The Role of the Medial Prefrontal Cortex in Spatial Margin of Safety Calculations.

Naturalistic observations show that animals pre-empt danger by moving to locations that increase their success in avoiding future threats. To test this in humans, we created a spatial margin of safety (MOS) decision task that quantifies pre-emptive avoidance by measuring the distance subjects place themselves to safety when facing different threats whose attack locations vary in predictability. Behavioral results show that human participants place themselves closer to safe locations when facing threats that attack in spatial locations with more outliers. Using both univariate and multivariate pattern analysis (MVPA) on fMRI data collected during a 2 h session on participants of both sexes, we demonstrate a dissociable role for the vmPFC in MOS-related decision-making. MVPA results revealed that the posterior vmPFC encoded for more unpredictable threats with univariate analyses showing a functional coupling with the amygdala and hippocampus. Conversely, the anterior vmPFC was more active for the more predictable attacks and showed coupling with the striatum. Our findings converge in showing that during pre-emptive danger, the anterior vmPFC may provide a safety signal, possibly via foreseeable outcomes, while the posterior vmPFC drives unpredictable danger signals.

Stem Cell Therapies for Restorative Treatments of Central Nervous System Ischemia-Reperfusion Injury.

Ischemic damage to the central nervous system (CNS) is a catastrophic postoperative complication of aortic occlusion subsequent to cardiovascular surgery that can cause brain impairment and sometimes even paraplegia. Over recent years, numerous studies have investigated techniques for protecting and revascularizing the nervous system during intraoperative ischemia; however, owing to a lack of knowledge of the physiological distinctions between the brain and spinal cord, as well as the limited availability of testing techniques and treatments for ischemia-reperfusion injury, the cause of brain and spinal cord ischemia-reperfusion injury remains poorly understood, and no adequate response steps are currently available in the clinic. Given the limited ability of the CNS to repair itself, it is of great clinical value to make full use of the proliferative and differentiation potential of stem cells to repair nerves in degenerated and necrotic regions by stem cell transplantation or mobilization, thereby introducing a novel concept for the treatment of severe CNS ischemia-reperfusion injury. This review summarizes the most recent advances in stem cell therapy for ischemia-reperfusion injury in the brain and spinal cord, aiming to advance basic research and the clinical use of stem cell therapy as a promising treatment for this condition.

Apple Pomace Compositional Data Highlighting the Proportional Contribution of Polymeric Procyanidins.

Recent years have seen an increase in research focusing on the amelioration of apple pomace waste for use in the food and nutraceutical industries. Much of this work has concentrated on the characterisation of the polyphenol composition of apple pomace materials to determine their role in conferring nutritional and health benefits. Although apples contain substantial quantities of polymeric procyanidins (condensed tannins), this class of compounds has received limited attention in apple research. This study quantified the polymeric procyanidins in apple pomace extracts using a rapid, methyl-cellulose precipitation (MCP) approach for the first time. In addition, a non-targeted metabolomics approach was applied to determine the most abundant phenolic classes present. Polymeric procyanidins were found to be the most abundant type of polyphenol in apple pomace extracts and were generally oligomeric in nature. Multivariate statistical analysis revealed that the ferric-reducing antioxidant power (FRAP) was most strongly correlated with the polymeric procyanidin concentration. Noting that polymeric procyanidins may not cross the cell layer to exert antioxidant activity in vivo, their presence in apple pomace extracts may therefore overestimate the FRAP. This work highlights the importance of polymeric procyanidins in the phenolic diversity of apple pomaces, and it is proposed that in future studies, rapid MCP assays may be used for their quantification.

Recycling of SLC38A1 to the plasma membrane by DSCR3 promotes acquired temozolomide resistance in glioblastoma.

PURPOSE: Glioblastoma multiforme (GBM) is a primary brain tumor with devastating prognosis. Although the O6-methylguanine-DNA methyltransferase (MGMT) leads to inherent temozolomide (TMZ) resistance, approximately half of GBMs were sufficient to confer acquired TMZ resistance, which express low levels of MGMT. The purpose of this study was to investigate the underlying mechanisms of the acquired TMZ resistance in MGMT-deficient GBM. METHODS: The function of Down syndrome critical region protein 3 (DSCR3) on MGMT-deficient GBM was investigated in vitro and in an orthotopic brain tumor model in mice. Purification of plasma membrane proteins by membrane-cytoplasmic separation and subsequent label free-based quantitative proteomics were used to identified potential protein partners for DSCR3. Immunofluorescence was performed to show the reverse transport of solute carrier family 38 member 1 (SLC38A1) mediated by DSCR3. RESULTS: DSCR3 is upregulated in MGMT-deficient GBM cells during TMZ treatment. Both DSCR3 and SLC38A1 were highly expressed in recurrent GBM patients. Silencing DSCR3 or SLC38A1 expression can increase TMZ sensitivity in MGMT-deficient GBM cells. Combination of proteomics and in vitro experiments show that DSCR3 directly binds internalized SLC38A1 to mediate its sorting into recycling pathway, which maintains the abundance on plasma membrane and enhances uptake of glutamine in MGMT-deficient GBM cells. CONCLUSIONS: DSCR3 is a crucial regulator of acquired TMZ resistance in MGMT-deficient GBM. The DSCR3-dependent recycling of SLC38A1 maintains its abundance on plasma membrane, leading to tumor progression and acquired TMZ resistance in MGMT-deficient GBM.

Controllable photonic spin hall effect of bilayer graphene.

Bilayer graphene, composed of two layers of monolayer graphene in AB stacking order, has emerged as an alternative platform for atomically thin plasmonic and optoelectronic devices. However, its behavior of photonic spin hall effect remains largely unexplored. In this work, we have theoretically observed that bilayer graphene has two obvious discontinuities but monolayer graphene only has a single step in the spectra of the spin shifts as a function of wavelength at the Brewster angle over the midinfrared frequency range, which enables a possible route of distinguishing monolayer graphene and bilayer graphene. Additionally, the magnitudes and positions of the peak and valley values in the spectrum of spin shifts of bilayer graphene can be tuned by its Fermi energy. We also achieved the enhanced out-of-pane spin shift of the glass-AB stacking bilayer graphene-air structure at both the Brewster angle (33.55°) and the critical angle (41.31°) with the aid of the high order of Laguerre-Gaussian beam. The realization of large and controlled spin shift in bilayer graphene indicates its promising applications in precision measurements and refractive index sensors at the midinfrared frequency region.

Comparison of the Safety and Efficacy of Three-Dimensional Guiding Templates and Free Hand Technique for Cervical Pedicle Screw Fixation: A Retrospective Study.

Aim. To compare the safety and efficacy of computed tomography (CT)-assisted three-dimensional guiding templates (3DGTs) and free-hand (FH) technique for posterior cervical pedicle screw fixation in cervical spondylotic myelopathy (CSM) treatment. Methods. Thirty-five patients (216 screws) with CSM and developmental cervical stenosis were randomly divided into groups A (FH) and B (3DGTs). All patients underwent modified posterior surgery with cervical pedicle screw insertion (C1-7). Preoperative, postoperative, and intergroup comparisons of efficacy were evaluated using the visual analog scale (VAS), Japanese Orthopaedic Association (JOA), and Short Form 12 (SF-12) scores and JOA score improvement rate. Incidence of intra- and postoperative complications was analyzed. Postoperative cervical spine CT was performed to evaluate (i) the pedicle screws' deviation angle from the optimal path (sagittal deviation, α; coronal deviation angle, ß), screw insertion point's deviation distance (d), and screw accuracy and (ii) the deviation angle and distance of screw entrance point of pedicle screws from the optimal channel. Results. All patients successfully completed the procedures. Groups A and B did not significantly differ in age, sex ratio, body mass index, operative time, or intraoperative blood loss amount. Postoperative VAS, JOA, and SF-12 scores improved in both groups. VAS, JOA, or SF-12 scores did not significantly differ between the 2 groups. The α, ß, and d scores were lower in group B, but accuracy was higher in group B. Conclusions. 3DGTs and FH technique show comparable outcomes with respect to neurological improvement and safety.

A Tumor-Penetrating Nanomedicine Improves the Chemoimmunotherapy of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors with a low survival rate. The therapeutic effect of chemotherapy and immunotherapy for PDAC is disappointing due to the presence of dense tumor stroma and immunosuppressive cells in the tumor microenvironment (TME). Herein, a tumor-penetrating nanoparticle is reported to modulate the deep microenvironment of PDAC for improved chemoimmunotherapy. The tumor pH-sensitive polymer is synthesized by conjugating N,N-dipentylethyl moieties and monomethoxylpoly(ethylene glycol) onto PAMAM dendrimer, into whose cavity a hydrophobic gemcitabine (Gem) prodrug is accommodated. They self-assemble into nanoparticles (denoted as SPN@Pro-Gem) with the size around 120 nm at neutral pH, but switch into small particles (≈8 nm) at tumor site to facilitate deep delivery of Gem into the tumor parenchyma. In addition to killing cancer cells that resided deeply in the tumor tissue, SPN@Pro-Gem could modulate the TME by reducing the abundance of tumor-associated macrophages and myeloid-derived suppressor cells as well as upregulating the expression level of PD-L1 of tumor cells. This collectively facilitates the infiltration of cytotoxic T cells into the tumors and renders checkpoint inhibitors more effective in previously unresponsive PDAC models. This study reveals a promising strategy for improving the chemoimmunotherapy of pancreatic cancer.

Establishing a papillary craniopharyngioma cell line by SV40LT-mediated immortalization.

BACKGROUND: Craniopharyngioma represents a troublesome tumor of the intracranial sellar region. There are currently no available well-characterized craniopharyngioma cell lines. This lack of reliable, immortal cell lines is a major reason for the slow progress in fundamental research related to craniopharyngioma. METHODS: We describe the development of an immortal papillary craniopharyngioma (PCP) cell line by transfecting primary PCP cells with the pLenti-simian virus 40 large T antigen(SV40LT). RESULTS: Three clones have been cultured for more than 14 months so far, while non-transfected cells ceased proliferation within three months of isolation. The established immortal PCP cell lines were identified to have BRAFV600E mutations, while no mutations in tumor suppressor genes were found in primary cells or immortal cells. Immortal cells had higher proliferation rates and formed tumors when implanted in the bran of nude mice. BRAF inhibition in immortal PCP cells altered cell morphology, inhibited cell proliferation and promoted apoptosis. CONCLUSION: We successfully developed PCP cell lines by SV40LT-mediated immortalization. These cell lines represent a powerful tool for fundamental and therapeutical studies on craniopharyngioma.

How cognitive and reactive fear circuits optimize escape decisions in humans.

Flight initiation distance (FID), the distance at which an organism flees from an approaching threat, is an ecological metric of cost-benefit functions of escape decisions. We adapted the FID paradigm to investigate how fast- or slow-attacking "virtual predators" constrain escape decisions. We show that rapid escape decisions rely on "reactive fear" circuits in the periaqueductal gray and midcingulate cortex (MCC), while protracted escape decisions, defined by larger buffer zones, were associated with "cognitive fear" circuits, which include posterior cingulate cortex, hippocampus, and the ventromedial prefrontal cortex, circuits implicated in more complex information processing, cognitive avoidance strategies, and behavioral flexibility. Using a Bayesian decision-making model, we further show that optimization of escape decisions under rapid flight were localized to the MCC, a region involved in adaptive motor control, while the hippocampus is implicated in optimizing decisions that update and control slower escape initiation. These results demonstrate an unexplored link between defensive survival circuits and their role in adaptive escape decisions.

Nanoparticle-Enabled Dual Modulation of Phagocytic Signals to Improve Macrophage-Mediated Cancer Immunotherapy.

Activation of the phagocytosis of macrophages to tumor cells is an attractive strategy for cancer immunotherapy, but the effectiveness is limited by the fact that many tumor cells express an increased level of anti-phagocytic signals (e.g., CD47 molecules) on their surface. To promote phagocytosis of macrophages, a pro-phagocytic nanoparticle (SNPACALR&aCD47 ) that concurrently carries CD47 antibody (aCD47) and a pro-phagocytic molecule calreticulin (CALR) is constructed to simultaneously modulate the phagocytic signals of macrophages. SNPACALR&aCD47 can achieve targeted delivery to tumor cells by specifically binding to the cell-surface CD47 and block the CD47-SIRPα pathway to inhibit the "don't eat me" signal. Tumor cell-targeted delivery increases the exposure of recombinant CALR on the cell surface and stimulates an "eat me" signal. Simultaneous modulation of the two signals enhances the phagocytosis of 4T1 tumor cells by macrophages, which leads to significantly improved anti-tumor efficacy in vivo. The findings demonstrate that the concurrent blockade of anti-phagocytic signals and activation of pro-phagocytic signals can be effective in macrophage-mediated cancer immunotherapy.

Nanoenabled Reversal of IDO1-Mediated Immunosuppression Synergizes with Immunogenic Chemotherapy for Improved Cancer Therapy.

Certain chemotherapeutics (e.g., oxaliplatin, OXA) can evoke effective antitumor immunity responses by inducing immunogenic cell death (ICD). Unfortunately, tumors always develop multiple immunosuppressive mechanisms, such as the upregulation of immunosuppressive factors, to counteract the effects of immunogenic chemotherapy. Indoleamine 2,3-dioxygenase-1 (IDO1), a tryptophan catabolic enzyme overexpressed in tumor-draining lymph nodes (TDLNs) and tumor tissues, plays a pivotal role in the generation of the immunosuppressive microenvironment. Reversing IDO1-mediated immunosuppression may strengthen the ICD-induced immune response. Herein, we developed a nanoenabled approach for IDO1 pathway interference, which is accomplished by delivering IDO1 siRNA to both TDLNs and tumor tissues with the help of cationic lipid-assisted nanoparticles (CLANs). We demonstrated that the contemporaneous administration of OXA and CLANsiIDO1 could achieve synergetic antitumor effects via promoting dendritic cell maturation, increasing tumor-infiltrating T lymphocytes and decreasing the number of regulatory T cells in a subcutaneous colorectal tumor model. We further proved that this therapeutic strategy is applicable for the treatment of orthotopic pancreatic tumors and offers a strong immunological memory effect, which can provide protection against tumor rechallenge.

A Collaborator's Reputation Can Bias Decisions and Anxiety under Uncertainty.

Informational social influence theory posits that under conditions of uncertainty, we are inclined to look to others for advice. This leaves us remarkably vulnerable to being influenced by others' opinions or advice. Rational agents, however, do not blindly seek and act on arbitrary information, but often consider the quality of its source before committing to a course of action. Here, we ask the question of whether a collaborator's reputation can increase their social influence and, in turn, bias perception and anxiety under changing levels of uncertainty. Human male and female participants were asked to provide estimations of dot direction using the random dot motion (RDM) perceptual discrimination task and were paired with transient collaborators of high or low reputation whom provided their own estimations. The RDM varied in degrees of uncertainty and joint performance accuracy was linked to risk of an electric shock. Despite providing identical information, we show that collaborating with a high reputation compared with a low reputation partner, led to significantly more conformity during the RDM task for uncertain perceptual decisions. Consequently, high reputation partners decreased the subjects' anxiety during the anticipatory shock periods. fMRI data showed that parametric changes in conformity resulted in increased activity in the ventromedial PFC, whereas dissent was associated with increased in activity in the dorsal anterior cingulate cortex (dACC). Furthermore, the dACC and insula, regions involved in anticipatory pain, were significantly more active when collaborating with a low reputation partner. These results suggest that information about reputation can influence both cognitive and affective processes and in turn alter the neural circuits that underlie decision-making and emotion.SIGNIFICANCE STATEMENT Humans look to others for advice when making decisions under uncertainty. Rational agents, however, do not blindly seek information, but often consider the quality of its source before committing to a course of action. Here, we ask the question of whether a collaborators' reputation can increase social influence and in turn bias perception and anxiety in the context of perceptual uncertainty. We show that when subjects are partnered with collaborators with a high reputation, this leads to increased conformity during uncertain perceptual decision-making and reduces anxiety when joint performance accuracy leads to an electric shock. Furthermore, our results show that information about reputation alters the neural circuits that underlie decision-making and emotion.

Lipid oxidation stability of ultra-high-temperature short-time sterilization sporoderm-broken pine pollen (UHT-PP) and 60 Co-irradiation sterilization sporoderm-broken pine pollen (60 Co-PP).

BACKGROUND: Pine pollen, a kind of Chinese traditional medicine, is rich in unsaturated fatty acids. During its processing, it is often needed to break the sporoderm in order to increase the availability of some ingredients, which can cause lipid oxidation and the development of rancidity during storage. RESULTS: The primal peroxide value (PV) of ultra-high-temperature short-time sterilization sporoderm-broken pine pollen (UHT-PP) was much higher (over 15 times) than raw pine pollen (R-PP) and 60 Co-irradiation sterilization sporoderm-broken pine pollen (60 Co-PP). The PV of UHT-PP first increased and then decreased shortly after; however, PV of R-PP and 60 Co-PP remained almost unchanged during storage. The volatiles associated with rancidity in UHT-PP were found to be significantly higher than 60 Co-PP, especially hexanal (nearly 30 times) and hexanoic acid (about 2 times), and a multi-organoleptic sensor analyzer (electronic nose system) was able to differentiate these three kinds of samples when the output was subjected to discriminant function analysis. During storage (30 days), hexanal first increased and then decreased (at about 5 days), and hexanoic acid continuously increased for UHT-PP; however, no significant change was noted for R-PP or 60 Co-PP. UHT-PP has a greater surface area than 60 Co-PP, although same sporoderm-broken processes were applied. Antioxidants (flavone, carotenoid and tocopherols, sterol compounds) in 60 Co-PP were significantly (P ≤ 0.05, by Duncan's multiple range test) higher than that in UHT-PP, although not significantly different for total phenolics. CONCLUSIONS: Rancidity occurs more readily in UHT-PP than in R-PP and 60 Co-PP during storage, probably because significant lipid oxidation and antioxidant degradation occurred during the UHT sterilization sporoderm-broken processing of pine pollen. © 2018 Society of Chemical Industry.

Komagataeibacter cocois sp. nov., a novel cellulose-producing strain isolated from coconut milk.

Phylogenetic analysis was performed on a cellulose-producing strain, designated WE7T, isolated from contaminated coconut milk. The analysis utilized nearly complete 16S rRNA gene sequences, as well as concatenated partial sequences of the housekeeping genes dnaK, groEL and rpoB, and allowed identification of the strain as belonging to the genus Komagataeibacter. DNA-DNA correlation or average nucleotide identity analysis was performed between WE7T and its closest phylogenetic neighbours, and the resulting values were below the species level (<70 % and <95 %), suggesting that the strain represents a novel species in genus Komagataeibacter. Strain WE7T was coupled with Komagataeibacter species more tightly than with Gluconacetobacter species in a 16S rRNA gene sequence phylogenetic tree. Strain WE7T can be differentiated from closely related Komagataeibacter and Gluconacetobacter entanii species by the ability to grow on the carbon sources d-mannitol, sodium d-gluconate and glycerol, the ability to form acid by d-fructose, sucrose, d-mannitol, d-galactose and ethanol, and the ability to grow without acetic acid. The major fatty acid of WE7T is C18 : 1ω9c (52.3 %). The DNA G+C content of WE7T is 63.2 mol%. The name Komagataeibacter cocois sp. nov. is proposed, with the type strain WE7T (=CGMCC 1.15338T=JCM 31140T).

An EPDM/MVQ polymer blend based magnetorheological elastomer with good thermostability and mechanical performance.

Magnetorheological elastomers (MREs) with outstanding magnetic-control properties are highly desirable for applications such as vibration attenuation, smart sensing, and soft robots. However, the low strength and thermolability of these materials still restrict their application in attenuating the vibration of large-scale devices. In this paper, we prepared an MRE based on ethylene-propylene-diene monomer (EPDM)/methylvinyl silicone rubber (MVQ) polymer blends. The resulting MRE showed good thermostability and mechanical properties. Good interfacial interaction and particle dispersion were achieved by modifying the surface of carbonyl iron powder (CIP) with silica coating by the sol-gel method. The compatibility between the EPDM and MVQ was promoted using silane coupling agents. Moreover, the resulting MRE had high mechanical strength and elongation at break. The dynamic viscoelastic properties of the MRE were tested using a rheometer. The influences of frequency, strain, matrices, temperature, and magnetic fields were discussed comprehensively, and relevant physical mechanisms were proposed. Finally, thermal aging tests were performed to evaluate the heat resistance of the MRE. Analytical results showed that the resulting MRE could be significantly applied to reduce the vibration of large devices because of its excellent mechanical properties and thermostability.

Crosslinked Aspartic Acids as Helix-Nucleating Templates.

Described is a facile helix-nucleating template based on a tethered aspartic acid at the N-terminus [terminal aspartic acid (TD)]. The nucleating effect of the template is subtly influenced by the substituent at the end of the side-chain-end tether as indicated by circular dichroism, nuclear magnetic resonance, and molecular dynamics simulations. Unlike most nucleating strategies, the N-terminal amine is preserved, thus enabling further modification. Peptidomimetic estrogen receptor modulators (PERMs) constructed using this strategy show improved therapeutic properties. The current strategy can be regarded as a good complement to existing helix-stabilizing methods.

Oxytocin selectively facilitates learning with social feedback and increases activity and functional connectivity in emotional memory and reward processing regions.

In male Caucasian subjects, learning is facilitated by receipt of social compared with non-social feedback, and the neuropeptide oxytocin (OXT) facilitates this effect. In this study, we have first shown a cultural difference in that male Chinese subjects actually perform significantly worse in the same reinforcement associated learning task with social (emotional faces) compared with non-social feedback. Nevertheless, in two independent double-blind placebo (PLC) controlled between-subject design experiments we found OXT still selectively facilitated learning with social feedback. Similar to Caucasian subjects this OXT effect was strongest with feedback using female rather than male faces. One experiment performed in conjunction with functional magnetic resonance imaging showed that during the response, but not feedback phase of the task, OXT selectively increased activity in the amygdala, hippocampus, parahippocampal gyrus and putamen during the social feedback condition, and functional connectivity between the amygdala and insula and caudate. Therefore, OXT may be increasing the salience and reward value of anticipated social feedback. In the PLC group, response times and state anxiety scores during social feedback were associated with signal changes in these same regions but not in the OXT group. OXT may therefore have also facilitated learning by reducing anxiety in the social feedback condition. Overall our results provide the first evidence for cultural differences in social facilitation of learning per se, but a similar selective enhancement of learning with social feedback under OXT. This effect of OXT may be associated with enhanced responses and functional connectivity in emotional memory and reward processing regions.

Periostin: a novel prognostic predictor for meningiomas.

The expression and role of periostin in meningiomas remains unknown. Tissue specimens of 175 convexity meningiomas were immunohistochemically examined with antibodies against periostin and Ki67. The expression levels of periostin and Ki67 were compared among different WHO groups. The role of periostin and Ki67 in postoperative prognosis of meningiomas was also analyzed. Negative (-) expression of Ki67 was observed in 101 (57.7 %) cases of all the surgical tissue samples. The Ki67 expressions differed significantly among the WHO groups (P < 0.001) and correlated positively with the WHO grade (r = 0.673, P < 0.001). Low/negative staining of periostin was observed in 116 (66.3 %) cases. The periostin expressions differed significantly among the WHO groups (P < 0.001). Periostin expression correlated positively with the WHO grade (r = 0.742, P < 0.001). There was a positive correlation between Ki67 expression and periostin (r = 0.513, P < 0.001). Both Ki67 expression and periostin expression was found statistically different between brain invasion tumor and non-invasion tumor (p < 0.001). The recurrence rate and PFS rate in both varied Ki67 expression groups and periostin expression groups was statistically different (P < 0.001). The survival time and PFS time in both varied Ki67 expression groups and periostin expression groups was also statistically different (P < 0.001). Periostin was expressed in tumor stroma of meningiomas. Both periostin and Ki67 may behave as a maker in predicting the grade and prognosis in meningiomas. Drugs that targets periostin aims at reducing invasion of meningioma patients should be further researched.

Tumor cells forming sinusoids connected to vasculature are involved in hemorrhage of pineal choriocarcinoma.

Intratumor hemorrhage is a poor prognostic factor in pineal choriocarcinoma (PCCC). The aim of this study was to understand the relationship of tumor cells to the blood vessels to gain insights into the formation of intratumor hemorrhage in PCCC. The clinical data indicated that total tumor removal by surgical procedures followed immediately by radiotherapy and chemotherapy improved the prognosis in PCCC. The PCCC tissues removed from the patients were examined by histology and immunohistochemistry. Hematoxylin and eosin staining showed that the tumor stroma mainly consists of hemorrhagic tissues with tumor cells scattered inside. The pattern of distribution suggests that the tumor cells were possibly flushed and compressed by the bleeding. The tumor cells tended to form sinusoids that lacked CD34, but laminin expression provided evidence of vasculogenic mimicry. Interestingly, CD34-positive blood vessels were found connected to these sinusoids, suggesting that blood may flow from the tumor vasculature to the sinusoids. This may subsequently cause the enlargement of the sinusoids, blood clotting, the widening of the blood lakes, and eventually extensive hemorrhagic necrosis. Our study identified the key features of the PCCC vasculature. The findings add to the previous understanding of the formation of vascular channels, blood lakes, and extensive hemorrhagic necrosis. The intimate connections between the tumor-formed sinusoids and the blood vessels might be a major cause of severe hemorrhage in PCCC. The new information may be useful for the development of treatment strategies for managing PCCC.

Relationships of LDLR genetic polymorphisms with cerebral infarction: a meta-analysis.

This meta-analysis was undertaken to identify the relationships between genetic polymorphisms in the LDLR gene and the risk of cerebral infarction. The Web of Science (1945-2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966-2013), EMBASE (1980-2013), CINAHL (1982-2013) and the Chinese Biomedical Database (CBM) (1982-2013) were searched for relevant articles without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios (OR) with their corresponding 95% confidence interval (CI) were calculated. Eight case-control studies with a total of 4,655 patients with cerebral infarction and 15,920 healthy control subjects were included in our meta-analysis. Five common polymorphisms in the LDLR gene were evaluated, including rs11669576 A > T, rs1433099 C > T, rs5925 C > T, rs688 C > T, rs1122608 T > G in the LDLR gene. The results of this meta-analysis revealed that cerebral infarction patients had a higher frequency of LDLR genetic polymorphisms than that of healthy controls (allele model: OR 1.17, 95% CI 1.05-1.30, P = 0.004; dominant model: OR 1.18, 95% CI 1.05-1.33, P = 0.007; homozygous model: OR 1.50, 95% CI 1.03-2.16, P = 0.032; respectively), especially for the rs11669576 A > T, rs1433099 C > T and rs5925 C > T polymorphisms. Among different ethnic subgroups, the results demonstrated positive correlations between LDLR genetic polymorphisms and an increased risk of cerebral infarction among both Asians and Caucasians under the allele and dominant models (all P < 0.05). Our findings indicate that LDLR genetic polymorphisms may be strongly involved in the pathogenesis of cerebral infarction, especially the rs11669576 A > T, rs1433099 C > T, rs5925 C > T polymorphisms.