Multi-Objective Optimization of Curing Profile for Autoclave Processed Composites: Simultaneous Control of Curing Time and Process-Induced Defects.

The contribution of this work is introducing a multi-objective optimization method based on finite element (FE) numerical simulation to simultaneously control the curing time and cure-induced defects of C-shaped composites during a curing cycle. Thermochemical and thermomechanical coupled analysis is performed and validated experimentally to understand the evolution details of temperature, degree of cure and curing deformation. Aiming to achieve the simultaneous control of manufacturing cost and composite quality, the curing profile is optimized by employing the critical factors including the total curing time, the maximum degree of cure difference, and the curing deformation. The optimization result shows that the designed curing profile can effectively reduce the curing time and guarantee the curing quality. The total curing time of the optimization is reduced by 19%. The verification experiment is also conducted to prove the accuracy and effectiveness of the proposed optimization method.

Chiari Malformations Type I without Basilar Invagination in Adults: Morphometric and Volumetric Analysis.

BACKGROUND: Chiari malformation type I (CMI) cases are frequently associated with basilar invagination (BI), which complicates the understanding of the pathology of CMI. We specifically evaluated the morphometric and volumetric alterations in the bony structures of CMI patients without BI. METHODS: Fifty adult CMI patients without BI treated at our institution from January 2015 to December 2019 were retrospectively studied. The morphometric and volumetric characteristics of the posterior cranial fossa (PCF) were analyzed using thin-slice computed tomography images. RESULTS: Compared with the controls, the clivus length (P < 0.001), supraoccipital length (P < 0.001), Klaus height index (P < 0.001), axial length (P < 0.001), clivo-axial angle (P < 0.001), tentorial angle (P < 0.05), and bony PCF volume (P < 0.001) of the CMI-only group were significantly smaller, and the distance between the Chamberlain line and the dens axis (P < 0.001), clivus angle (P < 0.001), and basal angle (P < 0.001) of the CMI-only group were significantly larger, while the distance between the McRae line and the dens axis, McRae line, anteroposterior diameter of the PCF, occipital angle, occipital canal angle, and tentorial Twining line angle showed no significant difference between the 2 groups. CONCLUSIONS: Hypoplasia of the clivus and occipital bone were confirmed in CMI patients without BI, thus providing further evidence for the notion that CMI is secondary to the underdevelopment of the PCF.

Preparation and evaluation of regioselectively substituted amylose derivatives for chiral separations.

Six novel regioselectively substituted amylose derivatives with a benzoate at 2-position and two different phenylcarbamates at 3- and 6-positions were synthesized and their structures were characterized by 1 H nuclear magnetic resonance (NMR) spectroscopy. Their enantioseparation abilities were then examined as chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC) after they were coated on 3-aminopropyl silica gels. Investigations indicated that the substituents at the 3- and 6-positions played an important role in chiral recognition of these amylose 2-benzoate serial derivatives. The derivatives demonstrated characteristic enantioseparation and some racemates were better resolved on these derivatives than on Chiralpak AD, which is one of the most efficient CSPs, utilizing coated amylose tris(3,5-dimethylphenylcarbamate) as the chiral selector. Among the derivatives prepared, amylose 2-benzoate-3-(phenylcarbamate/4-methylphenylcarbamate)-6-(3,5-dimethylphenylcarbamate) exhibited chiral recognition abilities comparable to that of Chiralpak AD and may be useful CSPs in the future. The effect of mobile phase on chiral recognition was also studied. In general, with the decreased concentration of 2-propanol, better resolutions were obtained with longer retention times. Moreover, when ethanol was used instead of 2-propanol, poorer resolutions were often achieved. However, in some cases, improved enantioselectivity was achieved with ethanol rather than 2-propanol as the mobile phase modifier.

Serotonergic projections to lumbar levels and its plasticity following spinal cord injury.

The descending serotonergic pathway, which originates in various populations of brainstem neurons, plays an important role in generating the rhythmic motor pattern associated with locomotor movement. Although the development of its innervation has been studied in rodent spinal cord, it has not been clearly identified how the projection of serotonergic pathway is related to its function. Here, we evaluated the pattern of serotonergic innervation on the lumbar spinal cord from embryonic day 14.5 (E14.5) to adulthood. Before birth, we found that 5-hydroxytryptamine (5-HT) fibers invade the lumbar cord as early as E14.5, penetrate into the gray matter from lateral funiculus by E16.5, and then mainly occupied the ventral horn by E18.5 before localizing in the dorsal horn. After birth, we found that 5-HT invasion of both dorsal horn and ventral horn were present by the 7th postnatal day (P7). Additionally, the 5-HT innervation of these two areas evolved progressively from a diffuse network to a more restricted pattern, particularly at the ventral horn within the motoneuron area from P21 to adulthood. This 5-HT innervation pattern in the lumbar cord provides anatomical evidence that serotonergic fibers establish direct connections with lumbar motoneurons, which offers us a solid foundation that enhancing the plasticity of serotonergic pathway following SCI may facilitate locomotor functional recovery. Therefore, we employed treadmill training to activate serotonergic plasticity after SCI. We found that mice which underwent treadmill training exhibited a better locomotor functional recovery. Meanwhile, the density of 5-HT fibers in the ventral horn was significantly increased and the synaptic formation of 5-HT fibers with lumbar motoneurons was also significantly rescued in the training group mice after SCI. These findings demonstrate that the descending serotonergic projection is a robust and flexible parallel pathway for modulating spinal locomotor function.

Resistance of interleukin-6 to the extracellular inhibitory environment promotes axonal regeneration and functional recovery following spinal cord injury.

Interleukin-6 (IL)-6 was originally discovered as a factor that contributes to the secondary pathological and inflammatory response in the central nervous system (CNS) following injury. However, accumulating evidence suggests that IL-6 is also involved in functional and structural recovery following CNS injury by promoting axonal sprou-ting. This suggests a potential dual role of IL-6 in CNS injury. However, the definitive function of IL-6 in neural injury and the corresponding underlying mechanisms are still topics of controversy. The present study was carried out to examine the potential function of IL-6 in resistance to neurite growth­inhibitory effects via regulation of the expression of growth associated protein-43 (GAP-43), myelin-associated neurite outgrowth inhibitor (Nogo-A) and its receptor (NgR). Rat dorsal root ganglion (DRG) neurons cultured in an inhibitory microenvironment mimicking injured CNS were used to investigate the effects of IL-6 on the outgrowth of neuronal processes. Additionally, IL-6 was subarachnoidally injected into rats to establish a spinal cord injury (SCI) model, and the neurobehavioral manifestations and neural morphology were subsequently evaluated to determine the effect of IL-6 on neural regeneration. Finally, the potential molecular mechanisms of IL-6-mediated rege-neration and functional recovery following CNS injury are discussed. The results of the present study demonstrated that the in vitro administration of IL-6 enhanced the neurite outgrowth of DRG neurons in a dose-dependent manner via resisting the inhibitory function of myelin proteins. All doses of the IL-6 subarachnoid injection improved the Basso, Beattie and Bresnahan scores following SCI, with a large number of axonal sproutings observed at the spinal lesion site, and several sprouting fibers being elongated and bypassing the lesion and entered the caudal spinal cord. Additionally, a significantly increased density area of diaminobenzidine-labeled neural fiber was observed in rats that received a subarachnoid injection of IL-6, and the rats exhibited increased expression of GAP-43 and decreased expression of Nogo-A. In conclusion, the results of the present study indicated that IL-6 interferes with the inhibitory functions of myelin proteins by upregulating the expression of GAP-43 and simultaneously downregulating the expression of Nogo-A and NgR to promote axonal sprouting and functional recovery following SCI.

The Critical Role of SRPK1 in EMT of Human Glioblastoma in the Spinal Cord.

Up to now, the serine-arginine protein kinase 1 (SRPK1) has been suggested as an important signal mediator, which is implicated in the development of cancers. Unfortunately, some molecular pathways in SRPK1-mediated epithelial-mesenchymal transition (EMT) in human spinal glioblastoma have been not elucidated. In this work, we detected the expression of SRPK1 in human spinal glioblastoma tissues and GBM cell lines and analyzed the relevant molecular proteins using in vitro experiments, including RT-PCR, gene silencing, and Western blot. In this study, RT-PCR and Western blot revealed that the expression of SRPK1 mRNA and protein became higher in all six spinal glioblastoma specimens; however, its expression was low in matched normal specimens. We also demonstrated SRPK1 expression facilitated the proliferation of U87 and U251 cells and inhibited the apoptosis in U87 and U251 cells. Also, SRPK1 promoted the expression of EMT-regulating markers, involving N-cadherin, Snail, and MMP9 and decreased the expression of mesenchymal marker E-cadherin. Moreover, knockdown of SRPK1 significantly inhibited the expression levels of p-Akt rather than t-Akt. In conclusion, knockdown of SRPK1 inhibited glioblastoma cell proliferation, invasion, and EMT process via suppressing p-Akt signaling pathway. This study also lays a new foundation for the clinically biological treatment.

Syntenin is expressed in human gliomas and may correlate with tumor migration.

INTRODUCTION: Invasion is usually recognized as the main reason for the high recurrence and death rates of gliomas. Therefore, properly understanding the molecular mechanisms of migration and invasion of human gliomas has become a focus and will be helpful for the treatment of gliomas. Syntenin has been demonstrated to be implicated in the migration, invasion and metastasis of many types of malignant tumors. Therefore, we investigated the expression of syntenin in human gliomas and its relationship with glioma migration. MATERIAL AND METHODS: Immunohistochemistry, Western blot and real time-polymerase chain reaction (RT-PCR) were performed to detect the expression of syntenin in human gliomas. Phosphorylated FAK in human gliomas was examined by western blot. RESULTS: Scattered syntenin positive glioma cells were detected by immunohistochemistry in normal tissue. Syntenin expression in grade II, III and IV gliomas increased with the degree of tumor malignancy, and no syntenin expression was detected in grade I gliomas. The level of phosphorylated FAK at the tyrosine 397 site also elevated with the degree of tumor malignancy. There was a positive correlation between the syntenin level and the pathological grade of gliomas (r s = 0.896, p < 0.05). Phosphorylated FAK was also upregulated along with the stage of glioma progression and the increase of syntenin expression. CONCLUSIONS: Our results indicate that the enhanced expression of syntenin and phosphorylated FAK may correlate with the increase of the malignancy of human gliomas. Syntenin may promote human glioma migration through interaction with FAK.

[Impact of topographic features of electrospun polymethylmethacrylate nanofibers on growth pattern of rat primary astrocytes].

OBJECTIVE: To evaluate the impact of the topographic features of electrospun polymethylmethacrylate (PMMA) nanofibers on growth pattern of primary rat astrocytes. METHODS: Rat astrocytes were cultured on fabricated random and aligned electrospun nanofibers. Using PMMA film as the control, the cells were transfected with a lentivirus harboring GFP gene to reveal the cell growth pattern on different substrates. RESULTS: oth random and aligned electrospun PMMA nanofibers could support the growth of rat astrocytes, but the topographic features of the fibers significantly affected their growth pattern. On aligned nanofibers, astrocytes extended long cell processes along the direction of the substrate fibers, and on random fibers the astrocytes formed shorter processes. On merged images of GFP expressions and substrate fibers, the cell processes of the astrocytes were shown to adhere to and elongate along the fibers both on random and aligned nanofibers. CONCLUSION: The topographic features of PMMA nanofibers can significantly influence the growth pattern of primary rat astrocytes. Aligned electrospun nanofibers has the potential to serve as scaffold material for reducing glia scar formation after spinal cord injury.

The synthesis and characterization of monodispersed chitosan-coated Fe3O4 nanoparticles via a facile one-step solvothermal process for adsorption of bovine serum albumin.

Preparation of magnetic nanoparticles coated with chitosan (CS-coated Fe3O4 NPs) in one step by the solvothermal method in the presence of different amounts of added chitosan is reported here. The magnetic property of the obtained magnetic composite nanoparticles was confirmed by X-ray diffraction (XRD) and magnetic measurements (VSM). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) allowed the identification of spherical nanoparticles with about 150 nm in average diameter. Characterization of the products by Fourier transform infrared spectroscopy (FTIR) demonstrated that CS-coated Fe3O4 NPs were obtained. Chitosan content in the obtained nanocomposites was estimated by thermogravimetric analysis (TGA). The adsorption properties of the CS-coated Fe3O4 NPs for bovine serum albumin (BSA) were investigated under different concentrations of BSA. Compared with naked Fe3O4 nanoparticles, the CS-coated Fe3O4 NPs showed a higher BSA adsorption capacity (96.5 mg/g) and a fast adsorption rate (45 min) in aqueous solutions. This work demonstrates that the prepared magnetic nanoparticles have promising applications in enzyme and protein immobilization.

Directed neurite growth of rat dorsal root ganglion neurons and increased colocalization with Schwann cells on aligned poly(methyl methacrylate) electrospun nanofibers.

Electrospun nanofibers are promising scaffolds for peripheral and central nervous system repair. The aim of this study was to examine the details of neurite growth of rat dorsal root ganglion neurons (DRGn) on randomly oriented and aligned poly(methyl methacrylate) (PMMA) nanofibers and the relationship between neurites and nanofibers on each substrate. Our substrate design involved electrospinning PMMA nanofibers directly onto bare glass coverslips with acceptable biocompatibility. We cocultured DRGn and Schwann cells on PMMA nanofibers and evaluated their response to each substrate. Compared with neurons cultured on PMMA film and randomly oriented nanofibers, DRGn on aligned PMMA nanofibers formed longer, parallel neurites in accordance with the orientation of the substrate nanofibers, although the average neurite number did not differ among the three groups. Regarding the relationship between neurites and nanofibers, the neurites of DRGn were in close contact with the substrate nanofibers, and the neurites seemed to follow aligned nanofibers more than randomly oriented nanofibers. Coculturing DRGn and Schwann cells on PMMA nanofibers revealed that on aligned nanofibers, neurites and Schwann cells had a higher chance of colocalization than on randomly oriented nanofibers or film; this colocalization may be beneficial during the process of myelination that follows. The results of this study enhance our understanding of the ability of aligned electrospun nanofibers to provide contact guidance to neural cells and strengthen the rationale for future in vivo studies.

Mda-9/syntenin promotes human brain glioma migration through focal adhesion kinase (FAK)-JNK and FAK-AKT signaling.

Invasion is usually recognized as the main reason for the high recurrence and death rates of glioma and restricts the efficacy of surgery and other therapies. Therefore, we aimed to investigate the mechanism involved in promotion effects of mda-9/syntenin on human glioma cell migration. The wound healing method was used to test the migration ability of human glioma cells CHG-5 and CHG-hS, stably overexpressing mda-9/syntenin. Western blotting was performed to determine the expression and phosphorylation of focal adhesion kinase (FAK) and JNK in CHG-5 and CHG-hS cells. The migration ability of CHG-hS cells was significantly higher than that of CHG-5 cells in fibronectin (FN)-coated culture plates. Phosphorylation of FAK on tyrosine 397, 576, and 925 sites was increased with time elapsed in CHG-hS cells. However, phosphorylated FAK on the tyrosine 861 site was not changed. Phosphorylated Src, JNK and Akt levels in CHG-hS cells were also significantly upregulated. Phosphorylation of JNK and Akt were abolished by the specific inhibitors SP600125 and LY294002, respectively. and the migration ability of CHG-hS cells was decreased, indicating that the JNK and PI3K/Akt pathways play important roles in regulating mda-9/syntenin-induced human brain glioma migration. Our results indicate Mda- 9/syntenin overexpression could activate FAK-JNK and FAK-Akt signaling and then enhance the migration capacity of human brain glioma cells.

Small interfering RNA targeting Krüppel-like factor 8 inhibits U251 glioblastoma cell growth by inducing apoptosis.

Small interfering RNAs (siRNAs) are small non-coding RNAs, comprising 21-23 nucleotides that regulate gene expression by transcriptionally repressing their complementary mRNAs. In particular, Krüppel-like factor 8 (KLF8) has been postulated to function as a tumor activator in various cancer cells, but not in glioblastoma. In the present study, we investigated the anti-tumorigenic effect of KLF8 siRNA in glioblastoma cells. U251 human glioblastoma cells were transfected with KLF8 siRNA and assayed for in vitro proliferation, cell cycle and cell apoptosis. The transfection of KLF8 siRNA reduced expression of KLF8 in the glioblastoma cells. KLF8 siRNA also reduced in vitro proliferation and enhanced cell apoptosis. These results indicate that KLF8 siRNA has an anti-tumorigenic effect on glioblastoma cells and suggest the possible use of KLF8 siRNA for the treatment of glioblastoma.

Quantitative analysis of glioma cell invasion by diffusion tensor imaging.

We aimed to quantitatively analyze the invasion of glioma cells by diffusion tensor imaging (DTI). Twenty patients with glioma, who required surgical decompression, were included in this study. Peritumoral edematous regional tissues were harvested for tumor cell counting and cell density analysis to establish standards for degrees of tumor infiltration. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of water molecules in brain in five regions of interest (ROI) were measured by DTI: (i) the glioma region; (ii) peritumoral edematous tissue; (iii) surrounding edematous tissue; (iv) white matter; and (v) contralateral white matter. The correlation between FA and ADC values from different ROI, and degree of tumor infiltration was analysed. FA values tended to increase from the glioma region outwards, and the maximum amplification appeared between peritumoral edematous and surrounding edematous regions. FA values from peritumoral edematous regions were negatively correlated with the degree of glioma infiltration. ADC values increased significantly in the peritumoral edematous region, but changes in other regions were variable. FA values from peritumoral edematous regions should be used as an evaluation index for the invasion of glioma cells.

Cerebral oxygen metabolism and neuroelectrophysiology in a clinical study of severe brain injury and mild hypothermia.

Mild hypothermia has an important role in the treatment of severe brain injury and there are therapeutic windows for this technique for patients with severe brain injury. We used a randomized, controlled, clinical study to investigate indexes of cerebral oxygen metabolism and neuroelectrophysiology to evaluate the efficacy of mild hypothermia treatment in severe brain injury. A total of 148 patients (106 males and 42 females), aged 18 to 64 years with acute severe brain injury were selected from June 1998 to June 2004 from the Department of Neurosurgery at The First Affiliated Hospital of Chongqing Medical University. All patients met the inclusion criteria: admission to hospital within 10 hours of injury; Glasgow Coma Scale (GCS) score 8; age < 65 years; no other severe combined visceral injury; and no severe co-morbidities of the heart, lung, liver, kidney, or other visceral organs. Patients were divided into groups according to brain injury severity: GCS scores 7-8, 5-6, and 3-4. Patients in each GCS score group were randomly assigned to two subgroups: hypothermia and normothermia. Brain oxygen metabolism indexes (partial pressure of oxygen in brain tissue [P(br)O(2)] and regional cerebral oxygen saturation [rSaO(2)]) as well as neuroelectrophysiology indexes (short-latency somatosensory evoked potential [SLSEP] and brain-stem auditory evoked potential [BAEP]) were recorded in the normothermia and hypothermia subgroups (32-34 degrees C) prior to and after cooling for 5 days. Brain oxygen metabolism indexes (P(br)O(2) and rSaO(2)) and neuroelectrophysiology indexes (SLSEP and BAEP) were also compared for patients who underwent mild hypothermia and those who did not. For patients with GCS 7-8, SLSEP, BAEP and rSaO(2) following cooling were significantly improved in the hypothermia subgroup and the P(br)O(2) was less in the hypothermia subgroup. For patients with GCS 5-6, the SLSEP, BAEP and rSaO(2) were improved following hypothermia on some days, and the PbrO(2) was greater in the hypothermia subgroup on some days. For patients with GCS 3-4, there was no difference between the hypothermia and normothermia subgroups. We conclude that hypothermia had a significant therapeutic effect on severe brain injury of patients with GCS 7-8, had no effect on patients with GCS 3-4, and an uncertain effect on patients with GCS 5-6. The indexes of cerebral oxygen metabolism and neuroelectrophysiology indicated primary and secondary brain injury, respectively, and provided an effective way to evaluate brain injury.

Isolated cerebellopontine angle craniopharyngioma.

Primary cerebellopontine angle craniopharyngioma is rare; only 5 surgically treated patients have been reported. We report a 54-year-old female with craniopharyngioma occurring in isolation in the cerebellopontine angle and compare this patient with previously published reports. The origin of and surgical strategy for such tumors are discussed.

Correlation between APOE -491AA promoter in epsilon4 carriers and clinical deterioration in early stage of traumatic brain injury.

The objective of this work was to investigate the relationship between apolipoprotein E (APOE) promoters (G-219T, C-427T, A-491T) polymorphisms and the clinical deterioration in early stage of traumatic brain injury (TBI) in a cohort of Chinese patients. In this study, we used the cohort of patients which has been reported previously. A total of 110 subjects with TBI (80 males and 30 females, with mean age of 43.87 years) were admitted from December 2003 to May 2004, and demographic and clinical data were collected. The clinical deterioration of patient's condition in acute stage (<7 days after TBI) was judged by either of the following criteria: decrease of Glasgow Coma Scale (GCS) score (compared with initial admission GCS), increase in hematoma volume or delayed hematoma both detected by repeated computed tomography (CT) scanning compared to that on admission. Venous blood was collected from patients with TBI on admission to determine the APOE promoter polymorphisms. The APOE genotyping was performed by means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). chi(2) test and logistic regression analyses were done by SPSS. In 110 Chinese patients, the distributions of APOE genotypes and alleles matched Hardy-Weinberg Law, and 19 subjects presented with deteriorated clinical condition in acute stage after hospitalization. chi(2) test showed insignificant differences in association of APOE promoter polymorphisms with clinical deterioration (p>0.05). But logistic regression analyses, after adjusting patients' age, injury severity and injury mechanism etc, showed that -491AA (OR=11.681, p=0.009, 95%, CI 1.824-74.790) and APOE epsilon4 were all risk factors, with injury severity and alcohol-drinking as other risk factors. In Chinese population, as a significant but not independent risk factor, only APOE -491AA promoter in epsilon4 carriers is apt to the clinical deterioration and may contribute to the poor outcome after TBI.

[Correlation analysis of increased blood glucose and insulin resistance after traumatic brain injury in rats].

OBJECTIVE: To study the pattern of the alterations of blood glucose, insulin and insulin sensitivity after traumatic brain injury in rats, and verify the occurrence of insulin resistance after the injury. METHODS: Based on Feeney's model of brain injury, the blood glucose and insulin concentration of the dogs measured 30 min before and at 6, 12, 24, 48, 72 and 120 h after injury. BG60-120, GIR60-120, and insulin sensitivity index (ISI) reflecting the insulin sensitivity were measured at 6, 24, 48, and 72 hours following severe traumatic brain injury using euglycemic-hyperinsulinemic clamp. RESULTS: Both the blood glucose and insulin concentration increased markedly in rats following moderate and severe brain injury. BG60-120 increased markedly, and GIR60-120 and ISI decreased significantly 6, 24, 48, and 72 h after severe brain trauma as compared with those of the sham operation group. Blood glucose concentration of rats following severe injury was positively correlated with insulin concentration and BG60-120 at the corresponding time points, but negatively with GIR60-120 and ISI. CONCLUSION: Both the blood glucose and insulin concentration increase markedly in rats following severe brain injury. Increased blood glucose even in the presence of high-level insulin is due to acute insulin resistance occurring after traumatic brain injury.

[Clinical research about brain oxygen metabolism and neuroelectrophysiology during mild hypothermia in patients with severe head injury].

OBJECTIVE: To observe the changes of brain oxygen metabolism and neuroelectrophysiology after severe brain injury, and the effects of hypothermia on severe brain injury. METHODS: 148 patients with severe brain injury (GCS 3 - 8, admitted within 10 hours from injury) were selected for this study. Patients were divided into 3 groups, Group GCS 7 - 8, Group GCS 5 - 6 and Group GCS 3 - 4. Every group were also randomly assigned to normothermia and hypothermia subgroup. Patients in the hypothermia group were cooled to 32 approximately 34 degrees C. SLSEP, BAEP, P(br)O(2) and rSaO(2) were recorded in each group at the same time. RESULTS: In the Group GCS 7 - 8, N20 in SLSEP, I/V in BAEP and rSaO(2) were improved significantly after mild hypothermia treatment, and P(br)O(2) was decreased by hypothermia; In the Group GCS 5 - 6, N20 in SLSEP, I/V in BAEP and rSaO(2) were improved by hypothermia, and P(br)O(2) was decreased in hypothermia subgroup; In the Group GCS 3 - 4, no significant difference was found. CONCLUSION: Mild hypothermia has a significant effect on patients of GCS 7 - 8 and a doubt effect on patients of GCS 5 - 6. It seem no effect on patients of GCS 3 - 4. Brain oxygen metabolism and neuroelectrophysiology are important to value the therapeutic effect on severe brain injury.

Effect of APOE polymorphisms on early responses to traumatic brain injury.

To investigate the relationship between apolipoprotein E (APOE) polymorphisms and the severity of traumatic brain injury (TBI) in acute stage in the cohort of mainland Chinese patients. We prospectively identified admissions to the two neurosurgical departments for head injury. A total of 110 subjects with TBI (80 males and 30 females, with mean age of 43.87 years) were enrolled from December 2003 to May 2004, and demographic and clinical data were collected. Venous blood was collected from patients with TBI on admission to determine the APOE genotype polymorphisms. The APOE genotyping was performed by means of PCR-RFLP. The deterioration of patients' condition in acute stage (<7 days after TBI) was judged by either of following criteria: decrease of GCS, increase in hematoma volume or delayed hematoma both detected by repeated CT scanning. Chi2-test and logistic regression analyses were done by SPSS. The distributions of APOE genotypes and alleles matched Hardy-Weinberg law. In 110 Chinese patients, 19 subjects presented with deteriorated clinical condition after hospitalization, and seven of 17 patients with APOE epsilon4 (41.2%) had a deteriorated condition which was significantly different from those without APOE epsilon4 (12 of 93 patients, 12.9%, P=0.01). However, neither the presence of epsilon2 nor of epsilon3 was significantly different from those absent of it (P>0.05). Logistic regression analyses showed that APOE epsilon4 was a risk factor (OR=4.836, P=0.011, 95% CI 1.443-16.208) to predispose to clinical deterioration after adjusting for patient age, sex, smoking or not, alcohol-drinking or not, injury severity, injury mechanisms, treatments, and pattern of TBI. This finding suggests that the patients with APOE epsilon4 predispose to clinical deterioration in acute phase after TBI and APOE polymorphisms play a role in early responses to TBI.