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Bu Yang Huan Wu decoction (BYHW) is a traditional Chinese medicine (TCM) that consists of several herbs and has been used in patients with ischemic stroke for centuries. Although powdered formula of BYHW has widely been prescribed in clinic nowadays, evidence-based effectiveness and mechanism of action of BYHW powdered product in stroke remain to be characterized. Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion for 24 h (ischemia/reperfusion; I/R) or sham surgery. After I/R, the rats were then given low dose (0.5 g/kg) and high dose (2.5 g/kg) of BYHW or vehicle by oral gavage twice a day for seven consecutive days. The results showed that I/R induced obvious cerebral infarction and neurobehavioral defects, in parallel with histological aberrations and extensive signaling of proinflammatory cytokines, including tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), in the stroke model. Post-I/R treatment with BYHW powdered product significantly reduced the infarct area and ameliorated neurofunctional defects in a dose-dependent manner. The dose dependence was associated with TNF-α downregulation and interleukin-10 (IL-10) induction. In summary, the present findings demonstrated that BYHW powdered product exhibited therapeutic efficacy for experimental stroke and a higher dose treatment may strengthen the effectiveness via inflammatory modulation.

Despite advances in the diagnosis and treatment of the central nervous system malignancy glioma, overall survival remains poor. Cytoskeleton-associated protein 2-like (CKAP2L), which plays key roles in neural progenitor cell division, has also been linked to poor prognosis in lung cancer. In the present study, we investigated the role of CKAP2L in glioma. From bioinformatics analyses of datasets from The Cancer Gene Atlas and the Chinese Glioma Genome Atlas, we found that CKAP2L expression correlates with tumor grade and overall survival. Gene set enrichment analysis (GSEA) showed that MITOTIC_SPINDLE, G2M_CHECKPOINT, and E2F_TARGETS are crucially enriched phenotypes associated with high CKAP2L expression. Using U87MG, U118MG, and LNZ308 human glioma cells, we confirmed that CKAP2L knockdown with siCKAP2L inhibits glioma cell proliferation, migration, invasion, and epithelial-mesenchymal transition. Interestingly, CKAP2L knockdown also induced cell cycle arrest at G2/M phase, which is consistent with the GSEA finding. Finally, we observed that CKAP2L knockdown led to significant increases in miR-4496. Treating cells with exogenous miR-4496 mimicked the effect of CKAP2L knockdown, and the effects of CKAP2L knockdown could be suppressed by miR-4496 inhibition. These findings suggest that CKAP2L is a vital regulator of miR-4496 activity and that CKAP2L is a potentially useful prognostic marker in glioma.

Traumatic brain injury (TBI) can lead to severe adverse clinical outcomes, including death and disability. Early detection of in-hospital mortality in high-risk populations may enable early treatment and potentially reduce mortality using machine learning. However, there is limited information on in-hospital mortality prediction models for TBI patients admitted to emergency departments. The aim of this study was to create a model that successfully predicts, from clinical measures and demographics, in-hospital mortality in a sample of TBI patients admitted to the emergency department. Of the 4881 TBI patients who were screened at the emergency department at a high-level first aid duty hospital in northern Taiwan, 3331 were assigned in triage to Level I or Level II using the Taiwan Triage and Acuity Scale from January 2008 to June 2018. The most significant predictors of in-hospital mortality in TBI patients were the scores on the Glasgow coma scale, the injury severity scale, and systolic blood pressure in the emergency department admission. This study demonstrated the effective cutoff values for clinical measures when using machine learning to predict in-hospital mortality of patients with TBI. The prediction model has the potential to further accelerate the development of innovative care-delivery protocols for high-risk patients.

Malignant brain tumors are responsible for catastrophic morbidity and mortality globally. Among them, glioblastoma multiforme (GBM) bears the worst prognosis. The GrpE-like 2 homolog (GRPEL2) plays a crucial role in regulating mitochondrial protein import and redox homeostasis. However, the role of GRPEL2 in human glioblastoma has yet to be clarified. In this study, we investigated the function of GRPEL2 in glioma. Based on bioinformatics analyses from the Cancer Gene Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we inferred that GRPEL2 expression positively correlates with WHO tumor grade (p < 0.001), IDH mutation status (p < 0.001), oligodendroglial differentiation (p < 0.001), and overall survival (p < 0.001) in glioma datasets. Functional validation in LN229 and GBM8401 GBM cells showed that GRPEL2 knockdown efficiently inhibited cellular proliferation. Moreover, GRPEL2 suppression induced cell cycle arrest at the sub-G1 phase. Furthermore, GRPEL2 silencing decreased intracellular reactive oxygen species (ROS) without impending mitochondria membrane potential. The cellular oxidative respiration measured with a Seahorse XFp analyzer exhibited a reduction of the oxygen consumption rate (OCR) in GBM cells by siGRPEL2, which subsequently enhanced autophagy and senescence in glioblastoma cells. Taken together, GRPEL2 is a novel redox regulator of mitochondria bioenergetics and a potential target for treating GBM in the future.

Glioblastomas are the most common type of adult primary brain neoplasms. Clinically, it is helpful to identify biomarkers to predict the survival of patients with gliomas due to its poor outcome. Shugoshin 2 (SGO2) is critical in cell division and cell cycle progression in eukaryotes. However, the association of SGO2 with pathological grading and survival in patients with gliomas remains unclear. We analyzed the association between SGO2 expression and clinical outcomes from Gene Expression Omnibus (GEO) dataset profiles, The Cancer Genome Atlas (TCGA), and Chinese Glioma Genome Atlas (CGGA). SGO2 mRNA and protein expression in normal brain tissue and glioma cell lines were investigated via quantitative RT-PCR, Western blot, and IHC staining. The roles of SGO2 in proliferation, migration, and apoptosis of GBM cells were studied with wound-healing assay, BrdU assay, cell cycle analysis, and JC-1 assay. The protein–protein interaction (PPI) was analyzed via Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). SGO2 mRNA expression predicted higher grade gliomas than non-tumor brain tissues. Kaplan–Meier survival analysis showed that patients with high-grade gliomas with a higher SGO2 expression had worse survival outcomes. SGO2 mRNA and protein expression were upper regulated in gliomas than in normal brain tissue. Inhibition of SGO2 suppressed cell proliferation and migration. Also, PPI result showed SGO2 to be a potential hub protein, which was related to the expression of AURKB and FOXM1. SGO2 expression positively correlates with WHO pathological grading and patient survival, suggesting that SGO2 is a biomarker that is predictive of disease progression in patients with gliomas.

Siou-Min Luo,1 Yi-Ping Wu,2 Li-Chun Huang,2 Shih-Ming Huang,1,2 Dueng-Yuan Hueng1– 3 1Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China; 2Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, Republic of China; 3Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of ChinaCorrespondence: Dueng-Yuan HuengDepartment of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of ChinaTel +886-2-8792-3100 #18802Email hondy2195@yahoo.com.twPurpose: Glioblastoma multiforme (GBM) is the primary aggressive malignancy of the brain with poor outcome. Curcumin analogues are polyphenolic compounds as the bioactive substances extracted from turmeric. This study aims to investigate the anti-cancer effects of four curcumin analogues. Furthermore, the molecular mechanisms of dimethoxycurcumin in human gliomas were analyzed by Western blot.Materials and Methods: Human LN229 and GBM8401 glioma cells were treated by four curcumin analogues with different number of methoxy groups. The cell viability, cell cycle, apoptosis, proliferation and ROS production of human gliomas were analyzed by flow cytometry. Moreover, the effects of four curcumin analogues on tumorigenesis of gliomas were conducted by wound healing assay and colony formation assay. Furthermore, the molecular mechanisms of dimethoxycurcumin in human gliomas were analyzed by Western blot.Results: Our data showed that four different curcumin analogues including curcumin, bisdemethoxycurcumin, demethoxycurcumin, and dimethoxycurcumin promote sub-G1 phase, G2/M arrest, apoptosis, and ROS production in human glioma cells. Moreover, dimethoxycurcumin suppressed cell viability, migration, and colony formation, induction of sub-G1, G2/M arrest, apoptosis, and ROS production in glioma cells. Moreover, the mechanism of dimethoxycurcumin is ROS production to increase LC3B-II expression to induce autophagy. Furthermore, dimethoxycurcumin suppressed apoptotic marker, BCL-2 to promote apoptosis in LN229 and GBM8401 glioma cells.Conclusion: Our study found that dimethoxycurcumin induced apoptosis, autophagy, ROS production and suppressed cell viability in human gliomas. Dimethoxycurcumin might be a potential therapeutic candidate in human glioma cells.Keywords: curcumin, bisdemethoxycurcumin, demethoxycurcumin, dimethoxycurcumin, glioblastoma

Simple hematoma evacuation is often performed in cases of chronic subdural hematoma (CSDH) associated with arachnoid cysts (ACs) on the same side after head injury. However, it is not clear which procedure is appropriate when ACs and CSDH are located on different sides. Here, we present a case of a 3-year-old boy with right frontal–temporal subdural hematoma and an AC over the left frontal–temporal region. Treatment involved craniotomy with hematoma evacuation, but no drainage of contralateral AC was applied. The patient was discharged 7 days after surgery without any neurologic deficits and no symptoms of headache or poor appetite. These results suggest that craniotomy and hematoma evacuation without intervention for the AC is adequate in patients with contralateral CSDH with a large AC.

Grade IV astrocytoma, also known as glioblastoma multiforme (GBM), is the most common and aggressive intracranial glial tumor. GBM is associated with very poor survival and effective treatments have remained elusive so far. Mounting evidence indicates that CD164 contributes to stemness and tumorigenesis in normal cells and is overexpressed in various tumor types, including glioblastoma. Using tissue microarray immunohistochemistry, we show that there is a significant correlation between CD164 expression and glioma type and grade. Depletion of CD164 expression in human glioblastoma cells with siRNA reduced proliferation, migration, and invasiveness. In parallel, immunoblotting showed that downregulation of CD164 expression decreased Akt activation and modified the expression of autophagy markers by upregulating Beclin-1 and LC3B and downregulating p62. These effects were mimicked by inhibition of Akt with MK2206, which suggests that CD164 induces autophagy via Akt/Beclin-1 signaling. We propose that CD164 may serve as a GBM molecular marker and a potential target in therapeutic strategies aimed to improve outcomes for this devastating brain tumor.

Siou-Min Luo,1 Wen-Chiuan Tsai,2 Chia-Kuang Tsai,1,3 Ying Chen,4 Dueng-Yuan Hueng1,5,6 1Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China; 2Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 3Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 4Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, Republic of China; 5Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 6Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, Republic of ChinaCorrespondence: Dueng-Yuan Hueng No. 325, Sec. 2, Chenggong Road, Neihu Dist., Taipei City, 114, Taiwan, Republic of ChinaTel +886-2-8792-7177Email hondy2195@yahoo.com.twPurpose: Glioblastoma multiforme is a highly malignant primary brain cancer with a poor prognosis. We recently reported that ARID4B could potentially serve as a biomarker associated with poor survival in glioma patients. However, the function of ARID4B in human gliomas remains unclear. The aim of this study is to investigate the molecular cell biology role of ARID4B in human glioma cells.Materials and Methods: Gene Expression Omnibus (GEO) and Human Protein Atlas (HPA) datasets were analyzed for the expression of ARID4B in WHO pathological grading, overall survival and immunohistochemical staining. Using quantitative RT-PCR and Western blotting, those findings were confirmed in normal brain tissue and glioma cell lines. ARID4B knockdown was conducted via lentivirus-based transfection of small hairpin RNA in human glioma cells to investigate cell proliferation, cell cycle, and apoptosis.Results: In the present study, our analysis of GEO datasets showed that ARID4B mRNA expression is higher in WHO grade IV tumors (n = 81) than in non-tumor control tissue (n = 23, P < 0.0001). ARID4B knockdown suppressed glioma cell proliferation and induced G1 phase arrest via the PI3K/AKT pathway. It also increased expression of HDAC1, leading to higher acetyl-p53 and acetyl-H3 levels and reduced glioma cell migration and invasion. These effects were mediated via downregulation of AKT pathway components, including p-mTOR, p-PI3K and p-AKT. ARID4B knockdown also led to downregulation of Cyclin D1, which increased apoptosis in human glioma cells.Conclusion: These findings that ARID4B expression correlates positively with WHO pathologic grading in glioma. ARID4B knockdown suppresses PI3K/AKT signaling and induces apoptosis in human glioma cells. These results suggests that ARID4B acts as an oncogene in human gliomas.Keywords: invasion, migration, cell proliferation, mTOR, Cyclin D1

Solute carrier family 16 member 1 (SLC16A1) is a crucial transcription factor in modifying cancer progression and metastasis. However, its character in defining the clinical prognosis of human gliomas has not been illuminated. In our analysis from PREdiction of Clinical Outcomes from Genomic Profiles (PRECOG), The Cancer Genome Atlas (TCGA), and Chinese Glioma Genome Atlas (CGGA), we found that SLC16A1 mRNA expression level was significantly increased in high-grade gliomas in contrast to low-grade gliomas and non-tumor controls (P

High-grade gliomas are the most threatening brain tumors due to aggressive proliferation and poor prognosis. Thus, utilizing genetic glioma biomarkers to forecast prognosis and guide clinical management is crucial. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) modulates cancer progression and metastasis. However, its detailed function in cancer remains largely uninvestigated. PLOD3 expression was evaluated with real-time PCR in glioblastoma (GBM) cell lines and by Gene Expression Omnibus dataset analysis and immunohistochemistry of glioma tissues. We investigated the clinical use of PLOD3 for determining glioma prognosis. The biological roles of PLOD3 in proliferation, migration and invasion of GBM cells were studied both in vitro with wound-healing and transwell assays and in vivo using an orthotopic xenograft mouse model. Hypoxia and western blotting were applied to discover the molecular mechanisms underlying PLOD3 functions. PLOD3 mRNA and protein expression were upregulated in glioma tissues compared to normal brain tissues. PLOD3 overexpression was correlated with negative survival in glioma patients. PLOD3 silencing suppressed cell proliferation and induced G1 phase arrest through p53-independent regulation of the p21 pathway. Inhibition of PLOD3 in glioma cells decreased VEGF expression, migration and invasion by downregulating mesenchymal markers, including Snail and Twist. Notably, knockdown of PLOD3 inhibited HIF-1α accumulation via the ERK signaling pathway under hypoxia. Taken together, these discoveries reveal that PLOD3 is a potential therapeutic target in human gliomas.

Neuropathic pain (NP) is difficult to treat due to complex pathophysiological mechanisms. Pulsed radiofrequency (RRF) has been used widely with neuromodulation effect in refractory chronic pain treatment. A recent study found that PRF treatment may decrease chronic pain-related anxiety-depressant symptoms in patients, even though the mechanisms are unclear. Additionally, accumulated evidence has shown serotonin uptake is correlated with various neuropsychiatric diseases. Therefore, we investigated the effects and underlying mechanisms of PRF on depression-like behaviors, resulting from spared nerve injury (SNI)-induced NP. We examined the indexes of mechanical allodynia, cold allodynia, depression-like behavior, and blood cytokines by dynamic plantar aesthesiometry, acetone spray test, forced swimming test, and ProcartaPlex multiplex immunoassays in male Wistar rats, respectively. Serotonin transporters (SERTs) in rat brains were examined by using 4-[18F]-ADAM/PET imaging. We found that specific uptake ratios (SURs) of SERTs were significantly decreased in the brain regions of the thalamus and striatum in rats with SNI-induced NP and depression-like behaviors. Additionally, the decrease in SERT density was correlated with the development of a depression-like behavior indicated by the forced swimming test results and pronounced IL-6 cytokines. Moreover, we demonstrated that PRF application could modulate the descending serotoninergic pathway to relieve pain and depression behaviors.

Glioblastoma multiforme (GBM) is the most frequently occurring and gravest primary tumor of the CNS in adults. The development of chemoresistance to temozolomide (TMZ), the first-line chemotherapy for GBM, is an important factor contributing to poor treatment outcomes. Down-regulation of O-6-methylguanine-DNA methyltransferase (MGMT) expression in GBM cells is an attractive strategy for overcoming TMZ resistance and improving outcomes. This study revealed that the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) exerts antitumorigenic effects on TMZ-sensitive and TMZ-resistant (TMZ-R) glioma cells. Pretreatment with SNAP not only induced apoptosis, mitochondrial dysfunction, and hypoxia-inducing factor 1, but also resensitized TMZ-R GBM cells to TMZ through down-regulation of MGMT expression. SNAP acted principally through post-translational modification of p53, phosphorylated N-myc downstream regulated gene 1, and MGMT protein stability in TMZ-R GBM cells. Additionally, when applied together, SNAP and TMZ enhanced the inhibition of tumor growth in vitro and in vivo. This study sheds new light on a potential strategy to overcome TMZ resistance in GBM and thus possesses the potential for prolonging survival of patients with GBM.-Tsai, C.-K., Huang, L.-C., Wu, Y.-P., Kan, I.-Y., Hueng, D.-Y. SNAP reverses temozolomide resistance in human glioblastoma multiforme cells through down-regulation of MGMT.

Forkhead box, class O, 1A (FOXO1A) is an important factor related to some human malignancies. We tested the association between FOXO1A cytoplasmic expression and World Health Organization grading system in primary brain tumors (PBTs). First of all, Western blot analysis was also performed in normal brain tissue and U87MG, LN229, GBM8401, and U118MG glioma cell lines protein lysates. Then, in order to realize FOXO1A gene expression in gliomas, U87MG, LN229, GBM8401 mRNA were applied to performed quantitative reverse transcription polymerase chain reaction (RT-PCR). At last, the immunohistochemical (IHC) analysis of FOXO1A was performed in 8 non-neoplastic brain tissues and 126 PBTs. The immunostain scores were obtained as the degree of cytoplasmic FOXO1A intensity multiplied by the percentage of positively stained tumor area. On the basis of the results of these in vitro studies, marked increase FOXO1A protein and mRNA expressions in glioma cell lines than in normal human tissue. On the view point of IHC stains, the average immunostain score of FOXO1A in all PBTs was significantly higher than non-neoplastic brain tissues. In addition, the immunostain scores of FOXO1A in high grade were higher than low-grade gliomas. Furthermore, higher cytoplasmic expression of FOXO1A might indicate the shorter overall survival rate in gliomas. Furthermore, FOXO1A expression was associated with isocitrate dehydrogenase I /2, ATRX, and p53 mutation by IHC staining. Therefore, the application of FOXO1A IHC stain might have some benefits to improve diagnostic accuracy, predict tumor progression, and evaluate survival time in glioma patients.

Intradural extramedullary lipomas are rare congenital and histologically benign tumors that represent

Glioblastoma has aggressive proliferative and invasive properties. We investigated the effect of caffeine on the invasion and the anti-cancer effect in human glioblastomas. Caffeine reduced the invasion in U-87MG, GBM8401 and LN229 cells. Caffeine decreased mRNA, protein expression, and activity of cathepsin B. Besides, mRNA and protein expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) was upregulated by caffeine treatment, whereas matrix metalloproteinase-2 (MMP-2) was downregulated. The expression of Ki67, p-p38, phospforylated extracellular regulated protein kinases (p-ERK), and membranous integrin β1 and β3 was decreased by caffeine. The Rho-associated protein kinase (ROCK) inhibitor, Y27632, blocked the caffeine-mediated reduction of cathepsin B, phosphorylated focal adhesion kinase (p-FAK), and p-ERK, and invasion. Moreover, caffeine decreased the tumor size, cathepsin B and Ki67 expression in animal model. Caffeine reduced the invasion of glioma cells through ROCK-cathepsin B/FAK/ERK signaling pathway and tumor growth in orthotopic xenograft animal model, supporting the anti-cancer potential in glioma therapy.

The high level of resistance of glioblastoma multiforme (GBM) to currently used chemotherapies and other conventional therapies, its invasive characteristics and the presence of stem-like cells are the major factors that make the treatment of GBM difficult. Recent studies have demonstrated that the homeostasis of energy metabolism, glycolysis and mitochondrial oxidation of glucose are important for GBM cell growth and chemo-resistance. However, it is not clear which specific gene(s) are involved in the homeostasis of energy metabolism and invasiveness of GBM cells. We performed a preliminary analysis of data obtained from Gene Expression Omnibus profiles and determined that malic enzyme 2 (ME2) expression was positively associated with WHO grade in human primary gliomas. Hence, we evaluated the detailed working mechanisms of ME2 in human GBM cell processes, including proliferation, cell cycle, invasion, migration, ROS, and ATP production. Our data demonstrated that ME2 was involved in GBM growth, invasion and migration. ME2 has two cofactors, NAD+ or NADP+, which are used to produce NADH and NADPH for ATP production and ROS clearance, respectively. If the catalytic activity of ME2 is determined to be critical for its roles in GBM growth, invasion and migration, small molecule inhibitors of ME2 may be valuable drugs for GBM therapy. We hope that our current data provides a candidate treatment strategy for GBM.

Background: High-grade primary gliomas are aggressively growing and have an unfavorable prognosis. The utility of prognostic biomarkers of outcome in glioma patients is important for medical practice. Cell division cycle-associated 7-like (CDCA7L) protein modifies cancer progression and metastasis. Nevertheless, its character in defining the clinical prognosis of human gliomas has not been illuminated. Subjects and Methods: The hypothesis of this study was that CDCA7L is upregulated in human gliomas. We studied two de-linked data from Gene Expression Omnibus (GEO) profile. The first dataset (GDS1816/225081_s_at/CDCA7L) in primary high-grade glioma included age, gender, and survival time. Another dataset (GDS1962/225081_s_at/CDCA7L) was also encompassed to estimate CDCA7L gene expression in each pathological grading. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) was used to survey the protein-protein interaction (PPI) network of CDCA7L-regulated oncogenesis. Results: Statistical analysis of the GEO profile revealed that the World Health Organization (WHO) Grade IV (n = 81) gliomas had higher CDCA7L mRNA expression level than in Grade II (n = 7, P = 2.15 × 10 −14) gliomas and nontumor controls (n = 23, P = 2.87 × 10 − 18). Kaplan-Meier analysis reported that patients with high CDCA7L mRNA levels (n = 49) had adverse survival than those with low CDCA7L expression (n = 28). The PPI analysis of CDCA7L-regulated oncogenesis showed CDCA7L as a potential hub protein. Conclusions: The expression of CDCA7L has a positive correlation with the WHO pathological grading and shorter survival. This finding suggests that CDCA7L may be a potential biomarker of prognosis in human gliomas.

Studies show that vertebral fractures could predict the risk of hip fractures. We aimed to evaluate the potential benefits of whether the timing of vertebroplasty (VP) for vertebral fracture associated with the risk of hip fracture for hip replacement.We identified 142,782 patients from the Taiwan National Health Insurance Database with thoracolumbar vertebral fracture (International Classification of Diseases, Ninth Revision, Clinical Modification:805.2-805.9) who were followed up from 2000 to 2013. These patients were divided into those who underwent VP (VP group) (International Classification of Diseases, Ninth Revision, Clinical Modification : 78.49) within 3 months and those who did not (non-VP group). After adjusting for the confounding factors, the Cox proportional hazards analysis was used to estimate the effect of early VP on reducing the risk of hip fracture. The difference in the risk of hip replacement, between the VP group and non-VP group was estimated using the Kaplan-Meier method with the log-rank test.In the 14-year follow-up, the cumulative incidence rate of hip replacement in the VP group was lower than that in the non-VP group (0.362% and 0.533%, respectively, long-rank P < .001). There was a significant difference between the 2 groups since the first-year follow-up.Our study showed that early VP performed to avoid progression of the kyphotic changes following thoracolumbar vertebral fracture may reduce the risk of hip fracture. These results, obtained from retrospective data, indicate that a prospective study is warranted.

Background: Clinical applications of transsylvian-transinsular (TS-TI) approaches to hypertensive basal ganglia hemorrhages (HBGHs) have an enormous difference in functional independence rate. The aim of this study is to investigate the clinical efficacy of minipterional craniotomy with rostral TS-TI approach to HBGH and compare functional independence rate with distal TS-TI variant. Methods: From April 2017 to April 2019, eleven patients with symptomatic HBGH accepting minipterional craniotomies with rostral TS-TI approaches were analyzed retrospectively. Results: The mean volume of preoperative hematoma was 57.08 ml with a 99.20% evacuation rate. Postoperative images revealed no rebleeding or newly developed hypodense lesion. Nine out of eleven patients got clear consciousness with functional independence at 3 months postoperatively. Conclusions: In comparison with distal TS-TI approach, minipterional craniotomy with rostral TS-TI approach to HBGH provides satisfactory outcome with higher functional independence rate.

Background: Glioblastoma (GBM), a malignant form of glioma, is characterized by resistance to therapy and poor prognosis. Accumulating evidence shows that the initiation, propagation, and recurrence of GBM is attributable to the presence of GBM stem cells (GBM-CSCs). Experimental approach: Herein, we investigated the effect of 4-Acetylantroquinonol B (4-AAQB), a bioactive isolate of Antrodia cinnamomea, on GBM cell viability, oncogenic, and CSCs-like activities. Results: We observed that aberrant expression of catenin is characteristic of GBM, compared to other glioma types (p = 0.0001, log-rank test = 475.2), and correlates with poor prognosis of GBM patients. Lower grade glioma and glioblastoma patients (n = 1152) with low catenin expression had 25% and 21.5% better overall survival than those with high catenin expression at the 5 and 10-year time-points, respectively (p = 3.57e-11, log-rank test = 43.8). Immunohistochemistry demonstrated that compared with adjacent non-tumor brain tissue, primary and recurrent GBM exhibited enhanced catenin expression (~10-fold, p &lt, 0.001). Western blot analysis showed that 4-AAQB significantly downregulated β-catenin and dysregulated the catenin/LEF1/Stat3 signaling axis in U87MG and DBTRG-05MG cells, dose-dependently. 4-AAQB–induced downregulation of catenin positively correlated with reduced Sox2 and Oct4 nuclear expression in the cells. Furthermore, 4-AAQB markedly reduced the viability of U87MG and DBTRG-05MG cells with 48 h IC50 of 9.2 M and 12.5 M, respectively, effectively inhibited the nuclear catenin, limited the migration and invasion of GBM cells, with concurrent downregulation of catenin, vimentin, and slug, similarly, colony and tumorsphere formation was significantly attenuated with reduced expression of c-Myc and KLF4 proteins. Conclusions: Summarily, we show for the first time that 4-AAQB suppresses the tumor-promoting catenin/LEF1/Stat3 signaling, and inhibited CSCs-induced oncogenic activities in GBM in vitro, with in vivo validation, thus projecting 4-AAQB as a potent therapeutic agent for anti-GBM target therapy.

The aim of this study is to analyze the combined impact of preoperative T1 slope (T1S) and C2-C7 sagittal vertical axis (C2-C7 SVA) on determination of cervical alignment after laminoplasty. Forty patients undergoing laminoplasty for cervical spondylotic myelopathy (CSM) with more than 2 years follow-up were enrolled. Three parameters, including cervical lordosis, T1S, and C2-C7 SVA, were measured by preoperative and postoperative radiographs. Receiver operating characteristics (ROC) curve analysis was used to determine the optimal cut-off values of preoperative T1S and C2-C7 SVA for predicting postoperative loss of cervical lordosis. Patients were classified into 4 categories based on cut-off values of preoperative T1S and C2-C7 SVA. The primary outcome was postoperative C2-C7 SVA. Change in radiographic parameters between 4 groups were compared and analyzed. Optimal cut-off values for predicting loss of cervical lordosis were T1S of 20 degrees and C2-C7 SVA of 22 mm. Patients with small C2-C7 SVA, no matter what the value of T1S, got slight loss of cervical lordosis and increase in C2-C7 SVA. Patients with low T1S and large SVA (T1 ≤20° and SVA >22 mm) got postoperative correction of kyphosis and decrease of C2-C7 SVA. However, patients with high T1S and large SVA (T1 >20° and SVA >22 mm) got mean postoperative C2-C7 SVA value of 37.06 mm, close to the threshold value of 40 mm. Determination of cervical alignment after laminoplasty relies on the equilibrium between destruction of cervical structure, kyphotic force, and adaptive compensation of whole spine, lordotic force. Lower T1S means bigger compensatory ability to adjust different severity of cervical sagittal malalignment, and vice versa.

Although proton magnetic resonance spectroscopy (1H-MRS) is a common method for the evaluation of intracranial meningiomas, controversy exists regarding which parameter of 1H-MRS best predicts the histopathological grade of an intracranial meningioma. In this study, we evaluated the results of pre-operative 1H-MRS to identify predictive factors for high-grade intracranial meningioma. Thirteen patients with World Health Organization (WHO) grade II-III meningioma (confirmed by pathology) were defined as high-grade; twenty-two patients with WHO grade I meningioma were defined as low-grade. All patients were evaluated by 1H-MRS before surgery. The relationships between the ratios of metabolites (N-acetylaspartate [NAA], creatine [Cr], and choline [Cho]) and the diagnosis of high-grade meningioma were analyzed. According to Mann-Whitney U test analysis, the Cho/NAA ratio in cases of high-grade meningioma was significantly higher than in cases of low-grade meningioma (6.34 ± 7.90 vs. 1.58 ± 0.77, p

Glioblastoma multiforme (GBM), the most prevalent brain tumor in adults, has extremely poor prognosis. Frequent genetic alterations that activate epidermal growth factor receptor (EGFR) and phosphatidylinositol-3 kinase (PI3K) signaling, as well as metabolic remodeling, have been associated with gliomagenesis. To establish a whole-animal approach that can be used to readily identify individual pathometabolic signaling factors, we induced glioma formation in the adult Drosophila brain by activating the EGFR-PI3K pathway. Glioma-induced animals showed significantly enlarged brain volume, early locomotor abnormalities, memory deficits, and a shorter lifespan. Combining bioinformatics analysis and glial-specific gene knockdown in the adult fly glioma model, we identified four evolutionarily conserved metabolic genes, including ALDOA, ACAT1, ELOVL6, and LOX, that were involved in gliomagenesis. Silencing of ACAT1, which controls cholesterol homeostasis, reduced brain enlargement and increased the lifespan of the glioma-bearing flies. In GBM patients, ACAT1 is overexpressed and correlates with poor survival outcomes. Moreover, pharmacological inhibition of ACAT1 in human glioma cell lines revealed that it is essential for tumor proliferation. Collectively, these results imply that ACAT1 is a potential therapeutic target, and cholesterol homeostasis is strongly related to glioma formation. This in vivo model provides several rapid and robust phenotypic readouts, allowing determination of the pathometabolic pathways involved in gliomagenesis, as well as providing valuable information for novel therapeutic strategies.

Introduction: In our study, we aimed to investigate the association between a traumatic brain injury (TBI) and subsequent erectile dysfunction (ED). This is a population-based study using the claims dataset from The National Health Insurance Research Database. Methods: We included 72,642 patients with TBI aged over 20 years, retrospectively, selected from the longitudinal health insurance database during 2000–2010, according to the ICD-9-CM. The control group consisted of 217,872 patients without TBI that were randomly chosen from the database at a ratio of 1:3, with age- and index year matched. Cox proportional hazards analysis was used to estimate the association between the TBI and subsequent ED. Results: After a 10-year follow-up, the incidence rate of ED was higher in the TBI patients when compared with the non-TBI control group (24.66 and 19.07 per 100,000, respectively). Patients with TBI had a higher risk of developing ED than the non-TBI cohort after the adjustment of the confounding factors, such as age, comorbidity, residence of urbanization and locations, seasons, level of care, and insured premiums (adjusted hazard ratio (HR) = 2.569, 95% CI [1.890, 3.492], p < .001). Conclusion: This is the first study using a comprehensive nationwide database to analyze the association of ED and TBI in the Asian population. After adjusted the confounding factors, patients with TBI have a significantly higher risk of developing ED, especially organic ED, than the general population. This finding might remind clinicians that it’s crucial in early identification and treatment of ED in post-TBI patients.

Primary high-grade gliomas possess invasive growth and lead to unfavorable survival outcome. The investigation of biomarkers for prediction of survival outcome in patients with gliomas is important for clinical assessment. The DEAD (Asp-Glu-Ala-Asp) box helicase 3, X-linked (DDX3X) controls tumor migration, proliferation, and progression. However, the role of DDX3X in defining the pathological grading and survival outcome in patients with human gliomas is not yet clarified. We analyzed the DDX3X gene expression, WHO pathological grading, and overall survival from de-linked data. Further validation was done using quantitative RT-PCR of cDNA from normal brain and glioma, and immunohistochemical (IHC) staining of tissue microarray. Statistical analysis of GEO datasets showed that DDX3X mRNA expression demonstrated statistically higher in WHO grade IV (n = 81) than in non-tumor controls (n = 23, p = 1.13 × 10(-10)). Moreover, DDX3X level was also higher in WHO grade III (n = 19) than in non-tumor controls (p = 2.43 × 10(-5)). Kaplan-Meier survival analysis showed poor survival in patients with high DDX3X mRNA levels (n = 24) than in those with low DDX3X expression (n = 53) (median survival, 115 vs. 58 weeks, p = 0.0009, by log-rank test, hazard ratio: 0.3507, 95% CI: 0.1893-0.6496). Furthermore, DDX3X mRNA expression and protein production significantly increased in glioma cells compared with normal brain tissue examined by quantitative RT-PCR, and Western blot. IHC staining showed highly staining of high-grade glioma in comparison with normal brain tissue. Taken together, DDX3X expression level positively correlates with WHO pathologic grading and poor survival outcome, indicating that DDX3X is a valuable biomarker in human gliomas.

The role of urocortin (UCN) is still ambiguous in human cancers. We tested the hypothesis that using UCN expression discriminates reactive gliosis from primary brain tumors (PBTs). Immunohistochemical analysis of UCN was performed in six reactive gliosis and 99 PBTs. The immunostain scores of UCN were calculated as the degree of intensity multiplied by the percentage of expressed tumor cells. Nuclear staining of UCN revealed weak intensity and small portion of positively stained cells in reactive gliosis. However, comparing with non-neoplastic tissues, higher immunostain scores of UCN were identified in each WHO grade of astrocytomas and meningiomas. Finally, neither WHO grade nor overall survival rate did not significantly correlate with UCN expression in astrocytomas and meningiomas. Our findings demonstrate for the first time that the application of UCN might be a novel biomarker for not only discriminating reactive gliosis from PBTs, but also deciding where the clear surgical margin was.

Neural stem cell (NSC) transplantation is an emerging strategy for restoring neuronal function in neurological disorders, such as Parkinson’s disease (PD), which is characterized by a profound and selective loss of nigrostriatal dopaminergic (DA) neurons. Adult neurogenesis generates newborn neurons that can be observed at specialized niches where endothelial cells (ECs) play a significant role in regulating the behavior of NSCs, including self-renewal and differentiating into all neural lineage cells. In this minireview, we highlight the importance of establishing an appropriate microenvironment at the target site of NSC transplantation, where grafted cells integrate into the surroundings in order to enhance DA neurotransmission. Using a novel model of NSC-EC coculture, it is possible to combine ECs with NSCs, to generate such a neurovascular microenvironment. With appropriate NSCs selected, the composition of the transplant can be investigated through paracrine and juxtacrine signaling within the neurovascular unit (NVU). With target site cellular and acellular compartments of the microenvironment recognized, guided DA differentiation of NSCs can be achieved. As differentiated DA neurons integrate into the existing nigrostriatal DA pathway, the symptoms of PD can potentially be alleviated by reversing characteristic neurodegeneration.

Object This study investigated the specific preoperative MRI features of patients with intracranial meningiomas that correlate with pathological grade and provide appropriate preoperative planning. Methods From 2006 to 2012, 120 patients (36 men and 84 women, age range 20–89 years) with newly diagnosed symptomatic intracranial meningiomas undergoing resection were retrospectively analyzed in terms of radiological features of preoperative MRI. There were 90 WHO Grade I and 30 WHO Grade II or III meningiomas. The relationships between MRI features and WHO histopathological grade were analyzed and scored quantitatively. Results According to the results of multivariate logistic regression analysis, age ≥ 75 years, indistinct tumorbrain interface, positive capsular enhancement, and heterogeneous tumor enhancement were identified factors in the prediction of advanced histopathological grade. The prediction model was quantified as a scoring scale: 2 × (age) + 5 × (tumor-brain interface) + 3 × (capsular enhancement) + 2 × (tumor enhancement). The calculated score correlated positively with the probability of high-grade meningioma. Conclusions This scoring approach may be useful for clinicians in determining therapeutic strategy and in surgical planning for patients with intracranial meningiomas.

Study design A single-center retrospective study. Objective To identify the relevant incidence and risk factors of delayed vertebral collapse and progressive kyphosis with spinal canal encroachment after percutaneous vertebroplasty (PVP) for vertebral compression fracture (VCF). Summary of background data Delayed vertebral collapse and progressive kyphosis with spinal canal encroachment are complications after PVP for VCF. Methods Between December 2002 and February 2011, 843 patients underwent PVP for VCFs for at least 2 years of minimum follow-up term in a tertiary referral center. All imaging measurements were obtained digitally, with comparisons of the Cobb angle and spinal canal stenosis on fractured vertebral level at 3 different time points of pre- and postvertebroplasty, and before revision surgery. Results Thirteen patients (14 fractures) who underwent PVP had delayed vertebral collapse and progressive kyphosis on the level of the fractured vertebra, 3 were male and 10 female, with a median age of 75 years (range, 66-89 yr). One had 2-level VCFs. All were treated with revision surgery of decompressive laminectomy for spinal canal stenosis with neurological complications. Twelve patients had additional instrument fixation. The involved vertebras were concentrated at the thoracolumbar junction region (T11-L2). The mean Cobb angles were measured at 23.67° before PVP, 15.90° after PVP, and 30.92° before revision surgery. The ratio of spinal canal stenosis was 35.45% and 49.48% before PVP and revision surgery, respectively. The occurrence rate of delayed complications was about 1.5% (13/843). Conclusion Conservative treatment and minimal invasive vertebral augmentation surgery can be selected from patients with stable VCFs. Close follow-up is warrant to monitor the occurrence of late collapse with neurological complications. Level of evidence N/A.

Pentraxin 3 (PTX3) and nuclear factor-like 2 (Nrf2) are known to induce tumor progression in certain malignancies but act as tumor suppressors in other human neoplasms. In this study, we not only tested the association between PTX3 expression and the World Health Organization (WHO) tumor grading system but also evaluated overall patient survival under variable expression of PTX3 and Nrf2 in primary brain tumors (PBTs). Immunohistochemistry (IHC) was performed for PTX3 and Nrf2 in 10 nonneoplastic brain tissues and 197 PBTs. IHC scores were calculated as the degree of cytoplasmic and nuclear PTX3 and Nrf2 staining intensity multiplied by the percentage of positively stained tissue area. The correlation between PTX3 and Nrf2 IHC scores and tumor grades as well as overall survival time was analyzed by Pearson product-moment correlation and Kaplan-Meier estimate. According to our results, PTX3 IHC scores showed a positive correlation with the WHO grades of gliomas and meningiomas. In addition, we also observed that higher PTX3 expression was associated with poor prognosis in gliomas but not in meningiomas. The concordance between PTX3 and Nrf2 immunohistochemistry (IHC) scores was analyzed using linear regression analysis. When compared to groups with high IHC scores for either one or both biomarkers, gliomas with low expression of both PTX3 and Nrf2 showed significantly better prognosis. In conclusion, we demonstrated that high PTX3 expression implied aggressive tumor behavior and shorter survival time in glioma patients. In addition, our results also showed that gliomas with low PTX3 and Nrf2 immunohistochemical expression could imply a longer overall survival time. Therefore, the combination of lower PTX3 and Nrf2 immunohistochemical expression may be important in offering a better prognosis in gliomas, although the detailed mechanism is yet to be elucidated.

Cavernous segment internal carotid artery (CSICA) injury during endoscopic transsphenoidal surgery for pituitary tumor is rare but fatal. The aim of this study is to investigate anatomical relationship between pituitary macroadenoma and corresponding CSICA using quantitative means with a sense to improve safety of surgery. In this retrospective study, a total of 98 patients with nonfunctioning pituitary macroadenomas undergoing endoscopic transsphenoidal surgeries were enrolled from 2005 to 2014. Intercarotid distances between bilateral CSICAs were measured in the 4 coronal levels, namely optic strut, convexity of carotid prominence, median sella turcica, and dorsum sellae. Parasellar extension was graded and recorded by Knosp–Steiner classification. Our findings indicated a linear relationship between size of pituitary macroadenoma and intercarotid distance over CSICA. The correlation was absent in pituitary macroadenoma with Knosp–Steiner grade 4 parasellar extension. Bigger pituitary macroadenoma makes more lateral deviation of CSICA. While facing larger tumor, sufficient bony graft is indicated for increasing surgical field, working area and operative safety.

Background: Nuclear factor erythroid 2-related factor 2 (NFE2L2, also known as Nrf2) is associated with cellular progression and chemotherapeutic resistance in some human cancers. We tested the relationship between Nrf2 expression and survival of patients with primary brain tumors (PBTs). Methods: In order to realize Nrf2 protein expression in gliomas, Western blot analysis was performed in normal brain tissue and U87MG, LN229, GBM8401 and U118MG glioma cell lines protein lysates. Then, U87MG, LN229, and GBM8401 mRNA were applied to performed quantitative RT-PCR for detect Nrf2 gene expression in glioma cell lines. At last, immunohistochemical analysis was used to determine the expression of Nrf2 in samples from 178 PBTs and 10 non-neoplastic brain tissues. Results: In these included in vitro studies, both Nrf2 protein and mRNA expression in all human glioma cell lines were higher than normal brain tissue. Similarly, on the viewpoint of immunohistochemistry, Nrf2 expression in gliomas were positively correlated with World Health Organization (WHO) grades. Additionally, compared with the expression of Nrf2 in non-neoplastic brain tissue, expression in meningiomas was of a stronger intensity and was present in a higher percentage of cells. Furthermore, scores were significantly higher in WHO grade II than in WHO grade I meningiomas. Finally, overall survival tended to be shorter in patients whose PBTs had higher expression of Nrf2, although the correlation was not statistically significant. Conclusions: Nrf2 overexpression positively correlated with WHO grade in gliomas and meningiomas. On the other hand, Nrf2 immunohistochemical stain could help pathologists to differentiate atypical meningiomas from benign tumors. Therefore, Nrf2 expression may be a useful biomarker to predict WHO grade and cellular behavior of PBTs.

AimsAlthough ARID4B is known to promote tumour metastasis in breast cancer and inhibit transformation and progression in leukaemia, the possible effect of ARID4B on primary brain tumours (PBTs) is not well characterised. We tested the hypothesis that expression of ARID4B correlates with WHO grade and survival in patients with PBTs.MethodsWestern blot analysis was performed on protein lysates prepared from normal brain tissue and glioma cell lines (U87MG, LN229, GBM8401 and U118MG). Subsequently, immunohistochemical analysis of ARID4B was performed on 2 tissue microarrays, including 12 normal brain tissues, 63 meningiomas with different subtypes, 232 gliomas of various grades and degrees of differentiation, 8 central neurocytomas and 4 chordomas. The ARID4B immunostaining score was calculated by multiplying the intensity score by the percentage of tumour cells expressing ARID4B.ResultsIn vitro, ARID4B protein expression was increased in some glioma cell lines. In addition, the average ARID4B immunostaining score was 38.03, 79.09, 129.76 and 119.32, respectively, in gliomas of WHO grade I, II, III and IV. Higher ARID4B immunostaining score was significantly correlated with more advanced WHO grade of gliomas (p=7.4×10–6) and meningiomas. Finally, higher ARID4B expression tended to the shorter survival rates, but did not reach statistical significance.ConclusionsARID4B overexpression presented in most of PBTs, rather than non-neoplastic brain tissue, and correlated with WHO grades in meningiomas and gliomas. Therefore, ARID4B is a satisfactory biomarker to highlight tumour component and predict tumour behaviour in primary brain neoplasms.

Aim: Although the World Health Organization(WHO) histological criteria distinguishing benign fromatypical and malignant meningioma are clear, discern-ing benign from atypical meningioma is still somewhatdifficult, leading to interobserver diagnostic variability.Osteopontin (OPN) and cortactin play important rolesin tumorigenesis, invasion and metastasis of severalhuman cancers. The aim of this study was to evaluatethe usefulness of OPN and cortactin immunohisto-chemistry for distinguishing between benign, atypicaland malignant meningioma and predicting their recur-rence.Methods and results: Seventy-five specimens (48 be-nign, 17 atypical and 10 malignant meningiomas)were investigated immunohistochemically. Themean immunohistochemical scoreimmunohistochemi-cal score ± SE of the mean of both OPN and cortactinwere significantly higher in grade II or grade IIImeningiomas than in grade I meningioma. Discrimi-nant analysis of immunohistochemical OPN expressionshowed correct classification of 97.7% of WHO grade Imeningiomas and 88.2% of WHO grade II meningio-mas (95.4% accuracy). However, the same analysis ofcortactin expression showed correct classification of95.8% of WHO grade I meningiomas and only 23.5%of WHO grade II meningiomas (76.9% accuracy). Acut-off for predicting grades I and II meningiomarecurrence was determined for OPN (3.0) but not forcortactin. Finally, logistic regression identified both thiscut-off (P < 0.05) and WHO grade (P < 0.05) asindependent risk factors for recurrence.Conclusions: OPN expression is a valuable marker fordiagnosis of atypical meningioma and prediction ofgrades I and II meningioma recurrence.Keywords: cortactin, immunohistochemical score, meningioma, osteopontinAbbreviations: DAB, diaminobenzidine; HPF, high-power field; OPN, osteopontin

Chordomas are low- to intermediate-grade malignant tumors that recapitulate the notochord. Chordomas belong to the dysontogenetic bone tumors and appear primarily in the region of the axial skeleton. Chordomas are divided into conventional, chondroid, sarcomatoid and dedifferentiated subtypes. The different subtypes of chordoma have varied survival periods. According to the literature to date, secondary pulmonary and lymph-node metastases occur most frequently, followed by liver, bone and skin metastases. To the best of our knowledge, there has been no previous report of one subtype of chordoma metastasizing or transforming into another subtype with a different histopathology. This study presents a 24-year-old man with secondary pulmonary conventional chordoma arising from a primary sarcomatoid chordoma of the sacrum. The patient was alive at the end of November, 2009 and the survival time exceeded eight years. This is the first case of a patient with primary sarcomatoid chordoma of the sacrum with complete remission in whom a secondary pulmonary conventional chordoma arose from the primary cancer.

Proteolipid protein 2 (PLP2), a membrane protein of the endoplasmic reticulum, is related to tumor proliferation and metastasis in some human cancers, but not in gliomas. First, we performed western-blot analysis, real-time quantitative PCR and immunohistochemical stains to detect PLP2 expression in 4 glioma cell lines and human glioma tissues. In addition, we used small interfering RNA (SiPLP2) and short hairpin RNA (shPLP2) to knockdown PLP2 expression in GBM8401 and LN229 glioma cell lines. After then, the alteration of PLP2 suppressed glioma cells behavior were examined by cell proliferation, wound healing, cell invasion, and colonies formation assays. Finally, the possible mechanism of PLP2 was analyzed by detecting the expression of the proteins related to cell-cycle checkpoints, cell-proliferative signaling factors, and cell-matrix interaction. Compared with normal brain cell lysates and mRNA, all glioma cell lines displayed PLP2 protein and mRNA overexpression. Besides, higher PLP2 IHC staining significantly correlated with more advanced tumor grades and poorer prognosis in human gliomas. Both siPLP2 transfected gliomas showed a clear inhibition of glioma cell proliferation, migration, and invasion as well as down-regulating p-p38, p-ERK, MMP-2, and MMP-9 expression. In conclusion, we successfully demonstrated that PLP2 overexpression played an oncogenic role in glioma development and aggressive tumor behavior.

Prediction of recurrence remains a challenge in histopathological benign/grade I tumors. Osteopontin (OPN) plays important roles in tumorigenesis, invasion, and metastasis of several human cancers. In this study, we investigated OPN protein expression by evaluating the differences between recurrent and non-recurrent histologically benign meningiomas. Thirty-two patients were enrolled, and 23 benign non-recurrent meningiomas and 9 benign recurrent meningiomas were followed for a mean of 34 months after complete surgical resection (Simpson grades I and II). Cytoplasmic OPN staining was evaluated by means of immunohistochemistry (IHC) score and by use of the Allred-8-unit system. We examined clinical biological data, their relationship with tumor recurrence, and the expression of OPN. Our results showed that meningioma recurrence correlated significantly with OPN IHC score (P = 0.001). An OPN Allred score between 0 and 3 was associated with a recurrence-free time of more than 25 months. In comparison, an OPN Allred score from 4 to 8 was indicative of a shorter average recurrence-free time. We concluded that OPN IHC score may play a role in prediction of the recurrence of the grade I meningiomas. Moreover, determination of the OPN Allred score is a reliable, quantitative tool for predicting recurrence-free time in benign meningioma patients.

Human malignant glioma cells are characterized by local invasion. In the present study, we investigated the role of osteopontin (OPN) in the invasiveness of human glioma cells isolated from grade IV tumors. We found that the expression levels of OPN in these cell lines paralleled matrix metalloproteinase-2 (MMP-2) expression and cell invasiveness potential. When U87MG glioma cells (with a high-OPN expression level) were stably transformed with specific small hairpin RNA to knock down OPN expression, MMP-2 secretion, cell invasiveness, and tumor growth in implanted brains were dramatically reduced. Conversely, forced expression of OPN in GBM-SKH glioma cells (which expressed OPN at a low level) increased MMP-2 secretion, enhanced cell invasiveness, and increased tumor growth in a rodent xenograft model. Expression of OPN was associated with increased expression of vimentin and decreased expression of glial fibrillary acidic protein. Treatment of glioma cells with 5-aza-2′-deoxycytidine (5-aza-dC) suppressed OPN expression in a concentration-dependent manner. Suppression of OPN expression by 5-aza-dC was associated with reductions in MMP-2 secretion, vimentin expression, cell invasion, intravasation, and tumor growth. These data suggest that OPN may play important roles in regulating cell invasion in glioma cells and that 5-aza-dC may serve as a therapeutic agent for human gliomas.

AIM The association between post-decompressive hydrocephalus and clinical neurological expression is still unclear. In order to investigate this relationship, the authors analyze series of ventricular morphology and level of consciousness at different clinical stages for patients accepting decompressive craniectomy (DC). MATERIAL AND METHODS From 2005 to 2011, 13 patients accepting DC under the diagnosis of malignant cerebral infarction were retrospectively evaluated in terms of ventricular frontal horn dilatation and level of consciousness, Glasgow Coma Scale score, at four different clinical stages: 1): pre-DC stage; 2): post-DC stage while stabilization; 3): post-cranioplasty stage; 4): post-shunt stage [for those with permanent cerebrospinal fluid (CSF) diversion]. RESULTS All 13 patients had ventricular dilatation and two of them had extra-axial CSF collection. Restoration of ventricular dilatation was not observed in all patients after bone flap placement, but extra-axial CSF collection resorbed spontaneously. Four patients accepting permanent CSF diversion had no improvement over neurological expression. Otherwise, two of them complicated with subdural effusion after shunt placement. CONCLUSION Decompressive craniectomy itself would lead to ventricular dilatation universally. There is no direct association between degree of ventriculomegaly and neurological expression. Permanent CSF diversion surgery as treatment for ventriculomegaly makes no clinical improvement with possible complications of overshunting.

Objectives Previous studies have identified the factors affecting the surgical outcome of cervical spondylotic myelopathy (CSM) following laminoplasty. Nonetheless, the effect of these factors remains controversial. It is unknown about the association between pre-operative cervical spinal cord morphology and post-operative imaging result following laminoplasty. The goal of this study is to analyze the impact of pre-operative cervical spinal cord morphology on post-operative imaging in patients with CSM. Methods Twenty-six patients with CSM undergoing open-door laminoplasty were classified according to pre-operative cervical spine bony alignment and cervical spinal cord morphology, and the results were evaluated in terms of post-operative spinal cord posterior drift, and post-operative expansion of the antero-posterior dura diameter. Results By the result of study, pre-operative spinal cord morphology was an effective classification in predicting surgical outcome – patients with anterior convexity type, description of cervical spinal cord morphology, had more spinal cord posterior migration than those with neutral or posterior convexity type after open-door laminoplasty. Otherwise, the interesting finding was that cervical spine Cobb's angle had an impact on post-operative spinal cord posterior drift in patients with neutral or posterior convexity type spinal cord morphology – the degree of kyphosis was inversely proportional to the distance of post-operative spinal cord posterior drift, but not in the anterior convexity type. Conclusions These findings supported that pre-operative cervical spinal cord morphology may be used as screening for patients undergoing laminoplasty. Patients having neutral or posterior convexity type spinal cord morphology accompanied with kyphotic deformity were not suitable candidates for laminoplasty.

Background Nanoparticles can be used for targeted drug delivery, in particular for brain cancer therapy. However, this requires a detailed analysis of nanoparticles from the associated microvasculature to the tumor, not easy because of the required high spatial resolution. The objective of this study is to demonstrate an experimental solution of this problem, based in vivo and post-mortem whole organ imaging plus nanoscale 3-dimensional (3D) X-ray microscopy. Results The use of gold nanoparticles (AuNPs) as contrast agents paved the way to a detailed high-resolution three dimensional (3D) X-ray and fluorescence imaging analysis of the relation between xenografted glioma cells and the tumor-induced angiogenic microvasculature. The images of the angiogenic microvessels revealed nanoparticle leakage. Complementary tests showed that after endocytotic internalization fluorescent AuNPs allow the visible-light detection of cells. Conclusions AuNP-loading of cells could be extended from the case presented here to other imaging techniques. In our study, they enabled us to (1) identify primary glioma cells at inoculation sites in mice brains; (2) follow the subsequent development of gliomas. (3) Detect the full details of the tumor-related microvasculature; (4) Finding leakage of AuNPs from the tumor-related vasculature, in contrast to no leakage from normal vasculature. Electronic supplementary material The online version of this article (doi:10.1186/s12951-015-0140-2) contains supplementary material, which is available to authorized users.

INTRODUCTION The fatal type of antiphospholipid syndrome is a rare but life-threating condition. It may be triggered by surgery or infection. Endoscopic transnasal-transsphenoidal surgery is a common procedure for pituitary tumor. We report a catastrophic case of a young woman died of fatal antiphospholipid syndrome following endoscopic transnasal-transsphenoidal surgery. METHODS AND RESULT A 31-year-old woman of a history of stroke received endoscopic transnasal-transsphenoidal surgery for a pituitary tumor. The whole procedure was smooth. However, the patient suffered from acute delirium on postoperative day 4. Then, her consciousness became comatose state rapidly with dilatation of pupils. Urgent magnetic resonance imaging of brain demonstrated multiple acute lacunar infarcts. The positive antiphosphoipid antibody and severe thrombocytopenia were also noted. Fatal antiphospholipid syndrome was diagnosed. Plasma exchange, corticosteroids, anticoagulant agent were prescribed. The hemodynamic condition was gradually stable. However, the consciousness was still in deep coma. The patient died of organ donation 2 months later. CONCLUSION If patients have a history of cerebral stroke in their early life, such as a young stroke, the APS and higher risk of developing fatal APS after major surgery should be considered. The optimal management of APS remains controversial. The best treatment strategies are only early diagnosis and aggressive therapies combing of anticoagulant, corticosteroid, and plasma exchange. The intravenous immunoglobulin is prescribed for patients with refractory APS.

The formation of spinal epidural abscess following acupuncture is very rare. We herein report the case of a 54-year-old woman who presented with progressive low back pain and fever with a root sign. She underwent surgical decompression, with an immediate improvement of the low back pain. A culture of the epidural abscess grew Serratia marcescens. One year postoperatively, magnetic resonance imaging revealed the almost complete eradication of the abscess. This case is the first case of Serratia marcescens-associated spinal epidural abscess formation secondary to acupuncture. The characteristics of spinal epidural abscess that develop after acupuncture and how to prevent such complications are also discussed.

Neurodegenerative disorders, chronic diseases that can severely affect the patient's daily life, include amyotrophic lateral sclerosis, Parkinson's, Alzheimer's, and Huntington's diseases. However, these diseases all have the common characteristic that they are due to degenerative irreversibility, and thus no efficient drugs or therapy methods can mitigate symptoms completely. Stem cell therapy, such as adipose tissue-derived stem cells (ADSCs), is a promising treatment for incurable disorders. In this review, we summarized the previous studies using ADSCs to treat neurodegenerative disorders, as well as their therapeutic mechanisms. We also suggested possible expectations for future human clinical trials involving minimized intracerebroventricular combined with intravenous administration, using different cell lineages to finish complementary therapy as well as change the extracellular matrix to create a homing niche. Depending on successful experiments in relevant neurodegenerative disorders models, this could form the theoretical basis for future human clinical trials.

Background: The transpedicular route in percutaneous vertebroplasty (PVP) is a well-established approach for the treatment of vertebral compression fractures (VCFs). However, the value of simple transpedicular biopsy in VCFs is less addressed. The purpose of this study is to evaluate the value of transpedicular biopsy during PVP for uncovering the malignancy in VCFs in a 10-year retrospective study. Materials and Methods: During the study period of the 1019 patients who underwent PVP for VCFs, 450 patients comprising of 127 male and 323 female underwent transpedicular biopsy during PVP for 705 fractured vertebras. The medical records were analyzed for age, gender, imaging studies, operation notes, pre-operative and post-operative diagnoses, date of vertebroplasty and biopsy, vertebral level and pathological reports. Results: Pathology of the specimens of the 450 patients confirmed non-malignant VCFs in 389 (86.44%) and malignancy in 61 (13.56%). The malignant pathology included: 52 (11.56%) distant metastases to vertebra, in 3 (0.67%) of the spinal metastases was unsuspected and in 49 (10.89%) of them the malignancy was suspected pre-operatively. There were 9 (2%) primary spinal malignancies, 2 (0.44%) unsuspected multiple myeloma and 7 (1.56%) pre-operatively suspected primary malignancies. The frequency of unsuspected malignancy was 1.11% (5/450) in this study. There was no complication associated with transpedicular biopsy during PVP. Conclusions: VCFs harbored 1.11% of unexpected malignancy. During the vertebroplasty, concomitant transpedicular vertebral biopsy is a safe and useful procedure for distinguishing non-malignant from malignant compression fractures, especially in diagnosing unsuspected malignancy.