A novel method for noninvasive quantification of fractional flow reserve based on the custom function.

Boundary condition settings are key risk factors for the accuracy of noninvasive quantification of fractional flow reserve (FFR) based on computed tomography angiography (i.e., FFRCT). However, transient numerical simulation-based FFRCT often ignores the three-dimensional (3D) model of coronary artery and clinical statistics of hyperemia state set by boundary conditions, resulting in insufficient computational accuracy and high computational cost. Therefore, it is necessary to develop the custom function that combines the 3D model of the coronary artery and clinical statistics of hyperemia state for boundary condition setting, to accurately and quickly quantify FFRCT under steady-state numerical simulations. The 3D model of the coronary artery was reconstructed by patient computed tomography angiography (CTA), and coronary resting flow was determined from the volume and diameter of the 3D model. Then, we developed the custom function that took into account the interaction of stenotic resistance, microcirculation resistance, inlet aortic pressure, and clinical statistics of resting to hyperemia state due to the effect of adenosine on boundary condition settings, to accurately and rapidly identify coronary blood flow for quantification of FFRCT calculation (FFRU). We tested the diagnostic accuracy of FFRU calculation by comparing it with the existing methods (CTA, coronary angiography (QCA), and diameter-flow method for calculating FFR (FFRD)) based on invasive FFR of 86 vessels in 73 patients. The average computational time for FFRU calculation was greatly reduced from 1-4 h for transient numerical simulations to 5 min per simulation, which was 2-fold less than the FFRD method. According to the results of the Bland-Altman analysis, the consistency between FFRU and invasive FFR of 86 vessels was better than that of FFRD. The area under the receiver operating characteristic curve (AUC) for CTA, QCA, FFRD and FFRU at the lesion level were 0.62 (95% CI: 0.51-0.74), 0.67 (95% CI: 0.56-0.79), 0.85 (95% CI: 0.76-0.94), and 0.93 (95% CI: 0.87-0.98), respectively. At the patient level, the AUC was 0.61 (95% CI: 0.48-0.74) for CTA, 0.65 (95% CI: 0.53-0.77) for QCA, 0.83 (95% CI: 0.74-0.92) for FFRD, and 0.92 (95% CI: 0.89-0.96) for FFRU. The proposed novel method might accurately and rapidly identify coronary blood flow, significantly improve the accuracy of FFRCT calculation, and support its wide application as a diagnostic indicator in clinical practice.

Research on individualized distribution approach of coronary resting blood flow for noninvasive calculation of fractional flow reserve.

BACKGROUND AND OBJECTIVES: The distribution of coronary resting blood flow is critical for accurately calculating the computed tomography (CT) angiography-derived fractional flow reserve (FFRCT). However, the diagnostic accuracy of FFRCT calculated by the fixed exponents between two risk factors and coronary resting blood flow, including myocardial mass and diameter of the coronary artery branch, was insufficient compared with invasive fractional flow reserve (FFR). In this study, we proposed the individualized distribution of coronary resting blood flow based on coronary ultrasound blood flow measurement, to improve the diagnostic accuracy of FFRCT calculation. METHODS: Five risk factors and an unknown coefficient K were integrated to calculate the individualized distribution of coronary resting blood flow. The K value was fit using the least square method based on coronary ultrasound blood flow measurement results of 30 volunteers. We developed a novel approach for calculating the individualized distribution of coronary resting blood flow and applied it to calculate FFRCT (FFRCTI). Then, we tested the performance of the individualized distribution approach by comparing it with the approach proposed by Taylor based on coronary ultrasound blood flow measurement results of 13 volunteers. Finally, we tested the diagnostic accuracy of FFRCT calculated by two approaches in invasive FFR of 121 vessels with coronary stenosis. RESULTS: We identified five risk factors and 6.83×10-5 for K value, including cardiac output, mean arterial pressure, myocardial mass, coronary artery volume, and diameter of the coronary artery branch, to calculate the individualized distribution of coronary resting blood flow. The mean square error of the individualized distribution approach (0.0088) was significantly less than that of the approach proposed by Taylor (0.0799). The diagnostic accuracy of FFRCTI calculated by the individualized distribution approach (91.74%) was higher than that of the approach proposed by Taylor (FFRCTT) (82.64%). CONCLUSIONS: The individualized distribution approach of coronary resting blood flow can significantly improve the diagnostic accuracy of FFRCT calculation compared with invasive FFR, and support its wide clinical application for diagnosing myocardial ischemia caused by coronary stenosis.

RNF8 enhances the sensitivity of PD-L1 inhibitor against melanoma through ubiquitination of galectin-3 in stroma.

The failure of melanoma immunotherapy can be mediated by immunosuppression in the tumor microenvironment (TME), and insufficient activation of effector T cells against the tumor. Here, we show that inhibition of galectin-3 (gal-3) enhances the infiltration of T cells in TME and improves the sensitivity of anti-PD-L1 therapy. We identify that RNF8 downregulated the expression of gal-3 by K48-polyubiquitination and promoted gal-3 degradation via the ubiquitin-proteasome system. RNF8 deficiency in the host but sufficiency in implanted melanoma results in immune exclusion and tumor progression due to the upregulation of gal-3. Upregulation of gal-3 decreased the immune cell infiltration by restricting IL-12 and IFN-γ. Inhibition of gal-3 reverses immunosuppression and induces immune cell infiltration in the tumor microenvironment. Moreover, gal-3 inhibitor treatment can increase the sensitivity of PD-L1 inhibitors via increasing immune cell infiltration and enhancing immune response in tumors. This study reveals a previously unrecognized immunoregulation function of RNF8 and provides a promising strategy for the therapy of "cold" tumors. Tremendous effects of melanoma treatment can be achieved by facilitating immune cell infiltration combined with anti-PD-L1 treatment.

Carbon ion irradiation induces DNA damage in melanoma and optimizes the tumor microenvironment based on the cGAS-STING pathway.

PURPOSES: Increased number of studies reveal the crucial role of the Cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway in anti-tumor immunity. In this study, we aim to explore the effect of cGAS/STING on tumor immune microenvironment of melanoma after carbon ion radiotherapy (CIRT) and the underlying mechanism. METHODS: C57BL/6 mouse tumor models were used to evaluate the efficacy of different treatments (X-ray, carbon ion, PD-L1 inhibitor and combination therapies) on tumor growth and process. Mass cytometry was performed to assess tumor-infiltrating lymphocytes (TILs). DNA damage response (DDR) and cGAS/STING pathway were investigated by immunofluorescence-co-localization assays, γ-H2AX, P53-binding protein 1 (53BP1), Breast Cancer 1 (BRCA1), and cGAS measurements. RESULTS: Carbon ion irradiation caused more DNA damages and cGAS-STING pathway activation compared with X-ray irradiation, and the former slowed the melanoma growth in syngeneic model. Although X-ray irradiation is not sensitive for melanoma treatment, carbon ion irradiation showed a significant anti-tumor effect for melanoma treatment. TILs analysis revealed that CIRT boosted the infiltration of natural killer (NK), CD4+, and CD8+ T cells, meanwhile increased the number of immune checkpoint (programmed death-1, PD-1, lymphocyte activation gene 3, LAG-3 and T-cell immunoglobulin and mucin domain-containing protein 3, TIM-3). Moreover, CIRT increased PD-L1 exposure on cell surface compared with X-ray group. Furthermore, CIRT combined with PD-L1 inhibitor therapy increased the number of T cells and NK cells in melanoma, and slowed the growth of melanoma compared with other therapies. CONCLUSIONS: Our findings showed that CIRT displayed biological effects by increasing DNA damages of tumor cells and improving immunity in melanoma, which indicated that CIRT might be a potential synergetic treatment for radiotherapy and radioimmunotherapy in melanoma patients. Our works put forward a new insight to provide an effective strategy for melanoma therapy. These findings may help in the design of strategies on melanoma in clinical studies.

Analysis of Risk Factors for Vulnerable Plaque Formation and Pathogenic in Carotid Artery.

OBJECTIVES: The formation of vulnerable carotid artery plaque may be closely related to a single factor or caused by multiple factors. This paper discusses the pathogenic risk factors for vulnerable plaque in patients with severe internal carotid artery (ICA) stenosis who received endarterectomy through regression analysis. MATERIALS AND METHODS: A total of 98 patients with a complete clinical and laboratory assessment underwent carotid endarterectomy. Metabolic syndrome (MetS) and MetS components, ICA plaque thickness and ICA peak systolic velocity, previous ischemic stroke or transient ischemic attack (TIA), and other risk factors were included in the pathogenic risk factor for vulnerable plaque. Univariate logistic regression analysis was used to determine vulnerable carotid plaque risk factors. If P <0.2, it was considered potential confounders. Binary logistic regression model was controlled for potential confounders. RESULTS: Among the 98 patients, stable carotid plaques 38 (39%) and unstable carotid plaques 60 (61%), male 76 (77.6%) and female 22 (22.4%), and Han Chinese 68 (68.4%) and Mongols 30 (30.6%). Univariate logistic regression to P <0.2 has 6 risk factors, which are previous ischemic stroke or TIA, ICA peak systolic velocity, ICA plaque thickness, body mass index, total cholesterol, and alcohol consumption. The significant result of the binary logistic regression analysis was the previous ischemic stroke or TIA (OR=4.52; 95% CI, 1.67-12.09), P =0.003 and ICA peak systolic velocity (OR=1.01; 95% CI, 1.00-1.02), P =0.014. CONCLUSIONS: The patients with previous ischemic stroke or TIA and higher ICA peak systolic velocity are associated with vulnerable plaque pathogenic features. There is no obligatory association between MetS and formation of carotid plaque vulnerability.

Clinical effects of neuroendoscopic hematoma evacuation for hypertensive intracerebral hemorrhage.

OBJECTIVE: To analyze the clinical effects of neuroendoscopic hematoma evacuation for the treatment of hypertensive intracerebral hemorrhage (ICH). METHODS: A total of 80 patients with hypertensive ICH who were admitted to our hospital were included as the subjects of this retrospective study. The patients were assigned into a neuroendoscopic hematoma evacuation group (n=35) and a small bone window craniotomy group (n=45). The post-operative hematoma residues and the clearance rate of the hematoma were compared between the two groups. The intraoperative blood loss, duration of the surgery, and Glasgow Coma Scale (GSC) scores before and after surgery were compared between the two groups. The operation time, intraoperative blood loss, the time consumed to stop bleeding, clearance rate of hematoma, manifestation of complications, and the prognosis 6 months after surgery were analyzed statistically. Self-made questionnaires were used to evaluate the satisfaction degree of patients with their lives and to assess the quality of life after surgery. RESULTS: The operation time, blood loss, and the time consumed to stop bleeding were less in the neuroendoscopic hematoma evacuation group than those in the small bone window craniotomy group (all P<0.05). The GCS scores in the neuroendoscopic hematoma evacuation group were significantly higher than those in the small bone window craniotomy group (P<0.05). The clearance rate of hematoma was higher in the neuroendoscopic hematoma evacuation group than that in the small bone window craniotomy group (P<0.05). CONCLUSION: As compared with small bone window craniotomy for removing hematoma, neuroendoscopic hematoma evacuation showed a better outcome in treating patients with hypertensive ICH. It could improve patients' clinical indications, which is worthy of being widely applied in clinical settings.

Knockdown of circular RNA tousled-like kinase 1 relieves ischemic stroke in middle cerebral artery occlusion mice and oxygen-glucose deprivation and reoxygenation-induced N2a cell damage.

Ischemic stroke (IS) is an essential contributor to the neurological morbidity and mortality throughout the world. The significance of circular RNA tousled-like kinase 1 (circTLK1) in IS has been documented. This study set out to explore the mechanism of circTLK1 in IS. Middle cerebral artery occlusion (MCAO) mouse models in vivo and oxygen-glucose deprivation and reoxygenation (OGD/R) cell models in vitro were first established, followed by evaluation of infarct volume and neurological impairment, and cell viability and apoptosis. The expression patterns of circTLK1, miR-26a-5p, phosphatase and tensin homolog (PTEN), insulin-like growth factor type 1 receptor (IGF-1 R), and glucose transporter type 1 (GLUT1) were detected by RT-qPCR and Western blotting. Co-localization of circTLK1 and miR-26a-5p in N2a cells was tested by fluorescence in situ hybridization assay. The binding relationships among circTLK1, PTEN, and miR-26a-5p were verified by dual-luciferase assay and RNA pull-down. circTLK1 and PTEN were highly expressed while miR-26a-5p was under-expressed in IS models. circTLK1 knockdown decreased infarct volume and neurological impairment in MCAO mouse models and relieved OGD/R-induced neuronal injury in vitro. circTLK1 and miR-26a-5p were co-located in the N2a cell cytoplasm. circTLK1 regulated PTEN as a sponge of miR-26a-5p. PTEN positively regulated IGF-1 R and GLUT1 expressions. miR-26a-5p inhibitor annulled the repressive effects of circTLK1 silencing on OGD/R-induced neuronal injury. sh-PTEN partially annulled the effects of the miR-26a-5p inhibitor on OGD/R-induced neuronal injury. In conclusion, circTLK1 knockdown relieved IS via the miR-26a-5p/PTEN/IGF-1 R/GLUT1 axis. These results may provide a new direction to IS potential therapeutic targets.

[Application of continuous monitoring of intracranial pressure and brain oxygen partial pressure in the treatment of patients with severe craniocerebral injury].

OBJECTIVE: To investigate the effects of continuous monitoring intracranial pressure (ICP) and brain oxygen partial pressure (PbtO2) on the prognosis of patients with severe craniocerebral injury. METHODS: A prospective randomized controlled trial was conducted. Seventy patients with severe craniocerebral injury with a Glasgow coma score (GCS) 4-8 admitted to the neurosurgical intensive care unit (NICU) of the People's Hospital of Inner Mongolia Autonomous Region from January 2017 to May 2020 were enrolled, and they were divided into ICP monitoring group and ICP+PbtO2 monitoring group by random number table. Patients in ICP monitoring group received ICP monitoring and were given traditional treatment of controlling ICP and cerebral perfusion pressure (CPP), the therapeutic target was ICP < 20 mmHg (1 mmHg = 0.133 kPa) and CPP > 60 mmHg. Patients in ICP+PbtO2 monitoring group were given ICP and PbtO2 monitoring at the same time, and oxygen flow was adjusted on the basis of controlling ICP and CPP to maintain the PbtO2 > 20 mmHg, and the therapeutic target of ICP and CPP was the same as the ICP monitoring group. ICP and PbtO2 values were recorded during monitoring in the two groups, the results of CPP, GCS and arterial blood gas analysis were recorded, and the prognosis at 3 months and 6 months after injury was compared by Glasgow outcome scale (GOS) score between the two groups. GOS score > 3 was considered as good prognosis. Kaplan-Meier survival curve was drawn, and the 3-month and 6-month cumulative survival rates of the two groups were analyzed. Linear regression analysis was used to further evaluate the relationship between PbtO2 and GOS score. RESULTS: Finally, a total of 70 patients with severe craniocerebral injury were enrolled in the analysis, 34 patients received ICP combined with PbtO2 monitoring and guided therapy, and 36 patients received ICP monitoring alone. The average ICP of ICP+PbtO2 monitoring group was significantly lower than that of ICP monitoring group (mmHg: 13.4±3.2 vs. 18.2±8.3, P < 0.01). Although the CPP in both groups was great than 60 mmHg, the average CPP of ICP+PbtO2 monitoring group was significantly higher than that of ICP monitoring group (mmHg: 82.1±10.5 vs. 74.5±11.6, P < 0.01). No significant difference was found in average GCS score or arterial partial pressure of carbon dioxide (PaCO2) between the ICP+PbtO2 monitoring group and ICP monitoring group [GCS score: 5.3±2.3 vs. 5.2±2.2, PaCO2 (mmHg): 33.5±4.8 vs. 32.6±5.2, both P > 0.05]. The average arterial partial pressure of oxygen (PaO2) of ICP+PbtO2 monitoring group was obviously higher than that of ICP monitoring group (mmHg: 228.4±93.6 vs. 167.3±81.2, P < 0.01). Compared with the ICP monitoring group, the good outcome rates of 3 months and 6 months after injury in the ICP+PbtO2 monitoring group were significantly higher (3 months: 67.6% vs. 38.9%, 6 months: 70.6% vs. 41.7%, both P < 0.05). Kaplan-Meier survival curve showed that the 3-month and 6-month cumulative survival rates of ICP+PbtO2 monitoring group were significantly higher than those of ICP monitoring group (3 months: 85.3% vs. 61.1%, Log-Rank test: χ2 = 5.171, P = 0.023; 6 months: 79.4% vs. 55.6%, Log-Rank test: χ2 = 4.511, P = 0.034). Linear regression analysis showed that PbtO2 was significantly correlated with GOS score at 3 months and 6 months after injury in patients with severe craniocerebral injury (r values were 0.951 and 0.933, both P < 0.01). CONCLUSIONS: PbtO2 compared with ICP monitoring guiding therapy is valuable in improving the prognosis of patients with severe craniocerebral injury. It can improve the prognosis at 3-6 months after injury.

Long non-coding RNA GAS5 retards neural functional recovery in cerebral ischemic stroke through modulation of the microRNA-455-5p/PTEN axis.

OBJECTIVE: Cerebral ischemic stroke (IS) threatens the daily life of individuals, with high mortality. Emerging studies have deciphered the independent roles of the long non-coding RNA growth-arrest-specific transcript 5 (GAS5), microRNA (miR)-455-5p and phosphatase and tensin homolog (PTEN) in IS, but the understanding of their integrated function is in its infancy. Therefore, this study focusing on the GAS5/miR-455-5p/PTEN axis was initiated. METHODS: Middle cerebral artery occlusion (MCAO) models were established by the suture method. GAS5, miR-455-5p and PTEN expression was detected in rat brain tissues after MCAO. Rats were injected with sh-GAS5 or miR-455-5p agomir before MCAO modeling. A neurobehavioral evaluation was conducted, and oxidative stress injury, apoptosis and mitochondrial function were detected in brain tissues of IS rats. The relationships between GAS5 and miR-455-5p, and between miR-455-5p and PTEN were verified. PC12 cells were transfected with sh-GAS5 or miR-455-5p mimic under oxygen and glucose deprivation/reoxygenation (OGD/R) conditions to evaluate cell viability and apoptosis. RESULTS: GAS5 and PTEN expression levels were elevated and miR-455-5p expression was reduced in brain tissues of MCAO rats and OGD/R-induced PC12 cells. GAS5 downregulation or miR-455-5p upregulation improved neurobehavior, attenuated apoptosis and oxidative injury, and relieved mitochondrial damage in brain tissues of IS rats. Silencing GAS5 or restoring miR-455-5p minimized OGD/R-induced cell damage. MiR-455-5p downregulation antagonized the effects of GAS5 inhibition on IS. CONCLUSION: This work elucidates that GAS5 downregulation upregulates miR-455-5p to repress PTEN expression, in turn attenuating IS, which may broaden the horizon of IS treatment.

Downregulation of KLF13 through DNMT1-mediated hypermethylation promotes glioma cell proliferation and invasion.

BACKGROUND: Recent evidence indicates that Kruppel-like factor 13 (KLF13) has critical roles in regulating cell differentiation, proliferation and may function as a tumor suppressor. However, its role in glioma progression is poorly understood. METHODS: Public database was used to explore the expression and prognostic value of KLF13 in glioma. Cell proliferation and invasion assays were used to explore the role of KLF13. Bisulfite sequencing and ChIP assay were used to determine the methylation of KLF13 promoter in glioma and the regulation of KLF13 by DNMT1. RESULTS: We found that KLF13 inhibited glioma cell proliferation and invasion, which could be reversed by AKT activation. DNMT1-mediated hypermethylation was responsible for downregulation of KLF13. Knocking down of DNMT1 restored KFL13 expression and inhibited cell proliferation and invasion as well. Patients with high expression of KLF13 might have a better prognosis. CONCLUSION: KLF13 suppressed glioma aggressiveness and the regulation of KLF13 could be a potential therapeutic target.

Highly stretchable HA/SA hydrogels for tissue engineering.

A highly stretchable hyaluronic acid (HA)/sodium alginate (SA) hydrogel was developed in this study based on an interpenetrating polymer network. HA/SA hydrogels were prepared by mixing two polysaccharides followed by covalent crosslinking via epoxy groups on HA molecules and ionic crosslinking via divalent ions on SA chains sequentially. The effect of HA/SA ratio on the pore size and distribution, swelling ratio, elongation and rheological properties as well as protein loading and release properties of HA/SA hydrogels was explored. Moreover, a surface modification method, layer-by-layer (LBL) assembly technique, was applied to modify the hydrogel to evaluate the hydrogel's tenability in varying biological performance. It was then shown that the hydrogels had the pore sizes ranging from 100 to 50 µm. With the increase in SA content of the resulting hydrogels, the pore size, swelling ratio, and storage modulus (G') and loss modulus (G″) of the hydrogel all decreased, whereas the in vitro bulk weight loss was fastened. Moreover, elongation at break (EB) value increased first, reached a peak value and then decreased, that is HA8/SA1 (HA:SA = 8:1) had the highest EB value of 417%. This hydrogel could retain 33.2% of the pre-loaded protein even after 72 h, which could be further attenuated when LBL was used to shell the hydrogel. The growth of fibroblasts on HA8/SA1 hydrogel gave preliminary assessment on its suitability as a cellular carrier, while the LBL modified HA8/SA1 hydrogel also favored the anchoring of keratinocytes, further enhancing its cell carrier role for tissue regeneration, especially skin engineering.

Decompressive Craniectomy With Bifrontal Coronal Incision in the Management of Fronto-Temporal Contusion and Laceration for Early Cranioplasty.

The present study aims to explore the effectiveness of decompressive craniectomy with bifrontal coronal incision in the management of severe contusion and laceration of bilateral fronto-temporal lobes, as well as the outcomes of early cranioplasty. The authors performed the bifrontal decompressive craniectomy on 56 patients with contusion and laceration of bilateral frontal and temporal lobes, and their follow-up treatment outcomes were tracked within 6 months using Glasgow Outcome Scale. The results showed that 33 patients (out of 56, 58.9%) have recovered, 12 patients (out of 56, 21.4%) have moderate defects, 5 patients (out of 56, 8.9%) have severe defects, 3 patients (out of 56, 5.3%) stayed in persistent vegetative status, and the remaining 3 patients (out of 56, 5.3%) have been dead. There was no persistent temporal hollowing. No patients required revision surgery with modified titanium mesh in this study. Particularly, 28 patients have successfully accepted the early cranioplasty with bone flap or computer-assisted design titanium mesh, and showed good recovery. These results together indicated that the decompressive craniectomy with bifrontal coronal incision in the management of severe contusion and laceration of bilateral fronto-temporal lobes can significantly relieve the comorbidity of intracranial hypertension, and improve the prognosis obviously, thus finally increasing the probability of successful rescue and decreasing the probability of mortality and disability.

Surgical treatment of unruptured dissecting intracranial aneurysms of vertebral-posterior inferior cerebellar artery region.

A lack of published surgical experience and higher symptomatic recurrence than previously recognized prompted the authors to present their experience with the surgical treatment of unruptured intracranial dissecting aneurysms (UIDAs). Hospital records, neuroimaging studies, operative reports, and follow-up records were retrospectively reviewed. All patients underwent surgical exploration of the lesion with proximal clipping of the parent artery through a far-lateral suboccipital craniotomy with or without partial condylar resection. The surgical treatment of vertebral artery-posterior inferior cerebellar artery UIDAs has acceptable risk regarding perioperative mortality and morbidity. The incidence of aneurysmal recurrence or the need for retreatment seems to be less than that associated with anticoagulation/antiplatelet therapy or endovascular treatment.

The Association Between Apolipoprotein E and Functional Outcome After Traumatic Brain Injury: A Meta-Analysis.

Traumatic brain injury (TBI) is a leading cause of death and disability. Previous studies have investigated the association of apolipoprotein E (APOE) ε4 with functional outcome after TBI and reported inconsistent results.The purpose of this study was to perform a systematic literature search and conduct meta-analyses to examine whether APOE ε4 is associated with poorer functional outcome in patients with TBI.We performed a systematic literature search in PubMed, Cochrane Library, Embase, Google Scholar, and HuGE.The eligibility criteria of this study included the following: Patients had TBI; the studies reported APOE genotype data or provided odds ratios (ORs) and the corresponding 95% confidence intervals (CIs); the functional outcome was assessed using the Glasgow Outcome Scale (GOS) or the Glasgow Outcome Scale Extended (GOSE); and patients were followed for at least 3 months after TBI.In all meta-analyses, we used random-effects models to calculate the odds ratio as a measure of association. We examined the association of APOE ε4 with functional outcome at different time points after TBI.A total of 12 studies met the eligibility criteria and were included in the meta-analyses. We did not find a significant association between APOE ε4 and functional outcome at 6 (P = 0.23), 12 (P = 0.44), and 24 months (P = 0.85) after TBI. However, APOE ε4 was associated with an increased risk of unfavorable long-term (≥6 months) functional outcome after TBI (OR = 1.36, 95% CI: 1.07-1.74, P = 0.01).Limitations of this study include The sample size was limited; the initial severity of TBI varied within and across studies; we could not control for potential confounding factors, such as age at injury and sex; a meta-analysis of the genotype dosage effect was not feasible; and we could not examine the association with specific factors such as neurobehavioral or specific cognitive functions.Our meta-analysis indicates APOE ε4 is associated with the long-term functional outcome of patients with TBI. Future studies that control for confounding factors, with large sample sizes and more homogeneous initial TBI severity levels, are needed to validate the findings from this study.

[Pathophysiological roles of matrix metalloproteinases and nitric oxide synthase in cerebral aneurysm].

OBJECTIVE: To explore the expressions of matrix metalloproteinases-2 (MMP-2), matrix metalloproteinases-9 (MMP-9) and inducible nitric oxide synthase (iNOS) in cerebral aneurysms, compare them with normal brain vessels tissue so as to gain a better understanding of the pathogenesis of cerebral aneurysms. METHODS: Twelve samples of cerebral aneurysms were obtained during operations and 10 cortical arteries as controls during surgery for temporal lobe epilepsy from 2009 to 2012 at Inner Mongolia People's Hospital and Beijing Tiantan Hospital. The activities of MMP-2, MMP-9 and iNOS in specimens were detected with spectrophotometry and substrate gel zymography. RESULTS: The MMP-2 and MMP-9 levels in cerebral aneurysm group were (199 598 ± 125 288) gray scale area × mg⁻¹ × L⁻¹ and (719 253 ± 376 519) gray scale area × mg⁻¹ × L⁻¹. Both in cerebral aneurysm group were significantly higher than that in control group (P < 0.05) . The TNOS and iNOS levels in cerebral aneurysm group were (23.6 ± 6.6) and (11.4 ± 2.6) U/mgprot. The difference of TNOS level was not significant between aneurysm and control groups (P > 0.05) while the levels of iNOS and iNOS/TNOS in cerebral aneurysm group were significantly higher than that in control group (P < 0.05). CONCLUSION: MMP-2, MMP-9 and iNOS are closely correlated with cerebral aneurysm.

Projections of glutamate decarboxylase positive and negative cerebellar neurons to the pretectum in the cat.

The pretectum is one of the primary visual centers, and plays an important role in the visuomotor reflexes. It also receives projections from the cerebellar nuclei that are considered to regulate these reflexes. Gamma aminobutylic acid (GABA) and glutamate are supposed to be two major neurotransmitters of the projection neurons of the cerebellar nuclei. We double labeled the projecting neurons with a tracer, biotinylated dextran amine (BDA), and with an antiserum to glutamate decarboxylase (GAD), the enzyme that synthesizes GABA. The results indicated that about 40% of the pretectal-projecting neurons of the cerebellar nuclei were GAD immunoreactive. The GAD positive pretectal-projecting neurons were significantly smaller than the GAD negative projecting neurons. Our findings thus suggest the existence of two distinct cerebello-pretectal projection systems: one is mediated by GABAergic inhibitory projections, while the other is mediated by non-GABAergic, probably glutamatergic excitatory ones.

Ventral lateral geniculate nucleus projects to the dorsal lateral geniculate nucleus in the cat.

The lamina C3 of the dorsal lateral geniculate nucleus of the cat does not receive retinal projections but instead receives visual information from the small subpopulation of W-type ganglion cells via the upper substratum of the stratum griseum superficiale of the superior colliculus. We herein report a projection from the lateral division of the ventral lateral geniculate nucleus into the lamina C3 of the dorsal lateral geniculate nucleus. As the lateral division receives projections from the contralateral retina and the ipsilateral upper stratum griseum superficiale of the superior colliculus, we suggest that these regions make up a small cell type W-cell neuronal network that provides visual information to layer I of the striate cortex via the lamina C3.