Long-term oral administration of Asarum heterotropoides f. mandshuricum (Maxim.) Kitag. decoction and its aristolochic acid analogs do not cause renal toxicity in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Asarum heterotropoides f. mandshuricum (Maxim.) Kitag. (AH) is widely used to treat influenza, COVID-19, allergic rhinitis, headache, toothache, rheumatoid arthritis, and peptic ulcer. However, its clinical use is controversial due to the concern of aristolochic acid nephropathy (AAN) caused by its component aristolochic acid analogs (AAs). AIM OF THE STUDY: The chronic toxicity of AH decoction and its main components AA IVa (AA-IVa) and aristolactam I (AL-I) was evaluated in mice. MATERIALS AND METHODS: AAs contents in AH were quantitated by liquid chromatography-mass spectrometry. A parallel design was employed to examine the potential chronic toxicity of AH decoction at doses equivalent to 0.5, 1.6, and 5.0 g/kg AH (approximately 10-100 times the clinical doses for humans) and its major AA components at doses equivalent to that in 5.0 g/kg AH to mice after consecutive daily oral administration for 12 and 24 weeks, and at 32 weeks after withdrawal for 8 weeks. RESULTS: AH crude herb contained 2.18 µg/g of AA-I, 48.49 µg/g of AA-IVa, and 14.0 µg/g of AL-I. AH decoction contained 5.45 µg/g of AA-IVa and 2.71 µg/g of AL-I. None of AA-II and AA-IIIa were detected in AH. After long-term administration of AH decoction and its major components AA-IVa and AL-I, mice showed no signs of illness or body weight changes. In addition, biochemical and pathohistological examinations showed that long-term administration of AH decoction and its major components AA-IVa and AL-I did not alter 1) serum levels of glutamic-pyruvic transaminase, glutamic oxalacetic transaminase, alkaline phosphatase, creatinine, and urea nitrogen, 2) renal tissue mRNA expression of kidney injury molecule 1 and neutrophil gelatinase-associated lipocalin, and 3) pathological morphology in the mouse liver, kidney, stomach, and bladder. CONCLUSIONS: AH has no obvious toxicity to mice and is relatively safe when it is used in the form of decoction. AA-IVa and AL-I, the two major AAs in AH, are not toxic to mice at the dose equivalent to that in the high dose of AH decoction. Considering the limited toxicological data on AH, we recommend that AH decoction medication should not overdose and the duration should not be too long.

Tempo-spatial infection risk assessment of airborne virus via CO2 concentration field monitoring in built environment.

The aerosol transmission was academically recognized as a possible transmission route of Coronavirus disease 2019 (COVID-19). We established an approach to assess the indoor tempo-spatial airborne-disease infection risks through aerosol transmission via real-time CO2 field measurement and occupancy monitoring. Compared to former studies, the proposed method can evaluate real-time airborne disease infection risks through aerosol transmission routes. The approach was utilized in a university office. The accumulated infection risk was calculated for three occupants with practical working schedules (from occupancy recording) and one hypothesis occupant with a typical working schedule. COVID-19 was used as an example. Results demonstrated that the individual infection risks diversified with different dwell times and working places in the office. For the three occupants with a practical working schedule, their 3-day accumulated infection risks were respectively 0.050%, 0.035%, 0.027% and 0.041% due to 11.6, 9.0 and 13.8 h exposure with an initial infector percentage of 1%. The results demonstrate that location and dwell time are both important factors influencing the infection risk of certain occupant in built environment, whereas existing literature seldom took these two points into consideration simultaneously. On the contrary, our proposed approach treated the infection risks as place-by-place, time-by-time and person-by-person diversified in the built environment. The risk assessment results can provide early warning for building occupants and contribute to the transmission control of air-borne disease.

Airborne infection risk assessment of COVID-19 in an inpatient department through on-site occupant behavior surveys

Airborne transmission is a possible infection route of the coronavirus disease 2019 (COVID-19). This investigation focuses on the airborne infection risk of COVID-19 in a nursing unit in an inpatient building in Shenzhen, China. On-site measurements and questionnaire surveys were conducted to obtain the air change rates and occupant trajectories, respectively. The aerosol transport and dose–response models were applied to evaluate the infection risk. The average outdoor air change rate measured in the wards was 1.1 h−1, which is below the minimum limit of 2.0 h−1 required by ASHRAE 170–2021. Considering the surveyed occupant behavior during one week, the patients and their attendants spent an average of 19.4 h/d and 15.1 h/d, respectively, in the wards, whereas the nurses primarily worked in the nurse station (3.0 h/d) and wards (2.4 h/d). The doctors primarily worked in their offices (2.6 h/d) and wards (1.1 h/d). Assuming one undetected COVID-19 infector emitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the nursing unit, we calculated the accumulated viral dose and infection probabilities of the occupants. After one week, the cumulative infection risks of the patients and attendants were almost equal (0.002), and were higher than those of the nurses (0.0013) and doctors (0.0004). Proper protection measures, such as reducing the number of attendants, increasing the air change rate, and wearing masks, were found to reduce the infection risk. It should be noted that the reported results are based on several assumptions, such as the speculated virological properties of SARS-CoV-2 and the particular trajectories of occupants. Moreover, only second generations of transmission were taken into consideration, whereas in reality, the week-long exposure may cause third generation of transmission or worse.

Comparison of COVID-19 infection risks through aerosol transmission in supermarkets and small shops.

Aerosol transmission is academically recognized as possible transmission route of Coronavirus disease 2019 (COVID-19). We established an approach to assess the airborne-disease infection risks through aerosol transmission based on the dose-response model and aerosol transport model. The accuracy of evaluation was guaranteed with on-site surveyed ventilation rate and occupant behavior. With the proposed approach, COVID-19 infection risks in 5 typical supermarkets and 21 small shops were evaluated. With one original infected early-shift staff, the average aerosols concentrations at steady-state are 1.06 × 10-3 RNA copies/m3 in the supermarkets and 4.73 × 10-2 RNA copies/m3 in the small shops. With the assumption of 5% original infected staff in the retail buildings, the infection probability of one customer is 1.40 × 10-6 for visiting one small shop and 6.22 × 10-6 for visiting one supermarket. The averaged infection risk in the supermarkets is higher than the small shops (p-value<0.001). On the other hand, the infection risks are higher for the staff working with the infected staff compared with the customers. The proposed approach can be applied to other occupied buildings and assist the pandemic control policy making for sustainable cities and society.

Study on ventilation rates and assessment of infection risks of COVID-19 in an outpatient building

A modified Wells-Riley model combining the airborne route and close contact route was proposed to predict the infection risks of coronavirus disease 2019 (COVID-19) in main functional spaces of an outpatient building in Shenzhen, China. The personnel densities and ventilation rates in the 20 waiting rooms, outpatient hall and hospital street were on-site measured. The average fresh air volume per person and occupant area per person in the 20 waiting rooms were 77.6 m3/h and 6.47 m2/per, satisfied with the Chinese standard. The average waiting time of the occupants was 0.69 h. Thus, assuming the proportion of infected people in the outpatient building was 2%, the daily average infection probabilities of COVID-19 in the 20 waiting rooms were 0.19–1.88% with a reasonable setting of the quanta produced by an infector (q = 45 quanta/h) and the effective exposure dose of pathogen per unit close contact time (β = 0.05 h−1). The design of the semi-closed hospital street with a height of 24 m improved its natural ventilation with a fresh air volume per person of 70–185 m3/h and further dilute the viral aerosol and decreased the infection risk to a negligible level (i.e., below 0.04% with an infector proportion of 2%). The assessment method provides real-time prediction of indoor infection risk and good assist in spread control of COVID-19.

Field study to characterize customer flow and ventilation rates in retail buildings in Shenzhen, China.

Reduction of the customers' exposure risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the retail buildings, i.e., supermarkets and small shops where residents purchase daily necessities is of prime importance during pandemic. In this study, the main influencing factors of the exposure risk of SARS-CoV-2, namely the occupant density, dwell time, and fresh air volume per person, were on-sited measured in 5 supermarkets and 21 small shops in Shenzhen, China. The small shops with an occupant area per person of 4.7 m2/per presented a more crowded environment than the supermarkets with an occupant area per person of 18.8 m2/per. The average dwell time of customers in the supermarkets linearly increased with the floor area and its probability distribution was fitted well by the Gamma distribution with a shape parameter of 3.0. The average dwell time of customers in the supermarkets was relatively longer than the combination of five types of small shops. In addition, the measured average outdoor air change rate of the small shops by natural ventilation was 10.7 h-1, while that of the supermarkets by mechanical ventilation was only 0.7 h-1. Correspondingly, the CO2 concentration in the small shops was 100-150 ppm lower than the supermarkets. The small shops provided an average fresh air volume per person of 216 m3/(h·per), far exceeding the supermarkets with a value of 95 m3/(h·per).