RESUMO
BACKGROUND: Deaths from COVID-19 are concentrated in older adults, and studies have reported that physical activity (PA) can reduce the risk of death from pneumonia. METHODS: Eight cohort studies and 2 case-control studies were included according to the inclusion and exclusion criteria established in this meta-analysis study followed the PRISMA guideline, 8 cohort studies and 2 case-control studies were finally included. Then, the research objects in these studies were classified to further study the dose-response relationship and non-dose-response relationship. RESULTS: The highest dose of PA reduced the risk of death by 59% (risk ratio =â 0.41; 95% confidence interval: 0.23-0.58) compared with the lowest dose of PA in middle-aged and elderly people. Furthermore, when the PA level wasâ <10 m/wk, the risk of death from pneumonia was reduced by 6% every 4.5 MET-h/wk increase. At a PA levelâ >â 10 m/wk, the risk of death from pneumonia increased by 5% every 4.5 MET-h/wk increase. At a PA levelâ >â 30 m/wk, PA is a risk factor for pneumonia-related death in middle-aged and elderly people. CONCLUSIONS: This meta-analysis showed that PA was associated with a reduced risk of dying from pneumonia in middle-aged and older adults, and that there was a significant nonlinear negative dose-response relationship between PA levels and the risk of dying from pneumonia. Therefore, moderate exercise was recommended.
Assuntos
COVID-19 , Exercício Físico , Pneumonia , Humanos , Idoso , Pneumonia/mortalidade , Pessoa de Meia-Idade , COVID-19/mortalidade , COVID-19/prevenção & controle , Fatores de Risco , SARS-CoV-2RESUMO
The new material introduced by the ITTF in 2014 for table tennis balls has attracted significant attention from players and coaches. Changes in both material selection and production procedures are likely to have affected the static performance of the ball. However, the raw data regarding the elasticity and hardness of these new material balls, encompassing various brands and structures, often lacks practical information crucial for players' rapid adaptation and daily training. The static properties tested in this study were provided by the ITTF, covering both hardness and elasticity. Based on computed variables, this study revealed that the hardness of seam balls at the equator was not consistently higher than that at the pole. Additionally, the study confirmed that the hardness and bounce height of new material balls exceeded those of celluloid. Furthermore, correlation analysis was conducted to examine the relationship between these two properties, revealing a significant correlation between the hardness of seamless balls and their elasticity. This study provides an analysis of the static performance of various types of new material balls, aiding players and coaches in better understanding official event balls and offering a theoretical foundation for the formulation of diverse training and game strategies.
Assuntos
Tênis , Dureza , ElasticidadeRESUMO
OBJECTIVE: To explore the parameters influencing intraoperative calculi excretion (ICE) during flexible ureteroscopy lithotripsy (fURL) using in vitro simulation experiments. METHODS: 3D-printed human kidney models were used to simulate the elimination of gravel during fURL. The factors influencing the ICE during fURL were analyzed by comparing the effects of different degrees of hydronephrosis (mild, moderate, and severe), surgical positions (supine and lateral position), ratios of endoscope-sheath diameter (RESD) (0.625, 0.725, and 0.825), gravel sizes (0.50-1.00 mm, 0.25-0.50 mm, and 0.10-0.25 mm), and ureteral access sheaths (UASs) (traditional UAS and negative-pressure UAS) on ICE. RESULTS: The impacts of various UAS, RESD, degree of hydronephrosis, surgical positions, and gravel sizes on ICE were all significant (p < 0.05). We found no evidence of multicollinearity for all the independent variables, and the linear regression equation fitted as ICE ( g / min ) = 0.102 + 0.083 ∗ UAS grade - 0.050 ∗ RESD grade - 0.048 ∗ hydronephrosis grade + 0.065 ∗ position grade - 0.027 ∗ gravel size grade (R2 = 0.569). CONCLUSION: Employing negative-pressure UAS, smaller RESD, milder hydronephrosis, lateral position, and smaller gravel size contribute to improved ICE during fURL. Among them, the adoption of negative-pressure UAS had the most substantial effects.
Assuntos
Hidronefrose , Cálculos Renais , Litotripsia , Cálculos Ureterais , Humanos , Ureteroscopia , Cálculos Renais/cirurgia , Ureteroscópios , Cálculos Ureterais/cirurgiaRESUMO
Cell senescence genes play a vital role in the pathogenesis of colorectal cancer, a process that may involve the triggering of genetic variations and reversible phenotypes caused by epigenetic modifications. However, the specific regulatory mechanisms remain unclear. Using CellAge and The Cancer Genome Atlas databases and in-house RNA-seq data, DNA methylation-modified cellular senescence genes (DMCSGs) were validated by Support Vector Machine and correlation analyses. In 1150 cases and 1342 controls, we identified colorectal cancer risk variants in DMCSGs. The regulatory effects of gene, variant, and DNA methylation were explored through dual-luciferase and 5-azacytidine treatment experiments, complemented by multiple database analyses. Biological functions of key gene were evaluated via cell proliferation assays, SA-ß-gal staining, senescence marker detection, and immune infiltration analyses. The genetic variant rs4558926 in the downstream of TACC3 was significantly associated with colorectal cancer risk (OR = 1.35, P = 3.22 × 10-4). TACC3 mRNA expression increased due to rs4558926 C > G and decreased DNA methylation levels. The CpG sites in the TACC3 promoter region were regulated by rs4558926. TACC3 knockdown decreased proliferation and senescence in colorectal cancer cells. In addition, subjects with high-TACC3 expression presented an immunosuppressive microenvironment. These findings provide insights into the involvement of genetic variants of cellular senescence genes in the development and progression of colorectal cancer.
Assuntos
Neoplasias Colorretais , Metilação de DNA , Epigênese Genética , Proteínas Associadas aos Microtúbulos , Humanos , Proteínas de Ciclo Celular/genética , Senescência Celular/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Ilhas de CpG , DNA , Regulação Neoplásica da Expressão Gênica , Proteínas Associadas aos Microtúbulos/genética , Microambiente TumoralRESUMO
Cr(III) is a common oxidation state of chromium, and its presence in the environment can occur naturally or as a result of human activities, such as industrial processes, mining, and waste disposal. This article explores the application of machine learning algorithms for the intelligent decision recognition and quantification of Cr(III) in chromium speciation. Three different machine learning models, namely, the Decision Tree (DT) model, the PCA-SVM (Principal Component Analysis-Support Vector Machine) model, and the LDA (Linear Discriminant Analysis) model, were employed and evaluated for accurate and efficient classification of chromium concentrations based on their fluorescence responses. Furthermore, stepwise multiple linear regression analysis was utilized to achieve a more precise quantification of trivalent chromium concentrations through fluorescence visualization. The results demonstrate the potential of machine learning algorithms in accurately detecting and quantifying Cr(III) in chromium speciation with implications for environmental and industrial applications in chromium detection and quantification. The findings from this research pave the way for further exploration and implementation of these models in real-world scenarios, offering valuable insights into various environmental and industrial contexts.
RESUMO
Immunogenic cell death (ICD), a type of cell death that activates the tumor-specific immune response and thus exerts anti-tumor effects, is an emerging target in tumor therapy, but research on ICD-related genes (ICDGs) in colorectal cancer (CRC) remains limited. This study aimed to identify the CRC-specific ICDGs and explore their potential roles. Through RNA sequencing for tissue samples from CRC patients and integration with The Cancer Genome Atlas (TCGA) data, we identified 33 differentially expressed ICDGs in CRC. We defined the ICD score based on these genes in single-cell data, where a high score indicated an immune-active microenvironment. Additionally, molecular subtypes identified in bulk RNA data showed distinct immune landscapes. The ICD-related signature constructed with machine learning effectively distinguished patients' prognosis. The summary data-based Mendelian randomization (SMR) and colocalization analysis prioritized CFLAR for its positive association with CRC risk. Molecular docking revealed its stable binding with chemotherapeutic drugs like irinotecan. Furthermore, experimental validation confirmed CFLAR overexpression in CRC samples, and its knockdown inhibited tumor cell proliferation. Overall, this study expands the understanding of the potential roles and mechanisms of ICDGs in CRC and highlights CFLAR as a promising target for CRC.
Assuntos
Neoplasias Colorretais , Morte Celular Imunogênica , Humanos , Análise da Randomização Mendeliana , Simulação de Acoplamento Molecular , Transcriptoma , Neoplasias Colorretais/genética , Microambiente TumoralRESUMO
OBJECTIVES: Laparoscopic resection for rectal cancer is currently the predominant treatment modality for rectal tumors, with an ongoing focus on reducing the incidence of postoperative complications. In an effort to decrease the occurrence of anastomotic leakage, two additional steps worth considering are reinforcing the anastomosis with a barbed suture and retaining an anal drain as part of the procedure. The results of the operation were analyzed by comparing them to cases where the anastomosis was performed with a stapler alone. METHODS: This study retrospectively analyzed patients who underwent laparoscopic radical rectal cancer surgery between July 2020 and March 2023. The patients were categorized into three cohorts based on the postoperative management following instrumented anastomosis: cohort A, the instrumented anastomosis alone group; cohort B, the reinforced suture group; and cohort C, the reinforced suture and indwelling transanal drainage tube group. Propensity score matching was performed twice in a 1:1 ratio, comparing cohort B to cohort A and cohort C to cohort B. The objective was to compare the benefits and drawbacks among the different groups in terms of operative time, postoperative outcomes and operative costs. RESULTS: 529 patients with laparoscopic resection for rectal cancer were eligible for inclusion. the instrumented anastomosis alone group, reinforced suture group and the reinforced suture and indwelling transanal drainage tube group were performed in 205 patients, 198 patients and 126 patients, respectively. Cohort A and Cohort B differed in three variables after PSM: total operative time (p = 0.018), postoperative hospital stay (p < 0.001) and incidence of anastomotic leakage (p = 0.038). Cohort B had a longer total operative time, shorter postoperative hospital stay and a lower incidence of anastomotic leakage. Similarly, cohort C had less postoperative drainage (P = 0.01) and a longer postoperative hospital stay (P = 0.003) when cohort B and cohort C were matched for propensity scores. There was no significant difference in the cost of surgery between the three cohorts. CONCLUSIONS: The incorporation of barbed suture reinforcement significantly reduces the occurrence of postoperative anastomotic leakage in rectal cancer surgeries. On the other hand, although trans-anal drainage was used as an additional measure to the reinforcement suture of the anastomosis, the utilization of trans-anal drainage tubes does not demonstrate a significant improvement in surgical outcomes.
Assuntos
Laparoscopia , Neoplasias Retais , Humanos , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Anastomose Cirúrgica/métodos , Drenagem/métodos , Laparoscopia/efeitos adversos , Suturas/efeitos adversosRESUMO
Background: Lysosomes are essential for the development and recurrence of cancer. The relationship between a single lysosome-related gene and cancer has previously been studied, but the relationship between the lysosome-related genes (LRGs) and colon adenocarcinoma (COAD) remains unknown. This research examined the role of lysosome-related genes in colon adenocarcinoma. Methods: 28 lysosome-related genes associated with prognosis (PLRGs) were found by fusing the gene set that is differently expressed between tumor and non-tumor in colon adenocarcinoma with the gene set that is related to lysosomes. Using consensus unsupervised clustering of PLRGs, the colon adenocarcinoma cohort was divided into two subtypes. Prognostic and tumor microenvironment (TME) comparisons between the two subtypes were then made. The PLRGs_score was constructed using the least absolute shrinkage and selection operator regression (LASSO) method to quantify each patient's prognosis and provide advice for treatment. Lastly, Western Blot and immunohistochemistry (IHC) were used to identify MOGS expression at the protein level in colon adenocarcinoma tissues. Results: PLRGs had more somatic mutations and changes in genetic level, and the outcomes of the two subtypes differed significantly in terms of prognosis, tumor microenvironment, and enrichment pathways. Then, PLRGs_score was established based on two clusters of differential genes in the cancer genome atlas (TCGA) database, and external verification was performed using the gene expression omnibus (GEO) database. Then, we developed a highly accurate nomogram to enhance the clinical applicability of the PLRGs_score. Finally, a higher PLRGs_score was associated with a poorer overall survival (OS), a lower tumor mutation burden (TMB), a lower cancer stem cell (CSC) index, more microsatellite stability (MSS), and a higher clinical stage. MOGS was substantially elevated at the protein level in colon adenocarcinoma as additional confirmation. Conclusion: Overall, based on PLRGs, we identified two subtypes that varied significantly in terms of prognosis and tumor microenvironment. Then, in order to forecast patient prognosis and make treatment suggestions, we developed a diagnostic model with major significance for prognosis, clinical relevance, and immunotherapy. Moreover, we were the first to demonstrate that MOGS is highly expressed in colon adenocarcinoma.
RESUMO
Background: Aerobic glycolysis is a process that metabolizes glucose under aerobic conditions, finally producing pyruvate, lactic acid, and ATP for tumor cells. Nevertheless, the overall significance of glycolysis-related genes in colorectal cancer and how they affect the immune microenvironment have not been investigated. Methods: By combining the transcriptome and single-cell analysis, we summarize the various expression patterns of glycolysis-related genes in colorectal cancer. Three glycolysis-associated clusters (GAC) were identified with distinct clinical, genomic, and tumor microenvironment (TME). By mapping GAC to single-cell RNA sequencing analysis (scRNA-seq), we next discovered that the immune infiltration profile of GACs was similar to that of bulk RNA sequencing analysis (bulk RNA-seq). In order to determine the kind of GAC for each sample, we developed the GAC predictor using markers of single cells and GACs that were most pertinent to clinical prognostic indications. Additionally, potential drugs for each GAC were discovered using different algorithms. Results: GAC1 was comparable to the immune-desert type, with a low mutation probability and a relatively general prognosis; GAC2 was more likely to be immune-inflamed/excluded, with more immunosuppressive cells and stromal components, which also carried the risk of the poorest prognosis; Similar to the immune-activated type, GAC3 had a high mutation rate, more active immune cells, and excellent therapeutic potential. Conclusion: In conclusion, we combined transcriptome and single-cell data to identify new molecular subtypes using glycolysis-related genes in colorectal cancer based on machine-learning methods, which provided therapeutic direction for colorectal patients.
Assuntos
Neoplasias Colorretais , Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Imunoterapia , Prognóstico , Glicólise/genética , Aprendizado de Máquina , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapiaRESUMO
Retroviruses, especially the pathogenic human immunodeficiency virus type 1 (HIV-1), have severely threatened human health for decades. Retroviruses can form stable latent reservoirs via retroviral DNA integration into the host genome, and then be temporarily transcriptional silencing in infected cells, which makes retroviral infection incurable. Although many cellular restriction factors interfere with various steps of the life cycle of retroviruses and the formation of viral latency, viruses can utilize viral proteins or hijack cellular factors to evade intracellular immunity. Many post-translational modifications play key roles in the cross-talking between the cellular and viral proteins, which has greatly determined the fate of retroviral infection. Here, we reviewed recent advances in the regulation of ubiquitination and SUMOylation in the infection and latency of retroviruses, focusing on both host defense- and virus counterattack-related ubiquitination and SUMOylation system. We also summarized the development of ubiquitination- and SUMOylation-targeted anti-retroviral drugs and discussed their therapeutic potential. Manipulating ubiquitination or SUMOylation pathways by targeted drugs could be a promising strategy to achieve a "sterilizing cure" or "functional cure" of retroviral infection.
Assuntos
Infecções por Retroviridae , Sumoilação , Humanos , Ubiquitinação , Proteínas Virais/metabolismo , Retroviridae/genética , Retroviridae/metabolismoRESUMO
Development of accurate and efficient TCs residue analysis methods is of great significance for the protection of environment, food safety and public health. Herein, a dual-responsive ratiometric fluorescence sensor being capable of simple and sensitive detection of tetracycline (TC) was presented, which was constructed by immobilizing europium ions (Eu3+) onto the mercaptopropionic acid stabilized copper nanoclusters (MPA-Cu NCs). In the presence of TC, the red fluorescence of Eu3+ was enhanced through antenna effect (AE), while the green fluorescence of MPA-Cu NCs was quenched through internal filter effect (IFE), leading to an obvious fluorescence color evolution from green to red for the probe solution. In addition to successful design of a smartphone-assisted colorimetric analysis platform for portable detection, a logic gate device capable of intelligently monitoring TC concentration is also designed.
Assuntos
Európio , Tetraciclinas , Európio/química , Cobre/análise , Corantes Fluorescentes/química , Antibacterianos/análise , Tetraciclina , Espectrometria de Fluorescência/métodosRESUMO
Since the abuse of antibiotic oxytetracycline (OTC) poses a serious threat to the environment and human health, it is of great importance to develop sensitive fluorescent probes for its rapid and in situ detection. Herein, a dual fluorescence response probe based on an aluminum-incorporated metal-organic framework (MOF) was presented for OTC assay. Unlike internal references that demonstrate an independent and stable fluorescence signal intensity in traditional dual-emissive probes, the fluorescence of rhodamine B immobilized in a prepared probe was gradually enhanced at a 585 nm emission wavelength with increasing concentrations of OTC under 405 nm excitation, while OTC also experienced an obvious fluorescence enhancement at a 521 nm emission wavelength due to a molecular conformation transition from the twisted to the extended state, realizing a molecular conformational transition-induced dual fluorescence enhancement for OTC detection under a single excitation wavelength. In addition to the mechanism exploration and double linear range for OTC quantification with nM level detection limits in solution, a paper-based portable test strip was successfully fabricated by loading the probe on glass fiber filter paper with an obvious fluorescence color change from orange to yellow upon increasing the addition of OTC. We expect that the proposed probe in this work would provide an example for the design of organic fluorophore-based sensors exhibiting multiple fluorescence responses under a single excitation.
Assuntos
Oxitetraciclina , Humanos , Antibacterianos , Rodaminas , Corantes Fluorescentes , Conformação MolecularRESUMO
Purpose: Traditional Chinese medicine (TCM) sometimes plays a crucial role in advanced cancer treatment. Despite the significant therapeutic efficacy in hepatocellular carcinoma (HCC) that Actinidia chinensis Planch root extract (acRoots) has proven, its complex composition and underlying mechanism have not been fully elucidated. Therefore, this study analyzed the multiple chemical compounds in acRoots and their targets via network pharmacology and bioinformatics analysis, with the overarching goal of revealing the potential mechanisms of the anti-HCC effect. Methods: The main ingredients contained in acRoots were initially screened from the traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the candidate bioactive ingredient targets were identified using DrugBank and the UniProt public databases. Second, the biological processes of the targets of active molecules filtered from the ingredients of acRoots were evaluated using gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Third, weighted gene coexpression network analysis (WGCNA) was performed to identify gene coexpression modules associated with HCC. The hub genes of acRoots in HCC were defined via contrasting the above module eigengenes with candidate target genes of acRoots. Furthermore, the target-pathway network was analyzed to explore the mechanism for anti-HCC effect of hub genes. Kaplan-Meier plotter database analysis was performed to validate the hub genes of acRoots correlation with prognostic values in HCC. In order to verify the results of the network pharmacological analysis, we performed a molecular docking approach on the active ingredients and key targets using the Discovery Studio software. The viability of SMMC-7721 and HL-7702 cells was determined by Cell counting kit-8 (CCK-8) after being treated with different concentrations of (+)-catechin (0, 50, 100, 150, 200, and 250 g/ml) for 24, 48, and 72 hours, respectively. Finally, qRT-PCR and Western blot involving human hepatocarcinoma cells were utilized to verify the impact of (+)-catechin on the hub genes associated with prognosis. Results: 6 out of 26 active ingredients extracted from TCMSP were deemed as the core ingredients of acRoots. 175 bioactive-ingredient targets of acRoots were obtained and a bioactive-ingredient targets network was established correspondingly. The biological processes (BP) of target genes mainly involved processes, such as toxic substance and wounding. The results of KEGG pathways indicated that the target genes were mainly enriched in pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, and other pathways. Also, the two hub genes (i.e., ESR1 and CAT) were closely associated with the prognosis of HCC patients. As a consequence, we predicated a series of signaling pathways, including estrogen signaling pathway and longevity regulation pathway, through which acRoots could facilitate the treatment for HCC. The molecular docking experiment ascertained that ESR1 and CAT had an effective binding force with (+)-catechin, one of the core ingredients of acRoots. Furthermore, (+)-catechin inhibited SMMC-7721 cell growth in a dose-dependent manner and a time-dependent manner. Finally, we suggest that the expression level of ESR1 and CAT is positively related to the (+)-catechin concentrations in in-vitro experiments. Conclusion: The bioactive ingredients of acRoots, including quercetin, (+)-catechin, beta-sitosterol, and aloe-emodin, have synergistic interactions in reinforcing the anticancer effect in HCC. Evidently, acRoots took effect by regulating multitargets and multipathways through its active ingredients. Further, (+)-catechin, the possible paramount anti-HCC active ingredient in acRoots, helped improve the prognosis of HCC patients by increasing the expression of ESR1 and CAT. Additionally, the findings yielded provide a conceptual guidance for the clinical treatment of HCC and the methods adopted are potentially applicable in the future comprehensive analysis of the underlying mechanisms of TCMs.
RESUMO
BACKGROUND: Post-transarterial chemoembolization (TACE) liver failure occurs frequently in hepatocellular carcinoma (HCC) patients. The identification of predictors for post-TACE liver failure is of great importance for clinical decision-making in this population. AIM: To investigate the occurrence rate and predictive factors of post-TACE liver failure in this retrospective study to provide clues for decision-making regarding TACE procedures in HCC patients. METHODS: The clinical records of HCC patients treated with TACE therapy were reviewed. Baseline clinical characteristics and laboratory parameters of these patients were extracted. Logistic models were used to identify candidates to predict post-TACE liver failure. RESULTS: A total of 199 HCC patients were enrolled in this study, and 70 patients (35.2%) developed post-TACE liver failure. Univariate and multivariate logistic models indicated that microspheres plus gelatin embolization and main tumor size > 5 cm were risk predictors for post-TACE liver failure [odds ratio (OR): 4.4, 95% confidence interval (CI): 1.2-16.3, P = 0.027; OR: 2.3, 95%CI: 1.05-5.3, P = 0.039, respectively]. Conversely, HCC patients who underwent tumor resection surgery before the TACE procedure had a lower risk for post-TACE liver failure (OR: 0.4, 95%CI: 0.2-0.95, P = 0.039). CONCLUSION: Microspheres plus gelatin embolization and main tumor size might be risk factors for post-TACE liver failure in HCC patients, while prior tumor resection could be a favorable factor reducing the risk of post-TACE liver failure.
RESUMO
Omicron variant of SARS-CoV-2 has become the predominant variant worldwide. VV116 is an oral drug with robust anti-SARS-CoV-2 efficacy in preclinical studies. We conducted an open, prospective cohort study to evaluate its safety and effectiveness in Chinese participants infected with the omicron variant from March 8th, 2022 to March 24th, 2022. 136 hospitalized nonsevere patients confirmed with COVID-19 were enrolled including 60 patients who received VV116 (300â mg, BID×5 days) in the treatment group and 76 patients who didn't receive VV116 in the control group besides standard treatment. Viral load shedding time and adverse events were collected during the follow-up. There was no significant difference in baseline characteristics between the VV116 group and the control group, except for a higher symptom prevalence in the control group (P = 0.021). The median time from the first positive test to the first VV116 administration was 5 (range: 2-10) days. Participants who received VV116 within 5 days since the first positive test had a shorter viral shedding time than the control group (8.56 vs 11.13 days), and cox regression analysis showed adjusted HR of 2.37 [95%CI 1.50-3.75], P < 0.001. In symptomatic subgroup, VV116 group had a shorter viral shedding time than the control group (P = 0.016). A total of 9 adverse events with no serious adverse events were reported in the VV116 group, all of them were resolved without intervention. VV116 is a safe, effective oral antiviral drug, which shows a better performance within the early onset of omicron infection.
Assuntos
Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , China/epidemiologia , Humanos , Estudos ProspectivosRESUMO
Empathy involves integrated affective and cognitive processes to share the emotional state of others. This evolutionarily conserved ability has also been identified in nonhuman primates and rodents. Our previous work demonstrated that social interaction with a cagemate rat in pain induces mechanical pain hypersensitivity in cagemate observer (CO) rats. Moreover, we also demonstrated that the medial prefrontal cortex (mPFC) and the locus coeruleus-norepinephrine (LC-NE) system are involved in this process. The LC sends noradrenergic innervations throughout the brain, and its innervation of the prefrontal cortex plays important roles in working memory and attention. The present study seeks to study the roles of the LC-to-mPFC pathway in pain empathy in rats. Selective ablation of the noradrenergic innervations of the mPFC through bilateral injections of the axonally transported catecholamine immunotoxin, saporin-conjugated antiserum to dopamine-ß-hydroxylase into the mPFC diminished mechanical pain hypersensitivity in CO rats. Bilateral intra-mPFC applications of the adrenergic α1 receptor antagonist prazosin and the ß receptor antagonist propranolol, but not the adrenergic α2 antagonist yohimbine, eliminated mechanical pain hypersensitivity in CO rats. In contrast, intra-mPFC applications of prazosin, yohimbine or propranolol did not affect the mechanical pain sensitivity of rats per se. Our results indicate that noradrenergic innervations in the mPFC mediate empathy for pain in rats via the α1 and ß receptors.
Assuntos
Empatia , Norepinefrina , Animais , Norepinefrina/metabolismo , Dor/metabolismo , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: This study has developed a new automatic algorithm for the quantificationy and grading of ankylosing spondylitis (AS)-hip arthritis with magnetic resonance imaging (MRI). METHODS: (1) This study designs a new segmentation network based on deep learning, and a classification network based on deep learning. (2) We train the segmentation model and classification model with the training data and validate the performance of the model. (3) The segmentation results of inflammation in MRI images were obtained and the hip joint was quantified using the segmentation results. RESULTS: A retrospective analysis was performed on 141 cases; 101 patients were included in the derived cohort and 40 in the validation cohort. In the derivation group, median percentage of bone marrow oedema (BME) for each grade was as follows: 36% for grade 1 (<15%), 42% for grade 2 (15-30%),and 22% for grade 3 (≥30%). The accuracy of 44 cases on 835 AS images was 85.7%. Our model made 31 correct decisions out of 40 AS test cases. This study showed that THE accuracy rate 85.7%. CONCLUSIONS: An automatic computer-based analysis of MRI has the potential of being a useful method for the diagnosis and grading of AS hip BME.
Assuntos
Aprendizado Profundo , Espondilite Anquilosante , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Edema/diagnóstico por imagem , Edema/etiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Espondilite Anquilosante/complicações , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/patologiaRESUMO
Oral squamous cell carcinoma (OSCC) is a malignant tumour originating from the mucosal lining of the oral cavity. Its characteristics include hidden onset, high recurrence, and distant metastasis after operation. At present, clinical treatment usually includes surgery, chemotherapy, radiotherapy, or the joint use of these modalities. Unfortunately, multidrug resistant is one of the important obstacles that causes cancer chemotherapy failure. Anlotinib, which has recently been proven to have good antitumour effects, is a novel multitargeted tyrosine kinase inhibitor. However, there are few studies of the anlotinib-associated mechanism in OSCC and its underlying molecular mechanism. In our study, in vitro models of human oral squamous cell carcinoma HSC-3 cells were used to determine the efficacy of anlotinib. On the one hand, we showed that anlotinib treatment significantly reduced the viability and proliferation of HSC-3 cells and decreased cell migration by inhibiting the activation of the Akt phosphorylation pathway. On the other side, anlotinib inhibited PI3K/Akt/Bad phosphorylation and promoted apoptosis of HSC-3 cells by activating RAS protein expression. In brief, these results indicated that anlotinib had prominent antitumour activity in OSCC, mainly by inhibiting the PI3K/Akt phosphorylation pathway. This work provides evidences and a basic principle for using anlotinib to treat patients with OSCC for clinical research.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Indóis/farmacologia , Neoplasias Bucais/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinolinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas ras/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Western Blotting , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Neoplasias Bucais/patologia , Proteínas ras/metabolismoRESUMO
The gut microbiota system plays a vital role in liver diseases. This study aimed to address the diversity of gut microbiota and its correlations with clinical parameters in healthy individuals, chronic liver disease (CLD), and hepatocellular carcinoma (HCC) patients. Fecal specimens of nine healthy individuals, 11 CLD, and 21 HCC were collected. The diversity of gut microbiota was examined by PCR and Illumina MiSeq sequencing and analyzed using 16S rRNA gene sequencing database. The correlations between gut microbiota and the clinical parameters of participants were also addressed. Compared to healthy individuals, Firmicutes at a phylum level decreased in CLD and HCC patients and Proteobacteria increased (p < 0.05). The composition of Blautia on a genus level in CLD and HCC patients significantly decreased compared to healthy controls (p < 0.05). Firmicutes composition was negatively associated with age and number of males (p < 0.05) and was positively associated with monocytes, high-density lipoprotein cholesterol (HDL-C), and estimated glomerular filtration rate (eGFR) levels (p < 0.05). At a genus level, Blautia composition was negatively associated with cirrhosis, age, and number of males (p < 0.01), while it was positively associated with red blood cells (RBCs), triglycerides, HDL-C, and lymphocyte levels (p < 0.05). Conclusively, there was a significant compositional difference in gut microbiota in CLD and HCC patients compared with healthy subjects. Firmicutes and Blautia in gut microbiota system lessened in CLD and HCC patients. Clinical biochemical parameters have an impact on the diversity of gut microbiota in liver diseases.