Intra-operative mapping and language protection in glioma.

ABSTRACT: The demand for acquiring different languages has increased with increasing globalization. However, knowledge of the modification of the new language in the neural language network remains insufficient. Although many details of language function have been detected based on the awake intra-operative mapping results, the language neural network of the bilingual or multilingual remains unclear, which raises difficulties in clinical practice to preserve patients' full language ability in neurosurgery. In this review, we present a summary of the current findings regarding the structure of the language network and its evolution as the number of acquired languages increased in glioma patients. We then discuss a new insight into the awake intra-operative mapping protocol to reduce surgical risks during the preservation of language function in multilingual patients with glioma.

[Characteristics of Soil Nitrogen and Phosphorus Losses Under Different Land-use Schemes in the Shipanqiu Watershed].

In order to understand the characteristics of soil nitrogen and phosphorus loss under different land use patterns in the small watershed of the Three Gorges Reservoir area and provide a scientific basis for the prevention and control of agricultural non-point source pollution, a field test method was used to study the paddy fields and drought in the small Shipanqiu Watershed in the Three Gorges Reservoir area. The characteristics of different runoff concentrations and the fluxes of nitrogen and phosphorus in surface runoff under the five land use schemes of paddy filed, slope land, woodlands, citrus orchards, and vegetable land. The results show that the annual total nitrogen loss followed the order of paddy field[17.73 kg·(hm2·a)-1] > citrus orchards[4.86 kg·(hm2·a)-1] > dry slope land[4.33 kg·(hm2·a)-1] > vegetable field[4.00 kg·(hm2·a)-1] > woodland[2.41 kg·(hm2·a)-1]. The annual total phosphorous loss followed the order of vegetable fields[4.97 kg·(hm2·a)-1] > Citrus orchards[1.87 kg·(hm2·a)-1] > paddy fields[0.93 kg·(hm2·a)-1] > woodlands[0.27 kg·(hm2·a)-1] > dry slope land[0.19 kg·(hm2·a)-1]. The nitrogen and phosphorus losses under the five land use methods were mainly concentrated from April to May with frequent rainfall events, accounting for 53.80%-96.52% and 56.03%-87.78% of the total annual nitrogen and phosphorus losses. Nitrogen loss was mainly in the form of nitrate nitrogen (16.16%-52.70%), and the total nitrogen loss flux and runoff showed a significant positive correlation (R2=0.9826). Particulate phosphorus was the main form of phosphorus loss in vegetable fields (83.30%), but in other land use schemes it is not significant. There were significant differences in the loss of different forms of nitrogen and phosphorus under the different land use schemes. Among them, measures should be taken in vegetable fields to deal with the problem of particulate phosphorus loss under conditions of heavy rainfall. Fertilization should be avoided in paddy fields during periods of concentrated rainfall. Scientific fertilization and reasonable land use configurations are important ways to control agricultural non-point source pollution in small watersheds.

Intratumoral Susceptibility Signals Reflect Biomarker Status in Gliomas.

Susceptibility-weighted imaging (SWI) can be a useful tool to depict vascular structures in brain tumors as well as micro-bleedings, which represent tumor invasion to blood vessels and could also be representative of tumoral angiogenesis. In this study, we investigated the relationship between SWI features and glioma grades, and the expression of key molecular markers isocitrate dehydrogenase 1 (IDH1), O-6-methylguanine-DNA methyltransferase (MGMT), and 1p19q. The gliomas were graded according to the intratumoral susceptibility signals (ITSS). We used the Mann-Whitney test to analyze the relationship between ITSS grades and the pathological level and status of these markers. Additionally, the area under the curve (AUC) was used to determine the predictive value of glioma SWI characteristics for the molecular marker status. In these cases, the ITSS grades of low-grade gliomas (LGG) were significantly lower than those of high-grade gliomas (HGG). Similarly, the ITSS grades of gliomas with IDH1 mutations and MGMT methylation were significantly lower than those of gliomas with Wild-type IDH1 and unmethylated MGMT. However, ITSS grades showed no relationship with 1p19q deletion status, while they did show significant predictive ability for glioma grade, IDH1 mutation, and MGMT methylation. These findings indicate an association between some molecular markers and cerebral microbleeds in gliomas, providing a new avenue for non-invasive prediction of molecular genetics in gliomas and an important basis for preoperative personalized surgical treatment based on molecular pathology.

Experimental study on diesel engine exhaust gas recirculation performance and optimum exhaust gas recirculation rate determination method.

In order to study the exhaust gas recirculation (EGR) performance of marine diesel engines, a venturi high-pressure EGR device was established to overcome the exhaust gas reflow problem based on a certain type of turbocharged diesel engine. The EGR performance test is accomplished and an optimal EGR decision-making optimization method based on grey correlation coefficient modified is proposed. The results show that the venturi tube EGR can basically meet the injection requirements of high-pressure exhaust gas and achieve good results. Through the venturi tube EGR, the NO X emissions reduce significantly with the maximum drop of 30.6%. The explosive pressure in cylinder reduces with the EGR rate increases and the cylinder pressure curve shows a single peak at low-speed conditions and double peaks at high-speed condition. However, the fuel consumption rate, NO X and smoke have been negatively affected. Due to small samples, the traditional evaluation method is difficult to determine the optimal EGR rate reasonably, while the proposed method can effectively solve this problem. It can weaken the shortcomings of subjective judgement and greatly improve the rationality of decision-making results.

Optimized modelling and application of exhaust gas recirculation performance evaluation of turbocharged diesel engine.

Aimed at the problem of exhaust gas recirculation (EGR) performance evaluation and optimal EGR rate determination of turbocharged diesel engines, an optimized decision-making method, based on grey theory and entropy weight, was proposed. The internal combustion pressure, fuel consumption rate, NOX, CO and smoke were selected as the decision-making targets and the initial decision-making model was established based on the traditional grey decision-making theory. According to the characteristics and optimization requirements of EGR, the optimal compromise between combustion and emission performance is proposed to transform into decision-making target weighting problem, then an optimized subjective weighting method based on expert scoring and grey relational analysis is proposed. Finally, the entropy weight method was used to solve the objective weight and the optimized multi-objective grey decision-making model was established, which can not only weaken the human error of subjective empowerment, but also fully explore the intrinsic relationship of the evaluation indexes. At last, an optimization simulation platform for EGR performance evaluation based on MATLB/GUIDE was designed and established. The results show that the optimization simulation platform can effectively improve the efficiency of simulation calculation, which is more convenient for practical engineering applications. The optimized method can successfully realize EGR performance evaluation and optimal EGR rate determination under different working conditions. The decision-making result was consistent with the present EGR control strategies, which provide a new research idea for EGR performance optimization.

Low c-Met expression levels are prognostic for and predict the benefits of temozolomide chemotherapy in malignant gliomas.

Aberrant c-Met has been implicated in the development of many cancers. The objective of this study was to identify an unfavorable prognostic marker that might guide decisions regarding clinical treatment strategies for high-grade gliomas. C-Met expression was measured using immunohistochemistry in 783 gliomas, and we further analyzed c-Met mRNA levels using the Agilent Whole Genome mRNA Microarray in 286 frozen samples. In vitro, we performed cell migration and invasion assays. Cell sensitivity to temozolomide (TMZ) chemotherapy was determined using MTT assays. Both mRNA and protein levels of c-Met were significantly associated with tumor grade progression and inversely correlated with overall and progression-free survival in high-grade gliomas (all P < 0.0001). These findings were nearly consistent at the mRNA level across 3 independent cohorts. Multivariable analysis indicated that c-Met was an independent prognostic marker after adjusting for age, preoperative Karnofsky Performance Status (KPS) score, the extent of resection, radiotherapy, TMZ chemotherapy, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Further analysis in vitro revealed that downregulating the expression of c-Met dramatically inhibited cell migration and invasion capacities, enhanced sensitivity to TMZ chemotherapy in H4 and U87 glioma cells. Our results suggest that c-Met may serve as a potential predictive maker for clinical decision making.

Isocitrate dehydrogenase 1 Gene Mutation Is Associated with Prognosis in Clinical Low-Grade Gliomas.

Isocitrate dehydrogenase 1 gene mutations are found in most World Health Organization grade II and III gliomas and secondary glioblastomas. Isocitrate dehydrogenase 1 mutations are known to have prognostic value in high-grade gliomas. However, their prognostic significance in low-grade gliomas remains controversial. We determined the predictive and prognostic value of isocitrate dehydrogenase 1 status in low-grade gliomas. The association of isocitrate dehydrogenase 1 status with clinicopathological and genetic factors was also evaluated. Clinical information and genetic data including isocitrate dehydrogenase 1 mutation, O 6-methylguanine DNA methyltransferase promoter methylation, 1p/19q chromosome loss, and TP53 mutation of 417 low-grade gliomas were collected from the Chinese Glioma Genome Atlas database. Kaplan-Meier and Cox proportional hazards regression analyses were performed to evaluate the prognostic effect of clinical characteristics and molecular biomarkers. Isocitrate dehydrogenase 1 mutation was identified as an independent prognostic factor for overall, but not progression-free, survival. Notably, isocitrate dehydrogenase 1 mutation was found to be a significant prognostic factor in patients with oligodendrogliomas, but not in patients with astrocytomas. Furthermore, O 6-methylguanine DNA methyltransferase promoter methylation (p = 0.017) and TP53 mutation (p < 0.001), but not 1p/19q loss (p = 0.834), occurred at a higher frequency in isocitrate dehydrogenase 1-mutated tumors than in isocitrate dehydrogenase 1 wild-type tumors. Younger patient age (p = 0.041) and frontal lobe location (p = 0.010) were significantly correlated with isocitrate dehydrogenase 1 mutation. Chemotherapy did not provide a survival benefit in patients with isocitrate dehydrogenase 1-mutated tumors. Isocitrate dehydrogenase 1 mutation was an independent prognostic factor in low-grade gliomas, whereas it showed no predictive value for chemotherapy response. Isocitrate dehydrogenase 1 mutation was highly associated with O 6-methylguanine DNA methyltransferase promoter methylation and TP53 mutation.

Expression of RINT1 predicts seizure occurrence and outcomes in patients with low-grade gliomas.

PURPOSE: Most patients with low-grade gliomas (LGGs) experience epileptic seizures as an initial symptom. However, the mechanism of LGG-related epilepsy is poorly understood. Genetic changes in brain tumors influence epileptic seizures, but few biomarkers have been associated with LGG-related seizures. We investigated the association between LGG-related epilepsy and tumor-specific molecular changes. METHODS: Clinical characteristics, RNA sequence data, and case follow-up data were reviewed for 76 patients with histologically confirmed LGG. Gene expression (n = 21,469) was compared between patients with preoperative epileptic seizures and those without preoperative epileptic seizures. The Engel classification was used at 6 months after surgery to evaluate the prognostic role of genes that passed the screen. RESULTS: Expression of RAD50 interactor 1 (RINT1) significantly differed between LGG patients with and without preoperative epileptic seizures (p = 0.003). This result was validated by applying the same analysis to RNA sequence data from The Cancer Genome Atlas (p = 0.048). Patients with high RINT1 expression were at increased risk of LGG-related seizures compared to those with low expression (p = 0.044). RINT1 was also identified as a predictor of seizure outcomes in patients with LGG at 6 months after tumor resection (p = 0.022). CONCLUSIONS: Our results suggest that high RINT1 expression may represent a risk factor for LGG-related seizures and may be associated with seizure outcomes.

[Development of biphasic drug-loading lipid emulsion of Salvia miltiorrhiza and its quality evaluation].

The feasibility of simultaneously loading both liposoluble and water-soluble components of Salvia miltiorrhiza in emulsion was discussed, in order to provide new ideas in comprehensive application of effective components in S. miltiorrhiza in terms of technology of pharmaceutics. With tanshinone II (A) and salvianolic acid B as raw materials, soybean phospholipid and poloxamer 188 as emulsifiers, and glycerin as isoosmotic regulator, the central composite design-response surface method was employed to optimize the prescription. The coarse emulsion was prepared with the high-speed shearing method and then homogenized in the high pressure homogenizer. The biphasic drug-loading intravenous emulsion was prepared to investigate its pharmaceutical properties and stability. The prepared emulsion is orange-yellow, with the average diameter of 241 nm and Zeta potential of -35.3 mV. Specifically, the drug loading capacity of tanshinone II (A) and salvianolic acid B were 0.5 g x L(-1) and 1 g x L(-1), respectively, with a good stability among long-term retention samples. According to the results, the prepared emulsion could load liposoluble tanshinone II (A) and water-soluble salvianolic acid B simultaneously, which lays a pharmaceutical foundation for giving full play to the efficacy of S. miltiorrhiza.

Prognostic value of MGMT promoter methylation and TP53 mutation in glioblastomas depends on IDH1 mutation.

Several molecular markers have been proposed as predictors of outcome in patients with glioblastomas. We investigated the prognostic significance of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and TP53 mutation status dependent on isocitrate dehydrogenase 1 (IDH1) mutation in glioblastoma patients. A cohort of 78 patients with histologically confirmed glioblastomas treated with radiation therapy and chemotherapy were reviewed retrospectively. We evaluated the prognostic value of MGMT promoter methylation and TP53 mutation status with regard to progression-free survival (PFS) and overall survival (OS). It was revealed that mutations in IDH1, promoter methylation of MGMT, TP53 mutation, age, Karnofsky performance status (KFS), and extension of resection were independent prognostic factors. In patients with an IDH1 mutation, those with an MGMT methylation were associated with longer PFS (p=0.016) and OS (p=0.013). Nevertheless, the presence of TP53 mutation could stratify the PFS and OS of patients with IDH1 wild type (p=0.003 and 0.029 respectively, log-rank). The MGMT promoter methylation and TP53 mutation were associated with a favorable outcome of patients with and without mutant IDH1, respectively. The results indicate that glioblastomas with MGMT methylation or TP53 mutations have improved survival that may be influenced by IDH1 mutation status.

[Effects of cyclic stretch on the induction of the transdifferentiation in human lung epithelial cells].

OBJECTIVE: To investigate the effect of mechanical stretch induced epithelial-mesenchymal transition in human lung epithelial cells BEAS-2B in vitro. METHODS: The human lung epithelial cells BEAS-2B were subjected to cyclic stretch by the FX-5000T system at 0.33 Hz of 10% or 20% elongation for 24, 48 and 72 hours respectively. The morphologic changes were observed by microscopy. The mRNA and protein expressions of E-cadherin, Cytokeratin-8 (CK-8), α-smooth muscle actin (α-SMA) and Vimentin were evaluated by immunofluorescence before and after mechanical stretch and fluorescent quantitation reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: (1) When stretch by 20% elongation for 48 hours, the morphological changes in BEAS-2B cells from cobblestone-like structure to elongated shape and obviously when stretch for up to 72 hours, while 10% elongation showed no significant morphological changes comparing to control. (2) Decreasing E-cadherin and CK-8 protein expression was associated with increased immunostaining for α-SMA protein at 72 hours after 20% mechanical stretch. (3) Expression of E-cadherin mRNA was decreased to 0.388±0.056 and 0.247±0.064 after 20% mechanical stretch for 48 hours and 72 hours compared with control without stretch (set 1, both P<0.05), expression of CK-8 mRNA was decreased to 0.436±0.060 at 72 hours after 20% mechanical stretch (P<0.01), α-SMA mRNA was increased to 1.437±0.267 (48 hours) and 1.261±0.247 (72 hours) after 20% mechanical stretch (both P<0.05), and Vimentin mRNA was increased to 1.679±0.172 (48 hours) after 20% mechanical stretch (P<0.05). Expression of E-cadherin mRNA was decreased to 0.387±0.081 at 72 hours after 10% mechanical stretch (P<0.05), Vimentin mRNA was increased to 1.688±0.179 at 48 hours after 10% mechanical stretch while other markers showed no significant changes comparing with control. CONCLUSIONS: Excessive mechanical stretch could induce epithelial-mesenchymal transition in lung epithelial cells BEAS-2B in vitro.

Direct evidence of the left caudate's role in bilingual control: an intra-operative electrical stimulation study.

Bilinguals need control mechanisms in order to switch between languages in different communication contexts (Green, 1998, Bilingualism: Language and Cognition, 1; Price, Green, & von Studnitz, 1999, Brain, 122). There has been neural evidence showing competition to control output in L2 vs. L1 in both cortical and sub-cortical areas, when language selection is carried out (Abutalebi & Green, 2007, Journal of Neurolinguistics, 20). Here we use intra-operative direct electrical stimulation to demonstrate that the head of the left caudate is critical not only in language switching tasks but other control tasks. A bilingual Chinese-English patient was instructed to perform both language switching and switching in color-shape naming tasks during awake glioma surgery. When stimulation was applied on the left caudate, failures or difficulties in both language switching and color-shape naming were observed, with the effects greater on language switching. Stimulation to neighboring brain regions either did not affect performance or generated mild problems specific to language switching. The results provide direct evidence of the necessary role of the left caudate in language control.