Activated SIRT1 contributes to DPT-induced glioma cell parthanatos by upregulation of NOX2 and NAT10.

Parthanatos is a type of programmed cell death dependent on hyper-activation of poly (ADP-ribose) polymerase 1 (PARP-1). SIRT1 is a highly conserved nuclear deacetylase and often acts as an inhibitor of parthanatos by deacetylation of PARP1. Our previous study showed that deoxypodophyllotoxin (DPT), a natural compound isolated from the traditional herb Anthriscus sylvestris, triggered glioma cell death via parthanatos. In this study, we investigated the role of SIRT1 in DPT-induced human glioma cell parthanatos. We showed that DPT (450 nmol/L) activated both PARP1 and SIRT1, and induced parthanatos in U87 and U251 glioma cells. Activation of SIRT1 with SRT2183 (10 µmol/L) enhanced, while inhibition of SIRT1 with EX527 (200 µmol/L) or knockdown of SIRT1 attenuated DPT-induced PARP1 activation and glioma cell death. We demonstrated that DPT (450 nmol/L) significantly decreased intracellular NAD+ levels in U87 and U251 cells. Further decrease of NAD+ levels with FK866 (100 µmol/L) aggravated, but supplement of NAD+ (0.5, 2 mmol/L) attenuated DPT-induced PARP1 activation. We found that NAD+ depletion enhanced PARP1 activation via two ways: one was aggravating ROS-dependent DNA DSBs by upregulation of NADPH oxidase 2 (NOX2); the other was reinforcing PARP1 acetylation via increase of N-acetyltransferase 10 (NAT10) expression. We found that SIRT1 activity was improved when being phosphorylated by JNK at Ser27, the activated SIRT1 in reverse aggravated JNK activation via upregulating ROS-related ASK1 signaling, thus forming a positive feedback between JNK and SIRT1. Taken together, SIRT1 activated by JNK contributed to DPT-induced human glioma cell parthanatos via initiation of NAD+ depletion-dependent upregulation of NOX2 and NAT10.

TAX1BP1 contributes to deoxypodophyllotoxin-induced glioma cell parthanatos via inducing nuclear translocation of AIF by activation of mitochondrial respiratory chain complex I.

Parthanatos is a type of programmed cell death initiated by over-activated poly (ADP-ribose) polymerase 1 (PARP1). Nuclear translocation of apoptosis inducing factor (AIF) is a prominent feature of parthanatos. But it remains unclear how activated nuclear PARP1 induces mitochondrial AIF translocation into nuclei. Evidence has shown that deoxypodophyllotoxin (DPT) induces parthanatos in glioma cells via induction of excessive ROS. In this study we explored the downstream signal of activated PARP1 to induce nuclear translocation of AIF in DPT-triggered glioma cell parthanatos. We showed that treatment with DPT (450 nM) induced PARP1 over-activation and Tax1 binding protein 1 (TAX1BP1) distribution to mitochondria in human U87, U251 and U118 glioma cells. PARP1 activation promoted TAX1BP1 distribution to mitochondria by depleting nicotinamide adenine dinucleotide (NAD+). Knockdown of TAX1BP1 with siRNA not only inhibited TAX1BP1 accumulation in mitochondria, but also alleviated nuclear translocation of AIF and glioma cell death. We demonstrated that TAX1BP1 enhanced the activity of respiratory chain complex I not only by upregulating the expression of ND1, ND2, NDUFS2 and NDUFS4, but also promoting their assemblies into complex I. The activated respiratory complex I generated more superoxide to cause mitochondrial depolarization and nuclear translocation of AIF, while the increased mitochondrial superoxide reversely reinforced PARP1 activation by inducing ROS-dependent DNA double strand breaks. In mice bearing human U87 tumor xenograft, administration of DPT (10 mg· kg-1 ·d-1, i.p., for 8 days) markedly inhibited the tumor growth accompanied by NAD+ depletion, TAX1BP1 distribution to mitochondria, AIF distribution to nuclei as well as DNA DSBs and PARP1 activation in tumor tissues. Taken together, these data suggest that TAX1BP1 acts as a downstream signal of activated PARP1 to trigger nuclear translocation of AIF by activation of mitochondrial respiratory chain complex I.

ATF3 contributes to brucine-triggered glioma cell ferroptosis via promotion of hydrogen peroxide and iron.

Ferroptotic cell death is characterized by iron-dependent lipid peroxidation that is initiated by ferrous iron and H2O2 via Fenton reaction, in which the role of activating transcription factor 3 (ATF3) remains elusive. Brucine is a weak alkaline indole alkaloid extracted from the seeds of Strychnos nux-vomica, which has shown potent antitumor activity against various tumors, including glioma. In this study, we showed that brucine inhibited glioma cell growth in vitro and in vivo, which was paralleled by nuclear translocation of ATF3, lipid peroxidation, and increases of iron and H2O2. Furthermore, brucine-induced lipid peroxidation was inhibited or exacerbated when intracellular iron was chelated by deferoxamine (500 µM) or improved by ferric ammonium citrate (500 µM). Suppression of lipid peroxidation with lipophilic antioxidants ferrostatin-1 (50 µM) or liproxstatin-1 (30 µM) rescued brucine-induced glioma cell death. Moreover, knockdown of ATF3 prevented brucine-induced accumulation of iron and H2O2 and glioma cell death. We revealed that brucine induced ATF3 upregulation and translocation into nuclei via activation of ER stress. ATF3 promoted brucine-induced H2O2 accumulation via upregulating NOX4 and SOD1 to generate H2O2 on one hand, and downregulating catalase and xCT to prevent H2O2 degradation on the other hand. H2O2 then contributed to brucine-triggered iron increase and transferrin receptor upregulation, as well as lipid peroxidation. This was further verified by treating glioma cells with exogenous H2O2 alone. Moreover, H2O2 reversely exacerbated brucine-induced ER stress. Taken together, ATF3 contributes to brucine-induced glioma cell ferroptosis via increasing H2O2 and iron.

FOXO3a protects glioma cells against temozolomide-induced DNA double strand breaks via promotion of BNIP3-mediated mitophagy.

FOXO3a (forkhead box transcription factor 3a) is involved in regulating multiple biological processes in cancer cells. BNIP3 (Bcl-2/adenovirus E1B 19-kDa-interacting protein 3) is a receptor accounting for priming damaged mitochondria for autophagic removal. In this study we investigated the role of FOXO3a in regulating the sensitivity of glioma cells to temozolomide (TMZ) and its relationship with BNIP3-mediated mitophagy. We showed that TMZ dosage-dependently inhibited the viability of human U87, U251, T98G, LN18 and rat C6 glioma cells with IC50 values of 135.75, 128.26, 142.65, 155.73 and 111.60 µM, respectively. In U87 and U251 cells, TMZ (200 µM) induced DNA double strand breaks (DSBs) and nuclear translocation of apoptosis inducing factor (AIF), which was accompanied by BNIP3-mediated mitophagy and FOXO3a accumulation in nucleus. TMZ treatment induced intracellular ROS accumulation in U87 and U251 cells via enhancing mitochondrial superoxide, which not only contributed to DNA DSBs and exacerbated mitochondrial dysfunction, but also upregulated FOXO3a expression. Knockdown of FOXO3a aggravated TMZ-induced DNA DSBs and mitochondrial damage, as well as glioma cell death. TMZ treatment not only upregulated BNIP3 and activated autophagy, but also triggered mitophagy by prompting BNIP3 translocation to mitochondria and reinforcing BNIP3 interaction with LC3BII. Inhibition of mitophagy by knocking down BNIP3 with SiRNA or blocking autophagy with 3MA or bafilomycin A1 exacerbated mitochondrial superoxide and intracellular ROS accumulation. Moreover, FOXO3a knockdown inhibited TMZ-induced BNIP3 upregulation and autophagy activation. In addition, we showed that treatment with TMZ (100 mg·kg-1·d-1, ip) for 12 days in C6 cell xenograft mice markedly inhibited tumor growth accompanied by inducing FOXO3a upregulation, oxidative stress and BNIP3-mediated mitophagy in tumor tissues. These results demonstrate that FOXO3a attenuates temozolomide-induced DNA double strand breaks in human glioma cells via promoting BNIP3-mediated mitophagy.

Endoplasmic reticulum stress regulates oxygen-glucose deprivation-induced parthanatos in human SH-SY5Y cells via improvement of intracellular ROS.

AIMS: Endoplasmic reticulum (ER) stress has been demonstrated to regulate neuronal death caused by ischemic insults via activation of apoptosis, but it still remains unclear whether ER stress participates in regulation of parthanatos, a new type of programmed cell death characterized by PARP-1 overactivation and intracellular accumulation of PAR polymer. METHODS: we used oxygen-glucose deprivation (OGD) and human SH-SY5Y cells to simulate neuronal damage caused by ischemia. RESULTS: Oxygen-glucose deprivation induced time-dependent death in SH-SY5Y cells, which was accompanied with upregulation of PARP-1, accumulation of PAR polymer, decline of mitochondrial membrane potentials and nuclear translocation of AIF. Pharmacological inhibition of PARP-1 with its specific inhibitor 3AB rescued OGD-induced cell death, as well as prevented PAR polymer accumulation, mitochondrial depolarization, and AIF translocation into nucleus. Similar results could be found when PARP-1 was genetically knocked down with SiRNA. These indicated that OGD triggered parthanatos in SH-SY5Y cells. Then, we found inhibition of overproduction of ROS with antioxidant NAC attenuated obviously OGD-induced parthanatos in SH-SY5Y cells, suggesting ROS regulated OGD-induced parthanatos. Additionally, OGD also induced upregulation of ER stress-related proteins. Mitigation of ER stress with chemical chaperone 4-PBA or trehalose suppressed significantly OGD-induced overproduction of ROS, PARP-1 upregulation, PAR polymer accumulation, and nuclear accumulation of AIF, and cell death in SH-SY5Y cells. CONCLUSION: Endoplasmic reticulum stress regulates OGD-induced parthanatos in human SH-SY5Y cells via improvement of intracellular ROS.

The comparison of teaching efficiency between massive open online courses and traditional courses in medicine education: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to investigate and compare the passing rates of Massive Open Online Courses (MOOCs) with Traditional Courses to indicate how to improve the teaching efficiency in Medicine Education. METHODS: A systematic search of relevant published literature was conducted to collect relevant retrospective cohort studies that compared the teaching efficiency of MOOCs and Traditional Courses. RESULTS: There are three retrospective cohort studies included in the final meta-analysis. There were no significant differences in the passing rates of MOOCs and Traditional Courses. CONCLUSIONS: it is necessary for universities to invest in online education to promote the development of MOOCs, which will probably have an advantage over Traditional Courses for postgraduate medical education in the near future.

Shikonin induces glioma cell necroptosis in vitro by ROS overproduction and promoting RIP1/RIP3 necrosome formation.

Necroptosis is a type of programmed necrosis regulated by receptor interacting protein kinase 1 (RIP1) and RIP3. Necroptosis is found to be accompanied by an overproduction of reactive oxygen species (ROS), but the role of ROS in regulation of necroptosis remains elusive. In this study, we investigated how shikonin, a necroptosis inducer for cancer cells, regulated the signaling leading to necroptosis in glinoma cells in vitro. Treatment with shikonin (2-10 µmol/L) dose-dependently triggered necrosis and induced overproduction of intracellular ROS in rat C6 and human SHG-44, U87 and U251 glioma cell lines. Moreover, shikonin treatment dose-dependently upregulated the levels of RIP1 and RIP3 and reinforced their interaction in the glioma cells. Pretreatment with the specific RIP1 inhibitor Nec-1 (100 µmol/L) or the specific RIP3 inhibitor GSK-872 (5 µmol/L) not only prevented shikonin-induced glioma cell necrosis but also significantly mitigated the levels of intracellular ROS and mitochondrial superoxide. Mitigation of ROS with MnTBAP (40 µmol/L), which was a cleaner of mitochondrial superoxide, attenuated shikonin-induced glioma cell necrosis, whereas increasing ROS levels with rotenone, which improved the mitochondrial generation of superoxide, significantly augmented shikonin-caused glioma cell necrosis. Furthermore, pretreatment with MnTBAP prevented the shikonin-induced upregulation of RIP1 and RIP3 expression and their interaction while pretreatment with rotenone reinforced these effects. These findings suggest that ROS is not only an executioner of shikonin-induced glioma cell necrosis but also a regulator of RIP1 and RIP3 expression and necrosome assembly.

A prediction model for lymph node metastases using pathologic features in patients intraoperatively diagnosed as stage I non-small cell lung cancer.

BACKGROUND: There is little information on which pattern should be chosen to perform lymph node dissection for stage I non-small-cell lung cancer. This study aimed to develop a model for predicting lymph node metastasis using pathologic features of patients intraoperatively diagnosed as stage I non-small-cell lung cancer. METHODS: We collected pathology data from 284 patients intraoperatively diagnosed as stage I non-small-cell lung cancer who underwent lobectomy with complete lymph node dissection from 2013 through 2014, assessing various factors for an association with metastasis to lymph nodes (age, gender, pathology, tumour location, tumour differentiation, tumour size, pleural invasion, bronchus invasion, multicentric invasion and angiolymphatic invasion). After analysing these variables, we developed a multivariable logistic model to estimate risk of metastasis to lymph nodes. RESULTS: Univariate logistic regression identified tumour size >2.65 cm (p < 0.001), tumour differentiation (p < 0.001), pleural invasion (p = 0.034) and bronchus invasion (p < 0.001) to be risk factors significantly associated with the presence of metastatic lymph nodes. On multivariable analysis, only tumour size >2.65 cm (p < 0.001), tumour differentiation (p = 0.006) and bronchus invasion (p = 0.017) were independent predictors for lymph node metastasis. We developed a model based on these three pathologic factors that determined that the risk of metastasis ranged from 3% to 44% for patients intraoperatively diagnosed as stage I non-small-cell lung cancer. By applying the model, we found that the values y > 0.80, 0.43 < y ≤ 0.80, y ≤ 0.43 plus tumour size >2 cm and y ≤0.43 plus tumour size ≤2 cm yielded positive lymph node metastasis predictive values of 44%, 18%, 14% and 0%, respectively. CONCLUSIONS: A non-invasive prediction model including tumour size, tumour differentiation and bronchus invasion may be useful to give thoracic surgeons recommendations on lymph node dissection for patients intraoperatively diagnosed as Stage I non-small cell lung cancer.

[A Retrospective Analysis on the Prevalence of Visceral Leishmaniasis in Gansu Province during 2005-2014].

OBJECTIVE: To review the prevalence of visceral leishmaniasis in Gansu Province during 2005-2014. METHODS: The data of visceral leishmaniasis cases in Gansu Province during 2005-2014 were collected and descriptive statistical analysis was performed. RESULTS: During 2005-2014, 1,260 cases of visceral leishmaniasis were reported in Gansu Province. The incidence showed a trend of annual increase from 2005 (90 cases, 7.14%) onwards, peaked in 2011 (168 cases, 13.33%), and decreased afterwards. In 2014, 85 cases (6.75%) were reported. Most of the cases were from the Longnan region and some areas in Gannan Tibetan Autonomous Prefecture. Specifically, the case number was highest in Wudu District of the Longnan region (506/1,260, 40.16%), followed by Wenxian County (302/1,260, 23.97%) and Zhouqu County (202/1,260, 16.03%). In total, the cases had a male-to-female ratio of 1.46:1, and concentrated in age group of 0-5 years (665/1,260, 52.78%), showing a trend of decrease with age increase. In addition, visceral leishmaniasis occured throughout the year, with a higher cumulative incidence from March to June [10.48% (132/1,260), 13.33% (168/1,260), 12.86% (162/1,260) and 11.67% (147/1,260), respectively]. CONCLUSION: From 2005 to 2014, the Longnan region and some areas of Gannan Prefecture are the major endemic areas of visceral leishmaniasis, with more cases in children under 5 and higher incidence from March to June.

[Analysis on genotype distributions and epidemiological characteristics of Yersinia pestis plague foci in Gansu province].

OBJECTIVE: To study the genotype distributions and epidemiological characteristics of Yersinia pestis in Gansu province. METHODS: Primers were designed according to the confirmed 23 differential sections, to genotype the 202 Yersinia pestis DNA of Gansu province by PCR, and to analyze its distribution and epidemiological characteristics. RESULTS: Yersinia pestis in Gansu province could be divided into eight genotypes: 1b, 5, 7, 8, 13, 26, new genotype 1 (GS1) and new genotype 2 (GS2). They were distributed in various regions. 1b, 8 and GS1 genotypes of Yersinia pestis had been identified since 1960s but the 7, 13 and 26 genotypes had not been isolated for more than 40 years while GS2 and 5 genotypes had been isolated since 1990s. CONCLUSION: 1b, 8 and GS1 genotypes of Yersinia pestis continued to be violently prevalent since 1960s but 7, 13 and 26 genotypes had not been isolated for more than 40 years while GS2 and 5 genotypes had started to be popular since 1990s.

[The tendency of prevalence of hypertension in two countries in Gansu province from 1990 to 2012].

OBJECTIVE: To study the variation tendency of hypertension in two rural areas in Gansu, and provide epidemiological evidence to evaluate the hypertension of rural residents. METHODS: Using equidistant random sampling method and cross-sectional sentinel monitoring, two remote natural villages, Yangzhuang and Xiangming, at Yellow river and Yangtze river valley were selected as hypertension monitoring site. From 1990 to 2012, clinical examination to the resident above 18 years old was carried out continuously for 23 years, 11 164 cases were included. RESULTS: Hypertension prevalence of tested cases increased with years, Yangzhuang monitoring site increased from 6.9% (16/232) in 1990 to 36.7% (216/597) in 2012 with an increase of 29.8%, and Xiangming monitoring site increased from 3.4% (16/474) in 1995 to 20.6% (120/582) in 2011 with an increase of 17.2%. Total prevalence of Yangzhuang (24.1%, 1505/6240) was significantly higher than Xiangming (11.4%, 578/4924) (χ(2) = 277.9, P < 0.01). Total hypertension prevalence of 18 - 35 years old group was 9.9% (292/2944) in Yangzhuang and 4.2% (63/1495) in Xiangming, Yangzhuang was higher than Xiangming (χ(2) = 43.7, P < 0.01). Total hypertension prevalence of above 35 years old group was 36.8% (1213/3296) in Yangzhuang and 14.1% (515/3429) in Xiangming, Yangzhuang was higher than Xiangming (χ(2) = 417.7, P < 0.01). The growth rates of hypertension prevalence in 18 - 35 years old group of both areas (Yangzhuang: 823.5%, Xiangming: 614.3%) were higher than 35 years old group (Yangzhuang:310.5%, Xiangming: 368.0%), but the hypertension prevalence of above 35 years old group was higher than 18 - 35 years old group. Hypertension prevalence of male was 25.4% (761/2992) in Yangzhuang and 11.7% (238/2047) in Xiangming, Yangzhuang was higher than Xiangming (χ(2) = 145.8, P < 0.01), hypertension prevalence of female was 22.7% (738/3248) in Yangzhuang and 11.2% (340/2877)in Xiangming, Yangzhuang was higher than Xiangming (χ(2) = 125.1, P < 0.01). While the difference between male and female had no statistical significance in both areas. CONCLUSION: Hypertension of the two monitoring points was in high epidemic trend, but with different epidemic trend. From different region and environment research to discuss the cause of hypertension can provide scientific evidence for prevention and control.

Role of mitochondrial function in the protective effects of ischaemic postconditioning on ischaemia/reperfusion cerebral damage.

OBJECTIVE: To investigate the effects of ischaemic postconditioning on brain injury and mitochondria in focal ischaemia and reperfusion, in rats. METHODS: Adult male Wistar rats (n = 15 per group) underwent sham surgery, ischaemia (2-h middle cerebral artery occlusion), or ischaemia followed by ischaemic postconditioning (three cycles of 30 s reperfusion/30 s reocclusion). Brain infarction size, neurological function, mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential and mitochondrial swelling were evaluated 24 h postsurgery. RESULTS: Infarct size was significantly smaller, and neurological function was significantly better, in the ischaemic postconditioning group than in the ischaemia group. Ischaemia resulted in significant increases in mitochondrial ROS production and swelling, and a reduction in mitochondrial membrane potential, all of which were significantly reversed by postconditioning. CONCLUSIONS: The protective role of ischaemic postconditioning in focal ischaemia/reperfusion may be due to decreased mitochondrial ROS production, reduced mitochondrial membrane potential and suppressed mitochondria swelling. Mitochondria are potential targets for new therapies to prevent brain damage caused by ischaemia and reperfusion.

[Study on the relationship between iodine status and growth in infants at the key period of brain development].

OBJECTIVE: To investigate the relationship between iodine nutrition and growth/development in infants at the key period of brain development. METHODS: All women from pregnancy to the end of lactation and the weaning infants within 3 years in the Linxia Hui Autonomous Prefecture (Linxia Prefecture) were added iodized oil in 2006 - 2010. In 2006, 2010 one town was randomly selected from each of the five directions (east, south, west, north, central) of each county in Linxia Prefecture. One village was chosen from every town and 20 infants, 20 pregnant women and 20 lactating women were randomly selected in each town. Urinary iodine (UI) of the infants, pregnant and lactating women were determined. DQ value, height and weight of part of infants were measured. According to the above sampling plan, UI of pregnant women, lactating women and infants had been monitored every year after intervention. 0-3 infants were choosing to be control before intervention. RESULTS: UI of 1056 and 2989 0-3 infants were investigated before and after the iodine oil intervention. After the 'iodine oil' intervention, the median UI of infants increased from 107.3 µg/L to 139.6 - 190.7 µg/L, the percentage of UI level that lower than 50 µg/L, decreased from 23.9% to 6.7% - 12.9%. DQ value increased from 92.8 to 104.3, the percentage of normal height and above increased from 65.0% to 82.1% and the percentage of the normal weight and above, increased from 59.3% to 81.4%. The outcomes of DQ value, height and weight showed statistically significant differences, compared to the pre-intervention outcomes (P < 0.05). The median UI of pregnant and lactating women increased from 89.3 µg/L to 118.2 - 187.8 µg/L and from 84.9 µg/L to 135.2 - 187.5 µg/L respectively. CONCLUSION: Infant's growth and development were retarded when iodine deficiency existed at the key period of brain development. Intake of oral iodine oil at key period of brain development could provide adequate nutrition thus improve growth and development on infants.

Sellar Chordoma Presenting as Pseudo-macroprolactinoma with Unilateral Third Cranial Nerve Palsy.

We described a 61-year-old female with a sellarchordoma, which presented as pseudo-macroprolactinoma with unilateral third cranial nerve palsy. Physical examination revealed that her right upper lid could not be raised by itself, right eyeball movement limited to the abduction direction, right pupil dilated to 4.5 mm with negative reaction to light, and hemianopsia in bitemporal sides. CT scanning showed a hyperdense lesion at sellar region without bone destruction. Magnetic resonance imaging (MRI) revealed the tumor was 2.3 cm×1.8 cm×2.6 cm, with iso-intensity on T1WI, hyper-intensity on T2WI and heterogeneous enhancement on contrast imaging. Endocrine examination showed her serum prolactin level increased to 1,031.49 mIU/ml. The tumor was sub-totally resected via pterional craniotomy under microscope and was histologically proven to be a chordoma. Postoperatively, she recovered uneventfully but ptosis and hemianopsia remained at the 6th month.

Proteasome inhibitor MG-132 induces C6 glioma cell apoptosis via oxidative stress.

AIM: Proteasome inhibitors have been found to suppress glioma cell proliferation and induce apoptosis, but the mechanisms are not fully elucidated. In this study we investigated the mechanisms underlying the apoptosis induced by the proteasome inhibitor MG-132 in glioma cells. METHODS: C6 glioma cells were used. MTT assay was used to analyze cell proliferation. Proteasome activity was assayed using Succinyl-LLVY-AMC, and intracellular ROS level was evaluated with the redox-sensitive dye DCFH-DA. Apoptosis was detected using fluorescence and transmission electron microscopy as well as flow cytometry. The expression of apoptosis-related proteins was investigated using Western blot analysis. RESULTS: MG-132 inhibited C6 glioma cell proliferation in a time- and dose-dependent manner (the IC(50) value at 24 h was 18.5 µmol/L). MG-132 (18.5 µmol/L) suppressed the proteasome activity by about 70% at 3 h. It induced apoptosis via down-regulation of antiapoptotic proteins Bcl-2 and XIAP, up-regulation of pro-apoptotic protein Bax and caspase-3, and production of cleaved C-terminal 85 kDa PARP). It also caused a more than 5-fold increase of reactive oxygen species. Tiron (1 mmol/L) effectively blocked oxidative stress induced by MG-132 (18.5 µmol/L), attenuated proliferation inhibition and apoptosis in C6 glioma cells, and reversed the expression pattern of apoptosis-related proteins. CONCLUSION: MG-132 induced apoptosis of C6 glioma cells via the oxidative stress.

Pilomyxoid astrocytoma in cerebellum.

Pilomyxoid astrocytoma is a new identified variant type of pilocytic astrocytoma, and typically locates in the hypothalamic and chiasmatic region. Herein, we reported a nine-year-old boy with pilomyxoid astrocytoma in the cerebellum. MRI scanning showed a tumor involved the cerebellar vermis, tonsil, the forth ventricle and brainstem. It was homogeneous isointensity on T1WI, relative hyper-intensity on T2WI, hyper-intensity on fluid attenuated inversion recovery (FLAIR) images, and uniform enhancement on contrast T1WI. The tumor was sub-totally removed and was proved histologically to be pilomyxoid astrocytoma. Follow-up at the 5th month, MRI showed the residual tumor enlarged at the brainstem. The patient survived 10 months after the operation, and finally died of respiration failure resulting from brainstem dysfunction.

Two subtypes of meningiomas with different imaging co-existed at sphenoid ridge.

Intracranial multiple meningiomas are not uncommon, but multiple meningiomas consisting of different subtypes are rare. Here, we describe an adult male patient with two meningiomas located at sphenoid ridge, with different features on MRI and CTA. Histological examination revealed that one was fibrous meningioma and the other was psammomatous meningioma.

Large cystic hypoglossal schwannoma with fluid-fluid level: a case report.

Hypoglossal schwannomas are rare skull base tumors. Furthermore, cystic hypoglossal schwannomas are extremely uncommon. We report the first case of a large cystic hypoglossal schwannoma with a fluid-fluid level. A 36-year-old woman presented with increased intracranial pressure and cerebellar signs without hypoglossal nerve palsy. Magnetic resonance imaging showed a predominantly cystic mass with a fluid-fluid level in the foramen magnum region extending into the hypoglossal canal. The intracranial tumor was largely removed via a midline suboccipital subtonsillar approach, leaving only a tiny residue in the hypoglossal canal. Histology confirmed a schwannoma with relative hypervascularity. Twenty months later, the tumor recurred and presented as a multicystic dumbbell-shaped lesion, extending intra- and extracranially through the enlarged hypoglossal canal. A complete resection of the intracranial and intracanalicular parts of the tumor was achieved with a small extracranial remnant treated by radiosurgery. Histology revealed a focal increased K(i)67 proliferative index. In this report, we discuss the possible reasons for the absence of hypoglossal nerve palsy and the potential mechanism of the formation of the fluid-fluid level, and we consider the treatment of this lesion.