Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.     

Circulating angiotensin converting enzyme 2 and COVID-19

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a widespread outbreak since December 2019. The SARS-CoV-2 infection-related illness has been dubbed the coronavirus disease 2019 (COVID-19) by the World Health Organization. Asymptomatic and subclinical infections, a severe hyper-inflammatory state, and mortality are all examples of clinical signs. After attaching to the angiotensin converting enzyme 2 (ACE2) receptor, the SARS-CoV-2 virus can enter cells through membrane fusion and endocytosis. In addition to enabling viruses to cling to target cells, the connection between the spike protein (S-protein) of SARS-CoV-2 and ACE2 may potentially impair the functionality of ACE2. Blood pressure is controlled by ACE2, which catalyzes the hydrolysis of the active vasoconstrictor octapeptide angiotensin (Ang) II to the heptapeptide Ang-(1-7) and free L-Phe. Additionally, Ang I can be broken down by ACE2 into Ang-(1-9) and metabolized into Ang-(1-7). Numerous studies have demonstrated that circulating ACE2 (cACE2) and Ang-(1-7) have the ability to restore myocardial damage in a variety of cardiovascular diseases and have anti-inflammatory, antioxidant, anti-apoptotic, and anti-cardiomyocyte fibrosis actions. There have been some suggestions for raising ACE2 expression in COVID-19 patients, which might be used as a target for the creation of novel treatment therapies. With regard to this, SARS-CoV-2 is neutralized by soluble recombinant human ACE2 (hrsACE2), which binds the viral S-protein and reduces damage to a variety of organs, including the heart, kidneys, and lungs, by lowering Ang II concentrations and enhancing conversion to Ang-(1-7). This review aims to investigate how the presence of SARS-CoV-2 and cACE2 are related. Additionally, there will be discussion of a number of potential therapeutic approaches to tip the ACE/ACE-2 balance in favor of the ACE-2/Ang-(1-7) axis.     

注射用核糖核酸Ⅱ改善晚期胰腺癌化疗患者整体获益可能性的真实世界研究北大核心

目的:评价注射用核糖核酸Ⅱ联合化疗在真实世界中治疗晚期胰腺癌的疗效和安全性。方法:基于LinkDoc数据库纳入2012年至2018年就诊于河南省肿瘤医院等10家研究中心且确诊为局部进展期和晚期胰腺癌的患者923例,试验组采用化疗联合注射用核糖核酸Ⅱ治疗,对照组采用单纯化疗治疗。采用倾向性评分匹配的方法均衡两组的基线信息,比较两组间的总生存期(overall survival,OS)、无进展生存期(progression-free survival,PFS)及不良事件和化疗相关不良反应的发生率。结果:试验组和对照组的中位OS分别为7.5个月和6.7个月,中位PFS分别为3.7个月和3.3个月,差异均无统计学意义(P>0.05)。试验组不良事件发生率略低于对照组(88.7%vs 92.1%),试验组化疗相关不良反应发生率略高于对照组(64.1%vs 57.1%),差异均无统计学意义(P>0.05)。结论:注射用核糖核酸Ⅱ联合化疗治疗晚期胰腺癌具有生存获益趋势,无肝转移患者是潜在的优势人群,该结论尚需前瞻性研究进一步确证。     

Statin use and medically attended acute respiratory illness among influenza vaccine recipients

BackgroundPrevious studies have suggested that statins decrease influenza vaccine effectiveness and increase risk of medically attended acute respiratory illness (MAARI).ObjectivesTo examine the association of incident statin use and MAARI in a cohort of influenza vaccine recipients.MethodsThis retrospective cohort study evaluated influenza vaccine recipients within the Tricare population. The primary outcome compared MAARI incidence during the follow-up period in a propensity score-matched cohort of incident statin users and statin non-users. Secondary analysis included propensity score-adjusted comparisons between incident statin users and statin non-users in the entire cohort and prespecified sub-cohorts with and without comorbidities. The propensity score was derived from 72 variables encompassing demographics, medical history, comorbidities, medication use, and healthcare utilization.ResultsMAARI incidence in statin users was similar to non-users in the propensity score-matched cohort (odds ratio [OR] 0.92; 95% confidence interval [CI] 0.84–1.01). In contrast, statin users with lower comorbidity had lower OR for MAARI compared to non-users (Charlson Score zero cohort: 0.85 [CI 0.74–0.98]; No Diabetes cohort: 0.88 [CI 0.80–0.96]).ConclusionIncident statin use was not associated with increased MAARI incidence and may be associated with lower incidence of MAARI in those with less comorbidity. This study thus offers reassurance regarding the effectiveness of the influenza vaccine in statin users.     

知母饮片炮制前后黄酮类和皂苷类成分变化研究

目的:测定知母饮片炮制前后3个黄酮类和2个皂苷类成分变化。方法:采用高效液相色谱-紫外检测法(HPLC-UV)测定3个黄酮类成分,色谱柱为岛津Intetsil ODS-3(4.6 mm×250 mm,5μm),流动相为乙腈-0.2%冰醋酸,梯度洗脱,进样量20μL,流速1.0 mL/min,柱温30℃;采用高效液相色谱-蒸发光散射检测法(HPLC-ELSD)测定2个皂苷类成分,色谱柱为岛津Intetsil ODS-3(4.6 mm×250 mm,5μm),流动相为乙腈-0.2%冰醋酸,梯度洗脱,进样量10μL,流速1.0 mL/min,氮气流量2.5 mL/min,蒸发温度80℃。结果:知母饮片炮制后知母皂苷BⅡ、新芒果苷、芒果苷含量下降,知母皂苷AⅢ含量上升,异芒果苷含量相对稳定。结论:知母饮片炮制后部分知母皂苷BⅡ会转化成知母皂苷AⅢ,新芒果苷、芒果苷会转化成其他成分,异芒果苷结构相对稳定,不易转化成其他成分。     

改良肌激动器治疗安氏Ⅱ类Ⅰ分类错(牙合)畸形的X线头影测量分析

目的探讨改良肌激动器矫治早期安氏Ⅱ类Ⅰ分类下颌后缩的错[牙合]畸形的临床疗效。方法选择口腔正畸门诊就诊的安氏Ⅱ类Ⅰ分类下颌后缩的错[牙合]患者20例,年龄在10~12岁之间,平均年龄10.6岁。采用改良肌激动器进行功能矫治,用winceph8.0对矫治前后X线头颅侧位片进行定点测量,所得数据应用SPSS23.0软件进行配对t检验。结果矫治后患者面型改善明显,磨牙基本中性关系,前牙覆[牙合]、覆盖基本正常,治疗后角度测量值SNB、ANB、NA-PA和U1-SN变化,差异有显著性(P<0.01),角度测量值SNA、SNMP、L1-MP、L1-NB、FH-Y轴和Z角变化,无显著性(P>0.05),线距测量值L1-NB、UL-EP和LL-EP跟治疗前比,变化无显著性(P>0.05)。结论改良肌激动器能够矫治早期安氏Ⅱ类Ⅰ分类错[牙合]畸形,值得在临床推广使用。     

刚果（金）维和任务区52例隐翅虫皮炎的调查和临床治疗

目的 调查研究刚果（金）维和任务区隐翅虫皮炎患者的发病特点、行为因素及临床治疗情况,为科学防控隐翅虫皮炎提供有效依据。方法 选择2018年5月—2020年4月在刚果（金）维和任务区中国二级医院临床诊断的52例隐翅虫皮炎患者为研究对象,对患者的一般资料、行为因素及临床特征进行流行病学调查,并分析药物的临床疗效。结果 刚果（金）任务区的隐翅虫皮炎具有明显的季节性,每年自10月起发病数逐渐增多,次年1—3月为高峰期。患者驻地主要分布在郊区,有50例（96.15%）,多见于户外工作者,为48例（92.3%）, 其中白天有明确隐翅虫接触史者21例（40.4%）,夜间开窗就寝者20例（38.5%）,夜间开荧光灯就寝者16例（30.8%）,未使用纱窗者18例（34.6%）,就寝时四肢裸露者15例（28.9%）,所有患者未使用蚊帐、驱蚊剂及防护服。颈部、前臂为最容易发生的部位;皮损主要呈斑片状红斑分布（80.77%）,并可见特征性条索状或“吻唇样”改变。患者自觉烧灼痛（88.46%）,少数为瘙痒感（11.54%）。常规予以5%碳酸氢钠溶液擦洗,口服抗组胺药、外用炉甘石洗剂、抗生素联合糖皮质激素软膏是有效治疗手段。对于眶周受累患者,口服强的松,用丁苯羟酸乳膏,获得良好效果。结论 掌握隐翅虫皮炎的流行病学特点,增强二级医院医护人员对隐翅虫皮炎的认识水平,准确识别临床特征,有助于早期诊断并选择合适的治疗方案。     

血必净注射液对EICU脓毒症患者炎症应激反应和心肌功能的影响

目的:探讨血必净注射液治疗急诊重症监护室(EICU)脓毒症患者的疗效,以及对机体炎症应激反应和心肌功能的影响。方法:采用随机数字表法将190例脓毒症分为常规组和血必净组,每组均95例。两组均严格按照脓毒症治疗指南(2016年版)给予常规抗脓毒症集束化治疗,血必净组在常规治疗基础上给予血必净注射液治疗,常规组给予等量的0.9%氯化钠注射液。观察两组治疗前和治疗7 d后急性和慢性健康状况评分系统Ⅱ(APACHE Ⅱ)评分,检测并比较治疗前后血清炎性因子肿瘤坏死因子-α(TNF-α)、超敏C-反应蛋白(hs-CRP)、降钙素原(PCT)、白介素-6(IL-6)和心肌损伤标志物血肌钙蛋白I(cTn I)、肌酸激酶同工酶(CK-MB)水平,统计两组EICU住院时间和28 d死亡率。结果:两组治疗7 d后血清TNF-α、hs-CRP、PCT、IL-6和cTn I、CK-MB水平均明显下降(P<0.05),且治疗组治疗7 d后上述炎性因子和心肌功能指标水平显著低于常规组,差异有统计学意义(P<0.05)。治疗组治疗7 d后APACHEⅡ评分明显低于常规组,EICU住院时间较常规组明显缩短,差异有统计学意义(P<0.05),两组28 d病死率比较差异无统计学意义(P>0.05)。结论:常规对症治疗联合血必净注射液能有效减轻脓毒症患者机体炎症应激反应和保护心肌功能,对改善病情程度和缩短EICU住院时间有一定价值。