and modes, diverse branching structures, contribute to the complexity of the compositions and structures of glycans, posing great challenges to glycomics research. Liquid chromatography can effectively remove matrix interferences and enhance glycan separation to improve the mass spectrometric response of glycans. Thus, liquid chromatography and liquid chromatography coupled with mass spectrometry are important technical tools that have been actively applied to solve these problems; these technologies play indispensable roles in glycomics research. Different studies have highlighted similarities and differences in the applications of various types of liquid chromatography, which also reflects the versatility and flexibility of this technology. In this review, we first discuss the enrichment methods for glycans and their applications in glycomics research from the perspective of chromatographic separation mechanisms. We then compare the advantages and disadvantages of these methods. Some glycan-enrichment modes include affinity, hydrophilic interactions, size exclusion, and porous graphitized carbon adsorption. A number of newly developed materials exhibit excellent glycan-enrichment ability. We enumerate the separation mechanisms of reversed-phase high performance liquid chromatography (RP-HPLC), high performance anion-exchange chromatography (HPAEC), hydrophilic interaction chromatography (HILIC), and porous graphitic carbon (PGC) chromatography in the separation and analysis of glycans, and describe the applications of these methods in the separation of glycans, glycoconjugates, and glyco-derivatives. Among these methods, HILIC and PGC chromatography are the most widely used, whereas HPAEC and RP-HPLC are less commonly used. The HILIC and RP-HPLC modes are often used for the separation of derived glycans. The ionization efficiency and detectability of glycans are significantly improved after derivatization. However, the derivatization process is relatively cumbersome, and byproducts inevitably affect the accuracy and completeness of the detection results. HPAEC and PGC chromatography exhibit good separation effects on nonderivative glycans, but issues related to the detection integrity of low-abundance glycans owing to their poor detection effect continue to persist. Therefore, the appropriate analytical method for a specific sample or target analyte or mutual verification must be selected. Finally, we highlight the research progress in various chromatographic methods coupled with mass spectrometry for glycomics analysis. Significant progress has been made in glycomics research in recent years owing to advancements in the development of chromatographic separation techniques. However, several significant challenges remain. As the development of novel separation materials and methods continues, chromatographic techniques may be expected to play a critical role in future glycomics research.
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Glicómica , Polisacáridos , Glicómica/métodos , Polisacáridos/análisis , Polisacáridos/química , Cromatografía Liquida/métodos , Espectrometría de Masas/métodosRESUMEN
Despite advancements in treatment modalities such as flow diverters, the optimal management of posterior communicating artery (PComA) aneurysms remains uncertain. While PComA aneurysms treated with the Pipeline Embolization Device (PED) has been reported, the characteristics and progression of incomplete occluded aneurysms remain unclear. Therefore, our study aims to investigate the occlusion status and recurrence rates of PComA aneurysms treated with PED. A retrospective review of consecutive PComA aneurysm patients treated with PED was conducted between January 2015 and December 2020. Only patients with radiological follow-up were included. PComA aneurysms were categorized into incomplete occlusion and complete occlusion group. The primary outcomes included the characteristics of incomplete occlusion at the follow-up angiography. Among 121 PComA aneurysms treated with PED at our institution, 80 aneurysms were eligible in our study. During the follow-up period, 19 (23.8%) aneurysms demonstrated incomplete occlusion. Notably, there were no instances of recurrence among the 80 followed-up cases. Baseline characteristics of patients and aneurysms were comparable between the groups with complete and incomplete occlusion. However, the incomplete occlusion group showed a lower rate of assisted coils embolization (21.2% vs. 55.7%, P = 0.017) and shorter median operative time (91.0 vs. 145.5 min, P = 0.039). Differences in functional outcomes, complications, and PComA occlusion status between the groups were not significant. Multivariate analysis revealed the use of coils was associated with lower odds of incomplete PComA aneurysm occlusion (OR 0.01, 95% CI 0.001-0.12; P = 0.001), while aneurysm size was associated with higher odds of incomplete occlusion (OR 1.25, 95% CI 1.10-1.46; P = 0.002). The treatment of PED for PComA aneurysm demonstrated favorable outcomes, with an acceptable rate of incomplete occlusion and no instances of recurrence observed. However, further research is needed to explore the optimal procedural strategy for large-sized PComA aneurysms.
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Embolización Terapéutica , Aneurisma Intracraneal , Recurrencia , Humanos , Aneurisma Intracraneal/terapia , Masculino , Embolización Terapéutica/métodos , Embolización Terapéutica/instrumentación , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Adulto , Angiografía CerebralRESUMEN
BACKGROUND: Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia. METHODS: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation. RESULTS: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression. CONCLUSIONS: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.
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Modelos Animales de Enfermedad , Inflamasomas , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE , Proteína con Dominio Pirina 3 de la Familia NLR , Fenantrenos , Transducción de Señal , Quinasa Syk , Vasodilatación , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , Quinasa Syk/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Fenantrenos/farmacología , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Vasodilatación/efectos de los fármacos , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/fisiopatología , Vasodilatadores/farmacología , Fosforilación , Ratones , Aorta/efectos de los fármacos , Aorta/fisiopatología , Aorta/metabolismo , Aorta/enzimología , Apolipoproteínas ERESUMEN
Traumatic peripheral nerve injuries (PNI), present with symptoms ranging from pain to loss of motor and sensory function. Difficulties in intraoperative visual assessment of nerve functional status necessitate intraoperative nerve conduction studies (INCSs) by neurosurgeons and neurologists to determine the presence of functioning axons in the zone of a PNI. This process, also referred to as nerve "inching", uses a set of stimulating and recording electrode hooks to lift the injured nerve from the surrounding surgical field and to determine whether an electrical stimulus can travel through the zone of injury. However, confounding electrical signal artifacts can arise from the current workflow and electrode design, particularly from the mandatory lifting of the nerve, complicating the definitive assessment of nerve function and neurosurgical treatment decision-making. The objective of this study is to describe the design process and verification testing of our group's newly designed stimulating and recording electrodes that do not require the lifting or displacement of the injured nerve during INCSs. Ergonomic in vivo analysis of the device within a porcine model demonstrated successful intraoperative manipulation of the device, while quantitative nerve action potential (NAP) signal analysis with an ex vivo simulated "inching" procedure on healthy non-human primate nerve tissue demonstrated excellent reproducible recorded NAP fidelity and the absence of NAP signal artifacts at all points of recording. Lastly, electrode pullout force testing determined maximum forces of 0.43 N, 1.57 N, and 3.61 N required to remove the device from 2 mm, 5 mm, and 1 cm nerve models, respectively, which are well within established thresholds for nerve safety. These results suggest that these new electrodes can safely and successfully perform accurate PNI assessment without the presence of artifacts, with the potential to improve the INCS standard of care while remaining compatible with currently used neurosurgical technology, infrastructure, and clinical workflows.
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Gestational diabetes mellitus (GDM) is a common condition in pregnant women that can affect the health of both the mother and the fetus. A healthy diet reduces the risk of GDM, while on the contrary, an unhealthy diet can increase the risk of developing GDM. Dietary interventions remain an important way to control GDM at this time. However, real-life diets are complex and varied, and the effect of these diets on gestational diabetes is unknown. This article summarizes research related to dietary control of GDM. Hopefully, this will help with dietary interventions for people with GDM.
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Diabetes Gestacional , Humanos , Diabetes Gestacional/dietoterapia , Diabetes Gestacional/prevención & control , Embarazo , Femenino , Dieta/métodos , Dieta Saludable/métodosRESUMEN
Diabetes accelerates vascular senescence, which is the basis for atherosclerosis and stiffness. The activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and oxidative stress are closely associated with the deteriorative senescence in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). For decades, Sodium Tanshinone IIA Sulfonate (STS) has been utilized as a cardiovascular medicine with acknowledged anti-inflammatory and anti-oxidative properties. Nevertheless, the impact of STS on vascular senescence remains unexplored in diabetes. Diabetic mice, primary ECs and VSMCs were transfected with the NLRP3 overexpression/knockout plasmid, the tumor necrosis factor alpha-induced protein 3 (TNFAIP3/A20) overexpression/knockout plasmid, and treated with STS to detect senescence-associated markers. In diabetic mice, STS treatment maintained catalase (CAT) level and vascular relaxation, reduced hydrogen peroxide probe (ROSgreen) fluorescence, p21 immunofluorescence, Senescence ß-Galactosidase Staining (SA-ß-gal) staining area, and collagen deposition in aortas. Mechanistically, STS inhibited NLRP3 phosphorylation (serine 194), NLRP3 dimer formation, NLRP3 expression, and NLRP3-PYCARD (ASC) colocalization. It also suppressed the phosphorylation of IkappaB alpha (IκBα) and NFκB, preserved A20 and CAT levels, reduced ROSgreen density, and decreased the expression of p21 and SA-ß-gal staining in ECs and VSMCs under HG culture. Our findings indicate that STS mitigates vascular senescence by modulating the A20-NFκB-NLRP3 inflammasome-CAT pathway in hyperglycemia conditions, offering novel insights into NLRP3 inflammasome activation and ECs and VSMCs senescence under HG culture. This study highlights the potential mechanism of STS in alleviating senescence in diabetic blood vessels, and provides essential evidence for its future clinical application.