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The problem of coal compression under buildings is common in underground mining of coal mines in China. The selection of traditional mining programme is subjective and lacks scientific rationality. In order to solve this problem, this paper studies the evaluation index system and model applicable to the selection of coal filling mining scheme under buildings. A multi-objective evaluation index system integrating economic, technical and adaptive factors is constructed. And an integrated optimization model is established, which is based on the traditional grey target model, combining the game theory optimal combination of weights with the hierarchical analysis method, entropy weight method, Critic method to determine the weights, and then introducing the TOPSIS model and the Mars distance to establish an improved grey target decision-making model. The validity of the evaluation index system and model is verified by taking the example of coal mining under pressure of buildings in five mining areas of a coal mine, which provides technical support for decision makers. This study helps to scientifically and reasonably carry out the preferred mining scheme of coal filling under building pressure.
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Background: Biomarkers that reflect brain damage or predict functional outcomes may aid in guiding personalized stroke treatments. Serum neurofilament light chain (sNfL) emerges as a promising candidate for fulfilling this role. Methods: This prospective, observational cohort investigation included 319 acute ischemic stroke (IS) patients. The endpoints were the incidence of early neurological deterioration (END, an elevation of two or more points in the National Institute of Health stroke scale score within a week of hospitalization compared with the baseline) and functional outcome at 3 months (an mRS score of >2 at 3 months was categorized as an unfavorable/poor functional outcome). The association of sNfL, which was assessed within 24 h of admission, with END and unfavorable functional outcomes at follow-up was assessed via multivariate logistic regression, whereas the predictive value of sNfL for unfavorable functional outcomes and END was elucidated by the receiver operating characteristic curve (ROC). Results: Of 319 IS individuals, 89 (27.90%) suffered from END. sNfL not only reflects the severity of stroke measured by NIHSS score (p < 0.05) but also closely related to the severity of age-related white matter changes. Higher initial NIHSS score, severe white matter lesions, diabetes mellitus, and upregulated sNfL were significant predictors of END. Similarly, the multivariate logistic regression analysis results showed that elevated sNfL, a higher baseline NIHSS score, and severe white matter lesions were substantially linked with unfavorable outcomes for 3 months. Similarly, sNfL was valuable for the prediction of the 3 months of poor outcome (95%CI, 0.504-0.642, p = 0.044). Kaplan-Meier analysis shows that patients with elevated sNfL levels are more likely to reach combined cerebrovascular endpoints (log-rank test p < 0.05). Conclusion: This investigation suggests that sNfL can serve as a valuable biomarker for predicting END and 3-month poor functional outcomes after an IS and has the potential to forecast long-term cardiovascular outcomes.
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Lactate dehydrogenase B (LDHB) reversibly catalyzes the conversion of pyruvate to lactate or lactate to pyruvate and expressed in various malignancies. However, the role of LDHB in modulating immune responses against hepatocellular carcinoma (HCC) remains largely unknown. Here, we found that down-regulation of lactate dehydrogenase B (LDHB) was coupled with the promoter hypermethylation and knocking down the DNA methyltransferase 3A (DNMT 3A) restored LDHB expression levels in HCC cell lines. Bioinformatics analysis of the HCC cohort from The Cancer Genome Atlas revealed a significant positive correlation between LDHB expression and immune regulatory signaling pathways and immune cell infiltrations. Moreover, immune checkpoint inhibitors (ICIs) have shown considerable promise for HCC treatment and patients with higher LDHB expression responded better to ICIs. Finally, we found that overexpression of LDHB suppressed HCC growth in immunocompetent but not in immunodeficient mice, suggesting that the host immune system was involved in the LDHB-medicated tumor suppression. Our findings indicate that DNMT3A-mediated epigenetic silencing of LDHB may contribute to HCC progression through remodeling the tumor immune microenvironment, and LDHB may become a potential prognostic biomarker and therapeutic target for HCC immunotherapy.
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Carcinoma Hepatocelular , ADN Metiltransferasa 3A , Epigénesis Genética , L-Lactato Deshidrogenasa , Neoplasias Hepáticas , Microambiente Tumoral , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Microambiente Tumoral/inmunología , Humanos , Animales , Ratones , L-Lactato Deshidrogenasa/metabolismo , L-Lactato Deshidrogenasa/genética , ADN Metiltransferasa 3A/metabolismo , Regulación Neoplásica de la Expresión Génica , Metilación de ADN , Isoenzimas/genética , Isoenzimas/metabolismo , Línea Celular Tumoral , Silenciador del Gen , PronósticoRESUMEN
SARS-CoV-2 evolves constantly with various novel mutations. Due to their enhanced infectivity, transmissibility and immune evasion, a comprehensive understanding of the association between these mutations and the respective functional changes is crucial. However, previous mutation studies of major SARS-CoV-2 variants remain limited. Here, we performed systematic analyses of full-length amino acids mutation, phylogenetic features, protein physicochemical properties, molecular dynamics and immune escape as well as pseudotype virus infection assays among thirteen major SARS-CoV-2 variants. We found that Omicron exhibited the most abundant and complex mutation sites, higher indices of hydrophobicity and flexibility than other variants. The results of molecular dynamics simulation suggest that Omicron has the highest number of hydrogen bonds and strongest binding free energy between the S protein and ACE2 receptor. Furthermore, we revealed 10 immune escape sites in 13 major variants, some of them were reported previously, but four of which (i.e. 339/373/477/496) are first reported to be specific to Omicron, whereas 462 is specific to Epslion. The infectivity of these variants was confirmed by the pseudotype virus infection assays. Our findings may help us understand the functional consequences of the mutations within various variants and the underlying mechanisms of the immune escapes conferred by the S proteins.
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COVID-19 , Evasión Inmune , Simulación de Dinámica Molecular , Mutación , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , SARS-CoV-2/genética , SARS-CoV-2/clasificación , SARS-CoV-2/inmunología , Humanos , COVID-19/virología , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/química , Filogenia , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/química , Unión Proteica , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
This study aimed to screen differentially expressed genes (DEGs) involved in the influence of antiangiogenic therapy on myeloid-derived suppressor cell (MDSC) infiltration and investigate their mechanisms of action. Data on DEGs after the action of antiangiogenic drugs in a pan-cancer context were obtained from the Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the clusterProfiler package in R software. Single-sample gene set enrichment analysis was performed using the gene set variation analysis package to evaluate the levels of immune cells and the activity of immune-related pathways. The relationships of DEGs with the infiltration levels of MDSCs and specific immune cell subpopulations were investigated via gene module analysis. The top 10 key genes were subsequently obtained from PPI network analysis using the cytoHubba plugin of the Cytoscape platform. When the DEGs of the four datasets were intersected, a DEG in the intersection of three datasets and 12 DEGs in the intersection of two datasets were upregulated, and 28 DEGs in the intersection of two datasets were downregulated. GO and KEGG pathway enrichment analyses revealed that the DEGs were associated with multiple important signaling pathways closely related to tumor onset and development, including cell differentiation, cell proliferation, the cell cycle, and immune responses. Most downregulated genes in lung adenocarcinoma (LUAD) were positively correlated with MDSC expression. Only MGP was negatively correlated; the correlation between CACNG6 and MDSC expression was statistically insignificant. In lung squamous cell carcinoma (LUSC), the relationships of PMEPA1, PCDH7, NEURL1B, and CACNG6 with MDSC expression were statistically insignificant; MGP was negatively correlated with MDSC expression. The top 10 key genes with the highest degree scores obtained using the cytoHubba plugin of Cytoscape were AURKB, RRM2, BUB1, NUSAP1, PRC1, TOP2A, NCAPH, CENPA, KIF2C, and CCNA2. Most of these genes were upregulated in LUAD and associated with immune cell infiltration and prognosis in tumors. An analysis of the relationships between DEGs and infiltration by other specific immune cells revealed the presence of consistent patterns in the downregulated genes, which exhibited positive correlations with the levels of Th2 cells, γδ T cells, and CD56dim NK cells, and negative correlations with other infiltrating immune cells. Antiangiogenic therapy may regulate MDSC infiltration through multiple important signaling pathways closely associated with tumor onset and development, such as cell differentiation, cell proliferation, the cell cycle, and immune responses. Antiangiogenic drugs may exert effects by affecting various types of infiltrating cells associated with immune suppression.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Células Supresoras de Origen Mieloide , Humanos , Inmunoterapia , Ciclo Celular , Microambiente Tumoral/genética , Proteínas Nucleares , Proteínas de Ciclo Celular , Proteínas de la MembranaRESUMEN
BACKGROUND: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). METHODS: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD's causal effects on the relative abundances of specific features of the gut microbiome. RESULTS: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. CONCLUSION: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.
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Microbioma Gastrointestinal , Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/genética , Estudio de Asociación del Genoma Completo , Reproducibilidad de los Resultados , Suplementos DietéticosRESUMEN
BACKGROUND: Gastric cancer is a highly prevalent cancer type and the underlying molecular mechanisms are not fully understood. Ubiquitin-specific peptidase (USP) 29 has been suggested to regulate cell fate in several types of cancer, but its potential role in gastric carcinogenesis remains unclear. METHODS: The expression of USP29 in normal and gastric cancer tissues was analyzed by bioinformatics analysis, immunohistochemistry and immunoblot. Gene overexpression, CRISPR-Cas9 technology, RNAi, and Usp29 knockout mice were used to investigate the roles of USP29 in cell culture, xenograft, and benzo[a]pyrene (BaP)-induced gastric carcinogenesis models. We then delineated the underlying mechanisms using mass spectrometry, co-immunoprecipitation (Co-IP), immunoblot, ubiquitination assay, chromatin immunoprecipitation (ChIP), quantitative real-time PCR (qRT-PCR), and luciferase assays. RESULTS: In this study, we found that USP29 expression was significantly upregulated in gastric cancers and associated with poor patient survival. Ectopic expression of USP29 promoted, while depletion suppressed the tumor growth in vitro and in vivo mouse model. Mechanistically, transcription factor far upstream element binding protein 1 (FUBP1) directly activates USP29 gene transcription, which then interacts with and stabilizes aurora kinase B (AURKB) by suppressing K48-linked polyubiquitination, constituting a FUBP1-USP29-AURKB regulatory axis that medicates the oncogenic role of USP29. Importantly, systemic knockout of Usp29 in mice not only significantly decreased the BaP-induced carcinogenesis but also suppressed the Aurkb level in forestomach tissues. CONCLUSIONS: These findings uncovered a novel FUBP1-USP29-AURKB regulatory axis that may play important roles in gastric carcinogenesis and tumor progression, and suggested that USP29 may become a promising drug target for cancer therapy.
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BACKGROUND: There is still no consensus on whether primary pontine hemorrhage (PPH) should be managed conservatively or treated promptly via surgical evacuation of the hematoma. The purpose of this study was to assess the therapeutic effect of robotic frameless stereotactic aspiration with thrombolysis in the treatment of PPH. METHODS: A total of 39 patients with PPH treated between January 2012 and November 2016 were included in the study. Sixteen patients underwent frameless stereotactic surgical treatment (ST group) and 23 patients underwent conservative treatment (CT group). Clinical and radiologic parameters were assessed, and the patient outcomes were analyzed over a 6-month follow-up period. RESULTS: Surgical treatment did not result in any intracranial infections, or complications. Baseline characteristics did not significantly differ between the two groups. At discharge, the average Glasgow Coma Scale (GCS) score and the overall Glasgow Outcome Scale (GOS) score were significantly higher in the ST group compared to the CT group (p < 0.05). The mortality rate (GOS score 1) was significantly lower in the ST group (18.75%, 3/16) than in the CT group (52.17%, 12/23). For patients with hematoma volumes of 5 to 10 mL or GCS scores of 6 to 8, following treatment, the ST group exhibited markedly higher GOS scores in comparison to the CT group. CONCLUSION: Our study suggests that robotic frameless stereotactic aspiration with thrombolysis is a safe and efficient method for the treatment of PPH. Patients with hematomas of 5 to 10 mL or GCS scores of 6 to 8 could benefit from surgery.
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In this paper, a full solid waste-based grouting material was prepared using three industrial solid wastes, i.e., sludge, coal gangue (CG), and ground granulated blast furnace slag (GGBS), based on the concepts of synergy and complementarity. The effects of the dosage of raw sewage sludge (SS), incineration-activated sewage sludge ash (SSA), and an alkali activator on the fluidity, water separation rate, and mechanical strength of solid waste-based grouting materials were systematically investigated. The mechanism of action was analyzed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Finally, the leaching characteristics and stabilization efficiency of heavy metals in solid-sample-based slurry stones were determined. The experimental results show that the slurry fluidity and water separation proportion are negatively correlated with the amount of sludge. The rate of decline first increases and then decreases. When the SSA content is greater than 10%, the precipitation rate can be controlled to within 5%. The optimal amount of alkaline activator is 8%, and its effect on the mechanical strength is more significant than that of sludge. With an increase in the SSA dosage, the compressive strength first increases and then decreases. At 25%, the strength still reaches 20.8 MPa, and the decrease from 0 to 25% is only 26.2%. On the contrary, the addition of SS continues to decrease the strength of the stone body by 81.9%. The high organic content and low volcanic ash activity in SS hinder the development of hydration cementation. In addition, the comparative analysis demonstrated the contribution of the volcanic ash activity possessed by SSA to the mechanical strength supplement after incineration. The incineration treatment caused the calcite (CaCO3) in SS to decompose at high temperatures, and more Ca sources were introduced in SSA. The incorporation of SSA in the cementation system resulted in higher Ca/Si and Ca/Al ratios, promoting the formation of C-(A)-S-H gel. Moreover, this incorporation enhances the stability of heavy metals within the slurry, reducing the potential environmental risk associated with the leaching of Cr and Ni from the raw materials. Consequently, these findings comply with the leaching requirements specified by the environmental standards. The research provides innovative insights into the synergistic resource utilization of SS and SSA with coal-based solid waste to prepare environmentally friendly, high-performance, and cost-effective grouting materials.
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BACKGROUND: The function and regulation of miRNAs in progression of chordoma were unclear. METHODS: Five miRNAs were identified by the machine learning method from the miRNA expression array. CCk-8 assay, EDU assay, wound healing migration assay, and trans-well assay were used to reveal the effect of the miRNAs in chordoma cell lines. Moreover, bioinformation analysis and the mRNA expression array between the primary chordomas and recurrent chordomas were used to find the target protein genes of miRNAs. Furthermore, qRT-PCR and luciferase reporter assay were used to verify the result. RESULTS: miR-186-5p, miR-30c-5p, miR-151b, and miR-125b-5p could inhibit proliferation, migration, and invasion of chordoma while miR-1260a enhances proliferation, migration, and invasion of chordoma. Recurrent chordoma has a worse disease-free outcome than the primary chordoma patients. AMOT, NPTX1, RYR3, and P2RX5 were the target protein mRNAs of miR-186-5p; NPTX1 was the target protein mRNAs of miR-125b-5p; and AMOT and TNFSF14 were the target protein mRNAs of miR-1260a. CONCLUSIONS: miR-186-5p, miR-125b-5p, miR-1260a, and their target protein mRNAs including AMOT, NPTX1, RYR3, P2RX5, TNFSF14 may be the basement of chordoma research.
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Cordoma , MicroARNs , Humanos , Cordoma/genética , Canal Liberador de Calcio Receptor de Rianodina/genética , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Recurrencia Local de Neoplasia/genética , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/genética , Línea Celular TumoralRESUMEN
BACKGROUND: Analyzing meningioma of distinct pathological types at the single-cell level can provide new and valuable insights into the specific biological mechanisms of each cellular subpopulation, as well as their vital interplay within the tumor microenvironment. METHODS: We recruited patients diagnosed with four distinct types of meningioma and performed single-cell RNA sequencing on their tumor samples, concurrently analyzing a publicly available dataset for comparison. Next, we separated the cells into discrete clusters and identified their unique identities. Using pseudotime analysis, we demonstrated cellular differentiation and dynamics. To investigate biological function, we employed weighted gene co-expression network analysis, gene regulatory network, and gene set enrichment analysis. Additionally, we conducted cell-cell communication analyses to characterize interactions among different clusters and validated a crucial interaction using multiple immunofluorescence staining. RESULTS: The single-cell transcriptomic profiles for five meningioma of different pathological types demonstrated that neoplastic cells exhibited high inter-sample heterogeneity and diverse biological functions featured by metabolic regulation. A small cluster of neoplastic cells (N5 cluster, < 3%) was most proliferative, indicated by high expression of MKI67 and TOP2A. They were primarily observed in our atypical and transitional meningioma samples and located at the beginning of the pseudotime differentiation branch for neoplastic cells. Macrophages, the most abundant immune cells present, showed two distinct developmental trajectories, one promoting and the other suppressing meningioma growth, with the MIF-CD74 interaction serving as the primary signaling pathway for MIF signals in the tumor environment. Unexpectedly, despite its small cluster size, the N5 cluster demonstrated a significant contribution in this interaction. By staining pathological sections of more samples, we found that this interaction was widely present in different types of meningiomas. CONCLUSIONS: Meningioma neoplastic cells' diverse types cause inter-sample heterogeneity and a wide range of functions. Some proliferative neoplastic cell may educate macrophages, which promotes tumorigenesis possibly through the MIF-CD74 interaction. It provides novel clues for future potential therapeutic avenues.
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Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/genética , Regulación Neoplásica de la Expresión Génica , Macrófagos/patología , Perfilación de la Expresión Génica , Comunicación Celular , Transcriptoma/genética , Neoplasias Meníngeas/genética , Análisis de la Célula Individual , Microambiente Tumoral/genéticaRESUMEN
Cancer cells show enhanced nucleotide biosynthesis, which is essential for their unlimited proliferation, but the underlying mechanisms are not entirely clear. Ubiquitin specific peptidase 29 (USP29) was reported to sustain neuroblastoma progression by promoting glycolysis and glutamine catabolism; however, its potential role in regulating nucleotide biosynthesis in tumor cells remains unknown. In this study, we depleted endogenous USP29 in MYCN-amplified neuroblastoma SK-N-BE2 cells by sgRNAs and conducted metabolomic analysis in cells with or without USP29 depletion, we found that USP29 deficiency caused a disorder of intermediates involved in glycolysis and nucleotide biosynthesis. De novo nucleotide biosynthesis was analyzed using 13C6 glucose as a tracer under normoxia and hypoxia. The results indicated that USP29-depleted cells showed inhibition of nucleotide anabolic intermediates derived from glucose, and this inhibition was more significant under hypoxic conditions. Analysis of RNA sequencing data in SK-N-BE2 cells demonstrated that USP29 promoted the gene expression of metabolic enzymes involved in nucleotide anabolism, probably by regulating MYC and E2F downstream pathways. These findings indicated that USP29 is a key regulator of nucleotide biosynthesis in tumor cells.
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Multiómica , Neuroblastoma , Humanos , ARN Guía de Sistemas CRISPR-Cas , Neuroblastoma/patología , Glucólisis , Glucosa , Línea Celular Tumoral , Proteína Proto-Oncogénica N-Myc/genética , Proteína Proto-Oncogénica N-Myc/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteasas Ubiquitina-Específicas/metabolismoRESUMEN
BACKGROUND: The causal association between the gut microbiome and the development of migraine and its subtypes remains unclear. METHODS: The single nucleotide polymorphisms concerning gut microbiome were retrieved from the gene-wide association study (GWAS) of the MiBioGen consortium. The summary statistics datasets of migraine, migraine with aura (MA), and migraine without aura (MO) were obtained from the GWAS meta-analysis of the International Headache Genetics Consortium (IHGC) and FinnGen consortium. Inverse variance weighting (IVW) was used as the primary method, complemented by sensitivity analyses for pleiotropy and increasing robustness. RESULTS: In IHGC datasets, ten, five, and nine bacterial taxa were found to have a causal association with migraine, MA, and MO, respectively, (IVW, all P < 0.05). Genus.Coprococcus3 and genus.Anaerotruncus were validated in FinnGen datasets. Nine, twelve, and seven bacterial entities were identified for migraine, MA, and MO, respectively. The causal association still exists in family.Bifidobacteriaceae and order.Bifidobacteriales for migraine and MO after FDR correction. The heterogeneity and pleiotropy analyses confirmed the robustness of IVW results. CONCLUSION: Our study demonstrates that gut microbiomes may exert causal effects on migraine, MA, and MO. We provide novel evidence for the dysfunction of the gut-brain axis on migraine. Future study is required to verify the relationship between gut microbiome and the risk of migraine and its subtypes and illustrate the underlying mechanism between them.
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Microbioma Gastrointestinal , Trastornos Migrañosos , Migraña con Aura , Humanos , Microbioma Gastrointestinal/genética , Estudios de Asociación Genética , Estudio de Asociación del Genoma Completo , Cefalea , Trastornos Migrañosos/genéticaRESUMEN
PURPOSE: To investigate the different clinical and cytogenetic features of skull base meningiomas (SBMs) and non-SBMs (NSBMs). METHODS: We conducted a retrospective study on a series of 316 patients with primary intracranial meningiomas. The t-test and the Chi-square test were used to analyze the differences between 194 SBMs and 122 NSBMs. The Cox analysis was used to determine prognostic factors for tumor recurrence. RESULTS: Compared with NSBMs, on average, the age of patients with SBMs was about 2.88 years younger (p = 0.024); the duration of operation of SBMs was 2.73 h longer (p < 0.001); the duration of hospital stays of patients with SBMs was about 6.76 days longer (p < 0.001); the tumor volume was 7.69 cm3 smaller (p = 0.025); the intraoperative blood loss was 147.61ml more (p = 0.039); the total cost of SBMs was 1.39 times more (p < 0.001); the preoperative KPS, postoperative KPS, and follow-up KPS of patients with SBMs were all respectively lower (p < 0.001); Gross total resection was less achieved (p < 0.001). SBMs (average of 20.80 per sample) had a smaller total number of copy number variations (CNVs) than NSBMs (29.98 per sample) (p = 0.009). Extremely large CNVs (> 5 Mb) were more likely to present in NSBMs (p < 0.001). Cox analysis showed that subtotal resection (p = 0.002) and the total number of CNVs (p = 0.015) were independent risk factors for tumor recurrence. CONCLUSIONS: The clinical and cytogenetic features of SBMs were different from NSBMs. Moreover, the degree of resection and the total number of whole-genome CNVs were independent prognostic factors for tumor recurrence.
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Neoplasias Meníngeas , Meningioma , Neoplasias de la Base del Cráneo , Humanos , Preescolar , Meningioma/genética , Meningioma/cirugía , Meningioma/patología , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/patología , Estudios Retrospectivos , Estudios de Seguimiento , Recurrencia Local de Neoplasia/genética , Variaciones en el Número de Copia de ADN , Neoplasias de la Base del Cráneo/genética , Neoplasias de la Base del Cráneo/cirugía , Neoplasias de la Base del Cráneo/patología , Análisis Citogenético , Resultado del TratamientoRESUMEN
Soft biological tissues perform various functions. Sensory nerves bring sensations of light, voice, touch, pain, or temperature variation to the central nervous system. Animal senses have inspired tremendous sensors for biomedical applications. Following the same principle as photosensitive nerves, we design flexible ionic hydrogels to achieve a biologic photosensor. The photosensor allows responding to near-infrared light, which is converted into a sensory electric signal that can communicate with nerve cells. Furthermore, with adjustable thermal and/or electrical signal outputs, it provides abundant tools for biological regulation. The tunable photosensitive performances, high flexibility, and low cost endow the photosensor with widespread applications ranging from neural prosthetics to human-machine interfacing systems.
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Biónica , Percepción del Tacto , Animales , Humanos , Hidrogeles , Tacto , NeuronasRESUMEN
Mortality is the most clinically serious outcome, and its prevention remains a constant struggle. This study was to assess whether intravenous or oral vitamin C (Vit-C) therapy is related to reduced mortality in adults. Data from Medline, Embase, and the Cochrane Central Register databases were acquired from their inception to 26 October 2022. All randomized controlled trials (RCTs) involving intravenous or oral Vit-C against a placebo or no therapy for mortality were selected. The primary outcome was all-cause mortality. Secondary outcomes were sepsis, COVID-19, cardiac surgery, noncardiac surgery, cancer, and other mortalities. Forty-four trials with 26540 participants were selected. Although a substantial statistical difference was observed in all-cause mortality between the control and the Vit-C-supplemented groups (p = 0.009, RR 0.87, 95% CI 0.78 to 0.97, I2 = 36%), the result was not validated by sequential trial analysis. In the subgroup analysis, mortality was markedly reduced in Vit-C trials with the sepsis patients (p = 0.005, RR 0.74, 95% CI 0.59 to 0.91, I2 = 47%), and this result was confirmed by trial sequential analysis. In addition, a substantial statistical difference was revealed in COVID-19 patient mortality between the Vit-C monotherapy and the control groups (p = 0.03, RR 0.84, 95% CI 0.72 to 0.98, I2 = 0%). However, the trial sequential analysis suggested the need for more trials to confirm its efficacy. Overall, Vit-C monotherapy does decrease the risk of death by sepsis by 26%. To confirm Vit-C is associated with reduced COVID-19 mortality, additional clinical random control trials are required.
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Ácido Ascórbico , COVID-19 , Adulto , Humanos , Causas de Muerte , Vitaminas , Suplementos DietéticosRESUMEN
Type 2 diabetes mellitus (T2DM) shares a common molecular mechanism and underlying pathology with dementia, and studies indicate that dementia is widespread in people with T2DM. Currently, T2DM-induced cognitive impairment is characterized by altered insulin and cerebral glucose metabolism, leading to a shorter life span. Increasing evidence indicates that nutritional and metabolic treatments can possibly alleviate these issues, as there is a lack of efficient preventative and treatment methods. The ketogenic diet (KD) is a very high-fat, low-carbohydrate diet that induces ketosis in the body by producing a fasting-like effect, and neurons in the aged brain are protected from damage by ketone bodies. Moreover, the creation of ketone bodies may improve brain neuronal function, decrease inflammatory expression and reactive oxygen species (ROS) production, and restore neuronal metabolism. As a result, the KD has drawn attention as a potential treatment for neurological diseases, such as T2DM-induced dementia. This review aims to examine the role of the KD in the prevention of dementia risk in T2DM patients and to outline specific aspects of the neuroprotective effects of the KD, providing a rationale for the implementation of dietary interventions as a therapeutic strategy for T2DM-induced dementia in the future.
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Demencia , Diabetes Mellitus Tipo 2 , Dieta Cetogénica , Cetosis , Humanos , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Cuerpos Cetónicos/metabolismo , Cetosis/metabolismoRESUMEN
With the advancement of technology, increasingly many newborns are receiving general anesthesia at a young age for surgery, other interventions, or clinical assessment. Anesthetics cause neurotoxicity and apoptosis of nerve cells, leading to memory and cognitive impairments. The most frequently used anesthetic in infants is sevoflurane; however, it has the potential to be neurotoxic. A single, short bout of sevoflurane exposure has little impact on cognitive function, but prolonged or recurrent exposure to general anesthetics can impair memory and cognitive function. However, the mechanisms underlying this association remain unknown. Posttranslational modifications (PTMs), which can be described roughly as the regulation of gene expression, protein activity, and protein function, have sparked enormous interest in neuroscience. Posttranslational modifications are a critical mechanism mediating anesthesia-induced long-term modifications in gene transcription and protein functional deficits in memory and cognition in children, according to a growing body of studies in recent years. Based on these recent findings, our paper reviews the effects of sevoflurane on memory loss and cognitive impairment, discusses how posttranslational modifications mechanisms can contribute to sevoflurane-induced neurotoxicity, and provides new insights into the prevention of sevoflurane-induced memory and cognitive impairments.
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OBJECTIVE: Rosai-Dorfman disease (RDD) is a rare, idiopathic, and non-neoplastic histio-proliferative disease that is uncommon in the central nervous system. Hence, reports of management of RDD in the skull base are scarce and only a few studies on skull base RDD are available. The objective of this study was to analyze the diagnosis, treatment, and prognosis of RDD in the skull base and explore an appropriate treatment strategy thereof. METHODS: Nine patients with clinical characteristics and follow-up data from our department between 2017 and 2022 were included in this study. From this information, the clinical profiles, imaging, treatment, and prognosis data were collected. RESULTS: There were 6 male and 3 female patients with skull base RDD. These patients ranged in age from 13 to 61 years, with a median age of 41 years. The locations included 1 anterior skull base orbital apex, 1 parasellar region, 2 sellar regions, 1 petroclivus, and 4 foramen magnum regions. Six patients underwent total resection and 3 underwent subtotal resection. Patient follow-up lasted 11-65 months, with a median duration of 24 months. One patient died, 2 experienced recurrence, and the other patients' lesions were stable. The symptoms worsened and new complications occurred in 5 patients. CONCLUSIONS: Skull base RDDs are intractable diseases with a high rate of complications. Some patients are at risk of recurrence and death. Surgery may be the basic treatment for this disease, and combined therapy including targeted therapy or radiation therapy may also be a valuable therapeutic strategy.