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Background Effective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19. Method In this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500 mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events. Results A total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians -6.0 days; 95% CI -6.0 to -4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose. Conclusions Although randomised trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating the COVID-19 pandemic.

7Background Effective therapies are urgently needed for the SARS-CoV-2 7 8pandemic. Chloroquine has been proved to have antiviral effect against 7 9coronavirus in vitro. In this study, we aimed to assess the efficacy and safety 8 0of chloroquine with different doses in COVID-19. 8 1 MethodIn this multicenter prospective observational study, we enrolled 8 2

ObjectivesToll‐like receptor 4 (TLR4) is abnormally expressed in oral cancer tissues and promotes cancer cell invasion. The purpose of this study was to clarify the mechanism by which autophagy regulates oral cancer invasion through the TLR4‐NF‐κB pathway.Subjects and MethodsWe examined TLR4 expression in oral cancer tissues and analysed the relationship between its expression and clinicopathological features. The invasion and migration of LPS‐stimulated oral cancer cells with up‐ or downregulation of TLR4 expression was detected in addition to NF‐κB signalling and autophagy levels. Furthermore, the role of autophagy in regulating TLR4‐mediated cell invasiveness was explored by silencing the expression of key autophagy genes ATG7 and p62.ResultsWe found that TLR4 overexpression was closely related to cervical lymphatic metastasis and poor survival. TLR4 activated the NF‐κB pathway to promote the invasiveness of OSCC cells, and autophagy partly inhibited invasiveness by suppressing the NF‐κB pathway. We observed that p62 translocated from the cytoplasm to the nucleus when autophagy was activated by LPS. Finally, silencing p62 further promoted LPS‐mediated cell invasiveness.ConclusionToll‐like receptor 4 significantly enhanced the invasiveness of OSCC cells. Autophagy may regulate cell invasiveness through the NF‐κB pathway by modulating both the cytoplasmic and nuclear levels of p62.

Background: Noxa, which is subset of the Bcl-2 family of proteins, was previously reported to have considerable therapeutic potential in diverse cancers. However, its expression and role in salivary gland adenoid cystic carcinoma (ACC) have not been well studied. This study aimed to elucidate the expression and role of Noxa in salivary gland ACC. Materials and Methods:The expression levels of NOXA and its association with overall survival in salivary gland ACC were analyzed by quantitative real-time PCR.We next examined the effects of Noxa overexpression or inhibition on colony formation, proliferation, apoptosis, and autophagy of salivary gland ACC cells. Furthermore, promoter analysis was performed to identify the potential transcriptional activator of NOXA.Results: NOXA was markedly down-regulated and significantly correlated with a more aggressive phenotype and poor overall survival of salivary gland ACC. Ectopic expression of Noxa suppressed the viability and growth of ACC cells, which involved the induction of apoptosis and autophagy. Moreover, the transcriptional activity of NOXA gene could be enhanced by p53. Conclusion:The findings of this study indicate that Noxa, activated transcriptionally by p53, suppress the progression of ACC, whereby it regulates proliferation, apoptosis, and autophagy. K E Y W O R D Sadenoid cystic carcinoma, apoptosis, autophagy, cell proliferation, Noxa