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Seventeen C20-O-alkyl/benzyl oxime derivatives were synthesized by a concise and effective method, which showed 15~240 folds better antiproliferative activity, more potent ion binding and transport ability and better selectivity indexes (SI) than salinomycin.

BackgroundBlood-brain barrier disruption is a prominent pathological characteristic of aneurysmal subarachnoid hemorrhage (aSAH), which can be measured as Ktransusing CT perfusion.PurposeTo monitor Ktranswithin 24 hours of aSAH and during the time window associated with a delayed cerebral ischemia (DCI) event (DCITW), and to explore its association with the trajectory of DCI, including outcome at three months.MethodsWe retrospectively assessed consecutive aSAH patients from a prospective database between July 2020 and September 2022. Patients were grouped according to the DCI occurrence and three months modified Rankin scale. Ktransat admission (admission Ktrans) and during DCITW (DCITW Ktrans) were compared between DCI and non-DCI groups, and between good outcome and poor outcome groups. The changes in Ktranswere also analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of DCI and poor outcome.ResultsOne hundred and twenty-eight patients (mean age, 61±12 [SD]; 75 women) were included. Both admission Ktrans(0.58±0.18 vs 0.47±0.12,P=0.002) and DCITW Ktrans(0.54±0.19 vs 0.41±0.14,PP=0.198). Ktransin the non-DCI group (0.47±0.12 vs 0.41±0.14,P=0.004) and good outcome group (0.49±0.14 vs 0.41±0.14,Ptransand admission Ktransas independent predictors of poor outcome (OR=1.73, 95%CI: 1.24-2.43,P=0.001) and DCI (OR=1.75, 95%CI: 1.25-2.44,P=0.001), respectively.ConclusionElevated Ktransat admission is associated with the occurrence of DCI, but not with outcome at three months. Continuous monitoring of Ktransfrom admission to DCITW can accurately identify reversible and irreversible changes in Ktrans, and can predict outcome.

Knowledge Organization Systems (KOS) as networks of knowledge have the potential to inform AI operations. This paper explores natural language processing and machine learning in the context of KOS ...

Luteolin (LUT) possesses multiple biologic functions and has beneficial effects for cardiovascular and cerebral vascular diseases. Here, we investigated the protective effects of LUT against subarachnoid hemorrhage (SAH) and the involvement of underlying molecular mechanisms. In a rat model of SAH, LUT significantly inhibited SAH-induced neuroinflammation as evidenced by reduced microglia activation, decreased neutrophil infiltration, and suppressed proinflammatory cytokine release. In addition, LUT markedly ameliorated SAH-induced oxidative damage and restored the endogenous antioxidant systems. Concomitant with the suppressed oxidative stress and neuroinflammation, LUT significantly improved neurologic function and reduced neuronal cell death after SAH. Mechanistically, LUT treatment significantly enhanced the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), while it downregulated nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation. Inhibition of Nrf2 by ML385 dramatically abrogated LUT-induced Nrf2 activation and NLRP3 suppression and reversed the beneficial effects of LUT against SAH. In neurons and microglia coculture system, LUT also mitigated oxidative stress, inflammatory response, and neuronal degeneration. These beneficial effects were associated with activation of the Nrf2 and inhibitory effects on NLRP3 inflammasome and were reversed by ML385 treatment. Taken together, this present study reveals that LUT confers protection against SAH by inhibiting NLRP3 inflammasome signaling pathway, which may be modulated by Nrf2 activation.

Purpose The output of academic literature has increased significantly due to digital technology, presenting researchers with a challenge across every discipline, including materials science, as it is impossible to manually read and extract knowledge from millions of published literature. The purpose of this study is to address this challenge by exploring knowledge extraction in materials science, as applied to digital scholarship. An overriding goal is to help inform readers about the status knowledge extraction in materials science. Design/methodology/approach The authors conducted a two-part analysis, comparing knowledge extraction methods applied materials science scholarship, across a sample of 22 articles; followed by a comparison of HIVE-4-MAT, an ontology-based knowledge extraction and MatScholar, a named entity recognition (NER) application. This paper covers contextual background, and a review of three tiers of knowledge extraction (ontology-based, NER and relation extraction), followed by the research goals and approach. Findings The results indicate three key needs for researchers to consider for advancing knowledge extraction: the need for materials science focused corpora; the need for researchers to define the scope of the research being pursued, and the need to understand the tradeoffs among different knowledge extraction methods. This paper also points to future material science research potential with relation extraction and increased availability of ontologies. Originality/value To the best of the authors’ knowledge, there are very few studies examining knowledge extraction in materials science. This work makes an important contribution to this underexplored research area.

The influence of mold temperature and filling velocity on the formation and distribution of the mesophase in ultrasonic micro-injection-molded isotactic polypropylene (iPP) was explored using a wide-angle X-ray diffraction (WAXD) technique. A Gaussian fitting method was used to decompose one-dimensional WAXD profiles into quantitative fractions of the crystalline lamellae, mesophase, and amorphous phase. It was found that the mesophase formation can only be detected up to a mold temperature of 60 °C due to its low thermal stability. Moreover, the content of the mesophase decreases distinctly as the filling velocity is increased. The component is mainly located in the core layer after examining the distribution of each crystal form along the thickness direction, irrespective of mold temperature and filling velocity. All these findings can be attributed to the correlation between the degree of molecular orientation and the cooling rate. A high cooling rate occurred during the micro-injection molding process produces the result that there is less time for the polymeric chains with a low level of orientation to crystallize into a well-ordered structure, thus yielding many mesophase crystals with a paracrystalline smectic arrangement especially in the core layer. Finally, a diagram for mesophase formation was constructed in mold temperature–filling velocity space, which offers a detailed road map for regulating mesophase fraction in ultrasonic micro-injection molding operations.

Neuroinflammatory injury, oxidative insults, and neuronal apoptosis are major causes of poor outcomes after subarachnoid hemorrhage (SAH). Pterostilbene (PTE), an analog of resveratrol, has been verified as a potent sirtuin 1 (SIRT1) activator. However, the beneficial actions of PTE on SAH-induced brain injury and whether PTE regulates SIRT1 signaling after SAH remain unknown. We first evaluated the dose-response influence of PTE on early brain impairment after SAH. In addition, EX527 was administered to suppress SIRT1 signaling. The results revealed that PTE significantly attenuated microglia activation, oxidative insults, neuronal damage, and early neurological deterioration. Mechanistically, PTE effectively enhanced SIRT1 expression and promoted nuclear factor-erythroid 2-related factor 2 (Nrf2) accumulation in nuclei. Furthermore, EX527 pretreatment distinctly repressed PTE-induced SIRT1 and Nrf2 activation and deteriorated these beneficial outcomes. In all, our study provides the evidence that PTE protects against SAH insults by activating SIRT1-dependent Nrf2 signaling pathway. PTE might be a therapeutic alternative for SAH.

Objective Hemodynamic factors are thought to play important roles in the pathogenesis, progression, and rupture of cerebral aneurysms. Previous hemodynamic studies have been based on comparisons between post-ruptured and unruptured aneurysms. Nevertheless, changes of aneurysm morphology after rupture render these results unreliable. Moreover, pressure, age, gender, and the morphology of the parent artery also influence these results. Therefore, in the present study, we identified hemodynamic and morphological characteristics of aneurysms prior to rupture using twelve mirror aneurysms. Materials and methods From our database, we retrospectively analyzed twelve mirror aneurysms (MANs) prior to rupture. Each mirror aneurysm was divided into the prior to rupture or the unruptured group. Patient-specific models were reconstructed from three-dimensional (3D) images of all patients. Hemodynamic and morphological factors were analyzed and compared. Results Compared with the unruptured side of MANs, aneurysms prior to rupture were significantly larger and significantly more irregular in shape; they also had significantly higher aspect ratio (AR), size ratio (SR), undulation index (UI), ellipticity index (EI), percentage of low wall shear stress area (LSA) and significantly lower normal wall shear stress (NWSS). The oscillatory shear index (OSI) and nonsphericity index (NSI) in the aneurysms prior to rupture were non-significantly higher than those of the unruptured group. Conclusion MANs prior to rupture may be extremely useful models to assess the risk of aneurysm rupture. Larger size, irregular shape, higher AR, SR, UI, NI, and lower WSS may be associated with aneurysms at risk for rupture.

This study offers one of the first causal evidence on the morbidity costs of fine particulates (PM2.5) for all age cohorts in a developing country, using individual-level healthcare spending data from the basic medical insurance program in Wuhan, China. Our instrumental variable (IV) approach uses thermal inversion to address potential endogeneity in PM2.5 concentrations and shows that PM2.5 imposes a significant impact on medical expenditures. The IV estimate suggests that a 10 μg/m3 reduction in monthly average PM2.5 leads to a 2.79% decrease in the value of health spending and a 0.70% decline in the number of transactions in pharmacies and health facilities. The effect is more salient for males, children, and older adults. Moreover, our estimates provide a lower bound of people’s willingness-to-pay, which amounts to CNY 51.85 (or USD 8.38) per capita per year for a 10 μg/m3 reduction in PM2.5.JEL CodesQ51, Q53, I11, I31Conflict of interestThe authors declare that they have no conflict of interest.

This meeting abstract was removed due to the OA licensing requirements of this journal. The full abstract is listed here : https://www.svin.org/files/SVIN_2021_Abstracts_for_Web.pdf

Background Extensive research has explored disparities in access to health care between people with and without disabilities, but much less is understood about disparities and associated factors within the disabled population. Objective The aim of this study was to examine differences in the prevalence of unmet health-care needs by residential status (hukou status) and disability type among people with disabilities. Methods Our data were from the National Survey on Basic Public Service Delivery of Persons with Disabilities. The analysis sample included a nationally representative sample of 9 642 112 adults (aged 16+ years) with disabilities. Associated factors were obtained at both individual level and community level. Cross-sectional multivariable logistic regression analyses were conducted to compare unmet medical, care, rehabilitation and accessibility needs among people with different residential statuses and different types of disabilities. Results The estimated prevalence of unmet medical, care, rehabilitation and accessibility needs is 15.4%, 10.2%, 45.6% and 13.7%, respectively. Rural hukou was associated with an important 13–40% increase in unmet health-care needs for people with disabilities in China. These rural–urban disparities in unmet health service needs can be partly explained by community-level factors, including access to facilities, social participation and health professionals. Disparities across the type of disability were smaller, but on average, people with multiple disabilities appeared to have the highest rates of unmet care, medical and accessibility needs, whereas those with physical disability had the highest unmet rehabilitation need. Conclusions Differences by residential status and impairment type were evident in all types of unmet health service needs. Targeted policy designs that meet the needs for justice and equality of people with disabilities are advisable. Public health and policy efforts are required to improve access to health service and meet the needs of people with disabilities, especially in rural practices and for particular disability groups.

Objective: Morphological and hemodynamic parameters might predict rupture of intracranial aneurysms (IAs). A practical model for the study is patients with ruptured mirror IAs in which one is ruptured and the other is unruptured. Although there have been analyses of the morphology and hemodynamics of ruptured mirror posterior communicating artery aneurysms (PComAAs), the sample sizes in these studies were small and only considered hemodynamics or morphological characters. Therefore, this study aimed to investigate the morphological and hemodynamic parameters associated with ruptured mirror PComAAs.Methods: We considered 72 patients with ruptured mirror PComAAs using computational fluid dynamics (CFDs). Ruptured mirror PComAAs were divided into ruptured and unruptured groups. Fourteen morphological and eight hemodynamic parameters were calculated and compared. Significant parameters were analyzed by the multivariate logistic regression to identify independent risk factors. Receiver operating characteristic (ROC) analysis was performed, and the area under the ROC curve (AUC) was calculated for all independent risk factors to determine the predictability and identify the optimal threshold.Results: Four hemodynamic and three morphological parameters were significantly different between ruptured and unruptured groups: normalized wall shear stress (NWSS), mean WSS, low wall shear WSS area (LSA%), size, aspect ratio (AR), size ratio (SR), and inflow angle (IA). Multivariate logistic regression analysis showed that AR, SR, NWSS, mean WSS, and LSA% were all independent factors significantly associated with PComAAs rupture. The ROC analysis for independent risk factors indicated that AR (0.751), NWSS (0.755), mean WSS (0.69), and LSA (0.778) had merely acceptable AUC values. Only SR (0.803) had a high acceptable AUC value. The threshold value of SR was 1.96.Conclusions: SR (>1.96) was the most significant parameter associated with IA rupture, whereas AR, NWSS, mean WSS, and LSA independently characterized the status of IA rupture.

This study examines the shear-induced formation of fibrillar form II crystals and subsequent form II to I transformation of an isotactic polybutene-1 sample through a combination of rheology, polarized optical microscopy (POM), and small- and wide-angle X-ray scattering (SAXS and WAXS) measurements. Strong shear flow was applied using a strain-controlled rheometer with parallel plate geometry, for which the shear rate increases linearly from the center to the perimeter. Highly oriented crystals were created by the shear flow, leading to the birefringent region shown in the POM images, which propagated from the perimeter to the center with increasing applied shear rate. The form II to I transformation, traced by WAXS, was greatly accelerated with increasing shear rate. This trend is explained as being due to the formation of fibrillar crystals and accordingly a large amount of highly oriented chains tethered between the crystal lamellae. The stress sustained by these tethered chains facilitates the nucleation of form I thereby accelerating the form II to I transformation.

We analyzed changes in China’s industrial electricity consumption using a structural decomposition model based on input-output analysis. China’s industrial electricity consumption changes during 2007–2012 were decomposed into four factors: electricity intensity, technology-input structural, final demand structure and total final demand. The results showed that changes in total final demand contributed most to increases in China’s industrial electricity consumption, which increased electricity consumption by 2091.34 billion kW h. As for aggregate demand, increased investment, urban residential consumption, and exports all played major roles. However, increases in total rural residents’ consumption and total inventory had little effect on the electricity consumption of various industrial sectors. The key reason for reductions in industrial electricity consumption was the decrease in electricity intensity in the heavy manufacturing industry, the service industry, and the energy industry. The decline in electricity consumption intensity in China reduced electricity consumption by 446.21 billion kW h.

Jinlong Yuan,1,&ast; Chenlei Huang,2,&ast; Zhenbao Li,1 Xiaochun Jiang,1 Xintong Zhao,1 Niansheng Lai,1 Dayong Xia,1 Degang Wu,1 Bingbing Zhang,1 Xuanzhi Wang,3 Xinggen Fang1 1Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, People’s Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, People’s Republic of China; 3Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinggen FangDepartment of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Zheshan West Road 2, Wuhu, 241001, People’s Republic of ChinaEmail 18805536056@163.comObjective: Hemodynamic parameters are associated with the recurrence of intracranial aneurysms (IAs). Studies showed that high velocity and wall shear stress (WSS) were associated with IAs recurrence after endovascular treatment; nevertheless, factors such as small sample size, locations of IAs, and types of IAs (ie, sidewall or bifurcation) were neglected. The purpose of this study was to identify the hemodynamic characteristics associated with recurrence of middle cerebral artery bifurcation aneurysms (MCABAs) after total embolization by the method of computer fluid dynamics (CFD).Methods: Following inclusion criteria, we included 92 MCABAs treated with coils only after total embolization from January 2014 to January 2019. We segmented into recurrent and non-recurrent groups according to follow-up digital subtraction angiography (DSA). The MCABA models, including pre-operatively and immediate post-operatively, were reconstructed using 3D-DSAs. The hemodynamic parameters pre-operatively and immediately post-operatively between the groups were calculated and analyzed.Results: There were no significant differences between the recurrent and non-recurrent groups for spatially averaged wall shear stress (SAWSS), maximum wall shear stress (MWSS), velocity, or oscillatory shear index (OSI) at the neck pre-operatively. In the recurrent group, the WSS (22.02± 5.11 vs 37.43± 8.27 pa, p < 0.001), MWSS (42.59± 17.02 vs 66.98± 18.61 pa, p=0.014), velocity (0.86± 0.19 vs 1.44± 0.61 m/s, p=0.01) preoperatively were significantly higher than postoperative values. By contrast, in the non-recurrent group, the WSS (26.53± 8.18 vs 22.29± 8.64pa, p=0.002), MWSS (42.71± 14.01 vs 37.15± 15.56 pa, p=0.013), velocity (1.08± 0.43 vs 0.23 (0.52, 0.57) m/s, p < 0.001) postoperatively were significantly lower than preoperative values. The OSI, whether in the recurrent group or the non-recurrent group, did not differ significantly between groups (p=0.79 and p=0.19).Conclusion: Higher WSS (SAWSS, MWSS) and flow velocity at the aneurysm neck after embolization might be related to recurrence of bifurcation IAs. These might be applied to clinical post-embolization management for the evaluation of bifurcation IAs recanalization.Keywords: computational fluid dynamic, hemodynamics, middle cerebral artery bifurcation aneurysms, recurrence

令和3年度博士論文要旨

BackgroundPrevious studies suggest that retirement, a major life event, affects overall healthcare utilization. We examine, the effects of retirement on inpatient healthcare utilization, including effect heterogeneity by gender, disease category, and type of health service.MethodsWe used routine health insurance claims data (N= 87,087) spanning the period 2021 - September 2013 from the Urban Employee Basic Medical Insurance (UEBMI), a mandatory social health insurance for working and retired employees in urban China. We applied a non-parametric fuzzy regression discontinuity design using the statutory retirement age in urban China as an exogenous instrument to measure the causal effect of retirement on six measures of inpatient healthcare utilization.ResultsRetirement reduced total hospital costs (-84.71 Chinese Yuan (CNY), 95% confidence interval (CI) -172.03 – 2.61), shortened length of hospital stays (-44.59, 95% CI -70.50 – -18.68), and increased hospital readmissions (0.06, 95% CI 0.00 – 0.12) and primary hospital visits (0.06, 95% CI 0.02 – 0.09) among women. Retirement did not significantly change inpatient healthcare utilization among men. The retirement effects among women varied by disease category. Specifically, retirement substantially increased hospitalizations for non-communicable diseases (NCDs), yet had only modest or no effect on hospitalizations for communicable diseases or injuries. Retirement effects among women also varied by the type of services. For relatively inexpensive services, such as nonoperative treatment, there were surges in the extensive margin (hospital readmission). For relatively expensive and invasive services, such as surgeries, retirement reduced the intensive margin (out-of-pocket expenditures and length of stay).ConclusionsRetirement decreases overall use of inpatient healthcare for women. The examination on the disease-related heterogeneous effects helps with the introduction and implementation of integrated healthcare delivery and appropriate incentive schemes to encourage better use of healthcare resources among older adults.

Scientific literature is one of the most significant resources for sharing knowledge. Researchers turn to scientific literature as a first step in designing an experiment. Given the extensive and growing volume of literature, the common approach of reading and manually extracting knowledge is too time consuming, creating a bottleneck in the research cycle. This challenge spans nearly every scientific domain. For the materials science, experimental data distributed across millions of publications are extremely helpful for predicting materials properties and the design of novel materials. However, only recently researchers have explored computational approaches for knowledge extraction primarily for inorganic materials. This study aims to explore knowledge extraction for organic materials. We built a research dataset composed of 855 annotated and 708,376 unannotated sentences drawn from 92,667 abstracts. We used named-entity-recognition (NER) with BiLSTM-CNN-CRF deep learning model to automatically extract key knowledge from literature. Early-phase results show a high potential for automated knowledge extraction. The paper presents our findings and a framework for supervised knowledge extraction that can be adapted to other scientific domains., Comment: Accepted by the 84th Annual Meeting of the Association for Information Science and Technology (ASIS&T 2021), short paper

Work presented at the workshop “Organizing Big Data, Information, and Knowledge” in ACM/JCDL 2020 (Association of Computing Machinery/Joint Conference on Digital Libraries).

Background: Aneurismal subarachnoid hemorrhage (aSAH) is a serious type of stroke with high mortality and disability. Identifying circulating biomarkers is helpful to improve theranostics of aSAH. In this study, we are for the first time to report circulating interleukin-6(IL-6) in neuron-derived small extracellular vesicles(NDSEVs) were identified to be the potential biomarkers in prognosis of aSAH. Methods: We extracted small extracellular vesicles from the plasma of aSAH patients and healthy controls and were enriched by sequential precipitation and anti-L1CAM antibody immunoabsorption. Subsequently,we determined IL-6 levels by an enzyme-linked immunosorbent assay (ELISA). Result: Plasma IL-6 NDSEVs showed distinct pattern differences between aSAH patients and healthy controls. The IL-6NDSEVs levels were increased and positively associated with disease monitoring and prognosis of aSAH patients. These data suggest an elevated neuroinflammatory cascade in aSAH patients.Conclusion: The IL-6NDSEVs maybe prospective biomarkers to indicate its progression, and thus may own great potential in applications such as prognostic evaluation of aSAH in the near future.

Background Some bereaved parents experience a decreasing trajectory of grief, while others fail to adapt over the long term and persistently suffer from negative health consequences. This study investigates the mediating role of social integration in the relationship between losing an only child and parental health in a family-oriented society. Method A sample of 1828 bereaved parents and 4739 non-bereaved parents was drawn from a 10-city survey in China. Regression methods were used to examine the impact of child loss on parental health, and Sobel test was applied to examine the mediating role of social integration. Results Bereaved parents who lost their only child have worse self-rated health and more negative affect than the non-bereaved parents, which lasted for years after the death of the only child. The Sobel test shows that 24.8% of the total effects on self-rated health and 6.7% of the total effects on negative affect can be explained via decreased social integration. The gender of parents and child as well as fertility intentions are important sources of heterogeneity in the Chinese culture. Limitation The results based on cross-sectional data may only reveal correlation rather than causality. The data was retrieved from self-reported questionnaires and there is a lack of objective measures of parental health. Moreover, the detailed mechanisms behind how child loss resulted in less social integration should be further explored. Conclusions Significant disparities in health outcomes and social integration were found for bereaved parents relative to the non-bereaved parents. Future work is needed to assess the health of bereaved parents, identify the vulnerable and disadvantaged groups, and design inclusive intervention programs.

Purpose Single coiling may be the optimal strategy for ruptured aneurysms. But assisted techniques may be needed in some aneurysms. The authors report their experience of double microcatheter technique in the treatment of ruptured aneurysms in anterior cerebral circulation. Methods Between 2012 and 2018, 82 patients with ruptured aneurysms in anterior cerebral circulation were treated with double microcatheter technique. The clinical records, angiographic results, procedure-related complications were reviewed. Clinical and angiographic follow-up was performed. Results Completely occlusion, neck remnant and partial occlusion were achieved in 56.6%, 36.1% and 7.2% in the whole procedures, respectively. The overall rate of morbidity was 8.5% (7/82). The rate of permanent morbidity was 3.7% (3/82). Three patients (3.7%) died before discharge. There was no procedure-related mortality. The favorable outcomes were obtained in 75.6% (62/82) of the whole patients at discharge. High Hunt-Hess grade and suffering from craniotomy or EVD were risk factors for clinical outcomes at discharge. Sixty-eight patients received clinical follow-up at a mean interval of 15.75±12.71 months. Favorable outcomes were obtained in 61 (89.7%) patients. Angiographic follow-up was performed in 44 patients at an average of 13.16±13.12 months. The recurrence rate is 34.1%. Seven of them (15.9%) received retreatment. Conclusion Double microcatheter technique is a safe and effective method for treatment of ruptured aneurysms in anterior cerebral aneurysms with low morbidity. Recurrence remains a problem. Patients should be followed up regularly.

To evaluate the changes of blood-brain barrier permeability (BBBP) after aneurysmal subarachnoid hemorrhage (aSAH) and find out whether BBBP within 24 h after onset can further improve prediction of delayed cerebral ischemia (DCI).CT perfusion (CTP) was performed within 24 h after onset and in the DCI time window (DCITW). Whole brain average values of flow extraction product (mKOne hundred and forty of 179 consecutive patients were included, 45 of whom (32%) developed DCI. mKBBBP measurement within 24 h after onset can improve the prediction of DCI. Early moderate BBB disruption may be reversible, whereas severe BBBP disruption indicates the risk of DCI.

Background The extensive involvement of microRNAs (miRNAs) in the pathogenesis of psoriasis is well documented. However, little is known about the contribution of specific miRNAs to the prevalence of this disease. Objectives To explore the role of miR-145-5p in psoriasis. Methods miRNA microarray analysis was performed in four patients with psoriasis and four controls. Quantitative reverse-transcriptase polymerase chain reaction and fluorescence in situ hybridization were used to identify the dysregulated miRNAs. Luciferase assays were performed to determine whether miR-145-5p targets mixed-lineage kinase (MLK)3. CCK-8 assay and Magnetic Luminex Assay were performed to measure cell proliferation and chemokine secretion. Western blot analysis was used to investigate the protein levels of MLK3 and its downstream effectors. Mouse models of psoriasis were established for in vivo experiments. Results miR-145-5p was downregulated in psoriatic lesional skin. Luciferase assays showed that MLK3 is a direct target of miR-145-5p. Overexpression of miR-145-5p in normal human epidermal keratinocytes (NHEKs) suppressed cell proliferation and secretion of chemokines. In contrast, silencing miR-145-5p promoted NHEK proliferation and increased chemokine secretion. Silencing MLK3 abrogated miR-145-5p inhibitor-induced promotion of cell proliferation and chemokine expression. miR-145-5p regulates nuclear factor-κB and signal transducer and activator of transcription 3 by targeting MLK3. Delivery of agomiR-145-5p into the skin decreased epidermal hyperplasia and ameliorated psoriasis-like dermatitis. Delivery of antagomiR-145-5p led to the opposite effects. Conclusions Our findings indicate that miR-145-5p negatively regulates proliferation and chemokine secretion of NHEKs by targeting MLK3, and downregulation of miR-145-5p contributes to skin inflammation in psoriasis lesions.

Competitive endogenous RNAs (ceRNAs) regulate RNA transcripts by competing for shared miRNAs and play critical roles in disease development. Psoriasis is a long-lasting, recurring chronic inflammatory skin disease characterized by hyperproliferation of keratinocytes. The keratinocyte response is triggered by the activation of inflammatory cytokines, like interleukin-22 (IL-22). We used lncRNA array analysis to detect differentially expressed lncRNAs in skin (HaCaT) cells treated with or without IL-22. We used hematoxylin and eosin (HE) staining to determine the pathological changes in skin cells and immunohistochemistry to evaluate the expression of S100A7. We used qRT-PCR and Western blotting to detect the expression levels of MSX2P1 and S100A7. We down-regulated the expression of MSX2P1 by infecting with lentiviral-vector shRNA. We measured cell proliferation, cell cycle status, and apoptosis by the CCK-8 assay, flow cytometry, and Annexin Ⅴ-FITC/PI staining, respectively. In addition, we used the luciferase reporter gene assay to determine the relationships between MSX2P1 or miR-6731-5p and S100A7, respectively. LncRNA array analysis revealed that 103 lncRNAs were up-regulated and 51 were down-regulated. Furthermore, qRT-PCR showed that the mRNAs levels of MSX2P1 was significantly altered in HaCaT cells treated with IL-22, compared with control cells; and MSX2P1 was mainly in the cytoplasm. Based on the IL-22-stimulated lncRNA-associated ceRNA network, we selected MSX2P1-miR-6731-5p-S100A7 for further study. HE staining exhibited characteristic features specific to psoriatic lesions. Immunohistochemistry demonstrated significantly increased expression levels of S100A7 in psoriatic lesions, compared with normal skin tissue. We observed a positive correlation between lncRNA-MSX2P1 expression and S100A7 expression. In addition, miR-6731-5p suppressed proliferation, accelerated apoptosis in IL-22-stimulated keratinocytes, and decreased the expressions of S100A7, IL-12β, IL-23, HLA-C, CCHCR1, TNF-α, and NF-κB proteins. Our data demonstrated that MSX2P1 facilitate the progression and growth of IL-22-stimulated keratinocytes by inhibiting miR-6731-5p and activating S100A7. We speculate that the biological network of MSX2P1-miR-6731-5p-S100A7 is a potential novel therapeutic target for the future treatment of psoriasis.

China’s disability policies are changing, some of which are gradually closer to the requirements of the Convention on the Rights of Persons with Disabilities. Based on the social model of d...

Background Aneurysmal subarachnoid hemorrhage (aSAH) is a severe type of stroke characterized by high rates of mortality and disability. Identifying circulating biomarkers is helpful to improve prognosis. In this study, for the first time, we identify circulating interleukin-6 (IL-6) levels in neuron-derived small extracellular vesicles (NDSEVs) as potential biomarkers in prognosis of aSAH.Methods We extracted small extracellular vesicles from the plasma of aSAH patients and healthy controls and enriched them using sequential precipitation and anti-L1CAM antibody immunoabsorption. Subsequently, we determined IL-6 levels using an enzyme-linked immunosorbent assay (ELISA).Results Plasma IL-6 NDSEVs showed distinct pattern differences between aSAH patients and healthy controls. There were significant correlations of IL-6concentrations in plasma with severity in aSAH. The AUCs of IL-6 for distinguishing the severe aSAH patients from mild aSAH patients were 0.961. After multivariate logistic regression analysis, only age, acute hydrocephalus,and the levels of IL-6 NDSEVs enabled prediction of neurological outcome at 1 year. The IL-6 NDSEVs levels were greater and positively associated with disease and prognosis of aSAH patients.Conclusions These data suggest a neuroinflammatory cascade in aSAH patients. IL-6 NDSEVs may be a biomarkers to monitor the progression of aSAH.

The aim of the present study was to explore the optimal treatment strategy for patients with vertebral artery dissecting aneurysms via the endovascular approach. A total of 47 patients (50 aneurysms, including 28 ruptured and 22 unruptured) underwent endovascular treatment between January 2012 and March 2018. Of these aneurysms, 18 were treated by parent artery occlusion, 11 by stent implantation and 21 by stent-assisted coiling. The complete occlusion rate was 100% (18/18) in aneurysms treated by parent artery occlusion and 46.9% (15/32) for stent implantation with or without coiling. External drainage was performed in 8 patients with ruptured aneurysms. Post-operative bleeding occurred in 2 patients treated by stent-assisted coiling. Ventriculo-peritoneal shunt was performed in 4 patients due to delayed hydrocephalus. Post-operative frontal hematoma occurred in one patient treated by stent-assisted coiling. The mortality was 6.4% (3/47) prior to discharge. The recurrence rate was 8.3% (1/12) in aneurysms treated by parent artery occlusion and 13.6% (3/22) in those treated by stent implantation with or without coiling. A total of 39 patients were followed up for 14.56±14.91 months. The good outcome rates were 100% (28/28) in patients with unruptured aneurysms and a Hunt-Hess grade of 1-3, and 72.7% (8/11) in patients with a Hunt-Hess grade of 4 or 5. In conclusion, the present study indicated that endovascular treatment is a safe and efficient method for patients with vertebral artery aneurysm. The treatment strategy should be based on the patient's condition and aneurysmal characteristics. Parent artery occlusion may be suitable for selected patients with ruptured vertebral artery aneurysms.

Cavitation in the impact copolymer polypropylene (ICP) and its corresponding homo-isotactic polypropylene (homo-iPP) during stretching was investigated using ultra-small angle X-ray scattering technique. Different from the iPP showing a suppressed cavitation around yielding at high deformation temperature (Td), the ICP presented a more intensive cavitation at elevated Td. This unusual Td dependency of cavitation around yielding observed in ICP was suggested to be caused by the changes of the stability of the rubber particles dispersed in iPP matrix. The rubber particles exhibit a multi-phase core-shell structure which contains crystallizable polyethylene segments in the core layer, the amorphous polymer of ethylene-propylene random copolymer in the inner shell layer, and the crystallizable polypropylene segments in the outer shell layer. The softening and melting from the inner shell to the core and the outer shell took place as the Td increased. It can be envisaged that the fraction of unstable regions inside the rubber particles and the debonding between the iPP matrix and the dispersed phase gradually increased providing more nucleation sites for cavities at high Td, a more intensive cavitation was thus observed.

A customized micro-injection molding apparatus with a pair of diamond windows in the filling cavity was specifically designed to simulate the extreme processing conditions inherent in the practical micro-molding process. This setup combined with synchrotron radiation allows real-time investigation of multi-scale structural development during the manufacturing process, which enables evaluation of flow-induced crystallization features for a range of polymeric materials. In this study, the structural evolution of high density polyethylene at the nanoscale was investigated by in situ synchrotron small angle X-ray scattering technique under injection molding. The respective structural parameters of kebab lamellae (including the long period, and the average thickness of crystalline lamellae and amorphous phase) and shish formation (such as the radius of gyration, length, and misorientation of the shish) were extensively analyzed from the resulting data. The growth of kebab crystals was found to exhibit a two-step behavior: melting of thin crystallites followed by a recrystallization process occur at the onset of molding whereas an annealing-induced perfectioning of the lamellae is activated at a later stage. In spite of the initial decrease of the shish length and radius, there is an overall increase in the length and misorientation of the shish structure at later times, which can be attributed to a crystallization of partially oriented chains onto the longitudinal surface of the existing shish. The results acquired by the unique combination of this apparatus and synchrotron radiation can provide an effective means to predict the structural formation and modulate the morphology of final products in practical micro-injection molding process of polymers.

In this paper, cushion suspension support system of low speed and heavy loading of the gas membrane flow field was in computational fluid dynamics analysis, explore the influence of air cushion suspension of performance support system air cushion structural parameters, and the air pressure in the process of air cushion lift proportional control system for mathematical modeling, thus to control the thickness of air cushion, based on pole assignment self-tuning controller, to improve the response and stability of the system, and the system in this paper the lifting process of air cushion suspension support system are analyzed and the gas film flow state, deepening the theoretical research of air cushion suspension technology.

Long noncoding RNAs (lncRNAs) serve important roles in the biology of autoimmune diseases and immune‑associated disorders. To identify lncRNAs specifically associated with psoriasis, the expression of lncRNAs from biopsies obtained from patients with psoriasis were compared with samples obtained from healthy volunteers using a microarray. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to detect the expression of 10 identified dysregulated lncRNAs. Cis‑ and trans‑regulated target genes of lncRNAs were predicted. The results of microarray analysis indicated that 2,194 lncRNAs and 1,725 mRNAs were significantly dysregulated. Gene Ontology and pathway analyses among the dysregulated genes were performed. Co‑expression network analysis was also performed to study molecular interactions. Several identified pathways were associated with psoriasis. Among the 2,194 dysregulated lncRNAs, 1,549 of these had cis‑ or trans‑regulated predicted target genes. Among the 1,725 dysregulated mRNAs, 289 of the cis‑regulated target genes and 262 of the trans‑regulated target genes may be regulated by the differentially expressed lncRNAs; 10 differentially expressed lncRNAs were randomly selected and then validated. Of these lncRNAs, 7 exhibited the same expression profile as determined via microarray analysis, of which 3 lncRNAs were upregulated and 4 lncRNAs were downregulated. To the best of our knowledge, the present study is the first in which a microarray has been used to investigate the expression profile of lncRNAs associated with psoriasis. Additionally, the expression levels of the 10 aforementioned lncRNAs associated with psoriasis were validated in the present study for the first time using RT‑qPCR. The findings demonstrated that lncRNAs may contribute to the pathogenesis of psoriasis and suggested their potential diagnostic and therapeutic value. Furthermore, the findings of the present study suggest that the combined actions of several lncRNAs may contribute to the pathogenesis of psoriasis.

Psoriasis is a common immune-mediated chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation, differentiation and apoptosis. However, the exact etiology and pathogenesis are still unclear. Evidence is rapidly accumulating for the role of microRNAs in psoriasis. It has been demonstrated that Interleukin-22 (IL-22) plays vital role in T cell-mediated immune response by interacting with keratinocytes in the pathogenesis of psoriasis. The aim of our study was to explore the possible functional role of miR-20a-3p in psoriasis and in IL-22 induced keratinocyte proliferation. Here, we found that miR-20a-3p was down-regulated in psoriatic lesions and in HaCaT cells (human keratinocyte cell line) treated by IL-22 stimulation. Functional experiments showed that overexpression of miR-20a-3p in HaCaT cells suppressed proliferation and induced apoptosis while its knockdown promoted cell proliferation and reduces cell apoptosis. Mechanistically, SFMBT1 was identified as the direct target of miR-20a-3p by dual luciferase reporter assay. SFMBT1 knockdown was demonstrated to inhibit cell growth and induced apoptosis, which was consistent with the function of miR-20a-3p upregulation in HaCaT cells. In addition, results of western blot analysis showed that miR-20a-3p upregulation or SFMBT1 knockdown changed the protein expression levels of TGF-β1 and survivin. Our findings suggest that miR-20a-3p play roles through targeting SFMBT1 and TGF-β1/Survivin pathway in HaCaT cells, and loss of miR-20a-3p in psoriasis may contribute to hyperproliferation and aberrant apoptosis of keratinocytes.

Psoriasis is an immune-mediated chronic skin disorder where T cells play a main role, and numerous inflammatory cytokines are implicated in its pathogenesis by initiating keratinocyte proliferation. Interleukin-22 (IL-22), an IL-10 family cytokines, is critical in the pathogenesis and development of psoriasis. To determine the target of microRNA (miR) -548a-3p and investigate its role in keratinocyte proliferation after treating human keratinocytes (HaCaT) with IL-22, we used quantitative reverse transcriptase PCR to measure the expression of miR-548a-3p in both HaCaT cells stimulated with IL-22 and psoriatic lesions, and then detected the biological function of miR-548a-3p in HaCaT cells by performing Counting Kit-8 (CCK-8) assays. Luciferase reporter assay was conducted to determine the target gene of miR-548a-3p. Immunohistochemistry and Western blot were performed to verify the target gene. Results showed that miR-548a-3p was significantly upregulated both in HaCaT cells treated with IL-22 and psoriatic lesions. The over expression of miR-548a-3p could promote the proliferation of HaCaT cells. Luciferase was mutated in the 3'UTR of PPP3R1, a gene coding Calcineurin. Immunohistochemistry and Western blot demonstrated that the expression of PPP3R1 decreased respectively in psoriatic lesions and HaCaT cells. In conclusion, the expression of miR-548a-3p is upregulated in IL-22 mediated keratinocyte proliferative disorder like psoriasis. The impact of miR-548a-3p on keratinocyte proliferation may be implemented by targeting PPP3R1 and T regulatory cells may be involved in the pathogenesis of psoriasis.

Tire force can be divided into normal force and tangential force when the vehicle is in tilting condition, the general load cell can't differentiate these two signals accurately. This paper introduces a portable wheel load measuring plate which is characterized by integrating the strain gauge with the upper platform and can be used in tilting condition. In order to decoupling these signals from component of forces, the structure of the upper platform is optimized and analyzed by commercial FEA software. Experimental results show that the maximal measuring error cause by eccentric load is 1.49 % and the maximal measuring error caused by tilting error is 2.49 %.

Two ruthenium(III) complexes containing ethylenediaminetetraacetate(edta), viz. [{Ru(Hedta)}2L]·xH2O L = 4,4′-bipyridine(bpy) (1) and 4,4′-azopyridine(Azpy) (2), have been synthesized by the reaction between K[Ru(Hedta)Cl]·1.5H2O and the corresponding N-heterocycles. Complex 1 was determined by single-crystal X-ray diffraction. The products were characterized by IR, UV–vis, cyclic voltammetry, and magnetic techniques. Their DNA-binding activities were investigated using electronic absorption spectroscopic methods and fluorescence quenching; the experimental results show that these two ruthenium complexes may bind to CT-DNA through intercalation modes.

Ezrin is overexpressed in a variety of neoplastic cells and is involved in the later stages of tumor progression and metastasis. The present study investigated the expression and functional significance of ezrin in human brain astrocytoma. Ezrin expression was examined in specimens from healthy human brains (10 autopsies) or human astrocytoma (107 cases) by immunohistochemistry. All healthy specimens were negative for ezrin expression, while this expression was positive in a great majority of human astrocytoma tissues (96/107; 89.7%; p < 0.05 vs. healthy). Ezrin expression was positively correlated with tumor grade (r = 0.551, p < 0.01). Analysis of clinicopathologic data revealed that the post-operation disease-free survival times were significantly (p < 0.001) different between those with a strong positive ezrin expression and those with a weak or negative expression. Specifically, median DFS in patients with a strongly positive ezrin expression was 13 months (range 2-46 months), while it was significantly (p < 0.001) longer in patients with weakly positive or negative expression (median of 28 months, range 6-56 months). In conclusion, there is a strong association between ezrin expression and increased malignancy in astrocytoma. Thus, enhanced ezrin expression may play an important role in the development of astrocytoma. Our results further indicate that ezrin may be useful for grading of astrocytoma and as a molecular marker for the prognosis.

The optimal treatment modalities of ruptured middle cerebral artery aneurysm are still controversial. The objective of this study is to analyze the outcomes of patients with ruptured middle cerebral artery aneurysms treated by endovascular coiling.From October 2011 to October 2015, 67 patients with 71 ruptured middle cerebral artery aneurysms received endovascular coiling in our hospital. We retrospectively reviewed the clinical, radiologic records and outcomes.Of all the 71 aneurysms (67 patients), 42 were treated by coil embolization merely, 27 by stent-assisted coiling and 2 unruptured aneurysms in patients with bilateral middle cerebral artery aneurysms without receiving treatment. Complete occlusion was achieved in 82.6% (57/69) of all the procedures. Each of incomplete and partial occlusion rates was 8.7% (6/69). Intraoperative rupture of aneurysms occurred in two procedures (2.9%). Thrombogenesis occurred in eight procedures (11.6%). Brain infarction occurred in eight patients (11.9%). Post-operative rebleeding occurred in seven patients (10.4%). Sixty-three patients were followed at a mean follow-up of 8.24 ± 7.16 months. The mortality and good outcome rate were 3.2% and 90.5%, respectively. Aneurysm recurrence occurred in 6 (13.3%) of the 45 aneurysms at a mean follow-up of 8.44 ± 7.83 months.Endovascular coiling is effective for patients with ruptured middle cerebral artery aneurysms. Individualized treatment should be assessed by experienced specialist. It is essential to perform randomized large trials to confirm the efficiency of endovascular coiling.

The changes in the tau protein phosphorylation and expression of bcl-2, and bax in rat parietal cortex neurons after focal cerebral ischemia-reperfusion (I/R) were explored, and the relationship between the tau protein phosphorylation and the expression of bax or apoptosis was clarified in order to elucidate the relationship between cerebral infarction and Alzheimer's disease. The rat focal cerebral I/R model was induced by occlusion of the right middle cerebral artery using the intraluminal suture method. The level of tau protein phosphorylation at Ser396, Ser404, Tyr231, Ser199/202 sites and the expression of bcl-2, bax and total tau 5 in rat parietal cortex during focal cerebral ischemia/reperfusion were detected by Western blot. The relationship between the tau protein phosphorylation and the expression of bax, or apoptosis was examined by TUNEL method and double-labeling immunofluorenscence method. The results showed that the level of tau hyperphosphorylation at Ser199 / 202, Ser396, Ser404, Tyr231 sites and the expression levels of bcl-2, and bax were significantly higher in I/R group than in the sham group, but the ratio of bcl-2/bax was decreased. Neuronal apoptosis, bax expression and the tau protein hyperphosphorylation were co-localized. It is suggested that Alzheimer's disease-like pathological changes occur after cerebral I/R. The highly abnormal phosphorylation of tau protein plays a key role in cerebral I/R-induced apoptosis. The cerebral infarction may contribute to Alzheimer's disease occurrence and development.

Enterprise stent has been widespread used in wide-necked intracranial aneurysms and good efficacy has been achieved, but there are few reports on its applications in very small ruptured intracranial aneurysms in literatures. This study aimed to evaluate the safety and efficacy of Enterprise stent-assisted coiling embolization of very small ruptured intracranial aneurysms. We retrospectively reviewed the clinical and imaging data from 37 patients with very small ruptured intracranial aneurysms who had SAC using Enterprise stents performed from February 2012 to July 2016 in our department. Data collected and analyzed included patient demographics, morphologic features of the aneurysm, treatment results, and follow-up results. Clinical outcomes were evaluated by the Glasgow Outcome Scale (GOS). Enterprise stents were successfully implanted in all 37 patients with very small ruptured intracranial aneurysms. Of the 37 individuals, 28 patients exhibited complete occlusion at Raymond grade I, 5 patients exhibited occlusion at Raymond grade II, and 4 patients at Raymond grade III. Procedure-related complications occurred in 3 of 37 patients (8.1%), including 1 case of intraprocedure aneurysm rupture who died from cerebral herniation caused by severe postoperative cerebral ischemia during the hospital stay, and the other 2 complications were acute in-stent thrombosis, and occlusion of parent artery caused by falling-off internal carotid artery plaque, respectively. A total of 36 patients underwent postoperative clinical follow-up visits for 6 to 24 months of which 31 patients recovered (GOS ≥ 4). One patient had hemiplegic paralysis, and no rehemorrhage was found. A total of 25 patients underwent follow-up digital subtraction angiography (DSA) at 3–21 months postintervention, in whom there were 22 cases with complete occlusion, 2 cases with recurrence of aneurysm neck, and 1 case with in-stent restenosis, but there was no patient with neurologic deficits. The Enterprise stent-assisted coiling embolization can be a safe and effective technique for treatment of very small ruptured intracranial aneurysms.