FOXO1 reshapes neutrophils to aggravate acute brain damage and promote late depression after traumatic brain injury

Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood.Methods:Using the combined single-cell transcriptomics,metabolomics,and proteomics analysis from TBI patients and the TBI mouse model,we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests.We also characterized the underlying mechanisms both invitro and invivo through molecular simulations,signaling detections,gene expression regulation assessments[including dual-luciferase reporter and chromatin immunoprecipitation(ChIP)assays],primary cultures or co-cultures of neutrophils and oligodendrocytes,intracellular iron,and lipid hydroperoxide concentration measurements,as well as forkhead box protein O1(FOXO1)conditional knockout mice.Results:We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model.Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI,aggravating acute brain inflammatory damage and promoting late TBI-induced depression.In the acute stage,FOXO1 upregulated cytoplasmic Versican(VCAN)to interact with the apoptosis regulator B-cell lymphoma-2(BCL-2)-associated X protein(BAX),suppressing the mitochondrial translocation of BAX,which mediated the antiapoptotic effect companied with enhancing interleukin-6(IL-6)production of FOXO1high neutrophils.In the chronic stage,the“FOXO1-transferrin receptor(TFRC)”mechanism contributes to FOXO1high neutrophil ferroptosis,disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein,which contributes to the progression of late depression after TBI.Conclusions:FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI,which provides insight into the heterogeneity,reprogramming activity,and versatility of neutrophils in TBI.

Acute drivers of neuroinflammation in traumatic brain injury

Neuroinflammation is initiated as a result of traumatic brain injury and can exacerbate evolving tissue pathology.Immune cells respond to acute signals from damaged cells,initiate neuroinflammation,and drive the pathological consequences over time.Importantly,the mechanism(s)of injury,the location of the immune cells within the brain,and the animal species all contribute to immune cell behavior following traumatic brain injury.Understanding the signals that initiate neuroinflammation and the context in which they appear may be critical for understanding immune cell contributions to pathology and regeneration.Within this paper,we review a number of factors that could affect immune cell behavior acutely following traumatic brain injury.

MK-801 attenuates lesion expansion following acute brain injury in rats: a meta-analysis

OBJECTIVE: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury.DATA SOURCES: Key terms were "stroke","brain diseases","brain injuries","brain hemorrhage, traumatic","acute brain injury","dizocilpine maleate","dizocilpine","MK-801","MK801","rat","rats","rattus" and "murine". PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform(VJIP) and SinoMed databases were searched from their inception dates to March 2018.DATA SELECTION: Studies were selected if they reported the effects of MK-801 in experimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments.OUTCOME MEASURES: The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury.RESULTS: A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P < 0.00001) and degree of cerebral edema(5 studies, n = 75, MD =-1.21, 95% CI:-1.50 to-0.91;P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test(2 studies, n = 60, MD =-10.88, 95% CI:-20.75 to-1.00;P = 0.03) and neurological function 24 hours after brain injury(11 studies, n = 335, MD =-1.04, 95% CI:-1.47 to-0.60;P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P = 0.004). Further network analysis showed that 0–1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model.CONCLUSION: MK-801 effectively reduces brain lesion volume and the degree of cerebral edema in rat models of experimental acute brain injury, providing a good neuroprotective effect. Additionally, MK-801 has a good safety profile, and its mechanism of action is well known. Thus, MK-801 may be suitable for future clinical trials and applications.

Hydroxyethylstarch revisited for acute brain injury treatment

Infusion of the colloid hydroxyethylstarch has been used for volume substitution to maintain hemodynamics and microcirculation after e.g., severe blood loss.In the last decade it was revealed that hydroxyethylstarch can aggravate acute kidney injury, especially in septic patients.Because of the serious risk for critically ill patients, the administration of hydroxyethylstarch was restricted for clinical use.Animal studies and recently published in vitro experiments showed that hydroxyethylstarch might exert protective effects on the blood-brain barrier.Since the prevention of blood-brain barrier disruption was shown to go along with the reduction of brain damage after several kinds of insults, we revisit the topic hydroxyethylstarch and discuss a possible niche for the application of hydroxyethylstarch in acute brain injury treatment.

Acute kidney injury in traumatic brain injury intensive care unit patients

BACKGROUND The exact definition of Acute kidney injury(AKI)for patients with traumatic brain injury(TBI)is unknown.AIM To compare the power of the“Risk,Injury,Failure,Loss of kidney function,and End-stage kidney disease”(RIFLE),Acute Kidney Injury Network(AKIN),Creatinine kinetics(CK),and Kidney Disease Improving Global Outcomes(KDIGO)to determine AKI incidence/stage and their association with the inhospital mortality rate of patients with TBI.METHODS This retrospective study collected the data of patients admitted to the intensive care unit for neurotrauma from 2001 to 2012,and 1648 patients were included.The subjects in this study were assessed for the presence and stage of AKI using RIFLE,AKIN,CK,and KDIGO.In addition,the propensity score matching method was used.RESULTS Among the 1648 patients,291(17.7%)had AKI,according to KDIGO.The highest incidence of AKI was found by KDIGO(17.7%),followed by AKIN(17.1%),RIFLE(12.7%),and CK(11.5%)(P=0.97).Concordance between KDIGO and RIFLE/AKIN/CK was 99.3%/99.1%/99.3%for stage 0,36.0%/91.5%/44.5%for stage 1,35.9%/90.6%/11.3%for stage 2,and 47.4%/89.5%/36.8%for stage 3.The in-hospital mortality rates increased with the AKI stage in all four definitions.The severity of AKI by all definitions and stages was not associated with inhospital mortality in the multivariable analyses(all P>0.05).CONCLUSION Differences are seen in AKI diagnosis and in-hospital mortality among the four AKI definitions or stages.This study revealed that KDIGO is the best method to define AKI in patients with TBI.

Effects of Remifentanil Pretreatment on Inflammatory Response in Rats with Acute Cerebral Ischemia Injury

[Objectives]This study was conducted to investigate the effects of remifentanil pretreatment on inflammatory factors in rats with acute cerebral ischemia.[Methods]Sixty SD rats were randomly divided into the normal control group,sham operation group,ischemic brain injury group,and remifentanil pretreatment group.Except the normal control group,each group was divided into three subgroups(six in each group)according to the sampling time points of 6,12 and 24 h after execution.After modeling,the rats were scored for neurological deficit,and observed for pathological changes of neurons in the brain tissue by HE staining and the brain infarct volume by TTC staining,and the expression levels of TNF-α,IL-6 and IL-8 were detected by RT-PCR.[Results]HE staining:No significant changes were observed in the pathological morphology of the brain tissue in the blank group and sham operation group;and the neuronal structure of rats in the acute cerebral ischemia group was obviously damaged,and the neuronal damage in the remifentanil pretreatment group was less than that in the acute cerebral ischemia group at each time point.TTC staining:The gray brain infarct area in the remifentanil pretreatment group was significantly smaller than that in the cerebral ischemia group(P<0.05).RT-PCR detection results:The expression levels of TNF-α,IL-6 and IL-8 in the blank group and sham surgery group did not show significant changes at different times(P>0.05);and compared with the cerebral ischemia group,the expression levels of TNF-α,IL-6,and IL-8 in the remifentanil pretreatment group were significantly reduced at all time points(P<0.05).[Conclusions]Remifentanil pretreatment could protect the brain by reducing the expression of inflammatory factors after cerebral ischemia injury.

Morphometric changes in the cortex following acute mild traumatic brain injury

Morphometric changes in cortical thickness(CT),cortical surface area(CSA),and cortical volume(CV) can reflect pathological changes after acute mild traumatic brain injury(m TBI).Most previous studies focused on changes in CT,CSA,and CV in subacute or chronic m TBI,and few studies have examined changes in CT,CSA,and CV in acute m TBI.Furthermore,acute m TBI patients typically show transient cognitive impairment,and few studies have reported on the relationship between cerebral morphological changes and cognitive function in patients with m TBI.This prospective cohort study included 30 patients with acute m TBI(15 males,15 females,mean age 33.7 years) and 27 matched healthy controls(12 males,15 females,mean age 37.7 years) who were recruited from the Second Xiangya Hospital of Central South University between September and December 2019.High-resolution T1-weighted images were acquired within 7 days after the onset of m TBI.The results of analyses using Free Surfer software revealed significantly increased CSA and CV in the right lateral occipital gyrus of acutestage m TBI patients compared with healthy controls,but no significant changes in CT.The acute-stage m TBI patients also showed reduced executive function and processing speed indicated by a lower score in the Digital Symbol Substitution Test,and reduced cognitive ability indicated by a longer time to complete the Trail Making Test-B.Both increased CSA and CV in the right lateral occipital gyrus were negatively correlated with performance in the Trail Making Test part A.These findings suggest that cognitive deficits and cortical alterations in CSA and CV can be detected in the acute stage of m TBI,and that increased CSA and CV in the right lateral occipital gyrus may be a compensatory mechanism for cognitive dysfunction in acute-stage m TBI patients.This study was approved by the Ethics Committee of the Second Xiangya Hospital of Central South University,China(approval No.086) on February 9,2019.

Effects of acute brain injury on the contents of neurotensin in brain areas,pituitary gland and plasma in rats

The changes of immunoreactive neurotensin(ir-NT)contents in the brain areas,pituitary gland and plasma in the traumatized rats were observed in the present study.The results of radioimmunoassay exhibited significant changes of the ir-NT contents inthe hypothalamus,pituitary gland,plasma,injured tissue,hippocampus,central gray andspinal cord in the posttraumatic rats at different intervals.A predominant characteristicsof the changes of ir-NT levels in the brain areas,pituitary gland and plasma was thedramatical decrease at various times except for the hypothalamus,central gray andhippocampus with biphasic alterations.The ir-NT contents in the frontal cortex andpons-medulla also displayed changes to different extent under the acute craniocerebraltrauma condition.These results suggest that NT may play a role in the pathophysiologyof traumatic head injury.

Influence of ginkgolide combined with edaravone on the brain function of elderly patients with acute cerebral infarction and its preventive effect on ischemia reperfusion injury

Objective: To explore the influence of ginkgolide combined with edaravone on the brain function of elderly patients with acute cerebral infarction and its preventive effect on ischemia reperfusion injury. Methods: A total of 126 patients with acute cerebral infarction who were treated in Dazhou Central Hospital between February 2016 and May 2017 were divided into the control group (n=67) and ginkgolide group (n=59) according to different therapies. Control group received routine intravenous thrombolysis + edaravone therapy, and ginkgolide group received routine intravenous thrombolysis + edaravone + ginkgolide therapy. The differences in brain function and nerve ischemia reperfusion injury extent were compared between the two groups. Results: At T1 and T2, serum nerve function indexes NT-proBNP and NSE levels of ginkgolide group were lower than those of control group whereas BDNF levels were higher than those of control group;serum inflammatory mediators MCP-1, NF-κB, CRP and TNF-α levels were lower than those of control group;serum apoptosis molecules caspase-3 and Bax levels were lower than those of control group whereas Bcl-2 levels were higher than those of control group. Conclusion: Ginkgolide combined with edaravone therapy on the basis of intravenous thrombolysis can effectively optimize the brain function and alleviate the ischemia reperfusion injury caused by inflammatory response and apoptosisis in elderly patients with acute cerebral infarction.

Effects of positive end-expiratory pressure on intracranial pressure,cerebral perfusion pressure,and brain oxygenation in acute brain injury:Friend or foe?A scoping review

Background Patients with acute brain injury(ABI)are a peculiar population because ABI does not only affect the brain but also other organs such as the lungs,as theorized in brain–lung crosstalk models.ABI patients often require mechanical ventilation(MV)to avoid the complications of impaired respiratory function that can follow ABI;MV should be settled with meticulousness owing to its effects on the intracranial compartment,especially regarding positive end-expiratory pressure(PEEP).This scoping review aimed to(1)describe the physiological basis and mechanisms related to the effects of PEEP in ABI;(2)examine how clinical research is conducted on this topic;(3)identify methods for setting PEEP in ABI;and(4)investigate the impact of the application of PEEP in ABI on the outcome.Methods The five-stage paradigm devised by Peters et al.and expanded by Arksey and O'Malley,Levac et al.,and the Joanna Briggs Institute was used for methodology.We also adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)extension criteria.Inclusion criteria:we compiled all scientific data from peer-reviewed journals and studies that discussed the application of PEEP and its impact on intracranial pressure,cerebral perfusion pressure,and brain oxygenation in adult patients with ABI.Exclusion criteria:studies that only examined a pediatric patient group(those under the age of 18),experiments conducted solely on animals;studies without intracranial pressure and/or cerebral perfusion pressure determinations,and studies with incomplete information.Two authors searched and screened for inclusion in papers published up to July 2023 using the PubMed-indexed online database.Data were presented in narrative and tubular form.Results The initial search yielded 330 references on the application of PEEP in ABI,of which 36 met our inclusion criteria.PEEP has recognized beneficial effects on gas exchange,but it produces hemodynamic changes that should be predicted to avoid undesired consequences on cerebral blood flow and intracranial pressure.Moreover,the elastic properties of the lungs influence the transmission of the forces applied by MV over the brain so they should be taken into consideration.Currently,there are no specific tools that can predict the effect of PEEP on the brain,but there is an established need for a comprehensive monitoring approach for these patients,acknowledging the etiology of ABI and the measurable variables to personalize MV.Conclusion PEEP can be safely used in patients with ABI to improve gas exchange keeping in mind its potentially harmful effects,which can be predicted with adequate monitoring supported by bedside non-invasive neuromonitoring tools.

Dynamic changes in growth factor levels over a 7-day period predict the functional outcomes of traumatic brain injury

Traumatic brain injury（TBI） can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1（Ang-1）, vascular endothelial growth factor（VEGF）, and granulocyte-colony stimulating factor（G-CSF）, play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended（GOSE）. Patients having a GOSE score of 〉 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1-5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI（within 7 days）. This study was registered with the Chinese Clinical Trial Registry（registration number： ChiCTR1800018251） on September 7, 2018.

Effect of Early Controlled Hypotension on Patients with Traumatic Brain Injury

Objective:To investigate the clinical effect of early controlled hypotensive therapy in patients with traumatic braininjury(TBI).Methods:68 patients with acute 1Bl in our hospital were selected for this investigation.They were evenly divided into a control group and an observation group according to the difference of blood pressure and basic level,whose lesion area after treatment,postoperative intracranial pressure after 2 d and 7d,and Gcs score of prognostic quality before and after treatment were made comparison.Results:The post-treatment lesion area of the observation group was lower than that in the control group(P<0.05);the postoperative intracranial pressure after 2d and 7d of the control group was better than the observation group(P<0.05),and the same with GCS score,which has statistical sigmificance(P< 0.05).Conclusion:Early controlled hypotensive therapy has a significant clinical effect on patients with brain trauuma,it can reduce the lesion area after treatment and postoperative intracranial pressure as well.

Haemodynamic management in brain death donors:Influence of aetiology of brain death

BACKGROUND In brain death donors(BDDs),donor management is the key in the complex donation process.Donor management goals,which are standards of care or clinical parameters,have been considered an acceptable barometer of successful donor management.AIM To test the hypothesis that aetiology of brain death could influence haemodynamic management in BDDs.METHODS Haemodynamic data(blood pressure,heart rate,central venous pressure,lactate,urine output,and vasoactive drugs)of BDDs were recorded on intensive care unit(ICU)admission and during the 6-h observation period(Time 1 at the beginning;Time 2 at the end).RESULTS The study population was divided into three groups according to the aetiology of brain death:Stroke(n=71),traumatic brain injury(n=48),and postanoxic encephalopathy(n=19).On ICU admission,BDDs with postanoxic encephalopathy showed the lowest values of systolic and diastolic blood pressure associated with higher values of heart rate and lactate and a higher need of norepinephrine and other vasoactive drugs.At the beginning of the 6-h period(Time 1),BDDs with postanoxic encephalopathy showed higher values of heart rate,lactate,and central venous pressure together with a higher need of other vasoactive drugs.CONCLUSION According to our data,haemodynamic management of BDDs is affected by the aetiology of brain death.BDDs with postanoxic encephalopathy have higher requirements for norepinephrine and other vasoactive drugs.

急性颅脑外伤患者肠道菌群多样性差异对继发性全身炎症反应综合征的临床预测价值

目的探讨急性颅脑外伤患者肠道菌群多样性差异对继发性全身炎症反应综合征(SIRS)的临床预测价值。方法回顾性分析2022年1月—2023年12月固原市人民医院急诊重症监护病房和神经外科重症监护病房收治的急性颅脑外伤患者60例。按SIRS诊断标准分为单纯急性颅脑外伤组(非SIRS组)与急性颅脑外伤后继发性SIRS组(SIRS组);收集患者一般资料并进行临床指标检测,通过16S rRNA基因测序比较两组肠道菌群多样性与菌属相对丰度,采用Pearson相关性分析肠道菌群与临床指标的关系,采用受试者工作特征(ROC)曲线分析肠道菌群对SIRS的预测价值。结果两组患者性别构成、年龄、红细胞计数、血小板计数比较,差异均无统计学意义(P>0.05)。SIRS组体温较非SIRS组高、心率较非SIRS组快、白细胞计数较非SIRS组多、C反应蛋白水平较非SIRS组高(P<0.05)。两组患者Chao1和Shannon指数比较,差异均无统计学意义(P>0.05)。两组患者拟杆菌属、瘤胃球菌属、阿克曼菌属、粪肠球菌属相对丰度比较,差异均无统计学意义(P>0.05)。SIRS组普雷沃菌属相对丰度低于非SIRS组(P<0.05),埃希菌-志贺菌属、棒状杆菌属相对丰度均高于非SIRS组(P<0.05)。Pearson相关性分析结果表明,体温、心率、白细胞计数及C反应蛋白与普雷沃菌属相对丰度均呈负相关(r=-0.574、-0.539、-0.554和-0.572,均P<0.05);体温、心率、白细胞计数及C反应蛋白与埃希菌-志贺菌属相对丰度呈正相关(r=0.751、0.743、0.657和0.770,均P<0.05),与棒状杆菌属相对丰度均呈正相关(r=0.782、0.762、0.707和0.799,均P<0.05)。ROC曲线分析结果表明,联合诊断的预测效能最高,曲线下面积为0.946(95%CI:0.871,1.000),敏感性为96.7%(95%CI:0.902,0.100),特异性为93.3%(95%CI:0.844,0.100)。结论肠道菌群组成的变化与颅脑损伤后SIRS的发展密切相关,特定菌属的丰度变化可作为SIRS发展的早期生物预警信号。

不同针灸介入时机对大脑中动脉供血区急性脑梗死神经功能预后的影响

目的观察不同针灸介入时机对大脑中动脉供血区急性脑梗死神经功能预后的影响。方法回顾性选取2020年1月—2022年8月收治的116例大脑中动脉供血区急性脑梗死患者的临床资料进行分析,根据针灸介入时机分为两组。两组均进行静脉溶栓及常规药物治疗,观察组61例患者于发病72 h内给予针灸治疗,对照组55例患者于发病2周时给予针灸治疗。检测两组不同时间点侧支循环代偿情况、脑损伤标志物的水平,评估两组不同时间点简易精神状态检查(Mini-mental state examination,MMSE)评分、神经功能评分、Barthel指数(Barthel index,BI)评分、肢体运动功能评分、中医症状评分的差异,统计两组疗效。结果治疗前,两组侧支循环代偿情况比较,差异无统计学意义(P>0.05)。治疗4周和随访时,两组患侧大脑前动脉平均血流速度与对侧大脑中动脉平均血流速度的比值(Ratio of the average flow ve⁃locity of the affected anterior cerebral artery to the average flow velocity of the contralateral middle cerebral artery,iVACA/cVM⁃CA)较治疗前升高,观察组同时间点较对照组更高(P<0.05);两组患侧大脑后动脉平均血流速度与对侧大脑中动脉平均血流速度的比值(Ratio of the average flow velocity of the affected posterior cerebral artery to the average flow velocity of the contralateral middle cerebral artery,iVPCA/cVMCA)与治疗前比较,差异无统计学意义(P>0.05)。治疗前,两组脑损伤标志物比较,差异无统计学意义(P>0.05)。治疗4周和随访时,两组脑源性神经营养因子(Brain-derived neurotrophic factor,BDNF)较治疗前升高,观察组同时间点较对照组更高(P<0.05);两组钙结合蛋白β(Calcium binding proteinβ,S100β)、神经胶质纤维酸性蛋白(Glial fibrillary acid protein,GFAP)较治疗前下降,观察组同时间点较对照组更低(P<0.05)。治疗前,两组Fugl-Meyer评分、中医症状评分等相关评分比较,差异无统计学意义(P>0.05)。治疗4周和随访时,两组MMSE评分、BI评分及上肢和下肢Fugl-Meyer评分较治疗前升高,观察组同时间点较对照组更高(P<0.05);两组美国国立卫生院神经功能缺损(National institutes of health stroke scale,NIHSS)评分、中医症状评分较治疗前下降,观察组同时间点较对照组更低(P<0.05)。观察组总有效率为88.52%(54/61)高于对照组的72.73%(40/55),差异有统计学意义(P<0.05)。结论发病72h内采用针灸治疗可改善大脑中动脉供血区急性脑梗死脑损伤标志物的表达,改善脑血流,促进神经功能的恢复,有利于疾病的康复。

急性一氧化碳中毒发生迟发性脑病的相关因素分析

目的分析急性一氧化碳(CO)中毒患者发生迟发性脑病的相关因素分析。方法选取2020年1月至2022年8月葫芦岛地区177例符合急性CO中毒诊断的住院患者,回顾性分析纳入病例的临床资料,应用Spearman相关性分析与CO中毒迟发性脑病相关的影响因素。结果177例患者中男性91例(51.41%),发病年龄集中在60岁以上,共86例(48.59%);发病时间集中在凌晨4~8点,共42例(23.73%);地域主要集中在农村,共139例(78.53%);文化程度主要集中在初中及以下,共113例(63.84%);中毒方式以取暖方式不当为主,共107例(60.45%);中毒场所主要在家中,共132例(74.58%)。177例患者中死亡2例,发生一氧化碳中毒迟发性脑病患者18例(10.17%)。既往合并基础病(心血管病,高血压,糖尿病,脑梗死)、就诊时间、昏迷时间及早期出现脏器损害(包括急性肝损伤,急性肾损伤)与一氧化碳中毒迟发性脑病呈正相关,GCS评分与一氧化碳中毒迟发性脑病呈负相关。结论急性一氧化碳中毒主要集中在农村的老年人群,中毒原因主要由家中取暖方式错误,其中合并基础疾病(心血管病,高血压,糖尿病,脑梗死)、就诊时间及昏迷时间长,GCS评分低,早期出现脏器损害均与发生迟发性脑病相关,应早期识别迟发性脑病的高危患者,对其尽早进行干预治疗,提高治愈率,降低并发症。

沉默信息调节因子1激活剂SRT1720减轻大鼠急性颅脑损伤的机制

背景:有研究显示在急性颅脑损伤小鼠模型中,以药物激活沉默信息调节因子1的转录和翻译水平后能明显升高脑组织中沉默信息调节因子1的表达,降低脑组织炎症应激和氧化应激水平,改善神经功能。目的:探讨腹腔注射沉默信息调节因子1激活剂SRT1720减轻大鼠急性颅脑损伤的机制。方法:取90只SD大鼠,采用随机数字表法分为3组,每组30只:假手术组不造模;模型组、激活剂组建立急性颅脑损伤模型,6 h后假手术组、模型组、激活剂组分别腹腔注射二甲亚砜溶液、二甲亚砜溶液、SRT1720,1次/d,连续注射28 d。设定取材时间点,检测大鼠神经功能、脑组织含水量、脑组织氧化应激与炎症反应、脑组织形态、细胞凋亡与血管新生以及脑组织中沉默信息调节因子1蛋白表达。结果与结论:①注射7,14,28 d时,与假手术组比较,模型组大鼠改良神经功能缺损评分、脑组织含水量及细胞凋亡率均升高(P<0.05);与模型组比较,激活剂组大鼠改良神经功能缺损评分、脑组织含水量及细胞凋亡率均降低(P<0.05);②注射7,14,28 d时,与假手术组比较,模型组大鼠脑组织中活性氧自由基、髓过氧化物酶水平升高(P<0.05),血清中丙二醛、肿瘤坏死因子α和白细胞介素6水平升高(P<0.05),血清中超氧化物歧化酶水平降低(P<0.05);与模型组比较,激活剂组大鼠大鼠脑组织中活性氧自由基、髓过氧化物酶水平降低(P<0.05),血清中丙二醛、肿瘤坏死因子α和白细胞介素6水平降低(P<0.05),血清中超氧化物歧化酶水平升高(P<0.05);③注射7,14,28 d的免疫组化染色显示,模型组大鼠脑组织中新生血管数量多于假手术组(P<0.05),激活剂组大鼠脑组织中新生血管数量多于模型组(P<0.05);注射7,14,28 d的Western blot检测显示,模型组大鼠脑组织中沉默信息调节因子1蛋白表达低于假手术组(P<0.05),激活剂组大鼠脑组织中沉默信息调节因子1蛋白表达高于模型组(P<0.05);注射7,14,28 d的苏木精-伊红染色显示,激活剂组大鼠脑组织损伤程度轻于模型组;④结果表明,腹腔注射SRT1720通过下调急性颅脑损伤大鼠脑组织氧化和炎性应激水平、抑制神经细胞凋亡、促进血管新生来减轻脑组织损伤。

中国儿童遗体器官捐献肾脏的功能维护、评估和应用指南

儿童遗体器官捐献是遗体器官捐献中重要的组成部分,其与成人器官捐献存在较大差异。为规范我国儿童遗体器官捐献肾脏的功能维护、评估和应用,中华医学会器官移植学分会发起制订《中国儿童遗体器官捐献肾脏的功能维护、评估和应用指南》,指南采用2009版牛津大学循证医学中心的证据分级与推荐强度标准制订,针对儿童遗体器官捐献肾脏有关的功能维护、评估及应用方面的29个临床问题,给出了33条推荐意见,旨在规范操作流程,为临床工作提供指引,全面提升我国器官捐献与移植质量。

脑肿瘤患者术中低血压与术后急性肾损伤的相关性

目的探讨脑肿瘤切除术中低血压与术后急性肾损伤(AKI)的相关性。方法筛选择期行脑肿瘤切除术的患者428例,男276例,女152例,年龄≥18岁,BMI 15~36 kg/m^(2),ASAⅡ或Ⅲ级。根据术后是否发生AKI将患者分为两组:AKI组和非AKI组。本研究定义了3个低血压阈值,分别为术中MAP<65 mmHg、60 mmHg和55 mmHg,采用多因素Logistic回归分析3个不同阈值下术中低血压与术后AKI的相关性。结果共有107例发生术后AKI。多因素回归分析结果显示,术中MAP<65 mmHg(OR=1.11,95%CI 1.03~1.20,P=0.010)和术中MAP<60 mmHg(OR=1.12,95%CI 1.02~1.23,P=0.017)与术后AKI的发生相关。结论术中MAP<65 mmHg和60 mmHg与脑肿瘤切除术后AKI的发生相关。

代谢组学在体外循环心脏手术器官损伤中的研究进展

体外循环(CPB)主要应用于心脏手术,CPB会造成脑、心、肾等重要脏器的损害,产生相关的并发症。代谢组学是研究生物体受外部刺激所产生的全部变化的代谢产物的科学,CPB后机体的代谢物成分会发生变化。研究心脏手术围术期的代谢变化,可以为疾病的发病机制提供重要的见解,并有潜力识别新的生物标志物。本综述主要介绍代谢组学的现状,以及其在CPB心脏手术对脑、心、肾、肺等重要脏器损伤中的研究进展,并就代谢组学在该领域的未来做一展望。