Objective:To investigate the clinical significance of homeobox gene D3 ( HOXD3) expression in glioma and its biological functions. Methods:A total of 1001 patients with glioma collected from Chinese Glioma Genome Atlas (CGGA) and the Cancer Genome Atlas (TCGA) were chosen in our study; their clinical data and transcriptome data were retrospectively analyzed. One-way analysis of variance was used to evaluate the differences of HOXD3 expressions in different pathological grading of glioma. These patients were divided into HOXD3 low expression group and HOXD3 high expression group according to the average value of HOXD3 expression. Kaplan-Meier survival analysis was used to compare the differences in survival time between patients from the HOXD3 high-expression group and HOXD3 low-expression group. Univariate and multivariate Cox regression analyses were used to investigate the effect of HOXD3 on the prognoses of patients with glioma. Gene ontology (GO) analysis, Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) were used to investigate the biological function of HOXD3. Pearson correlation analysis was used to analyze the correlation between HOXD3 expression and expressions of other genes. Results:(1) The expression level of HOXD3 gradually increased with the increase of pathological grading of glioma (in the CGGA data, the expression levels in grading II, III and IV gliomas were 0.737±0.085, 1.323±0.125 and 1.652±0.083, respectively; in TCGA data, the expression levels in grading II, III and IV gliomas were 0.082±0.008, 0.177±0.014 and 0.259±0.016, respectively). The HOXD3 expression levels among different pathological grading of glioma were statistical different ( P<0.05). (2) As compared with that in the HOXD3 low-expression group, the survival time of patients in the HOXD3 high-expression group was significantly shorter ( P<0.05). CGGA data showed that the HOXD3 expression ( HR=1.348, 95%CI: 1.171-1.552, P=0.000), tumor grading ( HR=2.793, 95%CI: 1.981-3.936, P=0.000) and isocitrate dehydrogenase 1 ( IDH1) mutation status ( HR=0.689, 95%CI: 0.492-0.964, P=0.029) were independent influencing factors for prognoses of glioma patients. TCGA data showed that the HOXD3 expression ( HR=2.147, 95%CI: 1.252-3.681, P=0.005), age ( HR=1.036, 95%CI: 1.026-1.046, P=0.000), tumor grading ( HR=3.178, 95%CI: 2.299-4.392, P=0.000) and IDH1 mutation status ( HR=0.440, 95%CI: 0.317-0.613, P=0.000) were independent influencing factors for prognoses of glioma patients. (3) GO, KEGG and GSEA analyses showed that HOXD3 was closely related to the cell cycle; the HOXD3 expression was positively correlated with various cell cycle associated genes ( P<0.05). Conclusion:HOXD3 is an independent influencing factor for prognoses of glioma patients, whose biological function is related to the periodic regulation of glioma.

Objiective: To evaluate the prognosis of visual function and the impact of surgery in pediatric patients with sellar mass lesions, as evidenced by diffusion tensor imaging (DTI) and visual evoked potentials. Methods: Twenty patients with sellar mass lesions were included in the study. DTI and visual evoked potentials were obtained before and after surgery. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were calculated for both optic nerves. DTI parameters and visual evoked potential amplitudes were compared for all patients to assess the correlation between DTI parameters and visual function. Results: The 20 patients were divided into two groups according the relationship between the lesions and the optic chiasm. The FA values increased significantly after operation, while the ADC values decreased (P<0.05). And the average amplitude of visual evoked potentials after operation was significantly higher than before operation (P<0.05). Conclusions: DTI assessments of the affected sides, with the resulting FA and ADC values, may help to estimate the visual improvement produced by surgical therapy in the early postoperative period. Surgical removal can improve visual function dramatically.

Objective To assess visual impairment by MR diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in children with sellar tumors. Methods DTI and DTT imaging were performed, and the fractional anisotropy (FA) values of the bilateral optic nerves were calculated and statistically analyzed in 24 children with sellar tumors (including 12 optic chiasm gliomas, 7 sellar craniopharyngiomas, 2 teratomas in the third ventricles, 2 hypothalamic hamartomas, and 1 clivus chordoma. Results The optic chiasms were destroyed by the tumors in 12 children with sellar tumors and were compressed by the tumors in 12 children with sellar tumors according to the locations and shapes of the optic chiasms and their spatial relationships with the tumors. The FA values of the bilateral optic nerves were significantly lower in 12 children with destroyed optic chiasms than those in 12 children with the compressed optic chiasms (P<0.05). Conclusions DTI and DTT imaging examination can clearly show the spatial relationship between sellar tumors and visual nerve fiber bundles in children with sellar tumors. The obtained FA values can be used to evaluate the nature and degree of damage to the optic nerve and visual pathway by the tumors.

Objective To investigate the fornix of patients undergoing resection of third ventricle tumor through transcallosal interforniceal approach.Methods The clinical data of 5 patients with third ventricle tumor were retrospectively analyzed who were admitted to Department of Neurosurgery,Tsinghua University Yuquan Hospital from December 2015 to June 2016.All patients received operation through transcallosal interforniceal approach.DTI (diffusion tensor imaging) was performed before and after operation.The fractional anisotropy (FA),apparent diffusion coefficient (ADC) values and length of fornix were measured.Results Total resection was achieved in 5 cases.At 1 month post operation,the DTI functional analysis showed that the FA value of fornix decreased slightly in 3 patients,the ADC value decreased slightly in 1 patient and the length of fornix decreased in 4 patients,compared with those before operation.Those parameters returned to preoperative levels at 3 months after operation.Conclusions The effects of operation on fornix were slight and temporary.After proficient operation,there was no significant change in the value of FA,ADC or the length of the fornix.DTI could be an effective method to evaluate the safety of operation.

Objective To investigate changes of hippoeampus-related brain functions in children following resection of the third ventricle tumors through transcallosal intefforniceal approach.Methods Nine children with the third ventricle tumors were randomly selected at Department of Neurosurgery,Tsinghua University Yuquan Hospital.Resting state functional MRI (rs-fMRI) was scanned for all patients before and after operation.Multiple aspects,including regional homogeneity (ReHo),ALFF (amplitude of low frequency fluctuations),fALFF (fractional ALFF) and changes of function connectivity [DMN (default mode network) and hippocampus as ROI (region of interest)] were compared before pre-and post-operative states.Results (1) At 1 month post operation,the decreased ReHo was observed in the left superior frontal cortex,while the elevated ReHo was seen in the right middle occipital gyrus,middle temporal gyrus and left central gyrus compared with pre-operative conditions.The elevated ReHo was in the left superior temporal gyrus and right central frontal gyrus at 2 months post operation compared with that at 1 month after operation.There was no difference of ReHo between 2 months after operation and preoperative state.(2) At 1 month post operation,decreased ALFF was in occipital lobe,while increased ALFF was observed in regions around surgical pathway.ALFF restored to preoperative state at 3 months post operation.(3) Decreased fALFF was shown in frontal lobe and occipital lobe after operation.At 3 months post operation,the fALFF restored to preoperative state.(4) The contact between bilateral frontal gyri and other brain areas was elevated at 1 month post operation and recovered to preoperative state at 3 months.Surgery had an effect on the connections between hippocampus and the whole brain.Conclusions The short-term effect of transcallosal interforniceal operations on ReHo,ALFF and fALFF in the brain regions of patients could recover to preoperative state with time.The operation may not interrupt the connections between DMN and hippocampus-related brain areas.

Objective To conduct the comparative observational study of serum neoplastic biomarker and immunohistochemistry in intracranial getm cell tumors (GCTs).Methods A retrospective study was conducted on clinical data of 28 cases of germ cell tumors undergoing surgery from March 2013 to July 2016 at Tsinghua University Yuquan Hospital.Presurgical serum neoplastic biomarkers including α-fetoprotein (AFP),β-human chorionic gonadotropin (β-HCG) and alkaline phosphatase (ALP) were measured and compared with postsurgical immunohistochemistry results of tumor specimens.Results Among the 28 cases of GCTs,germinoma was identified in 5 cases,teratoma in 2 cases,immature teratoma in 5 cases,choriocarcinoma in 1 case and mixed germ cell tumor in 15 cases.AFP was inconsisent in 8/28 cases,being positive in serum biomarker and negative in immunohistochemistry,and included 4 cases of immature teratoma and 4 mixed GCTs.β-HCG was incongruent in 5 cases (positive in serum and negative in immunohistochemistry).Among the 18 cases with pure germinoma component,placenta ALP (PLAP) immunohistochemistry revealed positive results in 15 cases,while serum ALP was significantly increased in only 4 cases and not detected in the remaining 14 cases.Conclusions The treatment and prognosis of intracranial GCTs might be correlated with different neoplastic components.Immunohistochemistry combined with serum biomarker could help demonstrate those neoplastic components more accurately and completely.

Objective To evaluate the effectiveness and safety of immunosuppressive therapy in neuromyelitis optica spectrum disorder (NMOSD) during pregnancy. Methods Sixteen NMOSD patients who had at least one pregnancy after NMOSD onset were enrolled. The patients were divided into two groups according to whether they received immunosuppressive therapy during pregnancy. The annual relapse rate (ARR) before pregnancy (BP); during the first (DP1), second (DP2), and third trimesters (DP3); first trimester postpartum (PP1); and second trimester postpartum (PP2) were calculated. The Expanded Disability Status Scale (EDSS) was used to evaluate the degree of disability. Pregnancy outcomes were recorded and the children were followed up and their health condition was evaluated. Results In the group taking prednisone alone or in combination with azathioprine as immunosuppressive therapies, there was no difference among ARRs of each period (DP1, DP2, DP3, PP1, PP2) and BP. Compared with EDSS BP, EDSS increased slightly 6months postpartum with no statistical significance (p=0.102). In the group without immunosuppressive therapy, ARR increased during PP1 (p=0.014) and EDSS increased 6months postpartum as compared to BP (p=0.017). Moreover, the added EDSS value was higher in the group without immunosuppressive therapy than in the group with therapy (p=0.038). In 22 pregnancies from 16 patients, 16 pregnancies ended in live births and 6 pregnancies ended in abortions, including 2 spontaneous and 4 induced abortions. None of the children had congenital diseases or malformations. There were no records of abnormal growth among the children during 6months to 12years of follow-up. Conclusion Untreated women showed a propensity for disease relapse in PP1 and increased degree of disability postpartum. Immunosuppressive therapy during pregnancy and postpartum period can reduce the risk of relapse and degree of disability. Immunosuppressive therapy with low-dose prednisone was relatively safe. However, the safety of azathioprine during pregnancy remains unclear and needs future reevaluation.

Objective To explore the application value of intraoperative neurophysiological monitoring in the surgery of spinal cord untethering.Methods A total of 35 patients with tethered cord syndrome admitted to Department of Neurosurgery,Yuquan Hospital,Tsinghua University from June 2014 to December 2016 were electrophysiologically monitored in terms of somatosensory evoked potentials (SEP) and electromyogram(EMG) during operation.The Hoffman scale was adopted to evaluate nerve function in all patients.The changes of electrophysiological parameters and the nerve functions were analyzed.The relationship between SEP monitoring results and Hoffman scale was investigated.Results Among 35 patients,the cortical potential P40 was recorded in 29 cases.There were continuous bursts of large myoelectric response in 21 patients during operation.All patients underwent nerve root stimulation to identify the cauda equina and iilum terminale,the latter were then cut.The follow-up period lasted 6-13 months with an average of 9.4 ± 5.8 months.Significant improvement of neurological function was reported in 8 patients,fair improvement in 18,and no improvement in 9 cases.Comparative analysis showed that in the patients with significant improvement,postoperative amplitude and latency were significant different from preoperative results (both P ＜ 0.05).In the patients with fair improvement,the latency rather than amplitude was significantly different (P ＜ 0.05) comparing pre-and postoperative data.In the patients with no change,there was no significant difference in the latency or amplitude post operation (both P ＞ 0.05).Conclusion Employed in the surgery of spinal cord untethering in children,intraoperative electrophysiological monitoring could effectively help avoid nerve damage,reduce the occurrence of postoperative complications,and improve the clinical outcomes.

Objective To analyze the treatment effects of intracranial germ cell tumors (ICGCTs) using microsurgery.Methods A retrospective study was conducted on the data of 32 cases of ICGCT who were admitted to Yuquan Hospital of Tsinghua University from October 2012 to June 2016.Among them,there were 6 cases of germinoma,14 cases of mixed ICGCT,4 cases of mature teratoma,6 cases of immature teratoma,1 case of malignant teratoma and 1 case of choriocarcinoma.Preoperative chemotherapy was performed in 4 cases.Postoperatively,16 cases received chemotherapy,3 cases underwent local radiotherapy,and 2 cases underwent chemotherapy plus local radiotherapy.The surgical outcomes were followed up.Results For the 32 cases,the average follow-up period was (21.8 ±13.5) months.The gross total resection (GTR) group included 17 cases (53.1％) and the remaining 15 cases (46.9％) did not receive GTR.Out of the 12 patients of tumor recurrence,3 cases (25.0％) belonged to the GTR group and the other 9 cases (75.0％) were in the non-GTR group.The recurrence rates in the two groups (3/17 vs.9/15) were significantly different (P ＜0.05).Pathological results indicated that the "teratoma" components were contained in 22 cases,accounting for 66.8％ of all cases in this study and 84.6％ of non-germinoma of germ cell tumors (NGGCTs).In 2 cases of tumor recurrence,their pathological results were inconsistent with the original features.No severe surgical complications were observed.By the end of follow-up,6 patients (18.8％) died,among whom 5 did not receive postoperative chemoradiotherapy and died from tumor recurrence.Conclusions Microsurgery seems to be one important approach in treatment of ICGCTs,particularly NGGCTs.Patients might benefit from the GTR of the lesions.Individualized radiation and chemotherapy before and after surgery could help reduce the tumor recurrence.

Objective: To study intracranial mixed germ cell tumor diagnosis and reasonable treatment strategy. Methods: Clinical data of 17 patients with intracranial mixed germ cell tumor in Tsinghua university Yuquan hospital from October 2012 to October 2016 were retrospective analysed, including the characteristics of the general, the serum tumor markers of AFP, β-HCG, and CEA, imaging findings, pathological results, treatment methods and prognosis. Results: There were 10 cases of male, 7 cases of female. The average age was (11.1±5.2) years old. Nine cases were gross total resection of lesions and 8 cases were subtotal resection of lesions. Eight cases (47.1%) were without recurrence and had more than four courses of chemotherapy after surgery, of which, 7 cases belonged to the gross total resection, and 1 case belonged to the subtotal resection. Nine (52.9%) patients relapsed, including 2 cases of the gross total resection and 7 cases of the subtotal resection. Among them, 4 cases were given second operations and 6 cases obtained satisfactory therapeutic effect by chemotherapy combined radiotherapy. There were 12 of 17 patients with pathological types contain teratoma (including mature, immature or malignant teratoma) ingredients, accounting for 70.6%. The average follow-up time was (17.5±12.1) months, 4 cases (23.5%) patients died. Conclusion: The diagnosis of intracranial mixed germ cell tumors needs comprehensive consideration of tumor markers in serum or cerebrospinal fluid, chemotherapy and radiotherapy before operation and pathological results. The gross total resection helps to reduce the chances of tumor recurrence. Rational chemotherapy and radiotherapy is helpful to prognosis.

Objective The authors report an extremely unusual presentation and management of a children pineal mixed germ cell tumor mainly composed of immature teratoma, aiming to summarize main theraptic points by literature review. Methods A cystic lesion located in the rear of third ventricle in a child was detected 3 years ago with no other therapy performed except for a ventriculo-peritoneal shunt. During the following 3 years, intermitted regular brain MRI demonstrated no evidence of lesion aggrandizement. However from 20 days before admission to our institute the patient began to present acutely with exacerbating clinical symptoms meanwhile brain MRI showed signs of abrupt revulsions of initial lesion without any incentive cause. Neurological examination revealed a significant rising of serum tumor marker level. Then surgical resection was performed immediately after admission which was followed by correlative two-course chemotherapy. Results Postoperative brain MRI demonstrated totally removing of the lesion in rear of third ventricle. Serum tumor marker level decreased remarkably after surgery and declined to normal level after two-course chemotherapy. No obvious neurological deficit occurred except for short-term memory difficulty which gradually recovered within two weeks. Soon after the second course chemotherapy the patient was currently asymptomatic and returned to school. Conclusions (1) To ensure definitive diagnosis and proper therapecutic protocols benefit from grasping clinical features of mixed germ cell tumor. (2) Overall preoperative investigation including serum tumor marker level is as critical as neurological imaging examination. (3) Surgical excision is confirmed to be the key modality of treatment. With the regarding of mixed germ cell tumor, never highlight total resection too much. (4) Postoperative adjuvant chemotherapy is recommended as further intensive treatment to improve the prognosis of mix germ cell tumor.

Objective To evaluate the clinical results of repairing skull defects with biomimetic bone (nano-hap/collagen composites, NHACs) in children. Methods Thirteen children with skull defects were treated with NHACs in our hospital. The NHACs molded with the help of a 3D printer were used in the operations. Results All 13 operations were successful, and patients recovered without infection. Only one patient suffered from subcutaneous hydrops post-operation. The implanted NHACs remained fixed well after 1 year, and their CT HU values raised gradually. Skull shapes of children developed normally. Recovery of neurological and cognitive function was significant. Conclusions NHAC, chosen to repair skull defects in children, can coexist with normal skull and reduce the negative effects on growth and development. NHAC could be a good choice for children with skull defects.

Objective To observe the fusion state of autologous skull in the decompression and bone grafting for occipitocervical fusion,in order to give experimental evidence for the clinical operation by planting occipital bone and the term of bone healing.Methods Establishing the rabbits decompression model and then taking a piece of frontoparietale to fix it from posterior occiput to C2 spinous.Taking orthophoric and lateral position DR photos on 8 、10、12 weeks after operation,observeing the planting bone by the second operation after 12 weeks.Results Among the ten rabbits,one case obtained bone absorption,one case obtained bone exodus because of infection,the others obtained bone healing.The healing rate was 80%.Conclusion Skull grafting can obtain bone healing in 12 weeks,this experiment can supply some experimental evidences for clinical occipital bone planting.