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.     

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.     

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。     

Passenger seating position and the risk of passenger death in traffic crashes: a matched cohort study

OBJECTIVE: To estimate the association of passenger seating position with the risk of death for passengers in traffic crashes. Design, setting, PARTICIPANTS: Matched cohort analysis of data from the National Highway Traffic Safety Administration Fatality Analysis Reporting System regarding 56 644 passengers in 23 308 passenger cars, light trucks, vans, and sport utility vehicles that crashed during 1990-2001. MAIN OUTCOME MEASURE: The adjusted risk ratio (aRR) for death of a rear seat passenger compared with a front seat passenger within 30 days of a crash. RESULTS: The aRR for all passengers in the rear seat in a crash was 0.79 (95% CI 0.77 to 0.82). This estimate varied by age, restraint use, and the presence of a front passenger airbag (p<0.001). For restrained passengers in cars with a front passenger airbag, the aRR was 0.62 (95% CI 0.48 to 0.81) for children 0-12 years, 0.96 (95% CI 0.88 to 1.06) for passengers 13-29 years, 1.03 (95% CI 0.93 to 1.15) for passengers 30-59 years, and 1.06 (95% CI 0.90 to 1.26) for passengers 60 years or older. The rear seat was associated with more protection in cars without front airbags and more protection for unrestrained passengers compared with restrained passengers. CONCLUSIONS: Previous studies have reported that the rear seat was safer for persons of all ages; thus seating a young child in the rear has often meant that older children and adults had to assume an increased risk of death by sitting in the front. These results suggest that when front passenger airbags are present and passengers are restrained, putting adults in front and children in back enhances child safety without sacrificing adult safety.     

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。     

Intentional mis-reporting of food consumption and its relationship with body mass index and psychological scores in women

BACKGROUND: The reasons for mis-reporting food consumption warrant investigation. OBJECTIVE: To document intention to mis-report food consumption and its associations with psychological measures in women. DESIGN: A total of 184 female volunteers aged 18-65 years, comprising 50 seeking help in primary care to lose weight with a body mass index (BMI) >/=30 kg m(-2) (obese-clinical group) and 134 nurses (nonclinical groups) (BMI <25 kg m(-2), n = 52; BMI 25-29.9 kg m(-2), n = 45; BMI >/=30 kg m(-2), n = 37) were studied. A questionnaire was administered containing three psychological tests (self-esteem, psychological well-being and Stunkard's three-factor eating questionnaire) and new items to address food intake mis-reporting. RESULTS: Overall, 68% of participants declared an inclination to mis-report (64% nonclinical, 78% clinical). Inclination to under-report was 29, 33 and 51% in the three nonclinical groups; and 46% among the obese clinical patients. Among the same groups, inclination to over-report were 39, 29, 11 and 32%. After adjusting for social deprivation and BMI, women inclined to mis-report had higher hunger (P = 0.008) and disinhibition (P = 0.005) scores than those intending to report accurately. These variables were associated with current dieting, frequency of dieting, self-reported bingeing and dissatisfaction with body weight. CONCLUSIONS: These findings indicate that intentional under-reporting and over-reporting of food consumption are common in women of all BMI categories and are associated with eating behaviour. Current dieting, frequency of dieting in the past, self-reported bingeing and dissatisfaction with body weight seem to mediate this relationship.     

我国城市地下水水质污染状况研究进展

综述了我国城市地下水水质污染状况的研究进展