Identifying the genetic mechanism of medium-low temperature fluoride-enriched geothermal groundwater by the self-organizing map and evaluating health risk in the Wugongshan area, southeast China.

Fluoride-enriched groundwater is a serious threat for groundwater supply around the world. The medium-low temperature fluoride-enriched geothermal groundwater resource is widely distributed in the circum-Wugongshan area. And the fluoride concentration of all geothermal samples exceeds the WHO permissible limit of 1.5 mg/L. The Self-Organizing Map method, hydrochemical and isotopic analysis are used to decipher the driving factors and genetic mechanism of fluoride-enriched geothermal groundwater. A total of 19 samples collected from the circum-Wugongshan geothermal belt are divided into four clusters by the self-organizing map. Cluster I, Cluster II, Cluster III, and Cluster IV represent the geothermal groundwater with the different degree of fluoride concentration pollution, the different hydrochemical type, and the physicochemical characteristic. The high F- concentration geothermal groundwater is characterized by HCO3-Na with alkalinity environment. The δD and δ18O values indicate that the geothermal groundwater origins from the atmospheric precipitation with the recharge elevation of 1000-2100 m. The dissolution of fluoride-bearing minerals is the main source of fluoride ions in geothermal water. Moreover, groundwater fluoride enrichment is also facilitated by water-rock interaction, cation exchange and alkaline environment. Additionally, the health risk assessment result reveals that the fluorine-enriched geothermal groundwater in the western part of Wugongshan area poses a more serious threat to human health than that of eastern part. The fluoride health risks of geothermal groundwater for different group show differentiation, 100% for children, 94.74% for adult females, and 68.42% for adult males, respectively. Compared with adult females and adult males, children faced the greatest health risks. The results of this study provide scientific evaluation for the utilization of geothermal groundwater and the protection of human health around the Wugongshan area.

Evolutionary Characteristics and Immunologic Divergence of Lung and Brain Metastasis Lesions in NSCLC.

Brain metastases (BM) is one of the main reasons for lung cancer-related deaths but lack prediction methods. Many patients with BMs do not benefit from immunotherapy. A comprehensive genomic analysis of matched primary tumors (PT) and their BM lesions may provide new insight into the evolutionary and immune characteristics. To describe evolutionary features and immune characteristic differences, we analyzed whole-exome sequencing data for 28 paired PT and BM samples from 14 patients with non-small cell lung cancer. In addition, we used another 26 matched PT and BM samples as a validation cohort. We found that total mutational signatures were relatively consistent between paired primary and brain metastatic tumors. Nevertheless, the shared mutations of the two lesions were fewer than the mutations present in each of the lesions alone. In the process of BM, driver genes undergo evolutionary branches. Typical driver genes, including EGFR and TP53, appear relatively conserved throughout evolution; however, specific signals are enriched in BM lesions. We found several main characteristics of lung cancer BMs that were different from primary lung cancer, such as genomic instability, novel driver genes, tumor mutation burden, and BM lesion private neoantigens. In addition, the estimated timing of dissemination showed that BMs might occur early in lung cancer. IMPLICATIONS: Mechanistic insight from this study provides new insight into the biology of the metastatic brain process and a new beneficial approach for preventing and treating lung cancer BMs.

Development of a preoperative index-based nomogram for the prediction of hypokalemia in patients with pituitary adenoma: a retrospective cohort study.

OBJECTIVE: To develop and validate a preoperative index-based nomogram for the prediction of hypokalemia in patients with pituitary adenoma (PA). METHODS: This retrospective cohort study included 205 patients with PAs between January 2013 and April 2020 in the Sun Yat-sen Memorial Hospital, Guangzhou, China. The patients were randomly classified into either a training set (N = 143 patients) and a validation set (N = 62 patients) at a ratio of 7:3. Variables, which were identified by using the LASSO regression model were included for the construction of a nomogram, and a logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) in the training set. The area under the curve (AUC) was used to evaluate the performance of the nomogram for predicting hypokalemia. Multivariate logistic regression analysis with a restricted cubic spline analysis was conducted to identify a potential nonlinear association between the preoperative index and hypokalemia. RESULTS: The incidence of hypokalemia was 38.05%. Seven preoperative indices were identified for the construction of the nomogram: age, type of PA, weight, activated partial thromboplastin time, urea, eosinophil percentage, and plateletocrit. The AUCs of the nomogram for predicting hypokalemia were 0.856 (95% CI [0.796-0.915]) and 0.652 (95% CI [0.514-0.790]) in the training and validation sets, respectively. Restricted cubic splines demonstrated that there was no nonlinear association between hypokalemia and the selected variables. CONCLUSION: In this study, we constructed a preoperative indices-based nomogram that can assess the risk of hypokalemia after the surgical treatment of pituitary adenomas. This nomogram may also help to identify high risk patients who require close monitoring of serum potassium.

Hsa_circ_0080229 upregulates the expression of murine double minute-2 (MDM2) and promotes glioma tumorigenesis and invasion via the miR-1827 sponging mechanism.

BACKGROUND: Glioma is the most common and fatal primary cranial tumor. The epidermal growth factor receptor (EGFR) plays an important role in the occurrence and treatment of glioma, which might function through a circular ribonucleic acid (circRNA)-related mechanism. Hsa_circ_0080229 (circ_0080229) has been identified as a circRNA arising from an EGFR gene in gliomas; however, little is known about its molecular mechanism to date. METHODS: To address this question, a series of experiments were conducted to confirm the effect of circ_0080229 in gliomas and identify the downstream mechanism. A quantitative real-time polymerase chain reaction (qRT-PCR) analysis and in-situ hybridization/fluorescence in-situ hybridization (ISH/FISH) testing were performed to identify the expression of circ_0080229 in patient samples. Bioinformatic analysis was carried out to explore the possible mechanism. Next, a series of in-vitro functional assays and in-vivo assays with a xenograft subcutaneous glioma model was carried out to confirm the effect of circ_0080229. Finally, qRT-PCR analysis and a Western Blot analysis were performed to verify the related mechanism. RESULTS: The expression of circ_0080229 was upregulated in both glioma tissues and cell lines related to unfavorable clinicopathologic characteristics. The expression of circ_0080229 was found to be inversely correlated with miR-1827, a micro-ribonucleic acid (miRNA) targeting murine double minute-2 (MDM2). The downregulation of circ_0080229 inhibited gliomas in vivo and suppressed U87 and U251 cell lines in vitro, which the transfection of the miR-1827 inhibitor could reverse. Concerning the mechanism, a block of circ_0080229 decreased MDM2 expression, while the inhibition of miR-1827 reversed this effect. Thus, circ_0080229 appears to target the downstream miR-1827/MDM2 signaling pathway. CONCLUSIONS: Our results showed that the silencing of circ_0080229 upregulates the expression of miR-1827, which in turn resulted in the suppression of MDM2, and the mediation of the downstream P53 signaling pathway. Circ_0080229 exerted an effect in mediating tumor progression through the MDM2 signaling pathway by sponging miR-1827. Its importance as a potential prognostic biomarker in gliomas has thus been established.

Whole-exome sequencing identifies somatic mutations associated with lung cancer metastasis to the brain.

BACKGROUND: Lung cancer is the most aggressive cancer, resulting in one-quarter of all cancer-related deaths, and its metastatic spread accounts for >70% of these deaths, especially metastasis to the brain. Metastasis-associated mutations are important biomarkers for metastasis prediction and outcome improvement. METHODS: In this study, we applied whole-exome sequencing (WES) to identify potential metastasis-related mutations in 12 paired lung cancer and brain metastasis samples. RESULTS: We identified 1,702 single nucleotide variants (SNVs) and 6,131 mutation events among 1,220 genes. Furthermore, we identified several lung cancer metastases associated genes (KMT2C, AHNAK2). A mean of 3.1 driver gene mutation events per tumor with the dN/dS (non-synonymous substitution rate/synonymous substitution rate) of 2.13 indicating a significant enrichment for cancer driver gene mutations. Mutation spectrum analysis found lung-brain metastasis samples have a more similar Ti/Tv (transition/transversion) profile with brain cancer in which C to T transitions are more frequent while lung cancer has more C to A transversion. We also found the most important tumor onset and metastasis pathways, such as chronic myeloid leukemia, ErbB signaling pathway, and glioma pathway. Finally, we identified a significant survival associated mutation gene ERF in both The Cancer Genome Atlas (TCGA) (P=0.01) and our dataset (P=0.012). CONCLUSIONS: In summary, we conducted a pairwise lung-brain metastasis based exome-wide sequencing and identified some novel metastasis-related mutations which provided potential biomarkers for prognosis and targeted therapeutics.

Decreased Level of Exosomal miR-5121 Released from Microglia Suppresses Neurite Outgrowth and Synapse Recovery of Neurons Following Traumatic Brain Injury.

Activated microglia can suppress neurite outgrowth and synapse recovery in the acute stage following traumatic brain injury (TBI). However, the underlying mechanism has not been clearly elucidated. Exosomes derived from microglia have been reported to play a critical role in microglia-neuron interaction in healthy and pathological brains. Here, we aimed to investigate the role of microglia-derived exosomes in regulating neurite outgrowth and synapse recovery following TBI. In our study, exosomes derived from microglia were co-cultured with stretch-injured neurons in vitro and intravenously injected into mice that underwent fluid percussion injury (FPI) by tail vein injection in vivo. The results showed that microglia-derived exosomes could be absorbed by neurons in vitro and in vivo. Moreover, exosomes derived from stretch-injured microglia decreased the protein levels of GAP43, PSD-95, GluR1, and Synaptophysin and dendritic complexity in stretch-injured neurons in vitro, and reduced GAP43+ NEUN cell percentage and apical dendritic spine density in the pericontusion region in vivo. Motor coordination was also impaired in mice treated with stretch-injured microglia-derived exosomes after FPI. A microRNA microarray showed that the level of miR-5121 was decreased most greatly in exosomes derived from stretch-injured microglia. Overexpression of miR-5121 in stretch-injured microglia-derived exosomes partly reversed the suppression of neurite outgrowth and synapse recovery of neurons both in vitro and in vivo. Moreover, motor coordination in miR-5121 overexpressed exosomes treated mice was significantly improved after FPI. Following mechanistic study demonstrated that miR-5121 might promote neurite outgrowth and synapse recovery by directly targeting RGMa. In conclusion, our finding revealed a novel exosome-mediated mechanism of microglia-neuron interaction that suppressed neurite outgrowth and synapse recovery of neurons following TBI.

Depletion of Microglia Attenuates Dendritic Spine Loss and Neuronal Apoptosis in the Acute Stage of Moderate Traumatic Brain Injury in Mice.

Microglia are the primary immune cells in the central nervous system and undergo significant morphological and transcriptional changes after traumatic brain injury (TBI). However, their exact contribution to the pathogenesis of TBI is still debated and remains to be elucidated. In the present study, thy-1 GFP mice received a colony-stimulating factor 1 receptor inhibitor (PLX3397) for 21 consecutive days, then were subjected to moderate fluid percussion injury (FPI). Brain samples were collected at 1 day and 3 days after FPI for flow cytometry analysis, immunofluorescence, dendrite spine quantification, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and Western blot. We found that PLX3397 treatment significantly attenuated the percentages of resident microglia and infiltrated immune cells. Depletion of microglia promoted neurite outgrowth, preserved dendritic spines and reduced total brain cell and neuronal apoptosis after FPI, which was accompanied by decreased the protein levels of endoplasmic reticulum stress marker proteins, C/EBP-homologous protein and inositol-requiring kinase 1α. Taken together, these findings suggest that microglial depletion may exert beneficial effects in the acute stage of FPI.

Mild hypothermia reduces endoplasmic reticulum stress-induced apoptosis and improves neuronal functions after severe traumatic brain injury.

BACKGROUND: Mild hypothermia is wildly used in clinical treatment of traumatic brain injury (TBI). However, the effect of mild hypothermia on endoplasmic reticulum (ER) stress-induced apoptosis after severe TBI is still unknown. METHODS: In the present study, we used BALB/c mice to investigate the efficacy of posttraumatic mild hypothermia in reducing ER stress. Severe TBI was induced by controlled cortical impact injury. Mild hypothermia treatment was performed immediately after surgery and maintained for 4 hr. The animals were euthanized at 1 and 7 days after severe TBI. The expression levels of ER stress marker proteins were evaluated using Western blot and immunofluorescence. Cell apoptosis rate was analyzed by TUNEL staining. Neuronal functions of the mice were assessed using rotarod test and Morris water maze. RESULTS: Our results revealed that mild hypothermia significantly attenuated ER stress marker proteins, including p-eIF2α/eIF2α, ATF4, CHOP and IRE-1α, and reduced apoptosis rate in the pericontusion region at 1 and 7 days after severe TBI. Interestingly, mild hypothermia also prevented the translocation of CHOP into nucleus. In addition, posttraumatic mild hypothermia significantly improved neuronal functions after severe TBI. CONCLUSIONS: Our findings illustrated that mild hypothermia could reduce ER stress-induced apoptosis and improve neuronal functions after severe traumatic brain injury.

Circular RNA hsa_circ_0076248 promotes oncogenesis of glioma by sponging miR-181a to modulate SIRT1 expression.

Glioma is one of the most common primary malignancies of the central nervous system, which has aggressive clinical behavior and a poorer prognosis. MicroRNAs (miRs) are a class of small noncoding RNAs that function as mediators of gene expression, which can be sponged by circRNA provided with a closed circular structure. Dysregulations of circular RNAs (circRNAs) and miRs have been implicated in the development and progression of glioma. In the current study, we investigated the role of circular RNA hsa_circ_0076248 in mediating the oncogenesis of glioma by sponging miR-181a to modulate silent information regulator 1 (SIRT1) expression in vitro and in vivo. The quantitative real-time polymerase chain reaction results showed that the expression of miR-181a was significantly decreased in glioma tissues and cell lines compared with normal brain tissues and normal gliocyte, respectively, and the expression of hsa_circ_0076248 and SIRT1 demonstrated the opposite. Bioinformatics analysis identified hsa_circ_0076248 could sponge miR-181a, and miR-181a could target the mRNA of SIRT1. Our results verified that downregulating hsa_circ_0076248 or upregulating miR-181a could depress the proliferation and invasion of glioma in vitro and in vivo. The experiment also showed that downregulating hsa_circ_0076248 or upregulating miR-181a could remarkably promote the temozolomide chemotherapy sensitivity. Furthermore, Western blot analysis testified that downregulating hsa_circ_0076248 or upregulating miR-181a could promote the expression of p53 and SIRT1. In summary, our study sheds light on the regulatory mechanism of hsa_circ_0076248 in glioma growth and invasion via sponging miR-181a, which downregulates the SIRT1 expression and also suggests that hsa_circ_0076248, miR-181a, and SIRT1 may serve as potential therapeutic targets for glioma.

Prospective Series of Nine Long Noncoding RNAs Associated with Survival of Patients with Glioblastoma.

OBJECTIVE: To analyze the long noncoding RNA (lncRNA) expression profile of glioblastoma multiforme (GBM) and identify prognosis-related lncRNAs, as well as their related protein-coding genes and functions. METHOD: The lncRNA expression profiles were obtained by microarray in six samples each of GBM and normal brain tissue. The lncRNAs expressed were significantly different between the two groups and used to detect their associations with patient survival time by downloading the related data from The Cancer Genome Atlas (TCGA). The total RNA-sequencing data of 152 patients diagnosed GBM level 3 with complete clinic information was downloaded. The survival time-dependent lncRNAs were identified by multivariate Cox regression analysis. For the survival time-dependent lncRNAs, we used the Pearson correlation coefficient and z test to search their associated protein-coding genes downloaded from TCGA. Functions of these genes were annotated by the Database for Annotation, Visualization, and Integrated Discovery (DAVID) for gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RESULTS: More than 1,000 antisense lncRNAs and enhancer lncRNAs were selected for analysis in this study. Data from 152 cases with RNA-seq of GBM level 3 with complete information on GBM were downloaded from the TCGA database. Univariate Cox regression analysis revealed 19 lncRNAs with survival time dependency. These nine lncRNAs were used to construct our survival model via multivariate Cox regression analysis: TP73-AS1, AC078883.3, RP11-944L7.4, HAR1B, RP4-635E18.7, HOTAIR, SAPCD1-AS1, AC104653.1, and RP5-1172N10.2. The nine lncRNAs associated with them were inputted into the DAVID database for gene ontology and KEGG function enrichment analysis. The result showed these genes were enriched with ion binding, transport, cell-cell signaling, plasma membrane parts, and more, and they were mainly related to neuroactive ligand-receptor interaction pathway, calcium signaling pathway, and the mitogen-activated protein kinase signaling pathway. CONCLUSION: The nine lncRNAs were a set of biomarkers for the prognosis of patients with GBM, enabling a more accurate prediction of survival and revealing more biological functions.

The Surgical Treatment of Posttraumatic Skull Base Defects with Cerebrospinal Fluid Leak.

Objectives The objective was to explore further the surgical treatment of posttraumatic skull base defects with cerebrospinal fluid (CSF) leak and to identify the most common factors affecting the surgical treatment of posttraumatic skull base defect with CSF leak retrospectively. Materials and Methods This study included 144 patients with head trauma having skull base defect with CSF leak who had been surgically treated at Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University from 1998 to June 2016. There were 113 (78.5%) males and 31 (21.5%) females, with age ranging from 1 to 78 years and mean age of 26.58 ± 14.95 years. We explored the surgical approaches for the treatment of the skull base defect and the graft materials used and also measured the association among surgical approaches; location, size, and type of skull base defects; presence or absence of associated intracranial pathologies; postoperative complications; outcome; age; Glasgow outcome score (GOS) at discharge; and days of hospital stay. Results The location, size, and types of skull base defect and the presence of associated intracranial pathologies were the common factors identified not only for choosing the appropriate surgical approach but also for choosing the materials for defect repair, timing of the surgery, and the method used for the defect as well as leak repair. The statistically significant correlation with p < 0.001 was found in this study. Conclusion From this study, we could conclude that size, location, and types of the defect and the presence of associated intracranial injuries were the common factors that affected the surgical treatment of posttraumatic skull base defect with CSF leak. Hence, the importance of careful evaluation of these factors is essential for proper selection of the surgical approach and for avoiding unnecessary hassles.

Development of temozolomide coated nano zinc oxide for reversing the resistance of malignant glioma stem cells.

Recently most of the researchers have turned their interest towards plant mediated synthesis of metal nanoparticles to avoid several environmental toxicants. In this manuscript, we have discussed the ecofriendly syntheses of zinc oxide nanoparticles (ZnO NPs) were achieved using Glycyrrhiza glabra (G. glabra) seed aqueous extract. The green synthesized ZnO NPs were characterized using analytical techniques like XRD, TEM, particle size histogram and Zeta potential. From the results, it was found that the green synthesized ZnO NPs were around 35nm in size with irregular spherical shape. The Zeta potential study of ZnO NPs was resulted to be high stabile with electronegative charge around -56.3mV. Further the G. glabra seed aqueous extract mediated synthesis of ZnO NPs were subjected to treat human glioblastoma cells with the help of temozolomide (TMZ) a commercially available drug by the method of MTT cell viability assay. The results stated that the ZnO NPs shows IC50 value around 30µg/mL results significantly. The plausible mechanism behind the mortality rate was also discussed in this manuscript.

Prognostic factors in patients treated with surgery for brain metastases: A single-center retrospective analysis of 125 patients.

BACKGROUD: Brain metastases are the most common malignant intracranial tumors, however, the prognosis of patients is still poor despite multiple treatment have been applicated. The aim of this study was to analyse parameters influence overall survival from patient, tumor and treatment. Summarized characteristics of long-time (>2 years) survivors furtherly. MATERIALS AND METHODS: In total, clinical data of 125patients between 2004 and 2015 were collected and the parameters from patients, tumor and treatment were evaluated. Univariate analysis was performed using Kaplan-Meier and Log-rank test, multivariate analysis was performed using Cox proportional hazards regression model, respectively. RESULTS: Median overall survival time was 14.5 (95% confidence interval were 12.3-16.7) months and median survival time was 34.5 (95% confidence interval were 30.1-38.9) months in long-time survivors, respectively.KPS, RPA, GPA, number of brain metastases, extracranial metastases, treatment pattern and resection method were identified influence survival time significantly by univariate analysis. KPS, number of brain metastases, extracranial metastases and treatment pattern were independent prognosis factors by multivariate analysis. Long-time survivors obtain higher KPS, complete resection, adjuvant therapy postoperative more commonly. CONCLUSION: Higher KPS, GPA I,RPA3.5∼4, single brain metastases, adjuvant therapy postoperative and complete resection were significant improve survival time, however, extracranial metastases significant decreased survival time. Patients who have good status and received multimodality therapy involved complete resection can survive longer time more commonly.

A simple classification of cranial-nasal-orbital communicating tumors that facilitate choice of surgical approaches: analysis of a series of 32 cases.

Cranial-nasal-orbital communicating tumors involving the anterior and middle skull base are among the most challenging to treat surgically, with high rates of incomplete resection and surgical complications. Currently, there is no recognized classification of tumors with regard to the choice of surgical approaches. From January 2004 to January 2014, we classified 32 cranial-nasal-orbital communicating tumors treated in our center into three types according to the tumor body location, scope of extension and direction of invasion: lateral (type I), central (type II) and extensive (type III). This classification considerably facilitated the choice of surgical routes and significantly influenced the surgical time and amount of hemorrhage during operation. In addition, we emphasized the use of transnasal endoscopy for large and extensive tumors, individualized treatment strategies drafted by a group of multidisciplinary collaborators, and careful reconstruction of the skull base defects. Our treatment strategies achieved good surgical outcomes, with a high ratio of total resection (87.5 %, 28/32, including 16 cases of benign tumors and 12 cases of malignant tumors) and a low percentage of surgical complications (18.8 %, 6/32). Original symptoms were alleviated in 29 patients. The average KPS score improved from 81.25 % preoperatively to 91.25 % at 3 months after surgery. No serious perioperative complications occurred. During the follow-up of 3 years on average, four patients with malignant tumors died, including three who had subtotal resections. The 3-year survival rate of patients with malignant tumors was 78.6 %, and the overall 3-year survival rate was 87.5 %. Our data indicate that the simple classification method has practical significance in guiding the choice of surgical approaches for cranial-nasal-orbital communicating tumors and may be extended to other types of skull base tumors.

H19 derived microRNA-675 regulates cell proliferation and migration through CDK6 in glioma.

The long non-coding RNA (LncRNA) H19 is one of the most highly abundant and conserved transcripts involved in the mammalian development and tumorigenesis. H19 is expressed in both embryonic cells and tumor cells, but its physical and pathological functions still need to be further studied. Our results showed that microRNA-675, a microRNA in the first exon of H19, expressed in glioma. Over-expression of microRNA-675 in a range of glioma cell lines resulted in their immoderate proliferation and migration. In addition, H19 derived microRNA-675 was down-regulated in the glioma, and CDK6, a pivotal regulator in cell cycle, was a target of microRNA-675. The survival of glioma patients with low CDK6 expression significantly increased as compared to patients with high CDK6 expression. Moreover, the CDK6 expression was inversely correlated with microRNA-675 expression in the glioma. Our results suggest that H19 derived microRNA-675 may regulate giloma cell proliferation and migration through CDK6, and predict a poor prognosis of glioma patients.

Functionalized nano-graphene oxide particles for targeted fluorescence imaging and photothermy of glioma U251 cells.

AIM: This study was to prepare the functionalized nano-graphene oxide (nano-GO) particles, and observe targeted fluorescence imaging and photothermy of U251 glioma cells under near infrared (NIR) exposure. MATERIAL AND METHODS: The functionalized nano-GO-Tf-FITC particles were prepared and then were incubated with U251 glioma cells. Estimation of CCK8 cell activity was adopted for measurement of cytotoxicity. The effect of fluorescein imaging was detected by fluorescence microscope with anti-CD71-FITC as a control. Finally, we detected the killing efficacy with flow cytometry after an 808 nm NIR exposure. RESULTS: Both nano-GO-Tf-FITC group and CD71-FITC group exhibited green-yellow fluorescence, while the control group without the target molecule nano-GO-FITC was negative. The nano-GO-Tf-FITC was incubated with U251 cells at 0.1 mg/ml, 1.0 mg/ml, 3.0 mg/ml and 5.0 mg/ml. After 48 h of incubation, the absorbance was 0.747 ± 0.031, 0.732 ± 0.043, 0.698 ± 0.051 and 0.682 ± 0.039, while the absorbance of control group is 0.759 ± 0.052. There is no significant difference between the nano-GO-FITC groups and control group. In addition, the apoptosis and death index of nano-GO-Tf-FITC group was significantly higher than that of nano-GO-FITC and blank control group (P < 0.05). CONCLUSION: The nano-GO-Tf-FITC particles with good biological compatibility and low cytotoxicity are successfully made, which have an observed effect of target imaging and photothermal therapy on glioma U251 cells.

miR-21 induces cell proliferation and suppresses the chemosensitivity in glioblastoma cells via downregulation of FOXO1.

miR-21 shares a potential oncogenic function. The overexpression of miR-21 was common in glioblastoma, which is the most common lethal primary intracranial tumor. The study aimed at miR-21 effect on Glioblastoma cell line A172 of proliferation, apoptosis, and chemosensitivity and its definite mechanism of target gene FOXO1. Effect and mechanism were evaluated by colony forming cell assay, annexin V-FITC/PI apoptosis assay, TUNEL apoptosis assay, luciferase-reporter activities assay, RNA interference, western-blot and Real-Time PCR. The statistics revealed miR-21 promoted A172 cell proliferation and suppressed the chemosensitivity, and also showed that miR-21 could bind with FOXO1 mRNA and prevent FOXO1 translation via its 3'UTR to regulate the function. These findings suggest that miR-21 plays an important role in cell proliferation and chemosensitivity by inhibiting FOXO1, and show much more significance for exploring miR-21 inhibitor in A172 therapy.

Methylation status of promoter 1 region of GDNF gene in human glioma cells.

OBJECTIVE: This study aimed to investigate the methylation status of promoter 1 region of glial cell line-derived neurotrophic factor (GDNF) in human glioma cells and to explore the effect of GDNF methylation on the expression of GDNF in glioma. METHODS: GDNF gene mutation was detected by sequencing in 10 patients with glioma and 5 healthy controls. Bisulfite modification for analysis of DNA methylation was done to detect the methylation status of promoter 1 region of GDNF in 20 patients with glioma (10 with poorly differentiated and 10 with well differentiated) and 5 healthy controls. RESULTS: There was no mutation at the promoter 1 region of GDNF gene in glioma. The incidence of methylation of GDNF gene at the promoter 1 region in healthy control, patients with poorly differentiated glioma and those with well differentiated glioma was 72.25%, 86.25% and 86.75%. The incidence of GDNF methylation in glioma was significantly higher than that in the normal brain (P<0.05); while there was no significant difference between well differentiated glioma and poorly differentiated glioma. CONCLUSIONS: Hypermethylation occurs in the promoter 1 region of GDNF and may influence the expression of GDNF in glioma.

[Preliminary application of absorbable fixation system on cranial bone flap reposition and fixation after craniotomy].

OBJECTIVE: To investigate the effectiveness and adverse effect of the absorbable fixation system on cranial bone flap reposition and fixation after craniotomy. METHODS: Between July 2010 and December 2011, 67 cases underwent cranial bone flap reposition and fixation with absorbable fixation system after craniotomy and resection of intracranial lesions. There were 38 males and 29 females with a median age of 32 years (range, 5 months to 73 years). The disease duration ranged from 3 months to 6 years (median, 25 months). Forty-one lesions were located at supratentorial and 26 at subtentorial, including at the frontotemporal site in 13 cases, at the frontoparietal site in 12 cases, at the temporal oprietal site in 8 cases, at the temporooccipital site in 5 cases, at the occipitoparietal site in 4 cases, and at the posterior cranial fossa in 25 cases. The diagnosis results were glioma in 15 cases, cerebral vascular diseases (aneurysm, arteriovenous malformation, and cavemous angioma) in 8 cases, meningioma in 7 cases, arachnoid cyst in 7 cases, acoustic neurinoma in 5 cases, cholesteatoma in 3 cases, primary trigeminal neuralgia in 5 cases, cerebral abscess in 3 cases, hypophysoma in 2 cases, craniopharyngioma in 2 cases, metastatic tumor in 2 cases, radiation encephalopathy in 2 cases, medulloblastoma in 1 case, ependymocytoma in 1 case, germinoma in 1 case, atypical teratoma/rhabdoid tumor in 1 case, facial spasm in 1 case, and subdural hematoma in 1 case. Intracranial lesion size ranged from 3 cm x 2 cm to 7 cm x 5 cm. The changes of local incision and general condition were observed. RESULTS: Subcutaneous effusion occurred in 2 supratentorial lesions and 3 subtentorial lesions, which was cured at 2 weeks after puncture and aspiration. All incisions healed primarily and no redness or swelling occurred. CT scans showed good reposition of the cranial bone flap and smooth inner and outer surfaces of the skull at 2 weeks after operation. All 67 patients were followed up 3-20 months (mean, 10.3 months). During follow-up, the skull had satisfactory appearance without discomfort, local depression, or effusion. Moreover, regular CT and MRI scans showed no subside, or displacement of the cranial bone flap or artifacts. CONCLUSION: Absorbable fixation system for reposition and fixation of the cranial bone flap not only is simple, safe, and reliable, but also can eliminate the postoperative CT or MRI artifact caused by metals fixation system.

[Endoscope-assisted surgical resection of acoustic neuroma].

OBJECTIVE: To explore the therapeutic efficacy and complications of endoscope-assisted surgical resection of acoustic neuroma. METHOD: Assisted by hard-tube ear endoscope, 11 patients with acoustic neuroma were operated via labyrinthine approach and retrosigmoid approach. RESULT: Total removal was achieved in 9 (81.8%) cases, while subtotal removal was achieved in 2 (18.2%) cases. Facial nerves and cochlear nerves were preserved completely during operation in all cases. After operation 9 (81.8%) cases had no facial paralysis, while the other 2 cases (18.2%) had mild peripheral facial paralysis. The same hearing level as that of preoperation in 2 patients (18.2%), hearing impairment in different degrees in 9 patients (81.8%), among which moderate sensorineural hearing loss in 1 patient, moderate to severe in 2 patients, severe in 3 patients, profound in 3 patients. CONCLUSION: The application of ear endoscope in acoustic neuroma surgery can improve the total removal rate of tumors and the salvage rate of vessels and nerves. However, its disadvantages make it an assistant method for microsurgery.