Factors associated with negative conversion of viral RNA in hospitalized children infected with SARS-CoV-2 Omicron variant in Shanghai, China: a retrospective analysis.

OBJECTIVES: This study aimed to identify the related risk factors and potential predictors of SARS-CoV-2 RNA negative conversion by describing the dynamics of viral shedding in infected children admitted to two hospitals from Shanghai during the Omicron variant outbreak. METHODS: This retrospective cohort included laboratory-confirmed cases of SARS-CoV-2 infection from Shanghai between March 28 and May 31, 2022. Clinical characteristics, personal vaccination, and household vaccination rates were collected through electronic health records and telephone interviews. RESULTS: A total of 603 paediatric patients confirmed to have COVID-19 were included in this study. Both univariate and multivariate analyses were performed to filter independent factors for the duration to viral RNA negative conversion. Data on the redetection of SARS-CoV-2 in the patients after they showed negative results on the RT‒PCR test (intermittent negative status) were also analysed. The median duration of virus shedding was 12 (interquartile range, IQR: 10-14) days. The severity of clinical outcome, personal vaccination-2doses, household vaccination rates, and abnormal defecation were factors indecently affecting negative conversion of SARS-CoV-2 RNA, suggesting that patients who had abnormal defecation or with more severe conditions would have delayed virological clearance, while patients who previously had 2 doses of vaccination or had higher household vaccination rates would have accelerated virological clearance. Loss of appetite (odds ratio (OR): 5.343; 95% CI: 3.307-8.632) and abnormal defecation (OR: 2.840; 95% CI: 1.736-4.645) were significantly associated with intermittent negative status. CONCLUSION: These findings could provide clues for the early identification of paediatric patients with prolonged viral shedding and could enrich the evidence for the development of prevention and control strategies, especially vaccination policies for children and adolescents.

Epidemiological, clinical, and household transmission characteristics of children and adolescents infected with SARS-CoV-2 Omicron variant in Shanghai, China: a retrospective, multicenter observational study.

OBJECTIVES: To describe the epidemiological, clinical, and household transmission characteristics of pediatric COVID-19 cases in Shanghai, China. METHODS: Pediatric patients with COVID-19 hospitalized in Shanghai from March-May 2022 were enrolled in this retrospective, multicenter cohort study. The symptoms and the risk factors associated with disease severity were analyzed. RESULTS: In total, 2620 cases (age range, 24 days-17 years) were enrolled in this study. Of these, 1011 (38.6%) were asymptomatic, whereas 1415 (54.0%), 190 (7.3%), and 4 (0.2%) patients developed mild, moderate, and severe illnesses, respectively. Household infection rate was negatively correlated with household vaccination coverage. Children aged 0-3 years, those who are unvaccinated, those with underlying diseases, and overweight/obese children had a higher risk of developing moderate to severe disease than children aged 12-17 years, those who were vaccinated, those without any underlying disease, and those with normal weight, respectively (all P <0.05). A prolonged duration of viral shedding was associated with disease severity, presence of underlying diseases, vaccination status, and younger age (all P <0.05). CONCLUSION: Children aged younger than 3 years who were not eligible for vaccination had a high risk of developing moderate to severe COVID-19 with a prolonged duration of viral shedding. Vaccination could protect children from COVID-19 at the household level.

Pingchuan formula improves allergic asthma in mice through inhibiting nuclear factor-kappa B / mitogen-activated protein kinase signaling pathway.

OBJECTIVE: To examine the role and decipher the mechanism of Pingchuan formula (PCF) in treating allergic asthma. METHODS: The mice were treated with saline, dexamethasone (DXM) and PCF for 1 week after the asthma model was established and their respiratory function including respiratory resistance (RI), pulmonary dynamic compliance (Cdyn) and maximum voluntary ventilation (MVV) were measured. In addition, cellular changes in bronchoalveolar lavage fluid (BALF) and pathological changes in lung biopsy as well as the expression level of -smooth muscle actin (α-SMA), transforming growth factor-beta1 (TGF-α1) in BALF and interleukin-5 (IL-5), interleukin-13 (IL-13), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), nuclear factor-kappa B-p65 (NF-κBp65), inhibitor-α of nuclear transcription factor κB (IκBα), p38 mitogen-activated protein kinase (p38MAPK), c-jun n-terminal kinase (JNK) and its phosphorylated proteins in lung tissue were also examined and compared among different groups. RESULTS: Our data suggested that the respiratory functions were significantly improved and the pathological changes ameliorated in the DXM group and the PCF group compared to the model group. Both DXM and PCF effectively decreased the number of eosinophils, lymphocytes, and neutrophils in BAL as well as the secretion of α-SMA and TGF-α1, IL-5, IL-13, while increased the expression of TNF-α and IFN-γ. Furthermore, our study indicated that the NF-κBp65, IκBα, p38MAPK and JNK pathways were inhibited under the treatment of PCF. CONCLUSION: Our data indicated that PCF can attenuate the inflammatory response in asthma through inhibiting the NF-κB/MAPK signaling pathway. This study not only supported the use of PCF in allergic asthma in clinic but also shed light upon afurther understanding of thediseasepathogenesis.

LncRNA HEIH Confers Cell Sorafenib Resistance in Hepatocellular Carcinoma by Regulating miR-98-5p/PI3K/AKT Pathway.

BACKGROUND: The hepatocellular carcinoma up-regulated EZH2-associated long non-coding RNA (HEIH) has been identified to act as an oncogene to promote cell tumorigenesis in hepatocellular carcinoma (HCC); however, the roles of HEIH in sorafenib resistance in HCC cells remain elusive. MATERIALS AND METHODS: The expression of HEIH and microRNA (miR)-98-5p was detected using quantitative real-time polymerase chain reaction. Cell viability, apoptosis, migration and invasion were analyzed using cell counting kit-8 assay, flow cytometry and transwell assay. Western blot was used to measure the levels of apoptosis-related protein and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related protein. The interaction between HEIH and miR-98-5p was confirmed by dual-luciferase reporter and RNA immunoprecipitation assay. In vivo experiments were performed using murine xenograft models. RESULTS: HEIH was up-regulated in sorafenib-resistant HCC tissues and cell lines, and HEIH silence weakened sorafenib resistance by suppressing cell viability, invasion and migration, decreasing the IC50 values to sorafenib, and increasing apoptosis in sorafenib-resistant HCC cells in vitro and reinforced the anti-tumor effects of sorafenib in vivo. HEIH was a sponge of miR-98-5p, and miR-98-5p inhibition reversed the sorafenib sensitivity induced by HEIH deletion in sorafenib-resistant HCC cells. MiR-98-5p inhibition could activate PI3K/AKT pathway, and enhanced sorafenib resistance by regulating the activation of PI3K/AKT pathway in sorafenib-resistant HCC cells. Besides, HEIH also activated PI3K/AKT pathway through regulating miR-98-5p in sorafenib-resistant HCC cells. CONCLUSION: HEIH conferred an advantage to sorafenib resistance in HCC by the activation of PI3K/AKT pathway through miR-98-5p, indicating a potential therapeutic strategy for HCC chemotherapy.