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BACKGROUND: This study aimed to compare the survival outcomes of patients with initially unresectable hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) who underwent or did not undergo salvage surgery followed by a triple combination conversion treatment consisted of locoregional treatment (LRT), tyrosine kinase inhibitors (TKIs), and anti-PD-1 antibodies. METHODS: The data from 93 consecutive patients with initially unresectable HCC and PVTT across 4 medical centers were retrospectively reviewed. They were converted successfully by the triple combination treatment and underwent or did not undergo salvage resection. The baseline characteristics, conversion schemes, conversion treatment-related adverse events (CTRAEs), overall survival (OS), and progression-free survival (PFS) of the salvage surgery and non-surgery groups were compared. Multivariate Cox regression analysis was performed to identify independent risk factors for OS and PFS. Additionally, subgroup survival analysis was conducted by stratification of degree of tumor response and type of PVTT. RESULTS: Of the 93 patients, 44 underwent salvage surgery, and 49 did not undergo salvage surgery. The OS and PFS of the salvage surgery and non-surgery groups were not significantly different (Pâ =â .370 and .334, respectively). The incidence and severity of CTRAEs of the 2 groups were also comparable. Subgroup analyses revealed that for patients with complete response (CR) or types III-IV PVTT, there was a trend toward better survival in patients who did not undergo salvage surgery. Multivariate analysis showed that baseline α-fetoprotein and best tumor response per mRECIST criteria were independent prognostic factors for OS and PFS. CONCLUSIONS: For patients with initially unresectable HCC and PVTT who were successfully converted by the triple combination therapy, salvage liver resection may not be necessary, especially for the patients with CR or types III-IV PVTT.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Inhibidores de Proteínas Quinasas , Terapia Recuperativa , Humanos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/complicaciones , Masculino , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/complicaciones , Femenino , Terapia Recuperativa/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Inhibidores de Proteínas Quinasas/uso terapéutico , Anciano , Vena Porta/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Adulto , Trombosis de la VenaRESUMEN
Identifying dysregulated plasma proteins in osteoporosis (OP) progression offers insights into prevention and treatment. This study found 8 such proteins associated with OP, suggesting them as therapy targets. This discovery may cut drug development costs and improve personalized treatments. PURPOSE: This study aims to identify potential therapeutic targets for OP using summary data-based Mendelian randomization (SMR) and colocalization analysis methods. Furthermore, we seek to explore the biological significance and pharmacological value of these drug targets. METHODS: To identify potential therapeutic targets for OP, we conducted SMR and colocalization analysis. Plasma protein (pQTL, exposure) data were sourced from the study by Ferkingstad et al. (n = 35,559). Summary statistics for bone mineral density (BMD, outcome) were obtained from the GWAS Catalog (n = 56,284). Additionally, we utilized enrichment analysis, protein-protein interaction (PPI) network analysis, drug prediction, and molecular docking to further analyze the biological significance and pharmacological value of these drug targets. RESULTS: In the SMR analysis, while 20 proteins showed significance, only 8 potential drug targets (GCKR, ERBB3, CFHR1, GPN1, SDF2, VTN, BET1L, and SERPING1) received support from colocalization (PP.H4 > 0.8). These proteins are closely associated with immune function in terms of biological significance. Molecular docking also demonstrated favorable binding of drugs to proteins, consistent with existing structural data, further substantiating the pharmacological value of these targets. CONCLUSIONS: The study identified 8 potential drug targets for OP. These prospective targets are believed to have a higher chance of success in clinical trials, thus aiding in prioritizing OP drug development and reducing development costs.
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Efficient charge carrier transport characteristics are critical to achieving the excellent performance of metal-oxide semiconductor gas sensors. Herein, SnO2/CeO2 heterojunction layered nanosheets with abundant oxygen vacancies were successfully synthesized through a simple solvothermal assisted high-temperature calcination method. The synergistic effect of oxygen vacancies and heterojunctions promoting the charge carrier transport properties at the SnO2/CeO2 interface for the enhanced sensing properties of triethylamine (TEA) was highlighted. As a result, the optimized SnO2/CeO2 exhibits improved gas sensing performance at 173 °C to 50 ppm of TEA. These include high response (205), excellent selectivity, low detection limit, and good long-term stability. This enhanced gas sensing property of SnO2/CeO2 is mainly attributed to the fact that the heterojunction and oxygen vacancies act as dual active sites synergistically inducing electron transfer, thereby effectively modulating the transport properties of the interfacial charge carriers, and thus facilitate the surface reactions efficiently. In this work, the dual-engineering strategy of synergistic interaction of heterojunction and oxygen vacancies can provide new perspectives for the design of advanced gas sensing materials.
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BACKGROUND: Osteoporosis (OP) is characterized by bone mass decrease and bone tissue microarchitectural deterioration in bone tissue. This study identified potential biomarkers for early diagnosis of OP and elucidated the mechanism of OP. METHODS: Gene expression profiles were downloaded from Gene Expression Omnibus (GEO) for the GSE56814 dataset. A gene co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) to identify key modules associated with healthy and OP samples. Functional enrichment analysis was conducted using the R clusterProfiler package for modules to construct the transcriptional regulatory factor networks. We used the "ggpubr" package in R to screen for differentially expressed genes between the two samples. Gene set variation analysis (GSVA) was employed to further validate hub gene expression levels between normal and OP samples using RT-PCR and immunofluorescence to evaluate the potential biological changes in various samples. RESULTS: There was a distinction between the normal and OP conditions based on the preserved significant module. A total of 100 genes with the highest MM scores were considered key genes. Functional enrichment analysis suggested that the top 10 biological processes, cellular component and molecular functions were enriched. The Toll-like receptor signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, osteoclast differentiation, JAK-STAT signaling pathway, and chemokine signaling pathway were identified by Kyoto Encyclopedia of Genes and Genomes pathway analysis. SIRT1 and ZNF350 were identified by Wilcoxon algorithm as hub differentially expressed transcriptional regulatory factors that promote OP progression by affecting oxidative phosphorylation, apoptosis, PI3K-Akt-mTOR signaling, and p53 pathway. According to RT-PCR and immunostaining results, SIRT1 and ZNF350 levels were significantly higher in OP samples than in normal samples. CONCLUSION: SIRT1 and ZNF350 are important transcriptional regulatory factors for the pathogenesis of OP and may be novel biomarkers for OP treatment.
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Osteoporosis , Sirtuina 1 , Humanos , Sirtuina 1/genética , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Osteoporosis/genética , Biomarcadores , Biología Computacional , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Proteínas RepresorasRESUMEN
INTRODUCTION: Although there has been abundant evidence of the association between dyslipidemia as a single factor and osteoporosis, the non-linear relationship between osteoporosis and the Atherogenic Index of Plasma (AIP) has not yet been thoroughly investigated. This study aimed to investigate the complex relationship between AIP and bone mineral density (BMD) to elucidate their interrelationship. METHODS: An analysis of 2007-2018 National Health and Nutrition Survey (NHANES) data was conducted for this study. The study enrolled 5,019 participants. Logarithmically multiplying triglycerides and high-density lipoprotein cholesterol yields the AIP (base 10). The measured variables consisted of BMD in the total femur (TF), femoral neck (FN), and lumbar spine (LS). The association between AIP and BMD was examined using a range of statistical models, such as weighted multivariable logistic regression, generalized additive model, etc. RESULTS: It was found that AIP was positively associated with BMD after adjusting for age, gender, race, socioeconomic status, degree of education, income, Consuming alcoholic beverages, osteoporosis status (Yes or No), ALT, AST, serum creatinine, and total calcium levels. Further studies supported the association link between elevated BMD and AIP. Furthermore, compared to men, females had a higher positive connection between AIP and BMD. In general, there was a curve in the reverse L-shape seen, with a point of change around 0.877, indicating a relationship between AIP and TF BMD. Moreover, a curve exhibiting an L-formed pattern, with a point of inflection at around 0.702, was seen between AIP and FN BMD. In addition, a J-shaped curve was seen, with a point of inflection at 0.092, which demonstrates the association between AIP and LS BMD. CONCLUSION: The AIP and TF BMD curves resemble inverted L shapes, as do the AIP and FN BMD curves. The relationship between AIP and LS BMD was further demonstrated by a J-shaped curve. The results indicate a possible association between AIP and bone mineral density, which should be explored in more detail.
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Aterosclerosis , Densidad Ósea , Osteoporosis , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Aterosclerosis/sangre , Osteoporosis/sangre , Adulto , HDL-Colesterol/sangre , Triglicéridos/sangre , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/patología , Cuello Femoral/diagnóstico por imagen , Anciano , Encuestas Nutricionales , Fémur/diagnóstico por imagen , Fémur/fisiopatologíaRESUMEN
BACKGROUND: To evaluate the reliability of the Soft Tissue Tension Cloud Chart (STTCC) technology, an original method combining multi-point Cervical Paravertebral Soft Tissue Test (CPSTT) with MATLAB software, we conducted a preliminary analysis on the immediate effects of Orthopaedic Manual Therapy (OMT) on cervical paravertebral soft tissue. METHODS: 30 patients with Cervical Spondylotic Radiculopathy (CSR) were included in this study. We analyzed the differences in CPSTT before and after treatment with Cervical Rotation-Traction Manipulation (CRTM), a representative OMT technique in Traditional Chinese Medicine, using the STTCC technology. RESULTS: The STTCC results demonstrated that post-treatment CPSTT levels in CSR patients were significantly lower than pre-treatment levels after application of CRTM, with a statistically significant difference (P < 0.001). Additionally, pre-treatment CPSTT levels on the symptomatic side (with radicular pain or numbness) were higher across the C5 to C7 vertebrae compared to the asymptomatic side (without symptoms) (P < 0.001). However, this difference disappeared after CRTM treatment (P = 0.231). CONCLUSIONS: The STTCC technology represents a reliable method for analyzing the immediate effects of OMT. CSR patients display uneven distribution of CPSTT characterized by higher tension on the symptomatic side. CRTM not only reduces overall cervical soft tissue tension in CSR patients, but can also balance the asymmetrical tension between the symptomatic and asymptomatic sides. TRIAL REGISTRATION: This study was approved by the Chinese Clinical Trials Registry (Website: . https://www.chictr.org.cn .) on 20/04/2021 and the Registration Number is ChiCTR2100045648.
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Manipulación Espinal , Radiculopatía , Espondilosis , Humanos , Rotación , Tracción/métodos , Reproducibilidad de los Resultados , Manipulación Espinal/métodos , Vértebras Cervicales , Radiculopatía/diagnóstico , Radiculopatía/terapia , Espondilosis/terapia , TecnologíaRESUMEN
Land reclamation is a widely adopted method for managing land shortage and promoting coastal economic development globally. However, its impacts on biodiversity vary based on distinct reclamation histories and land use management strategies in different regions. This study aims to examine the effects of reclamation history and land use types at different spatial scales on anuran communities in coastal reclaimed land, which are an important taxon in the coastal ecosystem. We used visual and acoustic encounter methods to survey anurans in 2016 and 2017 across 20 1-km radius coastal land reclamation landscapes with different reclamation histories (10, 20, and 60 y after reclamation) in Nanhui Dongtan of Shanghai, an important coastal land reclamation region along the Yangtze River Estuary. Landscape variables (farmlands, woodlands, and impermeable surface covers, and the landscape Shannon diversity index) at four different spatial scales (250 m, 500 m, 750 m and 1000 m) and water salinity in each landscape were measured. Our findings reveal differences in anuran communities between study sites with 10, 20, and 60 years of reclamation history. Abundances of the ornamented pygmy frog (Microhyla fissipes) and Beijing gold-striped pond frog (Pelophylax plancyi) in landscapes with a 10-year reclamation history were significantly lower compared to those with histories of 20 and 60 years. Zhoushan toad (Bufo gargarizans) abundance was significantly negatively related to farmland cover at the 1000 m scale and impermeable surface cover at the 250 m scale; Hong Kong rice-paddy frog (Fejervarya multistriata) abundance was significantly positively related to farmland cover at the 1000 m scale; ornamented pygmy frog abundance was positively related to farmland cover at the 1000 m scale; and Beijing gold-striped pond frog abundance was significantly positively and negatively related to the landscape Shannon diversity index at the 1000 m scale and to water salinity, respectively. Amphibians quickly migrated and colonized coastal reclaimed land from older natural lands. However, two anuran species with specific habitat requirements tended to avoid areas with shorter reclamation histories. The single-species models revealed different responses to various land uses at the various scales, which indicated that land use management was important to amphibian conservation in coastal reclamation regions.
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Biodiversidad , Ecosistema , Animales , China , Anuros , Agua , Conservación de los Recursos Naturales/métodosRESUMEN
STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: There is some controversy about the effects of calcitonin (CT) on lumbar spinal stenosis (LSS). This systematic review and meta-analysis is to assess the strength of the evidence supporting the use of CT in the treatment of patients with LSS. MATERIAL AND METHOD: We performed an electronic search depicting randomized controlled trials (RCTs) through 4 databases from the date of database creation to January 2023. 3 different researchers conducted independent literature screening, data extractions, and quality assessments. The outcome measures included visual analogue scale (VAS), walking distance, and oswestry disability index (ODI). Meta-analysis and trial sequence analysis (TSA) were carried out using RevMan 5.4, Stata 16.0, and TSA 0.9. GRADE 3.6 was used to evaluate the evidence quality. RESULTS: We accepted 9 studies with 496 participants. The meta-analysis revealed that CT offered no significant improvement in VAS, walking distance, or ODI in patients with LSS. CONCLUSION: There is no evidence that CT has a benefit in patients with LSS, either alone or in combination with other treatments, or depending on the route of administration, according to the systematic review and meta-analysis of relevant RCTs.
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Calcitonina , Vértebras Lumbares , Estenosis Espinal , Humanos , Conservadores de la Densidad Ósea/uso terapéutico , Calcitonina/uso terapéutico , Evaluación de la Discapacidad , Vértebras Lumbares/diagnóstico por imagen , Dimensión del Dolor , Ensayos Clínicos Controlados Aleatorios como Asunto , Estenosis Espinal/tratamiento farmacológicoRESUMEN
OBJECTIVES: To investigate the endoscopic ultrasonography (EUS) features of benign esophageal stenosis in children. METHODS: A retrospective analysis was conducted on the medical data of the children who were diagnosed with benign esophageal stenosis from February 2019 to February 2022. The clinical manifestations, EUS findings, and treatment outcome were analyzed to summarize the EUS features of benign esophageal stenosis in children. RESULTS: A total of 42 children with benign esophageal stenosis were included. Among these children, 19 (45%) had anastomotic stenosis after surgery for esophageal atresia, with unclear echogenic boundary of the esophageal walls and uneven thicknesses of the surrounding wall on EUS, and had 0-12 sessions of endoscopic treatment (average 2.1 sessions); 5 children (12%) had corrosive esophageal stenosis and 1 child (2%) had physical esophageal stenosis, with unclear stratification of the esophageal walls on EUS, and they had 2-9 sessions of endoscopic treatment (average 5.3 sessions); 1 child (2%) had patchy irregular hypoechoic areas of the esophageal walls on EUS and was diagnosed with tracheobronchial remnants with reference to pathology; 16 children (38%) had unexplained esophageal stenosis and unclear stratification of the esophageal walls on EUS, among whom 6 received endoscopic treatment. During follow-up, 95% (40/42) of the children had significant alleviation of the symptoms such as vomiting and dysphagia. CONCLUSIONS: For benign esophageal stenosis in children, EUS can help to evaluate the degree of esophageal wall involvement in esophageal stenosis lesions, possible etiologies, and the relationship between the esophagus and the lesion and provide an important basis for selecting treatment modality and avoiding complications, thereby helping to optimize the treatment regimen.
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Trastornos de Deglución , Estenosis Esofágica , Niño , Humanos , Estenosis Esofágica/diagnóstico por imagen , Estenosis Esofágica/etiología , Estenosis Esofágica/terapia , Endosonografía , Estudios RetrospectivosRESUMEN
The study of TCM manipulation's mechanism is the key scientific issue in the current manipulation research. It is the key and difficult point on the road of modernization and internationalization of Chinese orthopedics and traumatology. Meanwhile, it is also an important way to clarify systematically the scientific connotation of TCM manipulation. At present, our country is in an important period when multi-disciplinary intersection lead knowledge production, scientific innovation, and discipline development. The trend of cross-innovation between Chinese orthopedics and traumatology and other disciplines provides the carrier and method for the study of TCM manipulation's mechanism. Cervical spondylosis is the traditional dominant disease of Chinese orthopedics and traumatology. In recent years, many scholars have applied multi-disciplinary techniques and theories to explore the mechanism of TCM manipulation by focusing on the four dimensions of muscle, bone, blood vessel and nerve. The article takes the treatment of cervical spondylosis by TCM manipulation as the research entry point, and integrates the application status and implementation strategies of various techniques and theories under the background of multi-disciplinary intersection, which is conducive to the better combination, innovation and transformation of Chinese orthopedics and traumatology with other disciplines, and provides ideas and references for systematically clarifying the scientific connotation of TCM manipulation.
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Medicina Tradicional China , Espondilosis , Humanos , Espondilosis/terapiaRESUMEN
The increasing role of unmanned aerial vehicle (UAV) swarms in modern warfare poses a significant challenge to ground and air defense systems. Considering complex terrain environments and multi-sensor resources including radar and photoelectric systems constraints, a novel multi-sensor dynamic scheduling algorithm is proposed in this paper. Firstly, a transmission model with Fresnel zone under complex terrain and sensor models for radar/photoelectric systems are established. Considering the constraints of 6 factors, such as pitch angle, array scanning angle and threat levels, a detection model is developed subsequently. Secondly, to meet the real-time requirements of ground and air defense systems, a fast calculation method for Fresnel zone clearance using adaptive buffer is achieved. Thirdly, an improved Hungarian algorithm is proposed to solve the combinatorial optimization problem of sensor scheduling. Finally, simulation experiments are conducted to evaluate the algorithm performance under different conditions. The results demonstrate that the proposed approach significantly reduces the sensor switching rate while achieving a high sensor-UAV matching rate and high-threat matching rate. Furthermore, the simulation results verify the effectiveness of the proposed algorithm when applied to multi-sensor scheduling for defending UAV swarms.
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To investigate the fractal characteristics of rock crack distributions during the loading process, discrete element method was used to make rock samples with joints and record the crack propagation. The Box-counting method was used to quantitatively analyze the fractal dimension of the crack distribution at each moment, and the relationship between the crack fractal dimension and strain ratio was established based on fractal theory. The results indicated that the relationship between the fractal dimension of the crack distribution and strain ratio showed a strong linear characteristic. By transforming this linear relationship into a linear function, the slope of the function was found to be linked to the failure patterns of the sample, and a refinement coefficient (damage-fracture reduction factor) was identified from the slope as an effective basis for determining the degree of sample damage and fracture. The damage-fracture reduction factor can be categorized: 0.25-0.5 (spilt and fracture), 0.5-0.9 (synergy between fracture and damage), 0.9-1 (microcrack asymptotic damage). Owing to the linear fractal characteristics, an expression for the damage variables influenced by failure patterns can be established from the geometric aspect. In addition, the linear fractal characteristics of the cracks were verified in other acoustic emission and crack extension experiments.
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Phosphatidylinositol 3-kinase (PI3K) is one of the most attractive therapeutic targets for cervical cancer treatment. In this study, we designed and synthesized a series of benzimidazole derivatives and evaluated their anti-cervical cancer activity. Compound 4r exhibited strong antiproliferative activity in different cervical cancer cell lines HeLa, SiHa and Ca Ski, and relative lower cytotoxicity to normal hepatic and renal cell lines LO2 and HEK-293t (IC50 values were at 21.08 µM and 23.96 µM respectively). Its IC50 value was at 3.38 µM to the SiHa cells. Further mechanistic studies revealed that 4r induced apoptosis, arrested cell cycle in G2/M phase, suppressed PI3K/Akt/mTOR pathway and inhibit the polymerization of tubulin. Molecular docking study suggested that 4r formed key H-bonds action with PI3Kα (PDB ID:8EXU) and tubulin (PDB ID:1SA0). Zebrafish acute toxicity experiments showed that high concentrations of 4r did not cause death or malformation of zebrafish embryos. All these results demonstrated that 4r would be a promising lead candidate for further development of novel PI3K and tubulin dual inhibitors in cervical cancer treatment.
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Antineoplásicos , Bencimidazoles , Proliferación Celular , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Serina-Treonina Quinasas TOR , Moduladores de Tubulina , Tubulina (Proteína) , Neoplasias del Cuello Uterino , Pez Cebra , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/metabolismo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo , Bencimidazoles/farmacología , Bencimidazoles/química , Bencimidazoles/síntesis química , Tubulina (Proteína)/metabolismo , Proliferación Celular/efectos de los fármacos , Animales , Relación Estructura-Actividad , Fosfatidilinositol 3-Quinasas/metabolismo , Femenino , Estructura Molecular , Moduladores de Tubulina/farmacología , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/química , Apoptosis/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Simulación del Acoplamiento Molecular , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacosRESUMEN
Biomaterials with dual functions of osteoimmunomodulation and bone repair are very promising in the field of orthopedic materials. For this purpose, we prepared copper-based carbon dots (CuCDs) and doped them into oxychondroitin sulfate/poly-acrylamide hydrogel (OPAM) to obtain a hybrid hydrogel (CuCDs/OPAM). We evaluated its osteoimmunomodulatory and bone repair properties in vitro and in vivo. The obtained CuCDs/OPAM exhibited good rBMSCs-cytocompatibility and anti-inflammatory properties in vitro. It also could effectively promote rBMSCs differentiation and the expression of osteogenic differentiation factors from rBMSCs under an inflammatory environment. Moreover, CuCDs/OPAM could induce macrophage phenotype switching (from M1-type macrophages to M2-type macrophages) in vivo, which is beneficial for anti-inflammatory action and presents good osteoimmunomodulation capability to induce a bone immune microenvironment to promote the differentiation of rBMSCs. In conclusion, CuCDs/OPAM hydrogel has dual functions of osteoimmunomodulatory and bone repair and is a promising bone filling and repair material.
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Regeneración Ósea , Carbono , Cobre , Hidrogeles , Osteogénesis , Osteogénesis/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Regeneración Ósea/efectos de los fármacos , Carbono/química , Carbono/farmacología , Animales , Cobre/química , Cobre/farmacología , Diferenciación Celular/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Puntos Cuánticos/química , Ratones , Células Cultivadas , Macrófagos/efectos de los fármacos , Macrófagos/citologíaRESUMEN
The effect of hot isostatic pressing (HIP) on the microstructure and properties of hot dip aluminum coating cooled in a magnetic field was investigated in this study. In order to improve the microstructure and properties of magnetic dip aluminum coating, hot isostatic pressing technology was used for post-treatment. Initially, a traditional aluminum-impregnated coating was prepared on the surface of titanium alloy TA15, an alternating electromagnetic field was applied during the forming and solidification process of the coating. Finally, the coating was treated with hot isostatic pressing technology. Analyzed three different coatings of the microstructure and element distribution, and tested the microhardness of the coatings at various positions. The test results revealed that the TA15 titanium alloy hot-dip aluminum coatings obtained through the three different processes exhibited a gradient structure. Compared with the traditional hot-dipped aluminum air-cooled coating, when an appropriate intensity of alternating electromagnetic field was applied during the coating solidification process, the outer coating structure was enhanced, the number of holes was reduced, the microstructure density increased, and the number of cracks significantly decreased. The defects of the 800 °C hot isostatic magnetic cold and hot dip aluminum coating were repaired under high temperature and pressure, resulting in a uniform and fine microstructure. The comprehensive properties of the magnetic cold and hot dip aluminum coating on the surface of the titanium alloy were effectively enhanced through hot isostatic pressing.
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The core of clinic treatment of Parkinson's disease (PD) is to enhance dopamine (DA) signaling within the brain. The regulation of dopamine transporter (DAT) is integral to this process. This study aims to explore the regulatory mechanism of glial cell line-derived neurotrophic factor (GDNF) on DAT, thereby gaining a profound understanding its potential value in treating PD. In this study, we investigated the effects of GDNF on both cellular and mouse models of PD, including the glycosylation and membrane transport of DAT detected by immunofluorescence and immunoblotting, DA signal measured by neurotransmitter fiber imaging technology, Golgi morphology observed by electron microscopic, as well as cognitive ability assessed by behavior tests. This study revealed that in animal trials, MPTP-induced Parkinson's Disease (PD) mice exhibited a marked decline in cognitive function. Utilizing ELISA and neurotransmitter fiber imaging techniques, we observed a decrease in dopamine levels and a significant reduction in the intensity of dopamine signal release in the Prefrontal Cortex (PFC) of PD mice induced by MPTP. Intriguingly, these alterations were reversed by Glial Cell Line-Derived Neurotrophic Factor (GDNF). In cellular experiments, following MPP + intervention, there was a decrease in Gly-DAT modification in both the cell membrane and cytoplasm, coupled with an increase in Nongly-DAT expression and aggregation of DAT within the cytoplasm. Conversely, GDNF augmented DAT glycosylation and facilitated its membrane transport in damaged dopaminergic neurons, concurrently reversing the effects of GRASP65 depletion and Golgi fragmentation, thereby reducing the accumulation of DAT in the Golgi apparatus. Furthermore, overexpression of GRASP65 enhanced DAT transport in PD cells and mice, while suppression of GRASP65 attenuated the efficacy of GDNF on DAT. Additionally, GDNF potentiated the reutilization of neurotransmitters by the PFC presynaptic membrane, boosting the effective release of dopamine following a single electrical stimulation, ultimately ameliorating the cognitive impairments in PD mice.Therefore, we propose that GDNF enhances the glycosylation and membrane trafficking of DAT by facilitating the re-aggregation of the Golgi apparatus, thereby amplifying the utilization of DA signals. This ultimately leads to the improvement of cognitive abilities in PD mouse models. Our study illuminates, from a novel angle, the beneficial role of GDNF in augmenting DA utilization and cognitive function in PD, providing fresh insights into its therapeutic potential.
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Cognición , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Dopamina , Factor Neurotrófico Derivado de la Línea Celular Glial , Animales , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Glicosilación , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Ratones , Cognición/efectos de los fármacos , Dopamina/metabolismo , Masculino , Enfermedad de Parkinson/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Membrana Celular/metabolismo , Corteza Prefrontal/metabolismoRESUMEN
This research delves into the transfer and loss of energy in a discrete mass when subjected to forced vibration. Using discrete element method (DEM), we analyzed the dynamic behavior of regular spherical granular assemblies and the energy distribution characteristics under different excitation frequencies and reduced accelerations. Moreover, the energy transfer and dissipation process of granular assemblies under different vibration states are studied using an experimental method. The results show that the granular assemblies will produce collision energy dissipation, thermal energy dissipation, acoustic energy dissipation and other forms of energy dissipation in the forced vibration state and the proportion of different energy dissipation under different excitation is given. The collision and friction of granular assemblies are the key to affecting other forms of energy dissipation. When the excitation increases, the energy dissipation forms are generated inside the granular assemblies, and the proportion of collision energy dissipation of the granular assemblies increases. The acoustic energy above 20 kHz occupies the main part of the acoustic energy dissipation. Thermal energy consumption always exists, which takes a long time to play a role. The granular also have other forms of energy loss, which is hard to be measured, including Rayleigh waves generated by granular collision. In this study, the relationship between the forced vibration state of the granular assemblies and the energy loss distribution is established. Various types of energy transfer and conversion distribution which further enriches the energy dissipation of discrete element calculation of the granular assemblies is discussed and provides a reference for the energy loss analysis of the granular assemblies.
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Background: The Functional Movement Screen (FMS) is widely recognized by clinicians and trainers as a valuable tool for the prediction and prevention of training injuries in sports population. However, some studies suggested that FMS may not fully meet the needs of professional athletes. To address this, the Modified Functional Movement Screen (MFMS) has been specifically developed for athletes. Methods: A total of 527 male athletes in active service without prior training injuries 18.5 ± 1.2 years old) underwent the MFMS test, and their training injuries were monitored during a 2-year follow-up period. The ability of the MFMS to predict the risk of training injury was evaluated based on the receiver operating characteristic (ROC) curve of the total MFMS score. Binary logistic analysis was employed to examine the correlation between the 10 MFMS tests and the risk of training injury. Results: The injured group of athletes had significantly lower total MFMS scores compared to the healthy group (P < 0.001). The total MFMS score demonstrated a strong predictive ability for training injury risk, with an area under the ROC curve of 0.97 (P < 0.001). The calculated cut-off point was set at 22, yielding an odds ratio of 25.63, sensitivity of 0.94, and specificity of 0.88. Binary logistic regression analysis revealed a negative correlation between 6 MFMS tests and the risk of training injury. Conclusion: The MFMS can effectively predict the risk of training injuries. Athletes with a total MFMS score below 22 are more susceptible to experiencing injuries during training.
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BACKGROUND: The blood-spinal cord barrier (BSCB) is a unique protective barrier located between the circulatory system and the central nervous system. BSCB plays a vital role in various diseases. However, there is little systematic research and recording in this field by bibliometrics analysis. We aim to visualize this field through bibliometrics to analyze the hotspots and trends of BSCB and in order to facilitate an understanding of future developments in basic and clinical research. METHODS: To conduct a bibliometric study of original publications and their references, the keywords Blood Spinal-Cord Barrier and BSCB are searched and filtered from the Web of Science database (2000-2022), focusing on citations, authors, journals, and countries/regions. Additionally, clustering of the references and co-citation analysis was completed, including a total of 1926 articles and comments. RESULTS: From the results, 193 authors were identified, among which Sharma Hs played a key role. As far as the analysis result of the clustering of the references is concerned, the most common type in cluster analysis is spinal cord injury (SCI) which is a current and developing research field. The keywords are also the specific content under these clusters. The most influential organization is Univ Calif San Francisco, and "Proceedings of The National Academy of Sciences of The United States of America" magazine is the most cited magazine. CONCLUSION SUBSECTIONS: The research on BSCB is booming focusing mainly on "BSCB in SCI" including "activation," "pathway," and "drug delivery" which is also the trend of future research.
Asunto(s)
Sangre Fetal , Traumatismos de la Médula Espinal , Humanos , Sistema Nervioso Central , BibliometríaRESUMEN
Osteoporosis (OP) represents a substantial public health issue and is associated with increasing rates of morbidity and mortality. It is characterized by reduced bone mineral density, deterioration of bone tissue quality, disruption of the microarchitecture of bones, and compromised bone strength. These changes may be attributed to the following factors: intercellular communication between osteoblasts and osteoclasts; imbalanced bone remodeling; imbalances between osteogenesis and adipogenesis; imbalances in hormonal regulation; angiogenesis; chronic inflammation; oxidative stress; and intestinal microbiota imbalances. Treating a single aspect of the disease is insufficient to address its multifaceted nature. In recent decades, traditional Chinese medicine (TCM) has shown great potential in the treatment of OP, and the therapeutic effects of Chinese patent drugs and Chinese medicinal herbs have been scientifically proven. TCMs, which contain multiple components, can target the diverse pathogeneses of OP through a multitargeted approach. Herbs such as XLGB, JTG, GSB, Yinyanghuo, Gusuibu, Buguzhi, and Nvzhenzi are among the TCMs that can be used to treat OP and have demonstrated promising effects in this context. They exert their therapeutic effects by targeting various pathways involved in bone metabolism. These TCMs balance the activity of osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells), and they exhibit anti-inflammatory, immunomodulatory, anti-oxidative, and estrogen-like functions. These multifaceted mechanisms underlie the efficacy of these herbs in the management and treatment of OP. Herein, we examine the efficacy of various Chinese herbs and Chinese patent drugs in treating OP by reviewing previous clinical trials and basic experiments, and we examine the potential mechanism of these therapies to provide evidence regarding the use of TCM for treating OP.