Many observational studies have reported an association between thyroid function and type 2 diabetes mellitus (T2DM), but the causal relationship remains unclear. This study aims to examine the association between thyroid function and T2DM by using the National Health and Nutrition Examination Survey (NHANES) database 2007–2012 and Mendelian randomization (MR) analysis. A cross-sectional analysis was performed utilizing data from the NHANES, and logistic regression was employed to investigate the relationship between thyroid function and T2DM. Genome-wide association studies (GWAS) data of thyroid function and T2DM were obtained from the website of the IEU OpenGWAS project and the Thyroidomics Consortium. Single nucleotide polymorphisms (SNPs) strongly related to thyroid function were used as instrumental variables. Moreover, the inverse-variance weighting MR-Egger regression model and weighting median method were used to analyze the causal effect of thyroid function on T2DM. Cochran’s Q test, the MR-Egger intercept test, and “leave one out” cross-validation were applied to evaluate the pleiotropy and heterogeneity levels of the above included SNPs. In the NHANES study, no association was identified between thyroid function and the risk of T2DM in a fully adjusted model. A total of 17, 31, 7, and 79 SNPs were identified in the cohorts for free thyroxine (FT4), thyroid-stimulating hormone (TSH), hyperthyroidism, and hypothyroidism, respectively. The ORs with 95

This study aimed to investigate the correlation between Leishmania infection and dendritic cell infiltration and explore the underlying molecular mechanism how Leishmania infection regulates dendritic cell infiltration. Three datasets, GSE63931, GSE80008 and GSE77528 were combined and their batch effects were removed by Combat function in sva R package. Immune cell infiltrations were estimated using the Microenvironment Cell Populations-counter (MCP-counter) R package. Statistical results were verified by Student's t test. The differential expression of metadherin (MTDH) was identified by Limma R package. The correlation between MTDH expression and dendritic cell infiltration was estimated by Pearson's product moment correlation coefficient. GDS5086 was used to explore MTDH expression pattern in dendritic cells infected with Leishmania. Compared with normal samples, 5 types of immune cells showed differential infiltration in leishmaniasis samples, including T cells, CD8+ T cells, dendritic cells, cytotoxic lymphocytes and B lineage cells. Among these, only DCs were significantly suppressed in leishmaniasis samples. Notably, MTDH expression was differential between leishmaniasis and normal samples. There was a significant correlation between MTDH expression and dendritic cell infiltration. In conclusion, these results demonstrate that Leishmania infection leads to the downregulation of MTDH expression and the suppression of dendritic cell infiltration.

人类免疫缺陷病毒(human immunodeficiency virus,HIV)具有嗜神经性,超过70％的获得性免疫缺陷综合征(acquired immune deficiency syndrome,AIDS)出现不同程度神经系统病变.而 AIDS 合并慢性硬膜下血肿(chronic subdural hematoma,CSDH)临床少见.本文报道2例AIDA合并CSDH.

IntroductionThe safety outcomes of endovascular therapy for intracranial artery stenosis in a real-world stetting are largely unknown. The Clinical Registration Trial of Intracranial Stenting for Patients with Symptomatic Intracranial Artery Stenosis (CRTICAS) was a prospective, multicentre, real-world registry designed to assess these outcomes and the impact of centre experience.Methods1140 severe, symptomatic intracranial arterial stenosis (ICAS) patients treated with endovascular therapy were included from 26 centres, further divided into three groups according to the annual centre volume of intracranial angioplasty and stent placement procedures over 2 years: (1) high volume for ≥25 cases/year; (2) moderate volume for 10–25 cases/year and (3) low volume for <10 cases/year.ResultsThe rate of 30-day stroke, transient ischaemic attack or death was 9.7% (111), with 5.4%, 21.1% and 9.7% in high-volume, moderate-volume and low-volume centres, respectively (p<0.05). Multivariable logistic regression confirmed high-volume centres had a significantly lower primary endpoint compared with moderate-volume centres (OR=0.187, 95% CI: 0.056 to 0.627; p≤0.0001), while moderate-volume and low-volume centres showed no significant difference (p=0.8456).ConclusionCompared with the preceding randomised controlled trials, this real-world, prospective, multicentre registry shows a lower complication rate of endovascular treatment for symptomatic ICAS. Non-uniform utilisation in endovascular technology, institutional experience and patient selection in different volumes of centres may have an impact on overall safety of this treatment.

Objective To explore the expression of miRNA-221 in human gliomas and its effect on glioma cell line proliferation.Methods The expression levels of miRNA-221 were determined by qRT-PCR in 123 samples of glioma tissues and 36 samples of normal cerebral tissues.The effects of miRNA-221 on U87 and U251 cell proliferation were determined by MIT tests.Dual luciferase assay,qRT-PCR and western blot were used to validate the targets of miRNA-221.Results The expression level of miRNA-221 (0.62+ 0.2) was significantly higher in the glioma tissues than that (0.37±0.13) in the normal cerebral tissues (P＜0.01).The survival time was significantly shorter in 72 glioma patients with higher expression of miRNA-221 than that in 51 glioma patients with lower expression of miRNA-221 after the operation (P＜0.01).The over expression of miRNA-221 significantly promoted U251 and U87 cells proliferations (P＜0.05).The depletion of miRNA-221 caused the increases in mRNA and protein of PRDM2 expressions (P＜0.05) in the U251 and U87 cells.Conclusions The upregulation of miRNA-221 may be used as one of diagnostic indexes of human glioma.PRDM2 is one of target genes of miRNA-221.

Glioblastoma (GBM) accounts for about half of all malignant brain cancers. Although the treatment strategies for glioblastoma develop rapidly, a considerable number of patients could not benefit from temozolomide (TMZ)-based chemotherapy. Here, we revealed a miR-124-AURKA axis that regulated glioblastoma growth and chemosensitivity. Mechanistically, AURKA was up-regulated in glioblastoma tissues and associated with poor overall survival. While overexpression of AURKA enhanced tumor growth, genetic or pharmacological inhibition of AURKA led to growth-inhibitory and chemopotentiating effects in glioblastoma. AURKA was further identified as a target of miR-124. Furthermore, our data showed that miR-124 down-regulated AURKA expression and subsequently suppressed cell growth. Re-expression of AURKA significantly rescued miR124-mediated proliferation repression and chemosensitivity. In conclusion, our results demonstrated that miR-124 inhibited glioblastoma growth and potentiated chemosensitivity by targeting AURKA, which may represent promising targets and rational therapeutic options for glioblastoma.

Objective:To study the protective effect of miR-21 on the blood brain barrier after cerebral ischemia/reperfusion(I/R)injury.Methods:A rat model of cerebral I/R was established by suture method.The rats were randomly divided into the blank plasmid group,miR-21-mimic group and inhibitor miR-21 group.The expression of Bax protein in the cerebral cortex was detected by Western Blot,the integrity of cell morphology and blood brain barrier was detected by transmission electron microscope,the distribution of autophagy protein LC-3 in the cerebral cortex tissue was detected by immunofluorescence.Results:Western Blot showed that compared with the blank plasmid,the expression of Bax protein in brain tissue of rats in miR-21-mimic were significantly decreased,but increased expression of Bax protein in the brain tissue s was found in miR-21 in inhibitor-treated rats;electron microscopy results showed that compared with the blank plasmid group,Transmission electron microscopy showed that compared with the blank plasmid groups,miR-21-mimic groups in the surrounding astrocytes of lamina of endothelial cells process almost complete,Immunofluorescence showed that compared with the blank plasmid group,autophagy related protein LC-3 expression in the miR-21-mimic group was was decreased.Conclusions:MiR-21 could protect the blood brain barrier after cerebral I/R via down-regulating the expression of Bax protein,inhibiting apoptosis and autophagy.

Objective To explore the expression level and methylation status of SOX9 gene in human glioma,and find out the relationship between SOX9 and pathological grade of glioma.Methods Totally 113 glioma tissues and 34 normal brain tissues were collected.SOX9 expression was detected by RT-PCR method and methylation status was measured by PCR-MSP.The survival curve was analyzed by Kplan-Meier methods.Results The relative expression level of SOX9 mRNA was 0.203±0.097 and 0.496±0.213 in normal brain tissues and glioma tissue respectively,and significant difference was found between them (P ＜ 0.01).Survival curve showed that the survival time was obviously shorter in patients with high SOX9 gene expression than in those with low expression (P ＜0.01).The noumethylation rate ofSOX9 gene promoter region in glioma tissues were 11.1％ in grade Ⅰ,33.3％ in grade Ⅱ,53.8％ in grade Ⅲ,71.9％ in grade Ⅳ respectively.There was significant difference between high-grade (Ⅲ-Ⅳ) group and low-grade group (Ⅰ-Ⅱ) (P ＜ 0.01).Conclusions The expression ofSOX9 gene upregulate and methylation of SOX9 gene in the promoter region decrease in human glioma.The patient's survival time is closely correlated with expression level ofSOX9 gene.

Objective To evaluate the therapeutic outcome of microsurgery for dural arteriovenous fistulas (DAVF). Methods Clinical data of 6 patients with DAVF underwent microsurgery were analyzed retrospectively, including onset as subarachnoid hemorrhage in 2 patients, cerebral hemorrhage in 2, epilepsy in 1 and exophthalmos in 1. Results All the vascular malformations were resected, and the preoperative symptoms improved to different degree. DSA or CTA examinations were performed in all the patients 6 months after the operation. All the lesions were resected completely, and there was no recurrence or residue of vascular malformation. Six patients were followed up for mean period of 2.1 years, ranged from 1 to 5.5 years. However, there was no newly occurred cerebral hemorrhage or nervous dysfunction during the follow-up period, and the activities of daily living achieved gradeⅠ in 5 patients and gradeⅡ in 1. Conclusion Microsurgery is a safe and effective therapeutic method for DAVF.

SOX7 has been recently recognized as a tumor suppressor belonging to the SOX (SRY-related HMG-box) family of a transcription factor. However, its role in human gliomas is unknown. Our study showed that SOX7 expression was significantly downregulated in human gliomas. Statistical analysis showed that SOX7 suppression was associated with higher histological grades of tumors in glioma tissues. SOX7 could suppress tumor properties both in vivo and in vitro, and depletion of the HMG domain abolishes its tumor suppressive roles. In vitro assays demonstrated that SOX7 could downregulate Wnt/β-catenin transcription and decrease the expression of Cyclin D1 and c-Myc, while the mutant SOX7 lost these functions. These results suggested that the HMG-box is a key domain of SOX7 for negatively regulating the Wnt/β-catenin signaling pathway when functioning as a tumor suppressor in a glioma.

With secure and dependable antihypertensive effects, telmisartan is an antihypertensive drug. Telmisartan was reported showing distinct neuroprotective effect in cerebral IR injury but the underlying mechanisms are still unclear. The aim of this study was to evaluate the effect of telmisartan prevents cerebral ischemia-reperfusion (I/R) injury-mediated oxidative stress and inflammation in model rat to explore possible molecular mechanism. Male Sprague-Dawley (SD) rats were used to induce cerebral I/R injury using middle cerebral artery occlusion. 30 SD rats were randomly and evenly divided into 3 groups: Sham, I/R, telmisartan treated ischemia-reperfusion group. The results showed that telmisartan improved neurological impairments, inhibited apoptosis, resisted oxidative stress and inflammation in hippocampus of cerebral I/R injury rats. However, pretreatment with telmisartan inhibited the activation of adrenocorticotropic hormone (ACTH), vasopressin, catecholamine and natriuretic peptides activities in cerebral IR injury rat. These findings confirm the involvement of telmisartan prevents cerebral ischemia-reperfusion injury-mediated oxidative stress and inflammation in model rat.

As a phosphatase, SHP-2 has been identified to be involved in regulating several cell functions, including growth, division, adhesion and motility. Therefore, SHP‑2 may affect the response of glioma to radiotherapy, such as via enhancing angiogenesis. The present study aimed to investigate the function of SHP‑2, a protein tyrosine phosphatase, in the radiosensitivity of glioma. U251, U87 and SHG44 glioma cell lines were transfected with small interfering (si)RNA against SHP‑2 and cell proliferation was assessed using a cell counting kit 8 assay, cell apoptosis was assessed by fluorescence‑activated cell sorting and immunoblotting, cell invasion was determined by an invasion assay, and the vasculogenic mimicry capacity was assessed by a tube formation assay. SHP‑2 siRNA transfection reduced the proliferation and increased apoptosis in the glioma cell lines. Downregulation of SHP‑2 suppressed glioma cell invasion and vasculogenic mimicry. These results demonstrated that no significant difference was observed between glioma tissues and normal brain tissues, however, silencing of SHP‑2 inhibited cell proliferation, invasion and vasculogenic mimicry in the glioma cell lines. SHP‑2 may be a novel therapeutic target for glioma.

Glioma is the most common malignant tumor of neurosurgery, which morbidity accounting for 5% of systemic cancer, accounting for 70% of the tumors of children, and showed an increasing trend. High degree of malignant glioma grows rapidly, which has a very strong invasion of glioma.The 5-year survival rate is very low, because it is lack of effective cure. It is very difficult to deal the tumor with surgical resection and very vulnerable to relapse after a relatively poor prognosis, which have done great harm to human health and even life. With the development of molecular biology and biotechnology applications, it has become a new research direction of human cancer treatment to reveal the occurrence of glioma development mechanism and seek effective methods for gene therapy at the gene level. Reynolds and Richards have isolated cell populations from adult mouse striatum which can keep proliferating possessed with multiple differentiation potential and put forward concept of neural stem cells(neural stem cell, NSC). NSC have highly proliferation and self-renewal capacity and migration functions as well as the characteristics of a good fusion with normal brain tissue, which provides a good foundation for gene therapy for glioma.

目的 探讨脑胶质瘤果蝇zeste基因增强子同源物2(EZH2)蛋白的表达变化.方法 选取2010年5月至2011年12月手术切除的胶质瘤组织标本83例,其中2008年WHO分级Ⅰ级15例,Ⅱ级20,Ⅲ级26例,Ⅳ级22例;术前均未接受放疗或化疗.另外,收集30例颅脑损伤内减压手术切除的无肿瘤脑组织作为对照.采用实时荧光定量PCR法检测EZH2 mRNA表达.根据EZH2 mRNA表达水平分为高表达组(EZH2 mRNA≥0.3,48例)和低表达组(EZH2 mRNA＜0.3,35例),分析两组术后生存期.结果 胶质瘤组织EZH2 mRNA表达水平明显高于对照组(P＜0.01),高级别胶质瘤(WHOⅢ、Ⅳ级)组织EZH2mRNA表达水平明显高于低级别胶质瘤(WHO Ⅰ、Ⅱ级)组织(P＜0.01).低表达组患者术后生存期较高表达组显著延长(P＜0.01).结论 脑胶质瘤组织EZH2mRNA呈高表达,且其表达水平与病理分级具有相关性.

The purpose of this study was to investigate the functions of microRNA-9, which is a tissue-specific microRNA in central nervous system, in the vasculogenic mimicry (VM) of glioma cell lines in vitro and in vivo. Glioma cell lines U87MG, U251 and SHG44 were transfected with microRNA-9 mimic, microRNA-9 inhibitor or scramble sequences. The amount of microRNA-9 and Stathmin (STMN1) mRNA was determined by quantitative real-time PCR, and the protein expression of STMN1 was determined by western blot. Cell proliferation and apoptosis were assessed. The interactions between the 3'UTR of STMN1 and miR-9 was determined by luciferase reporter assay. The VM capacity in vitro was evaluated using VM formation assay, and the rescue experiment of STMN1 was carried out in U251 cells. The in vivo experiment was applied with animal models implanted with U87MG cells.MicroRNA-9 mimic transfection reduced proliferation and increased apoptosis in glioma cell lines (p < 0.05). MicroRNA-9 mimic up-regulated STMN1 mRNA levels but reduced its protein levels (p < 0.05), and luciferase activity of STMN1 was suppressed by microRNA-9 mimic transfection (p < 0.05). Furthermore, microRNA-9 mimic transfection suppressed tumor volume growth, as well as VM both in vitro and in vivo. The cell viability and microtube density were upregulated in U251 cells after STMN1 up-regulation (p < 0.05). STMN1 is a target of microRNA-9, and microRNA-9 could modulate cell proliferation, VM and tumor volume growth through controlling STMN1 expression. MicroRNA-9 and its targets may represent a novel panel of molecules for the development of glioma treatment.

Objective To investigate the relationship between the expression of connective tissue growth factor(CTGF) and aggressive of human pituitary adenom,that provides the theoretical basis for the biological treatment of pituitary adenoma. Methods Quantitative real time PCR( qRT-PCR) and Western blot were used to detecte the expression of CTGF in 16 cases of non-invasive pituitary adenoma and 52 cases of invasive pituitary adenoma(IPA) . Results CTGF expression was found in all cases of invasive pituitary adenomas and noninvasive pituitary adenomas. The expression of CTGF in invasive pituitary adenoma was higher than that of in noninvasive pituitary adenoma(P=0. 01) . Conclusions The expression of CTGF in invasive pituitary adenoma is significantly higher than that of in the noninvasive pituitary adenoma and related with the size of pituitary adenoma.

Objective: To investigate stathminin expression in human gliomas and normal brain specimans derived microvessels endothelial cells(GDMEC).Methods: Microvascular endothelial cells from human gliomas(GBMEC,n=68) and normal brain(NBMEC,n=20) were purified by incubating with magnetic beads coated with anti-CD105 antibody.There were 24 cases of low grade gliomas(WHOⅠ-Ⅱgrade) and 44 high grade gliomas(WHO Ⅲ-Ⅳgrade).Expression rates and cellular distribution of stathmin in GDMEC and NBMEC were also investigated by immunohistochemistry.Semiquantitative RT-PCR and Western blot were used for comparing the exp-ression of stathmin in GDMEC and NBMEC.Results: Immunohistochemical analysis demonstrated that the rates of stathmin expression in NBMEC,low grade GDMEC,and high grade GDMEC were 20%,66%,and 95%,respectively(P0.05).The expression of stathmin in GDMEC was higher than that in NBMEC.The difference betweenⅠ-Ⅱgrade,Ⅲ-Ⅳgrade and normal human brain tissues were significant(P0.01) respectively.The difference betweenⅠ-Ⅱgrade and Ⅲ-Ⅳ grade was significant(P0.01).Conclusions: With the rise of pathological grades of glioma,the expression of stathmin increased,and it may represent a novel tumor-related target for the therapy of malignant gliomas.

Objective To evaluate the side effect and efficacy of bevacizumab combined with temozolomide for recurrent glioma prospectively.Methods From February 2010 to September 2010,18 cases of recurrent glioma were enrolled in this study.All the patients received temozolomide(150-200mg/m2,d1-d5,oral administration,28 days was a cycle) and bevacizumab(5mg/kg,iv,once for every 14 days).Efficacy and side effects were evaluated after two cycles' chemotherapy.Six months' progression-free survival rate and overall survival rate were calculated.Results All of the 18 cases,there were 6 cases with PR(33.3%),9 cases with SD(50.0%) and 3 cases with PD(16.7%).The 6-month progression-free survival rate and overall survival rate were 66.7%(12/18) and 77.8%(14/18),respectively.Myelo-suppression and gastrointestinal tract reaction were the most common toxicities,mainly 1-2 degree.Conclusion Bevacizumab combined with temozolomide is effective for recurrent glioma.The side effect is mild and tolerable.Long-term efficacy should be further observed.

The purpose of this study was to investigate stathmin expression and its mechanisms of action in GDMEC. Microvascular endothelial cells were isolated from human gliomas (n=68) and normal brain specimans (n=20), and purified by magnetic beads coated with anti-CD105 antibody. The expression of stathmin mRNA and protein were detected by RT-PCR and western blotting, respectively. Stathmin expression was silenced by application of specific siRNA in high grade GDMEC. The proliferation, apoptosis and invasion behavior of GDMEC were investigated. The stathmin positive rate of endothelial cells in normal brain, grade I-II glioma and grade III-IV glioma was 20, 66 and 95.5%, respectively (P<0.05). When cells were treated with siRNA to silence stathmin, cell viability was reduced, the apoptosis rate increased and the migration of vascular endothelial cells was suppressed significantly (P<0.05). Down-regulation of stathmin suppressed neoangiogenesis of glioma and provides a potential target for glioma treatment.