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Introduction: Insulin-like growth factor type 1 receptor (IGF1R) is overexpressed in various malignant tumors, which relates to their transformation and recurrence. Craniopharyngioma is a benign tumor with malignant results, often accompanied by a severe inflammatory reaction. However, the relationship between IGF1R expression and the inflammatory response of craniopharyngioma is unclear. Methods: We enrolled 85 patients with adamantinomatous craniopharyngioma (ACP) in a study to explore the relationship between IGF1R expression and clinical features of this disease. Results: Patients in the IGF1R high-expression group had a significantly higher incidence of hypopituitarism, higher recurrence rate, and lower progression-free survival. β-Catenin can further regulate expression of the stem cell marker, CD44, by regulating IGF1R. Using immunofluorescence, we found that tumor stem cell-like cells did not express phosphorylated (p)-ERK, although p-ERK activation was evident in the surrounding cells. Picropodophyllin, a specific inhibitor of IGF1R, increased the expression of p-ERK protein and decreased the transcription level of interleukin-6. Conclusions: High expression of IGF1R might promote inflammation of ACP, which might be an unfavorable factor for pituitary function and prognosis. The high expression of IGF1R in tumor stem cell-like cells might inhibit the expression of p-ERK and promote the generation of inflammatory factors. IGF1R plays a stemness maintenance role in ACP and regulates the production of inflammatory factors through a p-ERK pathway, which suggests that targeting IGF1R and p-ERK might provide a new direction for alleviating tumor inflammation.

Background Adamantinomatous craniopharyngioma (ACP) is a benign tumor with malignant clinical manifestations. ACP adjacent to the hypothalamus often presents with more severe symptoms and higher incidence of hypothalamic dysfunction. However, the mechanism underlying hypothalamic dysfunction remains unclear. Methods Immunostaining was performed to determine the nerve damage to the floor of the third ventricle (3VF) adjacent to ACP and to examine the recruitment and senescence of hypothalamic neural stem cells (htNSCs). The accumulation of lipid droplets (LDs) in htNSCs was evaluated via BODIPY staining, oil red O staining, and transmission electron microscopy. In vitro and in vivo assays were used to evaluate the effect of cystic fluid or oxidized low-density lipoprotein and that of oxytocin (OXT) on htNSC senescence and the hypothalamic function. The protein expression levels were analyzed using western blotting. Results htNSCs with massive LD accumulation were recruited to the damaged 3VF adjacent to ACP. The LDs in htNSCs induced senescence and reduced neuronal differentiation; however, htNSC senescence was effectively prevented by inhibiting either CD36 or integrated stress response (ISR) signaling. Furthermore, OXT pretreatment reduced lipotoxicity via the inhibition of ISR signaling and the repair of the blood–brain barrier. Conclusions Reduced LD aggregation or ISR signaling inhibition prevented senescence in htNSCs and identified molecular pathways and potential therapeutic targets that may improve hypothalamic dysfunction in ACP patients.

Background: Novel therapeutic targets in epithelioid glioblastoma (E-GBM) patients are urgently needed. About half of these tumors show the point mutations of the B-Raf proto-oncogene (BRAF). Therefore, this is a target of special interest for this group of patients. Meanwhile, unlike conventional glioblastoma, E-GBM lacks specific prognostic markers.Case presentation: We present a case report of a long-term surviving 37-years-old male patient diagnosed with a BRAF V600E-mutated E–GBM with IDH wild-type. The tumor displayed atypical exophytic growth and an obvious proliferation of vascular endothelial cells. Notably, tumor tissue was found under subarachnoid space. After conventional postoperative treatment options (including radiotherapy and temozolomide chemotherapy) were exhausted, vemurafenib treatment was initiated. The patient maintained clinically stable, and follow-up MRI was consistent with stable disease for the following fifteen months up to now. To identify potential therapeutic targets of E-GBM, we carried out whole exome sequencing analysis and RNA-sequence to study the molecular characteristics of this E-GBM sample. The mutant genes were profiled using glioma RNA-sequencing data from Chinese Glioma Genome Atlas (CGGA) database. We found that CNTNAP3, mTOR, NFATC3, and NOM1 shared by DNA-sequence data and RNA-sequence data were independent prognostic factors. Biological function was associated with phenotypes of focal adhesion and cell cycle. A prognostic risk model was constructed based on the mutant genes for predicting the survival of glioma patients. Survival plot and a nomogram was used to verify that our prognostic risk model is reliable and accurate.Conclusions: Our findings provided a new sight on the BRAF inhibitor, in combination with which CNTNAP3, mTOR, NFATC3, and NOM1 inhibitors seem to be a valuable salvage treatment option for E-GBM.

Craniopharyngioma represents a troublesome tumor of the intracranial sellar region. There are currently no available well-characterized craniopharyngioma cell lines. This lack of reliable, immortal cell lines is a major reason for the slow progress in fundamental research related to craniopharyngioma. We describe the development of an immortal papillary craniopharyngioma (PCP) cell line by transfecting primary PCP cells with the pLenti-simian virus 40 large T antigen(SV40LT). Three clones have been cultured for more than 14 months so far, while non-transfected cells ceased proliferation within three months of isolation. The established immortal PCP cell lines were identified to have BRAFV600E mutations, while no mutations in tumor suppressor genes were found in primary cells or immortal cells. Immortal cells had higher proliferation rates and formed tumors when implanted in the bran of nude mice. BRAF inhibition in immortal PCP cells altered cell morphology, inhibited cell proliferation and promoted apoptosis. We successfully developed PCP cell lines by SV40LT-mediated immortalization. These cell lines represent a powerful tool for fundamental and therapeutical studies on craniopharyngioma.

Background The relationship between clinical responses in pediatric infradiaphragmatic craniopharyngioma (Q-CP) and inflammatory response is still unclear. The objective of this study was to investigate the clinical significance of tumor inflammatory response in pediatric Q-CPs. Methods The inflammatory response was evaluated by measuring the number of inflammatory cells in the tumor near adenohypophysis junction. The specimens were classified as mild, moderate, or severe based on the number of inflammatory cells. In addition, the levels of pro-inflammatory cytokines and chemokines in the specimens were measured using a cytokine antibody array. Clinical outcomes were analyzed and compared to the markers of inflammatory response. Results IL-6 and IL-8 were highly expressed in pediatric Q-CPs, and the transcription level of IL-6 was the highest in the severe group. Most patients (87.3%) had hypopituitarism; the severe inflammation group had an increased incidence of hypopituitarism, which correlated with significantly lower probability of recurrence-free survival and worsened functional status. Conclusions Inflammatory response is common in craniopharyngiomas and is closely related to their biological behavior and the patients' clinical prognosis. Further studies of the relationship between craniopharyngiomas and the inflammatory response will enable the discovery of potential therapeutic targets, which will reduce morbidity and result in better outcomes for pediatric Q-CP patients. Impact Pediatric infradiaphragmatic craniopharyngiomas are histologically benign brain tumors that often follow an aggressive clinical course.The inflammatory response in craniopharyngioma is common, which is closely related to the biological behavior and clinical prognosis.Several inflammatory and immune markers have been identified in CP; inflammation is an important role in the pathogenesis of hypopituitarism.The aim was to study the relationship between craniopharyngioma and inflammatory response and find potential therapeutic targets can reduce morbidity and result in better outcomes.

Herein, we report an interesting finding about the new application of oxytetracycline (OTC), as a fluorescent probe for the detection of calcium ion (Ca2+), which proved that it can offer an expeditious, highly sensitive, and selective detection method for Ca2+. Upon the addition of Ca2+, the fluorescence of OTC could be significantly enhanced with rapid response and high sensitivity, and achieved a good limit of detection as low as 125 nM in aqueous solution. The complex formed via Ca2+ coordinating to the hydroxyl group of OTC contributes to the fluorescence enhancement, which has been proved by several characterization methods including UV-vis analysis, binding constant determination, and fluorescence titration. The method avoided complexity for EDTA measurement of Ca2+ in running water as proposed previously. Taking advantage of good availability, stability and operability, the OTC was further successfully applied to the detection of Ca2+ in a real environment.

Introduction The mechanism by which adamantinomatous craniopharyngioma (ACP) damages the hypothalamus is still unclear. Cyst fluid rich in lipids and inflammatory factors is a characteristic pathological manifestation of ACP and may play a very important role in hypothalamic injury caused by tumors. Objective The objective of this study was to construct a reliable animal model of ACP cyst fluid-induced hypothalamic injury and explore the specific mechanism of hypothalamic injury caused by cyst fluid. Methods An animal model was established by injecting human ACP cyst fluid into the bilateral hypothalamus of mice. ScRNA-seq was performed on the mice hypothalamus and on an ACP sample to obtain a complete gene expression profile for analysis. Data verification was performed through pathological means. Results ACP cystic fluid caused growth retardation and an increased obesity index in mice, affected the expression of the Npy, Fgfr2, Rnpc3, Sst, and Pcsk1n genes that regulate growth and energy metabolism in hypothalamic neurons, and enhanced the cellular interaction of Agrp–Mc3r. ACP cystic fluid significantly caused inflammatory activation of hypothalamic microglia. The cellular interaction of CD74–APP is significantly strengthened between inflammatory activated microglia and hypothalamic neurons. Beta-amyloid, a marker of neurodegenerative diseases, was deposited in the ACP tumor tissues and in the hypothalamus of mice injected with ACP cyst fluid. Conclusion In this study, a novel animal model of ACP cystic fluid-hypothalamic injury was established. For the first time, it was found that ACP cystic fluid can trigger inflammatory activation of microglia to damage the hypothalamus, which may be related to the upregulation of the CD74–APP interaction and deposition of β-amyloid, implying that there may be a similar mechanism between ACP cystic fluid damage to the hypothalamus and neurodegenerative diseases.

Some patients with paediatric craniopharyngiomas (PCs) showed normal growth despite growth hormone deficiency, which is known as growth without GH (GWGH); however, its mechanism remains unclear. We aimed to develop a novel clinical score to predict the probability of GWGH in PCs. A total of 708 PC patients were prospectively enrolled from six hospitals, among which 431 patients were finally included. Data from four of the six hospitals (n = 325) were used to develop the innovative clinical score (ICS), which was further validated using the data from the other two hospitals (n = 106). To establish and validate the ICS, sequential logistic regression was used to analyse the clinical characteristics including tumour growth pattern and tumour size and so on. Furthermore, C-statistic was employed to calibrate the discriminatory ability of the established clinical score, while a calibration plot was adopted for further assessment. The overall incidence of GWGH was 16.9% (73/431). The ICS ranged from 2 to 23, with an optimism-corrected C-statistic of 0.820, Furthermore, the optimism-corrected C-statistic of external validation was 0.835, indicating good discriminatory power and robustness of the clinical score. Additionally, no apparent overestimation or underestimation was observed in the calibration plots, which showed excellent calibration power of the clinical score. Based on tumour growth patterns and PC patients’ clinical characteristics, individualized surgical strategies were promising to achieve long-term effective management of PC patients. The ICS is valuable for the evaluation of probability of developing postoperative GWGH. ClinicalTrials.gov ID: NCT00949156.

Remote sensing can be used for precision nutrient management to assess plant nitrogen (N) status in a spatially detailed and real-time manner. Despite recent advances in satellite- and drone technology and machine learning, neither differences between platforms nor methodological aspects for estimating plant N status have been sufficiently investigated. In this study, multispectral data obtained by ground (handheld Rapidscan), air- (unmanned aerial vehicle, UAV) and spaceborne (Sentinel-2) platforms were exploited to estimate plant N uptake (PNU), concentration (PNC) and N nutrition index (NNI). The test plant was potato grown for three years on a sandy soil in Denmark and the analysis was based on the critical N dilution curve. Parametric (PR) and non-parametric (random forest, RFR) regressions were conducted and compared in predicting mid-season PNU, PNC and NNI from band reflectances or vegetation indices (VIs) derived from each platform data. The results obtained by the UAV data had the highest accuracy, largely due to the fine spatial resolution. For both regression types, PNU and NNI correlated better than PNC to reflectance data. For the UAV data, validation Nash-Sutcliffe model efficiency (NSE) of PNU and NNI ranged between 0.64–0.95 and 0.41–0.92 respectively, with corresponding values for relative root mean square error (RRMSE) of 7.1–22% and 5.86–22%. The lower end of NSE and higher end RRMSE intervals systematically being from the PR, which demonstrates the robustness and the high accuracy of RFR in predicting plant N status. The other platforms resulted in acceptable results, with validation NSE and RRMSE for PNU and NNI of, respectively, 0.60–0.79 and 14–20%, 0.25–0.79 and 10–17% for Rapidscan, and 0.48–0.83 and 17–28%, 0.42–0.82 and 12–19% for Sentinel-2. The band reflectance and the VIs were equally suited as input predictors for the RFR algorithm. The N requirement calculated from all three datasets reflected the field observations well. The study reveals the potential of different regression methods for detailed spatial estimation of plant N status to guide in-season fertilization by matching the plant growth demands, emphasizing the strengths of the RFR. The procedure is helpful for the digital agriculture and the smart farming industry aiming to avoid excess application of N.

Obesity, cardiovascular disease, and relapse/progression have major impact on prognosis in pediatric brain tumor patients. Cranial MRI is part of routine follow-up. In a cross-sectional study, we analyzed nuchal skinfold thickness (NST) by a standardized method on MRI performed for brain tumor follow-up monitoring as a novel parameter for body composition and cardiovascular disease in 177 brain tumor patients (40 WHO grade 1-2 brain tumors; 31 grade 3-4 brain tumors; 106 craniopharyngioma), and 53 healthy controls. Associations of NST with body mass index (BMI), waist-to-height ratio, caliper-measured skinfold thickness, and blood pressure were analysed in brain tumor patients and healthy controls. Craniopharyngioma patients showed higher BMI, waist-to-height ratio, NST and caliper-measured skinfold thickness when compared with brain tumor patients and healthy controls, whereas these differences were not detectable between brain tumor patients and healthy controls. However, WHO grade 1-2 brain tumor patients were observed with higher BMI, waist circumference and caliper-measured triceps skinfold thickness when compared to WHO grade 3-4 brain tumor patients. NST showed high correlations with BMI, waist-to-height ratio, and caliper-measured skinfold thickness. NST, BMI and waist-to-height ratio had predictive value for cardiovascular disease in terms of increased blood pressure, and in multivariate analysis, only BMI was selected for the final model resulting in an odds ratio of 1.25 (1.14-1.379). In craniopharyngioma patients with hypothalamic involvement/lesion or gross-total resection, rate and degree of obesity were increased. As monitoring of MRI and body composition play an important role in follow-up after brain tumor, we conclude that NST could serve as a novel useful parameter for assessment of body composition and cardiovascular disease risk in brain tumor patients.

Intercepted photosynthetically active radiation (Ipar, MJ m-2 d-1) is a key biophysical variable governing plant photosynthetic rate and net primary productivity (NPP, g m-2 d-1). Under optimal growth conditions, Ipar scales proportionally to NPP by a factor termed ‘optimum radiation use efficiency’ (RUEopt). The Carnegie-Ames-Stanford approach (CASA) considers temperature and moisture constraints to RUEopt and has been widely used in remote sensing studies to estimate productivity of various ecosystems. However, scale effects on the CASA have not been sufficiently investigated nor quantified. In this study, data at scales of field (Rapidscan reflectance data), air- (unmanned aerial vehicle (UAV) imagery) and spaceborne (Sentinel-2 imagery), as well as for several environmental constraints, were utilized to develop and test the CASA. The test plant was potato grown for multiple years on sandy soils in Denmark. The results showed that data from all scales provided comparable estimates of daily fraction of Ipar (fIpar) and Ipar. Maximum air temperature and diffuse radiation were the most important environmental factors constraining RUEopt of potato. Taking these into account considerably improved the prediction of NPP with the CASA (R2 increase of 25–32 % compared to no constraints), whereas stress effects due to soil moisture and vapor pressure deficits were less important (relative improvement in R2 of 2–3 %). Hence, RUEopt was 4.66, 4.19 and 4.98 g MJ-1 for Rapidscan, UAV and Sentinel-2, respectively, which was about 47 %–59 % higher than the estimates of the observed actual radiation use efficiency. This study offers an operational method for deriving RUEopt at plant species level since remote sensing and meteorological data are both readily available, and demonstrates that environmental constraints of the CASA does vary, depending on the study region. The method can be used to predict dry matter production in-season for other crops as well, with potential for extending the approach to determine fertilization and irrigation demands.

BackgroundXuefu Zhuyu Decoction (XFZYD) is a well-known Traditional Chinese Medicine (TCM) formula that has many pharmacological effects, including enhancing immune function, improving hemorheology and regulating blood vessels bidirectionally. Modern pharmacological and clinical studies showed that XFZYD could ameliorate curative effect of glioblastoma (GBM). The aim of this study was to interpret core components and the hidden molecular mechanisms of XFZYD on GBM. MethodsHere, a novel network pharmacology strategy, which combined pharmacological data, next generation sequencing data, pharmacokinetic parameters and a novel node importance calculation method was designed to decipher the potential therapeutic mechanism of XFZYD on GBM. The partial components in core component group (CCG) were evaluated by in vitro expriments. We identified 117 chemical components analysis through ADME screening, then component-target network and GBM related genes were integrated as the component-target-pathogenic gene (C-T-P) network. ResultsThe results show that the enriched pathways of targets in the key functional network could cover 77.92% of the enriched pathways of pathogenic genes. A novel cumulative contribution rate (CCR) calculation model was designed and captured CCG with 21 components. The statistics results indicate that 15 enriched pathways of the targets of CCG were overlap with pathogenic genes enriched pathways. Finally, some core components in CCG were validated by in vitro experiments. Conclusion The results show that our proposed stategy for decoding CCG and infering the underlying mechanism with good reliability and accuracy. The validation results indicate that the CCG play a therapeutic role on GBM by targeting to PI3K-Akt signaling pathway and Toll-like receptor signaling pathway. Our strategy provides methodological reference for the optimization and secondary development of TCM formula.

Osteoporosis (OP) is a highly prevalent orthopedic condition in postmenopausal women and the elderly. Currently, OP treatments mainly include bisphosphonates, receptor activator of nuclear factor kappa-B ligand (RANKL) antibody therapy, selective estrogen receptor modulators, teriparatide (PTH1-34), and menopausal hormone therapy. However, increasing evidence has indicated these treatments may exert serious side effects. In recent years, Traditional Chinese Medicine (TCM) has become popular for treating orthopedic disorders. Erxian Decoction (EXD) is widely used for the clinical treatment of OP, but its underlying molecular mechanisms are unclear thanks to its multiple components and multiple target features. In this research, we designed a network pharmacology method, which used a novel node importance calculation model to identify critical response networks (CRNs) and effective proteins. Based on these proteins, a target coverage contribution (TCC) model was designed to infer a core active component group (CACG). This approach decoded the mechanisms underpinning EXD’s role in OP therapy. Our data indicated that the drug response network mediated by the CACG effectively retained information of the component-target (C-T) network of pathogenic genes. Functional pathway enrichment analysis showed that EXD exerted therapeutic effects toward OP by targeting PI3K-Akt signaling (hsa04151), calcium signaling (hsa04020), apoptosis (hsa04210), estrogen signaling (hsa04915), and osteoclast differentiation (hsa04380) via JNK, AKT, and ERK. Our method furnishes a feasible methodological strategy for formula optimization and mechanism analysis and also supplies a reference scheme for the secondary development of the TCM formula.

Assessment of presurgical hypothalamic involvement (psHI) and treatment-related hypothalamic damage (trHD) is relevant for the decision on risk-adapted treatment and rehabilitation strategies in craniopharyngioma. 129 surgical reports of childhood-onset craniopharyngioma patients recruited 2007–2014 in KRANIOPHARYNGEOM 2007 were analyzed. Data on psHI were available based on surgeon’s (63%), reference neuroradiologist’s (95%), and local radiologist’s (23%) assessment. The surgical degree of resection (DoR) was assessed by neurosurgeon (95%), reference neuroradiologist (73%), and local radiologist (61%). TrHD was assessed by neurosurgeon (33%), by reference neuroradiologist (95%), and by local radiologist (2%). Neurosurgical center size was categorized based on patient load. Surgical assessments on psHI (n = 78), DoR (n = 89) and trHD (n = 42) as documented in surgical reports could be compared with the assessment of respective parameters by reference neuroradiologist. Differences with regard to DoR (p = 0.0001) and trHD (p

Superoxide anion (O2•−) is one of the most important reactive oxygen species and its sensitive detection is of great significance and challenging in the field of environmental and hazardous chemicals monitoring. Herein, we report an off-on fluorescent probe based on ferric functionalized carbon dots (CDs) which were synthesized using p-phenylenediamine as starting material for the detection of O2•−. The initial green fluorescence of CDs was greatly quenched by Fe3+ based on energy transfer effect on account of the selective formation of ferric complex on the surface of CDs, but not by other metal ions. Interestingly, the fluorescence of CDs could be readily and selectively recovered upon the addition of O2•−, which can be used for the senstivie detection of superoxide. This type of off-on probe exhibited good photostability and high selectivity toward O2•− among other interfering substances including metal ions, reactive oxygen species as well as reductant substances. The probe showed good linearity with the concentration of O2•−, and the limit of detection for O2•− was estimated down to 25 pM in aqueous solution. Moreover, a paper based sensor for O2•− was fabricated with a visual detection limit as low as 4.4 nM, demonstrating a promising application for practical detection of superoxide anion.

Since graphene oxide (GO) has been found to be one of the toxic graphene-based nanomaterials, the environmental behavior of GO has been studied extensively in aqueous solution systems. In this work, the large ionic radius lanthanum (La) was doped onto the layered double hydroxides (LDHs), which was conducive to remove the negatively charged GO. The results showed that the coagulation of GO on La-doped LDHs was dependent on pH and the types of electrolytes. After calcined at 400 °C for 4 h, the maximum GO removal capacities could reach 565.8 mg/g on Mg/Al/La-CLDHs and 558.6 mg/g on Ca/Al/La-CLDHs at GO initial concentration of 120 mg/L and LDHs content of 0.2 g/L. The short equilibrium time and high removal capacity suggested the huge advantage of LDHs in practical applications. More importantly, the La-doped LDHs could still exhibit high removal capacities after five cycles, indicating that the La-doped LDHs hold good reusability and could be used for GO pollution cleanup from water. The coagulation of GO on La-doped LDHs was mainly dominated by electrostatic attraction and hydrogen bond. These findings were useful to understand the environmental fate and transport of GO nanoparticles in aqueous systems.

OBJECTIVE An assessment of the transcranial approach (TCA) and the endoscopic endonasal approach (EEA) for craniopharyngiomas (CPs) according to tumor types has not been reported. The aim of this study was to evaluate both surgical approaches for different types of CPs. METHODS A retrospective review of primary resected CPs was performed. A QST classification system based on tumor origin was used to classify tumors into 3 types as follows: infrasellar/subdiaphragmatic CPs (Q-CPs), subarachnoidal CPs (S-CPs), and pars tuberalis CPs (T-CPs). Within each tumor type, patients were further arranged into two groups: those treated via the TCA and those treated via the EEA. Patient and tumor characteristics, surgical outcomes, and postoperative complications were obtained. All variables were statistically analyzed between surgical groups for each tumor type. RESULTS A total of 315 patients were included in this series, of whom 87 were identified with Q-CPs (49 treated via TCA and 38 via EEA); 56 with S-CPs (36 treated via TCA and 20 via EEA); and 172 with T-CPs (105 treated via TCA and 67 via EEA). Patient and tumor characteristics were equivalent between both surgical groups in each tumor type. The overall gross-total resection rate (90.5% TCA vs 91.2% EEA, p = 0.85) and recurrence rate (8.9% TCA vs 6.4% EEA, p = 0.35) were similar between surgical groups. The EEA group had a greater chance of visual improvement (61.6% vs 35.8%, p = 0.01) and a decreased risk of visual deterioration (1.6% vs 11.0%, p < 0.001). Of the patients with T-CPs, postoperative hypothalamic status was better in the TCA group than in the EEA group (p = 0.016). Postoperative CSF leaks and nasal complication rates occurred more frequently in the EEA group (12.0% vs 0.5%, and 9.6% vs 0.5%; both p < 0.001). For Q-CPs, EEA was associated with an increased gross-total resection rate (97.4% vs 85.7%, p = 0.017), decreased recurrence rate (2.6% vs 12.2%, p = 0.001), and lower new hypopituitarism rate (28.9% vs 57.1%, p = 0.008). The recurrence-free survival in patients with Q-CPs was also significantly different between surgical groups (log-rank test, p = 0.037). The EEA required longer surgical time for T-CPs (p = 0.01). CONCLUSIONS CPs could be effectively treated by radical surgery with favorable results. Both TCA and EEA have their advantages and limitations when used to manage different types of tumors. Individualized surgical strategies based on tumor growth patterns are mandatory to achieve optimal outcomes.

Craniopharyngiomas may develop at any point along the pituitary–hypothalamus axis, from the sella turcica to the infundibularis partes of the third ventricle but they most commonly expand in the suprasellar cistern or within the third ventricle floor [1–3]. Tumors originate from along the path of embryonic development of Rathke’s pouch out pia mater of the third ventricle. Tumors are usually classified according to the involving anatomical sites; however, large tumors may severely compress, distort, or involve neural tissue (third ventricular floor, pituitary stalk, and optic tract structures), making preoperative evaluation difficult even with excellent-quality neuroradiological studies [3–7]. In such a small area of the sellar region, therefore, accurate typing is sometimes difficult when the tumor is large. Here we propose a clinical classification system (QST classification system) based on both the tumor’s original site and the relationship of the tumor to the suprasellar membranous structures (namely the diaphragma, the arachnoid membrane, and the pia mater) [1, 6–8].

To control tumor growth and recurrence, radiation therapies are suggested as alternatives for patients with craniopharyngiomas who could not tolerate surgery. Radiation therapy may delay or prevent recurrence; however, the side effects of radiotherapy were underestimated. This section presents a review of literature on radiological treatment of craniopharyngiomas. We discuss the issue of radiotherapy, their efficacy, and prognosis according to complications and quality of life. Based on pathology and QST classification, we aim to explain the difficulties of reoperation after radiotherapy.

OBJECTIVENuclear β-catenin, a hallmark of active canonical Wnt signaling, can be histologically detected in a subset of cells and cell clusters in up to 94% of adamantinomatous craniopharyngioma (ACP) samples. However, it is unclear whether nuclear β-catenin–containing cells within human ACPs possess the characteristics of tumor stem cells, and it is unknown what role these cells have in ACP.METHODSPrimary ACP cells were cultured from 12 human ACP samples. Adamantinomatous CP stem cell–like cells (CSLCs) showing CD44 positivity were isolated from the cultured primary ACP cells by performing magnetic-activated cell sorting. The tumor sphere formation, cell cycle distribution, stemness marker expression, and multidifferentiation potential of the CD44− cells and the CSLCs were analyzed.RESULTSCompared with the CD44− cells, the cultured human CSLCs formed tumor spheres and expressed CD44 and CD133; moreover, these cells demonstrated nuclear translocation of β-catenin. In addition, the CSLCs demonstrated osteogenic and adipogenic differentiation capacities compared with the CD44− cells. The CSLCs also displayed the capacity for tumor initiation in human–mouse xenografts.CONCLUSIONSThese results indicate that CSLCs play an important role in ACP development, calcification, and cystic degeneration.

Acid-base balance is associated with various cellular functions, and its disorders could cause several diseases. The real-time detection of intracellular pH fluctuation is of vital importance for the prevention of multiple diseases. Therefore, the development of pH-sensitive probes has always been a considerable requirement. Here, we report a ratiometric fluorescent probe Ox-L based on the 3H-indolium dye, which enables highly sensitive detection of pH fluctuations via the intramolecular charge transfer (ICT) process. The probe exhibits a large Stokes shift at 145 nm, excellent photostability, reversibility and low cytotoxicity— all which are conducive for intracellular pH imaging. Based on these properties, Ox-L has been suitably applied to visualize pH fluctuation in the living cell, and to monitor the periplasmic pH of E. coli. These results showed that the probe possesses great potential in biological systems.

// Yi Liu 1, * , Chao-hu Wang 1, * , Dan-ling Li 2, * , Shi-chao Zhang 1 , Yu-ping Peng 1 , Jun-xiang Peng 1 , Ye Song 1 , Song-tao Qi 1 , Jun Pan 1 1 Department of Neurosurgery, Nanfang Hospital of Southern Medical University, Guangzhou, China 2 Department of Biometric, College of Public Health of Southern Medical University, Guangzhou, Guangdong, China * These authors contributed equally to this work Correspondence to: Jun Pan, email: panjundu@hotmail.com Song-tao Qi, email: qisongtaosjwk@163.com Keywords: craniopharyngioma, metaplasia, Rathke’s cleft cyst, SE, TREM-1 Received: March 10, 2016 Accepted: June 30, 2016 Published: July 8, 2016 ABSTRACT Whether a mixed type of craniopharyngioma (CP) exists and whether papillary craniopharyngioma (pCP) is on a histopathological continuum with Rathke’s cleft cyst (RCC) remain controversial. Herein, we examined the expression and localization of β-catenin, BRAF p.V600E (V600E), and triggering receptor expressed on myeloid cells-1 (TREM-1) in 58 samples including 20 pCPs, 26 adamantinomatous craniopharyngiomas (aCP), and 12 RCCs. Five aCPs were diagnosed with mixed type CPs and the remaining 21 cases were pure aCPs. Four of the 12 RCCs presented with significant squamous epithelium (SE). V600E immunoreactivity was observed in all pCPs in the cytoplasm, but not in the nuclei. aCPs and RCCs, including mixed type CP, did not express V600E. Nuclear β-catenin translocation was detected exclusively in aCPs. TREM-1 was expressed in pCPs. Additionally, TREM-1 expression was detected in the SE of 5 “mixed type” CPs, while it was absent in pure aCPs. TREM-1 was expressed in 4 RCCs with SE, but not in the remaining 8 RCCs. TREM-1 mRNA levels were compared in cultured pCP and aCP cells. TREM-1 mRNA level was significantly (p < 0.001; up to 4.045 fold) higher in pCPs than in aCPs. Western blotting revealed a significantly (p < 0.001; up to 7.19 fold) lower level of TREM-1 expression in aCP cells compared to that in pCP cells. Our findings further supported that RCC and pCP may represent two ends of a morphological spectrum. A variant showing overlapping histological features of aCP and pCP should not be considered as a mixed type.