Aims and background The COVID-19 outbreak spread in China and is a threat to the world. We reported on the epidemiological, clinical, laboratory, and radiological characteristics of children cases to help health workers better understand and provide timely diagnosis and treatment. Methods Retrospectively, two research centers' case series of 67 consecutive hospitalized cases including 53 adult and 14 children cases with COVID-19 between 23 Jan 2020 and 15 Feb 2020 from Jinan and Rizhao were enrolled in this study. Epidemiological, clinical, laboratory, and radiological characteristics of children and adults were analyzed and compared. Results Most cases in children were mild (21.4%) and conventional cases (78.6%), with mild clinical signs and symptoms, and all cases were of family clusters. Fever (35.7%) and dry cough (21.4%) were described as clinical manifestations in children cases. Dry cough and phlegm were not the most common symptoms in children compared with adults (p = 0.03). In the early stages of the disease, lymphocyte counts did not significantly decline but neutrophils count did in children compared with adults (p = 0.02). There was a lower level of CRP (p = 0.00) in children compared with adults. There were 8 (57.1%) asymptomatic cases and 6 (42.9%) symptomatic cases among the 14 children cases. The age of asymptomatic patients was younger than that of symptomatic patients (p = 0.03). Even among asymptomatic patients, 5 (62.5%) cases had lung injuries including 3 (60%) cases with bilateral involvement, which was not different compared with that of symptomatic cases (p = 0.58, p = 0.74). ConclusionsThe clinical symptoms of children are mild, there is substantial lung injury even among children, but that there is less clinical disease, perhaps because of a less pronounced inflammatory response, and that the occurrence of this pattern appears to inversely correlate with age.

The death of cardiomyocytes either through apoptosis or necroptosis is the pathological feature of cardiac ischemia-reperfusion (I/R) injury. Phosphoglycerate mutase 5 (PGAM5), a mitochondrially-localized serine/threonine-protein phosphatase, functions as a novel inducer of necroptosis. However, intense debate exists regarding the effect of PGAM5 on I/R-related cardiomyocyte death. Using cardiac-specific PGAM5 knockout (PGAM5 CKO ) mice, we comprehensively investigated the precise contribution and molecular mechanism of PGAM5 in cardiomyocyte death. Our data showed that both PGAM5 transcription and expression were upregulated in reperfused myocardium. Genetic ablation of PGAM5 suppressed I/R-mediated necroptosis but failed to prevent apoptosis activation, a result that went along with improved heart function and decreased inflammation response. Regardless of PGAM5 status, mitophagy-related cell death was not apparent following I/R. Under physiological conditions, PGAM5 overexpression in primary cardiomyocytes was sufficient to induce cardiomyocyte necroptosis rather than apoptosis. At the sub-cellular levels, PGAM5 deficiency increased mitochondrial DNA copy number and transcript levels, normalized mitochondrial respiration, repressed mitochondrial ROS production, and prevented abnormal mPTP opening upon I/R. Molecular investigation demonstrated that PGAM5 deletion interrupted I/R-mediated Drp S637 dephosphorylation but failed to abolish I/R-induce Drp1 S616 phosphorylation, resulting in partial inhibition of mitochondrial fission. In addition, declining Mfn2 and OPA1 levels were restored in PGAM5 CKO cardiomyocytes following I/R. Nevertheless, PGAM5 depletion did not rescue suppressed mitophagy upon I/R injury. In conclusion, our results provide an insight into the specific role and working mechanism of PGAM5 in driving cardiomyocyte necroptosis through imposing mitochondrial quality control in cardiac I/R injury.

Background/objectivesAs a proinflammatory cytokine, interleukin-17 (IL-17) contributes to the inflammation of many autoimmune diseases. We examined IL-17 levels in serum and tissues from patients with chronic hepatitis B virus infection (HBV), and especially evaluated the role of IL-17 in the pathogenesis and progression of liver fibrosis.Materials and methodsWhole venous blood was obtained from four patient groups: chronic hepatitis B (CHB, n = 47), liver cirrhosis (LC, n = 49), primary hepatocellular carcinoma (PHC, n = 44), chronic liver failure (CLF, n = 33), and a normal control group (n = 20). HBsAg was positive in all patients. Liver biopsy samples were acquired from asymptomatic HBsAg carriers (ASC, n = 35), CHB (n = 57), and LC (n = 31) patients. We performed ELISA to measure IL-17 levels in serum samples, and used reverse RT-PCR to measure IL-17 mRNA levels in peripheral blood mononuclear cells (PBMC). IL-17 protein expression was detected in liver biopsy tissues by immunohistochemistry.ResultsCompared to normal controls, serum IL-17 protein and mRNA levels were significantly higher in the four infection groups. LC patients exhibited the highest serum IL-17 and PBMC mRNA levels. No significant differences were found between the other three groups. High levels of IL-17 were also observed in tissues from CHB and LC patients, compared to ASC. IL-17 expression was mainly located in the portal area and was positively correlated with inflammation grade and fibrosis stage.ConclusionsIL-17 expression was found to be increased with increasing degrees of liver fibrosis. This suggests that IL-17 may not only induce the inflammation, but also contribute to disease progression and chronicity.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5306959258322482

Background & Aims. AIM2 plays an important role in innate immunity, but its role in regulating the immune response to hepatitis B virus (HBV) is unknown. We hypothesized that AIM2 expression is positively correlated with HBV-mediated inflammation in patients with HBV-associated glomerulonephritis (HBV-GN), potentiating inflammation and leading to renal damage. We therefore analyzed the expression of AIM2 and inflammatory factors in HBV-GN tissues and cell lines relative to the inflammatory response to HBV infection and HBV status. Methods. Seventy-nine patients with chronic nephritis (CN) were included: 54 with HBV-GN and 24 with chronic glomerulonephritis (CGN). Expression of AIM2, caspase-1, and IL-1β was detected by immunohistochemistry in renal biopsies from each patient. Following siRNA-mediated knockdown of AIM2 in HBV-infected and HBV-uninfected human glomerular mesangial (HGM) cells, expression of caspase-1, IL-1β, and IL-18 was detected by qRT-PCR and Western blot. Results. AIM2 expression in HBV-GN biopsies (81.4%) was significantly higher than in CGN (4.0%) and positively correlated with caspase-1 and IL-1β expression in HBV-GN. In vitro, AIM2 knockdown reduced caspase-1, IL-1β, and IL-18 expression in HBV-infected and HBV-uninfected HGM cells. Conclusion. AIM2 elevation during HBV infection or replication may contribute to inflammatory damage, thus providing a putative therapeutic target for HBV-GN.

Background: The pandemic of coronavirus disease (Covid-19) seriously impacts the health and well-being of all of us. Aims: We aim to assess the psychological impact of Covid-19 on frontline health care workers (HCWs), including anxiety, depression and stress of threat of the disease. Method: The study was a cross-sectional survey among the frontline HCWs in a hospital at Jinan, China. Data were collected through an anonymous, self-rated questionnaire, including basic demographic data, a 10-item Covid-19 stress questionnaire, the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS). The risk and rate of anxiety, depression and stress of Covid-19 were estimated. Results: Among the 309 participants, there were 88 (28.5%) with anxiety and 172 (56.0%) with depression. Multivariate logistic regression analyses showed that age ⩽ 30 years, age > 30 to 45 years, working in confirmed case isolation wards, and worrying about disinfection measures being not sufficient were independently associated with anxiety with an odds ratio (95% confidence interval, CI) of 4.4 (1.6–12.2), 3.1 (1.1–8.8), 2.3 (1.4–4.0) and 2.5 (1.5–4.3), respectively; age ⩽ 30 years, age > 30 to 45 years, nurse and worrying about disinfection measure being not sufficient were independently associated with depression with an odds ratio (95% CI) of 3.8 (1.8–7.8), 2.7 (1.3–5.7), 2.5 (1.1–5.6) and 2.1 (1.3–3.5), respectively. Conclusions: A high prevalence of anxiety and depression was found among frontline HCWs during the COVID-19 outbreak. More psychological care should be given to young staffs and nurses. Measures to prevent professional exposure is important for HCWs’ physical and mental health.

E-cadherin is a well-known mediator of cell–cell adherens junctions. However, many other functions of E-cadherin have been reported. Collectively, the available data suggest that E-cadherin may also act as a gene transcriptional regulator. Here, evidence supporting this claim is reviewed, and possible mechanisms of action are discussed. E-cadherin has been shown to modulate the activity of several notable cell signalling pathways, and given that most of these pathways in turn regulate gene expression, we proposed that E-cadherin may regulate gene transcription by affecting these pathways. Additionally, E-cadherin has been shown to accumulate in the nucleus where documentation of an E-cadherin fragment bound to DNA suggests that E-cadherin may directly regulate gene transcription. In summary, from the cell membrane to the nucleus, a role for E-cadherin in gene transcription may be emerging. Studies specifically focused on this potential role would allow for a more thorough understanding of this transmembrane glycoprotein in mediating intra- and intercellular activities.

No abstract

BackgroundThe absent in melanoma 2 (AIM2), a cytosolic dsDNA inflammasome, can be activated by viral DNA to trigger caspase-1. Its role in immunopathology of chronic hepatitis B and C virus (HBV, HCV) infection is still largely unclear. In this study, the expression AIM2, and its downstream cytokines, caspase-1, IL-18 and IL-1β, in liver tissue of patients with chronic hepatitis B and C (CHB, CHC) were investigated.MethodsA total of 70 patients diagnosed with chronic hepatitis were enrolled, including 47 patients with CHB and 23 patients with CHC. A liver biopsy was taken from each patient, and immunohistochemistry was used to detect the expression of AIM2 and inflammatory factors caspase-1, IL-18, and IL-1β in the biopsy specimens. The relationship between AIM2 expression and these inflammatory factors was analyzed.ResultsThe expression of AIM2 in CHB patients (89.4 %) was significantly higher than in CHC patients (8.7 %), and among the CHB patients, the expression of AIM2 was significantly higher in the high HBV replication group (HBV DNA ≥ 1 × 105copies/mL) than in the low HBV replication group (HBV DNA < 1 × 105copies/mL). The expression of AIM2 was also correlated with HBV-associated inflammatory activity in CHB patients statistically. Additionally, AIM2 levels were positively correlated with the expression of caspase-1, IL-1β and IL-18 in CHB patients, which implied that the AIM2 expression is directly correlated with the inflammatory activity associated with CHB.ConclusionsAIM2 upregulation may be a component of HBV immunopathology. The underlying mechanism and possible signal pathway warrant further study.