Histone deacetylase 3-specific inhibitor RGFP966 attenuates oxidative stress and inflammation after traumatic brain injury by activating the Nrf2 pathway.

Background: Oxidative stress (OS) and inflammatory reactions play pivotal roles in secondary brain injury after traumatic brain injury (TBI). Histone deacetylase 3 (HDAC3) controls the acetylation of histones and non-histones, which has a significant impact on the central nervous system's reaction to damage. This research determined the implications of RGFP966, a new and specific inhibitor of HDAC3, for the antioxidant (AO) systems mediated by nuclear factor erythroid2-related factor 2 (Nrf2) and the Nod-like receptor protein 3 (NLRP3) inflammasome in TBI. The study also studied the underlying mechanisms of RGFP966's actions. Our objective was to examine the impacts and underlying RGFP966 mechanisms in TBI. Methods: In vitro, a rat cortical neuron OS model was induced by H2O2, followed by the addition of RGFP966 to the culture medium. Neurons were collected after 24 h for western blot (WB), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and 2'-7'-dichlorodihydrofluorescein diacetate staining. In vivo, RGFP966 (10 mg/kg) was administered post-TBI. Brain tissue water content and modified neurological severity scores were assessed 72 h post-injury. Cortical tissues surrounding the focal injury were subjected to western blot, TUNEL staining, Nissl staining and immunofluorescence/immunohistochemistry staining, and malondialdehyde level, hindered glutathione content and superoxide dismutase activity were measured. Serum was collected for the enzyme-linked immunosorbent assay. Nrf2-specific shRNA lentivirus was injected into the lateral ventricle of rats for 7 days, and cerebral cortex tissue was analyzed by WB and real-time polymerase chain reaction. Results: During in vitro and in vivo experiments, RGFP966 suppressed HDAC3 expression, promoted Nrf2 nuclear translocation, activated downstream AO enzymes, mitigated excessive reactive oxygen species production and alleviated nerve cell apoptosis. RGFP966 effectively reduced brain edema and histological damage and enhanced neurological and cognitive function in rats with TBI. RGFP966 markedly inhibited NLRP3 inflammasome activation mediated by high-mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4). Nrf2 knockdown in TBI rats attenuated the AO and anti-inflammatory, neuroprotective impacts of RGFP966. Conclusions: Overall, our findings demonstrate that RGFP966 can mitigate the first brain damage and neurological impairments in TBI. The underlying mechanism involves triggering the Nrf2-mediated AO system and negatively regulating the HMGB1/TLR4-mediated NLRP3 inflammasome pathway.

Comparative analysis of CRASH and IMPACT in predicting the outcome of 340 patients with traumatic brain injury.

Background: Both the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) and the Corticosteroid randomization after significant head injury (CRASH) models are globally acknowledged prognostic algorithms for assessing traumatic brain injury (TBI) outcomes. The aim of this study is to externalize the validation process and juxtapose the prognostic accuracy of the CRASH and IMPACT models in moderate-to-severe TBI patients in the Chinese population. Methods: We conducted a retrospective study encompassing a cohort of 340 adult TBI patients (aged > 18 years), presenting with Glasgow Coma Scale (GCS) scores ranging from 3 to 12. The data were accrued over 2 years (2020-2022). The primary endpoints were 14-day mortality rates and 6-month Glasgow Outcome Scale (GOS) scores. Analytical metrics, including the area under the receiver operating characteristic curve for discrimination and the Brier score for predictive precision were employed to quantitatively evaluate the model performance. Results: Mortality rates at the 14-day and 6-month intervals, as well as the 6-month unfavorable GOS outcomes, were established to be 22.06, 40.29, and 65.59%, respectively. The IMPACT models had area under the curves (AUCs) of 0.873, 0.912, and 0.927 for the 6-month unfavorable GOS outcomes, with respective Brier scores of 0.14, 0.12, and 0.11. On the other hand, the AUCs associated with the six-month mortality were 0.883, 0.909, and 0.912, and the corresponding Brier scores were 0.15, 0.14, and 0.13, respectively. The CRASH models exhibited AUCs of 0.862 and 0.878 for the 6-month adverse outcomes, with uniform Brier scores of 0.18. The 14-day mortality rates had AUCs of 0.867 and 0.87, and corresponding Brier scores of 0.21 and 0.22, respectively. Conclusion: Both the CRASH and IMPACT algorithms offer reliable prognostic estimations for patients suffering from craniocerebral injuries. However, compared to the CRASH model, the IMPACT model has superior predictive accuracy, albeit at the cost of increased computational intricacy.

An analysis of differences in Carbapenem-resistant Enterobacterales in different regions: a multicenter cross-sectional study.

OBJECTIVE: This study aimed to explore the characteristics of carbapenem-resistant Enterobacterales (CRE) patients in the intensive care unit (ICU) in different regions of Henan Province to provide evidence for the targeted prevention and treatment of CRE. METHODS: This was a cross-sectional study. CRE screening was conducted in the ICUs of 78 hospitals in Henan Province, China, on March 10, 2021. The patients were divided into provincial capital hospitals and nonprovincial capital hospitals for comparative analysis. RESULTS: This study involved 1009 patients in total, of whom 241 were CRE-positive patients, 92 were in the provincial capital hospital and 149 were in the nonprovincial capital hospital. Provincial capital hospitals had a higher rate of CRE positivity, and there was a significant difference in the rate of CRE positivity between the two groups. The body temperature; immunosuppressed state; transfer from the ICU to other hospitals; and use of enemas, arterial catheters, carbapenems, or tigecycline at the provincial capital hospital were greater than those at the nonprovincial capital hospital (P < 0.05). However, there was no significant difference in the distribution of carbapenemase strains or enzymes between the two groups. CONCLUSIONS: The detection rate of CRE was significantly greater in provincial capital hospitals than in nonprovincial capital hospitals. The source of the patients, invasive procedures, and use of advanced antibiotics may account for the differences. Carbapenem-resistant Klebsiella pneumoniae (CR-KPN) was the most prevalent strain. Klebsiella pneumoniae carbapenemase (KPC) was the predominant carbapenemase enzyme. The distributions of carbapenemase strains and enzymes were similar in different regions.

Application of electromagnetic disturbance technology in predicting ventriculoperitoneal shunt dependency after aneurysm-associated subarachnoid hemorrhage.

BACKGROUND: The aim of this study was to evaluate the predictive power of electromagnetic disturbance technology in patients with hydrocephalus after subarachnoid hemorrhage. METHODS: This prospective, observational cohort study was conducted at The First Affiliated Hospital of Zhengzhou University and Nanfang Hospital. A total of 155 patients with subarachnoid hemorrhage (SAH) were enrolled in this study. Disturbance coefficients were recorded using a continuous sinusoidal signal in real time after SAH. The patients were divided into two groups: hydrocephalus group (patients who underwent shunt insertion within a month after SAH) and non-hydrocephalus group (patients without need for a ventriculoperitoneal shunt). We used SPSS to draw a ROC Curve to assess the ability of disturbance coefficients to predict the probability of hydrocephalus. RESULTS: Hydrocephalus occurred in 37 patients after SAH. The average disturbance coefficient of patients with hydrocephalus decreased by 25.14±9.78, and the disturbance coefficient of patients with no hydrocephalus decreased by 6.58±10.10 (one aspect of the present invention is a system of non-invasively monitoring hydrocephalus, cerebral edema, and intracranial bleeding comprising of a source emitting electromagnetic waves to brain tissue, a detector detecting said wave that propagates through said tissue, a signal conditioning unit amplifying and filtering said wave, a quadrature detector estimating magnitude and phases of said wave, and a parameter estimator calculating the complex wave number, relative attenuation coefficient (RAC), relative phase shift (RPS), wave speed change (WSC), and travel-time difference (TTD) of said brain, and assessing status of hydrocephalus and cerebral edema). The difference was statistically significant (t=9.825, P<0.001). The decrease in disturbance coefficient can be used to predict the occurrence of hydrocephalus, and if the disturbance coefficient decreases by more than 15.5 (sensitivity, 92.37%; specificity, 86.49%), it can be used to indicate the occurrence of hydrocephalus. CONCLUSIONS: The disturbance coefficient can predict the occurrence of hydrocephalus. The greater decline of the disturbance coefficient, the greater probability of occurrence of intracranial hydrocephalus. Hydrocephalus can be early detected. However, the CT scan is necessary to confirm the occurrence of hydrocephalus. Early diagnosis and early treatment may improve the prognosis of patients with hydrocephalus after subarachnoid hemorrhage.

Preparation and study of the flame retardant properties of C60/PMMA microspheres.

In this paper, highly flame retardant C60/PMMA composites were prepared using an in situ polymerization method by introducing fullerene (C60) into polymethyl methacrylate (PMMA) to improve its combustion characteristics. The apparent morphologies of PMMA and C60/PMMA microspheres were observed by scanning electron microscopy (SEM), and the structure was characterized by infrared spectroscopy (FT-IR). The thermal stability and flame retardancy were characterized using a synchronous thermal analyzer, a cone calorimeter and an oxygen index tester. The results show that the maximum initial decomposition temperature of C60/PMMA-2 (prepared using C60 with a concentration of 2 mg mL-1) is 234.89 °C, which is about 59.89 °C higher than that of PMMA, and the thermal stability is the best. The limiting oxygen index of the C60/PMMA-2 composite is 21.8, which is 28.2% higher than that of pure PMMA. In addition, the peak heat release rate (PHRR) of C60/PMMA is reduced by 630.4 kW m-2 when compared with pure PMMA, which means that the flame retardant property is improved. Meanwhile, the mechanical properties of the PMMA are also improved by adding C60.

Development and Verification of Prognostic Prediction Models for Patients with Brain Trauma Based on Coagulation Function Indexes.

Objective: To assess the effect of adding coagulation indices to the currently existing prognostic prediction models of traumatic brain injury (TBI) in the prediction of outcome. Methods: A total of 210 TBI patients from 2017 to 2019 and 131 TBI patients in 2020 were selected for development and internal verification of the new model. The primary outcomes include death at 14 days and Glasgow Outcome Score (GOS) at 6 months. The performance of each model is evaluated by means of discrimination (area under the curve (AUC)), calibration (Hosmer-Lemeshow (H-L) goodness-of-fit test), and precision (Brier score). Results: The IMPACT Core model showed better prediction ability than the CRASH Basic model. Adding one coagulation index at a time to the IMPACT Core model, the new combined models IMPACT Core+FIB and IMPACT Core+APTT are optimal for the 6-month unfavorable outcome and 6-month mortality, respectively (AUC, 0.830 and 0.878). The new models were built based on the regression coefficients of the models. Internal verification indicated that for the prediction of 6-month unfavorable outcome and 6-month mortality, both the IMPACT Core+FIB model and the IMPACT Core+APTT model show better discrimination (AUC, 0.823 vs. 0.818 and 0.853 vs. 0.837), better calibration (HL, p = 0.114 and p = 0.317) and higher precision (Brier score, 0.148 vs. 0.141 and 0.147 vs. 0.164), respectively, than the original models. Conclusion: Our research shows that the combination of the traumatic brain injury prognostic models and coagulation indices can improve the 6-month outcome prediction of patients with TBI.

Preparation and Study on the Flame-Retardant Properties of CNTs/PMMA Microspheres.

In this paper, carbon nanotubes (CNTs)/poly(methyl methacrylate) (PMMA) composites with excellent thermal stability and flame retardancy were prepared by in situ polymerization. The morphology, structure, transmittance, thermal stability, flame retardancy, and mechanical properties of the materials were characterized with scanning electron microscopy (SEM), thermogravimetric analysis (TGA), cone calorimetry, etc. According to the results, the initial decomposition temperature of CNTs/PMMA prepared using carbon nanotubes with a concentration of 2 mg/mL increases from 175 to 187 °C when compared with pure PMMA, and the weight loss ratio decreases significantly at the same time. In addition, the maximum limiting oxygen index (LOI) value of CNTs/PMMA composites is 22.17, which is 26.9% higher than that of PMMA. SEM images of residues after LOI tests demonstrate that when CNTs/PMMA is heated, a dense and stable interconnected network structure (i.e., carbon layer) is formed, which can effectively inhibit the combustion of pyrolysis products, prevent the transfer of heat and combustible gas, and finally interrupt the combustion of composite materials. However, a 25% decrease in the transmittance of CNTs/PMMA composites is observed in the Ultraviolet-visible (UV-vis) spectra. Although the addition of CNTs reduces the transparency of PMMA, its tensile and impact strength are all improved, which illustrates that CNT is a competitive flame retardant for PMMA.

Clinical research on postoperative efficacy and related factors of early simulation hyperbaric oxygen therapy for severe craniocerebral injury.

In order to discuss the clinical efficacy of simulation hyperbaric oxygen therapy (HBOT) for severe craniocerebral injury and analyze the related factors of it, 108 patients who transferred to our department during December 2010 - December 2014 for ventilator treatment after operation of severe craniocerebral injury were taken as the subjects of the study. These patients were divided into conventional treatment group and simulation hyperbaric oxygen therapy group to contrast the curative effects. At the meantime, GOS score and length of stay in intensive care unit (ICU) of two groups 6 months after treatment, as well as changes in the indexes of the HBO group during treatment were performed statistical analysis. Then factors affecting prognosis of simulation HBOT were performed regression analysis and principal component analysis. The results showed that when compared to the control group, differences in cases with four GOS score and one GOS score in the treatment group were significant (p<0.05). Jugular venous oxygen saturation (SjvO2), jugular bulb oxygen partial pressure (PjO2), arterial partial pressure of oxygen (PaO2) and arterial oxygen saturation (SaO2) of the simulation HBO group before the first time treatment on the first day and after the first time treatment on the third day were significantly increased, with statistical significance (p<0.05); serum lactic acid (Lac) and blood glucose (Glu) decreased significantly (p<0.05). Prior to and during the first treatment on the first day, jugular bulb pressure (Pj) and central venous pressure (CVP) had no significant difference (p>0.05). Regression analysis indicated that factors affecting prognosis included cerebral contusion, coronary heart disease, hydrocephalus and tracheotomy. Principal component analysis found the factors were hydrocephalus, coronary heart disease, tracheotomy, cerebral contusion, cerebral infarction and glasgow coma scale (GCS) before treatment. Therefore, stimulation HBOT can significantly improve the prognosis of patients with severe craniocerebral injury. Paying attention to risk factors in clinics and giving timely interventional treatment can reduce morbidity and mortality in patients.