Implementation and impact of a multidisciplinary coagulation factor stewardship program at an academic medical center

Journal of Thrombosis and Thrombolysis -     

Subpicomolar diphenyleneiodonium inhibits microglial NADPH oxidase with high specificity and shows great potential as a therapeutic agent for neurodegenerative diseases

Activation of microglial NADPH oxidase (NOX2) plays a critical role in mediating neuroinflammation, which is closely linked with the pathogenesis of a variety of neurodegenerative diseases, including Parkinson's disease (PD). The inhibition of NOX2‐generated superoxide has become an effective strategy for developing disease‐modifying therapies for PD. However, the lack of specific and potent NOX2 inhibitors has hampered the progress of this approach. Diphenyleneiodonium (DPI) is a widely used, long‐acting NOX2 inhibitor. However, due to its non‐specificity for NOX2 and high cytotoxicity at standard doses (µM), DPI has been precluded from human studies. In this study, using ultra‐low doses of DPI, we aimed to: (1) investigate whether these problems could be circumvented and (2) determine whether ultra‐low doses of DPI were able to preserve its utility as a potent NOX2 inhibitor. We found that DPI at subpicomolar concentrations (10^?14 and 10^?13 M) displays no toxicity in primary midbrain neuron‐glia cultures. More importantly, we observed that subpicomolar DPI inhibited phorbol myristate acetate (PMA)‐induced activation of NOX2. The same concentrations of DPI did not inhibit the activities of a series of flavoprotein‐containing enzymes. Furthermore, potent neuroprotective efficacy was demonstrated in a post‐treatment study. When subpicomolar DPI was added to neuron‐glia cultures pretreated with lipopolysaccharide, 1‐methyl‐4‐phenylpyridinium or rotenone, it potently protected the dopaminergic neurons. In summary, DPI's unique combination of high specificity toward NOX2, low cytotoxicity and potent neuroprotective efficacy in post‐treatment regimens suggests that subpicomolar DPI may be an ideal candidate for further animal studies and potential clinical trials. GLIA 2014;62:2034–2043     

高校职工糖尿病前期干预研究

目的探讨生活干预联合药物控制延缓糖尿病前期发展为糖尿病的程度。方法对2011年6月某高校体检确诊为糖尿病前期200例职工进行观察,随机分为干预组(生活干预+药物控制)与对照组,观察期限为2年,比较两组患者1年后、2年后基础信息和糖尿病患病率。结果两组糖尿病前期职工干预前基础信息比较差异无统计学意义;观察组1年后糖尿病患病率为1%,对照组为13%,差异有统计学意义(x2=11.06,P0.01);观察组2年后糖尿病患病率为2%,对照组为20%,差异有统计学意义(x2=11.06,P0.01)。结论生活干预联合药物控制可能延缓糖尿病前期发展为糖尿病。     

Data-independent acquisition-based proteomics analysis correlating type 2 diabetes mellitus with osteoarthritis in total knee arthroplasty patients

Background:To explore the effects of type 2 diabetes mellitus (T2DM) on osteoarthritis (OA), 12 bone tissue samples were obtained surgically from the human total knee arthroplasty patients and analyzed by quantitative proteomics.Methods:Based on patient clinical histories, patient samples were assigned to diabetes mellitus osteoarthritis (DMOA) and OA groups. A data-independent acquisition method for data collection was used with proteomic data analysis to assess intergroup proteomic differences. Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis were used to further find the correlation between T2DM and OA.Results:GO functional analysis found 153 differentially expressed proteins between DMOA and OA groups, of which 92 differentially expressed proteins were significantly up-regulated and 61 were significantly down-regulated. Kyoto Encyclopedia of Genes and Genome pathway analysis found 180 pathways, including 9 pathways significantly enriched. Further data analysis revealed that 6 signaling pathways were closely associated with T2DM and OA.Conclusion:OA and DMOA onset and progression were closely related to synthesis and metabolism of extracellular matrix components (e.g., fibronectin, decorin, etc.). The effects of T2DM on OA occur though 2 major ways of oxidative stress and low-grade chronic inflammation, involving in 2 inhibited signaling pathways and 4 activated signaling pathways.     

A defect-rich ultrathin MoS2/rGO nanosheet electrocatalyst for the oxygen reduction reaction

The structural properties such as high specific surface area, good electrical conductivity, rich-defects of the catalyst surface guarantee outstanding catalytic performance and durability of oxygen reduction reaction (ORR) electrocatalysts. It is still a challenging task to construct ORR catalysts with excellent performance. Herein, we have reported column-like MoS₂/rGO with defect-rich ultrathin nanosheets prepared by a convenient solvothermal method. The structure and composition of MoS₂/rGO are systematically investigated. MoS₂/rGO shows a remarkable electrocatalytic performance, which is characterized by an outstanding onset potential of 0.97 V, a half-wave potential of 0.83 V, noticeable methanol tolerance, and durability of 93.7% current retention, superior to commercial Pt/C. The ORR process occurring on MoS₂/rGO is a typical four electron pathway. Therefore, this study achieves the design of a low-cost, highly efficient and stable nonprecious metal ORR electrocatalyst in alkaline media.

A column-like MoS₂/rGO with rich-defects nanosheets was prepared. The column-like structure, ultrathin nanosheets and the interaction of Mo atoms with graphene, and rich-defects is the guarantee of the outstanding ORR performance.     

重症高血压脑出血患者临床特征与预后相关性研究

目的 探讨急诊重症监护病房(EICU)重症高血压脑出血(HICH)患者临床特征与预后的相关性.方法 收集EICU行手术治疗的154例重症HICH患者的临床资料,根据出院后3个月格拉斯哥预后评分(GOS)分级将患者分为预后不良组(GOS Ⅰ、Ⅱ、Ⅲ级)74例和预后良好组(GOS Ⅳ、Ⅴ级)80例.应用脑室改良Graeb量...     

Clinical and pathological features in adult-onset NIID patients with cortical enhancement

Journal of Neurology - Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in multiple organs. On...     

Antioxidant and Anti-Inflammatory Properties of Rubber Seed Oil in Lipopolysaccharide-Induced RAW 267.4 Macrophages

Rubber seed oil (RSO) is a typical PUFA-enriched plant oil, but it has not been widely used as a healthy edible oil resource due to the lack of understanding of its nutritional values, health biological effects, and action mechanisms. This work was conducted to characterize the basic physicochemical properties, evaluate the antioxidant and anti-inflammatory properties, and explore the involved mechanisms of RSO in LPS-induced RAW 264.7 cells. In the present study, the basic physicochemical parameters of RSO indicated that RSO has good qualities as a potential edible plant oil resource. In LPS-induced macrophages, RSO supplementation displayed a significant antioxidant effect by decreasing ROS and MDA levels as well as elevating T-AOC. In addition, RSO supplementation showed an anti-inflammatory effect by reducing the production of NO, IL-1β, IL-6, and TNF-α while promoting the production of IL-10. Moreover, RSO supplementation decreased the mRNA expression of IL-6, IL-1β, TNF-α, iNOS, and MCP-1 genes while increasing the mRNA expression of the IL-10 gene. Furthermore, RSO supplementation increased Nrf2 protein expression and up-regulated antioxidant genes (HO-1 and NQO-1), which was accompanied by the decrease in TLR4 protein expression and NF-κB p65 phosphorylation as well as IκBα phosphorylation. This study provided some insight into the applications of RSO as a healthy edible oil resource.     

Mesenchymal Stem Cell–Derived Extracellular Vesicles Alleviate M1 Microglial Activation in Brain Injury of Mice With Subarachnoid Hemorrhage via microRNA-140-5p Delivery

BackgroundIt is documented that mesenchymal stem cells (MSCs) secrete extracellular vesicles (EVs) to modulate subarachnoid hemorrhage (SAH) development. miR-140-5p expression has been detected in MSC-derived EVs, while the mechanism of MSC-derived EVs containing miR-140-5p in SAH remains unknown. We aim to fill this void by establishing SAH mouse models and extracting MSCs and MSC-EVs.MethodsAfter ALK5 was silenced in SAH mice, neurological function was evaluated, neuron apoptosis was detected by TdT-mediated dUTP-biotin nick end labeling with NeuN staining, and expression of serum inflammatory factors (interleukin-6, interleukin-1β, and tumor necrosis factor-α) was determined by enzyme-linked immunosorbent assay. The effect of ALK5 on NOX2 expression was assessed by western-blot analysis. Targeting the relationship between miR-140-5p and ALK5 was evaluated by dual luciferase assay. Following extraction of MSCs and MSC-EVs, EVs and miR-140-5p were labeled by PKH67 and Cy3, respectively, to identify the transferring of miR-140-5p by MSC-EVs. SAH mice were treated with EVs from miR-140-5p mimic/inhibitor-transfected MSCs to detect effects of MSC-EV-miR-140-5p on brain injury and microglial polarization.ResultsALK5 silencing increased the neurological score and reduced neuron apoptosis and neuroinflammation in SAH mice. ALK5 silencing inhibited M1 microglia activation by inactivating NOX2. ALK5 was a target gene of miR-140-5p. MSC-derived EVs contained miR-140-5p and transferred miR-140-5p into microglia. MSC-EV-delivered miR-140-3p reduced ALK5 expression to contribute to repression of brain injury and M1 microglia activation in SAH mice.ConclusionsMSC-derived EVs transferred miR-140-5p into microglia to downregulate ALK5 and NOX2, thus inhibiting M1 microglia activation in SAH mice.     

Antigenic Evolution Characteristics and Immunological Evaluation of H9N2 Avian Influenza Viruses from 1994–2019 in China

The H9N2 subtype avian influenza viruses (AIVs) have been circulating in China for more than 20 years, attracting more and more attention due to the potential threat of them. At present, vaccination is a common prevention and control strategy in poultry farms, but as virus antigenicity evolves, the immune protection efficiency of vaccines has constantly been challenged. In this study, we downloaded the hemagglutinin (HA) protein sequences of the H9N2 subtype AIVs from 1994 to 2019 in China—with a total of 5138 sequences. The above sequences were analyzed in terms of time and space, and it was found that h9.4.2.5 was the most popular in various regions of China. Furthermore, the prevalence of H9N2 subtype AIVs in China around 2006 was different. The domestic epidemic branch was relatively diversified from 1994 to 2006. After 2006, the epidemic branch each year was h9.4.2.5. We compared the sequences around 2006 as a whole and screened out 15 different amino acid positions. Based on the HA protein of A/chicken/Guangxi/55/2005 (GX55), the abovementioned amino acid mutations were completed. According to the 12-plasmid reverse genetic system, the rescue of the mutant virus was completed using A/PuertoRico/8/1934 (H1N1) (PR8) as the backbone. The cross hemagglutination inhibition test showed that these mutant sites could transform the parental strain from the old to the new antigenic region. Animal experiments indicated that the mutant virus provided significant protection against the virus from the new antigenic region. This study revealed the antigenic evolution of H9N2 subtype AIVs in China. At the same time, it provided an experimental basis for the development of new vaccines.