Preclinical evaluation of a plant-derived SARS-CoV-2 subunit vaccine: Protective efficacy,immunogenicity, safety,and toxicity

Coronavirus disease 2019 (COVID-19) is an acute respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The prevention of SARS-CoV-2 transmission has become a global priority. Previously, we showed that a protein subunit vaccine that was developed based on the fusion of the SARS-CoV-2 receptor-binding domain (RBD) to the Fc portion of human IgG1 (RBD-Fc), produced in Nicotiana benthamiana, and adjuvanted with alum, namely, Baiya SARS-CoV-2 Vax 1, induced potent immunological responses in both mice and cynomolgus monkeys. Hence, this study evaluated the protective efficacy, safety, and toxicity of Baiya SARS-CoV-2 Vax 1 in K18-hACE2 mice, monkeys and Wistar rats. Two doses of vaccine were administered three weeks apart on Days 0 and 21. The administration of the vaccine to K18-hACE2 mice reduced viral loads in the lungs and brains of the vaccinated animals and protected the mice against challenge with SARS-CoV-2. In monkeys, the results of safety pharmacology tests, general clinical observations, and a core battery of studies of three vital systems, namely, the central nervous, cardiovascular, and respiratory systems, did not reveal any safety concerns. The toxicology study of the vaccine in rats showed no vaccine-related pathological changes, and all the animals remained healthy under the conditions of this study. Furthermore, the vaccine did not cause any abnormal toxicity in rats and was clinically tolerated even at the highest tested concentration. In addition, general health status, body temperature, local toxicity at the administration site, hematology, and blood chemistry parameters were also monitored. Overall, this work presents the results of the first systematic study of the safety profile of a plant-derived vaccine, Baiya SARS-CoV-2 Vax 1; this approach can be considered a viable strategy for the development of vaccines against COVID-19.     

新型冠状病毒肺炎疫情下喉镜检查的防护策略

目的探讨新型冠状病毒肺炎（COVID 19）疫情下耳鼻咽喉头颈外科喉镜室如何做好防护工作，在保证临床诊疗工作顺利完成的同时保护好医务人员及患者健康、避免院内交叉感染。方法本研究查阅相关资料并总结医院的疫情防控经验及应对策略，在患者合理分流、喉镜室工作环境的布置及工作人员的个人防护、喉镜检查前的准备工作、检查中的操作流程及注意事项及检查后的清洁消毒工作等方面做好疫情期间周详合理的工作安排。结果疫情期间，耳鼻咽喉头颈外科喉镜室每日临床工作顺利完成，所有医务人员及患者均未感染新型冠状病毒，也未出现其他院内交叉感染。结论耳鼻咽喉头颈外科喉镜室的防护策略合理有效，能够在完成临床诊疗工作的同时有效保护医患的健康。     

Male Sexual Function After Pediatric Kidney Transplantation—A Cross-sectional Nationwide Study

BackgroundData on adult sexual functioning after kidney transplantation (KTx) during childhood or adolescence are scarce.AimTo assess the long-term sexual and psychosocial quality of life after pediatric KTx.Methods29 young men (median age 27.1 years) were examined 18.7 years (median) after KTx. 56 age-matched healthy men (median age 30.0 years) served as controls.OutcomeWe studied the influence of sociodemographics, previous renal replacement therapy, current reproductive hormonal serum levels, testicular size, and data on several validated mental and physical questionnaires on participants' Derogatis Interview for Sexual Functioning self-report scores.ResultsThe KTx recipients had significantly poorer sexual functioning than their healthy peers. KTx men had less frequent sexual activity with a partner (P = .03) and poorer orgasms (P = .002) than the controls but no erectile dysfunction (P = .5).Clinical implicationsDepressive symptoms, relationship status, and longer dialysis duration predicted poor adult sexual functioning in KTx recipients, whereas age at transplantation or at the time of the study did not.Strengths & LimitationsThis study contributes extended follow-up data to the very scarce literature on adult sexual functioning in pediatric KTx recipients. Relatively small population and low participation rate limit the comprehensive data interpretation in a population-based cohort of male KTx recipients.ConclusionSexual functioning is often impaired in young men after pediatric KTx, emphasizing the need for long-term monitoring of sexual health and sexuality as important dimensions of quality of life.Tainio J, Jahnukainen T, Jalanko H, et al. Male Sexual Function After Pediatric Kidney Transplantation—A Cross-sectional Nationwide Study. J Sex Med 2020;17:2104–2107.     

女性难治性膀胱过度活动症患者心理弹性及保护性因素研究

目的探讨女性难治性膀胱过度活动症患者心理弹性状况及保护性因素，为改善其身心健康提供依据。方法采用心理弹性量表、症状自评量表、艾森克人格问卷、社会支持量表、焦虑及抑郁量表对80例女性难治性膀胱过度活动症患者进行问卷调查。结果女性难治性膀胱过度活动症患者心理弹性得分为（54.10±8.27）分，显著低于国内常模（P＜0.05）。患者的一般情况（病程、年龄、文化程度）对心理弹性的预测作用不明显（R2=0.14，F=18.10），当社会支持、SCL-90、人格特质、SAS、SDS进入方程后，对患者的心理弹性具有较明显的预测作用（R2=0.67，△R2=0.46，F=115.22）。结论女性难治性膀胱过度活动症患者心理弹性较差，社会支持、SCL-90、人格特质、焦虑抑郁情绪是其重要的影响因素，应重视患者存在的心理问题，发掘心理弹性的保护性因素并积极干预，促进其身心健康。     

Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response

Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4⁺ T cells in the lung. PA-specific CD4⁺ T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity.     

DNA vaccine encoding the moonlighting protein Onchocerca volvulus glyceraldehyde-3-phosphate dehydrogenase (Ov-GAPDH) leads to partial protection in a mouse model of human filariasis

River blindness, caused by the filarial parasite Onchocerca volvulus, is a major socio-economic and public health problem in Sub-Saharan Africa. In January 2015, The Onchocerciasis Vaccine for Africa (TOVA) Initiative has been launched with the aim of providing new tools to complement mass drug administration (MDA) of ivermectin, thereby promoting elimination of onchocerciasis in Africa. In this context we here present Onchocerca volvulus glyceraldehyde-3-phosphate dehydrogenase (Ov-GAPDH) as a possible DNA vaccine candidate. We report that in a laboratory model for filariasis, immunization with Ov-GAPDH led to a significant reduction of adult worm load and microfilaraemia in BALB/c mice after challenge infection with the filarial parasite Litomosoides sigmodontis. Mice were either vaccinated with Ov-GAPDH.DNA plasmid (Ov-pGAPDH.DNA) alone or in combination with recombinantly expressed Ov-GAPDH protein (Ov-rGAPDH). During the following challenge infection of immunized and control mice with L. sigmodontis, those formulations which included the DNA plasmid, led to a significant reduction of adult worm loads (up to 57% median reduction) and microfilaraemia (up to 94% reduction) in immunized animals. In a further experiment, immunization with a mixture of four overlapping, synthetic Ov-GAPDH peptides (Ov-GAPDHpept), with alum as adjuvant, did not significantly reduce worm loads. Our results indicate that DNA vaccination with Ov-GAPDH has protective potential against filarial challenge infection in the mouse model. This suggests a transfer of the approach into the cattle Onchocerca ochengi model, where it is possible to investigate the effects of this vaccination in the context of a natural host–parasite relationship.     

临床护理路径在心血管患者静脉留置针中的研究分析

目的:提高静脉留置针使用有效期,保证心血管患者得到及时用药,有效开放静脉抢救通道。方法:建立了心血管患者静脉留置针的临床护理路径(Clinical Nursing Pathway,CNP)。选择我院2018年1-12月期间接诊的静脉留置针心血管患者为研究对象,共100例,随机分组,即对照组(50例,常规护理)与实验组(50例,在常规护理基础上辅以临床护理路径),比较两组护理效果,包括留置时间、不良反应情况、患者满意度等。结果:护理后,两组患者留置时间无明显差异,但实验组不良反应发生率、静脉炎发生率低于对照组,差异有统计学意义(P<0.05);实验组满意度、一次性置管成功率高于对照组,而非计划性拔管率则低于对照组,差异有统计学意义(P<0.05)。结论:心血管患者静脉留置针护理中辅以临床护理路径,可减少不良反应,预防静脉炎,延长置管时间,提高护理满意度,值得优选。     

丹参对持续癫痫幼鼠脑损伤保护作用的实验研究

目的 探讨丹参对持续癫痫发作诱发幼鼠脑神经元损伤是否具有保护作用。方法 皮下及腹腔注射贝美格针诱发健康幼龄鼠癫痫持续状态发作。光镜下观察神经元病变情况；电镜观察海马神经元超微结构的改变。结果 持续癫痴组幼鼠脑组织光镜下可见明显的神经元病变。电镜下可见海马区神经元的超微结构病变。丹参治疗组神经元病变均轻于持续癫痴组；而正常对照组未见类似病变。结论 丹参在组织、细胞和亚细胞水平对持续癫病幼鼠脑神经元损伤具有一定的保护作用，为临床有效防治小儿惊厥性脑损伤提供了可靠的实验依据。     

乡镇中,小学教室噪声卫生防护距离的研究

本文对乡镇中，小学的交通噪声进行了调查研究，结果表明，在９：００～１６：４５时间内，中学的Ｌｅｑ值为８０ｄＢ（Ａ），Ｌ５０为７２ｄＢ（Ａ），小学的Ｌｅｑ值为８０５ｄＢ（Ａ），Ｌ５０为７３ｄＢ（Ａ）。文章还对不同距离的噪怕衰减情况进行统计分析，并制订出乡镇中，小学教室内噪声不超过５０ｄＢ（Ａ）防护距离为１２０米，不超过４５ｄＢ（Ａ）防护距离为２２０米。     

溶酶体保护蛋白/组织蛋白酶A基因敲除小鼠听力和耳形态学初步研究

目的研究溶酶体保护蛋白/组织蛋白酶A(protective protein/cathepsin A,PPCA)基因敲除小鼠听功能和耳形态学改变,探讨半乳糖唾液酸沉积症听力损害的病理生理机制。方法应用听性脑干反应(ABR)测试和颞骨连续切片,观察1月和2月龄的PPCA基因敲除纯合子(PPCA-/-)小鼠ABR反应阈和光镜下外耳、中耳及内耳形态改变,并以野生型(PPCA / )小鼠作对照。结果1月龄PPCA-/-小鼠ABR反应阈和耳形态无明显改变;2月龄时,短声和短音8、163、2 kHz反应阈较PPCA / 提高40~45 dB SPL,中耳黏膜增厚、听骨细胞囊泡化、变形和关节腔融合,血管纹增厚、螺旋神经节细胞、螺旋缘纤维细胞、前庭膜、基底膜及沿前庭阶外淋巴隙的间皮细胞囊泡化,但Corti器毛细胞及支持细胞正常。结论溶酶体保护蛋白/组织蛋白酶A缺乏可导致听力损害、中耳及耳蜗形态改变、中耳炎、听骨改变以及耳蜗螺旋神经节、血管纹、螺旋缘、前庭膜和基底膜等细胞的溶酶体储积,可能分别是传导性聋和感觉神经性聋的形成机制。