Tumor necrosis factor-stimulated gene-6 ameliorates early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome-mediated astrocyte pyroptosis

Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.

Brain abscess caused by Streptococcus anginosus group:Three case reports

BACKGROUND This case series investigated the clinical manifestations,diagnoses,and treatment of cerebral abscesses caused by Streptococcus anginosus.We retrospectively analyzed the clinical characteristics and outcomes of three cases of cerebral abscesses caused by Streptococcus anginosus and conducted a comprehensive review of relevant literature.CASE SUMMARY Case 1 presented with a history of left otitis media and exhibited high fever,confusion,and vomiting as primary symptoms.Postoperative pus culture indicated a brain abscess caused by Streptococcus constellatus infection.Case 2 experienced dizziness for two days as the primary symptom.Postoperative pus culture suggested an intermediate streptococcal brain abscess.Case 3:Enhanced head magnetic resonance imaging(MRI)and diffusion-weighted imaging revealed occupancy of the left temporal lobe,initially suspected to be a metastatic tumor.However,a postoperative pus culture confirmed the presence of a brain abscess caused by Streptococcus anginosus infection.The three cases presented in this case series were all patients with community-acquired brain abscesses resulting from angina caused by Streptococcus group infection.All three patients demonstrated sensitivity to penicillin,ceftriaxone,vancomycin,linezolid,chloramphenicol,and levofloxacin.Successful treatment was achieved through stereotaxic puncture,drainage,and ceftriaxone administration with a six-week course of antibiotics.CONCLUSION Preoperative enhanced head MRI plays a critical role in distinguishing brain tumors from abscesses.Selecting the correct early diagnostic methods for brain abscesses and providing timely intervention are very important.This case series was in accordance with the CARE guidelines.

Evaluation of the updated definition of early allograft dysfunction in donation after brain death and donation after cardiac death liver allografts

BACKGROUND:An updated definition of early allograft dysfunction(EAD) was recently validated in a multicenter study of 300 deceased donor liver transplant recipients.This analysis did not differentiate between donation after brain death(DBD) and donation after cardiac death(DCD) allograft recipients.METHODS:We reviewed our prospectively entered database for all DBD(n=377) and DCD(n=38) liver transplantations between January 1,2006 and October 30,2011.The incidence of EAD as well as its ability to predict graft failure and survival was compared between DBD and DCD groups.RESULTS:EAD was a valid predictor of both graft and patient survival at six months in DBD allograft recipients,but in DCD allograft recipients there was no significant difference in the rate of graft failure in those with EAD(11.5%) compared with those without EAD(16.7%)(P=0.664) or in the rate of death in recipients with EAD(3.8%) compared with those without EAD(8.3%)(P=0.565).The graft failure rate in the first 6 months in those with international normalized ratio ≥1.6 on day 7 who received a DCD allograft was 37.5% compared with 6.7% for those with international normalized ratio <1.6 on day 7(P=0.022).CONCLUSIONS:The recently validated definition of EAD is a valid predictor of patient and graft survival in recipients of DBD allografts.On initial assessment,it does not appear to be a useful predictor of patient and graft survival in recipients of DCD allografts,however a study with a larger sample size of DCD allografts is needed to confirm these findings.The high ALT/AST levels in most recipients of DCD livers as well as the predisposition to biliary complications and early cholestasis make these parameters as poor predictors of graft failure.An alternative definition of EAD that gives greater weight to the INR on day 7 may be more relevant in this population.

Partial improvement in performance of patients with severe Alzheimer's disease at an early stage of fornix deep brain stimulation

Deep brain stimulation is a therapy for Alzheimer＇s disease（AD） that has previously been used for mainly mild to moderate cases. This study provides the first evidence of early alterations in performance induced by stimulation targeted at the fornix in severe AD patients. The performance of the five cases enrolled in this study was scored with specialized assessments including the Mini-Mental State Examination and Clinical Dementia Rating, both before and at an early stage after deep brain stimulation. The burden of caregivers was also evaluated using the Zarit Caregiver Burden Interview. As a whole, the cognitive performance of patients remained stable or improved to varying degrees, and caregiver burden was decreased. Individually, an improved mental state or social performance was observed in three patients, and one of these three patients showed remarkable improvement in long-term memory. The conditions of another patient deteriorated because of inappropriate antipsychotic medications that were administered by his caregivers. Taken together, deep brain stimulation was capable of improving some cognitive aspects in patients with severe AD, and of ameliorating their emotional and social performance, at least at an early stage. However, long-term effects induced by deep brain stimulation in patients with severe AD need to be further validated. More research should focus on clarifying the mechanism of deep brain stimulation. This study was registered with ClinicalTrials.gov（NCT03115814） on April 14, 2017.

Matricellular proteins as possible biomarkers for early brain injury after aneurysmal subarachnoid hemorrhage

Aneurysmal subarachnoid hemorrhage remains devastating,and the most important determinant of poor outcome is early brain injury（EBI）.In clinical settings,as a surrogate marker of EBI,loss of consciousness at ictus,poor initial clinical grades,and some radiographic findings are used,but these markers are somewhat subjective.Thus,it is imperative to find biomarkers of EBI that have beneficial prognostic and therapeutic implications.In our opinion,an ideal biomarker is a molecule that is implicated in the pathogenesis of both EBI and subsequently developing delayed cerebral ischemia（DCI）,being a therapeutic target,and can be measured easily in the peripheral blood in an acute stage.A good candidate of such a biomarker is a matricellular protein,which is a secreted,inducible and multifunctional extracellular matrix protein.There are many kinds of matricellular proteins reported,but only tenascin-C,osteopontin,galectin-3 and periostin are reported relevant to EBI and DCI.Reliable biomarkers of EBI may stratify aneurysmal subarachnoid hemorrhage patients into categories of risk to develop DCI,and allow objective monitoring of the response to treatment for EBI and earlier diagnosis of DCI.This review emphasizes that further investigation of matricellular proteins as an avenue for biomarker discovery is warranted.

Neuroprotection mediated by the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage

The Wnt/Frizzled signaling pathway participates in many inflammation-linked diseases. However, the inflammatory response mediated by the Wnt/Frizzled signaling pathway in experimental subarachnoid hemorrhage has not been thoroughly investigated. Consequently, in this study, we examined the potential role of the Wnt/Frizzled signaling pathway in early brain injury in rat models of subarachnoid hemorrhage.Simultaneously, possible neuroprotective mechanisms were also investigated. Experimental subarachnoid hemorrhage rat models were induced by injecting autologous blood into the prechiasmatic cistern. Experiment 1 was designed to examine expression of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. In total, 42 adult rats were divided into sham(injection of equivalent volume of saline), 6-, 12-, 24-, 48-, 72-hour, and 1-week subarachnoid hemorrhage groups. Experiment 2 was designed to examine neuroprotective mechanisms of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. Rats were treated with recombinant human Wnt1(rhwnt1), small interfering Wnt1(siwnt1) RNA, and monoclonal antibody of Frizzled1(anti-Frizzled1) at 48 hours after subarachnoid hemorrhage. Expression levels of Wnt1, Frizzled1, β-catenin, peroxisome proliferator-activated receptor-γ, CD36, and active nuclear factor-κB were examined by western blot assay and immunofluorescence staining. Microglia type conversion and inflammatory cytokine levels in brain tissue were examined by immunofluorescence staining and enzyme-linked immunosorbent assay. Our results show that compared with the sham group, expression levels of Wnt1, Frizzled1, and β-catenin were low and reduced to a minimum at 48 hours, gradually returning to baseline at 1 week after subarachnoid hemorrhage. rhwnt1 treatment markedly increased Wnt1 expression and alleviated subarachnoid hemorrhage-induced early brain injury(within 72 hours), including cortical cell apoptosis, brain edema, and neurobehavioral deficits, accompanied by increasing protein levels of β-catenin, CD36, and peroxisome proliferator-activated receptor-γ and decreasing protein levels of nuclear factor-κB. Of note, rhwnt1 promoted M2-type microglia conversion and inhibited release of inflammatory cytokines(interleukin-1β, interleukin-6, and tumor necrosis factor-α). In contrast, siwnt1 RNA and anti-Frizzled1 treatment both resulted in an opposite effect. In conclusion, the Wnt/Frizzled1 signaling pathway may participate in subarachnoid hemorrhage-induced early brain injury via inhibiting the inflammatory response, including regulating microglia type conversion and decreasing inflammatory cytokine release. The study was approved by the Animal Ethics Committee of Anhui Medical University and First Affiliated Hospital of USTC,Division of Life Sciences and Medicine, University of Science and Technology of China(approval No. LLSC-20180202) in May 2017.

Role of Glucose-regulated Protein 78 in Early Brain Injury after Experimental Subarachnoid Hemorrhage in Rats

Early brain injury（EBI） plays a key role in the pathogenesis of subarachnoid hemorrhage（SAH）. This study investigated the role of glucose-regulated protein 78（GRP78） in EBI after SAH. Male Sprague-Dawley rats（n=108） weighing 260±40 g were divided into control, sham-operated, and operated groups. Blood was injected into the prechiasmatic cistern of rats in the operated group. Neurological scores, ultrastructures of neurons, apoptosis, and GRP78 expression in the hippocampus were examined using Garcia scoring system, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated d UTP nick-end labelling, and Western blotting at 1, 6, 12, 24, 48, and 72 h after SAH, respectively. The results showed that neurological scores were significantly decreased in the operated group as compared with those in control and sham-operated groups at 12, 24, 48, and 72 h. Metachromatin, chromatin pyknosis at the edge, endoplasmic reticulum swelling, and invagination of nuclear membrane were observed at 24 h in the operated group, indicating the early morphological changes of apoptosis. The number of apoptotic cells was significantly increased in the operated group as compared with that in control and sham-operated groups at 6, 12, 24, 48, and 72 h. The GRP78 protein expression levels in the operated group were significantly elevated at all time points and reached the peak at 12 h. GRP78 expression was positively associated with apoptosis cells and negatively with neurological scores. In conclusion, EBI was demonstrated to occur after SAH and GRP78 was involved in the development of EBI after SAH.

Elevated NKCC1 transporter expression facilitates early post-traumatic brain injury seizures

As a leading cause for morbidity and mortality in young adults,traumatic brain injury（TBI）,along with the poorly understood TBI-related seizures inducing their predispositions,pose a major health and socioeconomic problem in the world（Huang,2013）.

Obstructive sleep apnea aggravates neuroinflammation and pyroptosis in early brain injury following subarachnoid hemorrhage via ASC/HIF-1α pathway

Obstructive sleep apnea can worsen the prognosis of subarachnoid hemorrhage.Howeve r,the underlying mechanism remains unclear.In this study,we established a mouse model of subarachnoid hemorrhage using the endovascular perforation method and exposed the mice to intermittent hypoxia for 8 hours daily for 2 consecutive days to simulate sleep apnea.We found that sleep apnea aggravated brain edema,increased hippocampal neuron apoptosis,and worsened neurological function in this mouse model of subarachnoid hemorrhage.Then,we established an in vitro HT-22 cell model of hemin-induced subarachnoid hemorrhage/intermittent hypoxia and found that the cells died,and lactate dehydrogenase release increased,after 48 hours.We further investigated the underlying mechanism and found that sleep apnea increased the expression of hippocampal neuroinflammatory factors interleukin-1β,interleukin-18,inte rleukin-6,nuclear factorκB,pyro ptosis-related protein caspase-1,pro-caspase-1,and NLRP3,promoted the prolife ration of astrocytes,and increased the expression of hypoxia-inducible factor 1αand apoptosis-associated speck-like protein containing a CARD,which are the key proteins in the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling pathway.We also found that knockdown of hypoxia-inducible factor 1αexpression in vitro greatly reduced the damage to HY22 cells.These findings suggest that sleep apnea aggravates early brain injury after subarachnoid hemorrhage by aggravating neuroinflammation and pyroptosis,at least in part through the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling pathway.

Sarcopenia diagnosed using masseter muscle area predictive of early mortality following severe traumatic brain injury

Traumatic brain injury（TBI）represents a global pandemic and is currently a leading cause of injury related death worldwide.Unfortunately,those who survive initial injury often suffer devastating functional,social,and economic consequences.

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.

Classification of Brain Tumors Using Hybrid Feature Extraction Based on Modified Deep Learning Techniques

According to the World Health Organization(WHO),Brain Tumors(BrT)have a high rate of mortality across the world.The mortality rate,however,decreases with early diagnosis.Brain images,Computed Tomography(CT)scans,Magnetic Resonance Imaging scans(MRIs),segmentation,analysis,and evaluation make up the critical tools and steps used to diagnose brain cancer in its early stages.For physicians,diagnosis can be challenging and time-consuming,especially for those with little expertise.As technology advances,Artificial Intelligence(AI)has been used in various domains as a diagnostic tool and offers promising outcomes.Deep-learning techniques are especially useful and have achieved exquisite results.This study proposes a new Computer-Aided Diagnosis(CAD)system to recognize and distinguish between tumors and non-tumor tissues using a newly developed middleware to integrate two deep-learning technologies to segment brain MRI scans and classify any discovered tumors.The segmentation mechanism is used to determine the shape,area,diameter,and outline of any tumors,while the classification mechanism categorizes the type of cancer as slow-growing or aggressive.The main goal is to diagnose tumors early and to support the work of physicians.The proposed system integrates a Convolutional Neural Network(CNN),VGG-19,and Long Short-Term Memory Networks(LSTMs).A middleware framework is developed to perform the integration process and allow the system to collect the required data for the classification of tumors.Numerous experiments have been conducted on different five datasets to evaluate the presented system.These experiments reveal that the system achieves 97.98%average accuracy when the segmentation and classification functions were utilized,demonstrating that the proposed system is a powerful and valuable method to diagnose BrT early using MRI images.In addition,the system can be deployed in medical facilities to support and assist physicians to provide an early diagnosis to save patients’lives and avoid the high cost of treatments.

急性脑梗死患者溶栓后网膜素1水平对早期神经功能恶化的评估价值

目的探讨急性脑梗死患者溶栓后外周血网膜素1表达对早期神经功能恶化(early neurological deterioration,END)的评估价值。方法选取2021年2月至2022年2月郴州市第一人民医院神经内科明确诊断为急性脑梗死并行溶栓治疗的患者210例,根据溶栓后网膜素1水平分为低水平组70例(网膜素1<150μg/L),中水平组70例(150μg/L≤网膜素1≤200μg/L),高水平组70例(网膜素1>200μg/L),比较3组END发生情况。采用Pearson相关性分析网膜素1与END的相关性,用Cox回归分析发生END的影响因素,ROC曲线分析网膜素1对END的预测价值。结果210例急性脑梗死患者发生END 60例(28.6%)。低水平组、中水平组、高水平组END发生率比较,差异有统计学意义(45.7%vs 25.7%vs 14.3%,P<0.01),其中高水平组END发生率明显低于低水平组和中水平组,差异有统计学意义(P<0.01)。Pearson相关性分析显示,网膜素1与END发生呈负相关(r=-0.635,P<0.05)。多因素Cox回归分析显示,发病至溶栓时间、糖尿病、白细胞计数、网膜素1与急性脑梗死患者溶栓后发生END独立相关(P<0.05,P<0.01)。ROC曲线分析显示,网膜素1预测END发生的截断值为162.36μg/L,曲线下面积为0.868(95%CI:0.811~0.925),敏感性和特异性分别为73.3%、88.0%。结论急性脑梗死患者溶栓后外周血网膜素1水平与END的发生密切关联,网膜素1可作为评估END发生的生物标志物。

早期康复治疗联合家庭康复训练在小儿脑损伤及脑瘫患儿中的应用效果

目的探讨早期康复治疗联合家庭康复训练干预对小儿脑损伤及脑瘫患儿的临床效果。方法选取2020年2月至2022年9月泰安市妇幼保健院收治的52例小儿脑损伤及脑瘫患儿为研究对象,采用投掷硬币法将其分为参照组(n=26)和研究组(n=26)。参照组采用家庭康复训练方式;研究组采用早期康复治疗联合家庭康复训练方式,两组均保持为期2周的干预。比较两组小儿脑损伤及脑瘫患儿的护理总有效率、生存质量评分(社交功能评分、情感功能评分及生理功能评分)、日常生活能力量表(ADL)评分及肢体运动功能评定量表(FMA)评分。结果研究组小儿脑损伤及脑瘫患儿护理总有效率高于参照组,差异有统计学意义(P<0.05)。护理后,两组小儿脑损伤及脑瘫患儿社交功能评分、情感功能评分及生理功能评分高于护理前,且研究组高于参照组,差异有统计学意义(P<0.05)。护理后,两组小儿脑损伤及脑瘫患儿ADL评分及FMA评分高于护理前,且研究组高于参照组,差异有统计学意义(P<0.05)。结论临床给予小儿脑损伤及脑瘫患儿早期康复治疗联合家庭康复训练干预,对于患儿护理效果、生存质量、日常生活能力及肢体运动功能的提升具有显著效果。

动脉瘤性蛛网膜下腔出血患者血清和脑脊液LCN2早期表达分析

目的:分析动脉瘤性蛛网膜下腔出血(aneurysmal subarachnoid hemorrhage,aSAH)患者血清和脑脊液载脂蛋白2(lipocalin-2,LCN2)早期表达情况,探讨其与患者早期脑损伤(early brain injury,EBI)严重程度的相关性。方法:选择2020-2022年入住包头市中心医院神经内科诊断为aSAH且发病3 d内的患者为aSAH组;选取同期与患者年龄、性别相匹配的其他患者为对照组。采用酶联免疫吸附法测定两组血清和脑脊液LCN2水平。运用Hunt-Hess分级评定患者脑损伤严重程度并分为3组:Ⅰ组Hunt-HessⅠ级、Ⅱ组Hunt-HessⅡ级、Ⅲ组Hunt-HessⅢ-Ⅴ级,分析EBI严重程度与血清和脑脊液LCN2水平的相关性。结果:共入组47例患者。(1)aSAH组血清和脑脊液LCN2水平均高于对照组,差异有统计学意义(P<0.001)。(2)Ⅱ组血清和脑脊液LCN2水平均高于Ⅰ组,差异有统计学意义(P<0.05);Ⅲ组血清和脑脊液LCN2水平均高于Ⅱ组,差异有统计学意义(P<0.05),Hunt-Hess分级和血清LCN2、脑脊液LCN2均为正相关且差异有统计学意义(r_(s)>0,P<0.05)。(3)通过绘制ROC曲线表明:血清LCN2的ROC曲线下面积为0.876(特异度为100.00%,敏感度为61.70%),最佳诊断界限值为45.68 ng/mL;脑脊液LCN2的ROC曲线下面积为0.914(特异度为76.60%,敏感度为100.00%),最佳诊断界限值为15.08 ng/mL。结论:aSAH患者早期体液LCN2明显升高,并与EBI密切相关,可能参与EBI发病机制。

平均血小板体积和脑白质高信号对穿支动脉疾病型脑梗死早期神经功能恶化的预测价值

目的探讨平均血小板体积(MPV)和脑白质高信号(WMH)与穿支动脉疾病(PAD)型脑梗死患者早期神经功能恶化(END)的相关性。方法回顾性连续纳入2021年1月至2023年9月苏州市独墅湖医院神经内科收治的经头部MRI等检查诊断的PAD型脑梗死患者,按照入院后7 d内是否发生END分为END组和非END组。收集两组患者的人口学资料、临床资料,包括性别、年龄、体质量指数、高血压病、糖尿病、高脂血症、吸烟、早期(发病7 d内)是否合并肺部感染、入院美国国立卫生研究院卒中量表(NIHSS)评分、入院时收缩压、脑梗死部位(前、后循环供血区)及抗血小板聚集药物治疗方案(单抗、双抗)、白细胞计数、中性粒细胞/淋巴细胞比值、C反应蛋白、血小板计数、血小板压积、MPV、三酰甘油、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、血尿酸、同型半胱氨酸、糖化血红蛋白、D-二聚体及纤维蛋白原。根据头部MRI影像,按照改良Fazekas分级,将两组患者的WMH严重程度分为轻度负荷(改良Fazekas分级0~1级)和重度负荷(改良Fazekas分级2~3级)。采用单因素及多因素二元Logistic回归分析MPV和WMH程度与PAD型脑梗死患者发生END的相关性。结果共167例患者纳入本研究,其中END组40例,非END组127例,END发生率24.0%。单因素分析结果显示,END组患者的入院NIHSS评分、糖尿病、MPV以及WMH负荷程度均高于非END组,而血小板计数低于非END组(均P<0.05)。多因素Logistic回归分析显示,MPV和重度负荷WMH是PAD型脑梗死患者发生END的独立影响因素(OR值分别为1.460、2.549,95%CI值分别为1.066~2.000、1.161~5.595,P值分别为0.018、0.020)。受试者工作特征曲线显示,MPV水平及重度负荷WMH程度对PAD型脑梗死患者发生END均有预测价值,曲线下面积分别为0.704(95%CI:0.615~0.793,P=0.001)、0.616(95%CI:0.516~0.716,P=0.028)。结论MPV水平升高和重度负荷WMH是PAD型脑梗死患者发生END的独立影响因素,且MPV的预测价值较重度负荷WMH更高。

脑脊液特征指标辅助结核性脑膜炎快速筛查的效果评估

目的:探索利用若干脑脊液特征指标辅助提高敏感度,实现结核性脑膜炎(tuberculous meningitis,TBM)的快速筛查和早期治疗控制。方法:2011—2019年期间,依据纳入排除标准,从江苏省苏州市、四川省自贡市和贵州省贵阳市的结核病定点医疗机构收治的383例疑似TBM患者中,随机筛选100例临床诊断TBM患者,并按年龄、性别1∶1配对抽取100例非TBM患者,收集脑脊液白细胞计数、乳酸盐、蛋白总量、腺苷脱氨酶、葡萄糖等生化指标,并采用超高通量液相色谱法分离患者脑脊液代谢物,通过偏正交最小二乘判别法分析(OPLS-DA)筛选在不同类型患者中分布具有差异的生化和代谢物指标,通过机器学习构建决策树模型(boosted-CART),评估特征指标对于快速筛查各类型TBM患者的效果。结果:以P<0.05、OPLS-DA模型变量权重值>1和代谢物组间表达量差异倍数>1为标准,利用boosted-CART模型筛选脑脊液L-谷氨酰胺和葡萄糖水平作为特征指标,其cut-off值分别为607.06mmol/L(L-谷氨酰胺)和60.03mg/dl(葡萄糖)。上述两项指标联用,可将检出很可能和可能TBM患者的敏感度从66.7%(95%CI:24.1%~94.0%)提升至83.3%(95%CI:36.5%~99.1%),AUC值从0.667(95%CI:0.444~0.889)提升至0.708(95%CI:0.494~0.923),但效果不明显(Z=0.261,P>0.05)。结论:脑脊液L-谷氨酰胺和葡萄糖指标可提高TBM快速筛查的敏感度,利于TBM早诊早治和控制结核病传播。

神经元特异性烯醇化酶在宫内窘迫新生儿脑损伤早期的变化研究

目的:研究神经元特异性烯醇化酶(NSE)在宫内窘迫新生儿脑损伤早期的变化。方法:选取2015年1月—2018年7月广州市南方医科大学南方医院收治的62例宫内窘迫新生儿作为研究对象,依据出生第1天NSE水平是否>30.0μg/L分为低水平组与高水平组,各31例。两组均接受头颅MRI、NSE检查,比较不同时间点情况。结果:低水平组出生后1、4、7 d NSE水平低于高水平组,差异有统计学意义(P<0.05)。低水平组出生后7、14 d新生儿神经行为测定评分高于高水平组,差异有统计学意义(P<0.05)。低水平组头颅MRI检查异常信号阳性率低于高水平组,差异有统计学意义(P=0.019)。结论:早期NSE水平较高时,多数宫内窘迫新生儿脑损伤情况较为严重,提示NSE水平可为宫内窘迫新生儿脑损伤的早期诊断提供参考依据。

肺腺癌脑转移的诊疗进展

肺癌是目前已知发病率和病死率最高的恶性肿瘤,而肺癌脑转移是晚期肺腺癌患者中常见的致死性并发症,包括脑实质转移及脑膜转移两种方式。相对于脑实质转移,肺腺癌出现脑膜转移的发生率和临床诊断率都比较低,治疗手段相对受限,效果不佳,自然生存时间较短。单纯依据临床症状、影像学检查及脑脊液细胞学检查诊断,存在漏诊和误诊等情况,可延误患者治疗,而液体活检的出现可大幅提高其早期诊断率。外科手术、化疗、放疗、靶向治疗、抗血管生成治疗及免疫治疗等都可作为肺腺癌脑转移的治疗手段,但对于不同患者,如何选用适合且有效的治疗方案,至今尚无定论。因此,本文就肺腺癌脑转移的诊疗相关研究进展进行综述,以期为肺腺癌脑转移患者寻找最优治疗方案提供理论基础。

早期运动干预对脑缺血大鼠脑神经髓鞘的影响及机制研究

目的 探讨早期运动干预通过抑制内质网应激诱导的细胞凋亡对脑缺血大鼠脑神经髓鞘损伤的影响。方法 18只SD大鼠随机分为假手术(SHAM)组,大脑中动脉闭塞静息(MCAO-SED)组、大脑中动脉闭塞运动(MCAO-EX)组,每组6只。除SHAM组外,其他各组采用改进的Longa线栓塞法制备大脑中动脉闭塞模型。造模后MCAO-EX组大鼠置于跑步机上进行运动干预28 d。采用改良的神经功能缺损评分(mNSS)评估神经功能,MRI扫描(T2)检测脑梗死体积,免疫荧光染色检测髓磷脂碱性蛋白(MBP)表达,透射电子显微镜观察髓鞘的结构,Western blot法检测内质网应激相关蛋白表达,TUNEL染色检测细胞凋亡。结果 干预28 d后,同MCAO-SED组比,MCAO-EX组神经功能恢复良好,梗死体积减少,髓鞘完整性增加,MBP荧光强度表达增加,MBP的表达水平增加,同时转录激活因子6(ATF6)、磷酸化肌醇需求酶1(p-IRE1)、磷酸化蛋白激酶R样内质网激酶(p-PERK)、活化的胱天蛋白酶-3(cleaved caspase 3)蛋白的表达水平显著降低,细胞凋亡减少。结论 早期运动可抑制内质网应激诱导的细胞凋亡,促进脑神经髓鞘修复,减少梗死面积,改善神经功能。