Background: Immune inhibitory receptors play an important role in chronic infections. However, little is known about their role in hepatitis B virus (HBV) infection. Here, we analyzed the relationship between programmed death-1 (PD-1) and lymphocyte activation gene-3 (LAG-3) expression on CD4 + T cells and HBV disease progression. Results: PD-1 and LAG-3 expression was significantly higher on CD4 + T cells from HBV patients than on those from the HCs. In addition, a significant positive correlation was found between the PD-1 and LAG-3 expression levels and the ALT(alanine aminotransferase) level. CD4 + T cell function was inhibited by high PD-1 and LAG-3 levels, and CD4 + T cells with high PD-1 and LAG-3 expression lost the ability to secrete IFN-γ, IL-2 and TNF-α. Furthermore, blockade of the PD-1 and LAG-3 pathways reversed the damage to CD4 + T cell proliferation and cytokine secretion. Conclusions: CD4 + T cell exhaustion during chronic HBV had high PD-1 and LAG-3 expression and the absence of helper T cell cytokines, including IFN-γ, IL-2 and TNF-α. After blocking PD-L1 and LAG-3, CD4 + T cell function in chronic hepatitis B patients was partially restored.
Hepatitis B virus (HBV) infection is a worldwide health problem, with approximately one third of populations have been infected, among which 3-5% of adults and more than 90% of children developed to chronic HBV infection. Host immune factors play essential roles in the outcome of HBV infection. Thus, ineffective immune response against HBV may result in persistent virus replications and liver necroinflammations, then lead to chronic HBV infection, liver cirrhosis, and even hepatocellular carcinoma. Cytokine balance was shown to be an important immune characteristic in the development and progression of hepatitis B, as well as in an effective antiviral immunity. Large numbers of cytokines are not only involved in the initiation and regulation of immune responses but also contributing directly or indirectly to the inhibition of virus replication. Besides, cytokines initiate downstream signaling pathway activities by binding to specific receptors expressed on the target cells and play important roles in the responses against viral infections and, therefore, might affect susceptibility to HBV and/or the natural course of the infection. Since cytokines are the primary causes of inflammation and mediates liver injury after HBV infection, we have discussed recent advances on the roles of various cytokines [including T helper type 1 cells (Th1), Th2, Th17, regulatory T cells (Treg)-related cytokines] in different phases of HBV infection and cytokine-related mechanisms for impaired viral control and liver damage during HBV infection. We then focus on experimental therapeutic applications of cytokines to gain a better understanding of this newly emerging aspect of disease pathogenesis.
Pyogenic liver abscess (PLA) is a potentially life-threatening disease affecting many parts of the world, especially Asia. In this study, we explored the clinical and microbiological characteristics of PLA in Chinese patients.A 5-year (2010–2014) retrospective review of medical records on all PLA patients who were admitted to a tertiary teaching hospital was performed.Among 217 PLA cases who were confirmed cultural positive, Klebsiella pneumonia (K pneumonia) was the most common pathogen (n = 165, 76.0%), followed by Escherichia coli (n = 21, 9.7%). Notably, there is a higher incidence of diabetes mellitus in patients with K pneumoniae-induced PLA (KP-PLA) than that with non-K pneumoniae-induced PLA (non-KP-PLA)(43.0% vs 21.2%, P = .005). However, it was less prevalent for concomitant hepatobiliary disease (20.0% vs 34.6%, P = .039) and history of intraabdominal trauma or surgery (13.3% vs 38.5%, P < .001) in patients with KP-PLA. Although K pneumoniae are sensitive to most common antibiotics (antibiotic resistance rates below 10%), some strains (1.2%) developed resistant to carbapenem. These results confirmed K pneumoniae as the predominant pathogen of PLA in the area in which the study was conducted. More attention should be directed toward monitoring the emergence of carbapenem-resistant K pneumoniae.KP-PLA is frequently diagnosed in patients with metabolic diseases accompanied by serious consequences, and it is therefore prudent to see that they receive sensitivity-directed antibiotic therapy.
BackgroundThe keratocystic odontogenic tumor (KCOT) is a locally aggressive cystic jaw lesion that occurs sporadically or in association with nevoid basal cell carcinoma syndrome (NBCCS). PTCH1, the gene responsible for NBCCS, may play an important role in sporadic KCOTs. In this study, we analyzed and compared the distribution pattern of PTCH1 mutations in patients with sporadic and NBCCS-associated KCOTs.MethodsWe detected PTCH1 mutations in 14 patients with NBCCS-associated KCOTs and 29 patients with sporadic KCOTs by direct sequencing. In addition, five electronic databases were searched for studies detecting PTCH1 mutations in individuals with NBCCS-associated or sporadic KCOTs, published between January 1996 and June 2013 in English language.ResultsWe identified 15 mutations in 11 cases with NBCCS-associated KCOTs and 19 mutations in 13 cases with sporadic KCOTs. In addition, a total of 204 PTCH1 mutations (187 mutations from 210 cases with NBCCS-associated and 17 mutations from 57 cases with sporadic KCOTs) were compiled from 78 published papers.ConclusionsOur study indicates that mutations in transmembrane 2 (TM2) are closely related to the development of sporadic KCOTs. Moreover, for the early diagnosis of NBCCS, a genetic analysis of the PTCH1 gene should be included in the new diagnostic criteria.
A multiplex real-time PCR assay was developed to simultaneously detect and discriminate influenza A virus subtypes, including novel H1N1 (2009) and seasonal H3N2 virus, influenza B virus, and respiratory syncytial virus (RSV) in a single test tube, with detection sensitivity and specificity of 99% and 100%, respectively, for the four pathogens.
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