To further describe the effect of the “fragile population” and their “higher-risk” comorbidities on prognosis among hospitalized Omicron patients, this observational cohort study enrolled hospitalized patients confirmed with SARS-CoV-2 during the 2022 Omicron wave in Shanghai, China. The primary outcome was progression to severe or critical cases. The secondary outcome was viral shedding time from the first positive SARS-CoV-2 detection. A total of 847 participants were enrolled, most of whom featured as advanced age (>70 years old: 30.34%), not fully vaccinated (55.84%), combined with at least 1 comorbidity (65.41%). Multivariate cox regression suggested age >70 years old (aHR[95%CI] 0.78[0.61–0.99]), chronic kidney disease (CKD) stage 4–5 (aHR[95%CI] 0.61[0.46–0.80]), heart conditions (aHR[95%CI] 0.76[0.60–0.97]) would elongate viral shedding time and fully/booster vaccination (aHR[95%CI] 1.4 [1.14–1.72]) would shorten this duration. Multivariate logistic regression suggested CKD stage 4–5 (aHR[95%CI] 3.21[1.45–7.27]), cancer (aHR[95%CI] 9.52[4.19–22.61]), and long-term bedridden status (aHR[95%CI] 4.94[2.36–10.44]) were the “higher” risk factor compared with the elderly, heart conditions, metabolic disorders, isolated hypertension, etc. for severity while female (aHR[95%CI] 0.34[0.16–0.68]) and fully/booster Vaccination (aHR[95%CI] 0.35[0.12–0.87]) could provide protection from illness progression. CKD stage 4–5, cancer and long-term bedridden history were “higher-risk” factors among hospitalized Omicron patients for severity progression while full vaccination could provide protection from illness progression.

Aging is characterized by inevitable organ function decline over time, with consequent body deterioration and increased susceptibility to death. Astragalus polysaccharide (APS) has been reported to have anti-oxidative, anti-apoptotic, and anti-inflammatory properties. We investigated the potential protective effects of APS on hydrogen peroxide (H 2 O 2 ) induced hepatocyte senescence and identified related mechanisms in L02, Huh7, and LM3 cell lines. Aged female C57BL/6 mice were given APS for 1 week by intraperitoneal injection, and APS provided the strongest protective effect against H 2 O 2 -induced damage at 100 μM. APS reduced the expression of cell senescence markers and alleviated pathological damage in aged mouse liver. APS treatment decreased oxidative stress, apoptosis, NOD-like receptor protein-3-mediated pyroptosis, and maintained mitochondrial homeostasis. Notably, the protective effect of APS was weakened in the presence of chloroquine. APS might enrich autophagy by activating AMP-activated protein kinase (AMPK) and inhibiting mammalian target of rapamycin (mTOR). In conclusion, APS reduced reactive oxygen species levels, inhibited apoptosis and pyroptosis, and promoted mitophagy via AMPK/mTOR pathway to alleviate hepatocyte senescence in vitro and in vivo.

Background: Hepatocellular carcinoma (HCC) is a malignant cancer with rapid progression, vascular invasion, a high recurrence rate and poor prognosis, so it is necessary to take early measures to halt this process. Accumulating evidence indicates that collagen XV (translated by Col15a1) is a basement membrane molecule related to tumour metastasis in several organs. However, the potential function of collagen XV in the liver associated with HCC remains to be further elucidated.Methods: Col15a1 was overexpressed in HepG2 and HCCLM3 cells. CCK8 and colony formation assays were used to assess the capacity of cell proliferation, and Transwell and wound healing assays were utilized to measure cell migration. Western blotting and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) quantified the protein and mRNA expression levels of genes related to the epithelialmesenchymal transition (EMT). Then, the effect of collagen XV on tumour metastasis was confirmed in vivo.Finally, we inhibited discoidin domain receptor 1 (DDR1) via DDR1-IN-1 to explore whether the collagen XV interacted with DDR1 to regulate EMT.Results: Patients of HCC with higher expression of Col15a1 showed better survival than patients with low expression. Overexpression of collagen XV in HepG2 and HCCLM3 cells suppressed cell proliferation and migration in vitro and inhibited pulmonary and liver metastasis in vivo. In addition, collagen XV downregulated the DDR1 and transcription factor (Snail, Slug), regulated the EMT markers (Vimentin, E-cadherin, N-cadherin, and MMP9). Furthermore, inhibition of the DDR1 receptor by DDR1-IN-1 suppressed the gene promoting the EMT.Conclusions: Collagen XV functioned as a metastasis inhibitor in HCC by regulating the DDR1-Snail/ Slug axis to regulate EMT.