Background Tert-butylhydroquinone (TBHQ) is a redox-active food antioxidant, but its relationship to neuroblastoma (NB) remains uncertain. We integrated network toxicology, disease transcriptomics, structural modeling, and clinical cohort analyses to prioritize testable TBHQ–NB hypotheses. Methods We intersected 119 TBHQ-related targets with 2,105 NB-associated genes. The 55 shared targets were filtered against 3,386 differentially expressed genes from MYCN-overexpressing NCSC-derived tumors versus control NCSCs in GSE137975. Candidates were evaluated by PPI topology, molecular docking, a 100-ns simulation of the selected ERBB2 chain-A pose, and SEQC survival, clinical-feature, correlation, module, and Hallmark GSEA analyses. Results GSE137975 contained 1,759 upregulated and 1,627 downregulated genes. Intersecting these genes with the 55 shared targets yielded 11 candidates. Docking scores were − 7.3 kcal/mol for ERBB2, − 6.7 for AR, − 5.1 for FOXO1, and − 4.5 for NQO1; ERBB2 had the most favorable score among the modeled systems under their respective settings. The chain-A simulation supported persistence of the selected ERBB2–TBHQ pose under the simulation conditions. In SEQC, ERBB2 showed unadjusted survival and clinical associations, whereas adjusted ERBB2 hazard ratios were not statistically significant; global proportional-hazards diagnostics for the adjusted models indicated non-proportionality, limiting time-constant interpretation. ERBB2-low tumors were enriched for MYC/E2F/G2M and oxidative-phosphorylation programs. Conclusions The integrated evidence prioritizes ERBB2 and related candidates for experimental follow-up, supports a hypothesis linking TBHQ-relevant molecular networks to NB states, and provides a computational framework for future testing. Direct target engagement, pathway effects, and disease phenotypes warrant experimental validation.

Objective: Glioblastoma (GBM) is a tumor derived from aberrant proliferation of glial cells in the brain. The GTEx database revealed that long non-coding RNA (lncRNA) linear amplification using nonlinear components (LINC)01094 was highly expressed in GBM samples. Herein, this study aims to investigate the mechanism of LINC01094 in GBM in depth.Methods: Quantitative real-time PCR (RT-qPCR) was used to evaluate the expression levels of LINC01094, signal transducer and activator of transcription 3 (STAT3), microRNA-545-3p (miR-545-3p), and ubiquitin-conjugating enzyme E2N (UBE2N) in GBM cells. The role of LINC01094 in GBM was investigated both in vitro and in vivo. The regulatory mechanism of LINC01094 was determined using chromatin immunoprecipitation (ChIP), RNA pull down, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter experiments.Results: LINC01094 is significantly up-regulated in GBM cell lines. Functionally, knockdown of LINC01094 hampers cell proliferation and tumor growth, while promoting cell apoptosis and enhancing cell radiosensitivity. Mechanistically, signal transducer and activator of transcription 3 (STAT3) enhances the transcription activity of LINC01094. LINC01094 regulates ubiquitinconjugating enzyme E2N (UBE2N) expression via sponging miR-545-3p, thus regulating cell proliferation, apoptosis and radiosensitivity in GBM.Conclusion: STAT3/LINC01094/miR-545-3p/UBE2N axis plays a novel role in modulating tumorigenesis and radiosensitivity in GBM, which may provide a potential target for GBM treatment.

The antisense transcript of SATB2 protein (SATB2-AS1) is a novel long non-coding RNA (lncRNA) which is involved in the development of colorectal cancer, breast cancer and hepatocellular carcinoma. In the present study, it was aimed to investigate the consequent situation of SATB2-AS1 in tissue and cell lines of glioma. The expression of SATB2-AS1 in glioma cases was analyzed in The Cancer Genome Atlas datasets. The glycolytic metabolism was determined in glioma cells by detection of extracellular glucose level, oxygen consumption rate and extracellular acidification rate. Cell Counting Kit-8 assay and flow cytometry were used to assess cell proliferation and apoptosis in glioma cells. The interaction between SATB2-AS1 and microRNA (miR)-671-5p was verified by bioinformatic analysis, reverse transcription-quantitative PCR, dual luciferase reporter assay and RNA immunoprecipitation assay. The expression levels of the downstream targets of SATB2-AS1 were studied by western blotting. Results demonstrated that SATB2-AS1 was a downregulated lncRNA in low grade glioma and glioblastoma. Gain-of-function assay demonstrated that SATB2-AS1 inhibited cell proliferation, and glycolytic metabolism, while induced cell apoptosis in glioma cells. SATB2-AS1 sponged and suppressed the expression of an oncogenic miRNA miR-671-5p. By regulation of miR-671-5p, SATB2-AS1 upregulated cerebellar degeneration related protein 1 (CDR1) and Visinin-like 1 (VSNL1) expression in glioma cells. miR-671-5p overexpression partially reversed the antitumor effect of SATB2-AS1 in glioma. In conclusion, the current study demonstrated that there was a downregulation of SATB2-AS1 in glioma, and SATB2-AS1 regulated miR-671-5p/CDR1 axis and miR-671-5p/VSNL1 axis in glioma.

目的 探讨颅内动脉瘤(ICA)与ABO血型之间的相关性.方法 回顾性分析706例颅内动脉瘤患者(动脉瘤组)和414例非颅内动脉瘤患者(对照组)的临床资料,包括年龄、性别、既往病史、个人史、脑血管影像学资料及ABO血型等.采用Logistic回归模型进行单因素及多因素分析.结果 动脉瘤组患者中血型为A型者213例(30.2％)、B型203例(28.8％)、AB型77例(10.9％)、O型213例(30.2％).对照组患者中血型为A型者139例(33.6％)、B型120例(29.0％)、AB型31例(7.5％)、O型124例(30.0％).两组患者间ABO血型分布的差异无统计学意义(P＞0.05).按A型与非A型、B型与非B型、AB型与非AB型和O型与非O型分析,两组患者间分布的差异均无统计学意义(均P＞0.05).按ABO血型将颅内动脉瘤患者分成A型、B型、AB型和O型4个组,4组患者颅内动脉瘤的位置、数量、大小、状态及Hunt-Hess分级之间的差异均无统计学意义(均P ＞0.05).多因素Logistic回归分析显示,将年龄、性别、高血压、吸烟等危险因素当作协变量进行校正后,B型、AB型和O型患者患颅内动脉瘤的风险与A型患者无明显差异(均P＞0.05);血型A、B、AB及O型与颅内动脉瘤的发生均无相关性(均P＞0.05).结论 ABO血型与颅内动脉瘤的发生无明显关系.

Glioma is a common intracranial tumor originated from neuroglia cell. Chrysophanol is an anthraquinone derivative proved to exert anticancer effects in various cancers. This paper investigated the effect and mechanism of chrysophanol in glioma. Glioma cell lines U251 and SHG-44 were adopted in the experiments. The cells were treated with chrysophanol at different concentrations (0, 10, 20 50, 100 and 200 μM) for 48 h in the study, and then processed with MitoTempo. Mitochondria and cytosol were isolated to investigate the role of mitochondria during chrysophanol functioning on glioma cells. Cell viability was detected through 3-(4,5-Dimethyl-2-Thiazolyl)-2,5-Diphenyl Tetrazolium Bromide (MTT) assay, and cell apoptosis, cell cycle as well as relative reactive oxygen species (ROS) were assessed by flow cytometry. Expressions of Cytosol Cyt C, cleaved caspase-3, cleaved caspase-9, Cyclin D1 and Cyclin E were evaluated by western blot. In U251 and SHG-44 cells, with chrysophanol concentration rising, cell viability, expressions of Cyclin D1 and Cyclin E were decreased while cell apoptosis, levels of cleaved caspase-3, cleaved caspase-9 and Cytosol Cyt C as well as ROS accumulation were increased with cell cycle arrested in G1 phase. Besides, chrysophanol promoted ROS accumulation, cell apoptosis and transfer of Cyt C from mitochondria to cytosol in cells while MitoTempo partly reversed the effect of chrysophanol. Chrysophanol promoted cell apoptosis via activating mitochondrial apoptosis pathway in glioma.

目的 探讨后颅窝手术后并发尿崩症的原因及诊治措施.方法 回顾性分析1例后颅窝术后并发尿崩症患者的临床资料,并复习相关文献.结果 通过检测患者术后第1～16 d的尿量、尿比重,并结合其临床症状和体征,诊断为尿崩症.经对症治疗后,患者的尿崩症好转.结论 后颅窝手术后并发尿崩症可能的原因是术后脑组织水肿、缺血、血管活性物质刺激,以及麻醉和手术后机体应激反应对抗利尿激素(ADH)产生与释放的暂时性抑制.垂体后叶素或醋酸去氨加压素片的对症治疗和电解质检测及补液是主要的治疗措施.

GOLPH3, an oncoprotein, plays crucial roles in tumor etiology. Compelling evidences have demonstrated that GOLPH3 contributes to regulate tumor cell growth, migration and invasion under normal nutrient condition. However, the oncogenic activity of GOLPH3 under serum starvation remains largely unknown. In this study, we reported that GOLPH3 depletion led to marked reduction in adhesion of glioma U251 cells, particularly under serum deprivation. We found that silencing of GOLPH3 expression reduced the protein amount of ITGB1 only in serum-free medium. Further insights into the mechanism between GOLPH3 and ITGB1, we applied proteasome or lysosome inhibitor to block the degradation of ITGB1, and identified GOLPH3 silencing can prompt ITGB1 lysosomal degradation under serum starvation. Finally, we found the reductions in glioma cell adhesion and ITGB1 protein amount could be rescued by ITGB1 overexpression. Taken together, these results show that GOLPH3 contributes to the adhesion of glioma cells by regulating the lysosomal degradation of ITGB1 under serum starvation.

目的 总结脑积水脑室-腹腔分流术(VPS)后脑室内出血(IVH)的处理经验.方法 回顾性分析2015年9月1日至2018年9月1日VPS治疗的266例脑积水的临床资料.结果 266例中,7例VPS后发生IVH.采用脑室外引流术治疗2例,分流管调整术治疗1例,腰大池引流术3例,尿激酶局部注射1例;治疗后脑室内积血清除,脑室腹腔分流管均通畅.结论 IVH是脑积水VPS后常见并发症,造成IVH的原因除病人本身因素以外,手术是重要因素之一.对于VPS后IVH,可根据术后病人情况,灵活选择治疗方式.

目的:探讨经额下入路嗅沟脑膜瘤的显微外科手术方法及临床效果.方法:对我科2015年7月至2017年12月收治的15例嗅沟脑膜瘤患者的临床症状、手术效果及术后随访进行回顾性分析.结果:15例中存在嗅觉障碍8例,癫痫3例,视神经损伤4例,头痛及头晕9例,精神障碍2例;手术根据Simpson分级,Ⅰ级11例,Ⅱ级4例;术后平均随访12.4月,1例考虑复发,其余未见肿瘤复发.结论:经额下入路是嗅沟脑膜瘤显微手术治疗的有效路径.

目的 探讨PBL联合微信教学法在颅脑外伤实习生带教中的效果.方法 将我科60名实习生作为研究对象,将其随机分为两组,每组各30名实习生.实验组采用PBL联合微信教学,对照组采用LBL教学.考核两组基础知识、病例分析能力,并通过问卷调查了解其对教学方法的满意度.结果 实验组在基础知识掌握、病例分析能力上均优于对照组,且实验组的教学方法满意度高于对照组,组间各数据比较,差异具有统计学意义(P<0.05).结论 PBL联合微信教学法效果及满意度均优于传统教学法.

目的:分析脑出血神经外科治疗临床教学方式.方法:此次研究的人员均为徐州医科大学附属医院2015年10月—2017年4月神经外科实习医师,例数为60名,对以上实习生进行脑出血神经外科治疗临床教学.结果:老师对实习医师的满意度高达100%,其动手实践、综合能力、团队能力等分值均较为理想.结论:在神经外科教学中,与脑出血临床实践相结合,可以有效提高实习生的临床操作熟练度,加深其对疾病知识的了解.

目的:探讨第四脑室内原发性中枢神经系统淋巴瘤的诊断、治疗及研究进展.方法:回顾一例第四脑室内原发性中枢神经系统淋巴瘤的临床资料及诊疗经过,并收集相关文献进行分析总结.结果:第四脑室内原发性中枢系统淋巴瘤缺乏特异性影像学诊断指标,需病理及免疫组化确诊,术后放化疗是延长患者寿命的有效方法.结论:第四脑室内原发性中枢神经系统淋巴瘤发病率低,但恶性程度高,病理诊断明确后及时放化疗可延长患者生存期.

目的 评价脑室外引流术治疗原发性脑室出血的疗效.方法 回顾性分析30例行脑室外引流术的原发性脑室出血患者的临床资料,观察患者术后引流管放置时间、术后血肿清除率、颅内感染发生率、死亡率、慢性脑积水情况及术后6个月日常生活能力.结果 患者术后引流管保留时间最短4 d,最长11 d,平均时间6.2 d;根据拔管前头颅CT和术前头颅CT评估脑室内积血清除率最低61.0％,最高100.0％,平均清除率为79.5％;发生颅内感染7例,颅内感染发生率为23.3％;住院期间死亡7例,死亡率为23.3％;拔管后放置腰大池引流10例,用于引流血性及感染性脑脊液;术后6个月日常生活能力:治愈出院23例,失访3例,随访20例,其中恢复良好、生活自理17例,中度残疾2例,术后颅内感染并脑积水至死亡1例.结论 脑室外引流术是治疗脑室出血的有效方法,脑室外引流术后给予尿激酶注射是引流脑室血肿、再通脑脊液循环通路、减少慢性脑积水发生的有效措施,术中及术后注意无菌操作是减少术后并发症的有效措施.

Νeuronal precursor cell expressed and developmentally downregulated protein (Nedd4-1) is an E3 ubiquitin ligase with critical roles in the pathogenesis of cancer. Herein, we demonstrated that Nedd4-1 protein was upregulated in glioma tissues vs. that in non-cancerous tissues by western blotting and immunohistochemistry. Scratch migration and Transwell chamber assays indicated that downregulation of Nedd4-1 significantly reduced the migration and invasion of the glioma cell lines U251 and U87. Conversely, overexpression of Nedd4-1 obviously enhanced the migratory and invasive capacities in both cell lines. To investigate the role of Nedd4-1 and the intracellular pathways involved, we performed pull-down and co-immunoprecipitation assays, and recognized that Nedd4-1, TNIK and Rap2a formed a complex. Moreover, Nedd4-1 selectively ubiquitinated its specific substrates, the wild-type Rap2a (WT-Rap2a) and dominant-active Rap2a (DA-Rap2a) rather than the dominant-negative Rap2a (DN-Rap2a) in the U251 cells. Subsequently, we demonstrated that Rap2a was robustly ubiquitinated by Nedd4-1 along with the K63-linked, but not the K48-linked ubiquitin chain, which significantly inhibited GTP-Rap2a activity by GST-RalGDS pull-down assay. To further verify whether the ubiquitination of Rap2a by Nedd4-1 regulated the migration and invasion of glioma cells, Nedd4-1, HA-tagged ubiquitin and its mutants as well as WT-Rap2a were co-transfected in the U251 and U87 cell lines. The results confirmed that Nedd4-1 inhibited GTP-Rap2a activity, and promoted the migration and invasion of glioma cells. In brief, our findings demonstrated the important role of Nedd4-1 in regulating the migration and invasion of glioma cells via the Nedd4-1/Rap2a pathway, which may qualify Nedd4-1 as a viable therapeutic target for glioma.

Calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP) was previously reported to promote the proliferation of glioma cells. However, the effect of CacyBP/SIP on apoptosis of glioma is poorly understood. Here, our study shows that CacyBP/SIP plays a role in inhibiting doxorubicin (DOX) induced apoptosis of glioma cells U251 and U87. Overexpression of CacyBP/SIP obviously suppressed the DOX-induced cell apoptosis. On the contrary, silencing of CacyBP/SIP significantly promoted it. Further investigation indicated that inhibition of apoptosis by CacyBP/SIP was relevant to its nuclear translocation in response to the DOX treatment. Importantly, we found that the level of p-ERK1/2 in nuclei was related to the nuclear accumulation of CacyBP/SIP. Finally, the role of CacyBP/SIP was confirmed in vivo in a mouse model with the cell line stably silencing CacyBP/SIP. Taken together, our results suggest that CacyBP/SIP plays an important role in inhibiting apoptosis of glioma cells which might be mediated by ERK1/2 signaling pathway, which will provide some guidance for the treatment of glioma.

The identification of genes involved in carcinogenesis and tumor progression is of great interest, since these genes might be possible as candidates for new tumor targeted therapy strategies. Our previous study shows that Golgi phosphoprotein 3 (GOLPH3) is involved in glioma cell migration and invasion, the critical characteristics of malignant gliomas. In this study, we explored the mechanism of GOLPH3 affecting cell migration and invasion and found that GOLPH3 promotes glioblastoma (GBM) cell migration and invasion via the mammalian target of rapamycin(mTOR)‐Y‐box binding protein‐1 (YB1) pathway in vitro. Both the protein levels of GOLPH3 and YB1 were up‐regulated in human glioma tissues and they exhibited direct correlation with each other. In addition, down‐regulation of GOLPH3 inhibited glioma cell migration and invasion, while over‐expression of GOLPH3 enhanced them. Meanwhile, GOLPH3 down‐regulation led to a significant decrease of YB1 level as well as mTOR activity, both required for glioma cell migration and invasion. On the contrary, YB1 level and mTOR activity increased after GOLPH3 over‐expression. YB1 down‐regulation or mTOR ATP site inhibitor INK128 treatment inhibited cell migration and invasion, similar to the effect of GOLPH3 down‐regulation. Furthermore, over‐expression of GOLPH3 induced glioma cell migration and invasion was blocked by INK128 and YB1 down‐regulation. Taken together, these results show that GOLPH3 promotes glioblastoma cell migration and invasion via the mTOR‐YB1pathway, indicating that GOLPH3‐mTOR‐YB1 pathway might be a new therapeutic target for glioma treatment. © 2014 Wiley Periodicals, Inc.

The Fyn related kinase (FRK) is a noteworthy member of the Src non-receptor tyrosine kinase family for its distinctive tumor suppressive function. Recently, we have shown that FRK plays a protective role against the progression of glioma by suppressing cell migration and invasion. However, it is unclear whether the cell growth of glioma is also regulated by FRK and by which mechanism FRK alters its specific biological functions. In the current study, we found that FRK over-expression significantly suppressed the proliferation of glioma cells. In contrast, FRK knockdown by siRNA promoted glioma cell growth. In addition, FRK over-expression caused G 1 phase arrest as well as apoptosis of glioma cells. Further investigation disclosed that FRK-induced G1 arrest was accompanied by down-regulation of hyperphosphorylated retinoblastoma protein (pRb), which led to the consequent suppression of E2F1. More importantly, we found that over-expression of FRK inhibited proper cyclin D1 accumulation in the nucleus of proliferating cells. Taken together, our results demonstrate a combined mechanism for the anti-proliferative effects of FRK by inhibiting cyclin D1 nucleus accumulation and pRb phosphorylation in glioma cells.

Glioblastoma is the most common and fatal human brain malignancy in adults with highly proliferative capacity. Despite advances in surgery and adjuvant therapy, the median survival of patients has changed little over recent decades. Identifying molecules critical for glioma development is significant for devising effective targeted therapy. We previously reported that Bex2, a member of the brain expressed X-linked gene family, promoted the progression of glioma by promoting cell proliferation. In the present study, we investigated the main mechanism of Bex2 promoting the proliferation of glioblastoma cells. We found that Bex2 downregulation inhibited glioma cell proliferation and the expression of NF-κB p65, but Bex2 overexpression promoted them. Similarly, the proliferation of glioma cells was inhibited by p65 downregulation but increased by p65 overexpression. In addition, Bex2 overexpression-induced cell proliferation was abolished by p65 downregulation. Furthermore, Bex2 with nuclear localization signal deleted no longer promoted p65 expression. In conclusion, this study demonstrates that Bex2 promotes proliferation of human glioblastoma cells via NF-κB signaling pathway and Bex2 nuclear location is critical for p65 expression.

目的 探讨神经内镜辅助显微手术治疗原发性三叉神经痛的实用性及其优势.方法 回顾性分析62例应用神经内镜辅助显微血管减压手术治疗三叉神经痛的患者的临床资料和疗效.手术方式为经枕下乙状窦后入路,并在垫入Teflon垫片前后均置入30.神经内镜进行多角度观察,主要目的是观察神经全程及其周围血管,判别责任血管,并观察确认垫片位置,协助垫片调整.结果 62例三叉神经痛患者术后59例疼痛消失,3例疼痛减轻,无一例发生颅内感染、出血等并发症.结论 应用神经内镜辅助显微手术治疗三叉神经痛可以消除桥小脑角区显微手术的外科解剖死角,有助于正确地判断责任血管以及置入Teflon垫片,避免遗漏责任血管,协助调整垫片位置,能提高手术的疗效.