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Background The endoscopic endonasal approach (EEA) and the endoscopic supraorbital keyhole approach (eSKA) provide minimally invasive access to tuberculum sellae (TS) tumors. Evaluation of the operating maneuverability is helpful for approach selection. Herein, we compared the two approaches and aimed to provide quantitative anatomic data for surgical decision-making in the management of TS lesions. Methods Fifteen dissections were performed on five silicone-injected cadaveric heads. The EEA and eSKA (both right and left) were performed on each head. Surgical freedom and working angles in the axial and sagittal planes were calculated using the stereotactic navigation system in the selected six targets: the midpoint of the leading edge of the sphenoid sinus (leSS), the midpoint of the edge of the dorsum sellae (eDS), the ipsilateral medial opticocarotid recess (imOCR), the contralateral medial opticocarotid recess (cmOCR), the ipsilateral lateral opticocarotid recess (ilOCR), and the contralateral lateral opticocarotid recess (clOCR). Results The surgical freedom at the ilOCR and the axial working angles at the leSS, ilOCR, and imOCR (imOCR with excessive manipulation of the optic apparatus) were greater in the eSKA. The EEA provided greater surgical freedom and/or working angles at most targets than eSKA (the surgical freedom at the imOCR, cmOCR, clOCR, and eDS; the axial working angles at the cmOCR and clOCR; and the sagittal working angles at the leSS, imOCR, cmOCR, clOCR, and eDS). Conclusion The EEA provides greater surgical freedom and working angles for paramedian lesions, whereas the eSKA provides better surgical maneuverability for lesions with lateral extension.

Objective Biochemical remission rates of endoscopic endonasal transsphenoidal surgery (EETS) and its associated predictive factors were evaluated in patients with somatotrophin pituitary adenomas. Methods The patients who underwent EETS in Jinling Hospital were identified between 2011 and 2020. The surgeons' experience, preoperative insulin-like growth factor 1 (IGF-1), basal growth hormone (GH) levels, nadir GH levels, and the tumor characteristics were analyzed for their relationships with endocrine outcomes. Total 98 patients were included for single factor analysis and regression analysis. They were divided into three groups according to the admission chronologic order. Results The overall remission rate of the patients was 57% (56/98) for all the patients over 10 years. In the single factor analysis, we found that the tumor size, cavernous invasion, and sellar invasion were valuable to predict the endocrine outcome after surgery. As for the suprasellar invasion, no significant difference was found between the noninvasive group and the invasive group. The preoperative IGF-1 level (p = 0.166), basal GH level (p = 0.001), and nadir GH level (p = 0.004) were also different between the remission group and the nonremission group in the single factor analysis. The logistic regression analysis indicated that the preoperative nadir GH (odds ratio = 0.930, 95% confidence interval = 0.891–0.972, p = 0.001) was a significant predictor for the endocrine outcomes after surgery. Conclusion The surgeons' experience is an important factor that can affect the patients' endocrine outcomes after surgery. The macroadenomas with lateral invasion are more difficult to cure. Patients with higher preoperative nadir GH levels are less likely to achieve remission.

AIM: Cavernous sinus hemangiomas (CSHs) are hypervascular malformations and the surgical treatment is technically demanding. Although some articles have reported resection of CSHs using endoscopic endonasal transsphenoidal surgery (EETS), most of them were encountered for a lack of preoperative strategy guidance. Herein, we reported gross total resection (GTR) of intrasellar CSHs in two patients undergoing strategical EETS and compared EETS with frontotemporal craniotomy (FC) and stereotactic radiosurgery by literature review. MATERIAL AND METHODS: Two patients with CSHs who underwent EETS were reported. The literature review was conducted to exhaust studies that reported surgical treatment for CSHs. The tumor resection rate, and the postoperative short-term and long-term newly-developed or deteriorative cranial-nerve function rates were extracted. RESULTS: GTR was achieved with no postoperative complications in the two cases. Nine articles reported 14 cases undergoing EETS for CSHs and twenty-three articles reported 195 cases undergoing FC for CSHs. The GTR rates of EETS and FC were 57.14% (8/14) and 78.97% (154/195) respectively. The postoperative short-term and long-term newly-developed or deteriorative cranial-nerve function rates were 0% (0/7) and 0% (0/6) for the EETS group, and 57% (57/100) and 18.18% (18/99) for the FC group. According to the previous meta-analysis, stereotactic radiosurgery resulted in remarkable tumor shrinkage in 67.80% (40/59) of patients and partial shrinkage in 25.42% of patients. DISCUSSION: The results showed that the intrasellar type of CSHs could be removed safely by EETS without crossing the nerves in the CS.

BackgroundWe previously introduced the one-and-a-half (1½) nostril endoscopic transsphenoidal approach (OETA) to reduce the damage to the nasal structures. Here, we reported the modified approach which is called the endoscopic 1½-transseptal approach (EOTA) for pituitary surgery by combining the OETA and the microscopic transseptal approach to simplify intranasal procedures and protect nasal mucosa. In EOTA, we removed the sellar lesions in a corridor that is composed of the right submucosal space and the anterior left ½ nasal cavity.MethodsWe introduced EOTA with a detailed technical description and preliminary clinical outcomes. A total of 128 patients who underwent EOTA for pituitary surgery from July 2018 to September 2020 were reviewed for evaluation of the safety and efficacy of this approach.ResultsEOTA had a high gross total resection (GTR) rate and a 1ow complication rate. GTR was achieved in 106 (82.8%) patients, with 81.4% for pituitary adenomas and 93.3% for other non-adenomatous lesions. Post-operative complications included 3 patients (2.3%) with postoperative cerebrospinal fluid leak, 3 patients (2.3%) with diabetes insipidus, 5 patients (3.9%) with anterior pituitary insufficiency and 2 patients (1.6%) with meningitis. In addition, EOTA simplified the intranasal procedures, which led to shortened operation time (67.8 minutes). The results of ASK nasal-12, the Lund-Kennedy score, and the odor identification test showed that patients who underwent EOTA recovered quickly after surgery and the nasal cavity returned to the preoperative condition both apparently and physiologically one month after surgery.ConclusionsEOTA is a simple, safe and effective approach for pituitary lesions, which provides not only a sufficient surgical corridor for 2-surgeon/4- or 3-hands technique but also minimally invasive access to the sellar region.

Injuries to the central nervous system (CNS) often lead to severe neurological dysfunction and even death. However, there are still no effective measures to improve functional recovery following CNS injuries. Optogenetics, an ideal method to modulate neural activity, has shown various advantages in controlling neural circuits, promoting neural remapping, and improving cell survival. In particular, the emerging optogenetics has exhibited promising therapeutic methods for CNS injuries. In this review, we introduced the light-sensitive proteins and light stimulation system which are important components of optogenetic technology in detail and summarized the development trends. Meanwhile, we constructed a comprehensive picture of the current application of optogenetics in CNS injuries and highlighted recent advances for the treatment and functional recovery of neurological deficits. Finally, we discussed the therapeutic challenges and prospective uses of optogenetics therapy by photostimulation/photoinhibition modalities that would be suitable for clinical applications.

BackgroundBinostril endoscopic transsphenoidal approach (BETA) is the most used approach for sellar lesions nowadays, while its damage to the nasal structures may cause nasal discomfort and affect nasal functions including respiration and olfaction. With the purpose to improve the post-operative sinonasal quality of life (QoL), we introduced the one-and-a-half nostril endoscopic transsphenoidal approach (OETA) in 2016 which preserved more natural structures and registered a prospective randomized controlled trial (ChiCTR-IOR-16008222) to compare the two approaches regarding the surgical outcomes and complications.MethodsSixty patients with pituitary adenomas were recruited and randomly assigned to the OETA group and the BETA group between April 2016 and May 2017 in Jinling Hospital. The tumor resection rate, endocrinal and visual outcomes, and surgical complications between the OETA and BETA groups were analyzed. Besides, the questionnaire Anterior Skull Base Nasal Inventory-12 (ASK Nasal-12) was used to evaluate patients’ sinonasal QoL at seven time points (pre-operative; 2-weeks, 1-month, 3-months, 6-months, 12-months, and long-term post-operatively). The Sniffin’ Sticks were used to assess patients’ olfactory function objectively in a long term. Each patient was followed for at least 12 months post-operatively.ResultsThere was no significant difference in tumor resection rate, hormonal and visual outcomes, and surgical complications between the two groups. Regarding the ASK Nasal-12, patients in the OETA group complained less about dried nasal material at 2 weeks after surgery (P = 0.017). One month after surgery, the OETA group had better olfaction function (P = 0.019) compared with the BETA group. However, there was no significant difference in early and long-term postoperative sinonasal QoL between the two approaches according to the entire ASK Nasal-12 metric. The results of the Sniffin’ Sticks showed that the two groups had a similar olfactory performance at long-time follow-up.ConclusionIn this single tertiary center trial, the results showed that the OETA achieved the same surgical outcomes and post-operative sinonasal QoL as the BETA. Clinical Trial Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=13852, identifier: ChiCTR-IOR-16008222

Radiotherapy remains a mainstream treatment for patients with glioma. Yet intrinsic radioresistance has largely compromised the efficacy of the treatment. Increasing concerns have been raised that overexpression of the Nrf2, along with a hypoxic tumor microenvironment, may have contributed to the deterioration of radiotherapy in tumors. So, this study investigated the role of Nrf2 in the radiation therapy of glioma cells in hypoxia.To determine the expression levels of Nrf2 and HIF-1α, surgical mastectomy specimens from patients with glioma in our institute were analyzed by immunohistochemical staining. Glioblastoma multiforme (GBM) cell lines U251 and U87 with Nrf2 knocked down were produced by transfection with lentiviral particles. Cell lines were treated with ionizing radiation in hypoxiaNrf2 and its downstream pathway were upregulated in surgical specimens after radiotherapy, verified by GBM cell lines treated withDownregulation of Nrf2 could sensitize the lethal effect on GBM cells

BTB Domain and CNC Homolog 1 (Bach1) has been implicated in cancer progression, particularly in invasion, but little is unknown about its effect on glioma. Here, we confirmed that highly expressed Bach1 prominently promoted glioma invasion. Similar to the reported mechanisms in other tumors, Bach1 upregulation was also correlated with epithelial mesenchymal transition (EMT) in glioma cells. More importantly, proteomic analysis indicated that the main mechanism of Bach1 promoting invasion in glioma involved extracellular matrix (ECM). We further found thatBach1 upregulation was associated with the multiple mechanisms of ECM remodeling in glioma, including increasing the expression and deposition of ECM components, activating TGFBR2-smad2/3 signaling, promoting invadopodia formation and inducing the expression and secretion of MMP2. Meanwhile, Bach1 overexpression increased ferroptosis sensitivity in glioma cells. The ferroptosis inducer (sulfasalazine) obviously suppressed the gliomas with Bach1 upregulation in vitro and in vivo. Overall, Bach1 has a two-faced role in glioma. Highly expressed Bach1 promotes glioma invasion. Conversely, Bach1 upregulation is also a potential indicator of the sensitivity of ferroptosis inducers.

N6-methyladenosine (m6A) is the product of the most prevalent mRNA modification in eukaryotic cells. Accumulating evidence shows that tumor microenvironment (TME) plays a pivotal role in tumor development. However, the underlying relationship between m6A modification and the TME of a papillary renal cell carcinoma (PRCC) is still unclear. To investigate the relationship between m6A modification and prognosis and immunotherapeutic efficacy for PRCC, we looked for distinct m6A modification patterns based on 23 m6A-related genes. Next, the correlation between m6A modification patterns and TME-related characteristics was investigated. Then, the intersected differentially expressed genes were selected and the scoring system, denoted as m6A score, was established to evaluate m6A modification, prognosis, and immunotherapeutic efficacy. In this study, three distinct m6A expression clusters were identified. Based on the results of immune cell infiltration analysis and functional analysis, carcinogenic pathways, TME-related immune cells, and pathways were identified as well. More importantly, the established m6A score showed good value in predicting clinical outcomes according to results using external cohorts. Specifically, PRCC patients with low m6A score value showed better survival, immunotherapeutic response, and higher tumor mutation burden. Furthermore, immunohistochemistry using PRCC clinical samples from our medical center was carried out and verified our results. In conclusion, this study highlights the underlying correlation between m6A modification and the immune landscape and, hence, enhances our understanding of the TME and improved the therapeutic outlook for PRCC patients.

BackgroundLaparoscopic partial nephrectomy (LPN) is the standard of care for localized small renal cancer. The most critical step in this form of surgery is to localize the renal artery. In the present study, we describe a novel technique that uses the left lumbar vein (LV) to access the left renal artery during LPN.Materials and methodsThis was a retrospective review of 130 cases of transperitoneal laparoscopic partial nephrectomies (TLPNs) performed on patients with renal cancer in our center between January 2018 and December 2021. Either the LV or non-lumbar vein (N-LV) technique was used to locate and manage the left renal artery. We recorded relevant clinical data from all patients, including patient characteristics, tumor data, and perioperative outcomes (artery mobilization time, operative time, estimated blood loss, and complications). Comparative analysis was then carried out between the cases using LV or N-LV vein techniques.ResultsAll TLPNs were successfully accomplished without conversion to open approaches. There were no complications involving the renal vessels during the entire study. The LV technique resulted in a significantly shorter time to mobilize the renal and significantly less estimated blood loss (p ConclusionThe left LV represents an anatomical landmark for locating the left renal artery in TLPN. This approach has numerous advantages over the transperitoneal approach including facilitating access to the left renal artery and reducing the duration of surgery.

Adamantinomatous craniopharyngioma (ACP) is the most common tumor of the sellar region in children. The aggressive behavior of ACP challenges the treatment for it. However, immunotherapy is rarely studied in ACP. In this research, we performed unsupervised cluster analysis on the 725 immune-related genes and arrays of 39 patients with ACP patients in GSE60815 and GSE94349 databases. Two novel immune subtypes were identified, namely immune resistance (IR) subtype and immunogenic (IG) subtype. Interestingly, we found that the ACPs with IG subtype (34.78%, 8/23) were more likely to respond to immunotherapy than the ACPs with IR subtype (6.25%, 1/16) via tumor immune dysfunction and exclusion (TIDE) method. Simultaneously, the enrichment analysis indicated that the differentially expressed genes (DEGs) (p < 0.01, FDR < 0.01) of the IG subtype were chiefly involved in inflammatory and immune responses. However, the DEGs of the IR subtype were mainly involved in RNA processing. Next, immune infiltration analysis revealed a higher proportion of M2 macrophage in the IG subtype than that in the IR subtype. Compared with the IR subtype, the expression levels of immune checkpoint molecules (PD1, PDL1, PDL2, TIM3, CTLA4, Galectin9, LAG3, and CD86) were significantly upregulated in the IG subtype. The ssGSEA results demonstrated that the biofunction of carcinogenesis in the IG subtype was significantly enriched, such as lymphocyte infiltration, mesenchymal phenotype, stemness maintenance, and tumorigenic cytokines, compared with the IR subtype. Finally, a WDR89 (the DEG between IG and IR subtype)-based nomogram model was constructed to predict the immune classification of ACPs with excellent performance. This predictive model provided a reliable classification assessment tool for clinicians and aids treatment decision-making in the clinic.

N6-methyladenosine (m

Glioblastoma multiforme (GBM) is a common and aggressive form of brain tumor. The NSingle-cell and bulk RNA-sequencing data were acquired from the GEO and TCGA databases, respectively. We used bioinformatics and statistical tools to analyze associations between mAt the single-cell level, m

Dopamine agonist (DA) is the first choice for the treatment of prolactinomas, and drug resistance is unavoidable during treatment due to the heterogeneity of tumors. The two prolactinoma cell lines (GH3 cells and MMQ cells) were found to have different sensitivity and responding modes to the cabergoline (CAB) and bromocriptine (BRC). In this research, we disclosed the capability of ACT001, a derivative of parthenolide analogs, to activate AMPK by increasing the intracellular reactive oxygen species (ROS) level and AMP/ATP ratio to reverse DA resistance through dual pathways in prolactinoma cells. The results indicated that ACT001 could reverse the CAB resistance in GH3 cells by inhibiting the mTOR signaling pathway, inducing cell death through autophagy, and reverse the BRC resistance in MMQ cells by activating the EGR1 signaling pathway, inducing cell death through apoptosis. Our results suggested that ACT001 is a promising therapeutic compound for treating DA-resistant prolactinomas.

Background For prolactinoma patients, dopamine agonists (DAs) are indicated as the first-line treatment and surgery is an adjunctive choice. However, with the development of surgical technique and equipment, the effect of surgery has improved. The aim of this study was to assess the efficacy and safety of surgery versus DAs in patients with different types of prolactinomas. Methods A systematic search of literature using Web of Science, PubMed, Cochrane Library, and Clinical Trial databases was conducted until July 12, 2019. Prolactinoma patients treated with DAs (bromocriptine or cabergoline) or surgery (microscopic or endoscopic surgery) were included. Outcomes included the biochemical cure rate, recurrence rate, prolactin level, improvement rates of symptoms, and incidence rates of complications. A random-effects model was used to pool the extracted data. Qualitative comparisons were conducted instead of quantitative comparison. Results DAs were better than surgery in terms of the biochemical cure rate (0.78 versus 0.66), but surgery had a much lower recurrence rate (0.19 versus 0.57). Full advantages were not demonstrated in improvement rates of symptoms and incidence rates of complications with both treatment options. In microprolactinoma patients, the biochemical cure rate of endoscopic surgery was equal to the average cure rate of DAs (0.86 versus 0.86) and it surpassed the biochemical cure rate of bromocriptine (0.86 versus 0.76). In macroprolactinoma patients, endoscopic surgery was slightly higher than bromocriptine (0.66 versus 0.64) in terms of the biochemical cure rate. Conclusion For patients with clear indications or contraindications for surgery, choosing surgery or DAs accordingly is unequivocal. However, for patients with clinical equipoise, such as surgery, especially endoscopic surgery, in microprolactinoma and macroprolactinoma patients, we suggest that neurosurgeons and endocrinologists conduct high-quality clinical trials to address the clinical equipoise quantitatively.

Background: Several literatures reported that suturing dura was reliable in preventing cerebrospinal fluid (CSF) leak in transsphenoidal surgery. However, suturing and knotting is technically chall...

The treatment of hyperprolactinemia is based on the use of dopamine agonists, mainly bromocriptine (BRC) and cabergoline (CAB). They reduce tumour size effectively and restore gonadal function. However, there is a difference in drug sensitivity between CAB and BRC in patients with prolactinoma, although the underlying mechanisms are still unknown. Thus, we investigated whether there are differences in tumour sensitivity to CAB and BRC and their possible differential mechanisms in two prolactinoma cell lines. In our study, we found that GH3 cells are more sensitive to BRC and that MMQ cells are more sensitive to CAB. Moreover, BRC and CAB elicited cell death via different pathways; BRC induced prolactinoma cell death mainly through the apoptosis pathway, and CAB induced pituitary prolactinoma cell death mainly via the autophagic cell death pathway. Using gene microarray analysis, we found that BRC induces the apoptosis of prolactinoma cells through the ERK/EGR1 signalling pathway, whereas CAB induces autophagic death by inhibiting the AKT/mTOR signalling pathway. Our study showed the difference in tumour sensitivity and differential mechanisms in BRC- and CAB-treated prolactinoma cells, which provides a theoretical basis for the accurate treatment of prolactinoma.

BackgroundThe Ki-67 index is an indicator of proliferation and aggressive behavior in pituitary adenomas (PAs). This study aims to develop and validate a predictive nomogram for forecasting Ki-67 index levels preoperatively in PAs.MethodsA total of 439 patients with PAs underwent PA resection at the Department of Neurosurgery in Jinling Hospital between January 2018 and October 2020; they were enrolled in this retrospective study and were classified randomly into a training cohort (n = 300) and a validation cohort (n = 139). A range of clinical, radiological, and laboratory characteristics were collected. The Ki-67 index was classified into the low Ki-67 index (ResultsAge, primary-recurrence subtype, maximum dimension, and prolactin were included in the nomogram model. The areas under the curve (AUCs) of the nomogram model were 0.694 in the training cohort and 0.658 in the validation cohort. A well-fitted calibration curve was also generated for the nomogram model. A subgroup analysis revealed stable predictive performance for the nomogram model. A correlation analysis revealed that age (R = −0.23; p < 0.01), maximum dimension (R = 0.17; p < 0.01), and prolactin (R = 0.16; p < 0.01) were all significantly correlated with the Ki-67 index level.ConclusionsAge, primary-recurrence subtype, maximum dimension, and prolactin are independent predictors for the Ki-67 index level. The current study provides a novel and feasible nomogram, which can further assist neurosurgeons to develop better, more individualized treatment strategies for patients with PAs by predicting the Ki-67 index level preoperatively.

BackgroundThe glioma-associated stromal cell (GASC) is a recently identified type of cell in the glioma microenvironment and may be a prognostic marker for glioma. However, the potential mechanisms of GASCs in the glioma microenvironment remain largely unknown. In this work, we aimed to explore the mechanisms of GASCs in gliomas, particularly in high-grade gliomas (HGG).MethodsWe used glioma datasets from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). We utilized the Single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm to discriminate between patients with high or low GASC composition. The xCELL and CIBERSORT algorithms were used to analyze the composition of stromal cells and immune cells. Risk score and a nomogram model were constructed for prognostic prediction of glioma.ResultsWe observed for the first time that the levels of M2 macrophages and immune checkpoints (PD-1, PD-L1, PD-L2, TIM3, Galectin-9, CTLA-4, CD80, CD86, CD155, and CIITA) were significantly higher in the high GASC group and showed positive correlation with the GASC score in all glioma population and the HGG population. Copy number variations of DR3 and CIITA were higher in the high-GASC group. THY1, one of the GASC markers, exhibited lower methylation in the high GASC group. The constructed risk score was an independent predictor of glioma prognostics. Finally, a credible nomogram based on the risk score was established.ConclusionsGASCs stimulate glioma malignancy through the M2 macrophage, and are associated with the level of immune checkpoints in the glioma microenvironment. The methylation of THY1 could be used as prognostic indicator and treatment target for glioma. However, further studies are required to verify these findings.

Endoscopic endonasal surgery (EES) is one of the preferred options for skull base pathologies. Cerebrospinal fluid (CSF) leak is a significant complication of EES and neurosurgeons have proposed various reconstructive strategies to decrease this morbidity. We describe and compare the efficacy of these strategies.We searched PubMed, Cochrane Library, and Web of Science for publications between 1990 and November 2019. We defined a reconstruction hierarchy of seven levels from inside to outside: fat graft, intracranial intradural layer (inlay), intracranial extradural layer (onlay), buttress, mucosal flap, nasal packing and lumbar drainage. A single-arm analysis was performed for the primary outcome of CSF leak rate.Of 3641 records identified, 48 studies met the inclusion criteria. Pituitary tumors had lower postoperative CSF leak rate than other diseases (1.8% vs. 6.5%, RD = -4.7% [-7.1%, -2.1%]). In high CSF flow group, the post-operative leak rate was reduced by application of mucosal flap (4.3% vs. without mucosal flap at 12.8%, RD = -8.5% [-15.1%, -1.9%]). The use of inlay showed potential of decreasing the post-operative leak rate (5.0% vs. 7.2%, RD = -2.2% [-7.7%, 3.3%]). In low CSF flow group, tampon was better than balloon for nasal packing (1.0% vs. 10.5%, RD = -9.5% [-16.5%, -2.4%]).Mucosal flap and inlay for high-flow intraoperative CSF leak and tampon (compared with balloon) for low-flow intraoperative CSF leak, improved the postoperative CSF leak rate. Further studies are required to establish more robust evidence.

BackgroundPituitary adenomas (PAs) are the most common tumor of the sellar region. PA resection is the preferred treatment for patients with clear indications for surgery. Intraoperative cerebrospinal fluid (iCSF) leakage is a major complication of PA resection surgery. Risk factors for iCSF leakage have been studied previously, but a predictive nomogram has not yet been developed. We constructed a nomogram for preoperative prediction of iCSF leakage in endoscopic pituitary surgery.MethodsA total of 232 patients who underwent endoscopic PA resection at the Department of Neurosurgery in Jinling Hospital between January of 2018 and October of 2020 were enrolled in this retrospective study. Patients treated by a board-certified neurosurgeon were randomly classified into a training cohort or a validation cohort 1. Patients treated by other qualified neurosurgeons were included in validation cohort 2. A range of demographic, clinical, radiological, and laboratory data were acquired from the medical records. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and uni- and multivariate logistic regression were utilized to analyze these features and develop a nomogram model. We used a receiver operating characteristic (ROC) curve and calibration curve to evaluate the predictive performance of the nomogram model.ResultsVariables were comparable between the training cohort and validation cohort 1. Tumor height and albumin were included in the final prediction model. The area under the curve (AUC) of the nomogram model was 0.733, 0.643, and 0.644 in training, validation 1, and validation 2 cohorts, respectively. The calibration curve showed satisfactory homogeneity between the predicted probability and actual observations. Nomogram performance was stable in the subgroup analysis.ConclusionsTumor height and albumin were the independent risk factors for iCSF leakage. The prediction model developed in this study is the first nomogram developed as a practical and effective tool to facilitate the preoperative prediction of iCSF leakage in endoscopic pituitary surgery, thus optimizing treatment decisions.

Background The application of neuroendoscopy in intraventricular hemorrhage (IVH) has attracted more and more attention in recent years. Studies have shown that the use of neuroendoscopy for IVH evacuation has advantages over external ventricular drainage (EVD) alone. However, the cases of most current research are small and all of them are retrospective studies. The aim of this study is to explore the prognosis of patients with moderate to severe IVH who undergo endoscopic IVH evacuation surgery versus those who undergo EVD alone. Methods The study is a prospective, randomized, controlled, multi-center clinical trial. Nine hundred and fifty-six subjects with moderate to severe IVH across four tertiary hospitals in China will be randomly assigned (1:1) to receive either endoscopic IVH evacuation surgery or EVD. The primary objective is to compare patients’ survival rate at 12 months after surgery. Discussion The trial is designed to investigate the prognostic benefits of endoscopic IVH evacuation surgery for patients with moderate to severe IVH. Currently, it has never been investigated in a prospective randomized controlled clinical trial. Trial registration ClinicalTrials.gov, NCT04037267. Registered on 26 July 2019.

Objective This article determines which of the one-and-a-half nostril, mononostril, and binostril endoscopic endonasal transsphenoidal approaches provide a superior manipulation during surgery. Methods The three approaches were orderly performed on 10 silicon-injected cadaveric heads to quantitatively assess surgical freedom and attack angle for sella. Measurements were determined with a standardized method under neuronavigation system using data of computed tomography. Results The one-and-a-half nostril endoscopic transsphenoidal approach (OETA) offered superior exposed area than that of the mononostril approach (META), and similar to that of the binostril approach (BETA). For surgical freedom at anatomic targets, the OETA showed greater surgical flexibility at pituitary center, the right medial optic carotid recess (R-mOCR), the left mOCR, the medial intersection of the right cavernous internal carotid artery, and extension line of upper margin of the clivus (R-mICC) than those of the META, and similar to those of the BETA.For sagittal angle of attack to the R-mOCR, R-mICC, and L-mOCR, the OETA can provide better angular freedom for surgeon than that of the META, and similar to that of the BETA. The OETA had the same axial attack to the pituitary center with the BETA. The OETA and the META had limited surgical freedom at L-mICC, and both inferior to the BETA. Conclusion The OETA has similar exposed area, surgical freedom, and attack angle for most anatomic targets to the BETA without resecting contralateral nasal septal mucosa, and obviously superior to the META.

Additional file 1. SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents.

Glioblastoma (GBM, WHO grade 4) is a highly heterogeneous and aggressive primary malignant brain tumor. BTB domain and CNC homology 1 (BACH1) is a transcription factor, and it plays an essential role in regulating tumor metastasis, tumor metabolism, and tumor stem cell self-renewal. However, its role in glioma is still unclear. In this research, we confirmed that BACH1 as an independent prognostic indicator was enriched in GBMs. BACH1 was strongly correlated with immune responses in GBMs, especially the M0 and M2 tumor-associated macrophage (TAM) mediated immune responses. GBMs with high expression of BACH1 express high levels of immune checkpoints (ICs), glioma cell-derived TAM chemokines, and M2 TAM markers. Interestingly, single cell RNA-seq analysis showed that the expression level of BACH1 in TAMs was higher than that in the other cell types in GBM. Transcriptome analysis of U87-MG cells showed that compared with the BACH1-vector U87-MG group, glioma cell-derived TAM chemokines (including monocyte chemotactic protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and EGF) and ICs (including CD276, TIM-3, LAG3, TIGIT and LGALS9) were enriched in the BACH1-overexpressing U87-MG group. In addition, we constructed a polygenic risk scoring model and compound nomogram model based on BACH1, which might provide a reliable prognosis assessment tool for clinicians and aid in treatment decision-making in the clinic. In conclusion, this research identified that BACH1 might be a potential molecular signature for survival and immunotherapy response. GBMs with high expression of BACH1 have a stronger immunosuppressive tumor microenvironment (TME). Overexpression of BACH1 can upregulate the expression of glioma cell-derived TAM chemokines and ICs in vitro. Moreover, the risk model and nomogram model based on BACH1 can provide a reliable prognosis assessment tool. Therefore, BACH1 is a promising therapeutic target for GBMs.

Simulation-based training has been considered as the most promising curriculum for neurosurgical education to finally improve surgical skills with the greatest efficiency and safety. However, most of the simulators including physical models and virtual reality systems are relatively expensive, which limits their promotion. In this study, the authors tried to develop a realistic, low-cost, and reusable simulator for endoscopic third ventriculostomy (ETV) and evaluate its validity. A 3D-printed rigid skull with the ventricular system originated from a de-identified patient with obstructive hydrocephalus was constructed. The third ventricular floor was designed as a replaceable module. Thirty-nine neurosurgeons tested the simulator and a rating system was established to assess their performance. All participants filled out questionnaires to evaluate the simulator after training. Five neurosurgical students were recruited to finish the whole training for ten times in order to explore the learning curve of ETV. We found that (1) the more experienced surgeons performed obviously better than the rather inexperienced surgeons which verified that our model could reflect the ability of the trainees; (2) as the training progressed, the scores of the post-graduates increased and the fifth training average score was obviously higher than their first training average score. The feedback questionnaires showed the average scores for value of the simulator as a training tool and global rating were 3.15 and 3.54 (on a 4-point scale). Our model was practical for ETV training. The results of our program showed that our model could precisely reflect the operators’ ability to perform ETV and could make it more efficient to master basic skills.

Spontaneous cerebrospinal fluid (CSF) rhinorrhea represents an important clinical entity that is being observed with increasing prevalence, ranging from 14 to 55%. Spontaneous CSF rhinorrhea is associated with elevated intracranial pressure (ICP), which is rarely stopped without surgical intervention. Endoscopic endonasal repair is typically warranted for CSF rhinorrhea. However, the recurrence rate of CSF leaks after the endoscopic endonasal repair of skull base defects due to ICP is usually high. We describe a 25-year-old man without a history of head injury, tumor, or obesity. The onset of his symptoms occurred in 1 week in the form of a persistent clear left nostril rhinorrhea. Computed tomography (CT) and magnetic resonance images (MRI) showed signs of CSF in the left sphenoidal sinus, meningocele in the left frontal sinus, empty sella, hydrocephalus, and Chiari I malformation (CIM). Cine-MRI revealed the flow of CSF was obstructed at the aqueduct and the outlet of the fourth ventricle. Endoscopic third ventriculostomy (ETV) was performed for the patient with obstructive hydrocephalus. Post-operative CSF pressure measurement demonstrated elevated ICP. The patient still had case of CSF rhinorrhea, and subsequently underwent lumboperitoneal shunt (LPS) for treatment of ICP. The patient showed a prompt resolution of CSF leak. Ten months later, the patient showed a significant improvement in terms of his herniated tonsil and cessation of CSF rhinorrhea.

Overactivation of the Gs-mediated pathway by mutations of the G-protein α subunit (Gsα), a gsp oncogene, results in increased growth hormone (GH) hypersecretion and reduced tumor volume in patients with GH-secreting pituitary tumors. However, the mechanism underlying the clinical characteristics of gsp oncogene requires further investigation. Cyclic adenosine monophosphate-responsive element binding (CREB), as a downstream target gene of gsp oncogene, is implicated in activating maternally expressed gene 3 (MEG3). The present study proposes that gsp oncogene mediates MEG3-regulating GH hypersecretion, resulting in the small tumor size of GH-secreting tumors. Therefore, the present study detected Gsα mutations by polymerase chain reaction in GH-secreting tumors, and revealed that Gsα mutations were observed in 7/25 (28%) GH-secreting tumors. Gsp-positive tumors indicated significantly increased levels of phosphorylated p-CREB (P

Postoperative cerebrospinal fluid (CSF) leaks still occur in patients without intraoperative CSF leaks after endoscopic endonasal pituitary adenoma surgery. We propose a reconstructive technique, the sellar floor flap (SFF), for universal sellar anatomical reconstruction. A total of 113 patients without intraoperative CSF leaks after endoscopic endonasal pituitary adenoma surgery from July 2013 to June 2016 were reviewed: 43 underwent sellar reconstruction with the SFF (the SFF group) and 70 underwent sellar packing only (the nonreconstruction group). No case of postoperative CSF leak was reported in the SFF group, whereas 7 cases were reported in the nonreconstruction group ( P < .05). The SFF is suitable for universal reconstruction after endoscopic endonasal pituitary adenoma surgery and may decrease postoperative CSF leak.

Alpha lipoic acid (ALA) is a powerful antioxidant that has proven protective effects against brain damage following a traumatic brain injury (TBI) in rats. However, the molecular mechanisms underlying these effects are not well understood. This study investigated the effect of ALA on neural apoptosis and the potential mechanism of these effects in the weight-drop model of TBI in male Sprague-Dawley rats that were treated with ALA (20 or 100 mg/kg) or vehicle via intragastric administration 30 min after TBI. Brain samples were collected 48 h later for analysis. ALA treatment resulted in a downregulation of caspase-3 expression, reduced the number of positive cells in the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and improved neuronal survival. Furthermore, the level of malondialdehyde and glutathione peroxidase activity were restored, while Bcl-2-associated X protein translocation to mitochondria and cytochrome c release into the cytosol were reduced by ALA treatment. These results demonstrate that ALA improves neurological outcome in rats by protecting neural cell against apoptosis via a mechanism that involves the mitochondria following TBI.

Summary Objective To investigate the clinical application value of intraoperative magnetic resonance imaging (iMRI) in large invasive pituitary adenoma surgery. Methods A total of 30 patients with large pituitary adenoma underwent microscopic tumor resection under the assistance of an iMRI system; 26 cases received surgery through the nasal–transsphenoidal approach, and the remaining four cases received surgery through the pterion approach. iMRI was performed one or two times depending on the need of the surgeon. If a residual tumor was found, further resection was conducted under iMRI guidance. Results iMRI revealed residual tumors in 12 cases, among which nine cases received further resection. Of these nine cases, iMRI rescanning confirmed complete resection in six cases, and subtotal resection in the remaining three. Overall, 24 cases of tumor were totally resected, and six cases were subtotally resected. The total resection rate of tumors increased from 60% to 80%. Conclusion iMRI can effectively determine the resection extent of pituitary adenomas. In addition, it provides an objective basis for real-time judgment of surgical outcome, subsequently improving surgical accuracy and safety, and increasing the total tumor resection rate.

Object Aneurysmal subarachnoid hemorrhage (SAH) causes devastating rates of mortality and morbidity. Accumulating studies indicate that early brain injury (EBI) greatly contributes to poor outcomes after SAH and that oxidative stress plays an important role in the development of EBI following SAH. Astaxanthin (ATX), one of the most common carotenoids, has a powerful antioxidative property. However, the potential role of ATX in protecting against EBI after SAH remains obscure. The goal of this study was to assess whether ATX can attenuate SAH-induced brain edema, blood-brain barrier permeability, neural cell death, and neurological deficits, and to elucidate whether the mechanisms of ATX against EBI are related to its powerful antioxidant property. Methods Two experimental SAH models were established, including a prechiasmatic cistern SAH model in rats and a one-hemorrhage SAH model in rabbits. Both intracerebroventricular injection and oral administration of ATX were evaluated in this experiment. Posttreatment assessments included neurological scores, body weight loss, brain edema, Evans blue extravasation, Western blot analysis, histopathological study, and biochemical estimation. Results It was observed that an ATX intracerebroventricular injection 30 minutes post-SAH could significantly attenuate EBI (including brain edema, blood-brain barrier disruption, neural cell apoptosis, and neurological dysfunction) after SAH in rats. Meanwhile, delayed treatment with ATX 3 hours post-SAH by oral administration was also neuroprotective in both rats and rabbits. In addition, the authors found that ATX treatment could prevent oxidative damage and upregulate the endogenous antioxidant levels in the rat cerebral cortex following SAH. Conclusions These results suggest that ATX administration could alleviate EBI after SAH, potentially through its powerful antioxidant property. The authors conclude that ATX might be a promising therapeutic agent for EBI following SAH.

Concerns were increasingly raised that several types of cancers overexpressed the nuclear factor erythroid 2-related factor 2 (Nrf2), which contributed strikingly to cancer biological capabilities and chemoresistance. However, the role of Nrf2 in the tumor vascular biology had yet to be mechanistically determined. Here, we investigated the involvement of Nrf2 in glioblastoma (GB) angiogenesis in hypoxia. First, we detected the overexpression of Nrf2 and correlated its protein level with microvessel density (MVD) in human GB tissues. Then, we established the stable RNAi-mediated Nrf2-knockdown cells and mimicked hypoxic condition in vitro. The knockdown of Nrf2 inhibited cell proliferation in vitro and suppressed tumor growth in mouse xenografts with a concomitant reduction in VEGF expression and MVD. Similar antiangiogenic effects were documented in endothelial tube formation assays. The downregulation of Nrf2 in glioma cells led to much lower accumulation of HIF-1α protein and limited expression of VEGF and other HIF-1α target genes in mimicking hypoxia. Mechanistic investigations suggested that HIF-1α degradation during hypoxia could be attributed to reduced mitochondrial O2 consumption in Nrf2-inhibited cells. It can be concluded that Nrf2, with its capacity for affecting the protein level of HIF-1α expression, has good reasons to be considered as a critical transcription factor for controlling glioma angiogenesis.

Glioblastoma multiforme (GBM), the most commonly occurring primary intracranial tumor, is associated with a negative outcome, regardless of the availability of multimodal therapies. However, the identification of glioma stem cells (GSCs), which are small groups of cells within the GBM, has resulted in novel avenues for research. GSCs are resistant to numerous types of environmental stress, such as irradiation, antitumor drugs and hypoxia. Nuclear factor erythroid 2-related factor 2 (Nrf2) has a significant role the cellular response to oxidative stress and previous studies have supported the significance of Nrf2 in GBM; however, the role of Nrf2 in GSCs remains unclear. In the present study, Nrf2 in CD133− GBM cells and CD133+ GSCs from GBM were compared. GSCs from GBM, which express the surface marker CD133, were separated by magnetic cell sorting and analyzed by immunofluorescence in 24-well clusters and cell counting using flow cytometry. The expression of Nrf2 was detected at the transcriptional and translational levels in CD133+ and CD133− cells, and the result indicated that GSCs were successfully isolated from the GBM. The percentage of tumor stem cells in total cells was between 0.49 and 0.91%. Nrf2 was overexpressed in CD133+ GSCs when compared with CD133− GBM cells, which indicated that the expression of Nrf2 in GSCs was closely correlated with malignant proliferation and differentiation of the GBM. Therefore, it was concluded that Nrf2 may be a potential biomarker and rational therapeutic target in GBM.

Using the first-principles density functional theory, we have studied the electronic structures and magnetic properties of Mn/Fe codoped ZnO nanowires systematically. The calculated results of formation energy indicate that the configuration of the lowest energy where Mn and Fe atoms form nearest neighbors on the outer cylindrical surface layer along the [0001] direction, will be determined. The magnetic coupling of 8 types of Mn/Fe codoped ZnO nanowires was investigated and ferromagnetic state was found in certain configurations. The mechanism is from the fierce hybridization between 3d of Mn and Fe with O 2p near the Fermi level. The relative energy difference for configuration VIII is 0.221 eV, which indicates that room temperature ferromagnetism could be obtained in such a system and Mn/Fe codoped ZnO nanowires are a promising nanoscale spintronic material. (C) 2013 Elsevier B. V. All rights reserved.

The ERK and PI3K signaling cascades are aberrantly activated in human glioblastoma cells, resulting in the dysregulation of numerous downstream transcription factors. The dark side of the transcription factor, NF-E2-related factor 2 (Nrf2) in human cancer has been revealed. It has been accepted that high levels of Nrf2 promote tumor progression. In the present study, we investigated the effect of the ERK and PI3K signaling cascades on Nrf2 in human glioblastoma cells. Immunohistochemical staining for Nrf2 in clinical specimens showed that the expression and nuclear localization of Nrf2 were increased in human glioblastoma tissues when compared to peritumoral normal tissues. In addition, we detected decreased nuclear localization of Nrf2 following combined treatment with ERK and PI3K inhibitors in three human glioblastoma cell lines and selected the cell line (U251) most sensitive to the inhibitors for further study. Our data demonstrated that inhibition of ERK and PI3K not only suppressed the nuclear accumulation of Nrf2 protein but also decreased the expression of the Nrf2 protein. In addition, combined inhibition of ERK and PI3K also decreased the mRNA levels of Nrf2 target genes. Finally, we found that Nrf2 overexpression partly reversed the ERK and PI3K inhibitor-induced inhibition of cell viability. Therefore, the ERK and PI3K signaling cascades regulate the expression and activation of Nrf2 and control cell viability partly through Nrf2 in U251 human glioblastoma cells. Thus, targeting the ERK and PI3K signaling cascades for Nrf2 activation may provide new methods for the treatment of glioblastoma.

NF-E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays anti-apoptotic role in normal tissue and tumor. But the role of Nrf2 in apoptosis in glioma is still unknown. Here, we established this experiment to elucidate how Nrf2-ARE pathway participates in apoptosis in human glioblastoma cell U251.Two plasmids, pEGFP-Nrf2 and Si-Nrf2, were transfected to up- or downregulate the expression of Nrf2 in U251. After transfection, the apoptosis rate, expression of heme oxygenase-1 (HO-1), Bcl-2, Bax, caspases 3, 9 and activity of caspases 3, 9 were detected.After increasing expression of Nrf2, the apoptosis rate was reduced accompanied with upregulated expression of HO-1, Bcl-2/Bax, decreased expression and activity of caspases 3, 9. After decreasing expression of Nrf2, the apoptosis rate was enhanced accompanied with downregulated expression of HO-1, Bcl-2/Bax, increased expression and activity of caspases 3, 9.Our findings suggest that Nrf2 participates in the regulation of apoptosis in U251 through HO-1 and the 'intrinsic' apoptotic pathway.

Venous hypertension(VH) plays an important role in the pathogenesis of cerebral arteriovenous malformations (AVMs) and is closely associated with the HIF-1α/VEGF signaling pathway. Nuclear factor erythroid 2-related factor 2(Nrf2) significantly influences angiogenesis; however, the interplay between Nrf2 and VEGF under VH in brain AVMs remains unclear. Therefore, our study aimed to investigate the interplay between Nrf2 and VEGF due to VH in brain AVMs. Immunohistochemistry indicated that Nrf2 and VEGF were highly expressed in human brain AVM tissues. In vivo, we established a VH model in both wild-type (WT) and siRNA-mediated Nrf2 knockdown rats. VH significantly increased the expression of Nrf2 and VEGF. Loss of Nrf2 markedly inhibited the upregulation of VEGF, as determined by Western blot analysis and qRT-PCR. In vitro, primary brain microvascular endothelial cells (BMECs) were isolated from WT and Nrf2−/− mice, and a VEGF-Nrf2 positive feed-back loop was observed in BMECs. By trans well assay and angiogenesis assay, Nrf2 knockout significantly inhibited the migration and vascular tube formation of BMECs. These findings suggest that the interplay between Nrf2 and VEGF can contribute to VH-induced angiogenesis in brain AVMs pathogenesis.

Background Binostril endoscopic transsphenoidal approach (BETA) provides sufficient manipulation space and wide endoscopic vision, although it increases the trauma of nose. Mononostril endoscopic transsphenoidal approach (META) has minimal trauma of nose, at the expense of space within the operation. We describe a one-and-a-half nostril endoscopic transsphenoidal approach (OETA) that combines the advantages of BETA and META. Methods We introduced OETA for pituitary adenomas with a detailed technical description. A retrospective analysis was also performed on 57 consecutive patients who underwent one-and-a-half nostril endoscopic transsphenoidal surgery between March 2014 and June 2015 at Jinling hospital. Results The gross total resection rate was 79%. The gross complete resection rate of Knosp grade 3 tumors were 63.6, and 27.3% in grade 4 tumors. Postoperative hormone remission was achieved in 14 out of 18 (77.8%) patients with secreting adenomas. Postoperative abnormal visual function improvement was achieved in 23 out of 32 patients (73%) with preoperative visual dysfunction. The overall intra-operative CSF leak was 17.5%, with the postoperative CSF leak decreased to 3.5% after the sellar reconstruction with the unilateral “rescue” nasoseptal flap procedure. The main sinonasal complaints 2 weeks after surgery were: loss of sense of smell (28%), decrease in sense of taste (4%), trouble breathing during the day (18%), thick nasal discharge (36%), post nasal discharge (8%), dried nasal material (6%), and headache (6%). Three months after surgery, there were no reports of decrease of taste, post nasal discharge, or dried nasal material. Other complaints were decreased significantly. Six months after surgery, the main complaints of sinonasal quality of life were negligible, and overall health status was near complete recovery to preoperative status. Conclusions The one-and-a-half nostril endoscopic transsphenoidal approach for pituitary adenomas is a simple and reliable technique. It provides not only a sufficient surgical corridor for a 2-surgeon/4 or 3-hands technique, but also ensures minimal invasion of the nasal canal.

We aimed to present a practical three-dimensional (3D) printed simulator to comprehensively and effectively accelerate the learning curve of endoscopic endonasal transsphenoidal surgery (EETS). The 3D printed simulator consists of three parts: (1) skull frame, (2) the nasal passage and the nasal alar of the face, and (3) a modified sella turcica. We aimed to improve three basic operational skills of surgeons: drilling, curetting, and aspirating. Eighteen neurosurgeons and five post-graduates were recruited and consented for the training. For trainees, (1) as the training progressed, the scores increased gradually, (2) a significant increase in the average scores was observed in the tenth training compared to the first training, and (3) there is a significant decrease in trainee variability in the shortening of the gap. The 18 neurosurgeons were divided into three groups: experts, assistants, and observers. For all three basic operations, (1) the average score of experts was obviously higher than that of the assistants, observers, and trainees’ tenth training and (2) the average scores of assistants and observers were obviously higher than that of trainees’ first training. A significant high in the average score between the assistants and the observers was seen for aspirating, but not for drilling or curetting. For curetting and aspirating, the tenth training average score of trainees was obviously higher than that of assistants and observers. This 3D printed simulator allows different endoscopic basic operations to be simulated and improves the EETS techniques of surgeons. We believed it to be a practical, simple, and low-cost simulator.

Traumatic brain injury (TBI)-released excessive glutamate resulted in the activation of glutamate receptors including the metabotropic glutamate receptor 5 (mGluR5). To investigate the expression and cell distribution of mGluR5 in the rat cortex following TBI, western blot and quantitative real-time PCR were used to study the protein and mRNA level of mGluR5 respectively while immunohistochemistry analysis and double immunofluorescence with neural cell marker were used to define the cell distribution of mGluR5. Furthermore, we examined the effects of post-TBI administration of (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG), a selective mGluR5 agonist, on the neuronal degeneration in the cortex. In the present study, we found that the protein level of mGluR5 was up-regulated by traumatic brain injury, while TBI-induced mGluR5 mRNA expression displayed biphasic changes with up-regulation in the early time and down-regulation in the late time after TBI. And neuron, astrocyte and microglia in the cortex after TBI all expressed mGluR5. Moreover, CHPG treatment significantly reduced the number of degenerating neurons detected by Fluoro-Jade C staining. These findings demonstrate that expression of mGluR5 differentially changes both spatially and temporally after TBI and may be related to the neuroprotection after TBI. Therefore, understanding the expression and cell distribution of mGluR5 after TBI may give insight into pathophysiology after TBI and provide a new target for the therapy of TBI.

Radio frequency identification (RFID) technology has proved to be very effective in industries as diverse as aircraft manufacturing to health and care. The construction industry has been slow to take up on RFID and this paper will discuss the merits of the technology in its potential for application within the construction sector. The paper reports about the prototypical implementation of RFID-based information management in FM-scenarios. The prototypes were tested at University College Cork (UCC). The general applicability of RFID for decentralised information management could be demonstrated.

Wogonoside, a bioactive flavonoid extracted from the root of Scutellaria baicalensis Georgi, has shown preclinical anticancer efficacy in various cancer models. However, the effects of wogonoside on glioblastoma cells remain unclear. In the present study, we found that wogonoside exhibited a cytotoxic effect on human glioblastoma cells. The suppression of cell viability was due to the induction of mitochondrial apoptosis. Furthermore, the presence of autophagic hallmarks, including an increase in punctate microtubule associated protein 1 light chain 3 (LC3) dots, changes in cellular morphology and increased levels of autophagy-related proteins were observed in the wogonoside-treated cells. Wogonoside treatment also enhanced autophagic flux as reflected by the increased acidic vesicular organelle (AVO) formation, p62 degradation and LC3 turnover. Notably, blockade of autophagy by a chemical inhibitor or RNA interference decreased the anticancer effect of wogonoside. In addition, the p38 mitogen-activated protein kinase (MAPK) signaling pathway, the phosphatidylinositide 3-kinase/protein kinase B/mammalian target of rapamycin/p70S6 kinase (PI3K/AKT/mTOR/p70S6K) signaling pathway and reactive oxygen species (ROS) participated in wogonoside-induced autophagy and apoptosis. These findings support the initiation of further studies of wogonoside as a candidate for the treatment of human malignant glioma.

2-Amino-2-[2-(4-octylphenyl)]-1,3-propanediol hydrochloride (FTY720) is a potent immunosuppressant which has been approved by the Food and Drug Administration (FDA) as a new treatment for multiple sclerosis. As an immunosuppressant, it displays its anti-multiple sclerosis, immunosuppressive effects by activating sphingosine-1-phosphate receptors (S1PRs). In addition to the immunosuppressive effects, FTY720 also shows preclinical antitumor efficacy in several cancer models. In most cases, phosphorylation of FTY720 is not required for its cytotoxic effect, indicating the involvement of S1PR-independent mechanisms which are starkly different from the immunosuppressive property of FTY720. In the present study, we reviewed the rapidly advancing field of FTY720 in cancer therapy as well as some molecular targets of the unphosphorylated form of FTY720.