Targeting neuroinflammation in Alzheimer's disease:from mechanisms to clinical applications

Alzheimer’s disease is characterized by sustained neuroinflammation leading to memory loss and cognitive decline.The past decade has witnessed tremendous efforts in Alzheimer’s disease research;however,no effective treatment is available to prevent disease progression.An increasing body of evidence suggests that neuroinflammation plays an important role in Alzheimer’s disease pathogenesis,alongside the classical pathological hallmarks such as misfolded and aggregated proteins(e.g.,amyloid-beta and tau).Firstly,this review summarized the clinical and pathological characteristics of Alzheimer’s disease.Secondly,we outlined key aspects of glial cell-associated inflammation in Alzheimer’s disease pathogenesis and provided the latest evidence on the roles of microglia and astrocytes in Alzheimer’s disease pathology.Then,we revealed the double-edged nature of inflammatory cytokines and inflammasomes in Alzheimer’s disease.In addition,the potential therapeutic roles of innate immunity and neuroinflammation for Alzheimer’s disease were also discussed through these mechanisms.In the final section,the remaining key problems according to the current research status were discussed.

Effects of astragalus polysaccharides on ventricular remodeling and miRNA-21 in rats with acute myocardial infarction

Objective:To investigate the effect of Astragalus polysaccharides(APS)on myocardial remodeling and expression of miR-21 after myocardial infarction.Methods:Sixty SPF grade healthy male rats were divided into the sham operation group,the model group,astragalus polysaccharide low,medium and high dose groups and atorvastatin group randomly with 10 rats in each group.The left anterior descending coronary artery(LAD)was ligated to establish myocardial infarction model in rats,and the corresponding drug intervention was given for 4 weeks.The changes of myocardial morphology and collagen were observed by HE and Masson staining.The levels of IL-1β,IL-6,TNF-αand IL-10 were detected by ELISA.The mRNA expressions of miR-21,MMP2,TIMP-2,Col-I,and Col-III was detected by RT-PCR.The protein expressions of TLR4,MyD88 and NF-κB p65 were detected by Western blot.Results:Compared with the model group,APS could improve the pathological morphology of myocardial tissue,increase the level of IL-10 in myocardial tissue,reduce the staining area of collagen and the contents of IL-1β,IL-6 and TNF-α(P<0.05).At the same time,APS could decreased the expression of MMP2,Col-I and Col-ⅢmRNA and the ratio of MMP2/TIMP-2,and increased the expression of TIMP-2 mRNA and miR-21 significantly(P<0.05).Furthermore,APS could significantly reduce the expression of TLR4,p-NF-κB p65 and MyD88 protein in myocardial tissue of rats with myocardial infarction,and the differences were statistically significant when compared with the model group(P<0.05).Conclusion:APS can inhibit the activation of TLR4/MyD88/NF-κB signaling pathway by upregulating the expression of miR-21,which plays a therapeutic role in ventricular remodeling after acute myocardial infarction.

Investigation of gravity influence on EOR and CO_(2) geological storage based on pore-scale simulation

Gravity assistance is a critical factor influencing CO_(2)-Oil mixing and miscible flow during EOR and CO_(2)geological storage.Based on the Navier-Stokes equation,component mass conservation equation,and fluid property-composition relationship,a mathematical model for pore-scale CO_(2) injection in oilsaturated porous media was developed in this study.The model can reflect the effects of gravity assistance,component diffusion,fluid density variation,and velocity change on EOR and CO_(2) storage.For nonhomogeneous porous media,the gravity influence and large density difference help to minimize the velocity difference between the main flow path and the surrounding area,thus improving the oil recovery and CO_(2) storage.Large CO_(2) injection angles and oil-CO_(2) density differences can increase the oil recovery by 22.6% and 4.2%,respectively,and increase CO_(2) storage by 37.9% and 4.7%,respectively.Component diffusion facilitates the transportation of the oil components from the low-velocity region to the main flow path,thereby reducing the oil/CO_(2) concentration difference within the porous media.Component diffusion can increase oil recovery and CO_(2) storage by 5.7% and 6.9%,respectively.In addition,combined with the component diffusion,a low CO_(2) injection rate creates a more uniform spatial distribution of the oil/CO_(2) component,resulting in increases of 9.5% oil recovery and 15.7% CO_(2) storage,respectively.This study provides theoretical support for improving the geological CO_(2) storage and EOR processes.

Effects of omeprazole or pantoprazole on platelet function in non-ST-segment elevation acute coronary syndrome patients receiving clopidogrel

Background: This study evaluated the effect of omeprazole or pantoprazole on platelet reactivity in non-STsegment elevation acute coronary syndrome(NSTE-ACS) patients receiving clopidogrel.Methods: Consecutive patients with NSTE-ACS(n =620) from general hospital of Shenyang Military Command were randomized to the omeprazole or pantoprazole(20mg/d) group(1:1), and received routine dual antiplatelet treatment. Patients' reversion rate of adenosine diphosphate-induced platelet aggregation(ADP-PA) was assessed at baseline, 12 to 24 h after administration of medication, and after 72 h of percutaneous coronary intervention(PCI). The primary endpoint of the study was platelet reactivity assessed with ADP-PA at 30 days after PCI. Adverse events(AEs) were recorded for 30-day and 180-day follow-up periods.Results: There were no significant differences between both the groups in platelet response to clopidogrel at 12–24h after drug administration(54.09%±18.90% vs. 51.62%±19.85%, P=0.12), 72 h after PCI(52.15%±19.45% vs. 49.66%±20.05%, P=0.18), and 30 days after PCI(50.44%±14.54% vs. 48.52%±15.08%, P=0.17). The rate of AEs did not differ significantly between groups during the 30-day(15.2% vs. 14.8%, P=0.91) and 180-day(16.5% vs. 14.5%, P=0.50) follow-up periods after PCI.Conclusion: The addition of omeprazole or pantoprazole to clopidogrel did not restrict the effect of platelet aggregation by reducing the conversion of clopidogrel. Compared with clopidogrel alone, pantoprazole-clopidogrel and omeprazoleclopidogrel combinations did not increase the incidence of adverse clinical events during 30-day and 180-day follow-up periods after PCI.

“医养结合-四元联动”整合照护的全流程闭环护理模式在乙型肝炎肝硬化失代偿患者中的应用

背景由于乙型肝炎肝硬化失代偿病程长、病情迁延难愈,加之医院床位紧张,大部分患者病情稳定后需在家庭、社区或养老机构接受医疗护理,故做好医院-社区-居家-机构一体化的照护模式对患者的康复至关重要.目的评估"医养结合-四元联动"整合照护的全流程闭环护理模式在乙型肝炎肝硬化失代偿患者中的应用效果.方法本研究为单中心、前瞻性、随机对照研究,研究对象为2019-07/2020-07在本院完成院内治疗后正常出院的100例乙型肝炎肝硬化失代偿患者,按照电脑随机数字表法分为两组.常规组(50例)接受常规延续性护理,护理组(50例)实施"医养结合-四元联动"整合照护的全流程闭环护理模式.统计两组用药依从性及并发症,并观察干预前、干预3个月后情绪状态、社会支持、疾病不确定感、生活质量及自我管理行为的变化.结果护理组用药总依从性(98.00%)比常规组(84.00%)高,并发症发生率(10.00%)比常规组(26.00%)低(P均<0.05);护理组干预后简明心境问卷(profileof mood States, POMS)量表中紧张-焦虑、抑郁-沮丧、迷惑-混乱、愤怒-敌意及疲乏-迟钝评分均比常规组低,精力-活力评分比常规组高(P均<0.05);护理组干预后社会支持评定量表(social support rating scale, SSRS)、世界卫生组织生存质量测定量表简表(world health organization quality of life scale brief, WHOQOL-BREF)及自我管理行为量表各维度评分比常规组高,疾病不确定感量表(mishel uncertainty in illness scale for adult,MUIS-A)评分比常规组低(P均<0.05).结论 "医养结合-四元联动"整合照护的全流程闭环护理模式用于乙型肝炎肝硬化失代偿患者中具有较高的可行性,有利于提升患者用药依从性及社会支持度,改善情绪状态、自我管理行为,减轻疾病不确定感,提高后续的生活质量,减少并发症.

A promising strategy for repairing tissue damage:mitochondria transfer from mesenchymal stem cells

Mesenchymal stem cells(MSCs)are gaining the spotlight in research due to their abundant sources,immune privileges,and ability to proliferate and differentiate.These cells provide invaluable resources for stem cell-based therapy and present therapeutic opportunities in cell/tissue regeneration medicine.A growing evidence suggests that,mitochondria transfer from MSCs could rescue tissue degeneration caused by mitochondria damage.Although this emerging tissue regeneration treatment method brings hope for the treatment of mitochondria dysfunction related diseases,the necessary conditions and underlying mechanisms for mitochondrial transfer remain poorly understood.In this review,a large number of mitochondrial transfer phenomena between MSCs and recipient cells are summarized,with particular emphasis on the conditions and potential mechanisms of mitochondrial transfer from MSCs,so as to provide reference for the clinical application of MSCs transformation in the future.

A microblog recommendation algorithm based on social tagging and a temporal interest evolution model

Personalized microblog recommendations face challenges of user cold-start problems and the interest evolution of topics. In this paper, we propose a collaborative filtering recommendation algorithm based on a temporal interest evolution model and social tag prediction. Three matrices are first prepared to model the relationship between users, tags, and microblogs. Then the scores of the tags for each microblog are optimized according to the interest evolution model of tags. In addition, to address the user cold-start problem, a social tag prediction algorithm based on community discovery and maximum tag voting is designed to extract candidate tags for users. Finally, the joint probability of a tag for each user is calculated by integrating the Bayes probability on the set of candidate tags, and the top n microblogs with the highest joint probabilities are recommended to the user. Experiments using datasets from the microblog of Sina Weibo showed that our algorithm achieved good recall and precision in terms of both overall and temporal performances. A questionnaire survey proved user satisfaction with recommendation results when the cold-start problem occurred.