Repurposing niclosamide as a novel anti-SARS-Cov-2 drug by restricting entry protein CD147 (preprint)

Background The burst of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the global COVID-19 pandemic. But until today only limited numbers of drugs are discovered to treat COVID-19 patients. Even worse, the rapid mutations of SARS-CoV-2 compromise the effectiveness of existing vaccines and neutralizing antibodies due to the increased viral transmissibility and immune escape. CD147-spike protein, one of the entries of SRAR-CoV-2 into host cells, has been reported as a promising therapeutic target for developing drugs against COVID-19.Methods CRISPR-Cas9 induced gene knockout, western blotting, tet-off protein overexpression, ribonucleoprotein IP and RNA-IP were used to confirm the regulation of HuR on mRNA of CD147. Regulation of niclosamide on HuR nucleo-translocation was assessed by immunofluorescence staining of cell lines, IHC staining of tissue of mouse model and western blotting. Finally, the suppression of niclosamide on SARS-CoV-2 infection induced CD147 was evaluated by ACE2-expressing A549 cells and western blotting.Results We first discovered a novel regulation mechanism of CD147 via the RNA-binding protein HuR. We found that HuR regulates CD147 post-transcription by directly bound to its 3'-UTR. The loss of HuR reduced CD147 in multiple cell lines. Niclosamide inhibited CD147 function by blocking HuR cytoplasmic translocation and diminishing CD147 glycosylation. SARS-CoV-2 infection induced CD147 in ACE2-expressing A549 cells, which could be neutralized by niclosamide in a dose-dependent manner.Conclusion Together, our study reveals a novel regulation mechanism of CD147 and niclosamide can be repurposed as an effective COVID-19 drug by targeting the virus entry, CD147-spike protein.

Impactful publications of critical care medicine research in China: A bibliometric analysis

Background Although publications have been increasing rapidly, the research quality has yet to improve in the field of critical care medicine (CCM) in China. This study aimed at investigating the current status of and the influential factors for impactful publications in CCM research by Chinese authors. Methods Publications by authors with the affiliation of critical care medicine department or intensive care unit (CCM/ICU) in Chinese as well as American hospitals from 2001 to 2020 were retrieved from the Web of Science Core Collection (WoSCC) database for this bibliometric analysis. Moreover, statistical analyses to test factors affecting impactful publications by Chinese authors were performed. Results Of 13,487 articles retrieved by this search strategy, 6,622 were published by Chinese authors as first or corresponding authors. The annual publications by Chinese authors have been rapidly increasing from 2001 to 2020, and so did the citations to these articles. However, the proportion in the world of publications by Chinese authors was much less than that by American authors each year [M (IQR): 1.85 (9.592) vs. 27.77 (7.3), p < 0.001]. In addition, impactful articles were significantly less published by Chinese than by American authors, including articles either in journals with a high impact factor (p < 0.001) or in the top 10 journals in the field of CCM (5.4 vs 13.4%, p < 0.001), and articles with high citation frequency as well (p < 0.001). Moreover, the percentage of impactful publications by Chinese authors was likely associated with academic background and regions of the author's affiliations, funds support, public health events of COVID-19, and collaboration between authors. Conclusion Our results demonstrated that CCM research in China grew rapidly in the recent 20 years. However, the impactful publications remained limited, largely owing to the shortage of comprehensive research training, inactive collaboration, and underfunded CCM research.

Study on health-related quality of life and influencing factors of pediatric medical staff during the COVID-19 outbreak (preprint)

Aims To evaluate the health-related quality of life (HRQoL) status and explore its associated factors in pediatric medical staff during the COVID-19 epidemic so as to guide hospitals and administrators to formulate suitable interventions.Methods A cross-sectional study was conducted to investigate the HRQoL of pediatric medical staff. Univariable and multivariable logistic regression were used to analyze the associated factors.Results A total of 2,997 participants were recruited. Females scored worse than males in terms of emotional functioning (OR = 1.6, 95%CI: 1.2–2.1) and cognitive functioning (OR = 1.4, 95%CI: 1.1–1.8). The respondents aged 30–39 years and 40–49 years scored worse in nearly all domains of HRQoL compared health care professionals under 30 years old. Respondents with high education had lower scores in physical functioning (OR = 1.3, 95%CI: 1.0-1.7) and emotional functioning (OR = 1.5, 95%CI: 1.2–1.9).Compared with doctors, nurses had higher scores in all domains except for summary score and worry. The respondents whose working places had not set up pediatric fever clinics and isolated observation areas independently had better scores in all domains except for worry. The respondents who had ever treated patients with COVID-19 had lower scores in all domains.Conclusions During the COVID-19 outbreak, the HRQoL of pediatric medical staff decreased. The factors associated with HRQoL can be used to develop intervention to improve HRQoL in pediatric medical staff.