Fufang Luohanguo Qingfei granules reduces influenza virus susceptibility via MAVS-dependent type I interferon antiviral signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Luohanguo Qingfei granules (LQG) is a Chinese patent medicine, clinically used to treat flu-like symptoms including cough with yellow phlegm, impeded phlegm, dry throat and tongue. However, the protective activity of LQG against influenza infection is indeterminate. AIM OF THE STUDY: This study is to investigate the therapeutic effect of LQG on influenza infection and elucidate its underlying mechanism. MATERIALS AND METHODS: In vivo: A viral susceptible mouse model induced by restraint stress was established to investigate LQG's beneficial effects on influenza susceptibility. MAVS knockout (Mavs-/-) mice were used to verify the potential mechanism of LQG. In vitro: Corticosteroid (CORT)-treated A549 cells were employed to identify the active ingredients in LQG. Mice morbidity and mortality were monitored daily for 21 days. Histopathologic changes and inflammatory cytokines in lung tissues were examined by H&E staining and ELISA. RNA-seq was used to explore the signaling pathway influenced by LQG and further confirmed by qPCR. Immunoblotting and immunohistochemistry (IHC) were used to determine the protein levels. CO-IP and DARTS were applied to detect protein-protein interaction and compound-protein interaction, respectively. RESULTS: LQG effectively attenuated the susceptibility of restrained mice to H1N1 infection. LQG significantly boosted the production of IFN-ß transduced by mitochondrial antiviral-signaling protein (MAVS), while MAVS deficiency abrogated its protective effects on restrained mice infected with H1N1. Moreover, in vitro studies further revealed that mogroside Ⅱ B, amygdalin, and luteolin are potentially active components of LQG. CONCLUSION: These results suggested that LQG inhibited the mitofusin 2 (Mfn2)-mediated ubiquitination of MAVS by impeding the E3 ligase synoviolin 1 (SYVN1) recruitment, thereby enhancing IFN-ß antiviral response. Overall, our work elaborates a potential regimen for influenza treatment through reduction of stress-induced susceptibility.

Analysis of appendicitis management during COVID-19 pandemic: A study of Chinese adult cohorts.

Background: Healthcare seeking behavior has been widely impacted due to the restricted movements of individuals during the Coronavirus disease-19 (COVID-19) pandemic. This study aims to perform risk stratification in patients requiring timely intervention during the recovery periods. Methods: Operation notes of acute appendicitis (AA) patients within a hospital were analyzed during three six-month periods (23 January-23 July in 2019, 2020, and 2021, respectively). Patient data were collected retrospectively including demographics, pre-emergency status, perioperative information, postoperative outcomes, and follow-up results. Results: 321 patients were included in this study, with 111, 86, and 124 patients in 2019, 2020, and 2021 groups, respectively. The median age of patients decreased by 4 years in 2020 as compared to that in 2019. The proportion of pre-hospitalization symptoms duration of more than 48 h in the 2020 group was higher (36.05% in 2020 vs. 22.52% in 2019). Length of hospital stay (LOS) in 2020 was shorter than it was during the same period in 2019 (4.77 vs. 5.64) and LOS in 2021 was shorter than in 2019 (4.13 vs. 5.64). Compared to the lockdown period, the proportion of patients with recurrent AA was higher in the post-lockdown period (15.1% vs. 27.4%). The median age was 34 years (vaccinated) vs. 37 years (unvaccinated). Logistic regression suggests that elevated C-reactive protein (CRP) (OR = 1.018, CI = 1.010-1.028), white cell count (WBC) (OR = 1.207, CI = 1.079-1.350), female (OR = 2.958, CI = 1.286-6.802), recurrent (OR = 3.865, CI = 1.149-12.997), and fecalith (OR = 2.308, CI = 1.007-5.289) were associated with complicated appendicitis (CA). Conclusion: The lockdown measures during the COVID-19 epidemic are shown to be correlated with a reduction in the proportion of AA patients who underwent surgery, particularly in older adults. Risk factors for CA include elevated CRP, WBC, female, recurrent, and fecalith.