Objective To detect the expression of bone morphogenetic protein receptor Ⅱ ( BMPR Ⅱ ) in human focal cortical dysplasia ( FCD Ⅱ b). Methods Fourteen specimens of FCD Ⅱ b surgically removed and pathologically verified were collected from June 2008 to June 2010 and the expression of BMPR Ⅱ in the normal brain tissues and the pathological specimens was detected by means of immunohistochemistry and western blot. Results In the normal brain tissues, BMPR Ⅱ was widely expressed in the cortical neurons of the grey matter, with no positive immunostaining in the white matter. In the cortical lesion of FCD Ⅱ b, BMPR Ⅱ was strongly expressed in the misshapen cells including balloon cells (BCs) , dysmorphic neurons (DNs) and giant neurons (GNs). Positive BMPR Ⅱ expression was also observed in the reactive astroeytes and low level expression of BMPR Ⅱ was found in the normal-appearing (NA) neurons. Western-blot analysis showed that BMPR Ⅱ expression tended to be lowered in the FCD Ⅱ b specimens compared with the normal brain tissues ( P < 0. 05 ). Conclusion The expression of BMPR Ⅱ is altered and reduced in the FCD Ⅱ b, suggesting that BMP signal pathway may participate in the pathogenesis of FCD.

Objective To investigate the protective effect of inhibition of adenosine monophosphate activated protein kinase (AMPK) on blood brain barrier (BBB) and its mechanism in hypoxic/ischemic models.Methods Two hundred healthy male SD rats were randomly divided into sham-operated group,model group (ischemia 2 h-reperfusion 0,24 and 72 h [I/R]),and Compound C treated group (giving intraperitoneal injection of 20 mg/kg AMPK specific inhibitor Compound C).Focal cerebral ischemia rat models were established by occluding the middle cerebral artery (MCAO).Neurological deficit was determined by Zea Longa test,infarct size and brain water content were measured by TTC staining,leakage of BBB was determined by Evans blue (EB) staining.Expressions of matrix metalloproteinase (MMP)-2/MMP-9 and nuclear factor (NF)-κB,and release of inflammatory factors were detected by Western blotting.Results As compared with those in the model group,significantly reduced neurological deficit scores in Compound C treated group were noted at I/R 0,24 and 72 h (P＜0.05).After I/R 72 h,Compound C treated group had significantly reduced brain infarct size,brain water content and EB leakage as compared with model group (P＜0.05).The expressions of MMP2/MMP9 in model group (52.58±8.12 and 33.15±6.45) were significantly higher than those in the Compound C treated group (21.20±3.39 and 15.46±4.71,P＜0.05).What is more,as compared with the model group,Compound C treated group had significantly reduced expressions of NF-κB and inflammatory factors (P＜0.05).Conclusions Inhibition of AMPK shows a protective role in BBB after ischemic injury,mainly by inhibiting NF-κB signaling pathway,inhibiting the expression of MMP-2/MMP-9 to reduce the degradation of the base metal film,and maintain the integrity of BBB,thus,improving the ischemic symptoms,reducing the brain water content and reducing infarct size.

OBJECTIVETo investigate the capable use of transmaxillary approach for surgical removal of invasive skull base tumors, the indications and the key points of this approach.

METHODSFrom November 1998 to July 2001, 27 consecutive patients with skull base tumor were operated through transmaxillary approach, including 6 patients with nasopharyngeal carcinoma, 5 with nasopharyngeal angiofibroma, 5 with nasopharyngeal cystadenocarcinoma, 2 with olfactory neuroblastoma, 2 with poorly differentiated carcinoma, 2 with sarcoma, 1 with maxillary carcinoma, 2 with schwannoma, and 2 with chordoma. Most of them (18/27) were recurrent tumor and 17/27 tumors involved important intracranial structures. All patients were followed up 2 - 33 months (average 16 months) and the clinical data was reviewed.

RESULTSThe tumors could be totally removed in all patients. There were no operative mortality and morbidity. After operation, 2 patients died of cancer recurrence in 5 and 8 months separately. One patient had metastasis to the lungs 11 months after operation. Two patients had local recurrence in 7 and 12 months postoperation seperately and live with the tumor now. The rest patients are back to their routine life.

CONCLUSIONSTransmaxillary approach facilitates the surgical removal of invasive skull base tumors. The exposure is wide. The lesion as well as the important anatomy structures can be viewed directly and clearly. The tumor removal could be done more thoroughly and safely. This approach is suitable for the patients in whom tumor involves the skull base extensively and may be difficult to deal with by other approaches.

Adolescent ; Adult ; Aged ; Child ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; mortality ; pathology ; surgery ; Neoplasm Invasiveness ; Neurosurgical Procedures ; Skull Base Neoplasms ; mortality ; pathology ; surgery

OBJECTIVE: To analyze the pathogenic variants of the KIF1A gene and its corresponding protein structure in an autism spectrum disorder (ASD) family trio carrying harmful missense variants in the KIF1A gene. METHODS: The peripheral blood DNA of the patient and his parents was extracted and sequenced using whole exome sequencing (WES) technology and verified by Sanger sequencing. Bioinformatics software SIFT, PolyPhen-2, Mutation Taster, and CADD software were used to analyze the harmfulness and conservation of variants. The Human Brain Transcriptome (HBT) database was used to analyze the expression of the KIF1A gene in the brain. PredictProtein and SWISS-MODEL were further used to predict the secondary structure and tertiary structure of KIF1A wild-type protein and variant protein. PyMOL V2.4 was utilized to investigate the change of hydrogen bond connection after protein variant. RESULTS: The WES sequencing revealed a missense variant c.664A>C (p.Asn222His) in the child's KIF1A gene, and this variant was a de novo variant. The harmfulness prediction results suggest that this variant is harmful. By analyzing expression level of KIF1A gene in the brain. It is found that KIF1A gene widely expressed in various brain regions during embryonic development. By analyzing the variant protein structure, the missense variant of KIF1A will cause many changes in the secondary structure of protein, such as alpha-helix, beta-strand, and protein binding domain. The connection of hydrogen bond and spatial structure will also change, thereby changing the original biological function. CONCLUSION The KIF1A gene may be a risk gene for ASD.
Autism Spectrum Disorder/genetics* ; Child ; Female ; Humans ; Kinesin/genetics* ; Mutation ; Mutation, Missense ; Pregnancy ; Protein Domains ; Whole Exome Sequencing

OBJECTIVE: To carry out genetic testing for a patient with 45,X/46,XY mosaicism and autism spectrum disorder (ASD). METHODS: Peripheral blood samples of the patient and his parents were collected for the extraction of genomic DNA. Trio-based whole exome sequencing and Sanger sequencing were carried out thereafter. RESULTS: The proband and his father were found to harbor a heterozygous c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene. In addition, the proband was also found to harbor a de novo c.268C>T (p.Arg90Trp) missense variant of the MTRR gene. Based on guidelines of the American College of Medical Genetics and Genomics (ACMG), the c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene was predicted to be pathogenic (PVS1, PM1, PM2, PP3), while the c.268C>T (p.Arg90Trp) variant of the MTRR gene was predicted to be of uncertain significance. CONCLUSION Variants of the CACNA1I and MTRR genes, together with the chromosomal mosaicism, may have predisposed to the susceptibility to the ASD in this patient.
Autism Spectrum Disorder/genetics* ; Genomics ; Heterozygote ; Humans ; Mosaicism ; Whole Exome Sequencing

Objective:To investigate the characteristics and change trends of electroencephalogram (EEG) in patients with drug resistant epilepsy (DRE) after vagus nerve stimulation (VNS).Methods:Twenty-five patients with DRE, admitted to our hospital from July 2016 to May 2019, were chosen; all patients accepted VNS and followed up for 12 months. Long range video EEG (VEEG) monitoring was performed before VNS, and 3, 6 and 12 months after VNS, and the tracing time of each monitoring was longer than 12 h. The EEG characteristics of these patients before and different times after VNS were analyzed.Results:In the VEEG monitoring before VNS, 25 patients showed sharp wave, spike wave, sharp slow wave, and compound spike slow wave in the interictal period; 3 patients (12%) could locate the brain region. The interictal EEG of 11 patients 3 months after VNS showed different degrees of improvement as compared with the preoperative one, which manifested as mixed rhythms: mono-spiking as sharp wave, sharp slow wave or spike wave; 8 patients had McHugh grading I-II. The interictal EEG of 18 patients 6 months after VNS showed different degrees of improvement as compared with the preoperative one; 11 patients had McHugh grading I-II. The interictal EEG of 21 patients 12 months after VNS showed different degrees of improvement as compared with the preoperative one; 15 patients had McHugh grading I-II.Conclusion:The EEG improvement effect of DRE patients after VNS is gradually improved with time; in some patients, the EEG improvement is earlier than improvement of clinical symptoms.

Objective:To investigate the characteristics and change trends of electroencephalogram (EEG) in patients with drug resistant epilepsy (DRE) after vagus nerve stimulation (VNS).Methods:Twenty-five patients with DRE, admitted to our hospital from July 2016 to May 2019, were chosen; all patients accepted VNS and followed up for 12 months. Long range video EEG (VEEG) monitoring was performed before VNS, and 3, 6 and 12 months after VNS, and the tracing time of each monitoring was longer than 12 h. The EEG characteristics of these patients before and different times after VNS were analyzed.Results:In the VEEG monitoring before VNS, 25 patients showed sharp wave, spike wave, sharp slow wave, and compound spike slow wave in the interictal period; 3 patients (12%) could locate the brain region. The interictal EEG of 11 patients 3 months after VNS showed different degrees of improvement as compared with the preoperative one, which manifested as mixed rhythms: mono-spiking as sharp wave, sharp slow wave or spike wave; 8 patients had McHugh grading I-II. The interictal EEG of 18 patients 6 months after VNS showed different degrees of improvement as compared with the preoperative one; 11 patients had McHugh grading I-II. The interictal EEG of 21 patients 12 months after VNS showed different degrees of improvement as compared with the preoperative one; 15 patients had McHugh grading I-II.Conclusion:The EEG improvement effect of DRE patients after VNS is gradually improved with time; in some patients, the EEG improvement is earlier than improvement of clinical symptoms.

Objective:To explore the clinical application values of radiofrequency thermocoagulation (RF-TC) based on stereotactic electroencephalogram (SEEG) high-frequency oscillations (HFOs) analysis in patients with refractory epilepsy.Methods:Fourteen patients with refractory epilepsy treated with SEEG-guided RF-TC were selected from Department of Neurosurgery, PLA Western Theater Command General Hospital from August 2019 to December 2021. Automatic detection algorithm of Matlab was used to calculate the HFOs incidence in each montage, and the fitting curves of HFOs incidences were used to formulate the threshold of HFOs and delimit the HFOs regions (ripples and fast ripples). These patients were divided into non-seizure group and seizure group according to the prognoses 3 and 6 months after RF-TC. At the last follow-up, these patients were divided into good prognosis group and poor prognosis group according to Engel grading; the differences of ripple thermocoagulation rate and fast ripple thermocoagulation rate between the 2 groups were compared.Results:A total of 7,332 ripples and 1,144 fast ripples were detected in SEEG data from 14 patients. Six months after surgery, neurological dysfunction incidence was 14.3%, without permanent neurological dysfunction, intracranial infection, intracranial hemorrhage, or electrode equipment failure. Within 3 months of RF-TC, seizure-free rate was 71.4% (10/14), and fast ripple thermocoagulation rate in non-seizure group was significantly higher than that in seizure group ( P<0.05); within 6 months of RF-TC, seizure-free rate was 57.1% (8/14), and ripple thermocoagulation rate in non-seizure group was significantly higher than that in seizure group ( P<0.05). At last follow-up, 6 patients had good prognosis and 8 patients had poor prognosis; the ripple thermocoagulation rate in good prognosis group was significantly higher than that in poor prognosis ( P<0.05). Conclusions:HFOs can assist in designating epileptogenic regions. Patients with wider range of thermocoagulation ripples or fast ripples will have better short-term efficacy; patients with wider range ofthermocoagulation ripples will have better prognosis.

In order to search for new anti-inflammatory agents with strong activity and less toxicity relative to CDDO-Me, the ester prodrugs 2-8 of CDDO-Me were synthesized by treatment of oleanolic acid(OA)with DMF/K2CO3 to generate 1, followed by esterification of 1 with various aliphatic and aromatic carboxylic acids, respectively. All the target compounds showed strong inhibitory effects on LPS-induced NO production in RAW 264. 7 cells. Among them, compounds 2 and 7 possessed the most potent inhibitory effects with IC50=(2. 34±0. 67)and(3. 83±0. 97)nmol/L, respectively. Moreover, MTT assay indicated that all the target compounds(2-8)displayed much weaker anti-proliferative activity against RAW 264. 7 cell lines than CDDO-Me, suggesting that they may be less toxic than CDDO-Me.

The myelin-associated protein Nogo-A was considered to be the axon growth inhibitory factor, which participates in a variety of pathophysiological regulation of nervous system. In recent years, a growing number of studies have shown that Nogo-A protein is closely related to epilepsy by regulating dendritic plasticity, mediating abnormal nerve migration and regulating glial cell activation, etc. This article will review the research progress of Nogo-A in epilepsy in recent years.