RESUMEN
BACKGROUND: Researches have used intra-compartmental infusion and ballon tourniquest to create high intra-compartmental pressure in animal models of Acute Compartment Syndrome (ACS). However, due to the large differences in the modeling methods and the evaluation criteria of ACS, further researches of its pathophysiology and pathogenesis are hindered. Currently, there is no ideal animal model for ACS and this study aimed to establish a reproducible, clinically relevant animal model. METHODS: Blunt trauma and fracture were caused by the free falling of weights (0.5 kg, 1 kg, 2 kg) from a height of 40 cm onto the lower legs of rats, and the application of pressures of 100 mmHg, 200 mmHg, 300 mmHg and 400 mmHg to the lower limbs of rats using a modified pressurizing device for 6 h. The intra-compartmental pressure (ICP) and the pressure change (ΔP) of rats with single and combined injury were continuously recorded, and the pathophysiology of the rats was assessed based on serum biochemistry, histological and hemodynamic changes. RESULTS: The ΔP caused by single injury method of different weights falling onto the lower leg did not meet the diagnosis criteria for ACS (< 30 mmHg). On the other hand, a combined injury method of a falling weight of 1.0 kg and the use of a pressurizing device with pressure of 300 mmHg or 400 mmHg for 6 h resulted in the desired ACS diagnosis criteria with a ΔP value of less than 30 mmHg. The serum analytes, histological damage score, and fibrosis level of the combined injury group were significantly increased compared with control group, while the blood flow was significantly decreased compared with control group. CONCLUSION: We successfully established a new preclinical ACS-like rat model, by the compression of the lower leg of rats with 300 mmHg pressure for 6 h and blunt trauma by 1.0 kg weight falling.
Asunto(s)
Síndromes Compartimentales , Fracturas Óseas , Heridas no Penetrantes , Ratas , Animales , Síndromes Compartimentales/diagnóstico , Extremidad Inferior/lesiones , Presión , Fracturas Óseas/complicaciones , Heridas no Penetrantes/complicacionesRESUMEN
Cerebral ischemic stroke (CIS) is the main cause of disability. METTL3 is implicated in CIS, and we explored its specific mechanism. Middle cerebral artery occlusion (MCAO) rat model and oxygen-glucose deprivation/reperfusion (OGD/R) HAPI cell model were established and treated with LV-METTL3 or DAA, oe-METTL3, miR-335-3p mimics, or DAA, to assess their effects on MCAO rat neurological and motor function, cerebral infarction area, brain water content, microglial activation, blood-brain barrier (BBB) permeability, and NLRP3 inflammasome activation. METTL3, pri-miR-335-3p, mature miR-335-3p, and miR-335-3p mRNA levels were assessed by RT-qPCR; M1/M2 microglial phenotype proportion and M1/M2 microglia ratio, inflammatory factor levels, and m6A modification were assessed. MCAO rats manifested cerebral ischemia injury. METTL3 was under-expressed in CIS. METTL3 overexpression inhibited microglial activation and M1 polarization and BBB permeability in MCAO rats and inhibited OGD/R-induced microglial activation and reduced M1 polarization. METTL3 regulated miR-335-3p expression and inhibited NLRP3 inflammasome activation. m6A methylation inhibition averted METTL3's effects on NLRP3 activation, thus promoting microglial activation in OGD/R-induced cells and METTL3's effects on BBB permeability in MCAO rats. Briefly, METTL3 regulated miR-335-3p expression through RNA m6A methylation and inhibited NLRP3 inflammasome activation, thus repressing microglial activation, BBB permeability, and protecting against CIS.
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Adenina , Lesiones Encefálicas , Accidente Cerebrovascular Isquémico , MicroARNs , Accidente Cerebrovascular , Animales , Ratas , Adenina/análogos & derivados , Antivirales , Barrera Hematoencefálica , Infarto Cerebral , Glucosa , Inflamasomas , Microglía , MicroARNs/genética , Proteína con Dominio Pirina 3 de la Familia NLR , Metilación de ARNRESUMEN
Regulatory cell death is an important way to eliminate the DNA damage that accompanies the rapid proliferation of neural stem cells during cortical development, including pyroptosis, apoptosis, and so on. Here, the study reports that the absence of GSDMD-mediated pyroptosis results in defective DNA damage sensor pathways accompanied by aberrant neurogenesis and autism-like behaviors in adult mice. Furthermore, GSDMD is involved in organizing the mitochondrial electron transport chain by regulating the AMPK/PGC-1α pathway to target Aifm3. This process promotes a switch from oxidative phosphorylation to glycolysis. The perturbation of metabolic homeostasis in neural progenitor cells increases lactate production which acts as a signaling molecule to regulate the p38MAPK pathway. And activates NF-ð¿B transcription to disrupt cortex development. This abnormal proliferation of neural progenitor cells can be rescued by inhibiting glycolysis and lactate production. Taken together, the study proposes a metabolic axis regulated by GSDMD that links pyroptosis with metabolic reprogramming. It provides a flexible perspective for the treatment of neurological disorders caused by genotoxic stress and neurodevelopmental disorders such as autism.
RESUMEN
Acute compartment syndrome (ACS) is a syndrome in which local circulation is affected due to increased pressure within the compartment. We previously found in patients with calf fractures, the pressure of fascial compartment could be sharply reduced upon the appearance of tension blisters. Deep fascia, as the important structure for compartment, might play key role in this process. Therefore, the aim of the present study was to examine the differences in gene profile in deep fascia tissue in fracture patients of the calf with or without tension blisters, and to explore the role of fascia in pressure improvement in ACS. Patients with lower leg fracture were enrolled and divided into control group (CON group, n = 10) without tension blister, and tension blister group (TB group, n = 10). Deep fascia tissues were collected and LC-MS/MS label-free quantitative proteomics were performed. Genes involved in fascia structure and fibroblast function were further validated by Western blot. The differentially expressed proteins were found to be mainly enriched in pathways related to protein synthesis and processing, stress fiber assembly, cell-substrate adhesion, leukocyte mediated cytotoxicity, and cellular response to stress. Compared with the CON group, the expression of Peroxidasin homolog (PXDN), which promotes the function of fibroblasts, and Leukocyte differentiation antigen 74 (CD74), which enhances the proliferation of fibroblasts, were significantly upregulated (p all <0.05), while the expression of Matrix metalloproteinase-9 (MMP9), which is involved in collagen hydrolysis, and Neutrophil elastase (ELANE), which is involved in elastin hydrolysis, were significantly reduced in the TB group (p all <0.05), indicating fascia tissue underwent microenvironment reconstruction during ACS. In summary, the ACS accompanied by blisters is associated with the enhanced function and proliferation of fibroblasts and reduced hydrolysis of collagen and elastin. The adaptive alterations in the stiffness and elasticity of the deep fascia might be crucial for pressure release of ACS.
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Síndromes Compartimentales , Fascia , Proteómica , Humanos , Proteómica/métodos , Síndromes Compartimentales/metabolismo , Masculino , Fascia/metabolismo , Fascia/patología , Persona de Mediana Edad , Adulto , Femenino , Enfermedad Aguda , AncianoRESUMEN
Research have shown that sleep is associated with renal function. However, the potential effects of sleep duration or quality on kidney function in middle-aged and older Chinese adults with normal kidney function has rarely been studied. Our study aimed to investigate the association of sleep and kidney function in middle-aged and older Chinese adults. Four thousand and eighty six participants with an eGFR ≥60 ml/min/1.73 m2 at baseline were enrolled between 2011 and 2015 from the China Health and Retirement Longitudinal Study. Survey questionnaire data were collected from conducted interviews in the 2011. The eGFR was estimated from serum creatinine and/or cystatin C using the Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI). The primary outcome was defined as rapid kidney function decline. Secondary outcome was defined as rapid kidney function decline with clinical eGFR of <60 ml/min/1.73 m2 at the exit visit. The associations between sleep duration, sleep quality and renal function decline or chronic kidney disease (CKD) were assessed based with logistic regression model. Our results showed that 244 (6.0%) participants developed rapid decline in kidney function, while 102 (2.5%) developed CKD. In addition, participants who had 3-7 days of poor sleep quality per week had higher risks of CKD development (OR 1.86, 95% CI 1.24-2.80). However, compared with those who had 6-8 h of night-time sleep, no significantly higher risks of rapid decline in kidney function was found among those who had <6 h or >8 h of night time sleep after adjustments for demographic, clinical, or psychosocial covariates. Furthermore, daytime nap did not present significant risk in both rapid eGFR decline or CKD development. In conclusion, sleep quality was significantly associated with the development of CKD in middle-aged and older Chinese adults with normal kidney function.
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Insuficiencia Renal Crónica , Duración del Sueño , Calidad del Sueño , Anciano , Humanos , Persona de Mediana Edad , Tasa de Filtración Glomerular , Riñón/fisiopatología , Estudios Longitudinales , Insuficiencia Renal Crónica/epidemiologíaRESUMEN
OBJECTIVE: The objective of the present paper was to investigate the value of obturator oblique and pubic ramus inlet views in guiding anterior column acetabular screw insertion. METHODS: We collected pelvic CT scans at the diagnostic imaging center of our hospital between 2017 and 2019. Virtual three-dimensional (3D) models of the pelvis were created based on the CT scans. Then the transparency was adjusted to 30%. Two identical copies of the 3D model data were made. 3D model replications were divided into a control group and an experimental group. In the control group, the screw was inserted into the anterior acetabular column using obturator-outlet and iliac-inlet views. In the experimental group, the screw was guided under obturator oblique and pubic ramus inlet views. Based on whether the screw penetrated the hip joint and/or exited the pubic ramus, models were divided into three grades. Grade I: the screw travels completely within the anterior column bone corridor; Grade II: the screw exits the superior pubic ramus, but the length of the screw outside the channel does not exceed 1/2 of the anterior column; Grade III: the screw exits the superior pubic ramus and the length of the screw outside the corridor exceeds 1/2 of the anterior column. We compared the screw placement quality of the two groups and analyzed differences between genders. In addition, the distance between the screws and the acetabulum was recorded and compared among the two groups. RESULTS: A total of 110 hemipelves were selected, including those of 80 men and 30 women, with an average age of 46.76 ± 14.26 years. In the control group, the screw quality of 64 models (58.2%) was Grade I. In the experimental group, 94 models (85.5%) had Grade I screw placement quality. Grade II screw placement quality accounted for 18.2% of the control group and 7.3% of the experimental group. In the control and the experimental groups, there were 26 and 8 cases with Grade III screw placement quality, respectively. The quality of screw placement in the experimental group was significantly better than that in control group, and the difference between the two groups was statistically significant (P < 0.01). The distance between the screw and the acetabulum in the control group and experimental group was 0.92 ± 0.49 mm and 2.78 ± 1.15 mm, respectively. The difference between the two groups was statistically significant. CONCLUSION: Anterior column acetabular screws can be inserted successfully and more accurately using the obturator oblique and pubic ramus inlet views.