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OBJECTIVE: To explore the genetic basis and clinical phenotype of a Chinese pedigree affected with Focal segmental glomerulosclerosis (FSGS). METHODS: A male patient who was admitted to the First Affiliated Hospital of Zhengzhou University on July 26, 2018 was selected as the study subject. Clinical data of the patient was collected. Next generation sequencing and Sanger sequencing were carried out to detect the variant sites. Bioinformatic software was used to simulate the effect of candidate variant on the protein functions. RESULTS: Ultrasound exam of the patient showed enhanced echo for the renal parenchyma. Kidney biopsy had confirmed the pathological diagnosis of FSGS (non-specific). Electronic microscopy displayed segmental sclerosis of the glomeruli, mild hyperplasia of mesangial cells and matrix. The proband was found to harbor two novel variants of the PLCE1 gene, namely c.3199delA (p.N1067Mfs*15) and c.4441_4443delATC (p.1481_1481del), which were respectively inherited from his mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+PM2_Supporting+PP3; PM2_Supporting+PM3+PP3). Bioinformatic simulation suggested that both variants could significantly affect the tertiary structure of the PLCE1 protein. CONCLUSION: The c.4441_4443delATC and c.3199delA variants of the PLCE1 gene probably underlay the pathogenesis of the FSGS in this pedigree.
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Glomerulosclerose Segmentar e Focal , Fosfoinositídeo Fosfolipase C , Criança , Humanos , Masculino , Testes Genéticos , Glomerulosclerose Segmentar e Focal/genética , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Linhagem , Fosfoinositídeo Fosfolipase C/genéticaRESUMO
Hydration plays a crucial role in cement composites, but the traditional methods for measuring hydration heat face several limitations. In this study, we propose a machine learning-based approach to predict hydration heat at specific time points for three types of cement composites: ordinary Portland cement pastes, fly ash cement pastes, and fly ash-metakaolin cement composites. By adjusting the model architecture and analyzing the datasets, we demonstrate that the optimized artificial neural network model not only performs well during the learning process but also accurately predicts hydration heat for various cement composites from an extra dataset. This approach offers a more efficient way to measure hydration heat for cement composites, reducing the need for labor- and time-intensive sample preparation and testing. Furthermore, it opens up possibilities for applying similar machine learning approaches to predict other properties of cement composites, contributing to efficient cement research and production.
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BACKGROUND: Improving quality of life is vital for patients with atrial fibrillation (AF) after radiofrequency ablation. Quality of life can be affected not only by personal mastery but also by health promoting behavior as previously studied. However, it remains unclear whether health promoting behavior mediates the relationship between personal mastery and quality of life. OBJECTIVES: To explore whether health promoting behavior mediates the relationship between personal mastery and quality of life in patients with AF after radiofrequency ablation. METHODS: A cross-sectional design and convenience sampling were conducted at a tertiary hospital in China. Self-reported questionnaires were used to assess personal mastery, health promoting behavior and quality of life. SPSS and AMOS software were used for statistical analysis. RESULTS: A total of 202 patients with AF after radiofrequency ablation were enrolled (mean age 58.28 ± 12.70 years). The scores for personal mastery and quality of life were 22.52 ± 2.53 points and 62.58 ± 8.59 points, respectively, indicating a limited level. The health promoting behavior exhibited a moderate level, with scores averaging 103.82 ± 8.47 points. There was a positive correlation between the three variables (all P < 0.05). Health promoting behavior played a partial mediating role in the relationship between personal mastery and quality of life in patients with AF after radiofrequency ablation, accounting for 44.79 % of the total effect. CONCLUSIONS: In order to improve quality of life and prognosis, it is necessary to consider enhancing personal mastery and increasing patient compliance with health promoting behavior, which are important ways to improve their quality of life.
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Fibrilação Atrial , Ablação por Cateter , Qualidade de Vida , Humanos , Fibrilação Atrial/psicologia , Fibrilação Atrial/cirurgia , Qualidade de Vida/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Ablação por Cateter/métodos , Ablação por Cateter/psicologia , Inquéritos e Questionários , China/epidemiologia , Comportamentos Relacionados com a Saúde , Ablação por Radiofrequência/métodos , Ablação por Radiofrequência/psicologia , Idoso , Promoção da Saúde/métodos , AutorrelatoRESUMO
BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a type of chronic interstitial pneumonia, often fatal, with elusive causes and a bleak prognosis. Its treatment options are limited and largely ineffective. Early detection and precise diagnosis are pivotal in managing the disease effectively and enhancing patient survival rates. Recently, the quest for trustworthy biomarkers for IPF has gained momentum. Notably, emerging studies indicate that circular RNAs (circRNAs) found in exosomes may hold significant potential as valuable diagnostic markers. METHODS: In this study, we initially explored the expression profile of circRNAs in exosomes sourced from the blood of IPF patients and healthy volunteers, employing a human circRNA microarray. We then utilized RT-qPCR to corroborate the dysregulated circRNAs identified by the microarray during the training phase. Next, the circRNAs that displayed a significant increase during the training phase were selected for further validation in a larger cohort encompassing 113 IPF patients and 76 healthy volunteers. Ultimately, the expression level and function of hsa_circ_0044226 were substantiated through a series of in vivo and in vitro experiments. RESULTS: Utilizing a human circRNA microarray, we identified 11 dysregulated circRNAs in the exosomes derived from the blood of IPF patients and control volunteers. Subsequent RT-qPCR analysis revealed significant increases in three circRNAs (hsa_circ_0044226, hsa_circ_0004099, hsa_circ_0008898) within the IPF patients. Notably, hsa_circ_0044226 was markedly elevated in patients experiencing acute exacerbation of IPF (AE-IPF) compared to those with stable IPF (S-IPF). Additionally, an upregulation of hsa_circ_0044226 was observed in the blood exosomes derived from a bleomycin-induced IPF mouse model. CONCLUSION: The expression levels of hsa_circ_0044226, hsa_circ_0004099, and hsa_circ_0008898 in plasma exosomes introduce a new paradigm of biomarkers for the diagnosis and progression of IPF.
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Fibrose Pulmonar Idiopática , RNA Circular , Animais , Camundongos , Humanos , RNA Circular/genética , Biomarcadores , Prognóstico , Regulação para Cima , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/genéticaRESUMO
BACKGROUND: Farnesol is a Candida-secreted quorum-sensing molecule of great interest as a potential antifungal agent for serious and hardly curable infections-candidiasis, especially vulvovaginal candidiasis (VVC). METHODS: The effect of farnesol on cellular morphology and viability and evaluated the production of Th1 (IL-2), Th2 (IL-4), proinflammatory (IL-6), chemotactic (IL-8), and Th17 (IL-17) cytokines in the culture supernatants of vaginal epithelial cell line (VK2) were evaluated. Moreover, we tested the inhibitory effect of farnesol on C. albicans adhesion. Scanning electron microscopy was conducted to observe any VK2 cell ultrastructural changes. RESULTS: Only low concentrations (≤ 50 µmol/L) of farnesol did not affect the morphology and viability of the VK2 cells (P > 0.05). Farnesol reduced the adhesion of C. albicans to the VK2 cells. When treated with farnesol, statistical elevated levels of both IL-4 and IL-17 secreted by the infected VK2 cells were present in the culture supernatants (P < 0.05). CONCLUSIONS: Farnesol acts as a stimulator to up-regulate the Th17-type innate immune response, as well as Th2-type humoral immunity following C. albicans infection. Further research is required to select the optimal therapeutic dose to develop efficacious and safe mucosal immune adjuvant for treating VVCs.
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Candida albicans , Farneseno Álcool , Farneseno Álcool/farmacologia , Interleucina-17 , Interleucina-4 , Imunidade Inata , Células EpiteliaisRESUMO
Objective: To investigate the causes of death in patients with chronic renal failure (CRF) on maintenance hemodialysis and its influencing factors. Methods: This is a retrospective study. A total of 300 patients with chronic renal failure undergoing maintenance hemodialysis who were admitted to the Affiliated Hospital of Hebei University from March 2020 to October 2022 were selected as subjects. Various information of patients were collected. In addition, 80 dead patients in this group were investigated for the cause of death, including cardiovascular and cerebrovascular diseases, infections, multi organ failure, and other causes, and the death-related conditions of cardiovascular and cerebrovascular diseases, such as triglyceridr,,total cholesterol, and in blood lipid levels were analyzed. Results: Among the 80 dead patients, cardiovascular and cerebrovascular diseases accounted for a higher proportion of death (66%). Univariate Logistic regression analysis showed that advanced age, plasma homocysteine, blood parathyroid hormone, hyperphosphatemia, hypertension, high volume load and left ventricular hypertrophy were risk factors for death in patients with chronic renal failure on maintenance hemodialysis. Multivariate Logistic regression analysis showed that high volume load, left ventricular hypertrophy and anemia were risk factors for death on maintenance hemodialysis. The levels of hemoglobin (HGB) and high-density lipoprotein (HDL) in patients who died of cardiovascular and cerebrovascular diseases were significantly lower than those in the non-cardio-cerebrovascular death group (P=0.00), and the levels of serum phosphorus, TG and TC were significantly higher than those in the non-cardio-cerebrovascular death group (P, P=0.00; TG, P=0.02; TC, P=0.01). Conclusion: Cardiovascular and cerebrovascular diseases are the leading cause of death in patients with chronic renal failure on maintenance hemodialysis. Adequate dialysis and normal hemoglobin levels are favorable protective factors.
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BACKGROUND: Overexpressed endothelial cell specific molecule-1 (ESM-1) has been identified in various human malignancies, but its expression and function in clear cell renal cell carcinoma (ccRCC) progression are still uncovered. This study explored the critical roles as well as molecular mechanism of ESM-1 in ccRCC progression. METHODS: The ESM-1 expression in ccRCC tissues and cells was measured using Western blot assay. The function of ESM-1 knockdown in ccRCC cell viability, invasion as well as migration was analysed. Changes in specific proteins were also detected by Western blot analysis. RESULTS: The ESM-1 expression increased in ccRCC tissue samples and cells, which indicated poor prognosis. Moreover, ESM-1 silencing considerably inhibited ccRCC cell growth, invasion and migration in vitro. ESM-1 partially promoted ccRCC development through wingless-type mouse mammary tumour integration site family/beta-catenin (Wnt/ß-catenin signalling). CONCLUSIONS: ESM-1 acted as an oncogene by influencing the Wnt/ß-catenin pathway in ccRCC.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Animais , Camundongos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , beta Catenina/genética , beta Catenina/metabolismo , Via de Sinalização Wnt , Regulação Neoplásica da Expressão GênicaRESUMO
Because the increased frequency, intensity, and duration of extreme weather events have significantly challenged power systems, there has been an increased interest in resilient power systems. This article establishes a multicriteria resilience evaluation framework for urban power systems from a physical-cyber-human system perspective, in which the two principal elements responsible for power system function degradation are described, the three major domains comprising urban power systems are explained, four core capacities that positively contribute to power system resilience are proposed, and 15 (11 objective and four subjective) power system resilience evaluation indicators are identified. Fuzzy hesitant judgment and a Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) aggregation method are employed to minimize the expert divergence and maximize the group consensus. A validation method is designed and a comparison with commonly applied performance-based and attributes-based evaluation methods is conducted. The applicability of the evaluation framework is verified using data from four Chinese municipalities: Shanghai, Beijing, Chongqing, and Tianjin. It was found that Shanghai's resilience was the best, and Chongqing's physical resistance disadvantages would result in the greatest difficulties in coping with extreme event disturbances. Physical, cyber, and human domain resilience enhancement strategies are given for different cities separately. This study provides a practical tool to evaluate, compare, and enhance power system resilience for governments and public utilities.
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Sevoflurane, a commonly used anesthetic in surgery, is considered as an inducer of neurodegenerative diseases and postoperative complications including postoperative cognitive dysfunction. Evidence showed that specificity protein 1 (SP1) participated in the regulation of various cellular processes. Also, SP1 was found to modulate sevoflurane-induced hippocampal inflammatory injury both in vitro and in vivo. Our study aimed to illustrate the role of SP1 in mediating mitochondrial stress and autophagy in neurons under sevoflurane exposure. SiRNA for SP1 was transfected in to hippocampus neurons for the loss-of-function assay before sevoflurane stimulation. Meanwhile, recilisib was utilized for PI3K/Akt/mTOR signaling activation, GTS-21 and MLA (methylycaconitine citrate) were used to activate or inactivate alpha 7 nicotinic acetylcholine receptor (α7-nAChR), respectively. Sevoflurane induced SP1 upregulation and autophagy suppression. Interfering SP1 dramatically depressed the promoted oxidative stress and mitochondrial dysfunction induced by sevoflurane. Additionally, SP1 silence blocked sevoflurane-induced activation of PI3K/Akt/mTOR signaling and inhibition of α7-nAChR. Restoring PI3K/Akt/mTOR signaling or depressing CAP significantly reversed the repressive effects of SP1 knockdown on mitochondrial stress and autophagy imbalance in hippocampal cells. In conclusions, our research indicated that SP1 regulated sevoflurane-induced oxidative stress dysregulation, mitochondrial function and cell autophagy in hippocampus via mediating the PI3K/Akt/mTOR and α7-nAChR pathways. Therefore, it might provide a novel sight for sevoflurane-induced hippocampus injury and POCD therapy.
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Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Sevoflurano/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Hipocampo/metabolismo , Autofagia , Neurônios/metabolismo , Mitocôndrias/metabolismoRESUMO
The use of phase change materials (PCMs) in concrete is a double-edged sword that improves the thermal inertia but degrades the mechanical properties of concrete. It has been an essential but unsolved issue to enhance the thermal capacity of PCMs while non-decreasing their mechanical strength. To this end, this work designs a novel 3D printing phase change aggregate to prepare concrete with prominent thermal capacity and ductility. The work investigated the effects of 3D printing phase change aggregate on the compressive strength and splitting tensile strength of concrete. The compressive strength of phase change aggregate concrete is 21.18 MPa, but the ductility of concrete improves. The splitting tensile strength was 1.45 MPa. The peak strain is 11.69 × 10-3, nearly 13 times that of basalt aggregate concrete. Moreover, using 3D printing phase change aggregate reduced concrete's early peak hydration temperature by 7.1%. The thermal insulation capacity of the experiment cube model with phase change concrete has been improved. The results show that the novel 3D printing change aggregate concrete has good mechanical properties and latent heat storage, providing a guideline for applying PCMs in building materials.
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Background: The roles and potential diagnostic value of circRNAs in intracerebral hemorrhage (ICH) remain elusive. Methods: This study aims to investigate the expression profiles of circRNAs by RNA sequencing and RT-PCR in a discovery cohort and an independent validation cohort. Bioinformatics analysis was performed to identify the potential functions of circRNA host genes. Machine learning classification models were used to assess circRNAs as potential biomarkers of ICH. Results: A total of 125 and 284 differentially expressed circRNAs (fold change > 1.5 and FDR < 0.05) were found between ICH patients and healthy controls in the discovery and validation cohorts, respectively. Nine circRNAs were consistently altered in ICH patients compared to healthy controls. The combination of the novel circERBB2 and circCHST12 in ICH patients and healthy controls showed an area under the curve of 0.917 (95% CI: 0.869-0.965), with a sensitivity of 87.5% and a specificity of 82%. In combination with ICH risk factors, circRNAs improved the performance in discriminating ICH patients from healthy controls. Together with hsa_circ_0005505, two novel circRNAs for differentiating between patients with ICH and healthy controls showed an AUC of 0.946 (95% CI: 0.910-0.982), with a sensitivity of 89.1% and a specificity of 86%. Conclusion: We provided a transcriptome-wide overview of aberrantly expressed circRNAs in ICH patients and identified hsa_circ_0005505 and novel circERBB2 and circCHST12 as potential biomarkers for diagnosing ICH.
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Ultra-high-performance concrete (UHPC) has promising applications in civil engineering. However, the elastic modulus of UHPC is relatively low compared with its compressive strength, which may result in insufficient stiffness in service. This work was carried out to explore the feasibility of producing UHPC with high elastic modulus by nano-Al2O3 (NA). Based on particle densely packing theory, the initial mixture of UHPC was designed via the modified Andreasen and Andersen model. An experimental investigation was conducted to systematically examine the effects of NA on different properties of UHPC, including its fluidity, mechanical properties, durability, and microstructure. It was found that: (1) Compared with UHPC without NA, the flexural strength, compressive strength, and elastic modulus of UHPC were improved by 7.38-16.87%, 4.08-20.58%, and 2.89-14.08%, respectively, because of the incorporation of NA; (2) the addition of NA had a prohibiting impact on the threshold pore diameter and porosity of UHPC, which suggested that NA could be conducive to its pore structure; (3) the incorporation of NA led to a decline of 2.9-11.76% in the dry shrinkage of UHPC, which suggested that incorporating NA in a proper amount could reduce the risk of cracking and alleviate the dry shrinkage of UHPC; (4) the optimal amount of NA in UHPC was 1.0%, considering the effects of NA on workability, mechanical properties, microstructure, and the durability of UHPC.
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A growing body of research suggests that mathematical anxiety (MA) seriously affects an individual's math achievement. However, few studies have focused on the cognitive mechanisms of MA in elementary school children. Based on attention control theory (ACT), this research aimed to explore the cognitive mechanism of MA in elementary school children using two studies. In Study 1, the dual-task paradigm of number memory and computation span was used to investigate the difference in processing efficiency between the high-mathematical anxiety (HMA) group and the low-mathematical anxiety (LMA) group. In total, 59 students with HMA and 54 students with LMA participated in Study 1. The results showed that students with HMA had lower processing efficiency in dealing with high-load math tasks. To further investigate the underlying mechanism of low processing efficiency for students with HMA, Study 2 explored the attention bias toward math-related stimuli of students with HMA using the Posner paradigm. In total, 48 students with HMA and 49 students with LMA participated in Study 2. The results showed that math trials put children with HMA in a state of heightened vigilance in general, which might be related to the low processing efficiency in dealing with high-load math tasks. These findings support the ACT and further reveal the mechanism of MA in elementary school children from a cognitive perspective.
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Logro , Ansiedade , Ansiedade/psicologia , Criança , Cognição , Humanos , Matemática , Instituições AcadêmicasRESUMO
Stroke induced by basal ganglia infarction often impair cognitive function. The exploration of topological patterns in structural and functional networks associated cognitive impairment after stroke may contribute to understand the pathological mechanism of cognitive impairment caused by stroke. In this paper, graph theory analysis was applied to diffusion-weighted imaging (DWI) data and resting-state functional MRI (fMRI) data from 23 post-stroke patients with cognitive impairment (PSCI), 17 post-stroke patients without cognitive impairment (NPSCI), and 29 healthy controls (HC). Structural and functional connectivity between 90 cortical and subcortical brain regions was estimated and set threshold to construct a set of undirected graphs. Network-based statistics (NBS) was used to characterize altered connectivity patterns among the three groups. Compared to HC, the PSCI group demonstrated substantial reductions in all three types of connections-rich club, feeder, and local-in structural and functional networks. Specifically, in structural network analysis, reduced connections were observed within basal ganglia and basal ganglia-frontal networks, whereas in the functional network analysis, reduced connections were observed in fronto-parietal network (FPN) and cingulo-opercular networks (CON). Meanwhile, compared to HC, the NPSCI group demonstrated reductions in both feeder and local connections only within occipital area and occipital-temporal structural networks. The findings of reduced structural connectivity in regions stemming from a basal ganglia core and reduced functional connectivity in FPN and CON may indicate a bottom-up cognitive impairment induced by stroke. Graph analysis and connectomics may aid clinical diagnosis and serve as potential imaging biomarkers for post-stroke patients with cognitive impairment.
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Mapeamento Encefálico , Acidente Vascular Cerebral , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo , Gânglios da Base/diagnóstico por imagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Infarto/patologiaRESUMO
Introduction: Despite advances in the diagnosis and management, cryptococcal meningitis (CM) is still associated with high mortality due to insufficient knowledge about clinical characteristics and risk factors for poor outcomes. The aim of the present study is to provide additional evidence for regarding clinical characteristics, diagnosis, and factors associated with increased risk of mortality in CM patients. Methods: In this cohort study, we included eligible patients consecutively admitted to West China Hospital between January 2009 and December 2018. The clinical characteristics and diagnosis method of cerebrospinal fluid culture and India ink stain were analyzed. Independent risk factors were identified by a multivariable logistic regression. Results: A total of 186 CM patients were included in the analysis. After a 1-year follow-up, 63 patients had died. Headache is the most common presenting symptom (97.3%), followed by vomiting (72%), fever (71.5%), altered consciousness (45.7%), abnormal vision (32.8%), and seizure (15.1%). Older age, altered consciousness or seizures, lower white blood cell count or total protein in cerebrospinal fluid (CSF), and unidentified CSF cryptococcal antigen (CrAg) are all factors associated with increasing risk of death (P < 0.05). We also found a dose-dependent trend between the number of symptoms and risk of death (trend p < 0.001). Multivariate logistic regression revealed that age (P = 0.004, OR = 1.042, 95% CI 1.013-1.071), seizure (P = 0.025, OR = 3.105, 95% CI 1.152-8.369), altered consciousness (P < 0.001, OR=6.858, 95% CI 3.063-15.38), and unidentified CSF CrAg are the independent prognostic factors. In addition, we observed that diagnosis of 28.5% and 22.5% CM could not be established by a single testing of CSF India ink stain or culture, respectively. Use of multiple testing methods or combination of the two assays increases the detection rate. Conclusion: Our data show that older age, seizures, altered consciousness, and an inability to detect CSF CrAg are the independent risk factors of death within 1 year in CM patients. Moreover, we recommend use of multiple testing methods with CSF culture and India ink stain. Combined testing with both assays should be considered for initial CM diagnosis.
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Circular RNAs (circRNAs) are highly enriched in the brain and involved in many types of central nervous system pathologies. Herein, this study aimed to investigate the role and mechanism of circ_0007290 in ischemic stroke. The oxygen-glucose deprivation (OGD) model was established with the HCN-2 cells in vitro. Levels of genes and proteins was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. In vitro experiments were conducted using cell counting kit-8 (CCK-8) assay, EdU (5-ethynyl-2'-deoxyuridine) assay, flow cytometry and ELISA, respectively. The levels of lactate dehydrogenase (LDH) were measured using the commercial kit. RNA pull-down and dual-luciferase reporter assay were used to identify the target relationship between miR-496 and circ_0007290 or PDCD4 (programmed cell death protein 4). Circ_0007290 expression was elevated in acute ischemic stroke (AIS) patients and OGD-induced cell injury model. OGD stimulation induced neuronal apoptosis, promoted LDH release, and enhanced inflammation in HCN-2 cells, which all were reversed by the knockdown of circ_0007290. Mechanistically, circ_0007290 served as a sponge for miR-496 to relieve the repression of miR-496 on the expression of its target PDCD4. Moreover, miR-496 inhibition or PDCD4 overexpression abolished the inhibitory effects of circ_0007290 knockdown OGD-evoked neuronal injury. Knockdown of circ_0007290 alleviated OGD-induced neuronal injury by regulating miR-496/PDCD4 axis, providing a novel insight into the pathology of ischemic stroke.
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AVC Isquêmico , MicroRNAs , Proteínas Reguladoras de Apoptose/metabolismo , Glucose , Humanos , AVC Isquêmico/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Oxigênio/metabolismo , Proteínas de Ligação a RNA/genéticaRESUMO
Background: Amino acid (AA) metabolism plays a crucial role in cancer. However, its role in acute myeloid leukemia (AML) is still unavailable. We screened out AA metabolic genes, which related to prognosis, and analyzed their correlation with tumor immune microenvironment in AML. Methods: We evaluated 472 amino acid metabolism-related genes in 132 AML patients. The predictive risk model was developed according to differentially expressed genes, univariate Cox and LASSO analyses. We validated the risk signature by survival analysis and independence tests. Single-sample gene set enrichment analysis (ssGSEA), tumor immune microenvironment (TME), tumor mutation burden (TMB), functional enrichment, and the IC50 of drugs were assessed to explore the correlations among the risk model, immunity, and drug sensitivity of AML. Results: Six amino acid metabolism-related genes were confirmed to develop the risk model, including TRH, HNMT, TFEB, SDSL, SLC43A2, and SFXN3. The high-risk subgroup had an immune "hot" phenotype and was related to a poor prognosis. The high-risk group was also associated with more activity of immune cells, such as Tregs, had higher expression of some immune checkpoints, including PD1 and CTLA4, and might be more susceptible to immunotherapy. Xenobiotic metabolism, the reactive oxygen species (ROS) pathway, fatty acid metabolism, JAK/STAT3, and the inflammatory response were active in the high-risk subgroup. Furthermore, the high-risk subgroup was sensitive to sorafenib, selumetinib, and entospletinib. ssGSEA discovered that the processes of glutamine, arginine, tryptophan, cysteine, histidine, L-serine, isoleucine, threonine, tyrosine, and L-phenylalanine metabolism were more active in the high-risk subgroup. Conclusion: This study revealed that AA metabolism-related genes were correlated with the immune microenvironment of AML patients and could predict the prognosis and immunotherapy response of AML patients.
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Compared with other materials, high-volume fraction aluminum-based silicon carbide composites (hereinafter referred to as SiCp/Al) have many advantages, including high strength, small change in the expansion coefficient due to temperature, high wear resistance, high corrosion resistance, high fatigue resistance, low density, good dimensional stability, and thermal conductivity. SiCp/Al composites have been widely used in aerospace, ordnance, transportation service, precision instruments, and in many other fields. In this study, the ABAQUS/explicit large-scale finite element analysis platform was used to simulate the milling process of SiCp/Al composites. By changing the parameters of the tool angle, milling depth, and milling speed, the influence of these parameters on the cutting force, cutting temperature, cutting stress, and cutting chips was studied. Optimization of the parameters was based on the above change rules to obtain the best processing combination of parameters. Then, the causes of surface machining defects, such as deep pits, shallow pits, and bulges, were simulated and discussed. Finally, the best cutting parameters obtained through simulation analysis was the tool rake angle γ0 = 5°, tool clearance angle α0 = 5°, corner radius r = 0.4 mm, milling depth ap = 50 mm, and milling speed vc = 300 m/min. The optimal combination of milling parameters provides a theoretical basis for subsequent cutting.
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BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications of diabetes mellitus, with an incidence ranging from 60% to 90%. With the change in modern dietary structure, the incidence of diabetes is increasing year by year, and DPN is also on the rise. Tuina therapy has been widely used in the treatment of DPN, but there is no systematic review on the treatment of DPN. Therefore, this study aimed to conduct a meta-analysis of Tuina in the treatment of DPN to clarify its efficacy. METHODS: The following electronic databases will be searched: PubMed, the Cochrane Library, Embase, Web of Science, Medline, CNKI, Chinese Biomedical Literature Database, VIP, and Wan Fang databases. We will consider articles published between database initiation and May 2021. We will use Review Manager 5.4, provided by the Cochrane Collaborative Network for statistical analysis. Clinical randomized controlled trials related to Tuina for diabetic peripheral neuropathy were included in this study. Language is limited to both Chinese and English. Research selection, data extraction, and research quality assessments were independently completed by two researchers. We then assessed the quality and risk of the included studies and observed the outcome measures. RESULTS: This study provides a high-quality synthesis to assess the effectiveness and safety of Tuina for treating diabetic peripheral neuropathy. CONCLUSION: This systematic review will provide evidence to determine whether Tuina is an effective and safe intervention for patients with diabetic peripheral neuropathy. ETHICS AND DISSEMINATION: The protocol of the systematic review does not require ethical approval because it does not involve humans. This article will be published in peer-reviewed journals and presented at relevant conferences. REGISTRATION NUMBER: INPLASY202150027.
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Protocolos Clínicos , Neuropatias Diabéticas/tratamento farmacológico , Medicina Tradicional Chinesa/normas , Resultado do Tratamento , Neuropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/psicologia , Humanos , Medicina Tradicional Chinesa/métodos , Metanálise como Assunto , Revisões Sistemáticas como AssuntoRESUMO
OBJECTIVE: To investigate the effect of sevoflurane on inflammation of microglia in hippocampus of neonatal rats, and to investigate whether the related mechanism is related to Wnt/ß-Catenin/CaMKIV pathway. METHODS: Neonatal rats were anesthetized with 2% or 3% sevoflurane for 4 h a day for 3 consecutive days. Water maze test was used to detect the effect of sevoflurane anesthesia on memory function of neonatal rats. H&E and Nissl staining were used to observe the pathological damage of hippocampal area of neonatal rats induced by sevoflurane anesthesia. The expression of microglial marker Iba-1 was detected by Immunofluorescence. Immunofluorescence and WB were used to detect the expression CD32b, CD86, TNF-α, IL-6, Wnt3a, ß-Catenin and CaMKIV in hippocampus. To further explore the related mechanism, Wnt-3α inhibitor and activator was treated to study the effect of sevoflurane on microglial inflammation in hippocampus of neonatal rats. RESULTS: Sevoflurane anesthesia significantly increased escape latency time, reduced platform crossing times, and damaged the learning and memory ability of neonatal rats. H&E and Nissl staining results showed that sevoflurane anesthesia caused obvious damage to the hippocampus of neonatal rats. Sevoflurane anesthesia promoted the expression of Iba-1 and activated microglia. Sevoflurane anesthesia not only significantly increased the positive expression of CD32b, CD86, TNF-α and IL-6, but also decreased the expression of Wnt3a, ß-Catenin and CaMKIV. These results suggested that sevoflurane inhibited Wnt/ß-Catenin/CaMKIV pathway. CONCLUSION: Sevoflurane induces inflammation of microglia in hippocampus of neonatal rats by inhibiting Wnt/ß-Catenin/CaMKIV pathway.