RESUMEN
Blunt traumatic thoracic aortic injury (BTAI) is an extremely serious medical condition with a high rate of associated mortality. Recent advances in techniques such as thoracic endovascular repair offer new opportunities to manage the critical BTAI patients in an efficacious yet less invasive manner. A 65 year-old-male suffered from multiple injuries after a fall, including BTAI in the aortic arch, which resulted in dissection of the descending thoracic-abdominal aorta and iliac artery, development of an intimal flap in the left common carotid artery, and dissection of the left subclavian artery. Based on the imaging information of this patient and our clinical experience, the combined treatment of fenestrated thoracic endovascular repair and a chimney technique was immediately planned to fully repair these dissections and moreover prevent further dissection of the branching vessels, additionally to ensure sufficient blood flow in the left subclavian artery and left common carotid artery. The intervention yielded satisfactory early outcomes. Follow-up assessment at six months reported no symptoms or complications associated with the stent-graft. Computed tomography angiography further confirmed adequate stent-graft coverage of the aortic injury.
Asunto(s)
Aneurisma de la Aorta Torácica , Disección Aórtica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Anciano , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/cirugía , Prótesis Vascular , Humanos , Masculino , Diseño de Prótesis , Estudios Retrospectivos , Stents , Resultado del TratamientoRESUMEN
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD), an autoimmune astrocytopathic disease associated with the anti-aquaporin-4 (AQP4) antibody, is characterized by extensive necrotic lesions primarily located on the optic nerves and spinal cord. Tanshinone IIA (TSA), an active natural compound extracted from Salvia miltiorrhiza Bunge, has profound immunosuppressive effects on neutrophils. OBJECTIVE: The present study aimed to evaluate the effect of TSA on NMOSD mice and explore the underlying mechanisms. Mice were initially administered TSA (pre-TSA group, n = 20) or vehicle (vehicle group, n = 20) every 8 h for 3 days, and then NMOSD model was induced by intracerebral injection of NMOSD-immunoglobulin G (NMO-IgG) and human complement (hC). In addition, post-TSA mice (n = 10) were administered equal dose of TSA at 8 h and 16 h after model induction. At 24 h after intracerebral injection, histological analysis was performed to assess the inhibitory effects of TSA on astrocyte damage, demyelination, and neuroinflammation in NMOSD mice, and western blotting was conducted to clarify the effect of TSA on the NF-κB and MAPK signaling pathways. Furthermore, flow cytometry and western blotting were conducted to verify the proapoptotic effects of TSA on neutrophils in vitro. RESULTS: There was a profound reduction in astrocyte damage and demyelination in the pre-TSA group and post-TSA group. However, prophylactic administration of TSA induced a better effect than therapeutic treatment. The number of infiltrated neutrophils was also decreased in the lesions of NMOSD mice that were pretreated with TSA. We confirmed that prophylactic administration of TSA significantly promoted neutrophil apoptosis in NMOSD lesions in vivo, and this proapoptotic effect was mediated by modulating the caspase pathway in the presence of inflammatory stimuli in vitro. In addition, TSA restricted activation of the NF-κB signaling pathway in vivo. CONCLUSION: Our data provide evidence that TSA can act as a prophylactic agent that reduces NMO-IgG-induced damage in the mouse brain by enhancing the resolution of inflammation by inducing neutrophil apoptosis, and TSA may serve as a promising therapeutic agent for neutrophil-associated inflammatory disorders, such as NMOSD.
Asunto(s)
Abietanos/farmacología , Apoptosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Neuromielitis Óptica/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Neutrófilos/efectos de los fármacos , Abietanos/uso terapéutico , Animales , Encéfalo/metabolismo , Encéfalo/patología , Modelos Animales de Enfermedad , Ratones , Neuromielitis Óptica/metabolismo , Neuromielitis Óptica/patología , Fármacos Neuroprotectores/uso terapéutico , Neutrófilos/metabolismo , Neutrófilos/patologíaRESUMEN
Objective: In this paper, we present a comprehensive overview of our experience in establishing and leading distinct extracorporeal cardiopulmonary resuscitation (ECPR)-related teams to independently handle ECPR in the early stages in the emergency department. Methods: A retrospective analysis was conducted on the clinical data of 29 patients who underwent ECPR treatment in the emergency room between May 2018 and April 2022. A control group, consisting of 10 patients treated between May 2018 and September 2019 was managed using a standard rescue coordination mode. The 19 patients who received ECPR between October 2019 and April 2022 were treated by members of the department's 24-h extracorporeal life support team. We compared the implementation and operational challenges faced by the two groups, including item preparation, circuit setup, and ECPR initiation times, among other factors. Results: Gender, age, cardiac arrest risk factors, and other baseline data did not significantly differ between the two groups. Extracorporeal membrane oxygenation (ECMO) pipeline prefilling time (from 35.27±10.34 to 13.46±5.32), ECPR establishment time (from 62.35±29.61 to 30.98±13.41), and item preparation time (from 16.42±9.78 to 3.19±1.49) all considerably decreased when compared to the control group. The rate of return of spontaneous circulation recovery rose from 37.50 % to 77.78 % (P < 0.05). The consequences of gastrointestinal and pulmonary bleeding were greatly reduced while ECPR was being used, and the difference was statistically significant (P < 0.05). Significant improvements were made in the ECPR weaning rate (from 25.00 % to 38.89 %) and survival rate (from 20.0 % to 36.8 %). Conclusion: The establishment of a 24-h extracorporeal life support team significantly reduced the time needed for rescue during the early stage of independent setup of ECPR in the emergency department and serves as a guide for effective care of critically ill patients.
RESUMEN
Multiple sclerosis (MS) is an autoimmune-mediated chronic inflammatory demyelinating disease of the central nervous system (CNS) that poses significant treatment challenges. Currently, it is believed that inflammatory and neuroprotective reactive astrocytes, along with other resident CNS cells and immune cells, contribute to the pathophysiology of MS. In our study, we found that isoliquiritigenin (ILG), a bioactive chalcone compound, significantly reduces the clinical scores of experimental autoimmune encephalomyelitis (EAE) by 44â¯% (P < 0.05). Additionally, ILG significantly decreases the pathological scores of spinal cord inflammation and demyelination by 61â¯% and 65â¯%, respectively (both P < 0.0001). Furthermore, ILG affects the populations of CD4, Th1, Th17, and Treg cells in vivo. More importantly, ILG significantly promotes the activation of astrocytes in EAE (P < 0.0001). Additionally, ILG treatment indirectly inhibits inflammatory reactive astrocytes and promotes neuroprotective reactive astrocytes. It reduces spleen levels of TNFα, IL1α, C1qa, IL1ß, and IL17A by 95â¯% (P < 0.001), 98â¯% (P < 0.01), 46â¯% (P < 0.05), 97â¯% (P < 0.001), and 60â¯% (P < 0.001), respectively. It also decreases CNS levels of TNFα, IL1α, C1qa, IL1ß, and IL17A by 53â¯% (P < 0.05), 88â¯% (P < 0.05), 64â¯% (P < 0.01), 57â¯% (P < 0.05), and 60â¯% (P < 0.001), respectively. These results indicate that ILG exerts an immunoregulatory effect by inhibiting the secretion of pro-inflammatory cytokines. Consequently, ILG inhibits inflammatory reactive astrocytes, promotes neuroprotective reactive astrocytes, alleviates inflammation and improves EAE. These findings provide a theoretical basis and support for the application of ILG in the prevention and treatment of MS.
RESUMEN
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.
RESUMEN
BACKGROUND: In the context of aortic dissection, increasing pressure within the newly formed false lumen can result in the progressive compression of the true aortic channel. However, true lumen collapse in chronic type B aortic dissection (cTBAD) patients is rare, with few clinical or experimental studies to date having explored the causes of such collapse. CASE SUMMARY: In the present report, we describe a rare case of true-lumen collapse in an 83-year-old patient diagnosed with cTBAD, and we discuss potential therapeutic interventions for such cases. Following thoracic endovascular aortic repair (TEVAR), computed tomography angiography revealed satisfactory stent-graft positioning, no endoleakage, true lumen enlargement, thrombus formation in the false lumen, and slight enlargement of the true lumen distal to the stent-graft. Computational hemodynamic analyses indicated that the wall shear stress and pressure within the false lumen were significantly reduced following TEVAR. CONCLUSION: TEVAR treatment of cTBAD patients suffering from proximal true lumen collapse can facilitate some degree of effective remodeling.
RESUMEN
OBJECTIVE: To investigate the protective effect and underlying mechanism(s) of icariin (ICA) in preventing hydrogen peroxide (H2O2)-induced vascular endothelial cell injury via endoplasmic reticulum stress (ERS). METHODS: To study the effects of ICA on H2O2-induced damage, we used the cell counting kit-8 assay to detect cell viability and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay to determine cell adhesion and apoptosis, respectively. Spectrophotometry and enzyme-linked immunosorbent assay were used to measure the expression levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Subsequently, glucose-regulated protein 78 (GRP78), activating transcription factor-4 (ATF4) and eukaryotic initiation factor-2α (eIF2α) were detected using Western blotting. RESULTS: In human umbilical vein endothelial cells, different concentrations of ICA exhibited multiple effects, including reduced H2O2 damage, improved cell viability and adhesion, reduced cell apoptosis and increased SOD and GSH-Px activity. Among the ICA concentrations used, only the H2O2â¯+â¯100⯵mol/L ICA group had significant differences compared to the H2O2 group. ERS activators H2O2 and dl-dithiothreitol (DTT) significantly increased GRP78, ATF4 and eIF2α expressions, decreased cell activity and reduced SOD and GSH-Px activity. In contrast, the H2O2â¯+â¯100⯵mol/L ICA and H2O2â¯+â¯100⯵mol/L ICAâ¯+â¯DTT groups had significant inhibitory effects on the expressions of GRP78, ATF4 and eIF2α proteins, showing enhanced cell viability and SOD and GSH-Px activity. CONCLUSION: The results showed the dose-dependent effects of ICA against H2O2-induced injury in vascular endothelial cells. The inhibition of GRP78, ATF4 and eIF2α protein expressions in the ERS, and the subsequent alleviation of oxidative stress damage, might be the molecular mechanism.
Asunto(s)
Estrés del Retículo Endoplásmico/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Flavonoides/farmacología , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Apoptosis/efectos de los fármacos , Chaperón BiP del Retículo Endoplásmico , Células Endoteliales/citología , Células Endoteliales/metabolismo , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Peróxido de Hidrógeno/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismoRESUMEN
Atmospheric nitrogen (N) deposition, including dry and wet deposition, is an important inorganic and organic N source for ecosystems, and also a key link of the N biogeochemical cycle. Recently, considerable active nitrogen has been emitted into the atmosphere due to enhanced human activities. High N emission leads to high deposition which has caused a series of environment risks, and more attentions have been focused on this issue. This article gave an overview of the basic content about the present N deposition research, such as the component, process, spatial and temporal variation, as well as ecological effect. Then the sampling methods of wet and dry deposition in the field, analysis methods in laboratory and primary techniques of N source identification were summarized. The N deposition research trend in the future was emphasized.