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1.
Sci Rep ; 14(1): 6003, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472493

RESUMO

To investigate the efficacy and safety of drug-eluting bead-transarterial chemoembolization (DEB-TACE) combined with systemic chemotherapy in HR+/Her2- locally advanced breast cancer (LABC) patients. A controlled study was conducted on LABC patients treated at Jianyang People's Hospital and the First Affiliated Hospital of Chengdu Medical College from December 2020 to June 2022. The patients were randomly divided into the experimental group and the control group. The experimental group received DEB-TACE combined with the TAC regimen (175 mg/m2 paclitaxel-loaded albumin, 50 mg/m2 Doxorubicin, and 500 mg/m2 cyclophosphamide), while the control group received the TAC regimen intravenously. The therapeutic efficacy was evaluated using the mRECIST criteria. Statistical analysis was performed using SPSS 22.0 software, and baseline characteristics, overall response rate (ORR), pathological complete response (PCR), adverse reactions, and complications were compared between the two groups using paired t-test and chi-square test. A total of 60 patients were included, with 30 patients in the experimental group (50%) and 30 patients in the control group (50%). After the first treatment, the ORR was 90% in the experimental group and 60% in the control group (P < 0.05). The overall ORR was 100% in the experimental group and 83% in the control group (P < 0.05). PCR was achieved in 14 patients (47%) in the experimental group and 4 patients (13%) in the control group. The main adverse reactions in the experimental group were skin blistering, pigmentation, and pain. There was no statistically significant difference in vomiting and grade II or above bone marrow suppression between the two groups. No grade III or above adverse events occurred in either group. The comparison of tumor shrinkage between the two groups was P = 0.051, and axillary lymph node shrinkage was P < 0.05. The use of drug-eluting beads in combination with neoadjuvant chemotherapy is a feasible and safe treatment option for locally advanced breast cancer patients.


Assuntos
Neoplasias da Mama , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Resultado do Tratamento , Doxorrubicina
2.
Cereb Cortex ; 34(3)2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38511722

RESUMO

Neurovascular decoupling plays a significant role in dysfunction following an ischemic stroke. This study aimed to explore the effect of low- and high-frequency repetitive transcranial magnetic stimulation on neurovascular remodeling after ischemic stroke. To achieve this goal, we compared functional hyperemia, cerebral blood flow regulatory factors, and neurochemical transmitters in the peri-infract cortex 21 days after a photothrombotic stroke. Our findings revealed that low- and high-frequency repetitive transcranial magnetic stimulation increased the real-time cerebral blood flow in healthy mice and improved neurobehavioral outcomes after stroke. Furthermore, high-frequency (5-Hz) repetitive transcranial magnetic stimulation revealed stronger functional hyperemia recovery and increased the levels of post-synaptic density 95, neuronal nitric oxide synthase, phosphorylated-endothelial nitric oxide synthase, and vascular endothelial growth factor in the peri-infract cortex compared with low-frequency (1-Hz) repetitive transcranial magnetic stimulation. The magnetic resonance spectroscopy data showed that low- and high-frequency repetitive transcranial magnetic stimulation reduced neuronal injury and maintained excitation/inhibition balance. However, 5-Hz repetitive transcranial magnetic stimulation showed more significant regulation of excitatory and inhibitory neurotransmitters after stroke than 1-Hz repetitive transcranial magnetic stimulation. These results indicated that high-frequency repetitive transcranial magnetic stimulation could more effectively promote neurovascular remodeling after stroke, and specific repetitive transcranial magnetic stimulation frequencies might be used to selectively regulate the neurovascular unit.


Assuntos
Hiperemia , AVC Isquêmico , Acidente Vascular Cerebral , Animais , Camundongos , Estimulação Magnética Transcraniana/métodos , Fator A de Crescimento do Endotélio Vascular , Resultado do Tratamento
3.
Worldviews Evid Based Nurs ; 21(2): 158-182, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38429872

RESUMO

BACKGROUND: Non-pharmacological interventions have been used in the rehabilitation of stroke survivors, but their effects on stroke survivors' quality of life (QoL) are unknown. AIM: This review aimed to summarize the existing evidence regarding non-pharmacological interventions for QoL in stroke survivors and to evaluate the effectiveness of different types of interventions. METHODS: We systematically searched databases including PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical Literature Database, China Science and Technology Journal Database, and Wanfang data from the earliest available records to March 2023. Randomized controlled trials which explored the effects of non-pharmacological interventions on QoL in stroke patients were included. The meta-analysis was conducted to evaluate the effectiveness of different interventions on QoL. The Review Manager 5.3 was used to conduct the meta-analysis and the revised Cochrane risk-of-bias tool was used to assess the methodological quality of trials. RESULTS: A total of 93,245 records were identified, and 34 articles were reviewed and summarized, of which 20 articles were included in the meta-analysis. The summary of the findings of the included studies revealed fitness training, constraint-induced movement therapy (CIMT), physical exercise, music therapy (MT), and art-based interventions may have positive effects on QoL. The fitness training improved total QoL, especially in physical domains including physical functioning (mean difference [MD] = 10.90; 95% CI [7.20, 14.59]), role physical (MD = 10.63; 95% CI [6.71, 14.55]), and global health (MD = 8.76; 95% CI [5.14, 12.38]). The CIMT had a slight effect on general QoL (standardized mean difference [SMD] = 0.48, 95% CI [0.16, 0.80]), whereas significantly improved strength (MD = 8.84; 95% CI [1.31, 16.38]), activities of daily living/instrumental activities of daily living (ADL/IADL; MD = 10.42; 95% CI [2.98, 17.87]), and mobility (MD = 8.02; 95% CI [1.21, 14.83]). MT had a positive effect on the mental health domain (SMD = 0.54; 95% CI [0.14, 0.94]). LINKING EVIDENCE TO ACTION: Our findings suggest that fitness training and CIMT have a significant effect on improving physical QoL, while MT has a positive effect on improving psychological QoL. Future studies may use comprehensive and multicomponent interventions to simultaneously improve the patients' physical, psychological, and social QoL.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Qualidade de Vida , Atividades Cotidianas , Acidente Vascular Cerebral/terapia , Exercício Físico , Sobreviventes , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Brain Res Bull ; 209: 110908, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38402995

RESUMO

BACKGROUND: medial temporal lobe epilepsy (mTLE) is among the most common types of temporal lobe epilepsy (TLE) ,it is generally resistant to drug treatment, which significantly impacts the quality of life and treatment. Research on novel therapeutic approaches for mTLE has become a current focus. Our study aims to construct and analyze a competing endogenous RNA (ceRNA) network that targets neuroinflammation using publicly available data, which may offer a novel therapeutic approach for mTLE. METHODS: we utilized the R package to analyze GSE186334 downloaded from Gene Expression Omnibus database, subsequently constructing and identifying hub network within the ceRNA network using public databases. Lastly, we validated the expressions and interactions of some nodes within the hub ceRNA network in Sombati cell model. RESULTS: our transcriptome analysis identified 649 differentially expressed (DE) mRNAs (273 up-regulated, 376 down-regulated) and 36 DE circRNAs (11 up-regulated, 25 down-regulated) among mTLE patients. A total of 23 candidate DE mRNAs associated with neuroinflammation were screened, and two ceRNA networks were constructed. A hub network was further screened which included 3 mRNAs, 22 miRNAs, and 11 circRNAs. Finally, we confirmed the hsa-miR-149-5p is crucial in the regulatory effect of hsa_circ_0005145 on IL - 1α in the hub network. CONCLUSIONS: In summary, our study identified a hub ceRNA network and validated a potential circRNA-miRNA-mRNA axis targeting neuroinflammation. The results of our research may serve as a potential therapeutic target for mTLE.


Assuntos
Epilepsia do Lobo Temporal , MicroRNAs , Humanos , RNA Circular/genética , 60414 , Epilepsia do Lobo Temporal/genética , Doenças Neuroinflamatórias , Qualidade de Vida , MicroRNAs/genética , RNA Mensageiro
5.
Mol Med ; 30(1): 27, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378457

RESUMO

BACKGROUND: Isoorientin (ISO) is a glycosylated flavonoid with antitumor, anti-inflammatory, and antioxidant properties. However, its effects on bone metabolism remain largely unknown. METHODS: In this study, we aimed to investigate the effects of ISO on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation in vitro and bone loss in post-ovariectomy (OVX) rats, as well as to elucidate the underlying mechanism. First, network pharmacology analysis indicated that MAPK1 and AKT1 may be potential therapeutic targets of ISO and that ISO has potential regulatory effects on the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways, as well as oxidative stress. ISO was added to RAW264.7 cells stimulated by RANKL, and its effects on osteoclast differentiation were evaluated using tartrate-resistant acid phosphatase (TRAP) staining, TRAP activity measurement, and F-actin ring analysis. Reactive oxygen species (ROS) production in osteoclasts was detected using a ROS assay kit. The effects of ISO on RANKL-triggered molecular cascade response were further investigated by Western blotting, quantitative real-time polymerase chain reaction, and immunofluorescence staining. In addition, the therapeutic effects of ISO were evaluated in vivo. RESULTS: ISO inhibited osteoclastogenesis in a time- and concentration-dependent manner. Mechanistically, ISO downregulated the expression of the main transcription factor for osteoclast differentiation by inhibiting MAPK and PI3K/AKT1 signaling pathways. Moreover, ISO exhibited protective effects in OVX-induced bone loss rats. This was consistent with the results derived from network pharmacology. CONCLUSION: Our findings suggest a potential therapeutic utility of ISO in the management of osteoclast-associated bone diseases, including osteoporosis.


Assuntos
Reabsorção Óssea , Luteolina , Osteoporose , Feminino , Ratos , Animais , Reabsorção Óssea/patologia , Espécies Reativas de Oxigênio/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases , Farmacologia em Rede , Diferenciação Celular , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Osteoporose/tratamento farmacológico , Fatores de Transcrição NFATC/metabolismo
6.
J Leukoc Biol ; 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38266238

RESUMO

The overactivation of the osteoclasts is a crucial pathological factor in the development of osteoporosis. Myeloid zinc finger 1 (MZF1), belonging to the scan-zinc finger family, plays a significant role in various processes associated with tumor malignant progression and acts as an essential transcription factor regulating osteoblast expression. However, the exact role of MZF1 in osteoclasts has not been determined. In this study, the purpose of our study was to elucidate the role of MZF1 in osteoclastogenesis. First, we established MZF1-deficient female mice and evaluated the femur bone phenotype by Micro-CT and histological staining. Our findings indicate that MZF1-/- mice exhibited a low bone mass osteoporosis phenotype. RANKL could independently induce the differentiation of RAW264.7 cells into osteoclasts, and we found that the expression level of MZF1 protein decreased gradually. Then, the CRISPR/Cas 9 gene editing technique was used to build a RAW264.7 cell model with MZF1 knockout, and RANKL was used to independently induce MZF1-/- and WT cells to differentiate into mature osteoclasts. Tartrate-resistant acid phosphatase (TRAP) staining and F-actin fluorescence results showed that the MZF1-/- group produced more TRAP positive mature osteoclasts and larger actin rings. The expression of osteoclast-associated genes (including TRAP, CTSK, c-Fos and NFATc1) was evaluated by RT-qPCR and Western blot. The expression of key genes of osteoclast differentiation in MZF1-/- group was significantly increased. Furthermore, we found that cell viability was increased in the early stages of RANKL-induced cell differentiation in the MZF1-/- group cells. We examined some prevalent ferroptosis markers, including malondialdehyde, glutathione, and intracellular Fe, the active form of iron in the cytoplasm during the early stages of osteoclastogenesis. The results suggest that MZF1 may be involved in osteoclast differentiation by regulating RANKL-induced ferroptosis of osteoclasts. Collectively, our findings shed light on the essential involvement of MZF1 in the regulation of osteoclastogenesis in osteoporosis and provide insights into its potential underlying mechanism.

7.
Cell Rep ; 43(1): 113653, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38175758

RESUMO

Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the subgenus Sarbecovirus, members of which share high sequence similarity. Herein, we report one sarbecovirus antibody, 5817, which has broad-spectrum neutralization capacity against SARS-CoV-2 variants of concern (VOCs) and SARS-CoV, as well as related bat and pangolin viruses. 5817 can hardly compete with six classes of receptor-binding-domain-targeted antibodies grouped by structural classifications. No obvious impairment in the potency is detected against SARS-CoV-2 Omicron and subvariants. The cryoelectron microscopy (cryo-EM) structure of neutralizing antibody 5817 in complex with Omicron spike reveals a highly conserved epitope, only existing at the receptor-binding domain (RBD) open state. Prophylactic and therapeutic administration of 5817 potently protects mice from SARS-CoV-2 Beta, Delta, Omicron, and SARS-CoV infection. This study reveals a highly conserved cryptic epitope targeted by a broad sarbecovirus neutralizing antibody, which would be beneficial to meet the potential threat of pre-emergent SARS-CoV-2 VOCs.


Assuntos
Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Animais , Camundongos , Anticorpos Amplamente Neutralizantes , Microscopia Crioeletrônica , Anticorpos Neutralizantes , Epitopos , Anticorpos Antivirais
9.
Sensors (Basel) ; 23(24)2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38139707

RESUMO

Currently, aeroplane images captured by camera sensors are characterized by their small size and intricate backgrounds, posing a challenge for existing deep learning algorithms in effectively detecting small targets. This paper incorporates the RFBNet (a coordinate attention mechanism) and the SIOU loss function into the YOLOv5 algorithm to address this issue. The result is developing the model for aeroplane and undercarriage detection. The primary goal is to synergize camera sensors with deep learning algorithms, improving image capture precision. YOLOv5-RSC enhances three aspects: firstly, it introduces the receptive field block based on the backbone network, increasing the size of the receptive field of the feature map, enhancing the connection between shallow and deep feature maps, and further improving the model's utilization of feature information. Secondly, the coordinate attention mechanism is added to the feature fusion network to assist the model in more accurately locating the targets of interest, considering attention in the channel and spatial dimensions. This enhances the model's attention to key information and improves detection precision. Finally, the SIoU bounding box loss function is adopted to address the issue of IoU's insensitivity to scale and increase the speed of model bounding box convergence. Subsequently, the Basler camera experimental platform was constructed for experimental verification. The results demonstrate that the AP values of the YOLOv5-RSC detection model for aeroplane and undercarriage are 92.4% and 80.5%, respectively. The mAP value is 86.4%, which is 2.0%, 5.4%, and 3.7% higher than the original YOLOv5 algorithm, respectively, with a detection speed reaching 89.2 FPS. These findings indicate that the model exhibits high detection precision and speed, providing a valuable reference for aeroplane undercarriage detection.

10.
Neuro Endocrinol Lett ; 44(6): 384-390, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37776555

RESUMO

OBJECTIVE: To investigate the quantitative electroencephalography features of different brain lobe epilepsy. METHODS: The electroencephalogram data of adult patients diagnosed with epilepsy in the epilepsy clinic of the Second Affiliated Hospital of Shandong First Medical University from January 1, 2012 to December 31, 2016 were collected, 58 cases in total. They included 28 cases of frontal lobe epilepsy,12 cases of temporal lobe epilepsy, 9 cases of occipital lobe epilepsy, and 9 cases of parietal lobe epilepsy. Quantitative electroencephalography analysis technique was used to obtain the δ, θ, α1, α2, ß1 and ß2 power spectrum value in patients with different brain lobe epilepsy. The δ, θ, α, and ß relative power spectrum value are obtained by calculation. By comparing the quantitative electroencephalography indicators of the affected side and the healthy side, the quantitative electroencephalography characteristics of epilepsy in different lobes were obtained. RESULTS: θ power spectrum can be increased in the discharge lead of temporal lobe epilepsy. δ and θ power spectrum, δ relative power spectrum can be increased in the discharge lead of occipital lobe epilepsy. CONCLUSION: The increase in slow wave power spectrum in QEEG can serve as an auxiliary diagnosis for temporal lobe epilepsy and occipital lobe epilepsy.


Assuntos
Epilepsias Parciais , Epilepsia do Lobo Temporal , Epilepsia , Adulto , Humanos , Epilepsia do Lobo Temporal/diagnóstico , Eletroencefalografia/métodos , Encéfalo
11.
Medicine (Baltimore) ; 102(30): e34499, 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37505149

RESUMO

Matrix metalloproteinase 9 (MMP9), a zinc ion-dependent endopeptidase, is one of the most complex matrix metalloproteinases in the gelatinase family. During tissue remodeling, MMP9 leads to gelatin and collagen degradation, which in turn promotes tumor invasion and metastasis. However, comprehensive pan-cancer analysis has not been performed for MMP9. In addition, the diagnostic and prognostic value of MMP9 as a cancer biomarker remain poorly understood, as well as the utility of MMP9 expression as a predictor of immunological responses. Based on a comprehensive analysis of bioinformatics information, we investigated MMP9 expression in different cancers, correlations between MMP9 expression and cancer prognosis and gene mutations, and relationships between MMP9 expression and immune cell infiltration. Our results indicated that MMP9 was highly expressed in most malignant cancers. MMP9 expression was significantly positively or negatively associated with the clinical prognoses of patients with different kinds of cancer. Furthermore, MMP9 expression significantly correlated with infiltrating cells and the expression levels of immune checkpoint genes. This pan-cancer analysis provides comprehensive information on the potential value of MMP9 as a theranostic biomarker.


Assuntos
Metaloproteinase 9 da Matriz , Neoplasias , Humanos , Prognóstico , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias/genética
12.
Front Neurosci ; 17: 1129590, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37139516

RESUMO

Repetitive TMS has been used as an alternative treatment for various neurological disorders. However, most TMS mechanism studies in rodents have been based on the whole brain stimulation, the lack of rodent-specific focal TMS coils restricts the proper translation of human TMS protocols to animal models. In this study, we designed a new shielding device, which was made of high magnetic permeability material, to enhance the spatial focus of animal-use TMS coils. With the finite element method, we analyzed the electromagnetic field of the coil with and without the shielding device. Furthermore, to assess the shielding effect in rodents, we compared the c-fos expression, the ALFF and ReHo values in different groups following a 15 min 5 Hz rTMS paradigm. We found that a smaller focality with an identical core stimulation intensity was achieved in the shielding device. The 1 T magnetic field was reduced from 19.1 mm to 13 mm in diameter, and 7.5 to 5.6 mm in depth. However, the core magnetic field over 1.5 T was almost the same. Meanwhile, the area of electric field was reduced from 4.68 cm2 to 4.19 cm2, and 3.8 mm to 2.6 mm in depth. Similar to this biomimetic data, the c-fos expression, the ALFF and ReHo values showed more limited cortex activation with the use of the shielding device. However, compared to the rTMS group without the shielding application, more subcortical regions, like the striatum (CPu), the hippocampus, the thalamus, and the hypothalamus were also activated in the shielding group. This indicated that more deep stimulation may be achieved by the shielding device. Generally, compared with the commercial rodents' TMS coil (15 mm in diameter), TMS coils with the shielding device achieved a better focality (~6 mm in diameter) by reducing at least 30% of the magnetic and electric field. This shielding device may provide a useful tool for further TMS studies in rodents, especially for more specific brain area stimulation.

13.
J Psychiatr Res ; 162: 79-87, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37105022

RESUMO

BACKGROUND: Currently, there is increasing evidence from clinic, epidemiology, as well as neuroimaging, demonstrating neuropsychiatric abnormalities in COVID-19, however, whether there were associations between brain changes caused by COVID-19 and genetic susceptibility of psychiatric disorders was still unknown. METHODS: In this study, we performed a meta-analysis to investigate these associations by combing single-cell RNA sequencing datasets of brain tissues of COVID-19 and genome-wide association study summary statistics of psychiatric disorders. RESULTS: The analysis demonstrated that among ten psychiatric disorders, gene expression perturbations implicated by COVID-19 in excitatory neurons of choroid plexus were significantly associated with schizophrenia. CONCLUSIONS: Our analysis might provide insights for the underlying mechanism of the psychiatric consequence of COVID-19.


Assuntos
COVID-19 , Transtornos Mentais , Humanos , Estudo de Associação Genômica Ampla/métodos , Transtornos Mentais/genética , Predisposição Genética para Doença/genética , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Expressão Gênica , Polimorfismo de Nucleotídeo Único
14.
J Pharm Pharmacol ; 75(5): 677-685, 2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-36840643

RESUMO

OBJECTIVES: This study was aimed to evaluate the protective effects of phenylethanoid glycosides extract from Cistanche deserticola against atherosclerosis and its molecular mechanism. METHODS: Total phenylethanoid glycosides were extracted and purified from C. deserticola, and the C. deserticola extract (CDE) was used to treat a mice model of atherosclerosis. KEY FINDINGS: CDE containing 81.00% total phenylethanoid glycosides, with the contents of echinacoside and acteoside being 31.36% and 7.23%, respectively. A 13-week of CDE supplementation (1000 mg/kg body weight/day) significantly reduced atherosclerotic lesions in the aortic sinus and entire aorta in ApoE-/- mice fed with a high-fat diet. In addition, varying doses of CDE (250, 500 and 1000 mg/kg body weight/day) lowered plasma total cholesterol, triglyceride and non-high-density lipoprotein cholesterol levels. Transcriptomic analysis of the small intestine revealed the changes enriched in cholesterol metabolic pathway and the activation of Abca1 gene. Further validation using real-time quantitative PCR and western blot confirmed that CDE significantly increased the mRNA levels and protein expressions of ABCA1, LXRα and PPARγ. CONCLUSIONS: Our results demonstrate the beneficial effects of C. deserticola on atherosclerotic plaques and lipid homeostasis, and it is, at least partially, by activating PPARγ-LXRα-ABCA1 pathway in small intestine.


Assuntos
Aterosclerose , Cistanche , Glicosídeos , Animais , Camundongos , Apolipoproteínas/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Transportador 1 de Cassete de Ligação de ATP/efeitos dos fármacos , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Peso Corporal , Colesterol/metabolismo , Cistanche/química , Glicosídeos/química , Glicosídeos/farmacologia , Camundongos Knockout para ApoE , Extratos Vegetais/química , Extratos Vegetais/farmacologia , PPAR gama/efeitos dos fármacos , PPAR gama/metabolismo , Receptores X do Fígado/efeitos dos fármacos , Receptores X do Fígado/metabolismo
15.
Sensors (Basel) ; 23(4)2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36850690

RESUMO

Wire breakage is a major factor in the failure of prestressed concrete cylinder pipes (PCCP). In the presented work, an automatic monitoring approach of broken wires in PCCP using fiber-optic distributed acoustic sensors (DAS) is investigated. The study designs a 1:1 prototype wire break monitoring experiment using a DN4000 mm PCCP buried underground in a simulated test environment. The test combines the collected wire break signals with the previously collected noise signals in the operating pipe and transforms them into a spectrogram as the wire break signal dataset. A deep learning-based target detection algorithm is developed to detect the occurrence of wire break events by extracting the spectrogram image features of wire break signals in the dataset. The results show that the recall, precision, F1 score, and false detection rate of the pruned model reach 100%, 100%, 1, and 0%, respectively; the video detection frame rate reaches 35 fps and the model size is only 732 KB. It can be seen that this method greatly simplifies the model without loss of precision, providing an effective method for the identification of PCCP wire break signals, while the lightweight model is more conducive to the embedded deployment of a PCCP wire break monitoring system.

16.
Front Pharmacol ; 13: 1015926, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36304167

RESUMO

Cystic fibrosis (CF) is a life-threatening autosomal-recessive disease caused by mutations in a single gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). CF effects multiple organs, and lung disease is the primary cause of mortality. The median age at death from CF is in the early forties. CF was one of the first diseases to be considered for gene therapy, and efforts focused on treating CF lung disease began shortly after the CFTR gene was identified in 1989. However, despite the quickly established proof-of-concept for CFTR gene transfer in vitro and in clinical trials in 1990s, to date, 36 CF gene therapy clinical trials involving ∼600 patients with CF have yet to achieve their desired outcomes. The long journey to pursue gene therapy as a cure for CF encountered more difficulties than originally anticipated, but immense progress has been made in the past decade in the developments of next generation airway transduction viral vectors and CF animal models that reproduced human CF disease phenotypes. In this review, we look back at the history for the lessons learned from previous clinical trials and summarize the recent advances in the research for CF gene therapy, including the emerging CRISPR-based gene editing strategies. We also discuss the airway transduction vectors, large animal CF models, the complexity of CF pathogenesis and heterogeneity of CFTR expression in airway epithelium, which are the major challenges to the implementation of a successful CF gene therapy, and highlight the future opportunities and prospects.

17.
PLoS One ; 17(8): e0272428, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36006933

RESUMO

Aanti-epileptic drugs have been used for treating epilepsy for decades, meanwhile, more than one hundred genes have been identified to be associated with risk of epilepsy; however, the interaction mechanism between anti-epileptic drugs and risk genes of epilepsy was still not clearly understood. In this study, we systematically explored the interaction of epilepsy risk genes and anti-epileptic drug targets through a network-based approach. Our results revealed that anti-epileptic drug targets were significantly over-represented in risk genes of epilepsy with 17 overlapping genes and P-value = 2.2 ×10 -16. We identified a significantly localized PPI network with 55 epileptic risk genes and 94 anti-epileptic drug target genes, and network overlap analysis showed significant interactome overlap between risk genes and drug targets with P-value = 0.04. Besides, genes from PPI network were significantly enriched in the co-expression network of epilepsy with 22 enriched genes and P-value = 1.3 ×10 -15; meanwhile, cell type enrichment analysis indicated genes in this network were significantly enriched in 4 brain cell types (Interneuron, Medium Spiny Neuron, CA1 pyramidal Neuron, and Somatosensory pyramidal Neuron). These results provide evidence for significant interactions between epilepsy risk genes and anti-epileptic drug targets from the perspective of network biology.


Assuntos
Epilepsia , Encéfalo , Epilepsia/tratamento farmacológico , Epilepsia/genética , Humanos , Interneurônios , Neurônios , Células Piramidais
18.
Sensors (Basel) ; 22(13)2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35808478

RESUMO

The low energy conversion efficiency of electromagnetic acoustic transducers (EMATs) is a critical issue in nondestructive testing applications. To overcome this shortcoming, a butterfly coil EMAT was developed and optimized by numerical simulation based on a 2-D finite element model. First, the effect of the structural parameters of the butterfly coil EMAT was investigated by orthogonal test theory. Then, a modified butterfly coil EMAT was designed that consists of three-square permanent magnets with opposite polarity (TSPM-OP) to enhance the signal amplitude. Finally, the signal amplitude obtained from the three types of EMATs, that is, the traditional EMAT, the EMAT optimized by orthogonal test theory, and the modified EMAT with TSPM-OP, were analyzed and compared. The results show that the signal amplitude achieved by the modified butterfly coil EMAT with TSPM-OP can be increased by 4.97 times compared to the traditional butterfly coil EMAT.


Assuntos
Acústica , Transdutores , Simulação por Computador , Fenômenos Eletromagnéticos
19.
J Neuroinflammation ; 19(1): 141, 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35690810

RESUMO

BACKGROUND: Neuronal pyroptosis and neuroinflammation with excess microglial activation are widely involved in the early pathological process of ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive neuromodulatory technique, has recently been reported to be anti-inflammatory and regulate microglial function. However, few studies have elucidated the role and mechanism of rTMS underlying regulating neuronal pyroptosis and microglial polarization. METHODS: We evaluated the motor function in middle cerebral artery occlusion/reperfusion (MCAO/r) injury mice after 1-week intermittent theta-burst rTMS (iTBS) treatment in the early phase with or without depletion of microglia by colony-stimulating factor 1 receptor (CSF1R) inhibitor treatment, respectively. We further explored the morphological and molecular biological alterations associated with neuronal pyroptosis and microglial polarization via Nissl, EdU, TTC, TUNEL staining, electron microscopy, multiplex cytokine bioassays, western blot assays, immunofluorescence staining and RNA sequencing. RESULTS: ITBS significantly protected against cerebral ischemia/reperfusion (I/R) injury-induced locomotor deficits and neuronal damage, which probably relied on the regulation of innate immune and inflammatory responses, as evidenced by RNA sequencing analysis. The peak of pyroptosis was confirmed to be later than that of apoptosis during the early phase of stroke, and pyroptosis was mainly located and more severe in the peri-infarcted area compared with apoptosis. Multiplex cytokine bioassays showed that iTBS significantly ameliorated the high levels of IL-1ß, IL-17A, TNF-α, IFN-γ in MCAO/r group and elevated the level of IL-10. ITBS inhibited the expression of neuronal pyroptosis-associated proteins (i.e., Caspase1, IL-1ß, IL-18, ASC, GSDMD, NLRP1) in the peri-infarcted area rather than at the border of infarcted core. KEGG enrichment analysis and further studies demonstrated that iTBS significantly shifted the microglial M1/M2 phenotype balance by curbing proinflammatory M1 activation (Iba1+/CD86+) and enhancing the anti-inflammatory M2 activation (Iba1+/CD206+) in peri-infarcted area via inhibiting TLR4/NFκB/NLRP3 signaling pathway. Depletion of microglia using CSF1R inhibitor (PLX3397) eliminated the motor functional improvements after iTBS treatment. CONCLUSIONS: rTMS could alleviate cerebral I/R injury induced locomotor deficits and neuronal pyroptosis by modulating the microglial polarization. It is expected that these data will provide novel insights into the mechanisms of rTMS protecting against cerebral I/R injury and potential targets underlying neuronal pyroptosis in the early phase of stroke.


Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Animais , Isquemia Encefálica/metabolismo , Infarto da Artéria Cerebral Média/complicações , Camundongos , Microglia/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais , Acidente Vascular Cerebral/patologia , Receptor 4 Toll-Like/metabolismo , Estimulação Magnética Transcraniana
20.
Int J Hyperthermia ; 39(1): 725-732, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35584811

RESUMO

PURPOSE: To compare the accuracy and safety of robotic laser position (RLP) versus freehand for antenna CT-guided microwave ablation (MWA) of single hepatocellular carcinoma (HCC) (diameter < 3 cm). MATERIALS AND METHODS: This retrospective study was conducted between May 2020 and June 2021. A total of 40 patients with early HCC who underwent CT-guided MWA were divided into two groups: a freehand group (n = 20) and a RLP group (n = 20). Based on in-plane and out-of-plane data, the actual puncture point error (APPE), number of repositioning procedures, and operative duration were compared using the Mann-Whitney U test. Ablation-related complications were compared using the Chi-squared test. RESULTS: The mean diameter of HCC patients who received MWA was 2.4 ± 0.5 cm. For in-plane APPE, APPE was comparable between the two groups (p = 0.299). However, for the out-of-plane position, the APPE in the freehand group was higher than that in the RLP group (p = 0.027). The number of repositioning procedures was 0 (range, 0-0) for RLP-guided procedures and 3 (range, 2-5) for freehand procedures, showing a statistically significant difference between the two groups (p < 0.001). The mean operative duration for freehand procedures was 39 min, compared with 26 min for RLP-guided procedures, showing a significant difference (p = 0.013). No deaths or major complications were directly related to MWA. Minor complications in the freehand group were comparable with those in the RLP group (p = 0.313). CONCLUSION: RLP guidance significantly reduces the number of antenna repositioning procedures in MWA and improves puncture accuracy for target HCC out-of-plane. In addition, the operative duration of robotic guidance was shorter than that of freehand guidance.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Procedimentos Cirúrgicos Robóticos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/métodos , Humanos , Lasers , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
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