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We propose a novel strategy for tailoring the structure of fluorescent molecules to achieve emission at the tail end of the NIR-II window. The favorable spectroscopic properties and low cytotoxicity of YNs make them powerful tools for bioimaging. Notably, YN-4 exhibits a brightness 2.5 times greater than YN-3, 6 times that of IR-783, and 5 times that of ICG. This enhanced brightness enabled high-resolution imaging of mouse thoracic and abdominal cavities, tumor vasculature, and real-time monitoring of gastrointestinal motility using YN-4. Furthermore, covalent grafting of glucose onto the YN-Glu scaffold significantly improved tumor-targeting capability and facilitated tracking of glucose metabolism. This work aims to extend the application of fluorescent molecule imaging beyond the NIR-IIa window.
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Colorantes Fluorescentes , Indoles , Animales , Ratones , Indoles/química , Colorantes Fluorescentes/química , Humanos , Espectroscopía Infrarroja Corta/métodos , Imagen Óptica , Carbocianinas/química , Línea Celular Tumoral , Glucosa/metabolismo , Glucosa/químicaRESUMEN
INTRODUCTION: The clinical symptoms of Lumbar Disc Herniation (LDH) can be effectively ameliorated through Lever Positioning Manipulation (LPM), which is closely linked to the brain's pain-regulating mechanisms. Magnetic Resonance Imaging (MRI) offers an objective and visual means to study how the brain orchestrates the characteristics of analgesic effects. From the perspective of multimodal MRI, we applied functional MRI (fMRI) and Magnetic Resonance Spectrum (MRS) techniques to comprehensively evaluate the characteristics of the effects of LPM on the brain region of LDH from the aspects of brain structure, brain function and brain metabolism. This multimodal MRI technique provides a biological basis for the clinical application of LPM in LDH. METHODS AND ANALYSIS: A total of 60 LDH patients and 30 healthy controls, matched by gender, age, and years of education, will be enrolled in this study. The LDH patients will be divided into two groups (Group 1, n = 30; Group 2, n = 30) using a random number table method. Group 1 will receive LPM treatment once every two days, for a total of 12 times over 4 weeks. Group 2 will receive sham LPM treatment during the same period as Group 1. All 30 healthy controls will be divided into Group 3. Multimodal MRI will be performed on Group 1 and Group 2 at three time points (TPs): before LPM (TP1), after one LPM session (TP2), and after a full course of LPM treatment. The healthy controls (Group 3) will not undergo LPM and will be subject to only a single multimodal MRI scan. Participants in both Group 1 and Group 2 will be required to complete clinical questionnaires. These assessments will focus on pain intensity and functional disorders, using the Visual Analog Scale (VAS) and the Japanese Orthopaedic Association (JOA) scoring systems, respectively. DISCUSSION: The purpose of this study is to investigate the multimodal brain response characteristics of LDH patients after treatment with LPM, with the goal of providing a biological basis for clinical applications. TRIAL REGISTRATION NUMBER: https://clinicaltrials.gov/ct2/show/NCT05613179 , identifier: NCT05613179.
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Encéfalo , Desplazamiento del Disco Intervertebral , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Desplazamiento del Disco Intervertebral/terapia , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Adulto , Masculino , Femenino , Encéfalo/diagnóstico por imagen , Persona de Mediana Edad , Imagen Multimodal/métodos , Adulto Joven , Degeneración del Disco IntervertebralRESUMEN
Branched-chain amino acids (BCAAs), including leucine, valine, and isoleucine, play crucial roles in regulating metabolic balance and maintaining physiological functions in the body. Extensive studies have been focused on their implications in obesity, diabetes, and cardiovascular diseases. Nevertheless, accumulating evidence suggests that BCAAs metabolism also plays significant roles in tumorigenesis and progression. In this review, we overview recent progress of the study on BCAAs metabolism including its relationship with epigenetic regulation. Particularly, we discuss the metabolic reprogramming and metabolic sensing of BCAAs and its intermediate metabolites in tumor cells and microenvironment to decipher their functions. An enhanced understanding of the roles and mechanism of BCAAs metabolism in tumorigenesis and progression will contribute to development of novel therapeutic strategies against tumor.
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Aminoácidos de Cadena Ramificada , Carcinogénesis , Neoplasias , Aminoácidos de Cadena Ramificada/metabolismo , Humanos , Carcinogénesis/metabolismo , Neoplasias/metabolismo , Neoplasias/genética , Animales , Progresión de la Enfermedad , Epigénesis Genética , Microambiente TumoralRESUMEN
Eucalyptus was pretreated with diethylene glycol catalyzed by 0.02 mol/L CrCl3 for 10 min, resulting in 91 % delignification and 98 % cellulose recovery, with trace fermentation inhibitors generated. After the mild pretreatment, the accessibility and affinity of cellulase to eucalyptus was enhanced, especially since enzyme adsorption rate increased by 1.6-fold. Therefore, glucose yield of pretreated eucalyptus was 7.9-fold higher than that of untreated eucalyptus after hydrolyzed 48 h, in which the maximum glucose concentration reached 62 g/L from eucalyptus by adding Tween 80. According to the characterization analysis, the structure of the eucalyptus lignin-carbohydrate complexes structure was destroyed during the pretreatment, while lignin fragments was likely reacted with diethylene glycol to form the stabilized aromatic ethers. Moreover, the extracted Deg-lignin exhibited better performances than commercial alkali lignin such as higher fluorescence intensity, less negative surface charge, and lower particle size. The mild pretreatment method with diethylene glycol and CrCl3 provided a promising approach for co-production of fermentable sugars and high activity lignin from lignocellulosic biomass.
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Glicoles de Etileno , Eucalyptus , Fermentación , Lignina , Eucalyptus/química , Lignina/química , Glicoles de Etileno/química , Hidrólisis , Glucosa/metabolismo , Glucosa/química , Azúcares/química , Azúcares/metabolismo , Celulasa/metabolismo , Celulasa/química , BiomasaRESUMEN
Background and aims: Most studies have analyzed the relationship between resting heart rate (RHR) measured at only one time point and future clinical events. The current study aims to investigate the impact of long-term RHR changes on future clinical outcomes in a decade-long cohort with type 2 diabetes mellitus (T2DM). Methods: The two-staged follow-up involved 2,513 T2DM participants. The first stage (2008-2014) intended to identify levels and trends in RHR changes, while the second stage (2014-2018) attempted to collect new occurrence records of clinical results. Cox proportional hazards models were applied to predict hazard ratios (HRs), along with 95% confidence interval (CI) for the correlation between RHR changes and future events. Results: There is no significant correlation between baseline RHR levels and long-term clinical events. According to the range of RHR change, compared with the stable RHR group, the adjusted HRs for cardiovascular events and all-cause death in the large increase group were 3.40 (95% CI: 1.33-8.71, p=0.010) and 3.22 (95% CI: 1.07-9.64, p=0.037), respectively. While the adjusted HRs for all-cause death and major adverse cardiac and cerebrovascular events (MACCE) in the moderate decrease group were 0.55 (95% CI: 0.31-0.96, p=0.037) and 0.51 (95% CI: 0.26-0.98, p=0.046). According to the trend of RHR, compared with the normal-normal group, the adjusted HRs for composite endpoint events and cerebrovascular events in the normal-high group were 1.64 (95% CI: 1.00-2.68, p=0.047) and 2.82 (95% CI: 1.03-7.76, p=0.043), respectively. Conclusion: Changes in RHR had predictive value for long-term clinical events in diabetic populations. Individuals with significantly elevated RHR over a particular period of time showed an increased risk of adverse events.
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Diabetes Mellitus Tipo 2 , Frecuencia Cardíaca , Humanos , Masculino , Femenino , Frecuencia Cardíaca/fisiología , Diabetes Mellitus Tipo 2/fisiopatología , Persona de Mediana Edad , Estudios de Seguimiento , Anciano , Pronóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/fisiopatología , Descanso/fisiología , Adulto , Factores de Riesgo , Factores de TiempoRESUMEN
The activation of microglia and the production of cytokines are key factors contributing to progressive neurodegeneration. Despite the well-recognized neuronal programmed cell death regulated by microglial activation, the death of microglia themselves is less investigated. Nucleotide-binding oligomerization domain, leucine-rich repeat-containing X1 (NLRX1) functions as a scaffolding protein and is involved in various central nervous system diseases. In this study, we used the SM826 microglial cells to understand the role of NLRX1 in lipopolysaccharide (LPS)-induced cell death. We found LPS-induced cell death is blocked by necrostatin-1 and zVAD. Meanwhile, LPS can activate poly (ADP-ribose) polymerase-1 (PARP-1) to reduce DNA damage and induce heme oxygenase (HO)-1 expression to counteract cell death. NLRX1 silencing and PARP-1 inhibition by olaparib enhance LPS-induced SM826 microglial cell death in an additive manner. Less PARylation and higher DNA damage are observed in NLRX1-silencing cells. Moreover, LPS-induced HO-1 gene and protein expression through the p62-Keap1-Nrf2 axis are attenuated by NLRX1 silencing. In addition, the Nrf2-mediated positive feedback regulation of p62 is accordingly reduced by NLRX1 silencing. Of note, NLRX1 silencing does not affect LPS-induced cellular reactive oxygen species (ROS) production but increases mixed lineage kinase domain-like pseudokinase (MLKL) activation and cell necroptosis. In addition, NLRX1 silencing blocks bafilomycin A1-induced PARP-1 activation. Taken together, for the first time, we demonstrate the role of NLRX1 in protecting microglia from LPS-induced cell death. The underlying protective mechanisms of NLRX1 include upregulating LPS-induced HO-1 expression via Nrf2-dependent p62 expression and downstream Keap1-Nrf2 axis, mediating PARP-1 activation for DNA repair via ROS- and autophagy-independent pathway, and reducing MLKL activation.
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Calcium/calmodulin-dependent serine protein kinase (CASK) is a scaffold protein and plays critical roles in neuronal synaptic formation and brain development. Previously, CASK was shown to associate with EGFR to maintain the vulval cell differentiation in C. elegans. In this study, we explored the role of CASK in CHME3 microglial cells. We found that CASK silencing protects cells from H2O2-induced cell death by attenuating PARP-1 activation, mitochondrial membrane potential loss, reactive oxygen species production, and mitochondrial fission, but it increases oxidative phosphorylation. The PARP-1 inhibitor olaparib blocks H2O2-induced cell death, suggesting the death mode of parthanatos. CASK silencing also increases AKT activation but decreases AMPK activation under H2O2 treatment. Pharmacological data further indicate that both signaling changes contribute to cell protection. Different from the canonical parthanatos pathway, we did not observe the AIF translocation from mitochondria into the nucleus, suggesting a non-canonical AIF-independent parthanatos in H2O2-treated CHME3 cells. Moreover, we found that CASK silencing upregulates the EGFR gene and protein expression and increases H2O2-induced EGFR phosphorylation in CHME3 microglia. However, EGFR activation does not contribute to cell protection caused by CASK silencing. In conclusion, CASK plays a crucial role in microglial parthanatos upon H2O2 treatment via stimulation of PARP-1 and AMPK but the inhibition of AKT. These findings suggest that CASK might be an ideal therapeutic target for CNS disorders.
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The inadequacy of tactile perception systems in humanoid robotic manipulators limits the breadth of available robotic applications. Here, we designed a multifunctional flexible tactile sensor for robotic fingers that provides capabilities similar to those of human skin sensing modalities. This sensor utilizes a novel PI-MXene/SrTiO3 hybrid aerogel developed as a sensing unit with the additional abilities of electromagnetic transmission and thermal insulation to adapt to certain complex environments. Moreover, polyimide (PI) provides a high-strength skeleton, MXene realizes a pressure-sensing function, and MXene/SrTiO3 achieves both thermoelectric and infrared radiation response behaviors. Furthermore, via the pressure response mechanism and unsteady-state heat transfer, these aerogel-derived flexible sensors realize multimodal sensing and recognition capabilities with minimal cross-coupling. They can differentiate among 13 types of hardness and four types of material from objects with accuracies of 94% and 85%, respectively, using a decision tree algorithm. In addition, based on the infrared radiation-sensing function, a sensory array was assembled, and different shapes of objects were successfully recognized. These findings demonstrate that this PI-MXene/SrTiO3 aerogel provides a new concept for expanding the multifunctionality of flexible sensors such that the manipulator can more closely reach the tactile level of the human hand. This advancement reduces the difficulty of integrating humanoid robots and provides a new breadth of application scenarios for their possibility.
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Fijación Interna de Fracturas , Fracturas Óseas , Rótula , Anclas para Sutura , Humanos , Fijación Interna de Fracturas/métodos , Fijación Interna de Fracturas/instrumentación , Fracturas Óseas/cirugía , Rótula/lesiones , Rótula/cirugía , Resultado del Tratamiento , Masculino , Femenino , Adulto , Persona de Mediana EdadRESUMEN
Africa produces around 60% of the rice the continent consumes, relying heavily on rice imports to fulfill the rest of the domestic demand. Over the past 10 years, the rice-agricultural area increased nearly 40%, while average yield remained stagnant. Here we used a process-based crop simulation modelling approach combined with local weather, soil, and management datasets to evaluate the potential to increase rice production on existing cropland area in Africa and assess cropland expansion and rice imports by year 2050 for different scenarios of yield intensification. We find that Africa can avoid further increases in rice imports, and even reduce them, through a combination of cropland expansion following the historical trend together with closure of the current exploitable yield gap by half or more. Without substantial increase in rice yields, meeting future rice demand will require larger rice imports and/or land conversion than now.
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Oryza , África , Agricultura , SueloRESUMEN
YH-2 represents an innovative, non-invasive fluorescent probe featuring a structure based on flavonoid onium salts. It is characterized by a well-suited Stokes shift and emits in the near-infrared (NIR) wavelength range. Its capacity to distinguish between HeLa cells, HepG2 cells, and LO2 cells is attributed to differential intracellular viscosity. Experimental results validate the heightened viscosity of organelles, such as the endoplasmic reticulum (ER), mitochondria and lysosomes in tumor cells compared to LO2 cells. Of paramount importance, YH-2 demonstrates the capability to swiftly image tumors within a mere 20 min following tail vein injection and this imaging ability can be sustained for an extended period of up to 5 h. This method offers a potential tumor diagnostic strategy in vivo.
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Colorantes Fluorescentes , Lisosomas , Humanos , Células HeLa , Colorantes Fluorescentes/química , Mitocondrias/química , Retículo Endoplásmico , Cloruro de Sodio , Imagen Óptica/métodos , ViscosidadRESUMEN
Paeonia Radix Alba is the dried root of Paeonia lactiflora Pall.in the ranunculus family,which is mainly produced in Zhejiang(Hang Paeony),Anhui(Hao Paeony)and Sichuan(Chuan Paeony).It has the effects of calming liver,relieving pain,nourishing blood,regulating menstrual period,collecting Yin,and preventing perspiration.Similar to Paeonia Radix Alba,Paeonia Radix Rubra is the dried root of Paeonia lactiflora Pall.or Paeonia veitchii Lynch.in the ranunculus family.Although the chemical constituents are similar,the efficacy and clinical application of the two herbal medicines are obviously different owing to their various processing methods and techniques.Modern studies have shown that Paeonia Radix Alba is rich in multiple chemical constituents,mainly including monoterpenoids and their glycosides,triterpenoids and their glycosides,volatile oils,flavonoids,and polyphenols,and has a wide range of pharmacological effects such as analgesia,anti-inflammation,anti-depression,liver protection,anti-tumor,and anti-hyperglycemia.This paper reviews the progress of research on effective constituents of Paeonia Radix Alba and their pharmacological effects to provide references for the comprehensive development and utilization of Paeonia Radix Alba.
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Objective To observe the intervention effect of acupuncture at"Zusanli"(ST36)or"Neiguan"(PC6)on the ulcerative colitis(UC)model mice.And to analyze the similarities and differences of gene transcription expression between the diseased colon and the non-diseased heart after acupuncture intervention by using transcriptomics,to explore whether there are efficacy differences between the two acupoints.Methods The UC mouse model was established by inducing dextran sulfate sodium salt(DSS).After successful modeling,the mice were randomly divided into model group,Zusanli group,and Neiguan group,with 9 mice in each group.Zusanli group and Neiguan group intervened with acupuncture at"Zusanli"and"Neiguan",respectively,30 min each time,once a day,for 5 consecutive days.The control and model groups were only bound without acupuncture.Observe the general situation of mice in each group,calculate the disease activity index(DAI),observe the morphological changes of colon tissue by HE staining.Use transcriptome sequencing technology to sequence and biologically analyze the colon tissue of mice in each group,and compare and study whether the two acupoints have differences in acupoint efficacy from the perspective of diseased tissue.At the same time,take the heart tissues of each group for comparative analysis,and discuss whether the effects of the two acupoints are different from the perspective of non-diseased tissue.Results Compared with control group,the DAI score of the model group increased significantly(P<0.001),and HE staining results showed significant pathological damage;after acupuncture at Zusanli or Neiguan,the DAI scores of UC mice were reduced considerably(P<0.05),and the pathological damage was significantly improved.The results of transcriptome sequencing and bioinformatics analysis showed that the effects of acupuncture at Zusanli or Neiguan on the colon of diseased tissue involved multiple genes,and 825 differential genes with similar changes(co-DEGs)were mainly enriched in white blood cells and chemokine pathways;there were 168 differentially expressed genes(ST36 only-DEGs)affected only by Zusanli,which were enriched to gastric acid secretion and other pathways;there were 325 differentially expressed genes(PC6 only-DEGs)only affected by Neiguan,which were enriched in cytokine-cytokine receptor interaction and other pathways.There were 95 co-DEGs in the heart of non-diseased tissue,which were mainly enriched in positive regulation of defense response and response to interleukin-1;there were 28 ST36 only-DEGs;there were114 PC6 only-DEGs,which were enriched in cardiovascular diseases and other pathways.Conclusion Acupuncture of"Zusanli"and"Neiguan"could improve UC mice's symptoms and pathological colon changes.However,through transcriptomic analysis,it was found that the two acupoints had differences in gene transcription effects on the colon of diseased tissue and the heart of non-diseased tissue,suggesting that acupoints with different distribution positions had some similarities in macro efficacy.Still,there were some differences at a micro level.
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BACKGROUND: A Hoffa fracture is an unstable intra-articular break that is generally treated with surgery. OBJECTIVE: To evaluate the feasibility and clinical outcomes of using a suture anchor combined with auxiliary fixation for the treatment of a lateral femoral condyle Hoffa fracture. METHODS: The study retrospectively reviewed 8 patients (5 males and 3 females) with a lateral femoral condyle Hoffa fracture who had been treated by combining a suture anchor with auxiliary fixation between January 2016 and April 2020. The mean age of patients was 37.5 years (ranging from 23 to 45). According to Letenneur's classification, there were 4 cases of type I, 2 cases of type II, and 2 cases of type III fractures. The clinical outcomes were assessed using Letenneur's functional assessment. RESULTS: The follow-up duration ranged between 14-24 months. All patients achieved primary healing of the incision and fracture union, as well as normal flexion and extension of the knee joint, with 7 cases showing excellent outcomes and 1 case showing a good outcome. No postoperative complications, such as fracture displacement, anchor loosening, or fracture malunion, occurred in this series. CONCLUSION: Our results indicated that a suture anchor, combined with external fixation, was an effective treatment for a lateral femoral condyle Hoffa fracture. Accordingly, this procedure is worthy of wider clinical application.
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Fracturas del Fémur , Fractura de Hoffa , Masculino , Femenino , Humanos , Adulto , Fracturas del Fémur/cirugía , Estudios Retrospectivos , Fijación Interna de Fracturas/métodos , Tornillos Óseos , Fémur , Resultado del Tratamiento , Articulación de la RodillaRESUMEN
Labor and water scarcity requires crop establishment of double-season rice to be shifted from traditional transplanting to direct seeding. Owing to the limited thermal time, only ultrashort-duration cultivars of about 95 d can be used for direct-seeded, double-season rice (DDR) in central China. However, whether the shift in crop establishment of double-season rice can reduce greenhouse gas emissions without yield penalty remains unclear. Field experiments were conducted in Hubei province, central China with three treatments of crop establishment in the early and late seasons of 2017 and 2018. Treatments included DDR with ultrashort-duration cultivars (DDRU), transplanted double-season rice with ultrashort-duration cultivars (TDRU), or with widely grown cultivars which have short duration of about 110 d (TDRS). It was found that crop growth duration of DDRU was 6-20 days shorter than that of TDRU and TDRS, respectively. Ultrashort-duration cultivars under DDRU achieved 15.1 t ha-1 of annual yield that was 9.4% higher than TDRU, and only 3.2% lower than TDRS. DDRU reduced the annual cumulative CH4 emission by 32.0-46.1%, but had no difference in N2O emission in comparison with TDRU and TDRS. The highest CO2 emission was TDRS followed by DDRU, and then TDRU. As a result, shifting from TDRU and TDRS to DDRU decreased global warming potential and yield-scaled greenhouse gas intensity by 28.9-53.2% and 20.7-63.8%, respectively. These findings suggest that DDR can be a promising alternative to labor- and water-intensive TDR in central China that offers important advantages in mitigating agricultural greenhouse gas emissions without sacrificing grain yield.
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Syk is a tumor suppressor gene in some solid tumors. Currently, it remains unknown how Syk gene hypermethylation is controlled by DNA methyltransferase (DNMT) and p53. In colorectal cancer HCT116 cells, we found that protein and mRNA levels of Syk were much higher in WT than in p53-/- cells. Both p53 inhibitor PFT-α and p53 silencing can reduce the protein and mRNA expression of Syk in WT cells, while DNMT inhibitor 5-Aza-2'-dC can increase Syk expression in p53-/- cells. Interestingly, the DNMT expression in p53-/- HCT116 cells was higher than that in WT cells. PFT-α can not only enhance Syk gene methylation but also increase DNMT1 protein and mRNA levels in WT HCT116 cells. In metastatic lung cancer cell lines A549 and PC9, which express WT p53 and gain function of p53, respectively, PFT-α can also downregulate Syk mRNA and protein expression. However, the Syk methylation level was increased by PFT-α in A549 but not in PC9 cells. Likewise, 5-Aza-2'-dC transcriptionally increased Syk gene expression in A549 cells, but not in PC9 cells. In summary methylation of Syk promoter requires DNMT1, and p53 can upregulate Syk expression via downregulation of DNMT1 at the transcriptional level.
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Neoplasias , Proteína p53 Supresora de Tumor , Línea Celular Tumoral , ADN/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/genética , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , ADN (Citosina-5-)-Metiltransferasas/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Metilación de ADN/genética , Regulación hacia Abajo/genética , Epigénesis Genética/genética , Neoplasias/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Quinasa Syk/genética , Quinasa Syk/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Regulación hacia Arriba/genética , HumanosRESUMEN
BACKGROUND: This study aimed to analyze and study the clinical effect of suture anchors in the treatment of radial head fractures (RHFs). METHODS: A total of 11 patients (five male and six female) with RHFs who were treated from March 2016 to June 2021 were included in this study. They were 17-61 (average 38.5) years old. In terms of the Johnston-Mason classification, two cases were type II, seven cases were type III, and two cases were type IV. All patients were treated with open reduction and anchor internal fixation. RESULTS: All 11 patients were followed up, all incisions healed by first intention, and the duration of follow-up was 14-20 months. The average operation time was 40 ± 15 min. The clinical healing time was 4-6 (average 5) weeks. No patients had any complications, such as traumatic arthritis, malunion, nerve injury, joint stiffness, or incision infection. The clinical effects were evaluated according to the Mayo Elbow Performance Score. The scores of all 11 cases were 90-95, all excellent. CONCLUSION: The application of suture anchor internal fixation in the treatment of RHFs has the advantages of accurate reduction, no need for a secondary operation to remove the fixation materials, less trauma, fewer complications, good fracture healing, and good recovery of elbow extension, flexion, and rotation functions.
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Articulación del Codo , Fracturas Radiales de Cabeza y Cuello , Fracturas del Radio , Humanos , Masculino , Femenino , Adulto , Anclas para Sutura , Resultado del Tratamiento , Fracturas del Radio/diagnóstico por imagen , Fracturas del Radio/cirugía , Fracturas del Radio/etiología , Articulación del Codo/diagnóstico por imagen , Articulación del Codo/cirugía , Fijación Interna de Fracturas/efectos adversos , Rango del Movimiento Articular/fisiología , Estudios RetrospectivosRESUMEN
Adenosine triphosphate (ATP) released from dying cells with high concentrations is sensed as a danger signal by the P2X7 receptor. Sodium iodate (NaIO3) is an oxidative toxic agent, and its retinal toxicity has been used as the model of dry age-related macular degeneration (AMD). In this study, we used NaIO3-treated mice and cultured retinal cells, including BV-2 microglia, 661W photoreceptors, rMC1 Müller cells and ARPE-19 retinal epithelial cells, to understand the pathological action of P2X7 in retinal degeneration. We found that NaIO3 can significantly decrease the photoreceptor function by reducing a-wave and b-wave amplitudes in electroretinogram (ERG) analysis. Optical coherence tomography (OCT) analysis revealed the degeneration of retinal epithelium and ganglion cell layers. Interestingly, P2X7-/- mice were protected from the NaIO3-induced retinopathy and inflammatory NLRP3, IL-1ß and IL-6 gene expression in the retina. Hematoxylin and eosin staining indicated that the retinal epithelium was less deteriorated in P2X7-/- mice compared to the WT group. Although P2X7 was barely detected in 661W, rMC1 and ARPE-19 cells, its gene and protein levels can be increased after NaIO3 treatment, leading to a synergistic cytotoxicity of BzATP [2'(3')-O-(4-benzoylbenzoyl)adenosine-5'-triphosphate tri(triethyleneammonium)salt] and NaIO3 administration in ARPE-19 cells. In conclusion, the paracrine action of the ATP/P2X7 axis via cell-cell communication is involved in NaIO3-induced retinal injury. Our results show that P2X7 antagonist might be a potential therapy in inflammation-related retinal degeneration.