[The diagnostic value of neuron-specific enolase, central nervous system specific protein and interleukin-6 in sepsis-associated encephalopathy].

Objective: To investigate the diagnostic value of neuron-specific enolase(NSE), central nervous system specific protein(S100ß), interleukin-6(IL-6) in sepsis-associated encephalopathy(SAE). Methods: Clinical data of patients admitted to ICU and diagnosed with sepsis were collected from January 2015 to June 2016 in Xiangya Hospital, Central South University. SAE was defined as cerebral dysfunction in the presence of sepsis that also fulfilled the exclusion criteria. The acute physiology and chronic health score (APACHE Ⅱ), sequential organ failure assessment (SOFA), NSE, S100ß, IL-6, ICU stay time and 28-day mortality were compared between the two groups. NSE, S100ß and IL-6 were measured on the 1st and 3rd day in ICU to determine the optimal cut-off value of SAE. Results: Among 59 enrolled patients, 36 were assigned to SAE group while 23 were non-SAE group. The SAE group had a significantly higher APACHE Ⅱ and SOFA scores, as well as the length of ICU stay (P<0.01). The levels of NSE, S100ß and IL-6 in the two groups both increased on the 1st day, and decreased on the 3rd day. The level of NSE on the 1st day[19.28(13.00, 30.52) µg/L vs 16.61(7.58, 22.01 µg/L)] and the 3rd day[16.03(9.40, 21.29) µg/L vs 11.39(8.49, 15.00) µg/L, P=0.029], IL-6 on the 1st day[676.25(81.34, 5 000.00) mg/L vs [209.10(42.27, 648.20) mg/L, P=0.005] and the 3rd day[157.10(72.85, 687.63) mg/L vs 55.92(31.62, 177.00) mg/L, P=0.026] of SAE group was significantly higher than those of non-SAE group. However S100ß between groups on the 1st day [0.33(0.15, 0.54) µg/L vs 0.23(0.16, 0.53) µg/L] and the 3rd day[0.19(0.10, 0.29) µg/L vs 0.10(0.05, 0.17) µg/L] was neither significant (P>0.05). The diagnostic values for SAE of NSE, S100ß and IL-6 were 14.36 µg/L, 0.14 µg/L and 91.305 mg/L with sensitivity 61.1%, 61.1%, 72.2% and specificity 73.9%, 69.6%, 69.6%, respectively. The diagnostic AUC of NSE and IL-6 combination was 0.774, 95%CI 0.651-0.896. Conclusion: All sepsis patients have different degrees of brain injury. NSE combined with IL-6 on the 3rd day in ICU demonstrates the diagnostic significance of SAE.

Effects of perioperative intracranial pressure monitoring-guided treatment on cerebrospinal fluid BDNF and S100B protein levels and prognosis in patients with severe traumatic brain injury / 中国基层医药

Objective:To investigate the effects of perioperative intracranial pressure monitoring-guided treatment on cerebrospinal fluid brain-derived neurotrophic factor (BDNF) and S100B protein levels, and prognosis in patients with severe traumatic brain injury.Methods:A total of 84 patients with severe traumatic brain injury who received treatment at Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from March 2015 to August 2020 were included in this case-control study. These patients were divided into a study group ( n = 48) and a control group ( n = 36) based on different treatment methods. The control group was treated with routine treatment, while the study group underwent perioperative intracranial pressure monitoring-guided treatment. Clinical efficacy, BDNF, S100B protein, and prognosis were compared between the two groups. Results:The total effective rate in the study group was 87.5% (42/48), which was significantly higher than 69.4% (25/36) in the control group ( χ2 = 4.15, P = 0.042). After treatment, the BDNF level [(0.181 ± 0.021) μg/L] in the study group was significantly higher, and S100B [(4.3 ± 1.8) μg/L] level in the study group was significantly lower, compared with the control group ( t = 3.09, -4.86, both P < 0.001). The poor prognosis rate in the study group was 47.9% (23/48), which was significantly lower than 69.4% (25/36) in the control group ( χ2 = 3.89, P = 0.048). According to patient prognosis, these patients were divided into a good prognosis group and a poor prognosis group. The intracranial pressure level of patients in the poor prognosis group was significantly higher than that in the good prognosis group ( t = 4.12, P < 0.001). The area under the curve of intracranial pressure level for evaluating prognosis in patients with severe traumatic brain injury was 0.880 (95% CI: 0.809-0.950, P < 0.001). Conclusion:Perioperative intracranial pressure monitoring-guided treatment can greatly improve the levels of cerebrospinal fluid BDNF and S100B in patients with severe traumatic brain injury and improve the prognosis.

Protective effect and mechanism of Angong Niuhuang pill in sepsis-associated brain dysfunction of rats / 中华危重病急救医学

Objective:To observe the protective effect of Angong Niuhuang pill on brain function of rats with sepsis, explore its protective mechanism, and provide the experimental basis for clinical application of Angong Niuhuang pill in the treatment of sepsis-associated encephalopathy (SAE).Methods:Thirty male Sprague-Dawley (SD) rats were divided into sham operation group, sepsis model group and Angong Niuhuang pill group according to random number table method, with 10 rats in each group. The sepsis model was established by cecal ligation and puncture (CLP); rats in sham operation group received open and closed abdomen. The rats in the Angong Niuhuang pill group were given Angong Niuhuang pill (0.3 g/kg) by gastric irrigation daily for 3 days before CLP, and the drugs were administrated 12 hours after modeling again. After 24 hours of CLP, the neuroreflex scores were evaluated, white blood cell count (WBC), the levels of serum neuron-specific enolase (NSE) and S100β were detected. Then the brain tissue was harvested. After hematoxylin-eosin (HE) staining, the pathological changes of brain tissue were observed under the light microscope. The mRNA expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in brain tissue were detected by polymerase chain reaction.Results:Compared with the sham operation group, the total score of neuroreflex scores in the sepsis model group and the Angong Niuhuang pill group were significantly reduced (4.43±1.40, 6.57±1.90 vs. 9.40±0.84, both P < 0.05), WBC, serum NSE, S100β were significantly increased [WBC (×10 9/L): 8.07±1.32, 5.84±0.94 vs. 3.60±0.32; NSE (μg/L): 1.04±0.14, 0.61±0.07 vs. 0.16±0.04; S100β (ng/L): 255.624±30.25, 97.72±15.41 vs. 46.88±12.03, all P < 0.05], and the mRNA expressions of IL-6 and TNF-α in brain tissue were significantly increased [IL-6 mRNA (2 -ΔΔCt): 5.668±2.195, 3.605±1.014 vs. 0.997±0.329; TNF-α mRNA (2 -ΔΔCt): 18.996±0.913, 1.746±0.710 vs. 0.674±0.132, all P < 0.05]. Compared with the sepsis model group, the total score of neuroreflex scores in the Angong Niuhuang pill group was significantly increased (6.57±1.90 vs. 4.43±1.40, P < 0.05), WBC, serum NSE, S100β concentration, and the mRNA expressions of IL-6 and TNF-α in the brain were significantly reduced [WBC (×10 9/L): 5.84±0.94 vs. 8.07±1.32, NSE (μg/L): 0.61±0.07 vs. 1.04±0.14, S100β (ng/L): 97.72±15.41 vs. 255.62±30.25, IL-6 mRNA (2 -ΔΔCt): 3.605±1.014 vs. 5.668±2.195, TNF-α mRNA (2 -ΔΔCt): 1.746±0.710 vs. 18.996±0.913, all P < 0.05]. Brain histopathological observation showed that the hippocampal neurons in the sepsis model group were disordered arrangement, a large number of neuronal nuclei were contracted, and the tissue was loose with obvious edema. Compared with the sepsis model group, the Angong Niuhuang pill group had less nuclear shrinkage and tissue edema. Conclusions:The pretreatment of the Angong Niuhuang pill can improve the brain dysfunction of septic rats and reduce the expression of pro-inflammatory cytokines in the brain. It is speculated that the Angong Niuhuang pill can protect the brain function in sepsis by inhibiting the inflammatory reaction in the brain.

Microwave & Magnetic (M2) Proteomics of a Mouse Model of Mild Traumatic Brain Injury.

Short-term increases in oxidative stress and decreases in motor function, including debilitating effects on balance and motor control, can occur following primary mild traumatic brain injuries (mTBI). However, the long-term effects on motor unit impairment and integrity as well as the molecular mechanisms underlying secondary injuries are poorly understood. We hypothesized that changes in central nervous system-specific protein (CSP) expression might correlate to these long-term effects. To test our hypothesis, we longitudinally assessed a closed-skull mTBI mouse model, vs. sham control, at 1, 7, 30, and 120 days post-injury. Motor impairment was determined by rotarod and grip strength performance measures, while motor unit integrity was determined using electromyography. Relative protein expression was determined by microwave & magnetic (M2) proteomics of ipsilateral brain tissue, as previously described. Isoprostane measurements were performed to confirm a primary oxidative stress response. Decoding the relative expression of 476 ± 56 top-ranked proteins for each specimen revealed statistically significant changes in the expression of two well-known CSPs at 1, 7 and 30 days post-injury: P < 0.001 for myelin basic protein (MBP) and P < 0.05 for myelin associated glycoprotein (MAG). This was confirmed by Western blot. Moreover, MAG, αII-spectrin (SPNA2) and neurofilament light (NEFL) expression at 30 days post-injury were directly related to grip strength (P < 0.05). While higher-powered studies of larger cohorts merit further investigation, this study supports the proof-of-concept that M2 proteomics is a rapid method to quantify putative protein biomarkers and therapeutic targets of mTBI and suggests the feasibility of CSP expression correlations to long-term effects on motor impairment.

The diagnostic value of neuron-specific enolase, central nervous system specific protein and interleukin-6 in sepsis-associated encephalopathy / 中华内科杂志

Objective To investigate the diagnostic value of neuron-specific enolase(NSE),central nervous system specific protein (S100β),interleukin-6 (IL-6) in sepsis-associated encephalopathy (SAE).Methods Clinical data of patients admitted to ICU and diagnosed with sepsis were collected from January 2015 to June 2016 in Xiangya Hospital,Central South University.SAE was defined as cerebral dysfunction in the presence of sepsis that also fulfilled the exclusion criteria.The acute physiology and chronic health score (APACHE Ⅱ),sequential organ failure assessment (SOFA),NSE,S100β,IL-6,ICU stay time and 28-day mortality were compared between the two groups.NSE,S1003 and IL-6 were measured on the 1 st and 3rd day in ICU to determine the optimal cut-off value of SAE.Results Among 59 enrolled patients,36 were assigned to SAE group while 23 were non-SAE group.The SAE group had a significantly higher APACHE Ⅱ and SOFA scores,as well as the length of ICU stay (P ＜ 0.01).The levels of NSE,S1003 and IL-6 in the two groups both increased on the 1st day,and decreased on the 3rd day.The level of NSE on the 1st day [19.28 (13.00,30.52) μg/L vs 16.61 (7.58,22.01 μg/L)] and the 3rd day[16.03 (9.40,21.29) μg/L vs 11.39(8.49,15.00) μg/L,P=0.029],IL-6 on the 1st day[676.25(81.34,5 000.00) mg/L vs [209.10(42.27,648.20) mg/L,P =0.005] and the 3rd day [157.10 (72.85,687.63) mg/L vs 55.92 (31.62,177.00) mg/L,P =0.026] of SAE group was significantly higher than those of non-SAE group.However S100β between groups on the 1st day [0.33(0.15,0.54) μg/L vs 0.23(0.16,0.53) μg/L] and the 3rd day[0.19(0.10,0.29) μg/L vs 0.10(0.05,0.17) μg/L] was neither significant (P ＞0.05).The diagnostic values for SAE of NSE,S1003 and IL-6 were 14.36 μg/L,0.14 μg/L and 91.305 mg/L with sensitivity 61.1％,61.1％,72.2％ and specificity 73.9％,69.6％,69.6％,respectively.The diagnostic AUC of NSE and IL-6 combination was 0.774,95％ CI 0.651-0.896.Conclusion All sepsis patients have different degrees of brain injury.NSE combined with IL-6 on the 3rd day in ICU demonstrates the diagnostic significance of SAE.

The diagnostic value of neuron-specific enolase, central nervous system specific protein and interleukin-6 in sepsis-associated encephalopathy / 中华内科杂志

Objective To investigate the diagnostic value of neuron-specific enolase(NSE),central nervous system specific protein (S100β),interleukin-6 (IL-6) in sepsis-associated encephalopathy (SAE).Methods Clinical data of patients admitted to ICU and diagnosed with sepsis were collected from January 2015 to June 2016 in Xiangya Hospital,Central South University.SAE was defined as cerebral dysfunction in the presence of sepsis that also fulfilled the exclusion criteria.The acute physiology and chronic health score (APACHE Ⅱ),sequential organ failure assessment (SOFA),NSE,S100β,IL-6,ICU stay time and 28-day mortality were compared between the two groups.NSE,S1003 and IL-6 were measured on the 1 st and 3rd day in ICU to determine the optimal cut-off value of SAE.Results Among 59 enrolled patients,36 were assigned to SAE group while 23 were non-SAE group.The SAE group had a significantly higher APACHE Ⅱ and SOFA scores,as well as the length of ICU stay (P ＜ 0.01).The levels of NSE,S1003 and IL-6 in the two groups both increased on the 1st day,and decreased on the 3rd day.The level of NSE on the 1st day [19.28 (13.00,30.52) μg/L vs 16.61 (7.58,22.01 μg/L)] and the 3rd day[16.03 (9.40,21.29) μg/L vs 11.39(8.49,15.00) μg/L,P=0.029],IL-6 on the 1st day[676.25(81.34,5 000.00) mg/L vs [209.10(42.27,648.20) mg/L,P =0.005] and the 3rd day [157.10 (72.85,687.63) mg/L vs 55.92 (31.62,177.00) mg/L,P =0.026] of SAE group was significantly higher than those of non-SAE group.However S100β between groups on the 1st day [0.33(0.15,0.54) μg/L vs 0.23(0.16,0.53) μg/L] and the 3rd day[0.19(0.10,0.29) μg/L vs 0.10(0.05,0.17) μg/L] was neither significant (P ＞0.05).The diagnostic values for SAE of NSE,S1003 and IL-6 were 14.36 μg/L,0.14 μg/L and 91.305 mg/L with sensitivity 61.1％,61.1％,72.2％ and specificity 73.9％,69.6％,69.6％,respectively.The diagnostic AUC of NSE and IL-6 combination was 0.774,95％ CI 0.651-0.896.Conclusion All sepsis patients have different degrees of brain injury.NSE combined with IL-6 on the 3rd day in ICU demonstrates the diagnostic significance of SAE.