Proteasome Inhibitor PS-341 Effectively Blocks Infection by the Severe Fever with Thrombocytopenia Syndrome Virus

Severe fever with thrombocytopenia syndrome(SFTS) is an emerging hemorrhagic fever disease caused by SFTSV, a newly discovered phlebovirus that is named after the disease. Currently, no effective vaccines or drugs are available for use against SFTSV infection, as our understanding of the viral pathogenesis is limited. Bortezomib(PS-341), a dipeptideboronic acid analog, is the first clinically approved proteasome inhibitor for use in humans. In this study, the antiviral efficacy of PS-341 against SFTSV infection was tested in human embryonic kidney HEK293 T(293 T) cells. We employed four different assays to analyze the antiviral ability of PS-341 and determined that PS-341 inhibited the proliferation of SFTSV in 293 T cells under various treatment conditions. Although PS-341 did not affect the virus absorption, PS-341 treatment within a non-toxic concentration range resulted in a significant reduction of progeny viral titers in infected cells.Dual-luciferase reporter assays and Western blot analysis revealed that PS-341 could reverse the SFTSV-encoded nonstructural protein(NS) mediated degradation of retinoic acid-inducible gene-1(RIG-I), thereby antagonizing the inhibitory effect of NSs on interferons and blocking virus replication. In addition, we observed that inhibition of apoptosis promotes virus replication. These results indicate that targeting of cellular interferon pathways and apoptosis during acute infection might serve as the bases of future therapeutics for the treatment of SFTSV infections.     

Systems Neuroprotective Mechanisms in Ischemic Stroke

Ischemic stroke, although causing brain infarction and neurological deficits, can activate innate neuroprotective mechanisms, including regional mechanisms within the ischemic brain and distant mechanisms from non-ischemic organs such as the liver, spleen, and pancreas, supporting neuronal survival, confining brain infarction, and alleviating neurological deficits. Both regional and distant mechanisms are defined as systems neuroprotective mechanisms. The regional neuroprotective mechanisms involve release and activation of neuroprotective factors such as adenosine and bradykinin, inflammatory responses, expression of growth factors such as nerve growth factors and neurotrophins, and activation and differentiation of resident neural stem cells to neurons and glial cells. The distant neuroprotective mechanisms are implemented by expression and release of endocrine neuroprotective factors such as fibroblast growth factor 21, resistin like molecule γ, and trefoil factor 3 from the liver; brain-derived neurotrophic factor and nerve growth factor from the spleen; and neurotrophin 3 and vascular endothelial growth factor C from the pancreas. Furthermore, ischemic stroke induces mobilization of bone marrow hematopoietic stem cells and endothelial progenitor cells into the circulatory system and brain, contributing to neuroprotection. The regional and distant mechanisms may act in coordination and synergy to protect the ischemic brain from injury and death. This paper addresses these mechanisms and associated signaling networks.     

益生菌联合早期肠内营养干预对 重症脑卒中患者营养状态及肠道菌群的影响

目的探讨益生菌联合早期肠内营养干预对重症脑卒中患者营养状态及肠道菌群的影响。方法选取2014年1月至2018年6月于我院住院治疗的重症脑卒中患者70例,随机分为观察组和对照组各35例。两组患者均予控制颅内压、营养神经细胞、抗生素预防感染、保护胃黏膜和维持水电解质酸碱平衡等基础治疗。对照组患者留置鼻饲管行常规肠内营养治疗,观察组患者在对照组治疗基础上加用双歧杆菌四联活菌片水化后鼻饲管注入,1.5 g/次,3次/d,连用10 d。观察两组患者治疗前和治疗10 d后营养状态指标[血清总蛋白(TP)、转铁蛋白(TF)、上臂三头肌肌围(MAMC)]的变化,并比较治疗后肠道菌群(双歧杆菌、乳杆菌、拟杆菌、肠球菌、大肠埃希菌)数量变化。结果治疗10 d后,两组患者血清TP、TF水平和MAMC较治疗前显著下降(P0.05),且治疗后观察组患者TP、TF水平和MAMC高于对照组(P0.05);同时治疗后观察组患者粪便中双歧杆菌、乳杆菌和拟杆菌数量高于对照组,肠球菌和大肠埃希菌数量低于对照组(P0.05)。结论益生菌联合早期肠内营养干预不仅可显著减缓重症脑卒中患者的营养状态恶化;而且能有效地纠正肠道菌群失调,维持肠道微生态的稳定。     

Whole‐brain microcirculation detection after ischemic stroke based on swept‐source optical coherence tomography

The occurrence and development of ischemic stroke are closely related to cerebral blood flow. Real‐time monitoring of cerebral perfusion level is very useful for understanding the mechanisms of the disease. A wide field of view (FOV) is conducive to capturing lesions and observing the progression of the disease. In this paper, we attempt to monitor the whole‐brain microcirculation in middle cerebral artery occlusion (MCAO) rats over time using a wide FOV swept‐source OCT (SS‐OCT) system. A constrained image registration algorithm is used to remove motion artifacts that are prone to occur in a wide FOV angiography. During ischemia, cerebral perfusion levels in the left and right hemispheres, as well as in the whole brain were quantified and compared. Changes in the shape and location of blood vessels were also recorded. The results showed that the trend in cerebral perfusion levels of both hemispheres was highly consistent during MCAO, and the position of the blood vessels varied over time. This work will provide new insights of ischemic stroke and is helpful to assess the effectiveness of potential treatment strategies.      

In silico epitope-based vaccine design against influenza a neuraminidase protein: Computational analysis established on B- and T-cell epitope predictions

ObjectiveInfluenza A virus belongs to the most studied virus and its mutant initiates epidemic and pandemics outbreaks. Inoculation is the significant foundation to diminish the risk of infection. To prevent an incidence of influenza from the transmission, various practical approaches require more advancement and progress. More efforts and research must take in front to enhance vaccine efficacy.MethodsThe present research emphasizes the development and expansion of a universal vaccine for the influenza virus. Research focuses on vaccine design with high efficacy. In this study, numerous computational approaches were used, covering a wide range of elements and ideas in bioinformatics methodology. Various B and T-cell epitopic peptides derived from the Neuraminidase protein N1 are recognized by these approaches. With the implementation of numerous obtained databases and bioinformatics tools, the different immune framework methods of the conserved sequences of N1 neuraminidase were analyzed. NCBI databases were employed to retrieve amino acid sequences. The antigenic nature of the neuraminidase sequence was achieved by the VaxiJen server and Kolaskar and Tongaonkar method. After screening of various B and T cell epitopes, one efficient peptide each from B cell epitope and T cell epitopes was assessed for their antigenic determinant vaccine efficacy. Identical two B cell epitopes were recognized from the N1 protein when analyzed using B-cell epitope prediction servers. The detailed examination of amino acid sequences for interpretation of B and T cell epitopes was achieved with the help of the ABCPred and Immune Epitope Database.ResultsComputational immunology via immunoinformatic study exhibited RPNDKTG as having its high conservancy efficiency and demonstrated as a good antigenic, accessible surface hydrophilic B-cell epitope. Among T cell epitope analysis, YVNISNTNF was selected for being a conserved epitope. T cell epitope was also analyzed for its allergenicity and cytotoxicity evaluation. YVNISNTNF epitope was found to be a non-allergen and not toxic for cells as well. This T-cell epitope with maximum world populace coverages was scrutinized for its association with the HLA-DRB1*0401 molecule. Results from docking simulation analyses showed YVNISNTNF having lower binding energy, the radius of gyration (Rg), RMSD values, and RMSE values which make the protein structure more stable and increase its ability to become an epitopic peptide for influenza virus vaccination.ConclusionsWe propose that this epitope analysis may be successfully used as a measurement tool for the robustness of an antigen–antibody reaction between mutant strains in the annual design of the influenza vaccine.     

英国等地不明原因儿童肝炎的暴发情况及病因

2022年3月31日,苏格兰首先报告了5例患有不明原因重症肝炎的儿童。世界卫生组织(World Health Organization,WHO)于4月15日就不明原因儿童肝炎发布指导性意见,对确诊病例、可疑病例和流行病学相关病例进行了定义。截至4月21日,已有12个国家报告169例确诊病例,从1月龄至16岁不等。临床表现为急性肝炎,谷草转氨酶(aspartate aminotransferase,AST)或谷丙转氨酶(alanine aminotransferase,ALT)＞500 IU/L,多数患儿有黄疸、恶心、腹痛、乏力、嗜睡和胃肠道症状,包括腹泻和呕吐,大多数患儿无发热。17例接受了肝移植,至少报告1例死亡。考虑到流行病学特点和患儿的临床特征,感染性因素导致该疾病的可能性更大。病例的实验室检查结果均排除了甲、乙、丙、丁和戊型肝炎,并提示腺病毒可能与不明原因儿童肝炎有关,但其他感染性因素或环境因素仍不能完全排除。本文对此次不明原因儿童肝炎的发展情况及其可能病因进行了介绍。该疾病存在输入性风险,我国应对此早做准备。     

不同剂量右美托咪定静脉维持对重型颅脑损伤患者术后生命体征、免疫功能和血清神经细胞因子的影响

摘要 目的：观察不同剂量右美托咪定静脉维持在重型颅脑损伤患者中的应用价值。方法：选取2018年9月~2020年9月期间江苏大学附属宜兴市人民医院麻醉与重症医学科接收的重型颅脑损伤患者96例,根据随机数字表法分为三组：A组（右美托咪定剂量为0.3μg/kg?h）、B组（右美托咪定剂量为0.5 μg/kg?h）和C组（右美托咪定剂量为0.7 μg/kg?h）,各32例。观察三组患者不同时间点的生命体征、免疫功能、镇静镇痛情况、血清神经细胞因子,记录三组不良反应发生情况。结果：B组、C组术后24 h、术后72 h的心率（HR）、呼吸频率（RR）、平均动脉压（MAP）低于A组（P<0.05）。B组、C组术后24 h、术后72 h的Ramsay镇静评分、视觉模拟评分法（VAS）评分低于A组（P<0.05）。B组、C组术后24 h、术后72 h的CD3⁺、CD4⁺/CD8⁺高于A组（P<0.05）。B组、C组术后24 h、术后72 h的神经元特异性烯醇化酶（NSE）、中枢神经特异性蛋白（S100β）低于A组（P<0.05）。C组的不良反应总发生率高于A组、B组（P<0.05）。结论：重型颅脑损伤患者术中给予右美托咪定剂量为0.5 μg/kg?h、0.7 μg/kg?h维持,可有效维持患者生命体征平稳,促进患者免疫功能和血清神经细胞因子水平改善,但0.7 μg/kg?h剂量的右美托咪定使用后不良反应发生率相对更高。     

阿替普酶联合阿加曲班对急性缺血性脑卒中患者内皮损伤、血液流变学和神经功能损伤因子的影响

摘要 目的：探讨阿替普酶联合阿加曲班治疗急性缺血性脑卒中（AIS）对患者内皮损伤、血液流变学和神经功能损伤因子的影响。方法：采用随机数字表法,将南方医科大学珠江医院神经内科2019年8月~2021年7月期间收治的94例AIS患者分为对照组（n=47）和研究组（n=47）。对照组患者接受阿替普酶治疗,研究组患者接受阿替普酶联合阿加曲班治疗,对比两组疗效、内皮损伤指标、血液流变学指标、神经功能损伤因子、美国国立卫生研究所卒中量表（NIHSS）评分、Barthel指数（BI）评分和不良反应。结果：与对照组治疗后相比,研究组治疗后的临床总有效率更高（P<0.05）。与对照组治疗后相比,研究组治疗后内皮素-1（ET-1）水平更低,降钙素基因相关肽（CGRP）、一氧化氮（NO）水平更高（P<0.05）。与对照组治疗后相比,研究组治疗后血浆黏度（PV）、全血黏度（WBV）、红细胞压积（HCT）、纤维蛋白原（FIB）水平更低（P<0.05）。与对照组治疗后相比,研究组治疗后神经元特异性烯醇化酶（NSE）、S100β蛋白水平更低（P<0.05）。与对照组治疗后相比,研究组治疗后NIHSS评分更低,BI评分更高（P<0.05）。两组不良反应发生率组间对比无差异（P>0.05）。结论：阿替普酶联合阿加曲班应用于AIS患者,可改善机体血液流变学,减轻内皮功能损伤和神经功能损害。     

重症创伤患者ICU后综合征心理障碍影响因素分析

摘要 目的：探究重症创伤患者ICU后综合征（PICS）心理障碍影响因素。方法：本次研究纳入60例重症创伤患者,按照是否存在PICS分为对照组（20例）和PICS组（40例）。进行不同治疗情况PICS心理障碍影响因素单因素分析。PICS心理障碍患者急性生理与慢性健康状况评分系统（APACHEII）和医院焦虑和抑郁量表（HADS）评分、Ogawa改良创伤评分系统、匹兹堡睡眠质量指数量表（PSQI）评分进行单因素分析,并进行PICS心理障碍的相关性分析,PICS心理障碍影响因素Logistic回归分析。结果：（1）PICS组年龄<30比例较对照组升高,30-50患者比例较对照组降低（P<0.05）。PICS组文化程度文盲和小学患者比例较对照组升高,初中和高中及以上患者比例较对照组降低（P<0.05）。（2）PICS组手术、手术时间1~3 h和＞3 h、ICU时间10~14 d、镇静药物和有创机械通气患者比例较对照组升高（P<0.05）。（3）PICS组APACHEII评分<20和20~25患者比例较对照组降低,APACHEII评分25~30和＞30患者比例较对照组升高（P<0.05）;PICS组HADS评分<5和5~15患者比例较对照组降低,HADS评分15~25和≥25患者比例较对照组升高（P<0.05）;PICS组得分低于9分的轻度损伤者和得分10~16分的中度损伤的患者比例较对照组降低,得分≥17分为重度损伤的患者比例较对照组升高（P<0.05）;PICS组得分≤7分的睡眠质量较好的患者比例较对照组降低（P<0.05）,得分>7分的睡眠障碍的患者比例较对照组升高（P<0.05）。（4）PICS组年龄、手术时间、ICU时间、APACHEII评分、HADS评分、PSQI得分以及创伤指数评分较对照组升高（P<0.05）;（5）PICS心理障碍与年龄、文化程度、手术时间、ICU时间、镇静药物、无创机械通气、有创机械通气、APACHEII评分、HADS评分、创伤指数评分以及PSQI评分相关（P<0.05）。结论：PICS组年龄、手术时间、ICU时间、APACHEII评分和HADS评分较对照组升高;PICS心理障碍与年龄、文化程度、手术时间、ICU时间、镇静药物、无创机械通气、有创机械通气、APACHEII评分、HADS评分、创伤指数评分以及PSQI评分相关。