Neuroprotective effect of histone deacetylase 3 specific inhibitor RGFP966 on traumatic brain injury by inhibiting pyroptosis / 中华神经医学杂志

Objective:To investigate the neuroprotective effect of histone deacetylase 3 (HDAC3) specific inhibitor RGFP966 on traumatic brain injury (TBI) and its mechanism in rats.Methods:Forty-eight SD rats were randomly divided into sham-operated group, TBI group, TBI+vehicle group and TBI+RGFP966 group ( n=12). Rats in the later 3 groups accepted hydraulic impact brain injury to establish TBI models; and then, RGFP966 (dissolved in 1% DMSO at a dose of 10 mg/kg) was injected intraperitoneally 30 min after modeling, twice a day for 3 d, in TBI+RGFP966 group; same amount of DMSO was injected into TBI+vehicle group at the same time. Three d after modeling, neurological function was tested by modified neurological severity score (mNSS), water content of brain tissues was detected by dry-wet weight method, proportion of injured neurons at the frontal cortical tissues on the affected side was detected by Nissl staining, expressions of HDAC3 and pyroptosis related proteins were detected by immunohistochemical staining and Western blotting, and serum content of inflammatory factors was detected by ELISA. Results:Three d after modeling, compared with the TBI+vehicle group, the TBI+RGFP966 group had significantly decreased mNSS scores (9.83±0.75 vs. 6.67±0.82), water content of the injured cerebral cortex (82.73%±0.36% vs. 80.92%±0.66%), proportion of damaged neurons (75.60%±7.44% vs. 55.87%±4.10%), and HDAC3 protein expression (0.67±0.09 vs. 0.51±0.07), and significantly increased acetylated H3 (Ace-H3) and acetylated H4 (Ace-H4) protein expressions (0.81±0.02 vs. 1.22±0.02; 0.74±0.01 vs. 1.07±0.02), and statistically decreased protein expressions of nuclear factor-κB (NF-κB, 1.20±0.05 vs. 0.94±0.04), NOD-like receptor thermal protein domain associated protein 3 (NLRP3, 0.72±0.02 vs. 0.40±0.03), Caspase-1 containing cysteine (Caspase-1), dermatin D N-terminal fragment (GSDMD-N, 0.71±0.03 vs. 0.52±0.01), significantly decreased NF-κB and NLRP3 immunohistochemical staining scores, and significantly decreased serum contents of tumor necrosis factor-α, interleukin(IL)-1β and IL-18 ( P<0.05). Conclusion:Early intervention with RGFP966 after TBI can reduce the pyroptosis and inflammatory reaction of nerve cells and play neuroprotective role, whose mechanism may be related to inhibited activation of NF-κB/NLRP3/GSDMD pathway.

Risk factors for intracranial hematoma progression in patients with traumatic brain injury at early stage / 中华神经医学杂志

Objective:To investigate the risk factors for intracranial hematoma progression in patients within 24 h of traumatic brain injury.Methods:A prospective study was performed; 184 patients with traumatic brain injury admitted to our hospital from January 2018 to June 2021 were enrolled. According to the states of intracranial hematoma indicated by head CT within 24 h of injury, these patients were divided into intracranial hematoma progression group ( n=52) and intracranial hematoma stable group ( n=132). The clinical data of patients in the two groups were compared and the independent risk factors for intracranial hematoma progression were screened by multivariate Logistic regression analysis. Results:As compared with intracranial hematoma stable group, patients in the intracranial hematoma progression group had significantly advanced age, significantly higher systolic blood pressure and blood glucose levels, statistically higher proportions of patients with parenchymal hemorrhage, subarachnoid hemorrhage, and multiple hematomas, significantly longer prothrombin time, significantly higher international standardization index and D-dimer level, significantly higher proportion with patients with fibrinogen<2.0 g/L, statistically increased K value (blood coagulation time) of thromboelastic map, proportion of patients with α Angle (blood coagulation angle)<64°, level of vascular endothelial biomarker syndecan-1 (Syn-1), and von willebrand factor (vWF) activity, and significantly decreased Glasgow Coma Scale (GCS) scores at admission and platelet count ( P<0.05). Multivariate Logistic regression analysis showed that age ( OR=1.066, 95%CI: 1.018-1.117, P=0.007), systolic blood pressure ( OR=1.076, 95%CI: 1.041-1.111, P<0.001), multiple hematoma ( OR=6.559, 95%CI: 2.025-21.245, P=0.002), fibrinogen<2.0 g/L ( OR=6.164, 95%CI: 1.586-23.954, P=0.009), K value ( OR=6.500, 95%CI: 1.755-24.082, P=0.005) and Syn-1 level ( OR=1.111, 95%CI: 1.015-1.215, P=0.022) were independent risk factors for intracranial hematoma progression in patients with traumatic brain injury at early stage. Conclusion:Traumatic brain injury patients, at early stage, with advanced age, multiple intracranial hematoma, high systolic blood pressure, low fibrinogen, prolonged K value and high Syn-1 level are trend to have intracranial hematoma progression.

Effect of bundle comprehensive brain protection treatments on cerebral oxygen metabolism,endothelin and intracranial pressure of patients with severe craniocerebral trauma / 中华神经医学杂志

Objective To explore how the bundle comprehensive brain protection treatments affects cerebral oxygen metabolism,endothelial cell function and intracranial pressure of patients with severe craniocerebral trauma.Methods One hundred and twenty patients with severe craniocerebral trauma were selected from January 2014 to November 2016 in our hospital.The patients were randomly divided into control group and observation group (n=60).Patients from the control group were given normal treatment;whilst patients from the observation group were additionally treated with bundle comprehensive brain protection treatments.The cerebral oxygen metabolism levels (jugular bulb venous oxygen saturation [SjVO2],cerebral extraction of oxygen [CEO2] and arteriovenous oxygen difference [AVDO2]),endothelin (ET) level and intracranial pressure (ICP) were calculated and compared before and after treatment.Results The levels of SjVO2,CEO2 and AVDO2,and ET and ICP levels showed no significant differences between the obvseration group and control group before treatment (P＞0.05).After treatment,the levels of SjVO2,CEO2 and AVDO2 in the observation group were significantly higher than those in the control group (P＜0.05);as compared with those in the control group,the ET and ICP levels in the observation group were significantly decreased (P＜0.05).Conclusion The bundle comprehensive brain protection treatments could improve cerebral oxygen metabolism and endothelial function,and decrease the ET and ICP levels of patients with severe craniocerebral trauma,which has important value in clinical practice.

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 [p0.05]. 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

Perioperative nutritional risk screening and postoperative complications of colorectal cancer patients / 中华临床营养杂志

Objective To evaluate the perioperative nutritional risk of patients with colorectal cancer. Methods Totally, the nutritional risk of 144 colorectal cancer patients who were newly admitted to our hospital and were radiotherapy-naive or chemotherapy-naive were evaluated using Nutritonal Risk Screening 2002 (NRS2002 ) before operation and two weeks after operation. Meanwhile, hemoglobin, serum levels of albumin and prealbumin, total lymphocyte count were measured and the postoperative complications were observed. Results The incidence of preoperative nutritional risk was 22. 91% (33/144). The predicted incidence of postoperative nutritional risk was 43. 06% (62/144), while the actual incidence was 54. 86% (79/144) (x2 =4. 016, P < 0.05). About 10. 13% of patients whose preoperative nutritional risk score≥3 experienced complications, while only 1. 54% of patients whose preoperative nutritional risk score < 3 had complications (x2 = 3. 065, P < 0.05). Conclusions The perioperative (especially postoperative) nutrition risk is high in patients with colorectal cancer. Patients with higher nutrition risk tend to experience postoperative complications.