Activation of AMPK/MnSOD signaling mediates anti-apoptotic effect of hepatitis B virus in hepatoma cells

AIM: To investigate the anti-apoptotic capability of the hepatitis B virus(HBV) in the HepG2 hepatoma cell line and the underlying mechanisms.METHODS: Cell viability and apoptosis were measured by MTT assay and flow cytometry, respectively. Targeted knockdown of manganese superoxide dismutase(Mn SOD), AMP-activated protein kinase(AMPK) and hepatitis B virus X protein(HBx) genes as well as AMPK agonist AICAR and antagonist compound C were employed to determine the correlations of expression of these genes.RESULTS: HBV markedly protected the hepatoma cells from growth suppression and cell death in the condition of serum deprivation. A decrease of superoxide anion production accompanied with an increase of Mn SOD expression and activity was found in Hep G2.215 cells. Moreover, AMPK activation contributed to the up-regulation of Mn SOD. HBx protein was identified to induce the expression of AMPK and Mn SOD. CONCLUSION: Our results suggest that HBV suppresses mitochondrial superoxide level and exerts an antiapoptotic effect by activating AMPK/Mn SOD signaling pathway, which may provide a novel pharmacological strategy to prevent HCC.

Comparison of acute pneumonia caused by SARS-CoV-2 and other respiratory viruses in children:a retrospective multi-center cohort study during COVID-19 outbreak

Background:Until January 18,2021,coronavirus disease-2019(COVID-19)has infected more than 93 million individuals and has caused a certain degree of panic.Viral pneumonia caused by common viruses such as respiratory syncytial virus,rhinovirus,human metapneumovirus,human bocavirus,and parainfluenza viruses have been more common in children.However,the incidence of COVID-19 in children was significantly lower than that in adults.The purpose of this study was to describe the clinical manifestations,treatment and outcomes of COVID-19 in children compared with those of other sources of viral pneumonia diagnosed during the COVID-19 outbreak.Methods:Children with COVID-19 and viral pneumonia admitted to 20 hospitals were enrolled in this retrospective multi-center cohort study.A total of 64 children with COVID-19 were defined as the COVID-19 cohort,of which 40 children who developed pneumonia were defined as the COVID-19 pneumonia cohort.Another 284 children with pneumonia caused by other viruses were defined as the viral pneumonia cohort.The epidemiologic,clinical,and laboratory findings were compared by Kolmogorov-Smirnov test,t-test,Mann-Whitney U test and Contingency table method.Drug usage,immunotherapy,blood transfusion,and need for oxygen support were collected as the treatment indexes.Mortality,intensive care needs and symptomatic duration were collected as the outcome indicators.Results:Compared with the viral pneumonia cohort,children in the COVID-19 cohort were mostly exposed to family members confirmed to have COVID-19(53/64 vs.23/284),were of older median age(6.3 years vs.3.2 years),and had a higher proportion of ground-glass opacity(GGO)on computed tomography(18/40 vs.0/38,P<0.001).Children in the COVID-19 pneumonia cohort had a lower proportion of severe cases(1/40 vs.38/284,P=0.048),and lower cases with high fever(3/40 vs.167/284,P<0.001),requiring intensive care(1/40 vs.32/284,P<0.047)and with shorter symptomatic duration(median 5d vs.8d,P<0.001).The proportion of cases with evaluated inflammatory indicators,biochemical indicators related to organ or tissue damage,D-dimer and secondary bacterial infection were lower in the COVID-19 pneumonia cohort than those in the viral pneumonia cohort(P<0.05).No statistical differences were found in the duration of positive PCR results from pharyngeal swabs in 25 children with COVID-19 who received antiviral drugs(lopinavir-ritonavir,ribavirin,and arbidol)as compared with duration in 39 children without antiviral therapy(median 10d vs.9d,P=0.885).Conclusions:The symptoms and severity of COVID-19 pneumonia in children were no more severe than those in children with other viral pneumonia.Lopinavir-ritonavir,ribavirin and arbidol do not shorten the duration of positive PCR results from pharyngeal swabs in children with COVID-19.During the COVID-19 outbreak,attention also must be given to children with infection by other pathogens infection.

A Rare Case of Multiple Scar Contractures after Burn Injury

A nine-year-old girl sustained extreme postburn contractures of the face, neck, both axillae, elbows, wrists, and ankles, due to flame injury 5 years ago. No primary and plastic surgical burn treatment was available in a remote area of China. From October, 2005 to April, 2007, all adhesions were released in five operations and the huge defects covered with local musculo-cutaneous flaps, z-plasties, and with thick split skin gafts. This led to an optimal functional result and an aesthetic restoration of the face, giving her, back her self-esteem in daily life.

Efficacy and safety of atomized inhalation for Shuanghuanglian on chronic pharyngitis:a Meta-analysis of the randomized controlled trials

Objective: As a Chinese drugs preparation to clear heat and remove toxicity, Shuanghuanglian (SHL) has been widely used, but the clinical efficacy and safety of SHL on chronic pharyngitis remain unclear, especially the application of atomized inhalation of SHL need to be verified. The aim of this study was to evaluate its clinical efficacy and safety for chronic pharyngitis. Methods: From the Cochrane Library, Pubmed, EMbase, Wanfang Datebase, CNKI (China National Knowledge Infrastructure), VIP (Chinese Scientifc Journals Database), CBM (Chinese Biomedicine Database), We got the qualified randomized controlled trials(RCTs) and adopted RevMan5.3 software and the risk of bias tool according to the Cochrane to perform a metaanalysis. Results: Ten RCTs, a total of 950 cases (involving 472 cases in SHL group and 478 in control group) were included. The results showed that the clinical efficacy in SHL group was superior to control group [Chi2=5.61, 95%CI (4.29, 11.43), P<0.05], and four literatures reported no obvious adverse reactions in SHL group. Conclusion: Application of atomized inhalation of SHL may have a potential advantage in treating chronic pharyngitis. However, due to the limitation of the quality and sample size of those studies, the accuracy of the result should be treated with caution, higher standardized researches are required to justify the conclusion.

uPAR promotes tumor-like biologic behaviors of fibroblast-like synoviocytes through PI3K/Akt signaling pathway in patients with rheumatoid arthritis

Urokinase-type plasminogen activator receptor(uPAR),is a multifunctional receptor on cell surface,widely present in endothelial cells,fibroblasts,and a variety of malignant cells.Current studies have suggested that uPAR overexpressed on synovial tissues or in synovial fluid or plasma in patients with rheumatoid arthritis(RA).However,there are limited researches regarding the role of uPAR on fibroblast-like synoviocytes of rheumatoid arthritis(RA-FLSs)and its underlying mechanisms.Here,our studies show that the expression of uPAR protein was significantly higher in fibroblast-like synoviocytes(FLSs)from RA than those from osteoarthritis or traumatic injury patients.uPAR gene silencing significantly inhibited RA-FLSs cell proliferation,restrained cell transformation from the G0/G1 phase to S phase,aggravated cell apoptosis,interfered with RA-FLSs cell migration and invasion,and reduced activation of the PI3K/Akt signaling pathway,which may be associated withβ1-integrin.Cell supernatants from uPAR gene-silenced RA-FLSs markedly inhibited the migration and tubule formation ability of the HUVECs(a human endothelial cell line).Therefore,we demonstrate that uPAR changes the biological characteristics of RA-FLSs,and affects neoangiogenesis of synovial tissues in patients with RA.All of these may be associated with theβ1-integrin/PI3K/Akt signaling pathway.These results imply that targeting uPAR and its downstream signal pathway may provide therapeutic effects in RA.