目的 探讨环氧化酶 2(COX-2)和前列腺素 2(PGE2)在无功能性垂体腺瘤(NFPA)患者中的表达及与肿瘤侵袭性的关系.方法 选取 2021 年 1 月—2022 年 8 月于徐州医科大学附属医院和徐州市中心医院行经蝶垂体肿瘤切除术的患者共 82 例.根据垂体瘤有无侵袭性,将上述患者分为侵袭性NFPA组和非侵袭性NFPA组.收集患者血清及其垂体肿瘤组织,进行相关实验室检查、血清及肿瘤组织匀浆COX-2、PGE2 水平测定.结果 单因素分析显示,侵袭性NFPA组血清 COX-2、PGE2 均显著高于非侵袭性 NFPA组(P<0.05).多因素Logistic回归分析显示,肿瘤直径、血清COX-2 和血清PGE2 是NFPA发生浸润侵袭的独立危险因素(P<0.05).血清COX-2、PGE2 均与垂体肿瘤组织匀浆COX-2、PGE2 水平呈正相关(P<0.05).ROC曲线显示,血清COX-2、PGE2 以及二者联合诊断NFPA侵袭性的AUC分别为 0.804、0.802、0.830(P均<0.05).此外,NFPA患者血清COX-2、PGE2 均与肿瘤直径、Hardy-Wilson分级和分期、Knosp分级、Ki-67 指数呈正相关(P<0.05).结论 NFPA患者血清COX-2、PGE2 水平与其肿瘤侵袭性密切相关,血清COX-2 联合PGE2 水平升高可作为评价NF-PA侵袭性的有效指标.

目的 分析治疗高血压脑出血(HICH)采用去骨瓣减压术式与术后硬膜下积液的关系.方法 HICH患者124例分为行额颞顶部标准大骨瓣的去骨瓣减压术46例(A组)和额颞顶部马蹄瓣的去骨瓣减压术78例(B组),比较两组术后硬膜下积液发生率,分析HICH患者骨窗面积、骨窗最高水平面至头顶水平面的距离、骨窗最低水平面至中颅底的距离与硬膜下积液的关系.结果 A组术后硬膜下积液发生率高于B组(P＜0.01).HICH患者术后硬膜下积液发生比例随骨窗面积增大而增高(P＜0.01),骨窗最高水平面至头顶水平面的距离越大,则术后硬膜下积液发生比例越低(P＜0.01),骨窗最低水平面至中颅底的距离越小,则术后硬膜下积液发生比例越高(P＜0.05).结论 需在有效减压的基础上,合理设计去除的骨瓣相对位置并缩小其面积,从而更好预防HICH患者术后硬膜下积液发生.

Background AdipoR2, which belongs to the seven-transmembrane-domain receptor family, has been shown to play an important role in the development of human tumours, but the underlying mechanisms are poorly understood. In this study, we found that AdipoR2 expression correlates with glioma grade. In addition, we also investigated the mechanisms behind the antiproliferative effects of AdipoR2 in U251 cells (a human glioma cell line) using colony formation and WST-8 growth assays. Methods The U251 cell line was cultured in vitro. Western blotting was used to detect the expression of relevant proteins. Quantitative RT-PCR was used to detect AdipoR1 and AdipoR2 expression. Flow cytometry was used to detect cell cycle assay results. The gene expression profiles of glioma samples from the CGGA database were analysed by MATLAB and GSEA software. Results The AMPK/mTOR pathway plays a central role in the regulation of cell proliferation, differentiation and migration and may promote tumorigenesis. Therefore, we can control cancer progression by modulating the AMPK/mTOR pathway. However, there is no information on the relationship between AdipoR and AMPK/mTOR in central nervous system tumours such as GBM. In this study. We found 648 upregulated genes and 436 downregulated genes correlated with AdipoR2 expression in 158 glioma samples. GSEA suggested that AdipoR2 is a cell cycle-associated gene. The results of the flow cytometry analysis indicated that AdipoR2 induced G0/G1 cell cycle arrest in U251 cells. Furthermore, we identified the AMPK/mTOR signalling axis to be involved in AdipoR2-induced cell cycle arrest. Conclusions Our results suggest that AdipoR2 may represent a novel endogenous negative regulator of GBM cell proliferation. These findings also suggest that AdipoR2 may be a promising therapeutic target in GBM patients.

目的 探究显微镜外科手术在窦旁脑膜瘤患者中的应用价值.方法 选择收治的窦旁脑膜瘤患者42例,将患者进行随机分组,对照组给予常规手术治疗,研究组给予显微外科手术治疗,比较两组患者的手术时间、术中出血量、住院时间、治疗有效率和肿瘤全切率.结果 治疗有效率高于对照组,肿瘤全切率高于对照组.结论 显微外科手术用于窦旁脑膜瘤患者中能够缩短手术时间,减少术中出血,增加治疗有效率,提升肿瘤全切率,促进患者术后恢复,推荐临床应用.

Glioblastoma (GBM) cells with stem cell-like properties are called glioma stem cells (GSCs). GSCs display highly treatment resistance and are responsible for tumor recurrence. Napabucasin (BBI608), a novel small molecule inhibitor of STAT3, has been identified to eliminate stemness-like tumor cells in some cancers. However, the influence of Napabucasin on GBM cells, especially on GSCs, is currently unclear. In this study, we explored the influence and underlying mechanisms of Napabucasin on GBM cells. STAT3 expression and its correlation with the glioma grade and patient survival were analyzed using CGGA and TCGA glioma databases. The influence of Napabucasin on proliferation, stemness, the cell cycle, apoptosis, and invasion of human GBM cell lines U87MG and LN229 was tested by CCK8, EdU incorporation, colony formation, Transwell invasion, and three-dimensional spheroid assays as well as flow cytometry, qPCR, and western blot analysis. The ability of Napabucasin to inhibit cell proliferation of U87MG tumor xenografts in mice was assessed using a live animal bioluminescence imaging system and immunohistochemistry. Napabucasin suppressed the proliferation, colony formation, and invasion of U87MG and LN229 cells. Furthermore, Napabucasin induced cell cycle arrest and apoptosis. More importantly, Napabucasin treatment obviously inhibited expression of stemness-associated genes including STAT3 and suppressed the spheroid formation of glioma cells in vitro. Napabucasin also disrupted the NF-κB signaling pathway via downregulation of RelA (p65). Finally, glioma growth was effectively impaired by Napabucasin in nude mice bearing intracranial glioma xenografts. Napabucasin treatment may be a novel approach for the treatment of GBM, particularly GSCs.

Peroxisome proliferator-activated receptor α (PPARα) is a member of the nuclear hormone receptor superfamily and functions as a transcription factor. Previous work showed that PPARα plays multiple roles in lipid metabolism in tissues such as cardiac and skeletal muscle, liver, and adipose tissue. Recent studies have discovered additional roles for PPARα in cell proliferation and metabolism, as well as tumor progression. PPARα is aberrantly expressed in various cancers, and activated PPARα inhibits the proliferation of some tumor cells. However, there have been no studies of PPARα in human gliomas. Here, we show that PPARα is expressed at lower levels in anaplastic gliomas and glioblastoma multiforme (GBM) tissue compared with low-grade gliomas tissue, and low expression is associated with poor patient prognosis. PPARα activates transcription of dynamin-3 opposite strand (DNMO3os), which encodes a cluster of miR-214, miR-199a-3p, and miR-199a-5p microRNAs. Of these, miR-214 is transcribed at particularly high levels. PPARα-induced miR-214 expression causes downregulation of its target E2F2. Finally, miR-214 overexpression inhibits glioma cell growth in vitro and in vivo by inducing cell cycle arrest in G0/G1. Collectively, these data uncover a novel role for a PPARα-miR-214-E2F2 pathway in controlling glioma cell proliferation.

>丙戊酸钠脑病(VHE)是一种应用丙戊酸钠所引起的罕见并发症,其临床表现不典型,极易与普通癫痫发作相混淆。徐州中心医院神经外科曾收治1例脑膜瘤术后并发VHE病例,并于诊疗过程中发现地西泮可能延缓了VHE病情的恢复,现将其临床资料报道如下。患者,女,55岁,体质量75 kg,因"头晕伴双上肢麻木3

Enhancer of zeste homolog 2 (EZH2) is the catalytic unit of polycomb repressive complex 2 (PRC2) which epigenetically silences many genes involved in tumor-suppressive mechanisms via the trimethylation of lysine 27 of histone H3 (H3K27me3). We recently found that overexpression of EZH2 was associated with poor outcome of glioblastoma (GBM). In this study, we examined the antitumor effects of the EZH2 inhibitor GSK343 on glioma cells in vitro and in vivo. The proliferation and cell cycle of glioma cells was measured. Wound healing assay and transwell invasion assay were performed to evaluate the capacity of migration and invasion of glioma cells. Western blot, qPCR, immunoprecipitation and fluorescent staining were used to test the levels of EZH2 and associated proteins. Spheroid formation assay and clonogenic assays were conducted to assess the stemness of glioma stem cells. Finally, the effect of GSK343 was measured through a nude mice model with intracranially xenotransplanted glioma. We found that GSK343 reduced proliferation, attenuated cell motility and reversed epithelial-mesenchymal transition in U87 and LN229 glioma cells. GSK343 also suppressed the stemness of cell lines and patient derived glioma stem cells. Further, GSK343 inhibited histone H3K27 methylation and upregulated the expression of EZH2 target genes thereby regulating the levels of markers involved in epithelial-mesenchymal transition and stemness. Taken together, our results indicate that GSK343 could be a potential drug against glioblastoma.

目的 研究Zeste基因增强子人类同源2(EZH2)抑制剂GSK126对胶质瘤细胞系U87和LN229细胞增殖的影响.方法 GSK126处理U87和LN229细胞后,采用CCK-8和平板克隆实验检测该抑制剂对胶质瘤细胞增殖的影响,用流式细胞仪测定其对细胞周期的影响,Western blot检测H3K27me3、p21、cyclin E和CDK2的表达.结果 经GSK126处理后,U87和LN229细胞增殖能力下降(P＜0.05);GSK126处理能够诱导细胞停滞于G0/G1期(P＜0.05),p21蛋白表达量上升,而H3K27me3、cyclin E和CDK2表达量下调(P＜0.05).结论 GSK126能显著抑制胶质瘤细胞增殖,并通过上调p21表达来阻滞细胞周期.

Caffeine is one of the most commonly ingested neuroactive compounds and exhibits anticancer effects through induction of apoptosis and suppression of cell proliferation. However, the mechanisms underlying these effects are currently unknown. In this study, we investigated the mechanisms of caffeine-induced apoptosis in U251 cells (human glioma cell line). We analyzed the inhibitory effects of caffeine on cell proliferation by performing WST-8 and colony formation assays; in addition, cell survival was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and flow cytometric analysis. Western blotting was used to investigate the role played by FoxO1 in the proapoptotic effects of caffeine on glioma cells. Results showed that caffeine inhibited proliferation and survival of human glioma cells, induced apoptosis, and increased the expression of FoxO1 and its proapoptotic target Bim. In addition, we found that FoxO1 enhanced the transcription of its proapoptotic target Bim. In summary, our data indicates that FoxO1-Bim mediates caffeine-induced regression of glioma growth by activating cell apoptosis, thereby providing new mechanistic insight into the possible use of caffeine in treating human cancer.

EZH2 is up-regulated in various cancer types, implicating its role in tumorigenesis. Our recent data have shown that repression of EZH2 inhibited glioma growth by inhibition β-catenin signaling. Here, we identified several miRNAs that were repressed by EZH2, which in turn regulate β-catenin expression by its 3'UTR, such as miR-1224-3p, miR-328 and miR-214. Further, EZH2 silenced miR-328 expression by binding to miR-328 promoter and promoting methylation of miR-328 promoter. Finally, miR-328 largely abrogated EZH2 effects on β-catenin expression and glucose metabolism in glioma cells. Taken together, we propose a model for a coordinated EZH2-β-catenin oncoprotein axis, and epigenetic link between histone modification and DNA methylation, mediated by EZH2-scilenced miRNAs.

In recent years, microRNA has become a hotspot in research on diseases, especially in the initiation and progression of different types of cancer. In this study, we found that miR-218 could inhibit growth and metabolism in gliomas by directly targeting E2F2. First, we obtained data from the Chinese Glioma Genome Atlas (CGGA) database to analyze miR-218 expression in different grades of gliomas. The effects of miR-218 on cell cycle progression and cell proliferation in U87 and U251 cell lines were investigated by flow cytometry, specifically CCK8 assay and tablet cloning, respectively. Glucose consumption and lactate production of glioma cell lines were measured by correlative test kits. Furthermore, we used Western blot analysis and luciferase reporter assay to identify the direct and functional target of miR-218. Data from the CGGA database and real-time quantitative reverse transcription-PCR demonstrated that miR-218 was obviously reduced in human glioblastoma tissues, as well as in the cell lines. When miR-218 level was elevated in vitro, cell cycle progression was arrested in the G1 phase, and cell proliferation was dramatically inhibited. Both glucose consumption and lactate production of glioma cells were significantly reduced. Western blot analysis and luciferase reporter assay revealed that E2F2 was a direct target of miR-218 in glioma cells. This investigation demonstrated that elevated E2F2 expression could partly weaken the effect of miR-218 in vitro. This study also showed that miR-218 may be a repressor in glioma by directly targeting E2F2, as well as a potential therapeutic target in gliomas.

目的 探讨长链非编码RNAHOT AIR对人脑胶质瘤细胞侵袭的促进作用.方法 采用HOTAIR-siRNA寡聚核苷酸转染胶质瘤U87和U251细胞系,通过实时荧光定量PCR技术检测HOTAIR在胶质瘤细胞中的表达水平.利用Westem blot验证上皮间质化相关通路蛋白(Snail、Stat3和-catenin)、标记蛋白(E-cadherin、CDH13和Vimentin)和侵袭迁移相关基质金属蛋白酶(MMP2、MMP9)的表达变化.采用Transwell实验,观察敲低HOTAIR后其对胶质瘤细胞侵袭的影响.结果 下调HOTAIR表达后,U87和U251细胞的上皮间质化相关信号通路蛋白降低,E-cadherin和CDH13升高,Vimentin降低,MMP2和MMP9表达下降,细胞侵袭能力减弱(P＜0.01).结论 HOTAIR通过诱导上皮间质化促进了胶质细胞侵袭能力.

Fenofibrate, a fibric acid derivative, is known to possess lipid-lowering effects. Although fenofibrate-induced peroxisome proliferator-activated receptor alpha (PPARα) transcriptional activity has been reported to exhibit anticancer effects, the underlying mechanisms are poorly understood. In this study, we investigated the mechanisms behind the antiproliferative effects of fenofibrate in U87MG cells (human glioma cell line) using the WST-8 Cell Proliferation Assay Kit. Furthermore, we examined genome-wide gene expression profiles and molecular networks using the DAVID online software. Fenofibrate reduced the expression of 405 genes and increased the expression of 2280 genes. DAVID analysis suggested that fenofibrate significantly affected cell cycle progression and pathways involved in cancer, including the mTOR signaling pathway and insulin signaling pathway. Results of flow cytometry analysis indicated that fenofibrate induced cell cycle G 0 /G 1 arrest in U87MG cells. Furthermore, we identified the FoxO1–p27 kip signaling axis to be involved in fenofibrate-induced cell cycle arrest. Our findings suggest that in addition to its known lipid-lowering effects, fenofibrate may be used as an antitumor agent in glioma therapy.

Objective To investigate the influence of long noncoding RNA HOX transcript antisense RNA (HOTAIR) on human glioma cell metabolism and growth.Methods The fluorescently labeled small interfering (si-HOTAIR) was used to transfect glioma U87 and U251 cell lines.The real-time polymerase chain reaction (RT-PCR) was used to detect the expression level of HOTAIR in glioma cells.CCK8 test and colony formation assay were used to detect the growth changes of the glioma cells.Seahorse BioScience XF glycilysis stress test kit and XF mitochondrial stress test kit were used to detect the cell aerobic glycolysis and mitochondrial function.Western blot was used to detect glycolysis related enzymes,including the expression levels of glucose-6-phosphate isomerase (GPI),Pyruvate kinase M2 (PKM2),and lactate dehydrogenase A (LDHA).Results The transfection efficiency of si-HOTAIR in U87and U251cells observed under a fluorescence microscope was more than 90％.The HOTAIR expression in the cells of the si-HOTAIR group was downregulated significantly compared with the negative control group (P ＜ 0.01).The proliferative ability and clonal formation ability of the U87and U251 glioma cells of the si-HOTAIR group were significantly lower that than those of the negative group (P ＜ 0.01).After downregulation of HOTAIR,the aerobic glycolysis capacity of glioma cells were diminished,showing reduced based glycolysis level (P ＜ 0.05),diminished maximum glycolytic capacity (P ＜ 0.01),and decreased remaining amount of glycolysis (P ＜ 0.01).The expression levels of GPI,PKM2 and LDHA of the si-HOTAIR group were lower than those of the negative control group (P ＜ 0.01).After downregulation of HOTAIR,the mitochondrial function in glioma cells was impaired,showing decreased basal respiration level (U87 cells P ＜ 0.01),decreased mitochondrial coupling efficiency,and diminished residual respiration ability (P ＜ 0.05).Conclusions Downregulation of HOTAIR expression may impair the glycolytic capacity and mitochondrial function of glioma cells,simultaneously influence the growing ability of glioma cells.

Aerobic glycolysis (production of lactate from glucose in the presence of oxygen) is a hallmark of cancer. Fenofibrate is a lipid-lowering drug and an agonist of the peroxisome proliferator-activated receptor alpha (PPARα). We found that FF inhibited glycolysis in a PPARα-dependent manner in glioblastoma cells. Fenofibrate inhibited the transcriptional activity of NF-κB/RelA and also disrupted its association with hypoxia inducible factor1 alpha (HIF1α), which is required for the binding of NF-κB/RelA to the PKM promoter and PKM2 expression. High ratios of PKM2/PKM1 promote glycolysis and inhibit oxidative phosphorylation, thus favoring aerobic glycolysis. Fenofibrate decreased the PKM2/PKM1 ratio and caused mitochondrial damage. Given that fenofibrate is a widely used non-toxic drug, we suggest its use in patients with glioblastoma multiforme (GBM).

Objective To explore the effects of p65 silence by small molecular RNA interference (p65-siRNA ) on glioma cell growth and glucose metabolism .Methods After p65 expression was reduced by siRNA ,the growth and cycle of glioma cells U87 and U251 were examined with MTT assay and flow cytometry ,and the change of downstream function protein of p65 was detected by Western blot .Results After reduction of p65 expression ,the growth of U87 and U251 cells was suppressed and blocked in G1 phase with reduced glucose metabolism and the expressions of cyclin Dl and PKM2 in downstream function protein of p65 .Conclusion The p65-siRNA can effectively suppress the glioma cells growth and glucose metabolism .

The ecological situation in China's present stage is very grim, and strengthening the construction of ecological civilization is an important part of China's socialist modernization general layout. The key of ecological civilization construction is to correctly deal with the relationship between man and nature, strengthen publicity and education, build eco-cultural system, and try hard to establish the ecological civilization concepts of respecting for nature, complying with nature and protecting nature, promote the strategic implementation of the main functional areas, accelerate the mode transformation of economic development, achieve both economic growth and environmental protection; at the same time, strengthen the system construction, improve GDP evaluation system, provide a strong institutional prerequisite and guarantee for the construction of ecological civilization.

The ship gas turbine exhaust ejector is the central component parts, which can reduce or even eliminate the infrared radiation signal of ship gas turbine exhaust systems. In the design of exhaust ejector, structure forms of nozzle have a significant influence on its ejector effect. A rational nozzle, which is made to work in a narrow space and reduce the exhaust temperature effectively while minimizing the impact of flow of gas turbine body, has always been a focus and difficulty. Based on summary of the work of predecessors, an independent innovation is proposed in the article. The new design improves the performance by changing transitional form of nozzle and its angular size. Meanwhile, the performance of the design has been predicted and the structure has been optimized by CFD method.