The current study aimed to explore the role of autophagy in cerebral ischemia–reperfusion injuries (CIRI) and elucidate the efficacy of liensinine treatment. An in vitro ischemia–reperfusion (I/R) neuronal cell model was established and pretreated with liensinine or rapamycin (RAPA). Cell proliferation and survival were detected using a cell counting kit-8 (CCK-8) assay, while cell damage and apoptosis were detected using the lactate dehydrogenase (LDH) leakage rate and flow cytometry. Autophagy activity was detected using monodansylcadaverine (MDC) staining. Thereafter, I/R models were established in vivo in rats and the presence of neurological deficits was examined. Hematoxylin–eosin (HE) and triphenyl tetrazolium chloride (TTC) staining was used to detect pathological damage in brain tissue and the volume ratio of the cerebral infarction. The levels of PI3K/AKT pathway-related proteins and autophagy-related proteins (mTOR, LC3, P62, and TSC2) were detected using Western blot. The findings showed that liensinine treatment increased cell viability, decreased cell injury and apoptosis, and inhibited autophagy. The addition of RAPA to promote autophagy inhibited cell viability and enhanced cell injury and apoptosis. The I/R rats in the model group exhibited deficient neurological function, while those in the liensinine treatment group showed restoration of normal neural function and reduction of the necrotic area and infarct volume ratio in the brain tissue. Furthermore, liensinine treatment also inhibited the PI3K/Akt pathway activity and autophagy. However, addition of RAPA reversed the effects of liensinine treatment and aggravated brain tissue injury. Therefore, liensinine can play a neuroprotective role in CIRI by inhibiting autophagy through regulation of the PI3K/Akt pathway.

OBJECTIVES: To compare the efficacy of neuroendoscopic hematoma evacuation (NHE) and burr hole craniotomy (BHC) for treating septated chronic subdural hematoma (sCSDH) and analyze the technical advantages of NHE in sCSDH treatment by data analysis. METHODS: This study recruited 77 patients with sCSDH According to the type of operation, the patients were divided into NHE (n = 45) or BHC (n = 32) groups. Clinical data were retrospectively analyzed to evaluate and compare the efficacy of NHE and BHC for treating sCSDH. - RESULTS: NHE demonstrated higher complete hematoma clearance and postoperative midline recovery rates and shorter subdural drainage and postoperative bed rest durations compared with BHC (P < 0.05). The average NHE time (72.27 +/- 18.27 minutes) was longer than that of BHC (54.91 +/- 16.04 minutes) (P < 0.05). The average follow-up period was 30.9 (range, 7e51) months. The results revealed that 1 and 12 cases recurred in the NHE (2.2%) and BHC (18.8%) groups, respectively (P < 0.05). Additionally, a statistically significant difference in the Modified Rankin Scale scores of the 2 groups was observed 6 months after the operation (P < 0.05). During the follow-up period, neither group demonstrated any obvious operative complications. CONCLUSIONS: NHE is more effective than BHC for treating sCSDH and is worth popularizing on a large scale; however, ways to better deal with the outer membrane of hematoma warrant further consideration.

目的 探讨分隔型慢性硬膜下血肿(sCSDH)的神经内镜治疗效果.方法 回顾性分析2018年1月-2021年7月该院46例接受神经内镜治疗的sCSDH患者的临床资料.术后随访3～6个月,统计疗效及复发情况.结果 平均手术时间(73.4±15.7)min,完全清除血肿40例(87.0％),分隔完全游离45例(97.8％),平均置管时间(30.1±7.9)h,平均住院时间(5.5±1.8)d,症状改善且恢复良好者42例(91.3％),复发1例(2.2％).结论 神经内镜治疗sCSDH疗效显著,更适合患有基础疾病的高龄患者,值得临床推广普及.

Glioma is the most common primary tumor of the central nervous system (CNS) that develops chemotherapy resistance. The microRNA (miRNA) miR-9 is a tissue-specific miRNA of the CNS that may serve a key role in the modulation of chemotherapy sensitivity. The aim of the present study was to investigate the effect of miR-9 on glioma chemotherapy sensitivity by altering the expression of miR-9 in U251 glioma cells by viral transfection and subsequently treating with gradient concentrations of temozolomide (TMZ). Cell viability, apoptosis and the cell cycle were examined, and drug resistance genes were analyzed by western blotting. The role of nuclear factor B (NF-B) in this regulation was also examined. The results revealed that the susceptibility of glioma cells to TMZ was enhanced by miR-9 overexpression. When miR-9 and TMZ were applied together, the apoptotic rate and percentage of cells arrested at the G2/M stage were significantly higher compared with either treatment alone. Topoisomerase II expression was suppressed by miR-9 via the NF-B signaling pathway, which may be responsible for the sensitization. The results of the present study suggested that miR-9 may be a potential target for glioma chemotherapy.

Through the microarray analysis, long noncoding RNA TPT1-AS1 (TPT1-AS1) was identified in the development of glioma. However, the specific effect of TPT1-AS1 on glioma autophagy in the recent years has not fully been investigated. Therefore, the purpose of our present study is to investigate the function of TPT1-AS1 on affecting autophagy of glioma cells through regulation of microRNA-770-5p (miR-770-5p)-mediated stathmin 1 (STMN1). Initially, the expression of TPT1-AS1, miR-770-5p, and STMN1 were determined in glioma cell lines, followed by the prediction and validation of their interaction. After that, the effects of TPT1-AS1, miR-770-5p, and STMN1 on the in vitro glioma cell proliferation and autophagy were assessed using EdU assay and macrophage-derived chemokine (MDC) and on the in vivo tumor development and autophagy were evaluated using a nude mouse xenograft tumor assay and immunofluorescence assay. In comparison with the normal cells, the glioma cells displayed upregulated expression of TPT1-AS1 and STMN1, but a downregulated miR-770-5p expression. miR-770-5p, which directly targeted STMN1, could be downregulated by TPT1-AS1. Subsequently, in glioma cells, TPT1-AS1 can function to competitively bind to miR-770-5p, thus regulatEing STMN1 expression. Moreover, glioma cell proliferation and autophagy could be mediated through the TPT1-AS1/miR-770-5p/STMN1 axis. From our data we conclude an inhibitory function of TPT1-AS1 in glioma cell autophagy by downregulating miR-770-5p and upregulating STMN1, which may be instrumental for the therapeutic targeting and clinical management of glioma.

IDH1 R132H mutation is an important marker of survival in patients with gliomas. Although there are many changes of genes in tumour malignant progression, IDH1 R132H mutation status in glioma progression remained unclear. Here, an in-depth characterization of IDH1 R132H mutations were assessed by immunohistochemistry in 55 paired primary-recurrent astrocytomas tissues, including 5 paired primary pilocytic astrocytoma (pPA, WHO grade I), 35 paired primary low grade astrocytoma (pLGA, WHO grade II and III) and 15 paired primary high grade astrocytoma (pHGA/ Glioblastoma, WHO grade IV). Meanwhile, the DNA was isolated from paired samples, and PCR amplification was used for IDH1 exon4 sequencing. Nonparametric test, KM and Cox models were used to examine the statistical difference and survival function. We found that the percent of IDH1 R132H mutation was 68.6% (24/35) in pLGA group, but no IDH1 mutation was found in pPA and pHGA groups. Meanwhile, the results from immunohistochemistry and DNA sequencing showed that, compared with primary astrocytoma, there was no change of IDH1 status in recurrent astrocytoma whatever tumour pathological grade raise or indolent. The pPA group has the longest recurrence-free period (RFP) and overall survival (OS) in three groups (p<0.01), while the pHGA group has the shortest ones (p<0.01). In pLGA group, the IDH1 R132H mutation subgroup has longer RFP than IDH1 wild type subgroup (p<0.01), but the OS has no statistical difference between two subgroups (p>0.6). Additionally, IDH1 R132H mutation independently predicted a long RFP in patients with pLGA (HR 1.073, 95% CI 0.151-0.775, p<0.01).

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.

Glioma is the most common malignant tumor in neurosurgery,with its high mortality and morbidity, it brings heavy psychological-economic burden and huge physical-mental harm to patients and their families.But the treatment has been stagnant in recent years,so there is an urgent need to identify a new research direction and therapeutic target.miR-21 is a hot topic of the field recently.A number of studies have found that miR-21 is over-expressed in glioma,and it is closely related to apoptosis,invasiveness and other tumor-relevant factors. Both in vivo and vitro experiments found that inhibition of miR-21 expression can promote apoptosis and reduce tumor volume,which shows that miR-21 have a key role in the occurrence and development of glioma, and miR-21 may be a new target for the treatment of glioma with great potential .

蛋白酪氨酸磷酸酶家族由130多种蛋白酪氨酸磷酸酶组成,它们和蛋白质酪氨酸激酶家族一起调控蛋白质中酪氨酸残基的磷酸化以及去磷酸化的动态平衡,它们的活性直接决定细胞内蛋白质的磷酸化水平的高低.SHP-2是蛋白酪氨酸磷酸酶家族的一员,在各种细胞和组织中均有广泛的表达,参与多个信号传导通路,介导细胞的生长、分化、迁移、粘附及凋亡等.SHP-2的表达异常会导致多种疾病的产生,但是相关综述较少,同时未见文献报道其在胶质瘤中的作用,因此本文简要介绍SHP-2的结构、功能、信号传导,并阐述了SHP-2与常见疾病的关系.

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.

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.