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BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is a mild form of hepatic encephalopathy that lacks observable signs and symptoms. Nevertheless, MHE can cause neurocognitive dysfunction, although the neurobiological mechanisms are not fully understood. Here, the effects of hippocampal iron deposition on cognitive function and its role in MHE were investigated. MATERIALS AND METHODS: Eighteen rats were assigned to experimental and control groups. MHE was induced by thioacetamide. Spatial memory and exploratory behavior were assessed by the Morris water and elevated plus mazes. Hippocampal susceptibility was measured by quantitative susceptibility mapping, iron deposition in the hippocampus and liver by Prussian blue staining, and inflammatory cytokine and ferritin levels in the hippocampus were measured by ELISA. RESULTS: MHE rats showed impaired spatial memory and exploratory behavior (P < 0.05 for all parameters). The bilateral hippocampal susceptibility values were significantly raised in MHE rats, together with evidence of neuroinflammation (increased pro-inflammatory and reduced anti-inflammatory cytokine levels (all P < 0.05). Further analysis indicated good correlations between hippocampal susceptibility values with latency time and inflammatory cytokine levels in MHE but not in control rats. CONCLUSION: MHE induced by thioacetamide was associated with hippocampal iron deposition and inflammation, suggesting that iron overload may be an important driver of neuroinflammatory responses.
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Disfunción Cognitiva , Encefalopatía Hepática , Sobrecarga de Hierro , Ratas , Animales , Encefalopatía Hepática/complicaciones , Enfermedades Neuroinflamatorias , Tioacetamida , Disfunción Cognitiva/etiología , Inflamación/inducido químicamente , Inflamación/complicaciones , Citocinas , Sobrecarga de Hierro/complicaciones , HierroRESUMEN
Biodegradable polymeric nanoparticles have received growing interest as one of the most promising agents for drug delivery. In the present work, functional and core-crosslinked poly(ethylene glycol) with poly(ϵ-caprolactone) (PEG5k -PCL10k ) block copolymer and lecithin as biodegradable polymer doped with polyaniline was used to assemble nanoparticles which were prepared for targeted delivery and controlled release of cisplatin. The morphology of the polyaniline nanoparticles was determined by dynamic light scattering and the prepared nanoparticles showed a size of 83(±1)â nm and a uniform spherical shape. For targeting to HER2 receptors, Herceptin was applied to guide the nanoparticles to breast cancer cells. Studies on cellular uptake and drug release of the nanocarriers showed that the prepared nanoparticles were efficiently taken up by breast cancer cells and the drug was released efficiently under acidic conditions when exposed to a near-infrared laser (808â nm, 1.54â W) for 5â min. Our research highlights the great potential of near-infrared light and pH dual-responsive release by core-crosslinked nanoparticles in nanobiomedicine.
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Compuestos de Anilina/química , Cisplatino/química , Portadores de Fármacos/química , Nanopartículas/química , Polietilenglicoles/química , Cisplatino/farmacocinética , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Humanos , Rayos InfrarrojosRESUMEN
Objective: To explore the effectiveness of Nice knot technique for wound closure in Gustilo type â ¢A and â ¢B open tibial fractures. Methods: A retrospective study was performed on 22 patients with Gustilo type â ¢A and â ¢B open tibial fractures, who underwent wound closure using the Nice knot technique and were admitted between June 2021 and June 2022. There were 15 males and 7 females. The age ranged from 18 to 67 years, with an average of 41.9 years. The causes of injury included traffic accident in 11 cases, falling from height in 7 cases, and heavy object injuries in 4 cases. Fractures were located on the left side in 9 cases and on the right side in 13 cases. And 9 cases were type â ¢A fractures and 13 were type â ¢B fractures according to Gustilo classification. All patients had extensive soft tissue injuries, and no vascular or neurological damage was observed. The time from injury to debridement was 3-8 hours (mean, 6.5 hours). The sizes of wounds before operation and at 2 weeks after operation were measured and wound healing rate at 2 weeks after operation were calculated. The wound healing time and wound healing grading were recorded. The Vancouver Scar Scale (VSS) score was used to assess the wound scar after wound healed and the excellent and good rate was calculated. Results: The wound area was 21.0-180.0 cm 2 (mean, 57.82 cm 2) before operation, and it was 1.2-27.0 cm 2 (mean, 6.57 cm 2) at 2 weeks after operation. The wound healing rate at 2 weeks after operation was 76%-98% (mean, 88.6%). After operation, 2 cases needed to adjust Nice knot due to skin cutting and 1 case occurred soft tissue infection on the wound. The other patient's wounds healed. The average wound healing time was 27.8 days (range, 18-44 days). And the wound healing were grade A in 13 cases and grade B in 9 cases. VSS score was 2-9, with an average of 4.1; 10 cases were rated as excellent, 10 as good, and 2 as poor, with an excellent and good rate of 90.9%. All patients were followed up 9-24 months (mean, 14.6 months). During follow-up, no deep infection or osteomyelitis occurred. Two cases experienced fracture non-union, and were treated with compression fixation and bone grafting. The fractures of the other patients all healed, with a healing time of 85-190 days (mean, 148.2 days). Conclusion: Nice knot technique can be used in wound closure of Gustilo type â ¢A and â ¢B open tibial fractures effectively, which is easy to operate.
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Fracturas Abiertas , Fracturas de la Tibia , Masculino , Femenino , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Cicatriz , Estudios Retrospectivos , Resultado del Tratamiento , Fracturas de la Tibia/cirugía , Cicatrización de Heridas , Fijación Interna de Fracturas/métodos , Fracturas Abiertas/cirugíaRESUMEN
In this paper, a wideband transmission unit cell is proposed for programmable metasurfaces operating in the Ka-band. The unit cell features a compact period of only 2.91 mm, corresponding to 0.34 λ0 at the center frequency of 35 GHz. A receiving layer, consisting of a patch loaded with two PIN diodes, is utilized to achieve 1-bit phase modulation, while a U-shaped patch serves as the transmitting layer to enable selection of linear polarization hold or conversion. Based on the multi-resonance principle, the proposed unit cell exhibits broadband behavior, as demonstrated by simulation results under periodic boundary conditions, which indicate a 3 dB transmission bandwidth of 29.4-40 GHz (30.5%). Two unit cells were fabricated and tested in a standard waveguide, with the minimum insertion loss of the two states tested being 1.2 dB and 3 dB bandwidths of 30.1-31.2 GHz and 33.5-38.5 GHz, respectively. The maximum 180° phase error is 10°, indicating the high quality of the proposed unit cell.
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BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is a common neuropsychiatric complication in patients with cirrhosis. Alterations in monoamine neurotransmitters have been associated with the pathogenesis of MHE. We investigated the levels of hippocampal noradrenergic neurotransmitter in a rat model of thioacetamide-induced chronic liver failure-related MHE, and their role in cognitive impairment. MATERIALS: 18 male Sprague-Dawley (SD) rats were equally divided in MHE and control groups. A rat model of MHE was established by intraperitoneal injection of thioacetamide (TAA) for 12 weeks. Cognitive function was assessed using the Morris water maze (MWM) test and locomotor activity and exploratory behavior assessed with open field test. The concentration of hippocampal noradrenaline (NE) was detected by ELISA, and the magnetic susceptibility value in the hippocampus was detected by quantitative susceptibility mapping. Hippocampal iron content was quantified by Prussian blue staining. RESULTS: MHE rats performed significantly poorer than their control counterparts in the MWM test, as seen by decreased number of platform crossings and time in the target quadrant, and increased path length to reach the target zone (P < 0.05 for all parameters). In the open field test, the MHE group exhibited lower locomotor activity and exploratory behavior than the control group (P < 0.05 for all parameters). We detected pronounced iron staining in the hippocampus of MHE rats, whereas no iron-stained particles were found in control rats. We observed an imbalance of inflammatory (increased pro- and decreased anti-) cytokines in the hippocampus of MHE rats. Further analysis of the data showed that the level of hippocampal noradrenaline in MHE rats was significantly lower than that of control rats (P < 0.05). We observed a correlation between the level of inflammatory cytokine and noradrenaline land susceptibility value in the rat hippocampus of the MHE group. CONCLUSION: Our results suggest that MHE associated with TAA-induced chronic liver failure is associated with alterations in noradrenergic neurotransmission. We propose that iron imbalance in the brain might lead to reduction in the levels of noradrenaline, and cognitive impairment.
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Disfunción Cognitiva , Enfermedad Hepática en Estado Terminal , Encefalopatía Hepática , Animales , Encéfalo/metabolismo , Disfunción Cognitiva/patología , Citocinas/metabolismo , Enfermedad Hepática en Estado Terminal/complicaciones , Enfermedad Hepática en Estado Terminal/patología , Encefalopatía Hepática/complicaciones , Encefalopatía Hepática/patología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Masculino , Norepinefrina , Ratas , Ratas Sprague-Dawley , Tioacetamida/toxicidadRESUMEN
BACKGROUND: To investigate the performance of synthetic relaxometry, three-dimensional pseudo-continuous arterial spin labelling (pCASL) and diffusion-weighted imaging (DWI) in differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs) and to compare with the conventional MRI. METHODS: Seventy-two patients with gliomas (including 27 LGGs and 45 HGGs) were studied using synthetic magnetic resonance imaging (sy-MRI), pCASL, and DWI with a 3.0 T MR scanner. T1 relaxometry (T1), T2 relaxometry (T2), as well as proton density (PD) from sy-MRI, cerebral blood flow (CBF) from pCASL, apparent diffusion coefficient (ADC) from DWI and enhancement quality (EQ), proportion enhancing (PE) from conventional contrast enhanced image based Visually-Accessible-Rembrandt-Images (VASARI) scoring system, were all analyzed by two radiologists. The Student's t-test, Mann-Whitney U test or Fisher's exact test was used to compare the parameters between LGGs and HGGs. The diagnostic performance of each parameter and their combination for glioma grading were analyzed. RESULTS: Significant statistical differences in T1, PD, CBF, ADC, EQ and PE are observed between LGGs and HGGs (all P < 0.001). The ADC values have higher discrimination abilities compared with other univariable parameters, with the AUC of 0.905. AUC values for conventional contrast-enhanced method, EQ and PE from VASARI, and conventional contrast-free method, CBF + ADC, are 0.873 and 0.912 respectively. The combined T1, PD, CBF and ADC model had the best performance for differentiating LGGs and HGGs with AUC, sensitivity and specificity of 0.993, 95.5%, 100%, respectively. CONCLUSIONS: Relaxometry parameters derived from synthetic MRI contributed to the discrimination of low-grade gliomas from high-grade gliomas. Proposed contrast-free approach combining T1, PD, CBF and ADC showed a strong discriminative power, and outperformed conventional approaches.
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Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/patología , Imagen de Difusión por Resonancia Magnética/métodos , Glioma/patología , Humanos , Imagen por Resonancia Magnética/métodos , Clasificación del Tumor , Estudios Retrospectivos , Sensibilidad y Especificidad , Marcadores de SpinRESUMEN
Hyperglycemia has been shown to aggravate ischemic brain damage, in which the inflammatory reaction induced by hyperglycemia is involved in the worsening of cerebral ischemia-reperfusion injury. However, the role of microglial polarization in hyperglycemia-aggravating cerebral ischemia-reperfusion injury remains unknown. The present study investigated whether diabetic hyperglycemia inhibited or activated microglia, as well as microglial subtypes 1 and 2. Rats were used to establish the diabetic hyperglycemia and middle cerebral artery occlusion (MCAO) model. The markers CD11b, CD16, CD32, CD86, CD206, and Arg1 were used to show M1 or M2 microglia. The results revealed increased neurological deficits, infarct volume, and neural apoptosis in rats with hyperglycemia subjected to MCAO for 30 min and reperfused at 1, 3, and 7 days compared with the normoglycemic rats. Microglia and astrocyte activation and proliferation were inhibited in hyperglycemic rats. Furthermore, M1 microglia polarization was promoted, while that of M2 microglia was inhibited in hyperglycemic rats. These findings suggested that the polarization of M1 and M2 microglia is activated and inhibited, respectively, in hyperglycemic rats and may be involved in the aggravated brain damage caused by ischemia-reperfusion in diabetic hyperglycemia.
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Isquemia Encefálica/complicaciones , Hiperglucemia/patología , Inflamación/patología , Macrófagos/inmunología , Microglía/inmunología , Daño por Reperfusión/complicaciones , Animales , Apoptosis , Modelos Animales de Enfermedad , Hiperglucemia/etiología , Infarto de la Arteria Cerebral Media/fisiopatología , Inflamación/etiología , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Microglía/metabolismo , Microglía/patología , Ratas , Ratas Sprague-DawleyRESUMEN
Functional drug delivery systems enabling various favorable characteristics including specific targets, efficient cellular uptake and controllable release. At present work, a folate and cRGD dual modified nanoparticles based on NIR light and glutathione dual stimuli-responsive release system was successfully prepared and which simultaneously deliver cisplatin and ICG to tumor sites to enhance controllability. The prepared nanoparticles showed a stable uniform spherical morphology of 77.59â¯nm particle size range in PBS (pHâ¯=â¯7.4, 25⯰C) and the encapsulated cisplatin were rapidly released in acidic environment especially added glutathione (GSH) and NIR irradiation. Moreover, the prepared nanoparticles can be efficiently internalized by tumor cells through the enhanced dual targeted ligands (folate and cRGD) for ICG imaging. The cytotoxicity assays showed that the cells viability decreased to 1.95% (SGC-7901) when been exposed to NIR light, and which further decreased to 1.25% in MCF-7 cells. Thus, the prepared nanoparticles showed excellent performance for photothermal conversion therapy of tumor cells and especially on human breast tumor cells. Our research highlights the great potential of stimuli-responsive smart nanoparticles in biomaterial and nano-biomedicine.