[18F]SynVesT-1 and [18F]FDG quantitative PET imaging in the presurgical evaluation of MRI-negative children with focal cortical dysplasia type II.

PURPOSE: MRI-negative children with focal cortical dysplasia type II (FCD II) are one of the most challenging cases in surgical epilepsy management. We aimed to utilize quantitative positron emission tomography (QPET) analysis to complement [18F]SynVesT-1 and [18F]FDG PET imaging and facilitate the localization of epileptogenic foci in pediatric MRI-negative FCD II patients. METHODS: We prospectively enrolled 17 MRI-negative children with FCD II who underwent [18F]SynVesT-1 and [18F]FDG PET before surgical resection. The QPET scans were analyzed using statistical parametric mapping (SPM) with respect to healthy controls. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of [18F]SynVesT-1 PET, [18F]FDG PET, [18F]SynVesT-1 QPET, and [18F]FDG QPET in the localization of epileptogenic foci were assessed. Additionally, we developed a multivariate prediction model based on dual trace PET/QPET assessment. RESULTS: The AUC values of [18F]FDG PET and [18F]SynVesT-1 PET were 0.861 (sensitivity = 94.1%, specificity = 78.2%, PPV = 38.1%, NPV = 98.9%) and 0.908 (sensitivity = 82.4%, specificity = 99.2%, PPV = 93.3%, NPV = 97.5%), respectively. [18F]FDG QPET showed lower sensitivity (76.5%) and NPV (96.6%) but higher specificity (95.0%) and PPV (68.4%) than visual assessment, while [18F]SynVesT-1 QPET exhibited higher sensitivity (94.1%) and NPV (99.1%) but lower specificity (97.5%) and PPV (84.2%). The multivariate prediction model had the highest AUC value (AUC = 0.996, sensitivity = 100.0%, specificity = 96.6%, PPV = 81.0%, NPV = 100%). CONCLUSIONS: The multivariate prediction model based on [18F]SynVesT-1 and [18F]FDG PET/QPET assessments holds promise in noninvasively identifying epileptogenic regions in MRI-negative children with FCD II. Furthermore, the combination of visual assessment and QPET may improve the sensitivity and specificity of diagnostic tests in localizing epileptogenic foci and achieving a preferable surgical outcome in MRI-negative FCD II.

Individual cerebellar metabolic connectome in patients with MTLE and NTLE associated with surgical prognosis.

PURPOSE: This study aimed to comprehensively explore the different metabolic connectivity topological changes in MTLE and NTLE, as well as their association with surgical outcomes. METHODS: This study enrolled a cohort of patients with intractable MTLE and NTLE. Each individual's metabolic connectome, as determined by Kullback-Leibler divergence similarity estimation for the [18F]FDG PET image, was employed to conduct a comprehensive analysis of the cerebral metabolic network. Alterations in network connectivity were assessed by extracting and evaluating the strength of edge and weighted connectivity. By utilizing these two connectivity strength metrics with the cerebellum, we explored the network properties of connectivity and its association with prognosis in surgical patients. RESULTS: Both MTLE and NTLE patients exhibited substantial alterations in the connectivity of the metabolic network at the edge and nodal levels (p < 0.01, FDR corrected). The key disparity between MTLE and NTLE was observed in the cerebellum. In MTLE, there was a predominance of increased connectivity strength in the cerebellum. Whereas, a decrease in cerebellar connectivity was identified in NTLE. It was found that in MTLE, higher edge connectivity and weighted connectivity strength in the contralateral cerebellar hemisphere correlated with improved surgical outcomes. Conversely, in NTLE, a higher edge metabolic connectivity strength in the ipsilateral cerebellar hemisphere suggested a worse surgical prognosis. CONCLUSION: The cerebellum exhibits distinct topological characteristics in the metabolic networks between MTLE and NTLE. The hyper- or hypo-metabolic connectivity in the cerebellum may be a prognostic biomarker of surgical prognosis, which might aid in therapeutic decision-making for TLE individuals.

Individualized Structural Perturbations on Normative Brain Connectome Restrict Deep Brain Stimulation Outcomes in Parkinson's Disease.

BACKGROUND: Patients with Parkinson's disease (PD) respond to deep brain stimulation (DBS) variably. However, how brain substrates restrict DBS outcomes remains unclear. OBJECTIVE: In this article, we aim to identify prognostic brain signatures for explaining the response variability. METHODS: We retrospectively investigated a cohort of patients with PD (n = 141) between 2017 and 2022, and defined DBS outcomes as the improvement ratio of clinical motor scores. We used a deviation index to quantify individual perturbations on a reference structural covariance network acquired with preoperative T1-weighted magnetic resonance imaging. The neurobiological perturbations of patients were represented as z scored indices based on the chronological perturbations measured on a group of normal aging adults. RESULTS: After applying stringent statistical tests (z > 2.5) and correcting for false discoveries (P < 0.01), we found that accelerated deviations mainly affected the prefrontal cortex, motor strip, limbic system, and cerebellum in PD. Particularly, a negative network within the accelerated deviations, expressed as "more preoperative deviations, less postoperative improvements," could predict DBS outcomes (mean absolute error = 0.09, R2 = 0.15). Moreover, a fusion of personal brain predictors and medical responses significantly improved traditional evaluations of DBS outcomes. Notably, the most important brain predictor, a pathway connecting the cognitive unit (prefrontal cortex) and motor control unit (cerebellum and motor strip), partially mediates DBS outcomes with the age at surgery. CONCLUSIONS: Our findings suggest that individual structural perturbations on the cognitive motor control circuit are critical for modulating DBS outcomes. Interventions toward the circuit have the potential for additional clinical improvements. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Preoperative structural-functional coupling at the default mode network predicts surgical outcomes of temporal lobe epilepsy.

OBJECTIVE: Structural-functional coupling (SFC) has shown great promise in predicting postsurgical seizure recurrence in patients with temporal lobe epilepsy (TLE). In this study, we aimed to clarify the global alterations in SFC in TLE patients and predict their surgical outcomes using SFC features. METHODS: This study analyzed presurgical diffusion and functional magnetic resonance imaging data from 71 TLE patients and 48 healthy controls (HCs). TLE patients were categorized into seizure-free (SF) and non-seizure-free (nSF) groups based on postsurgical recurrence. Individual functional connectivity (FC), structural connectivity (SC), and SFC were quantified at the regional and modular levels. The data were compared between the TLE and HC groups as well as among the TLE, SF, and nSF groups. The features of SFC, SC, and FC were categorized into three datasets: the modular SFC dataset, regional SFC dataset, and SC/FC dataset. Each dataset was independently integrated into a cross-validated machine learning model to classify surgical outcomes. RESULTS: Compared with HCs, the visual and subcortical modules exhibited decoupling in TLE patients (p < .05). Multiple default mode network (DMN)-related SFCs were significantly higher in the nSF group than in the SF group (p < .05). Models trained using the modular SFC dataset demonstrated the highest predictive performance. The final prediction model achieved an area under the receiver operating characteristic curve of .893 with an overall accuracy of .887. SIGNIFICANCE: Presurgical hyper-SFC in the DMN was strongly associated with postoperative seizure recurrence. Furthermore, our results introduce a novel SFC-based machine learning model to precisely classify the surgical outcomes of TLE.

[18F]FDG PET metabolic patterns in mesial temporal lobe epilepsy with different pathological types.

OBJECTIVES: To investigate [18F]FDG PET patterns of mesial temporal lobe epilepsy (MTLE) patients with distinct pathologic types and provide possible guidance for predicting long-term prognoses of patients undergoing epilepsy surgery. METHODS: This was a retrospective review of MTLE patients who underwent anterior temporal lobectomy between 2016 and 2021. Patients were classified as having chronic inflammation and gliosis (gliosis, n = 44), hippocampal sclerosis (HS, n = 43), or focal cortical dysplasia plus HS (FCD-HS, n = 13) based on the postoperative pathological diagnosis. Metabolic patterns and the severity of metabolic abnormalities were investigated among MTLE patients and healthy controls (HCs). The standardized uptake value (SUV), SUV ratio (SUVr), and asymmetry index (AI) of regions of interest were applied to evaluate the severity of metabolic abnormalities. Imaging processing was performed with statistical parametric mapping (SPM12). RESULTS: With a mean follow-up of 2.8 years, the seizure freedom (Engel class IA) rates of gliosis, HS, and FCD-HS were 54.55%, 62.79%, and 69.23%, respectively. The patients in the gliosis group presented a metabolic pattern with a larger involvement of extratemporal areas, including the ipsilateral insula. SUV, SUVr, and AI in ROIs were decreased for patients in all three MTLE groups compared with those of HCs, but the differences among all three MTLE groups were not significant. CONCLUSIONS: MTLE patients with isolated gliosis had the worst prognosis and hypometabolism in the insula, but the degree of metabolic decrease did not differ from the other two groups. Hypometabolic regions should be prioritized for [18F]FDG PET presurgical evaluation rather than [18F]FDG uptake values. CLINICAL RELEVANCE STATEMENT: This study proposes guidance for optimizing the operation scheme in patients with refractory MTLE and emphasizes the potential of molecular neuroimaging with PET using selected tracers to predict the postsurgical histology of patients with refractory MTLE epilepsy. KEY POINTS: • MTLE patients with gliosis had poor surgical outcomes and showed a distinct pattern of decreased metabolism in the ipsilateral insula. • In the preoperative assessment of MTLE, it is recommended to prioritize the evaluation of glucose hypometabolism areas over [18F]FDG uptake values. • The degree of glucose hypometabolism in the epileptogenic focus was not associated with the surgical outcomes of MTLE.

Long-term Efficacy of Bilateral Globus Pallidus Stimulation in the Treatment of Meige Syndrome.

OBJECTIVE: This study aimed to investigate the long-term efficacy and prognosis of bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) in patients with benign essential blepharospasm (BEB) and complete Meige syndrome, and to search for the best therapeutic subregion within the GPi. MATERIALS AND METHODS: Data were collected for 36 patients with Meige syndrome who underwent bilateral GPi-DBS surgery at our hospital between March 2014 and February 2022. Using the Burk-Fahn-Marsden Dystonia Rating Scale (BFMDRS)-Movement (BFMDRS-M) and BFMDRS-Disability (BFMDRS-D), the severity of the symptoms of patients with complete Meige syndrome was evaluated before surgery and at specific time points after surgery. Patients with BEB were clinically evaluated for the severity of blepharospasm using BFMDRS-M, the Blepharospasm Disability Index (BDI), and Jankovic Rating Scale (JRS). Three-dimensional reconstruction of the GPi-electrode was performed in some patients using the lead-DBS software, and the correlation between GPi subregion volume of tissue activated (VTA) and symptom improvement was analyzed in patients six months after surgery. The follow-up duration ranged from six to 99 months. RESULTS: Compared with preoperative scores, the results of all patients at six months after surgery and final follow-up showed a significant decrease (p < 0.05) in the mean BFMDRS-M score. Among them, the average BFMDRS-M improvement rates in patients with BEB at six months after surgery and final follow-up were 60.3% and 69.7%, respectively, whereas those in patients with complete Meige syndrome were 54.5% and 58.3%, respectively. The average JRS and BDI scores of patients with BEB also decreased significantly (p < 0.05) at six months after surgery and at the final follow-up (JRS improvement: 38.6% and 49.1%, respectively; BDI improvement: 42.6% and 57.4%, respectively). We were unable to identify significantly correlated prognostic factors. There was a significant correlation between GPi occipital VTA and symptom improvement in patients at six months after surgery (r = 0.34, p = 0.025). CONCLUSIONS: Our study suggests that bilateral GPi-DBS is an effective treatment for Meige syndrome, with no serious postoperative complications. The VTA in the GPi subregion may be related to the movement score improvement. In addition, further research is needed to predict patients with poor surgical outcomes.

A HIF1A/miR-485-5p/SRPK1 axis modulates the aggressiveness of glioma cells upon hypoxia.

The high aggressiveness of gliomas remains a huge challenge to clinical therapies, and the hypoxic microenvironment in the core region is a critical contributor to glioma aggressiveness. In this study, it was found that miR-485-5p was low expressed within glioma tissue samples and cells. GO enrichment annotation indicated that the predicted downstream targets miR-485-5p were enriched in hypoxia response and decreased oxygen level. In glioma cells, miR-485-5p overexpression suppressed cell viability, migratory ability, and invasive ability under both normoxic and hypoxic conditions. Through direct binding, miR-485-5p suppressed SRPK1 expression. Under hypoxia, SRPK1 overexpression enhanced hypoxia-induced glioma cell aggressiveness and significantly reversed the effects of miR-485-5p overexpression. Moreover, HIF1A could target the miR-485-5p promoter region to inhibit the transcription. HIF1A, miR-485-5p, and SRPK1 form a regulatory axis, which modulates glioma cell aggressiveness under hypoxia. In conclusion, we identify a HIF1A/miR-485-5p/SRPK1 axis that modulates the aggressiveness of glioma cells under hypoxia. The axis could potentially provide new research avenues in the treatment of gliomas considering the hypoxic environment in its core.

The Role of Hippocampal Neurogenesis in ANT-DBS for LiCl-Pilocarpine-Induced Epileptic Rats.

PURPOSE: Abnormal neurogenesis in the hippocampus after status epilepticus (SE) has been suggested as a key pathogeny of temporal lobe epilepsy. This study aimed to investigate the effect of deep brain stimulation of the anterior thalamic nucleus (ANT-DBS) on hippocampal neurogenesis in LiCl-pilocarpine-induced epileptic rats and to analyze its relationship with postoperative spontaneous recurrent seizures (SRS) and anxiety. METHOD: SE was induced by a systemic LiCl-pilocarpine injection in adult male rats. Rats in the DBS group underwent ANT-DBS immediately after successful SE induction. SRS was only recorded during the chronic stage. An elevated plus maze was used to evaluate the level of anxiety in rats 7, 28, and 60 days after SE onset. After the elevated plus-maze experiment, rats were sacrificed under anesthesia in order to evaluate hippocampal neurogenesis. Doublecortin (DCX) was used as a marker for neurogenesis. RESULTS: During the chronic stage, SRS in rats in the DBS group were significantly decreased. The level of anxiety was increased significantly in rats in the DBS group 28 days after SE, while no significant differences in anxiety levels were found 7 and 60 days after SE. The number of DCX-positive cells in the hippocampus was significantly increased 7 days after SE and was significantly decreased 60 days after SE in all rats in which SE was induced. However, the number of DCX-positive cells in the DBS group was significantly lower than that in the other groups 28 days after SE. CONCLUSIONS: ANT-DBS may suppress SRS and increase the postoperative anxiety of epileptic rats by influencing hippocampal neurogenesis.

Factors associated with prognosis of dysembryoplastic neuroepithelial tumors patients after surgical resection: a retrospective observational study.

OBJECTIVE: To explore factors that might be associated with prognosis of dysembryoplastic neuroepithelial tumors (DNTs). METHODS: DNTs patients who were admitted to the Department of Neurosurgery of Xiangya Hospital between 1 January 2010 and 31 December 2018 and underwent surgical resection were retrospectively analyzed. Clinical, neuroimaging, and pathological features of DNTs were compared among patients with different outcomes and analyzed using the Kaplan-Meier curves and univariable Cox regression analysis. RESULTS: Thirty-three DNTs patients were included finally, of which the average age at seizure onset was 11.59 ± 7.46 years old and the average duration of seizures prior to surgical resection was 3.00 ± 4.68 years. After surgical resection, the patients were followed up for 2.39 ± 1.97 years, and 28 patients (84.85%) were seizure-free (class I of the Engel Outcome Scale) while five patients (15.15%) were seizure-continuous (class II or III of the Engel Outcome Scale). When compared with seizure-free patients, seizure-continuous patients had greater age at seizure onset and longer duration of seizures before surgical resection (p < .05). No variables were found to be statistically significantly associated with prognosis in univariable Cox regression analysis, but patients with extra-temporal DNTs were found to have better prognosis than those with temporal DNTs (log-rank test p = .048). CONCLUSIONS: Elder seizure onset age, longer duration of seizures prior to surgical resection, and a temporal location may be risk factors of poor prognosis for DNTs patients after surgical resection.

Efficacy and safety of vagus nerve stimulation in the treatment of refractory epilepsy. / è¿·èµ°ç¥žç»åˆºæ¿€æœ¯æ²»ç–—éš¾æ²»æ€§ç™«ç—«çš„ç–—æ•ˆå’Œå®‰å ¨æ€§.

OBJECTIVES: Vagus nerve stimulation (VNS) is a neuromodulative therapeutic technique for patients with drug-resistant epilepsy who are not suitable for resection or who have experienced a failed resection. This study aims to explore the efficacy and safety of VNS in patients with refractory epilepsy, and to analyze the influential factors for the efficacy. METHODS: A retrospective review of clinical data were conducted for 35 patients, who were treated for refractory epilepsy through VNS surgery in the Department of Neurosurgery, Xiangya Hospital, Central South University from April 2016 to August 2019. All patients were analyzed in terms of the clinical and follow-up data. RESULTS: After a mean follow-up of 26 months (6-47 months), outcome was as follows: 7 patients were MuHugh class I, 13 patients were MuHugh class II, 8 patients were MuHugh class III, and 7 patients were MuHugh class IV-V. The total efficacy rate in the short duration group was significantly higher than that in the long duration group (77.8% vs 50.0%, P=0.013), whereas different ages (P=0.382), gender (P=0.824), types of seizure (P=0.829), and MRI features (P=0.791) showed no correlation with efficacy. None patients developed permanent complication postoperatively. CONCLUSIONS: VNS is a safe and effective option in treating patients with refractory epilepsy, especially for those with short duration.

Optimal surgical approaches and treatment outcomes in patients with jugular foramen schwannomas: a single institution series of 31 cases and a literature review.

Complete resection of jugular foramen schwannomas (JFSs) with minimal cranial nerve complications remains difficult even for skilled neurosurgeons. Between November 2011 and November 2017, 31 consecutive patients diagnosed with JFSs underwent a single-stage operation performed by the same neurosurgeon. We retrospectively analyzed clinical characteristics, surgical approaches, treatment outcomes, and follow-up data for these patients. JFSs were classified according to the Samii classification system. A retrosigmoid approach was used to resect type A tumors, while a suboccipital transjugular process (STJP) approach was used to resect type B tumors. Notably, the present study is the first to report the use of a paracondylar-lateral cervical (PCLC) approach for the treatment of type C and D tumors. Type A-D tumors were observed in seven, four, four, and 16 patients, respectively. Gross-total resection was achieved in 29 patients (93.5%). There were no cases of intracranial hematoma, re-operation, tracheotomy, or death. Adjunctive gamma knife treatment was used to manage residual tumors in two patients. Neurological deficits relieved in half of patients at the last follow-up. By reviewing the studies published on PubMed, the approaches gradually be more conservative, rather than widely expose the skull base. Nonetheless, endoscope and stereotactic radiosurgery plays an important role in the management of JFSs. Both tumor removal and neurological function retention can be obtained by choosing individual treatment.

Clinical outcomes after medial temporal lobe epilepsy surgery: Anterior temporal lobectomy versus selective amygdalohippocampectomy.

OBJECTIVE: To compare the anterior temporal lobectomy (ATL) with transsylvian selective amygdalohippocampectomy (SeAH) in 72 patients with medial temporal lobe epilepsy (MTLE) regarding the seizure control and neuropsychological outcomes.
 Methods: Clinical data and follow-up data were collected and retrospectively analyzed. SeAH and ATL were used in 39 and 33 patients, respectively. All eligible patients were followed up at least one year. Wechsler Adult Intelligence Scale-Revised and the Wechsler Memory Scale-Revised were used to test the patients' neuropsychology before and after the surgery for one year.
 Results: Fifty-nine patients (81.9%) achieved satisfactory seizure control (62.5% Engel Class I and 19.4% Class II). ATL obtained 84.8% satisfactory seizure control (28 patients), and the success rate was 79.5% (31 patients) for SeAH. There was no significant difference in seizure control between SeAH and ATL (P=0.760). The postoperative verbal IQ of SeAH group increased significantly in both side surgery (P<0.05), while the increase was not significant in the group of ATL of both side surgery (P>0.05). Regarding left-side surgery, postoperative verbal memory and total memory were increased significantly in the group of SeAH (P<0.05), while the increases were not significant in the group of ATL (P>0.05). In the right-side surgery, postoperative verbal memory and total memory were increased significantly in the two surgery strategy groups (P<0.05), while no significant increases were seen in non-verbal memory of the two surgery strategy groups (P>0.05).
 Conclusion: Microsurgery for the treatment of refractory MTLE is successful and safe, and should be encouraged. The seizure outcome is not different between ATL and SeAH, while regarding as verbal IQ and verbal memory outcomes, SeAH may be superior to ATL in dominant hemisphere surgery.

The lncRNA H19 interacts with miR-140 to modulate glioma growth by targeting iASPP.

H19, one of the first found cancer-associated long non-coding RNAs (lncRNAs), is involved in the development and progression of many types of tumors. An aberrant expression of H19 was observed in hepatocellular carcinoma, cervical cancer, breast cancer, ovarian cancer, and colorectal cancer. However, the exact effects and molecular mechanisms of H19 in glioma progression are still unknown up to now. In this study, we investigated the role of H19 in human glioma cell lines and clinical tumor samples in order to determine the function of this molecule. In our research, lncRNA-H19 was specifically upregulated in glioma cell lines and promoted glioma cell growth through targeting miR-140. Knockdown of H19 inhibited the proliferation and invasion of human glioma cell and suppressed its metastasis in vitro and in vivo. In addition, miR-140 dependent inhibitor of apoptosis-stimulating protein of p53 (iASPP) regulation was required in H19 induced glioma cell growth. These findings indicated that H19 might regulate the tumor growth and metastasis via miR-140 dependent iASPP regulation. Taken together, our data indicated that H19 might be an oncogenic lncRNA that promoted proliferation and metastasis of glioma and could be regarded as a therapeutic target in human glioma.

[Pretemporal transcavernous approach tailored surgery of cavernous sinus tumors: a consecutive series of 31 cases report].

OBJECTIVE: To investigate the indications of the pretemporal transcavernous approach for cavernous sinus tumors resection and design individually tailored surgery according to the extent of tumors and operation requirements. METHODS: A retrospective analysis of clinical data, surgical outcomes and complications in a series of 31 cases with cavernous sinus tumor operated via the individually tailored pretemporal transcavernous approach between May 2012 and September 2015 in Department of Neurosurgery, Xiangya Hospital, Central South University. There were 13 male and 18 female patients, aging from 17 to 67 years with a mean of (41±14) years. The patients included 18 cases of shwannomas, 4 cases of meningiomas, 3 cases of cavernous hemangiomas, 2 cases of invasive pituitary adenomas, 1 case of chordoma, 1 case of chondroma, 1 case of recurrent teratoma, 1 case of metastatic nasopharyngeal carcinoma. The first followed-up visit was on the 3(rd) month after surgery, and if tumor progression or recurrence was observed on MRI, the Gamma knife treatment was recommended, the patient was followed up every 6 months, otherwise the patient was followed up again 6 months later, then, every 12 months. RESULTS: Gross total removal of tumors was achieved in 22 cases of 31 patients (71.0%), containing 17 cases of shwannomas, 3 cases of hemangiomas, 1 case of chondroma, 1 case of teratoma; subtotal removal in 6 cases (19.3%), including 3 cases of meningiomas, 1 case of pituitary adenoma, 1 case of chordoma, 1 case of metastatic carcinoma; partial removal in 3 cases (9.7%), comprising 1 case of meningioma, 1 case of recurrent shwannoma, 1 case of recurrent pituitary adenoma. The symptoms of cranial never aggravated in 5 cases, the new postoperative cranial never palsy was observed in 7 cases. There was no surgical mortality, intracranial hematoma, intracranial infection and cerebrospinal fluid leakage cases, ect. Twenty-eight cases were followed up for more than 3 months (3 to 40 months), 1 case of chordoma had tumor progression; the nerve function was restored in 5 cases, among the 12 cases with postoperatively new occurred or deteriorated cranial nerve paralysis. CONCLUSIONS: The pretemporal transcavernous approach can be used to resect tumors limited in cavernous sinus or tumors simultaneously involving the cavernous sinus and its vicinity areas, it can be individually tailored based on the extent and exposure of the tumor. This approach can improve the surgical results in terms of high tumor resection rate, less complication, is an ideal approach for cavernous sinus tumor resection.

MiRNA-125a-5p inhibits glioblastoma cell proliferation and promotes cell differentiation by targeting TAZ.

Glioblastoma (GBM) is the most lethal brain tumor due to the resistance to conventional therapies, such as radiotherapy and chemotherapy. TAZ, an important mediator of the Hippo pathway, was found to be up-regulated in diverse cancers, including in GBM, and plays important roles in tumor initiation and progression. However, little is known about the regulation of TAZ expression in tumors. In this study, we found that miR-125a-5p is an important regulator of TAZ in glioma cells by directly targeting the TAZ 3' UTR. MiR-125a-5p levels are inversely correlated with that of TAZ in normal astrocytes and a panel of glioma cell lines. MiR-125a-5p represses the expression of TAZ target genes, including CTGF and survivin, and inhibits cell proliferation and induces the differentiation of GBM cells; whereas over-expression of TAZ rescues the effects of miR-125a-5p. This study revealed a mechanism for TAZ deregulation in glioma cells, and also demonstrated a tumor suppressor role of miR-125a-5p in glioblastoma cells.

[Microsurgical removal and prognostic analysis of petroclival meningiomas].

OBJECTIVE: To identify factors that predictive of quality of life after microsurgical removal of petroclival meningiomas. METHODS: A consecutive series of 71 cases of petroclival meningiomas received microsurgical removal between July 1991 and April 2010 were analyzed retrospectively. Quality of life was measured using Karnofsky performance scale (KPS). Complete pre-operative, post-operative and follow-up data were obtained from all 71 patients including 18 male and 53 female patients with the mean age of (47 ± 11) years (aging from 15 to 68 years). The duration between onset of symptoms and diagnosis ranged from 1 week to 180 months with the mean duration of (32 ± 30) months. And the tumor size was 15-72 mm with the average of (44 ± 11) mm. Main presentations included headache, unsteady gait, hemiparesis, dysphagia, hoarseness, facial numbness or pain, Bell's palsy, hearing impairment etc. The preoperative KPS was 40-100 with the average of 69 ± 11. The retrosigmoid (-transtentorial) approach was performed in most cases (91.5%). Intergroup χ² test and logistic regression analysis were conducted for prognostic factor characterization. RESULTS: The gross total resection (all were Simpson gradeII) reached in 48 cases (67.6%) and 1 case died postoperatively. The main new neurological dysfunctions were cranial nerve paralysis and hemiplegia with the postoperative KPS of 20-100 with the average of 73 ± 16.Sixty-four cases were followed for 4-132 months with the average of (61 ± 48) months. Seven patients died during follow-up, tumor recurrence and progression were identified in 6 and 8 cases, respectively. The KPS at the last visit ranged from 50 to 100 with the average of 83 ± 13. The extent of tumor resection (OR = 0.280, 95% CI: 0.081-0.967, P = 0.044), preoperative brainstem edema (OR = 0.100, 95% CI: 0.027-0.372, P = 0.001), relationships between tumor and neurovascular structures (OR = 0.288, 95% CI: 0.084-0.985, P = 0.047) and depth of invasion into cavernous sinus (OR = 0.254, 95% CI: 0.061-1.057, P = 0.048) had significant correlations with the prognostic quality of life. CONCLUSIONS: With regard of the choice of surgical approaches, the extent of tumor resection, the protection of neurovascular structures surrounding the tumor and the management of perioperative period, the therapeutic strategies for each patient should be customized to achieve better prognosis.

Efficacy of antiangiogenic targeted immunotoxin DTAT and DTATEGF against glioblastoma multiforme.

OBJECTIVE: To investigate the in vitro and in vivo anticancer efficacy of the immunotoxin DTAT and DTATEGF against globlastoma multiforme. METHODS: The in vitro cytotoxicity of DTAT and DTATEGF was measured using MTT assay. In vivo studies were performed in which 18 nude mice were randomly divided into 3 groups and the glioma xenograft intracranial mouse model was constructed with U87-luc cell line of human glioma. Then 1 µg of DTAT, or DTATEGF, or a control protein Bickel3 was delivered intracranially by convection-enhanced delivery (CED) via an osmotic minipump. The brain tumor fluorescence signal intensity was investigated by bioluminescent imaging (BLI). Microvessel density (MVD) was measured by immunchistochemistry SABC method in each group. RESULTS: In vitro DTAT and DTATEGF were found highly potent against U87-luc cell line, with IC(50) <0.01 nmol/L and IC(50)<1 nmol/L, respectively. In vivo BLI monitoring of the control group showed progressively increasing luminescence, while in the two treatment groups, luminescence was reduced on day 8, and increased slowly (P<0.05). The MVD of DTAT (31.6±5.2)/mm(2) and DTATEGF (25.1±6.5)/mm(2) groups had significant difference with that of the control group (51.3±7.4) /mm(2) (P<0.01). CONCLUSION: Both DTAT and DTATEGF have potential in clinical application against globlastoma multiforme because of their ability to target the tumor cells and neovasculature simultaneously.

Functional Hydrogel Co-Remolding Migration and Differentiation Microenvironment for Severe Spinal Cord Injury Repair.

Spinal cord injury (SCI) activates nestin+ neural stem cells (NSCs), which can be regarded as potential seed cells for neuronal regeneration. However, the lesion microenvironment seriously hinders the migration of the nestin+ cells to the lesion epicenter and their differentiation into neurons to rebuild neural circuits. In this study, a photosensitive hydrogel scaffold is prepared as drug delivery carrier. Genetically engineered SDF1α and NT3 are designed and the scaffold is binary modified to reshape the lesion microenvironment. The binary modified scaffold can effectively induce the migration and neuronal differentiation of nestin+ NSCs in vitro. When implanted into a rat complete SCI model, many of the SCI-activated nestin+ cells migrate into the lesion site and give rise to neurons in short-term. Meanwhile, long-term repair results also show that implantation of the binary modified scaffold can effectively promote the maturation, functionalization and synaptic network reconstruction of neurons in the lesion site. In addition, animals treated with binary scaffold also showed better improvement in motor functions. The therapeutic strategy based on remolding the migration and neuronal differentiation lesion microenvironment provides a new insight into SCI repair by targeting activated nestin+ cells, which exhibits excellent clinical transformation prospects.

Punicic acid ameliorates obesity-related hyperlipidemia and fatty liver in mice via regulation of intestinal flora and lipopolysaccharide-related signaling pathways.

Punicic acid (PA), mainly found in pomegranate seed oil (PSO), has attracted increasing attention due to its potential to mitigate obesity. The regulation of intestinal microflora was identified as a crucial factor and an effective strategy to reverse obesity-related hyperlipidemia and non-alcoholic fatty liver disease (NAFLD). To assess the impact of PSO on hyperlipidemia related to obesity, we investigated the hepatic lipid status and gut microbiota regulation in mice over 13 weeks of feeding a high-fructose high-fat diet (HFHFD). Serum lipid markers, including TG, TC and LDL-C, were markedly reduced in hyperlipidemic mice. PSO supplementation reduced hepatic lipid accumulation and steatosis, inhibited the expression of pro-inflammatory mediators (including IL-6 and IL-1ß), and restored the normal levels of the anti-inflammatory cytokine IL-10. In addition, PSO also alleviated oxidative stress and increased T-AOC and SOD activities, as well as GSH levels, while reducing the MDA content in the liver of HFHFD-fed mice. The activation of TLR4/MyD88/NF-κB and TLR4/IL-22/STAT3 signaling pathways in the liver due to the HFHFD was also evidently inhibited by PSO. Furthermore, supplementation of PSO ameliorated the HFHFD-induced dysbiosis of intestinal microflora, resulting in a markedly increased proportion of Muribaculaceae, a decreased ratio of Blautia, and elevated levels of microbiota-derived short-chain fatty acids (SCFAs). Moreover, the expression of tight junction proteins correlated with intestinal barrier function was notably restored in the colon. The collected results indicate that PSO may be an effective nutraceutical ingredient for attenuating lipid metabolic disorders.

[Efficacy of bispecific targeted immunotoxin DTATEGF against NSCLC brain metastatic tumor PC9-BrM3 cells].

OBJECTIVE: To investigate the in vitro and in vivo anticancer efficacy of the immunotoxin DTATEGF against human NSCLC brain metastatic tumor PC9-BrM3 cell line. METHODS: The effect of the immunotoxin DTATEGF was tested for its ability to inhibit the proliferation of PC9-BrM3 cells in vitro by MTT assay. The cell cycle and the apoptosis of cells with 1 pmol/L DTATEGF were examined by flow cytometry. In vivo, 2 µg of DTATEGF or control Bickel3 was given intratumor to nude mice with established PC9-BrM3 xenografts on their hips, and tumor volumes were measured and tumor samples were investigated by immunchistochemistry SABC method. The microvessel density (MVD) was measured in each group. RESULTS: In vitro, DTATEGF killed PC9-BrM3 cells and showed an IC50 of 1 pmol/L. The apoptotic rate in the 1 pmol/L DTATEGF group was (64.0±0.5)% , significantly higher than that in the control group (1.5±0.4)% (P<0.01). The cell cycle was obviously inhibited by DTATEGF in a dose-dependent manner. The percentage of cells treated with 1 pmol/L DTATEGF in SubG0/G1 phase was (32.0±1.5)%, significantly higher than that in the control group (2.0±0.4)% (P<0.01). In vivo, DTATEGF significantly inhibited the growth of PC9-BrM3 hip tumors (P<0.05). The MVD of the DTATEGF group was (15.6±4.6)/mm2, significantly lower than that of the control group (31.2±5.4)/mm2 (P<0.01). CONCLUSION: DTATEGF inhibits the growth of the PC9-BrM3 cell line and induces its apoptosis. It is highly efficacious against human metastatic NSCLC brain tumor and against neovascularization.