Glucose-decorated engineering platelets for active and precise tumor-targeted drug delivery.

Precise targeted delivery of therapeutic agents is crucial for tumor therapy. As an emerging fashion, cell-based delivery provides better biocompatibility and lower immunogenicity and enables a more precise accumulation of drugs in tumor cells. In this study, a novel engineering platelet was constructed through cell membrane fusion with a synthesized glycolipid molecule, DSPE-PEG-Glucose (DPG). The obtained glucose-decorated platelets (DPG-PLs) maintained their resting state with structural and functional integrities, while they would be activated and triggered to release their payloads once they arrive at the tumor microenvironment. Glucose decoration was verified to impart the DPG-PLs with stronger binding effects toward tumor cells that overexpress GLUT1 on their surfaces. Together with the natural homing property toward tumor sites and bleeding injury, doxorubicin (DOX)-loaded platelets (DPG-PL@DOX) exhibited the strongest antitumor effects on a mouse melanoma model, and the antitumor effect was significantly enhanced in the tumor bleeding model. DPG-PL@DOX provides an active and precise solution for tumor-targeted drug delivery, especially for postoperative treatments.

miR-181b promotes angiogenesis and neurological function recovery after ischemic stroke.

Promotion of new blood vessel formation is a new strategy for treating ischemic stroke. Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke. miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model, while its effect on ischemic stroke remains elusive. In this study, we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell proliferation and enhanced angiogenesis. In rat models of focal cerebral ischemia, overexpression of miR-181b reduced infarction volume, promoted angiogenesis in ischemic penumbra, and improved neurological function. We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3'-UTR of phosphatase and tensin homolog (PTEN) mRNA to induce PTEN downregulation, leading to activation of the protein kinase B (Akt) pathway, upregulated expression of vascular endothelial growth factors, down-regulated expression of endostatin, and promoted angiogenesis. Taken together, these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stroke through activating the PTEN/Akt signal pathway and promoting angiogenesis.

Exploration of Risk Factors for Poor Prognosis of Non-Traumatic Non-Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a devastating neurological disease associated with high rates of mortality and disability. Aneurysms are the main cause of non-traumatic subarachnoid hemorrhages. However, non-traumatic non-aneurysmal subarachnoid hemorrhage (naSAH), another clinical type of SAH, has been poorly studied for its prognosis and risk factors. METHOD AND RESULT: We collected demographic and clinical variables for 126 naSAH and 89 aneurysmal subarachnoid hemorrhage (aSAH) patients, including age and gender; hospitalization days; hematological indicators; clinical score scales; past medical history; and personal history. We found that the monocytes in naSAH (0.50 ± 0.26) patients were lower than in aSAH patients (0.60 ± 0.27). The prevalence of diabetes in naSAH (30.2%) patients was higher than in aSAH (14.5%) patients. The naSAH patients were divided into good and poor outcome groups based on the modified Rankin Scale at the 90th day (90-day mRS) after discharge. A univariate analysis showed that there were significant differences in age, white blood cell count (WBC), monocyte count, D-dipolymer, neuron-specific enolase (NSE), random blood glucose (RBG), aspartate transaminase (AST), urea and free triiodothyronine (FT3) between the two groups. A logistic regression showed that aging and high level NSE were independent risk factors for a poor outcome. The predictive ability of age (area under curve (AUC) = 0.71) and NSE (AUC = 0.68) were analyzed by a receiver operating characteristic (ROC) curve. The results of the logistic regression suggested that age, D-dipolymer, NSE, RBG, urea and FT3 distinguished and predicted the prognosis of naSAH. The discriminant analysis of the above variables revealed that the discriminant accuracy was 80.20%. CONCLUSIONS: Compared with aSAHs, naSAHs are more likely to occur in patients with diabetes, and the level of monocytes is lower. Moreover, the prognosis of elderly patients with an naSAH is relatively poor, and the level of NSE in the course of the disease also reflects the prognosis. Multivariate comprehensive analysis is helpful to judge the prognosis of patients at a small cost.

QTL detection for bread wheat processing quality in a nested association mapping population of semi-wild and domesticated wheat varieties.

BACKGROUND: Wheat processing quality is an important factor in evaluating overall wheat quality, and dough characteristics are important when assessing the processing quality of wheat. As a notable germplasm resource, semi-wild wheat has a key role in the study of wheat processing quality. RESULTS: In this study, four dough rheological characteristics were collected in four environments using a nested association mapping (NAM) population consisting of semi-wild and domesticated wheat varieties to identify quantitative trait loci (QTL) for wheat processing quality. A total of 49 QTL for wheat processing quality were detected, explaining 0.36-10.82% of the phenotypic variation. These QTL were located on all wheat chromosomes except for 2D, 3A, 3D, 6B, 6D and 7D. Compared to previous studies, 29 QTL were newly identified. Four novel QTL, QMlPH-1B.4, QMlPH-3B.4, QWdEm-1B.2 and QWdEm-3B.2, were stably identified in three or more environments, among which QMlPH-3B.4 was a major QTL. Moreover, eight important genetic regions for wheat processing quality were identified on chromosomes 1B, 3B and 4D, which showed pleiotropy for dough characteristics. In addition, out of 49 QTL, 15 favorable alleles came from three semi-wild parents, suggesting that the QTL alleles provided by the semi-wild parent were not utilized in domesticated varieties. CONCLUSIONS: The results show that semi-wild wheat varieties can enrich the existing wheat gene pool and provide broader variation resources for wheat genetic research.

Efficiency and mechanism of reducing ammonia volatilization in alkaline farmland soil using Bacillus amyloliquefaciens biofertilizer.

Ammonia volatilization from the farmland caused by the application of synthetic nitrogen fertilizer is the most important source of anthropogenic ammonia emissions. Biofertilizer application has been considered as an alternative option for agriculture sustainability and soil improvement. In this study, field trials were carried out to investigate the efficiency of Bacillus amyloliquefaciens (BA) biofertilizer on alleviating ammonia volatilization in alkaline farmland soil and increasing crop yield and nitrogen utilization. Potential response mechanisms were investigated from soil enzyme, nitrogen cycle function genes and microbial community levels. Compared with conventional fertilization, BA biofertilizer application reduced the ammonia volatilization by 68%, increased the crop yield and nitrogen recovery by 19% and 19%, respectively. Soil enzyme activity analysis showed that BA biofertilizer inhibited the urease activity and enhanced the potential ammonia oxidation (PAO). In addition, BA biofertilizer application also increased the bacterial amoA gene abundance, while decreased the ureC gene abundance. BA biofertilizer also significantly altered the community structure and composition, and especially raised the abundance of ammonia oxidation bacteria (AOB), while no changes were observed in abundance of nitrite oxidation bacteria (NOB). Briefly, BA biofertilizer was approved to reduce the transformation of fertilizer nitrogen to NH4+-N, simultaneously accelerating NH4+-N into the nitrification process, thus decreasing the NH4+-N content remained in alkaline soil and consequently alleviating the ammonia volatilization. Thus, these results suggested that the application of BA biofertilizer is a feasible strategy to improve crop yields and reduce agricultural ammonia emissions.

Granulocyte-colony stimulating factor, a potential candidate for the treatment of Parkinson's disease.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) activates the PI3K/Akt pathway to exert neuroprotective effects. The current study aimed to determine if G-CSF reverses behavioral deficits, even after motor malfunction occurs in Paraquat (PQ)-treated mice. METHODS: Male C57BL/6 mice (8 weeks old) were divided into 3 groups: PQ + G-CSF-treated group (n=8); PQ + saline-treated group (n=8); and saline-treated control group (n=8). Spontaneous locomotor activity was evaluated together with the pole test. The DA, 3, 4-dihydroxyphenyl acetic acid (DOPAC), and homovanillic acid (HVA) levels in the bilateral striatum were determined by HPLC. The number of substantia nigra pars compacta tyrosine hydroxylase (TH)-immunoreactive neurons was calculated using an unbiased cell counting stereology method, the activities of total GSH-PX and SOD, and the malondialdehyde (MDA) content were assessed. RESULTS: After G-CSF treatment, spontaneous motor activity and the Tturn and TLA times in the CSF group were significantly lower than the control group, and the striatal dopamine level in the striatum and the number of TH-positive neurons in the substantia nigra (SN) were significantly increased compared to the control group (5478 ± 654 vs. 3647±488 DA neurons, P < 0.05). Compared to the control group, the GSH-PX and SOD activities were increased, while the MDA level was significantly decreased in the SN (P<0.05). CONCLUSIONS: The data strongly suggest that G-CSF reverses behavioral deficits in PQ-treated mice with movement disorders. Thus, G-CSF may be utilized as a prospective drug candidate for the treatment of Parkinson's disease.

Associated Factors and Prognostic Implications of Non-convulsive Status Epilepticus in Ischemic Stroke Patients With Impaired Consciousness.

Background and Purpose: Non-convulsive status epilepticus (NCSE) is common in patients with disorders of consciousness and can cause secondary brain injury. Our study aimed to explore the determinants and prognostic significance of NCSE in stroke patients with impaired consciousness. Method: Consecutive ischemic stroke patients with impaired consciousness who were admitted to a neuro intensive care unit were enrolled for this study. Univariate and multivariable logistic regression were used to identify factors associated with NCSE and their correlation with prognosis. Results: Among the 80 patients studied, 20 (25%) died during hospitalization, and 51 (63.75%) had unfavorable outcomes at the 3-month follow-up. A total of 31 patients (38.75%) developed NCSE during 24-h electroencephalogram (EEG) monitoring. Logistic regression revealed that NCSE was significantly associated with an increased risk of death during hospital stay and adverse outcomes at the 3-month follow-up. Patients with stroke involving the cerebral cortex or those who had a severely depressed level of consciousness were more prone to epileptogenesis after stroke. Conclusion: Our results suggest that NCSE is a common complication of ischemic stroke, and is associated with both in-hospital mortality and dependency at the 3-month follow-up. Long-term video EEG monitoring of stroke patients is, therefore required, especially for those with severe consciousness disorders (stupor or coma) or cortical injury.

Upregulation of C Terminus of Hsc70-Interacting Protein Attenuates Apoptosis and Procoagulant Activity and Facilitates Brain Repair After Traumatic Brain Injury.

Traumatic brain injury (TBI) could highly induce coagulopathy through breaking the dynamic balance between coagulation and fibrinolysis systems, which may be a major contributor to the progressive secondary injury cascade that occurs after TBI. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibition is reported to exert neuroprotection in TBI, making it a potential regulatory target involved in TBI-induced coagulation disorder. PTEN level is controlled in a major way by E3 ligase-mediated degradation through the ubiquitin-proteasome system. The C terminus of Hsc70-interacting protein (CHIP) has been shown to regulate proteasomal degradation and ubiquitination level of PTEN. In the present study, CHIP was overexpressed and knocked down in mouse brain microvascular endothelial cells (bEnd.3) and tissues during the early phase of TBI. In vitro cell proliferation, cell apoptosis, migration capacity, and invasion capacity were determined. The changes of procoagulant and apoptosis molecules after TBI were also detected as well as the micrangium density and blood-brain barrier permeability after in vivo TBI. In vitro results demonstrated that CHIP overexpression facilitated bEnd.3 cell proliferation, migration, and invasion and downregulated cell apoptosis and the expressions of procoagulant molecules through promoting PTEN ubiquitination in a simulated TBI model with stretch-induced injury treatment. In vivo experiments also demonstrated that CHIP overexpression suppressed post-TBI apoptosis and procoagulant protein expressions, as well as increased microvessel density, reduced hemorrhagic injury, and blood-brain barrier permeability. These findings suggested that the upregulation of CHIP may attenuate apoptosis and procoagulant activity, facilitate brain repair, and thus exerts neuroprotective effects in TBI.

[Bacillus amyloliquefaciens Biofertilizer Mitigating Soil Ammonia Volatilization].

In this study, we investigated the effectiveness and microbial mechanism of Bacillus amyloliquefaciens biofertilizer on reducing ammonia volatilization in farmland soil. Pot experiments were carried out to explore the effects of B. amyloliquefaciens biofertilizer (BB) and chemical fertilizer on soil ammonia volatilization, crop yield and quality, and soil microbial community. Four fertilization strategies were tested, namely no fertilizer (CK), 100% chemical fertilizer (C), 50% BB and 50% chemical fertilizer (B1), and 100% BB (B2). The dynamic flow-through chamber method was used to determine the soil ammonia volatilization flux after fertilization. The soil bacterial community during the peak period of ammonia volatilization was analyzed using 16S rDNA high-throughput sequencing. The results showed that the amount of ammonia volatilization in B1 and B2 decreased by 79.5% and 84.8%, respectively, as compared with treatment C. B2 had the lowest nitrate content and the highest yield; the yield of B2 increased by 50.5% and 12.3% as compared to that of CK and C, respectively. B1 had the highest content of vitamin C, which was 67.6 mg ·kg-1. The application of BB improved the diversity and richness of soil bacterial community, especially the relative abundance of Bacillus and Nitrospira. This shows that BB plays an important role in preventing air pollution and improving nitrogen utilization.

Bacillus subtilis biofertilizer mitigating agricultural ammonia emission and shifting soil nitrogen cycling microbiomes.

Excessive ammonia (NH3) emitted from nitrogen fertilizer application in farmland have caused serious disturbance to global environment, including reduction of visibility, formation of regional haze, and increase of nitrogen deposition. Application of biofertilizer has been considered as an effective approach for soil improvement and agriculture sustainability. In this study, a field experiment was conducted to evaluate the potential of B. subtilis biofertilizer on mitigating NH3 volatilization and to investigate the underlying mechanisms. Compared with organic fertilizer, the incorporation of B. subtilis biofertilizer reduced NH3 volatilization by up to 44%. Moreover, the application of B. subtilis biofertilizer reduced the abundance of ureC gene, and increased the abundance of functional genes (bacterial amoA and comammox amoA) and ammonia-oxidizing bacteria (AOB). This indicated that the conversion of fertilizer nitrogen to NH4+-N was decreased and the nitrification process was increased. In brief, the application of B. subtilis biofertilizer reduced the "source" and increased the "sink" of NH4+-N, thus reducing the retention of NH4+-N in alkaline soil, and mitigating NH3 volatilization. These results indicated that B. subtilis biofertilizer is an effective control strategy for agricultural NH3 emission, maintaining high crop yield and mitigating environmental disturbance.

A Brain-Penetrating Hsp90 Inhibitor NXD30001 Inhibits Glioblastoma as a Monotherapy or in Combination With Radiation.

Glioblastoma multiforme (GBM) is a highly heterogeneous disease, which is initiated and sustained by various molecular alterations in an array of signal transduction pathways. Heat-shock protein 90 (Hsp90) is a molecular chaperone and is critically implicated in folding and activation of a diverse group of client proteins, many of which are key regulators for glioblastoma biology. We here assessed the anti-neoplastic efficacy of a novel brain-penetrating Hsp90 inhibitor NXD30001 as a monotherapy and combined with radiation in vitro and in vivo. Our results demonstrated that NXD30001 potently inhibited neurosphere formation, growth, and survival of CD133+ GBM cells with the half maximal inhibitory concentration at low nanomolar range, but CD133- GBM cells were less sensitive to NXD30001. NXD30001 also increased radio-sensitivity in glioblastoma stem cells (GSCs) at suboptimal concentrations. Moreover, NXD30001 dose-dependently decreased phosphorylation levels of multiple Hsp90 client proteins which play key roles in GBM, such as EGFR, Akt, c-Myc, and Notch1. In addition, NXD30001 could impair DNA damage response and endoplasmic reticulum stress response after radiotherapy by alteration of the related proteins expression. In a murine orthotopic model of human glioblastoma, NXD30001 marvelously induced tumor regression and extended median survival of tumor-bearing mice by approximately 20% when compared with the vehicle group (37 d vs 31 d, P<0.05). Radiotherapy solely increased median survival of tumor-bearing mice from 31 d to 38 d (P<0.05), while NXD30001 combined with radiation further extended survival to 43 d (P<0.05). We concluded that GSCs are more sensitive to NXD30001 than non-stem GBM cells, and NXD30001 in combination with radiation exerts better inhibitive effect in GBM progression than monotherapy.

PTEN inhibition enhances angiogenesis in an in vitro model of ischemic injury by promoting Akt phosphorylation and subsequent hypoxia inducible factor-1α upregulation.

Angiogenesis is an important pathophysiological response to cerebral ischemia. PTEN is a lipid phosphatase whose loss activates PI3K/Akt signaling, which is related to HIF-1α upregulation and enhanced angiogenesis in human cancer cells. However, the specific roles of PTEN in endothelial cell functions and angiogenesis after cerebral ischemia remain unknown. Therefore, we sought to examine the potential effects of PTEN inhibition on post-ischemic angiogenesis in human blood vessel cells and to determine the underlying mechanism. In this present study, human umbilical vein endothelial cells (HUVECs) were exposed to oxygen-glucose deprivation (OGD), cell proliferation, migration and apoptosis, in vitro tube formation and expression of PTEN/Akt pathway and angiogenic factors were examined in HUVECs after treatment with PTEN inhibitor bisperoxovanadium (bpV) at different doses. The results showed that bpV significantly increased the cell proliferation and reduced cell apoptosis indicating that the drug exerts a cytoprotective effect on HUVECs with OGD exposure. bpV also enhanced cell migration and tube formation in HUVECs following OGD, and upregulated HIF-1α and VEGF expressions, but attenuated endostatin expression. Additionally, western blotting analysis demonstrated that Akt phosphorylation in HUVECs was significantly increased after bpV treatment. These findings suggest that PTEN inhibition promotes post-ischemic angiogenesis in HUVECs after exposure to OGD and this enhancing effect might be achieved through activation of the Akt signal cascade.

Clinical significance of changes in serum neuroglobin and HIF-1α concentrations during the early-phase of acute ischemic stroke.

BACKGROUND: Neuroglobin (NGB) has been described as a neuroprotective agent in cerebral ischemia, hypoxia inducible factor (HIF) has shown an important role in modulating hypoxic and ischemic injury, and therefore they have the potential to impact outcomes after acute ischemic stroke (AIS). Thus, we investigated early changes in the concentrations of serum NGB and HIF-1α after AIS and evaluated the relations of both NGB and HIF-1α to stroke severity and prognosis. METHODS: We prospectively measured the serum concentrations of NGB and HIF-1α in 40 patients with AIS at 24, 48, 72, and 96h after stroke. Correlation combined with infarct size and National Institutes of Health Stroke Scale (NIHSS) score of the patients was analyzed. Receiver operating characteristic (ROC) curve was used to appraise their value in predicting the 90-day outcome after AIS. RESULTS: Serum NGB concentrations increased and peaked at 72h after AIS, whereas serum concentrations of HIF-1α increased for 48h. Peak serum NGB concentration correlated significantly with both infarct size (R2=0.484, p<0.001) and admission NIHSS score (R2=0.578, p<0.001), while serum HIF-1α concentration was only correlated to a patient's infarct size (R2=0.394, p<0.001). ROC curve analysis suggested that the serum NGB concentration had a significantly better predictive power for poor outcome. CONCLUSIONS: NGB level increased in serum after AIS accompanied by increases in serum HIF-1α, and was suggested as a predictor of stroke severity and poor prognosis.

Changes in serum vascular endothelial growth factor and endostatin concentrations associated with circulating endothelial progenitor cells after acute ischemic stroke.

Angiogenesis is an important pathophysiological response to cerebral ischemia, and can be modulated by vascular endothelial growth factor (VEGF) and endostatin. Circulating endothelial progenitor cells (EPCs) also play an important role as an endogenous repair mechanism for ischemic injury. We sought to investigate early changes in the expression of VEGF and endostatin in serum and the circulating EPCs in patients with acute ischemic stroke (AIS) and analyzed the relations between them. The peripheral blood and serum samples were obtained from 30 patients at 1, 3, 5 and 7 d after AIS. Flow cytometry was used to quantify EPCs, and VEGF and endostatin were measured by enzyme linked immunosorbent assay. Correlation analysis was performed to assess the relations between them. Receiver operating characteristic (ROC) curve was used to appraise the value of EPCs levels in predicting the 90-day prognosis after AIS. Compared with control subjects, circulating EPCs numbers increased from a very lower initial level (P < 0.001) until 7 d after AIS. Serum VEGF and endostatin levels increased and peaked at 3 d and 5 d post-stroke (both P < 0.001), respectively. A significant correlation (P = 0.001) was found between peak serum VEGF concentration and peak endostatin concentration. VEGF/endostatin ratio at day 1 and day 3 after AIS significantly correlated with circulating EPCs numbers at day 5 (P < 0.001) and day 7 post-stroke (P < 0.001). ROC curve analysis suggested that circulating EPCs number at day 7 had a significantly predictive power for good prognosis. VEGF and endostatin may mediate EPCs proliferation in the early phase of ischemic stroke, and the circulating EPCs levels can be a predictor of clinical outcome in AIS.

Efficacy and safety comparison of DL-3-n-butylphthalide and Cerebrolysin: Effects on neurological and behavioral outcomes in acute ischemic stroke.

Cerebrolysin and DL-3-n-butylphthalide (NBP) have each shown neuroprotective efficacy in preclinical models of acute ischemic stroke (AIS) and passed clinical trials as therapeutic drugs for AIS. The present study was a clinical trial to assess and compare the efficacy and safety of NBP and Cerebrolysin in the reduction of neurological and behavioral disability following AIS. A randomized, double-blind trial was conducted with enrolment of 60 patients within 12 h of AIS. In addition to routine treatment, patients were randomly assigned to receive a 10-day intravenous administration of NBP, Cerebrolysin or placebo. National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI) scores were used to evaluate the efficacy of the treatment in the patients with AIS at 11 and 21 days after the initiation of therapy. Adverse events were also analyzed among the three groups. After 10 days of treatment with NBP or Cerebrolysin, the NIHSS and BI scores at day 21 showed statistical differences compared with those in the placebo group (P<0.05). The improvements of NIHSS and BI scores in the NBP and Cerebrolysin groups were higher than those in the placebo group at days 11 and 21 (P<0.05). A statistically significant difference in the improvement of 21-day NIHSS scores was observed between the two treatment groups (P<0.05). No significant difference was found among the three groups with regard to the rate of adverse events. Favorable outcomes and good safety were observed in the patients with moderate AIS treated with NBP or Cerebrolysin. The results indicate that NBP may be more effective than Cerebrolysin in improving short-term outcomes following AIS. This trial is registered at ClinicalTrials.gov with clinical trial identifier number NCT02149875.

Neuroglobin and Nogo-a as biomarkers for the severity and prognosis of traumatic brain injury.

OBJECTIVE: To identify the early changes of serum neuroglobin and Nogo-A concentrations and the relations to traumatic brain injury (TBI) severity and prognosis. METHODS: Serum samples were obtained and analyzed from 34 patients with TBI within the first 96 h after injury. Comparative analysis combined with Glasgow Coma Scale (GCS) scores and the 6-month prognosis of these patients was performed. RESULTS: Significant correlations were found between peak serum neuroglobin and Nogo-A concentrations and a patient's GCS score on admission (p < 0.001). The mean peak serum neuroglobin and Nogo-A concentrations were both significantly higher in patients with an unfavorable outcome at 6 months after injury (p < 0.05). CONCLUSIONS: Serum neuroglobin and Nogo-A levels could be suggested as biomarkers for predicting TBI severity and prognosis.

Endostatin/collagen XVIII is increased in cerebrospinal fluid after severe traumatic brain injury.

Recent studies have suggested that endogenous angiogenesis inhibitor endostatin/collagen XVIII might play an important role in the secondary brain injury following traumatic brain injury (TBI). In this study, we measured endostatin/collagen XVIII concentrations serially for 1 week after hospitalization by using the enzyme-linked immunosorbent assay method in the cerebrospinal fluid (CSF) of 30 patients with TBI and a Glasgow Coma Scale (GCS) score of 8 or less on admission. There was a significant trend toward increased CSF levels of endostatin after TBI versus control from 72 h after injury. In patients with GCS score of 3-5, CSF endostatin concentration was substantially higher at 72 h after injury than that in patients with GCS score of 6-8 (P < 0.05) and peaked rapidly at day 5 after injury, but decreased thereafter. The CSF endostatin concentration in 12 patients with an unfavorable outcome was significantly higher than that in 18 patients with a favorable outcome at day 5 (P = 0.043) and day 7 (P = 0.005) after trauma. Receiver operating characteristic curve analysis suggested a reliable operating point for the 7-day CSF endostatin concentration predicting poor prognosis to be 67.29 pg/mL. Our preliminary findings provide new evidence that endostatin/collagen XVIII concentration in the CSF increases substantially in patients with sTBI. Its dynamic change may have some clinical significance on the judgment of brain injury severity and the assessment of prognosis. This trial is registered with the ClinicalTrials.gov Identifier: NCT01846546.

The influence of hemocoagulation disorders on the development of posttraumatic cerebral infarction and outcome in patients with moderate or severe head trauma.

Posttraumatic cerebral infarction (PTCI) is a severe secondary insult of head injury and often leads to a poor prognosis. Hemocoagulation disorder is recognized to have important effects on hemorrhagic or ischemic damages. We sought to assess if posttraumatic hemocoagulation disorders were associated with cerebral infarction, and evaluate their influence on outcome among patients with moderate or severe head trauma. In this study, PTCI was observed in 28 (10.57%) of the 265 patients within the first week after injury. In multivariate analysis, the thrombocytopenia (odds ratio (OR) 2.210, 95% confidence interval (CI) 1.065-4.674), abnormal prothrombin time (PT) (OR 3.241, 95% CI 1.090-7.648), D-dimer (>2 mg/L) (OR 7.260, 95% CI 1.822-28.076), or disseminated intravascular coagulation (DIC) scores (≥ 5) (OR 4.717, 95% CI 1.778-12.517) were each independently associated with an increased risk of PTCI. Admission Glasgow Coma Scale (GCS) score, abnormal activated partial thromboplastin time (APTT) and fibrinogen, and D-dimer (>2 mg/L) and DIC scores (≥ 5) showed an independent predictive effect on poor outcome. In conclusion, recognition of this important treatable cause of PTCI and the associated risk factors may help identify the group at risk and tailor management of patients with TBI.

Effects of spherical aberration on visual acuity at different contrasts.

PURPOSE: To evaluate the effect of spherical aberration on visual acuity by correcting and inducing spherical aberration using an adaptive optics vision simulator. SETTING: Laboratory of Vision Science, Capital Medical University, Beijing, and Institute of Optics and Electronics, Chinese Academy of Sciences, Chengdu, China. METHODS: An adaptive optics vision simulator comprising a wavefront sensor and a 37-segmented deformable mirror was used to correct and induce aberrations of the eye. The effective ocular wavefront aberration was manipulated with the deformable mirror, as the resulting visual performance was simultaneously measured. Subjective visual acuity measurements were performed with a 6.0 mm pupil. Visual acuity at different contrasts was measured when spherical aberration was fully corrected and the other natural aberrations in the eye were present and when spherical aberration values were induced with the other aberrations corrected. RESULTS: The natural root-mean-square (RMS) value of spherical aberration in the 8 subjects examined was between -0.11 microm and 0.14 microm. There was no significant improvement in visual acuity with spherical aberration corrected and the subjects' natural aberrations present. When all aberrations were corrected, a decrease in visual acuity occurred when spherical aberration RMS was induced at 0.2 microm and 0.3 microm. CONCLUSIONS: When fluctuation of other natural aberrations in the eye were present, there was a slight effect on visual acuity when the spherical aberration RMS was approximately 0.1 microm. Therefore, an RMS value of 0.1 microm could be an acceptable amount of spherical aberration when correcting spherical aberrations.

Effects of monochromatic aberration on visual acuity using adaptive optics.

PURPOSE: To investigate the effect on visual acuity of correcting specific Zernike aberrations. METHODS: Visual acuity was tested for 12 young subjects using a Freiburg Acuity Test procedure under conditions with wavefront aberrations corrected by an adaptive optics system. The adaptive optics system consists of a Hartmann-Shack wavefront sensor, a deformable mirror, relevant optical channels and closed loop control system. Five aberration correction paradigms were used to correct different Zernike terms. RESULTS: With the second order aberration fully corrected, a significant improvement in visual acuity was observed (0.056 logMAR, t = 2.79, p = 0.018). Further correction of third order Zernike aberrations resulted in an additional improvement of 0.041 logMAR (t = 2.63, p = 0.023). But an additional correction of spherical aberration did not produce a significant increase in visual acuity (t = 1.10, NS). Full correction of aberrations achieved the best visual acuity with an improvement of 0.022 logMAR (t = 2.46, p = 0.032). The visual acuity was found to increase with the root mean square values of the residual aberrations with a linear relationship (r = 0.63, p < 0.0001). CONCLUSIONS: Correction of monochromatic wavefront aberrations improves visual acuity for normal eyes and the improvement of visual acuity is proportional to the change of root mean square of wavefront aberrations.