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Soil respiration (Rs) is a crucial ecological process of carbon (C) cycling in the terrestrial ecosystems, and soil erosion has a significant impact on its C budget and balance. However, the variations of Rs rate and their CO2 efflux induced by erosion are currently poorly understood. To this end, four landscape positions (top, up, middle and toe) with different erosional and depositional characteristics were selected on a typical eroded slope in southern China to conduct field experiments, aiming to explore the effects of erosion and deposition on Rs among various sites. From March 2021 to February 2022, the in-situ Rs were measured using an automated soil respiration system, together with soil temperature at 5 cm depth (Ts5) and water content at 10 cm depth (SWC10). We initially constructed various Rs models across a one-year period, based on its relationships with Ts5 and SWC10. Subsequently, the seasonal changes of Rs at different erosional sites were simulated by the optimum models, and their annual CO2 fluxes were further estimated. The results showed that Rs rates at all sites displayed a bimodal seasonal pattern, with the highest values in May and August. And the measured Rs of the eroding and depositional sites were 0.05-7.71 and 1.47-13.03 µmol m-2 s-1, respectively. Also, remarkably higher Ts5 and SWC10 were observed in depositional sites versus the eroding sites (P < 0.05). Additionally, Rs rates at all sites were positively correlated with SOC and Ts5, but negatively correlated with SWC10. Herein, Rs models to single- and double-variable were established at different positions, and we found that the fitted R2 and AIC differed on various sites, primarily in erosional and depositional sites. Furthermore, through the best-fitting models (higher R2 and lowest AIC) we screened, the average Rs values of 3.03 and 4.46 µmol m-2 s-1 were quantitatively estimated for the eroding and depositional sites, respectively. Finally, it could be further assessed that the mean annual soil CO2-C efflux of eroded site (1104.14 g m-2) was significantly lower than that of depositional site (1629.46 g m-2). These findings highlighted the effect of erosion and deposition on Rs, which will facilitate a better understanding of C cycling in terrestrial ecosystems.
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Dióxido de Carbono , Suelo , Dióxido de Carbono/análisis , Ecosistema , Frecuencia Respiratoria , China , TemperaturaRESUMEN
Ecological restoration projects aim to comprehensively intervene in damaged or deteriorating ecosystems, restore them, improve the provision of ecosystem services, and achieve harmonious coexistence between humans and nature. Implementing ecological restoration projects leads to continuous changes in land use/land cover. Studying the long-term changes in land use/land cover and their impacts on ecosystem services, as well as the trade-off and synergy between these services, helps evaluate the long-term effectiveness of ecological restoration projects in restoring ecosystems. Therefore, this study analyzes the land use/land cover, and ecosystem services of the Hainan Tropical Forest Park in China to address this. Since 2000, the area has undergone multiple ecological restoration projects, divided roughly into two stages: 2003-2013 and 2013-2021. The InVEST model is used to quantify three essential ecosystem services in mountainous regions (water yield, carbon storage, and soil conservation), and redundancy analysis identifies the primary driving factors influencing their changes. We conducted spatial autocorrelation analysis to examine the interplay among ecosystem services under long-term land use/land cover change. The results indicate a decrease in the total supply of water yield (-5.14%) and carbon storage (-3.21%) in the first phase. However, the second phase shows an improvement in ecosystem services, with an increase in the total supply of water yield (11.45%), carbon storage (27.58%), and soil conservation (21.95%). The redundancy analysis results reveal that land use/land cover are the primary driving factors influencing the changes in ecosystem services. Furthermore, there is a shift in the trade-off and synergy between ecosystem services at different stages, with significant differences in spatial distribution. The findings of this study provide more spatially targeted suggestions for the restoration and management of tropical montane rainforests in the future.
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Conservación de los Recursos Naturales , Ecosistema , Humanos , Conservación de los Recursos Naturales/métodos , Bosques , Suelo , Carbono , AguaRESUMEN
BACKGROUND: Due to the high mortality and disability rate of intracranial hemorrhage, headache is not the main focus of research on cerebral arteriovenous malformation (AVM), so research on headaches in AVM is still scarce, and the clinical understanding is shallow. This study aims to delineate the risk factors associated with headaches in AVM and to compare the effectiveness of various intervention treatments versus conservative treatment in alleviating headache symptoms. METHODS: This study conducted a retrospective analysis of AVMs who were treated in our institution from August 2011 to December 2021. Multivariable logistic regression analysis was employed to assess the risk factors for headaches in AVMs with unruptured, non-epileptic. Additionally, the effectiveness of different intervention treatments compared to conservative management in alleviating headaches was evaluated through propensity score matching (PSM). RESULTS: A total of 946 patients were included in the analysis of risk factors for headaches. Multivariate logistic regression analysis identified that female (OR 1.532, 95% CI 1.173-2.001, p = 0.002), supply artery dilatation (OR 1.423, 95% CI 1.082-1.872, p = 0.012), and occipital lobe (OR 1.785, 95% CI 1.307-2.439, p < 0.001) as independent risk factors for the occurrence of headaches. There were 443 AVMs with headache symptoms. After propensity score matching, the microsurgery group (OR 7.27, 95% CI 2.82-18.7 p < 0.001), stereotactic radiosurgery group(OR 9.46, 95% CI 2.26-39.6, p = 0.002), and multimodality treatment group (OR 8.34 95% CI 2.87-24.3, p < 0.001) demonstrate significant headache relief compared to the conservative group. However, there was no significant difference between the embolization group (OR 2.24 95% CI 0.88-5.69, p = 0.091) and the conservative group. CONCLUSIONS: This study identified potential risk factors for headaches in AVMs and found that microsurgery, stereotactic radiosurgery, and multimodal therapy had significant benefits in headache relief compared to conservative treatment. These findings provide important guidance for clinicians when developing treatment options that can help improve overall treatment outcomes and quality of life for patients.
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Cefalea , Malformaciones Arteriovenosas Intracraneales , Humanos , Femenino , Malformaciones Arteriovenosas Intracraneales/complicaciones , Malformaciones Arteriovenosas Intracraneales/terapia , Masculino , Cefalea/etiología , Cefalea/terapia , Adulto , Estudios Retrospectivos , Factores de Riesgo , Persona de Mediana Edad , Adulto Joven , Tratamiento Conservador/métodos , Resultado del Tratamiento , Embolización Terapéutica/métodos , AdolescenteRESUMEN
A highly selective turn-on fluorescent and naked-eye colourimetric dual-channel probe for cyanide anions (CN-) has been designed and characterized. In the mixed solution (DMSO / H2O, 9:1, v / v), only CN- could cause an increase in the UV absorption intensity and the corresponding fluorescence intensity increased, and other anions had no significant effect on the probe. After treatment with cyanide in the probe solution, the solution showed a noticeable colour change, from light yellow to purple. Moreover, a fluorescence spectrophotometer can be used to observe that the fluorescence intensity of the solution is significantly enhanced. The response of the colourimetric and fluorescent dual-channel probe to CN- was attributed to nucleophilic addition, and the mechanism was determined by 1H NMR spectroscopy. In addition, this probe was used to detect CN- in actual water samples, including river water, drinking water, and tap water. The spiked CN- recovery rate is very high (97.2%-100.06%), and analytical precision is also very high (RSD < 2%), which shows its feasibility and reliability for detecting cyanide ions in actual water samples.
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Colorimetría , Cianuros/análisis , Colorantes Fluorescentes/química , Contaminantes Químicos del Agua/análisis , Aniones/análisis , Colorantes Fluorescentes/síntesis química , Estructura Molecular , Espectrometría de FluorescenciaRESUMEN
BACKGROUND: The proto-oncogene dishevelled (Dvl) is a critical component of the Wnt/ß-catenin signaling pathway, and its elevated expression in various tumor types is associated with malignancy. However, a role for Dvl in glioma has not been explored. MATERIALS AND METHODS: To determine whether Dvl expression is elevated in human glioma, we examined the protein levels in 67 human glioma samples and 3 normal brain specimens by Western blotting and immunohistochemistry. To investigate a possible association of Dvl with the malignant phenotype in glioma, the correlation of the Dvl immunoreactivity score (IRS) with ß-catenin IRS, the tumor proliferation index (PI), and tumor invasion index (II) were determined for each sample. RESULTS: The Dvl IRS, ß-catenin IRS, PI, and II increased significantly with the pathologic grade of glioma (P <0.001) with average scores of 3.46 ± 3.45, 3.92 ± 3.28, 30.93 ± 17.92, and 20.43 ± 11.79, respectively. Furthermore, the PI and II were significantly higher for the Dvl-positive group than the Dvl-negative group (P <0.001). Correlation analysis demonstrated that ß-catenin IRS, PI, and II were positively correlated with Dvl IRS. CONCLUSIONS: Dvl overexpression may contribute to the malignant proliferation and invasion of human glioma.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Fosfoproteínas/metabolismo , Vía de Señalización Wnt/fisiología , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/patología , Proliferación Celular , Proteínas Dishevelled , Femenino , Glioma/patología , Humanos , Antígeno Ki-67/metabolismo , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Invasividad Neoplásica , Proto-Oncogenes Mas , Adulto Joven , beta Catenina/metabolismoRESUMEN
Extracellular vesicles (EVs) mediate the intercellular crosstalk by transferring functional cargoes. Recently, we have discovered that BaP/BPDE exposure suppresses trophoblast cell migration/invasion and induces miscarriage, which are also regulate by lncRNAs at intracelluar levels. However, the EVs-mediated intercellular regulatory mechanisms are completely unexplored. Specifically, whether EVs might transfer BPDE-induced toxic lncRNA to fresh recipient trophoblast cells and suppress their migration/invasion to further induce miscarriage is completely unknown. In this study, we find that BPDE exposure up-regulates a novel lnc-HZ11, which suppresses EGR1/NF-κB/CXCL12 pathway and migration/invasion of trophoblast cells. Intercellular studies show that EV-HZ11 (lnc-HZ11 in EVs), which is highly expressed in BPDE-exposed donor cells, suppresses EGR1/NF-κB/CXCL12 pathway and migration/invasion in recipient cells by transferring lnc-HZ11 through EVs. Analysis of villous tissues collected from UM (unexplained miscarriage) patients and HC (healthy control) group shows that the levels of BPDE-DNA adducts, lnc-HZ11 or EV-lnc-HZ11, and EGR1/NF-κB/CXCL12 pathway are all associated with miscarriage. Mouse assays show that BaP exposure up-regulates the levels of lnc-Hz11 or EV-Hz11, suppresses Egr1/Nf-κb/Cxcl12 pathway, and eventually induces miscarriage. Knockdown of lnc-Hz11 by injecting EV-AS-Hz11 could effectively alleviate miscarriage in BaP-exposed mice. Furthermore, EV-HZ11 in serum samples could well predict the risk of miscarriage. Collectively, this study not only discovers EVs-HZ11-mediated intercellular mechanisms that BaP/BPDE suppresses trophoblast cell migration/invasion and induces miscarriage but also provides new approach for treatment against unexplained miscarriage through EV-HZ11.
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Aborto Espontáneo , Movimiento Celular , Vesículas Extracelulares , ARN Largo no Codificante , Trofoblastos , Regulación hacia Arriba , Vesículas Extracelulares/metabolismo , Trofoblastos/metabolismo , Humanos , Femenino , ARN Largo no Codificante/genética , Ratones , Animales , Embarazo , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , FN-kappa B/metabolismoRESUMEN
Molecular hybridization is a well-established strategy for developing new drugs. In the pursuit of promising photosensitizers (PSs) with enhanced photodynamic therapy (PDT) efficiency, a series of novel 5-fluorouracil (5FU) gallium corrole conjugates (1-Ga-4-Ga) were designed and synthesized by hybridizing a chemotherapeutic drug and PSs. Their photodynamic antitumor activity was also evaluated. The most active complex (2-Ga) possesses a low IC50 value of 0.185 µM and a phototoxic index of 541 against HepG2 cells. Additionally, the 5FU-gallium corrole conjugate (2-Ga) exhibited a synergistic increase in cytotoxicity under irradiation. Excitedly, treatment of HepG2 tumor-bearing mice with 2-Ga under irradiation could completely ablate tumors without harming normal tissues. 2-Ga-mediated PDT could disrupt mitochondrial function, cause cell cycle arrest in the sub-G1 phase, and activate the cell apoptosis pathway by upregulating the cleaved PARP expression and the Bax/Bcl-2 ratios. This work provides a useful strategy for the design of new corrole-based chemo-photodynamic therapy drugs.
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Apoptosis , Fluorouracilo , Galio , Fotoquimioterapia , Fármacos Fotosensibilizantes , Porfirinas , Fluorouracilo/farmacología , Fluorouracilo/química , Fluorouracilo/uso terapéutico , Humanos , Galio/química , Galio/farmacología , Animales , Porfirinas/farmacología , Porfirinas/química , Porfirinas/uso terapéutico , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/uso terapéutico , Ratones , Apoptosis/efectos de los fármacos , Células Hep G2 , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Ratones Endogámicos BALB C , Ratones DesnudosRESUMEN
Study on corrole photosensitizers (PSs) for photodynamic therapy (PDT) has made remarkable progress. Targeted delivery of PSs is of great significance for enhancing therapeutic efficiency, decreasing the dosage, and reducing systemic toxicity during PDT. The development of PSs that can be specifically delivered to the subcellular organelle is still an attractive and challenging work. Herein, we synthesize a series of azide-modified corrole phosphorus and gallium complex PSs, in which phosphorus corrole 2-P could not only precisely target the endoplasmic reticulum (ER) with a Pearson correlation coefficient (PCC) up to 0.92 but also possesses the highest singlet oxygen quantum yields (ΦΔ = 0.75). This renders it remarkable PDT activity at a very low dosage (IC50 = 23 nM) towards HepG2 tumor cell line while ablating solid tumors in vivo with excellent biosecurity. Furthermore, 2-P exhibits intense red fluorescence (ΦF = 0.25), outstanding photostability, and a large Stokes shift (190 nm), making it a promising fluorescent probe for ER. This study provides a clinically potential photosensitizer for cancer photodynamic therapy and a promising ER fluorescent probe for bioimaging.
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Neoplasias , Fotoquimioterapia , Porfirinas , Azidas , Fluorescencia , Fósforo , Colorantes Fluorescentes/farmacología , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Retículo Endoplásmico , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológicoRESUMEN
The mechanism by which ubiquitin-specific protease 18 (USP18) (enzyme commission: 3.4.19.12) inhibition in cancer promotes cell pyroptosis via the induction of interferon (IFN)-stimulated genes has been recently demonstrated. It is also known that USP18 influences the epithelial-mesenchymal transition of glioma cells. In the present study, the upregulation of USP18 in glioma was revealed through bulk transcriptome analysis, which was associated with poor prognosis in patients with glioma. Furthermore, USP18 levels affected the response to immunotherapy in patients with glioma. Single-cell transcriptome and enrichment analyses demonstrated that USP18 was associated with type 1 IFN responses in glioma T cells. To demonstrate the effect of USP18 expression levels on glioma cells, USP18 expression was knocked down in U251 and U87MG ATCC cell lines. A subsequent Cell Counting Kit-8 assay revealed that glioma cell viability was significantly decreased 4 days after USP18 knockdown. In addition, the knockdown of USP18 expression significantly inhibited the clonogenicity of U251 and U87MG ATCC cells. In conclusion, the present study demonstrated that knockdown of USP18 expression inhibited the proliferation of glioma cells, which may be mediated by the effect of USP18 on the IFN-I response.
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BACKGROUND: Human Deltex 2 (DTX2) is a ubiquitin E3 ligase that functions as an oncogene and has been shown to participate in many human cancers. However, the role of DTX2 in glioma progression has remained obscure. In this study, we explore the mechanism underlying the function of DTX2 in glioma progression. METHODS: The associations between DTX2 expression and clinical characteristics of glioma were determined by bioinformatic analysis of data from The Cancer Genome Atlas and Human Protein Atlas. The expression of DTX2 in glioma tissues was detected using immunohistochemistry and western blotting. Lentivirus-mediated gene knockdown and overexpression were used to determine the effects of DTX2 and helicase-like transcription element (HLTF) on glioma cell proliferation and migration with CCK-8, cell colony formation, transwell, and wound healing assays; flow cytometry in vitro; and animal models in vivo. The interaction of the DTX2 and HLTF proteins was verified by immunoprecipitation assay and confocal microscopy. RESULTS: DTX2 was highly expressed in glioma samples, and this was correlated with worse overall survival. Silencing of DTX2 suppressed glioma cell viability, colony formation, and migration and induced cell apoptosis. In vitro ubiquitination assays confirmed that DTX2 could downregulate HLTF protein levels by increasing ubiquitination of the HLTF protein. We also observed that HLTF inhibited proliferation and migration of glioma cells. Subcutaneous xenografts with DTX2-overexpressing U87 cells showed significantly increased tumor volumes and weights. CONCLUSIONS: We have identified DTX2/HLTF as a new axis in the development of glioma that could serve as a prognostic or therapeutic marker.
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Glioma , Animales , Humanos , Línea Celular Tumoral , Glioma/genética , Glioma/metabolismo , Proliferación Celular/genética , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Apoptosis , Proteínas de Unión al ADN/genética , Factores de Transcripción/genéticaRESUMEN
The cell division cycle associated (CDCA) genes regulate the cell cycle; however, their relationship with prognosis in glioma has been poorly reported in the literature. The Cancer Genome Atlas (TCGA) was utilized to probe the CDCA family in relation to the adverse clinical features of glioma. Glioma single-cell atlas reveals specific expression of CDCA3, 4, 5, 8 in malignant cells and CDCA7 in neural progenitor cells (NPC)-like malignant cells. Glioma data from TCGA, the China Glioma Genome Atlas Project (CGGA) and the gene expression omnibus (GEO) database all demonstrated that CDCA2, 3, 4, 5, 7 and 8 are prognostic markers for glioma. Further analysis identified CDCA2, 5 and 8 as independent prognostic factors for glioma. Lasso regression-based risk models for CDCA families demonstrated that high-risk patients were characterized by high tumor mutational burden (TMB), low levels of microsatellite instability (MSI), and low tumor immune dysfunction and rejection (TIDE) scores. These pointed to immunotherapy for glioma as a potentially viable treatment option Further CDCA clustering suggested that the high CDCA subtype exhibited a high macrophage phenotype and was associated with a higher antigen presentation capacity and high levels of immune escape. In addition, hsa-mir-15b-5p was predicted to be common regulator of CDCA3 and CDCA4, which was validated in U87 and U251 cells. Importantly, we found that CDCAs may indicate response to drug treatment, especially rapamycin, in glioma. In summary, our results suggest that CDCAs have potential applications in clinical diagnosis and as drug sensitivity markers in glioma.
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Glioma , Humanos , Pronóstico , Glioma/tratamiento farmacológico , Glioma/genética , Inmunoterapia , Biología Computacional , Biomarcadores , Proteínas de Ciclo Celular/genética , Proteínas NuclearesRESUMEN
Metastasis remains a major challenge in the successful management of malignant diseases. The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon, stomach, and pancreatic cancers, as well as melanoma, breast cancer, and sarcoma. As an important factor that influences the development of metastatic liver cancer, alternative splicing drives the diversity of RNA transcripts and protein subtypes, which may provide potential to broaden the target space. In particular, the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence, progression, aggressiveness, and drug resistance of cancers caused by the selective splicing of specific genes. This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer. It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes, abnormal splicing, and the contribution of hypoxia to these changes during metastasis.
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The biological functional roles of LGR5 (leucine-rich repeat containing G protein-coupled receptor 5, also known as GPR49), a novel potential marker for stem-like cells in glioblastoma (GSCs), is poorly acknowledged. Here, we demonstrated that LGR5 was detected in glioblastoma tissues and GSCs. Bioinformatics analysis revealed that LGR5 is closely related to neurogenesis and neuronal functions, and preferentially expressed in Proneural subtype of GBMs. Furthermore, LGR5 is regulated by Proneural factor OLIG2, which is important for both neurogenesis and GSC maintenance. Biological experiments in GSC cells validated the bioinformatics analysis results and revealed that LGR5 regulated the tumor sphere formation capacity, an important stem cell property for GSCs. Therefore, LGR5 expression may be functionally correlated with the neurogenic competence, and be regulated by OLIG2 in GSCs.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Glioma/metabolismo , Glioma/patología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Proteínas del Tejido Nervioso/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Adolescente , Adulto , Anciano , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Diferenciación Celular/genética , Biología Computacional , Bases de Datos Genéticas , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes/genética , Glioblastoma/genética , Glioblastoma/patología , Glioma/genética , Humanos , Masculino , Persona de Mediana Edad , Proteínas del Tejido Nervioso/genética , Neuronas/patología , Factor de Transcripción 2 de los Oligodendrocitos , Análisis de Componente Principal , Receptores Acoplados a Proteínas G/genética , Esferoides Celulares/metabolismo , Esferoides Celulares/patología , Células Tumorales Cultivadas , Adulto JovenRESUMEN
Background: The safety of extracranial-intracranial (EC-IC) bypass in the management of anterior circulation intracranial aneurysms (IAs) remains to be determined. This systematic review aims to summarize the existing evidence and provide guidance for the precise management of IAs. Data source: We constructed search strategies and comprehensively searched Pubmed, Medline, Embase, Web of science, and Cochrane library. Methods: This systematic review was actualized according to the PRISMA statement. We evaluated study quality using the methodological index for non-randomized study (MINORS). Effect sizes were pooled using a random-effects model. Heterogeneity between studies was assessed using the I 2 test. Publication bias was assessed using the Egger's test. The registration number for this systematic review is CRD42023396730. Result: This systematic review included a total of 21 articles, involving 915 patients. Postoperative bypass patency rate was 99% (95% CI 0.98-1.00); short-term follow-up was 98% (95% CI 0.94-1.00); long-term follow-up was 95% (95% CI 0.93-0.97). The long-term follow-up occlusion rate of saphenous vein was higher than that of radial artery (OR 6.10 95% CI 1.04-35.59). Short-term surgery-related mortality was 0.3% (95% CI 0.000-0.012); long-term follow-up was 0.4% (95% CI 0.000-0.013); The proportion of patients with a score of 0-2 on the modified Rankin Scale (mRS) during long-term follow-up was 92% (95% CI 0.86-0.98). The incidence rates of long-term follow-up complications were: ischemic 3% (95% CI 0.01-0.06); hemorrhagic 1% (95% CI 0.00-0.03); neurological deficit 1% (95% CI 0.00-0.03); other 3% (95% CI 0.01-0.06). Limitation: Most of the included studies were retrospective studies. Studies reporting preoperative status were not sufficient to demonstrate postoperative improvement. Lack of sufficient subgroup information such as aneurysm rupture status. Conclusion: EC-IC therapy for anterior circulation IAs has a high safety profile. Higher level of evidence is still needed to support clinical decision. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023396730, identifier: CRD42023396730.
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Glioma is the most common tumor of the central nervous system (CNS). Drug resistance, and lack of effective treatment methods make the treatment effect of glioma patients unsatisfactory. The recent discovery of cuproptosis has led to new thinking about the therapeutic and prognostic targets of glioma. The transcripts and clinical data of glioma samples were obtained from The cancer genome atlas (TCGA). The cuproptosis-related lncRNA (CRL)-based glioma prognostic models were built through least absolute shrinkage and selection operator (LASSO) regression analysis in the train set and validated in the test set. Kaplan-Meier survival curve, risk curve analysis, and time-dependent receiver operating characteristic (ROC) curve were used to assess the predictive ability and risk differentiation ability of the models. Univariate and multivariate COX regression analyses were conducted on the models and various clinical features, and then nomograms were constructed to verify their predictive efficacy and accuracy. Finally, we explored potential associations of the models with immune function, drug sensitivity, and the tumor mutational burden of glioma. Four CRLs were selected from the training set of 255 LGG samples and the other four CRLs were selected from the training set of 79 GBM samples to construct the models. Follow-up analysis showed that the models have commendable prognostic value and accuracy for glioma. Notably, the models were also associated with the immune function, drug sensitivity, and tumor mutational burden of gliomas. Our study showed that CRLs were prognostic biomarkers of glioma, closely related to glioma immune function. CRLs may affect uniquely the sensitivity of glioma treatment. It will be a potential therapeutic target for glioma. CRLs will offer new perspectives on the prognosis and therapy of gliomas.
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Apoptosis , Glioma , ARN Largo no Codificante , Humanos , Biomarcadores , Estimación de Kaplan-Meier , Pronóstico , CobreRESUMEN
OBJECTIVE: The effect of surgical clipping (SC) and endovascular coiling (EC) on the incidence of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) has always been a controversial topic. Hence, it is necessary to reanalyze the effects of the 2 surgical methods on DCI, which determines the choice of the most favorable method for patients who are suitable for both surgical modalities. METHODS: A multicenter retrospective observational cohort study was performed to evaluate all consecutive patients with aSAH admitted to 5 medical centers in China between April 2019 and June 2021. Univariable and multivariable analyses were used to confirm risk factors of DCI after aSAH. A 1:1 propensity score matching model was generated in the EC and SC groups to reduce the influence of all confounding factors on DCI. RESULTS: A total of 412 patients were included, and 115 patients (27.9%) developed DCI. After propensity score matching for controlling demographic information, past medical history, admission clinical status, aneurysm characteristics, and inflammatory factors associated with DCI, 133 patients with SC and 133 patients with EC treatment were matched. The results of the matched cohorts indicate a significantly lower incidence of DCI when patients received EC than SC (31.9% vs. 20%; adjusted odds ratio, 1.87; 95% confidence interval, 1.08-3.29; P = 0.027). CONCLUSIONS: The study found that the patients who received SC treatment had a higher incidence of DCI than did those who received EC and suggested that ruptured intracerebral aneurysm is preferentially coiled rather than clipped if the aneurysm is suitable for both surgical modalities.
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Aneurisma Roto , Isquemia Encefálica , Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/epidemiología , Hemorragia Subaracnoidea/cirugía , Estudios Retrospectivos , Incidencia , Puntaje de Propensión , Infarto Cerebral/complicaciones , Isquemia Encefálica/etiología , Isquemia Encefálica/complicaciones , Aneurisma Roto/cirugíaRESUMEN
Gliomas have a high incidence rate in central nervous tumors. Although many breakthroughs have been made in the pathogenesis and treatment of glioma, the recurrence and metastasis rates of patients have not been improved based on the uniqueness of glioma. Glioma destroys the surrounding basement membrane (BM), leading to local infiltration, resulting in the corresponding clinical and neurological symptoms. Therefore, exploring the biological roles played by BM associated genes in glioma is particularly necessary for a comprehensive understanding of the biological processes of glioma and its treatment. Differential expression and univariate COX regression analyses were used to identify the basement membrane genes (BMGs) to be included in the model. LASSO regression was used to construct the BMG model. The Kaplan-Meier (KM) survival analysis model was used to assess the prognosis discrimination between training sets, validation sets, and clinical subgroups. Receiver-operating characteristic (ROC) analysis was used to test the prognostic efficacy of the model. Use calibration curves to verify the accuracy of nomograms. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and gene set enrichment analysis (GSEA) were used to analyze the function and pathway enrichment among the model groups. ESTIMATE and other 7 algorithms including CIBERSORT were used to evaluate the immune microenvironment. "pRRophetic" was used to evaluate drug sensitivity. This study demonstrated that high-risk genes (LAMB4, MMP1, MMP7) promote glioma progression and negatively correlate with patient prognosis. In the tumor microenvironment (TME), high-risk genes have increased scores of macrophages, neutrophils, immune checkpoints, chemokines, and chemokine receptors. This study suggests that BMGs, especially high-risk-related genes, are potential sites for glioma therapy, a new prospect for comprehensively understanding the molecular mechanism of glioma.
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Glioma , Humanos , Pronóstico , Glioma/genética , Nomogramas , Algoritmos , Membrana Basal , Microambiente Tumoral/genéticaRESUMEN
Background: Currently, there is a lack of intuitive analysis regarding the development trend, main authors, and research hotspots in the field of cerebral arteriovenous malformation treatment, as well as a detailed elaboration of possible research hotspots. Methods: A bibliometric analysis was conducted on data retrieved from the Web of Science core collection database between 2000 and 2022. The analysis was performed using R, VOSviewer, CiteSpace software, and an online bibliometric platform. Results: A total of 1,356 articles were collected, and the number of publications has increased over time. The United States and the University of Pittsburgh are the most prolific countries and institutions in the field. The top three cited authors are Kondziolka D, Sheehan JP, and Lunsford LD. The Journal of Neurosurgery and Neurosurgery are two of the most influential journals in the field of brain arteriovenous malformation treatment research, with higher H-index, total citations, and number of publications. Furthermore, the analysis of keywords indicates that "aruba trial," "randomised trial," "microsurgery," "onyx embolization," and "Spetzler-Martin grade" may become research focal points. Additionally, this paper discusses the current research status, existing issues, and potential future research directions for the treatment of brain arteriovenous malformations. Conclusion: This bibliometric study comprehensively analyses the publication trend of cerebral arteriovenous malformation treatment in the past 20 years. It covers the trend of international cooperation, publications, and research hotspots. This information provides an important reference for scholars to further study cerebral arteriovenous malformation.
RESUMEN
Arteriovenous malformation (AVM) recurrence after embolization was rarely reported. This study aimed to explore the potential risk factors of recurrence in angiographically obliterated AVMs treated with endovascular embolization. This study reviewed AVMs treated with embolization only in a prospective multicenter registry from August 2011 to December 2021, and ultimately included 92 AVMs who had achieved angiographic obliteration. Recurrence was assessed by follow-up digital subtraction angiography (DSA) or magnetic resonance imaging (MRI). Hazard ratios (HRs) with 95% confidence intervals were calculated using Cox proportional hazards regression models. Nineteen AVMs exhibited recurrence on follow-up imaging. The recurrence rates after complete obliteration at 6 months, 1 year, and 2 years were 4.35%, 9.78%, and 13.0%, respectively. Multivariate Cox regression analysis identified diffuse nidus (HR 3.208, 95% CI 1.030-9.997, p=0.044) as an independent risk factor for recurrence. Kaplan-Meier analysis confirmed a higher cumulative risk of recurrence with diffuse nidus (log-rank, p=0.016). Further, in the exploratory analysis of the effect of embolization timing after AVM rupture on recurrence after the complete obliteration, embolization within 7 days of the hemorrhage was found as an independent risk factor (HR 4.797, 95% CI 1.379-16.689, p=0.014). Kaplan-Meier analysis confirmed that embolization within 7 days of the hemorrhage was associated with a higher cumulative risk of recurrence in ruptured AVMs (log-rank, p<0.0001). This study highlights the significance of diffuse nidus as an independent risk factor for recurrence after complete embolization of AVMs. In addition, we identified a potential recurrent risk associated with early embolization in ruptured AVMs.
RESUMEN
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Identification of the underlying mechanism of HCC progression and exploration of new therapeutic drugs are urgently needed. Here, a compound library consisting of 419 FDA-approved drugs was taken to screen potential anticancer drugs. A series of functional assays showed that desloratadine, an antiallergic drug, can repress proliferation in HCC cell lines, cell-derived xenograft (CDX), patient-derived organoid (PDO) and patient-derived xenograft (PDX) models. N-myristoyl transferase 1 (NMT1) was identified as a target protein of desloratadine by drug affinity responsive target stability (DARTS) and surface plasmon resonance (SPR) assays. Upregulation of NMT1 expression enhanced but NMT1 knockdown suppressed tumor growth in vitro and in vivo. Metabolic labeling and mass spectrometry analyses revealed that Visinin-like protein 3 (VILIP3) was a new substrate of NMT1 in protein N-myristoylation modification, and high NMT1 or VILIP3 expression was associated with advanced stages and poor survival in HCC. Mechanistically, desloratadine binds to Asn-246 in NMT1 and inhibits its enzymatic activity, disrupting the NMT1-mediated myristoylation of the VILIP3 protein and subsequent NFκB/Bcl-2 signaling. Conclusively, this study demonstrates that desloratadine may be a novel anticancer drug and that NMT1-mediated myristoylation contributes to HCC progression and is a potential biomarker and therapeutic target in HCC.