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Objectives: Gut-brain axis dysfunction has emerged as a key contributor to the pathogenesis of Crohn's disease (CD). The elucidation of neural alterations may provide novel insights into its management. We aimed to develop a multiparameter brain MRI-based radiomics model (RM) for characterizing neural alterations in CD patients and to interpret these alterations using multiomics traits., Methods: This prospective study enrolled 230 CD patients and 46 healthy controls (HCs). Participants voluntarily underwent brain MRI and psychological assessment (n = 155), blood metabolomics analysis (n = 260), and/or fecal 16S rRNA sequencing (n = 182). The RM was developed using 13 features selected from 13,870 first-order features extracted from multiparameter brain MRI in training cohort (CD, n = 75; HCs, n = 32) and validated in test cohort (CD, n = 34; HCs, n = 14). Multiomics data (including gut microbiomics, blood metabolomics, and brain radiomics) were compared between CD patients and HCs., Results: In the training cohort, area under the receiver operating characteristic curve (AUC) of RM for distinguishing CD patients from HCs was 0.991 (95% confidence interval (CI), 0.975-1.000). In test cohort, RM showed an AUC of 0.956 (95% CI, 0.881-1.000). CD-enriched blood metabolites such as triacylglycerol (TAG) exhibited significant correlations with both brain features detected by RM and CD-enriched microbiota (e.g., Veillonella). One notable correlation was found between Veillonella and Ctx-Lh-Middle-Temporal-CBF-p90 (r = 0.41). Mediation analysis further revealed that dysbiosis, such as of Veillonella, may regulate the blood flow in the middle temporal cortex through TAG., Conclusion: We developed a multiparameter MRI-based RM that characterized the neural alterations of CD patients, and multiomics data offer potential evidence to support the validity of our model. Our study may offer clues to help provide potential therapeutic targets., Critical Relevance Statement: Our brain-gut axis study developed a novel model using multiparameter MRI and radiomics to characterize brain changes in patients with Crohn's disease. We validated this model's effectiveness using multiomics data, making it a potential biomarker for better patient management., Key Points: Utilizing multiparametric MRI and radiomics techniques could unveil Crohn's disease's neurophenotype. The neurophenotype radiomics model is interpreted using multiomics data. This model may serve as a novel biomarker for Crohn's disease management., Competing Interests: Declarations. Ethics approval and consent to participate: This prospective study was approved by the Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University (No. [2021]215-2), and there was informed consent for all patients. Consent for publication: All authors approved the final manuscript and the submission to this journal. Competing interests: C.Z. is an employee of Siemens Healthineers, but he had no control over the inclusion of any data or information that might have presented a conflict of interest. All authors declare no relevant relationships., (© 2024. The Author(s).)

Objective: To compare the clinical efficacy of ligament advanced reinforcement system (LARS) and autogenous hamstring tendon plus high-strength suture in arthroscopic reconstruction of posterior cruciate ligament(PCL)., Methods: A total of 96 patients with simple PCL injury treated with arthroscopic posterior cruciate ligament reconstructive surgery admitted to our hospital between August 2019 and December 2021 were selected for complete follow-up. There were 78 males and 18 females, 40 cases of left leg and 56 cases of right leg, the aged from 20 to 56 years old with an average of (32.50±8.68 ) years old. The transplants were divided into two groups:LARS group (52 cases) and autogenous hamstring tendon plus high-strength suture group (44 cases). In the LARS group, there were 42 males and 10 females;with an average age of (31.84±8.62) years old;body mass index (BMI) was (24.73±2.29) kg﹒m -2 ;7 mm LARS was used to reconstruct PCL. In the autologous tendon group, there were 36 males and 8 females, with an average age of (33.06±8.99) years old, BMI was (23.52±2.16) kg·m -2 , and the PCL was reconstructed with four strands of hamstring tendons and three pieces of Ethibond suture. All patients underwent functional rehabilitation guided exercise and were followed up regularly after surgery to objectively evaluate the stability of the knee joint by KT-1000 measurement of knee relaxation, and subjective evaluation of knee function by Lysholm score, Tegner score, and International Knee Documentation Council (IKDC) score. Data from preoperative, 3, 6, and 12 month follow-up were collected and analyzed by SPSS software to compare postoperative recovery and ligament relaxation between the two groups of patients., Results: Ninety-six patients were followed up for 12 months. KT-1000 measurement of knee joint in autogenous tendon group and LARS group before operation [(10.73±1.46) points vs (10.55±1.53) points], 6 months after operation[(3.02±0.75) points vs (2.35±0.60) points], 12 months after operation[(3.77±1.76) points vs (2.44±0.60) points]. There was significant difference between the two groups at 6 and 12 months after operation ( P <0.05), but there was no significant difference between the two groups at 3 months after operation ( P >0.05). In the autogenous tendon group and LARS group, before operation and 12 months after operation, total Lysholm score [(40.6±16.8), (91.25±6.35) points vs (51.92±18.52), (92.35±5.30) points], Tegner score[(1.8±0.7), (5.8±0.6) points vs(1.7±0.8)、(5.7±0.7) points] and total IKDC score[(54.50±6.33), (83.90±3.93) points vs (54.40±4.24), (83.62±3.64) points], the differences were statistically significant ( P <0.05), indicating that the knee function of the two groups was improved after surgery. At 3 and 6 months after operation in the autogenous tendon group and LARS group, the total Lysholm score[(65.86±11.54), (74.60±6.46) points vs (73.46±6.42), (86.73±4.62) points], Tegner score[(2.5±0.6), (3.5±0.5) points vs (4.3±0.7), (5.0±1.4) points], the total scores of IKDC [(55.78±2.68), (70.62±4.74) points vs (65.31±4.60), (79.71±2.93) points]. The difference between two groups was statistically significant ( P <0.05). The results showed that the function of the knee joint in the LARS group was better than that the autologous tendon group. However, at 12 months after the operation, there was no significant difference in the score of knee joint function between the two groups ( P >0.05). The results showed that the stability of LARS group was better than that of autologous tendon group., Conclusion: Both the autogenous hamstring tendon plus high-strength suture and LARS reconstruction can significantly improve the knee function and stability, with satisfactory postoperative results. Howervr the LARS provides superior postoperative stability.

Introduction: Fatty acid binding protein 5 (FABP5) exhibits heightened expression levels in triple-negative breast cancer. The inhibitor of FABP5, Stony Brook fatty acid-binding protein inhibitor 26 (SBFI-26), has demonstrated the capacity to suppress cell proliferation, migration, and invasion. This study delves into the functional mechanism and impact of combining SBFI-26 with docetaxel in treating MDA-MB-231 cells of triple-negative breast cancer., Methods: Various concentrations of docetaxel and SBFI-26 were chosen for individual or combined treatments. The effects of SBFI-26, docetaxel, or their combination on cell cycle arrest and apoptosis were assessed using flow cytometry. Western blotting was utilised to detect the expression of apoptosis-related proteins, namely cysteinyl aspartate-specific proteases 3 (Caspase3), B cell leukemia/lymphoma 2 (Bcl-2), and Bcl-2 associated X (Bax), while intracellular reactive oxygen species (ROS) levels were determined using a fluorescence spectrophotometer., Results: The IC50 values for SBFI-26 and docetaxel in inhibiting MDA-MB-231 cells were determined to be 106.1 μM and 86.14 nM, respectively. Significantly, the combination treatment augmented the proportion of G1 phase (apoptotic) cells by 3.67-fold compared to the control group ( P  < 0.0001). Furthermore, the apoptosis rate in the combination group was 2.59-fold higher than that in the docetaxel group ( P  < 0.0001) and demonstrated a significant increase of 1.82-fold compared with the SBFI-26 group ( P  < 0.001). Analyses revealed a decrease in the protein expression of Bcl-2, while Bax and Caspase3 exhibited an increase in the combination group for MDA-MB-231 cells. Moreover, the combined treatment group demonstrated a 2.97-fold increase ( P  < 0.0001) in ROS fluorescence intensity compared to the control group, a noteworthy 1.39-fold increase ( P  < 0.01) compared to the SBFI-26 treatment group, and a substantial 1.70-fold increase ( P  < 0.0001) compared to the docetaxel treatment group., Conclusion: These findings suggest that the co-administration of SBFI-26 with docetaxel effectively enhances apoptosis in triple-negative breast cancer MDA-MB-231 cells by elevating intracellular ROS levels., Competing Interests: The authors declare that there is no conflict of interest., (© 2025 The Author(s).)

Purpose: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC., Materials and Methods: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq)., Results: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine-cytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics., Conclusions: These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2023. Korean Gastric Cancer Association.)

Ferroptosis is a newly described regulated form of cell death that contributes to the progression of non-small cell lung cancers (NSCLCs). MicroRNA-302a-3p (miR-302a-3p) plays critical roles in the tumorigenicity of different cancers; however, its function and underlying mechanism in ferroptosis and NSCLCs remain unclear. Human NSCLCs cells were incubated with miR-302a-3pmimic or inhibitor in the presence or absence of erastin or RSL3. Cell viability, colony numbers, lactate dehydrogenase (LDH) releases, lipid peroxidation and intracellular iron level were measured. Besides, the synergistic effects of cisplatin and paclitaxel with miR-302a-3p were determined. miR-302a-3p level was reduced in human NSCLCs cells and tissues. ThemiR-302a-3p mimic induced lipid peroxidation, iron overload and ferroptosis, thereby inhibiting cell growth and colony formation of NSCLCs cells. Conversely, the miR-302a-3p inhibitor block ederastin- or RSL3-related ferroptosis and tumor suppression. Additionally, we found that miR-302a-3p directly bound to the 3'-untranslational region of ferroportin to decrease its protein expression, and that ferroportin overexpression significantly prevented miR-302a-3p mimic-induced ferroptosis and tumor inhibition. Moreover, the miR-302a-3p mimic sensitized NSCLCs cells to cisplatin and paclitaxel chemotherapy. miR-302a-3p functions as a tumor inhibitor, at least partly, via targeting ferroportin to induce ferroptosis of NSCLCs.

Glioma is the most common and deadly tumor in central nervous system. According to previous studies, long noncoding RNAs (lncRNA) and transcription factors were significant factors of gliomas progression by regulating gliomas immune microenvironment. In our study, we built two independent cohorts from CGGA and TCGA. And we extracted 253 immune-related lncRNA correlated with prognosis. After LASSO analysis and multivariate Cox regression analysis, 8 immune-related lncRNA were used to construct classifier. The effectiveness of classifier was confirmed in both CGGA (AUC = 0.869) and TCGA (AUC = 0.902) cohorts. The correlation between transcription factors and immune-related lncRNA was calculated by WCGNA. Eventually, we built a network between 8 lncRNA and transcription factors. The function of core immune-related lncRNA in gliomas immune microenvironment was also investigated by CIBERTSORT. Our research provided a strong classifier of immune-related lncRNA to predict gliomas patient outcome. We also found the correlation between core immune-related lncRNA and transcription factors. These results may stimulate new strategy of immunotherapy in gliomas patients., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Yixin Tian et al.)

The rational design of catalytically active sites in porous materials is essential in electrocatalysis. Herein, atomically dispersed Fe-N x sites supported by hierarchically porous carbon membranes are designed to electrocatalyze the hydrazine oxidation reaction (HzOR), one of the key techniques in electrochemical nitrogen transformation. The high intrinsic catalytic activity of the Fe-N x single-atom catalyst together with the uniquely mixed micro-/macroporous membrane support positions such an electrode among the best-known heteroatom-based carbon anodes for hydrazine fuel cells. Combined with advanced characterization techniques, electrochemical probe experiments, and density functional theory calculation, the pyrrole-type FeN 4 structure is identified as the real catalytic site in HzOR., (© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Vasculogenic mimicry (VM) refers to the fluid-conducting channels formed by aggressive tumor cells rather than endothelial cells (EC) with elevated expression of genes associated with vascularization. VM has been considered as one of the reasons that glioblastoma becomes resistant to anti-VEGF therapy. However, the molecular basis underlying VM formation remains unclear. Here we report that the insulin-like growth factor-binding protein 2 (IGFBP2) acts as a potent factor to enhance VM formation in glioma. Evidence showed that elevated IGFBP2 expression was positively related with VM formation in patients with glioma. Enforced expression of IGFBP2 increased network formation of glioma cells in vitro by activating CD144 and MMP2 (Matrix Metalloproteinase 2). U251 cells with stable knockdown of IGFBP2 led to decreased VM formation and tumor progression in orthotopic mouse model. Mechanistically, IGFBP2 interacts with integrin α5 and β1 subunits and augments CD144 expression in a FAK/ERK pathway-dependent manner. Luciferase reporter and ChIP assay suggested that IGFBP2 activated the transcription factor SP1, which could bind to CD144 promoter. Thus, IGFBP2 acts as a stimulator of VM formation in glioma cells via enhancing CD144 and MMP2 expression.

Ethylene response factor (ERF) has been widely studied in regulating fruit ripening in tomato, apple, banana and kiwifruit, but little is known in pear. In this study 1-methylcyclopropene (1-MCP) treatment, an inhibitor of ethylene perception, was conducted at approximately 30 days before harvest to delay fruit ripening in a climacteric white pear cultivar Yali. Transcriptome libraries were constructed and sequenced in pre-ripening, ripening, and 1-MCP treated fruits. Data analysis showed that 73 candidate genes related to fruit ripening were induced by 1-MCP, among which two were positively related, namely 1-aminocyclopropane-1-carboxyla oxidase and an ERF gene (designated as ACO54 and ERF24). Transient transformations in pear fruit revealed that over-expression of ACO54 enhance transcription level of ERF24 and most ripening-related genes. Meanwhile, over-expression of ERF24 raises expression level of ACO54 and partially ripening-related genes. Moreover, dual-luciferase and yeast-one-hybrid assays unravel an interaction between ERF24 and the ACO54 promoter. Therefore, the ERF24 could directly regulate ACO54 expression by binding to its promoter. These results suggested that the first identified ERF24 is involved in regulating fruit ripening in Chinese white pear., (© 2017 Scandinavian Plant Physiology Society.)

Morin, is a natural bioflavonoid isolated from Chinese herbs of the Moraceae family, has been reported to possess antidiabetic activity. However, the role of morin on glomerular mesangial cells (MCs) proliferation and extracellular matrix (ECM) accumulation in diabetic condition is still unclear. Therefore, in this study, we investigated the role of morin on cell proliferation and ECM accumulation in rat glomerular MCs cultured under high glucose (HG) condition. Our results showed that morin inhibited HG-induced MC proliferation, arrested HG-induced cell-cycle progression, reversed HG-inhibited expression of p21 Waf1/Cip1 and p27 Kip1 . It also inhibited HG-induced ECM expression, ROS generation and NOX4 expression in MCs. Furthermore, morin suppressed HG-induced phosphorylation of p38 MAPK and JNK1/2 in MCs. These data suggest that morin inhibits HG-induced MC proliferation and ECM expression through suppressing the activation of p38 MAPK and JNK signaling pathways. Thus, morin may be useful for the prevention or treatment of diabetic nephropathy., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The association between the CCDC26 rs4295627 single nucleotide polymorphism (SNP) and the glioma risk has been studied previously, but these studies have yielded conflicting results. The aim of the present study is to analyze this association more vigorously, by means of a meta-analysis. A comprehensive literature search was performed in databases PubMed and EMBASE. Six articles including 12 case-control studies in English with 11,368 controls and 5891 cases were eligible for the meta-analysis. We conducted subgroup analyses by the source of controls, ethnicity, and country. Our meta-analysis revealed that the rs4295627 SNP was associated with the glioma risk in a heterozygote model (TG versus TT: odds ratio = 1.35, 95% confidence interval = 1.26-1.45, P = 0.066). Moreover, our results suggested that the rs4295627 SNP was associated with a notably increased risk of glioma among Caucasians except for Swedes in 4 models (the homozygote model, recessive model, dominant model, and additive model). Nonetheless, in Sweden and China, the results showed no associations. No evidence of the publication bias was uncovered. Thus, our meta-analysis suggests that the rs4295627 SNP is associated with an increased risk of glioma. Additional studies are needed to derive more precise conclusion.

Vasculogenic mimicry (VM) refers to the process by which highly aggressive tumor cells mimic endothelial cells to form vessel-like structures that aid in supplying enough nutrients to rapidly growing tumors. Histone deacetylases (HDACs) regulate the expression and activity of numerous molecules involved in cancer initiation and progression. Notably, HDAC3 is overexpressed in the majority of carcinomas. However, thus far, no data are available to support the role of HDAC3 in VM. In this study, we subjected glioma specimens to immunohistochemical and histochemical double-staining methods and found that VM and HDAC3 expression were related to the pathological grade of gliomas. The presence of VM correlated with HDAC3 expression in glioma tissues. The formation of tubular structures, as determined by the tube formation assay to evaluate VM, was impaired in U87MG cells when transfected by siRNA or treated with an HDAC3 inhibitor. Importantly, the expression of VM-related molecules such as MMP-2/14 and laminin5γ2 was also affected when HDAC3 expression was altered. Furthermore, U87MG cells were treated with a phosphoinositide 3-kinase (PI3K) inhibitor or/and ERK inhibitor and found that the PI3K and ERK signaling pathways play key roles in VM; whereas, in VM, the two signaling pathways did not act upstream or downstream from each other. Taken together, our findings showed that HDAC3 contributed to VM in gliomas, possibly through the PI3K/ERK-MMPs-laminin5γ2 signaling pathway, which could potentially be a novel therapeutic target for gliomas., (© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)

The poor therapeutic effect of traditional antiangiogenic therapy on glioblastoma multiforme (GBM) may be attributed to vasculogenic mimicry (VM), which was previously reported to be promoted by cancer stem-like cells (SLCs). All-trans retinoic acid (ATRA), a potent reagent which drives differentiation, was reported to be able to eradicate cancer SLCs in certain malignancies. The aim of the present study was to investigate the effects of ATRA on the VM formation ability of U87 glioblastoma SLCs. The expression of cancer SLC markers CD133 and nestin was detected using immunocytochemistry in order to identify U87 SLCs. In addition, the differentiation of these SLCs was observed through detecting the expression of glial fibrillary acidic protein (GFAP), β-tubulin III and galactosylceramidase (Galc) using immunofluorescent staining. The results showed that the expression levels of GFAP, β-tubulin III and Galc were upregulated following treatment with ATRA in a dose-dependent manner. Furthermore, ATRA significantly reduced the proliferation, invasiveness, tube formation and vascular endothelial growth factor (VEGF) secretion of U87 SLCs. In conclusion, the VM formation ability of SLCs was found to be negatively correlated with differentiation. These results therefore suggested that ATRA may serve as a promising novel agent for the treatment of GBM due to its role in reducing VM formation.

Adipocyte-derived stem cells have emerged as a novel source of stem cell therapy for their autologous and readily accessible and pluripotent potential to differentiate into different lineages such as neural stem cells (NSCs) and endothelial progenitor cells (EPCs). Transplantation of NSCs and EPCs has been promising for the repair of brain injury. We explored using co-transplanted hydrogel scaffold to improve the survival of the transplanted cells and recovery of neurological function. Adult Wistar rats were transplanted with EPC-hydrogel, NSC-hydrogel, NSC-EPC-hydrogel, EPC only, or NSC only 7 days after cortical contusion injury. Behavioral tests were performed to evaluate neurological function before, and 1, 2, 3, and 4 weeks after transplantation. Size of injury, extent of vascularization, as well as the survival and differentiation of the transplanted EPCs and NSCs, were evaluated at week 5. All transplantation groups displayed significantly better neurological function compared with the control groups. Improved neurological function correlated with significantly smaller injury volumes than that of the saline group. Using immunostaining, we have shown that while transplanted NSCs differentiated into both neurons and astrocytes, the EPCs were incorporated into vessel epithelia. The extent of reactive gliosis (based on glial fibrillary acidic protein immunostaining) was significantly reduced in all treatment groups (NSC-EPC-hydrogel, NSC-hydrogel, and EPC-hydrogel) when compared with the saline group, with the highest reduction in the NSC-EPC-hydrogel transplantation group. Thus, co-transplantation of hydrogel scaffold provides a more conducive environment for the survival and differentiation of NSCs and EPCs at the site of brain injury, leading to improved vascularization and better recovery of neurological function.

A previous report has confirmed the existence and clinical significance of vasculogenic mimicry (VM) in glioma. However, its conclusions about the negative clinical significance of VM in glioblastoma are based on a small group of patients and, thus, might be unconvincing. The aim of the present study was to reevaluate the clinical significance of VM in glioblastoma. Patients were classified as VM-positive or VM-negative according to CD34 and periodic acid-Schiff staining. The association between VM and the clinical characteristics of the patients was analyzed. Univariate and multivariate analyses were carried out to identify the independent prognostic factors for overall survival using the Cox regression hazard model. Survival times were estimated using the Kaplan-Meier method and compared using the log-rank test. Of all 86 glioblastomas, 23 were found to have VM. The presence of VM in glioblastoma was not associated with gender, age, Karnofsky performance status, hydrocephalus, tumor burden, microvessel density, tumor relapse, or the extent of tumor resection. The univariate and multivariate analyses revealed that VM is an independent prognostic factor for overall survival. The median survival time for patients with VM was 11.17 months compared with 16.10 months for those without VM (P = 0.017). In addition to VM, an age of 65 years or older, a KPS of 60 or less, a large tumor burden are significant prognostic factors for patient survival. Our data suggest that VM might be an independent adverse prognostic factor in newly diagnosed GBM, further prospective studies are needed to answer this question.

Objective: The purpose of this study was to evaluate the safety and efficacy of transorbital puncture for the retreatment of previously embolized cavernous sinus dural arteriovenous fistulas (DAVFs) via a superior ophthalmic vein (SOV) approach., Materials and Methods: During a 12-year period, 9 consecutive patients with previously embolized cavernous sinus DAVFs underwent retreatment via the transorbital SOV approach., Results: All of the nine cases of previously embolized cavernous sinus DAVFs were successfully embolized. Clinical follow-ups were conducted in all nine cases at the duration of 17-141 months (61.22 ± 39.13 months). No recanalization occurred during the follow-up period. A subtle ptosis appeared in two patients and disappeared in one of the two cases after a 4-year follow-up. One patient suffered from paroxysmal positional vertigo and bruit for nearly 2 years after the treatment, but the follow-up angiography demonstrated no recurrence. One patient had persistent visual impairment caused by the initial venous stasis retinopathy. One patient with a history of a procedure-related transient decrease in visual acuity had it return to the normal level. The remaining four cases had clear improvement in the ocular symptoms and became completely asymptomatic during the follow-up period. No patient worsened or developed new symptoms., Conclusion: The approach of surgical cannulation of the SOV for the retreatment of previously embolized cavernous sinus DAVFs was proved feasible and efficient, especially when the transarterial and transfemoral venous approaches were inaccessible. However, if the SOV is not dilated enough or is located deeply in the orbit, transorbital venous puncture access may not be possible.

MicroRNAs (miRNAs) are small noncoding RNAs that function as tumor suppressors or oncogenes. MicroRNA-107 (miR-107), a transcriptional target of p53, is deregulated in many cancer cell lines. Here, we showed that miR-107 is down-regulated in glioma tissues and cell lines, in particular, p53-mutated U251 and A172. Transfection of wild-type p53 into these cells stimulated miR-107 expression. To investigate the role of miR-107 in tumorigenesis, we constructed a lentiviral vector overexpressing miR-107. Notably, miR-107 inhibited proliferation and arrested the cell cycle at the G0-G1 phase in glioma cells. Transduction of Lenti-GFP-miR-107 into glioma cells inhibited CDK6 and Notch-2 protein expression. Our findings collectively demonstrate that p53-induced miR-107 suppresses brain tumor cell growth and down-regulates CDK6 and Notch-2 expression, supporting its tumor suppressor role and utility as a target for glioma therapy., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Human placental decidua basalis-derived mesenchymal stem cells (DBMSCs) have been identified as valuable sources for cell transplantation. In this study, we found that DBMSCs could be induced to form neural stem cells in the form of neurospheres. These neurospheres were further differentiated into dopamine neuron-like cells with a cocktail of cytokines. The differentiated DBMSCs were verified through the presence of a neuron-like morphology, the expression of specific dopamine neuron makers, and the production of dopamine. In addition, this differentiation capacity of DBMSCs was not affected by long-term culture, and the cells maintained a normal karyotype in vitro. The dopamine neuronal differentiation and the relative safety transplantation potential of DBMSCs may facilitate stem cell therapeutic approaches to Parkinson's disease.

Vasculogenic mimicry (VM), a process involving the formation of a tubular structure by highly invasive and genetically dysregulated tumor cells, can supplement the function of blood vessels to transport nutrients and oxygen to maintain the growth of tumor cells in many malignant tumors. We aimed to explore the existence of VM and its clinical significance in medulloblastoma in this study. VM was identified in 9 out of 41 (22%) medulloblastoma tissues. Immunohistochemical studies revealed that the presence of VM was associated with the expression of MMP-2, MMP-14, EphA2 and laminin 5γ2. Tumor tissues with VM were associated with lower microvessel density (MVD), which was indirect evidence of the blood supply function of VM. Survival analysis and log-rank tests showed that patients with VM had shorter overall survival time than those without VM. Multivariate analysis and the Cox proportional hazards model identified VM as independent prognostic factor for overall survival. Our results confirmed the existence of VM for the first time and revealed that VM is a strong independent prognostic factor for survival in patients with medulloblastoma.

Glioma, the most common tumor of the central nervous system (CNS), currently results in a high rate of morbidity and mortality. The expression of CD133, a stem-like cell marker expressed in the glioma cells, is believed to lead to tumorigenesis in the human brain. Thus, it is necessary to find a proper method to specifically kill the CD133(+) glioma cells. Dendritic cell (DC)/tumor hybrids are proven to be able to induce an effective immune response, leading to killing of glioma cells in vitro. We isolated CD133(+) cells from a population of primary glioma cells, and cultured autologous DCs and T cells at the same time. Next, we electrofused the DCs with the CD133(+) glioma cells and with CD133- ones, in order to explore a new strategy for glioma therapy. We then exposed the T cells to five separate groups of cells: DC/CD133(+) hybrids, DC/CD133(-) hybrids, DCs alone, unsorted glioma cells alone and mixed DCs-glioma cells. A cytotoxicity assay showed that T cells stimulated by either type of hybrid were able to kill cultured autologous glioma cells significantly more effectively than those stimulated by the other three cell types (P<0.05). The amounts of IFN-γ secreted by T cells stimulated by the two types of fused cells were obviously increased compared to those stimulated by the other three cell types (P<0.05). However, no significant differences were noted between the effects of the two hybrids, neither in the cytotoxicity assay nor in the IFN-γ release assay (P>0.05). Therefore, both DC/CD133(+) and DC/CD133(-) hybrids can cause significant T cell immune responses in vitro. There were no significant differences between the immune responses caused by the two types of hybrids., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The immunological consequences of cryoablation for gliomas are largely unknown. cryoablation is an attractive therapeutic option for tumors due to its minimally invasive nature. cryoablation is also potentially immunogenic. With an aim to explore changes in cellular immunity following argon-helium cryosurgery, we established Wistar rat models bearing subcutaneous C6 glioma and divided the rats into the normal control (30 rats), sham-operated (33 rats), surgical resection (30 rats), and cryosurgery (33 rats) groups with corresponding treatments. The tumor cell morphology was observed, and changes in the T lymphocyte subset and NK lymphocyte subset and the ratio of Th1/Th2 were assessed with flow cytometry following the cryosurgery. The results showed that subcutaneous tumor implantation was successful in all cases and this was confirmed histologically. Compared with surgical resection that caused significant reduction in CD3(+), CD4(+), CD14(+), CD16+56 cell percentages, cryosurgery resulted in significantly increased percentages of CD3(+), CD4(+), CD14(+), CD16+56 cells (P < 0.05) with a increase of the Th1/Th2 ratio 7 days after the operation. These results demonstrate that in addition to tumor cell destruction, cryosurgery also results in enhanced cellular immunity, suggesting the great potential of argon-helium cryosurgery in clinical management of gliomas.

Background Aims: This study aimed to observe nine factors expressed in rat ischemic brain after transplantation of bone marrow stromal cells (BMSC) and/or endothelial progenitor cells (EPC). These factors were vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF-l), transforming growth factor-β (TGF-β), platelet-derived growth factor-BB (PDGF-BB), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF)., Methods: Adult Wistar rats were divided randomly into four groups: a vehicle group, BMSC group, EPC group and BMSC combined with EPC group. The rats were subjected to middle cerebral artery occlusion (MCAO) then implanted intravenously with 3 × 10(6) BMSC, EPC, BMSC/EPC or phosphate-buffered saline (PBS) 24 h after MCAO. Neurologic functional deficits were measured on days 1, 7, 14, 28 after transplantation. On day 7 after transplantation, quantitative reverse transcription (qRT)-polymerase chain reaction (PCR) and Western blot were employed to detect the expression of VEGF, SDF-1, bFGF, IGF-l, TGF-β, PDGF-BB, BDNF, GDNF and NGF., Results: The neurologic evaluation found that the neurologic severity scores were no different between the four groups on day 1, and the scores of rats in the BMSC/EPC group were significantly lower than those of rats in the other groups on days 7, 14 and 28 after transplantation. The expressions of bFGF, VEGF and BNDF were significantly higher in the BMSC/EPC group compared with the other groups., Conclusions: The intravenous transplantation of BMSC combined with EPC could promote the functional rehabilitation of rats with focal cerebral ischemia, and the mechanism may be related to the enhanced expression of factors.

Inhibition of tumor neovascularization has profound effects on the growth of solid tumors. Our previous studies have shown the effect of VEGF165-PE38 recombinant immunotoxin on proliferation and apoptosis in human umbilical vein endothelial cells in vitro. In this study, we explored the direct inhibition of angiogenesis in chick chorioallantoic membrane and antiangiogenic therapy in a malignant glioma model. HEK293 cells were transfected with the pVEGF165PE38-IRES2-EGFP plasmid. ELISA was used to confirm the expression of VEGF165-PE38 in the transfected cells. These cells released 1396 + or - 131.9 pg VEGF165-PE38/1x10(4) cells/48 h into the culture medium and the supernatant was capable of inhibiting the growth of capillary-like structures in chick chorioallantoic membrane assay. In a murine malignant glioma model, plasmid was directly administered via multiple local intratumoral delivery. After day 16 the tumor volume in mice treated with pVEGF165PE38-IRES2-EGFP was significantly lower than that in mice in the control groups. Immunohistochemistry studies showed that the treated group had decreased expression of CD31. Quantitative analysis of microvessel density in the treated group was 1.99 + or - 0.69/0.74 mm(2), and was significantly lower than that in the control groups (9.33 + or - 1.99/0.74 mm(2), 8.09 + or - 1.39/0.74 mm(2) and 8.49 + or - 1.69/0.74 mm(2)). Immunohistochemistry analysis indicated that immunotoxin VEGF165-PE38 was distributed in the treated group in malignant glioma tissue. Our findings provide evidence that the in vivo production of VEGF165-PE38 through gene therapy using a eukaryotic expression plasmid had potential antiangiogenic activity in malignant glioma in vivo.

Mesenchymal stem cells are capable of differentiating into dopaminergic-like cells, but currently no report has been available to describe the induction of human umbilical vein mesenchymal stem cells (HUVMSCs) into dopaminergic-like cells. In this study, we induced HUVMSCs in vitro into neurospheres constituted by neural stem-like cells, and further into cells bearing strong morphological, phenotypic and functional resemblances with dopaminergic-like cells. These HUVMSC-derived dopaminergic-like cells, after grafting into the brain of a rat model of Parkinson's disease (PD), showed a partial therapeutic effect in terms of the behavioral improvement. Nerve growth factor was reported to improve the local microenvironment of the grafted cells, and we therefore further tested the effect of dopaminergic-like cell grafting combined with nerve growth factor (NGF) administration at the site of cell transplantation. The results showed that NGF administration significantly promoted the survival of the grafted cells in the host brain and enhanced the content of dopaminergic in the local brain tissue. Behavioral test demonstrated a significant improvement of the motor function of the PD rats after dopaminergic-like cell grafting with NGF administration as compared with that of rats receiving the cell grafting only. These results suggest that transplantation of the dopaminergic-like cells combined with NGF administration may represent a new strategy of stem cell therapy for PD.

LINGO-1 (leucine-rich repeat and Ig domain-containing, Nogo receptor-interacting protein) is an important component of the NgR receptor complex involved in RhoA activation and axon regeneration. The authors report on passive immunization with LINGO-1 polyclonal antiserum, a therapeutic approach to overcome NgR-mediated growth inhibition after spinal cord injury (SCI). The intrathecally administered high-titer rabbit-derived antiserum can be detected around the injury site within a wide time window; it blocks LINGO-1 in vivo with high molecular specificity. In this animal model, passive immunization with LINGO-1 antiserum significantly decreased RhoA activation and increased neuronal survival. Adult rats immunized in this manner show recovery of certain hindlimb motor functions after dorsal hemisection of the spinal cord. Thus, passive immunotherapy with LINGO-1 polyclonal antiserum may represent a promising repair strategy following acute SCI.

Purpose: Spinal cord injury (SCI) results in severe neurological deficit. However, the functional recovery following SCI is very poor due to the neural lost and limited axonal regeneration. To date, there was no effective treatment. Recent studies have shown that bone marrow stromal cells (BMSCs) transplantated into the central nervous system (CNS) can survive and differentiate into neuronal-like cells. Additionally, granulocyte colony-stimulating factor (G-CSF) can mobilize hematopoietic stem cells and inhibit neural cell apoptosis. Thus, we aimed to evaluate the combined effect of BMSC transplantation and G-CSF administration on rats with traverse spinal cord injury., Methods: BMSCs were cultured in vitro, labeled with Hoechst33342, and then transplanted into the lesion site with or without G-CSF administration (50 microg/kg/day) for 5 subsequent days. The groups included an untreated control, along with treatment by G-CSF alone, BMSCs alone, and G-CSF + BMSCs., Results: In this study, by the end of eighth week after SCI injury, the animals in group treated with G-CSF + BMSCs showed higher BBB scores than the other two groups. Morphometric assessment showed that the lesion areas in the rats of the G-CSF + BMSCs group were much smaller. Compared with the control, BMSC, and G-CSF groups, less expression of apoptosis cells and more neural-cell markers around the spinal cord injury were found in rats treated with G-CSF + BMSCs., Conclusions: The animals with the combination treatment achieved a better functional and morphologic recovery, although partial. This synergistic effect between BMSCs and G-CSF may be attributed to extrinsic and endogenous neurogenesis in the traverse spinal cord injury.

Objective: To investigate the biocompatibility of a novel cavernous nickel-titanium alloy with rat bone marrow stromal cells (BMSCs) in vitro., Methods: Rat BMSCs were cultured on the surface of compact, microporous and macroporous nickel-titanium alloys, and the cell proliferation on day 3 during the culture was assessed using MTT assay. On day 7 of the cell culture, the cells were labeled with Hoechst33342 for cell counting under a fluorescence microscope. Scanning electron microscopy (SEM) was performed on day 7 of cell culture to observe the morphological changes of the cells., Results: The cell proliferation rate and cell numbers differed significantly between the cavernous alloy groups and the compact alloy group (P<0.05), but similar between the former two groups (P>0.05). SEM showed that compared with the compact alloy, microporous and macroporous nickel-titanium alloys had better biocompatibility with the BMSCs, and the cells on the surface of the cavernous alloys had normal cell morphology., Conclusion: Cavernous nickel-titanium alloy has good biocompatibility and can promote the adhesion, aggregation and proliferation of rat BMSCs in vitro.

Bone marrow stroma cells-derived neural stem cells (BMSCs-D-NSCs) transplantation is a promising strategy for the treatment of nervous system disorders. The development of a non-invasive method to follow the fate of BMSCs-D-NSCs in vivo is very important for the future application of this treatment. In this paper, we show for the first time, that BMSCs-D-NSCs from rhesus monkeys can be labeled in vitro with the superparamagnetic iron oxide (SPIO) contrast agent Feridex and Poly-L-lysine (PLL) without affecting morphology, cell cycle, telomerase activity, proliferation and differentiation ability of the labeled cells. Furthermore, when autografted into the striatum, these cells survived, differentiated and were incorporated into the brain, and could be reliably tracked using MRI, as confirmed by histological examination of the grafting sites with PKH(67) fluorescence. These results suggest that Feridex labeling of BMSCs-D-NSCs is feasible, efficient and safe for MRI tracing following autografting into the rhesus monkey nervous system.

Human mesenchymal stem cells-like cells (hMSCs-like cells) were used as a tumor treatment platform for the systemic delivery of immunotoxin genes. VEGF165-PE38 recombinant immunotoxin served as the model system. hMSCs-like cells were isolated, expanded, and electroporated with the pIRES2-VEGF165PE38-EGFP plasmid. RT-PCR and ELISA were used to confirm the expression of VEGF165-PE38 in the transfected hMSCs-like cells. These cells released 1390 +/- 137 pg VEGF165-PE38/10(4)cells over 48 h into the culture medium and the supernatant was capable of selectively killing human umbilical vein endothelial cells (HUVECs) and increasing apoptosis in these cells. In contrast, RPMI8226 was not inhibited by identical supernatants. Thus, these results lay the foundation for further studies on the potential role of hMSCs-like cells as a targeted therapeutic delivery vehicle for immunotoxins.

Background: The diagnostic value of virtual imaging combined with three-dimensional computed tomographic angiography (3D-CTA) for intracranial aneurysms has not been fully elucidated yet. This study aimed to evaluate the value of combined application of virtual imaging techniques and 3D-CTA in diagnosing patients with aneurismal subarachnoid hemorrhage (SAH) at the acute stage., Methods: Eighty patients with non-traumatic SAH received 3D-CTA examinations. The raw CT data of these patients were reconstructed and transferred into the 3D mode through the surgical plan system based on virtual reality (VR) image, and the 3D virtual images of skulls and brain blood vessels were acquired. The location, size and shape of aneurysms and their anatomic relationship with adjacent tissues were measured from many points of view., Results: Seventy-three aneurysms were detected in 68 of the 80 patients, but 2 aneurysms were detected in 2 of the 5 patients who had been found free of aneurysms previously and had received 3D-CTA examinations for a second time one month later. The 3D virtual images produced by the virtual imaging system were clear and vivid, and they could reveal the location and size of the aneurysm and its relations to the parent artery and skull directly., Conclusions: The imaging of 3D-CTA is convenient, reliable and fast in diagnosing intracranial aneurysms and can be regarded as the first choice for the diagnosis and treatment of ruptured intracranial aneurysms. Combined with the surgical plan system based on the VR image, 3D-CTA may obtain more imaging information about aneurysms.

By using chlorophyll fluorescence kinetics technique, the effects of different irrigation intervals, i.e., 5 d (T1), 10 d (T2), 15 d (T3), 20 d (T4), and 25 d (T5), on the photosynthesis of 2-year Tieguanyin tea plants were investigated in the field, with no irrigation as the control. The results showed that the leaf water potential and chlorophyll content decreased with increasing irrigation interval, while the net photosynthesis (P) increased first and decreased then, reaching its highest value (15.55, micromol x m(-2) x s(-1)) in treatment T2. The ratio of the variable to maximal fluorescence (F(v)/F(m)), the variable fluorescence quenching (deltaF(v)), and the variable fluorescence quenching rate (deltaF(v)/F(o)) all got the highest in treatment T2, being 0.844, 342.5, and 4.03, respectively. The initial fluorescence (F(o)) decreased with increasing irrigation interval, while a reverse changing trend of F(o) was observed in the control, demonstrating that PS II reaction center was damaged by drought stress. In conclusion, irrigating per 10 d was favorable to the photosynthetic electron transport and CO2 assimilation of the tea plants, which would enhance their photosynthesis efficiency.

Objective: To evaluate the perfusion characteristics of the peritumoral brain edema of intracranial meningiomas using 16-slice spiral CT perfusion imaging., Methods: Dynamic contrast-enhanced single-location sequence CT scan was performed in 19 patients with intracranial meningiomas and peritumoral brain edema. The regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) and the mean transit time (MTT) were calculated for the peritumoral brain edema and the contralateral white matter and comparatively analyzed., Results: The rCBF and rCBV in the peritumoral brain edema were significantly lower than those of the contralateral white matter in patients with meningiomas (rCBF: 14.26-/+7.44 vs 26.92-/+15.71 ml/100 g tissue.min, P<0.05; rCBV: 0.96-/+0.35 vs 2.47-/+1.69 ml/100 g tissue, P<0.05). But the MTT showed no significant difference between the peritumoral brain edema and the contralateral white matter (P>0.05)., Conclusion: The rCBF and rCBV are significantly lowered in the peritumoral brain edema in comparison with those of the contralateral white matter. Vascular compression by the edema fluid may have a major effect on the tissue blood flow and blood volume.

Objective: To investigate the correlation between power Doppler vascularity index (PDVI) and microvessel density (MVD) and evaluate the angiogenesis in high-grade gliomas and the adjacent edema in patients with glioma using intraoperative power Doppler ultrasound (PDUS) during gross total resection., Methods: In 25 cases of high-grade gliomas undergoing gross total tumor resections, PDUS was performed intraoperatively and the regions of interest within the tumor and the adjacent edema were analyzed with Photoshop software to measure the tumoral and peritumoral blood flow quantified as PDVI. The tumoral and adjacent MVD were determined using immunohistochemical staining for CD34. The correlation between PDVI in the gliomas and the adjacent edema and MVD in the corresponding areas were analyzed using Spearman correlation test., Results: The measurement of both PVDI and MVD revealed significant difference in vascularity between the gliomas and the adjacent edema (t=0.000, P<0.01), and PDVI was positively correlated to MVD measurement (r=0.7248 in the tumors and r=0.6608 in the adjacent edema)., Conclusions: The difference in the vascularity between the tumor and adjacent edema allows their distinction by PDUS during operation for high-grade glioma. Intraoperative PDUS provides an accurate and reliable means for measuring vascularity in the glioma and the adjacent edema tissue.

Objective: To investigate the value of virtual imaging technique in diagnosis of intracranial aneurysms., Methods: Fifty-four cases of 54 intracranial aneurysm diagnosed by three-dimensional CT angiography (3D-CTA) examinations were enrolled in this study. Three-dimensional virtual images of the skull and cerebral vessels were acquired by three-dimensional reconstruction of the original CT images using the surgical planning system, and the location, size and shape of the aneurysms and their anatomical relationship with the adjacent tissues were observed and measured from several angles. All the patients underwent surgical planning and simulated surgical operations using the virtual surgical instruments available in the system., Results: All the 54 cases had successful three-dimensional virtual image reconstruction and the surgical planning operations. The virtual imaging system generated clear and vivid three-dimensional virtual images which clearly visualized the location and size of the aneurysms and their precise anatomical relations to the parent arteries and skull. This virtual reality imaging system also allowed simulation of simple surgical procedures., Conclusion: The surgical planning system based on the virtual reality imaging can serve as a useful means to assist the diagnosis and provide precise imaging details of intracranial aneurysms.

Objective: To investigate the anti-tumor effects of melittin against malignant human glioma cells in vitro., Methods: Two malignant human glioma cell lines (U87 and U251) were treated with melittin at various concentrations, and the cell growth inhibition and apoptosis were evaluated using MTT assay, flow cytometry and agarose gel electrophoresis., Results: Melittin could obviously inhibit the proliferation of the two glioma cell lines (P<0.05). At the concentrations of 1, 10, 20, 40, 80, 160, 200 mg/L, melittin resulted in U87 cell apoptosis rates of 12.80%, 16.92%, 22.69%, 34.05%, 41.82%, 59.87%, and 80.25%, and in U251 cell apoptosis rate of 11.61%, 16.21%, 22.03%, 30.57%, 41.10%, 58.33%, and 79.12%, respectively, showing a dose-dependent effect in its action of inducing cell apoptosis., Conclusion: Melittin inhibits the proliferation and induces apoptosis of malignant human glioma cell lines in vitro.

Appreciation of the different methods of tissue handling is a prerequisite to obtaining accurate and biologically relevant tissue-based information. When a tissue sample is removed from its environment, biological changes are induced within its constituent cell population. It is inevitable that artefacts will be induced through obtaining and processing tissues, irrespective of whether the samples comprise a few cells derived by fine-needle aspiration or larger specimens obtained surgically. Depending upon the level of sophistication of the analytical methods subsequently employed, such changes might be irrelevant, or might result in acquisition of spurious data. While even brief ischemia alters expression of some genes, detectable by appropriate molecular techniques, the same changes might make no appreciable difference to tissue histomorphology. Furthermore, the phenotype of viable cells is known to change during tissue collection and handling. For example, transitional epithelial cells voided in urine are not phenotypically identical to those retained within the urothelium. Such phenotypic changes are temporary and might be of little consequence to subsequent analyses. Surprisingly, many cells in tissues preserved in an ischemic state can remain viable for several hours, and are believed to remain genotypically stable in the short term.

Objective: To investigate the effect of N-acetyl-cysteine (NAC) and depakine (DP) on the changes of membrane potential and peroxidate in rat cortex neurons exposed to ferrous chloride (FeCl(2))., Methods: Cultured cortex neurons of newly born SD rats were randomly divided into control group (PBS group), model group (FeCl(2) group), NAC pretreatment group (NAC group), DP pretreatment group (DP group) and NAC+DP pretreatment group (NAC+DP group). In the latter three groups, NAC (0.08 mg/ml) and DP (0.1 mg/ml) were added in the cell culture 2 and 3 h before FeCl(2) (1 mmol/L) exposure, respectively. After exposure to FeCl(2), the membrane potential of the neurons was detected with fluorescent dye DiBAC4(3) (bis-(1,3-dibutylbarbituric acid) trimethine oxonol), and the peroxidate level with 2,7-dichlorofluorescin diacetate (H(2)DCF) by laser confocal scanning microscope (LCSM) and nuclear factor-KappaB (NF-KappaB) level with immunocytochemistry., Results: Compared with FeCl(2) group, the expression of NF-KappaB and peroxidate level in the neurons were decreased significantly in NAC and NAC+DP groups (P<0.01), but not in DP group (P>0.05). FeCl(2) depolarized the membrane potential and increased the expression of NF-KappaB in the neurons. Compared with FeCl(2) group, significant changes in the membrane potential were observed in DP and NAC+DP groups (P<0.01) but not in NAC or PBS group (P>0.05)., Conclusion: Both NAC and DP can protect the neurons from FeCl(2)-induced damage but through different pathways, and their combined use can significantly alleviate neuronal damages due to FeCl(2) exposure. Antioxidants such as NAC in combination with antiepileptic drugs may produce favorable effect in prevention and treatment of posttraumatic epilepsy.

Objective: To assess the value of (1)H-magnetic resonance spectroscopy ((1)H-MRS) in evaluating cerebral vasospasm resulting from subarachnoid hemorrhage (SAH)., Methods: Six dogs were subjected to autologous non-heparinized blood injection via cisternal puncture twice at one-day interval to establish models of SAH, and another 6 received injections with normal saline in an identical manner. (1)H-MRS scan was performed on the 3rd, 7th and 14th days after the injections to measure the changes of N-acetylaspartate (NAA), creatine (Cr) and choline (Cho). After the (1)H-MRS scan, all the dogs underwent brain digital subtraction angiography (DSA) for determining the basilar artery diameter., Results: DSA results on day 3 presented development of obvious vasospasm of the basilar artery, which was most evident on day 7 and recovered obviously on day 14. (1)H-MRS results demonstrated obvious changes of NAA, Cho and Cr on days 3 and 7 in SAH model group, and NAA declined to the lowest level on day 3 followed by gradual ascending till reaching the normal level on day 14. Cho decreased slightly on day 3, then increased and reached the peak level on day 7 and then decreased. Cr rose steadily from day 3 to 14, but since day 7, the rise slowed down obviously and Cr maintain a level not significantly different from that on day 14 (P>0.05). The functional results of (1)H-MRS were consistent with the DSA results., Conclusion: (1)H-MRS can be used to monitor the development of cerebral vasospasm resulting from SAH as a good evaluation method for functional imaging.

Objective: To detect 3-dimensional images of anti-N-methyl-D-aspartate receptor Nr1 (NMDAr1) polycolonal IgG affixed on mica in physiological environment., Methods: The images and data were obtained from a contact mode and commercial Si3N4 probed tip by using atomic force microscope (AFM)., Results: The anti-NMDAr1 polycolonal IgG has a characteristic structure described as an ellipse spherical shape of 136.4 A x 62.8 A x 26.1 A. On the section of the ellipse edge there were two peaks about 13 nm in width., Conclusions: Using AFM to investigate biomacromolecule can make us deeply understand the structure of IgG, which will instruct us to detect the membrane receptor protein as a labelling agent.

Objective: To study the changes of heat shock protein 70 (HSP70) in the brain of rabbits with craniocerebral missile injury (CMI) and their impact on the injury in a hot and humid environment (HHE)., Methods: Twenty-four New Zealand white rabbits were randomized into 3 equal groups, namely normal temperature (NT) control group (subjected to treatment at temperature of 22.0+/-0.5 degrees C with relative humidity of 50%), NT gunshot group with CMI and HHE gunshot group with CMI. The rabbits in the latter two groups were subjected to normal temperature of 22.0+/-0.5 degrees C with relative humidity of 50% and environmental temperature of 39.0+/-0.5 degrees C with relative humidity of 80% to 85%, respectively, after establishment of CMI models. HSP70 in the brain tissues and lymphocytes was detected by Western blotting and visualized using chemoluminescence and X-ray films, followed by quantitative gel image analysis., Results: Expressions of HSP70 in the cortex, hypothalamus and lymphocytes increased apparently in HHE gunshot group, and the changes of HSP70 in the lymphocytes were consistent with those in the cerebral cortex and hypothalamus., Conclusion: HSP70 expression in the brain tissues and the lymphocytes increase evidently after MCI in HHE.

Objective: To study the activation of p38 mitogen-activated protein kinase (MAPK) in the brain of rabbits after craniocerebral gunshot injury in a hot and humid environment (HHE) and explore its possible mechanism., Methods: Craniocerebral gunshot injury model was established in 30 New Zealand white rabbits, which were subsequently exposed to environment of normal temperature (at 22.0% +/- 0.5 degrees C; with relative humidity of 50%) or HHE at 39.0 +/- 0.5 degrees C; with relative humidity of 80%-85% for 10 min, 30 min, 1 h, 1.5 h, and 2 h groups, respectively, with 5 rabbits in each group. p38 MAPK activity in the brain tissues of the rabbits following the injury and environmental exposure were detected by Western blotting and analyzed semi-quantitatively by Bio-Profil gel image analysis system., Results: p38 MAPK activity in the cortex and hypothalamus was significantly elevated following gunshot injury and HHE exposure, reaching the peak level at 1 h of HHE exposure and then decreased. p38 MAPK activity was significantly higher in the hypothalamus than in the cortex., Conclusion: p38 MAPK activity increases in the early stage following craniocerebral gunshot injury and HHE exposure in rabbits, the mechanism of which might involve the secondary brain insult.

Objective: To determine the three-dimensional (3D) conformation of staphylococcal protein A-gold (SPA-G) single molecule using atomic force microscope (AFM) so as to evaluate the feasibility of using this molecule for in situ labeling of the neuronal membrane protein., Methods: AFM was used to acquire the images of SPA-G binding to the surface of mica under physiological condition for determining the 3D conformation of the molecule., Results: SPA-G single molecule was shown to contain a characteristic structure with a chain in the shape of mirror image of the letter C, which had the dimension of 48.80 nm x 42.13 nm x 20.53 nm., Conclusion: AFM provide a new means for morphological investigation of the biomacromolecule at the nanometer scale in physiological conditions, and SPA-G can be utilized for in situ labeling of the neuronal membrane receptors.

Objective: Atomic force microscope (AFM) is one of the most recent imaging and manipulation techniques in biological science. Among its various merits, AFM typically enables simple sample preparation, acquisition of three-dimensional images to identify single atoms under different conditions, detection of the interactive forces between two single biomolecules and their manipulation. AFM is currently applied in the research of the structure and function, at the nanometric scale, of various tissues, cells, microbes and biomolecules, and studies of the interaction between two biomolecules as well as the manipulation of some biological processes. AFM possesses the potential to become an important instrument in life science research, in spite of its current limits that require improvements such as in carbon nanotube tip, rigidity of soft biological samples and result interpretation.

Objective: To investigate the therapeutic effect of photodynamic therapy (PDT) combined with interstitial chemo- therapy on gliomas after microsurgery., Methods: Twenty-eight patients with glioma received microsurgery for glioma resection as much as possible, during which PDT was carried out and an Ommaya bursa implanted into the cavity left by the resected tumor. PDT was performed again 24 h after the operation and carmustine injected into the Ommaya bursa for interstitial chemotherapy at the different time after the operation. The follow-up study lasted for 2 years., Results: Two of the 28 patients had relapse of glioma within 1 year after the operation, with the 1-year survival rate of 89.3% (25/28) and 2-year survival rate of 65.7% (17/28)., Conclusions: PDT combined with interstitial chemotherapy following microsurgery provides a safe and effective treatment of glioma, which can inhibit glioma growth, decrease the recurrence rate, prolong the patients' survival and improve their quality of live.

Objective: To investigate the changes in subcellular localization of NMDAR1 on cultured cortical neurons in response to different methods for fixation of neuron cells., Methods: Subcellular localization of NMDAR1 in cultured cortical neurons fixed with different fixatives and procedures was studied by immunocytochemical avidin-biotin peroxidase (ABC) method., Results: Neurons fixed with -20 degrees Celsius pure acetone and -20 degrees Celsius pure methanol for 5 min presented typical positive staining of NR1 subunit located on the polar membrane of the neurons where the dendrites originated and on the stem of the dendrites. The neurons fixed with 4% formaldehyde alone for 20 min or in the presence of 0.5% glutaraldehyde (1:1) for 10 min resulted in false-negative staining. Fixation of the neurons with 95% ethanol for 10 min yielded false-negative staining on the membrane and false-positive staining in the nuclei., Conclusions: Each antigen may have its specific demand for fixation method in immunocytochemistry, and for NMDAR1 antigen, mild fixation is recommended as by -20 degrees Celsius pure acetone and -20 degrees Celsius pure methanol for 5 min. NMDAR1 distributes on the polar membrane of the neurons where the dendrites originate and on the dendritic stem.

Objective: To analyze the clinical characteristics, pathogenesis and management of traumatic interhemispheric subdural hematomas (ISH)., Methods: Thirty-one traumatic ISH cases were reviewed and analyzed retrospectively., Results: Of the 31 patients, 29 were cured and 2 died of multi-system organ failure (MSOF) and cerebral hernia respectively. Typically, ISH manifested hemiplegia or paralysis of the counterlateral lower limb known as falx syndrome., Conclusions: CT scans showing hematocele in the interhemispheric subdural space in excess of 20 ml, or with a thickness of hematocele over 1cm, may serve as a diagnostic criteria for ISH. For the treatment of ISH, surgery and conservative management are suggested on the basis of functional disturbance or the stability of the disease.