Hepatitis E virus re-infection accelerates hepatocellular carcinoma development and relapse in a patient with liver cirrhosis: A case report and review of literature

BACKGROUNDHepatitis E virus (HEV) superinfection is a suspected promoting factor for hepatocellular carcinoma (HCC) in patients with chronic hepatitis and cirrhosis. However, to date, very few cases of HEV-related HCC have been reported. Nevertheless, the role of HEV re-infection in cirrhotic liver without other chronic hepatitis infections has rarely been explored.CASE SUMMARYA 53-year-old male farmer was diagnosed with liver cirrhosis and splenomegaly in August 2016, accompanied with negative HEV-IgM and positive HEV-IgG. No evidence of hepatitis B virus or hepatitis C virus infection was found. Since then the patient was evaluated for liver function and viral parameters every 3 mo. In June 2017, the patient presented severe fatigue with whole body itching and was diagnosed with HCC. Afterwards this patient experienced quick HCC development, progression, relapse, and metastasis in the following 8 mo, and presented persistent dual positivity of HEV-IgM and HEV-IgG. This patient had a long history of smoking and alcohol consumption.CONCLUSIONThis unique case invokes the importance of HEV surveillance and treatment among cirrhotic patients, HCC cases, and blood donors.     

Analysis of S1 gene of avian infectious bronchitis virus isolated in southern China during 2011–2012

Sixty-two strains of avian infectious bronchitis virus (IBV) were isolated from diseased chickens at different farms in southern China during 2011–2012, and 66.1 % of the isolated strains were associated with typical nephritis. Analysis of the S1 gene sequences amplified from the 62 isolated strains together with 40 reference strains published in Genbank showed nucleotide homologies ranging from 63.5 to 99.9 % and amino acid homologies ranging from 57.9 to 100 %. Phylogenetic analysis revealed that all Chinese IBV strains were clustered into six distinct genetic groups (I–VI). Most of the isolated strains belonged to group I, and the isolation of group V strains was increased compared with an earlier period of surveillance. Current vaccine strains used in China (H120, H52, W93, and Ma5) formed the group Mass which is evolutionarily distant from Chinese isolates. Alignment of S1 amino acid sequences revealed polymorphic and diverse substitutions, insertions, and deletions, and the S1 protein of major pandemic strains contained 540 amino acids with a cleavage site sequence of HRRRR or RRF(L/S)RR. Further analysis showed that recombination events formed a new subgroup. Taken together, these findings suggest that various IBV variants were co-circulating and undergoing genetic evolution in southern China during the observation period. Therefore, long-term continuing surveillance is significantly important for prevention and control of IBV infection.     

Changes in NK and NKT cells in mesenteric lymph nodes after a Schistosoma japonicum infection

The mesenteric lymph node (MLN) is the main draining lymph node in mouse enterocoelia, which contains many types of immune cells. Among these cells, natural killer (NK) and natural killer T (NKT) cells belong to innate lymphoid cells (ILCs), which have potent activities for controlling a variety of pathogenic infections. In this study, C57BL/6 mice were infected with Schistosoma japonicum for 5–7 weeks. Lymphocytes were isolated from the MLN to detect changes in the phenotype and function of NK and NKT cells using a fluorescence activating cell sorter (FACS). These results demonstrated that a S. japonicum infection could significantly increase the percentage of NK cells in the mouse MLN, (P?<?0.05). We found an increase in the cell number of both NK and NKT cells. In addition, we found that NK and NKT cells from infected mice expressed higher levels of CD69 compared to normal mice (P?<?0.05). These results demonstrated that a S. japonicum infection could induce MLN NK and NKT cell activation. Moreover, we found that the expression of CD4 was increased in infected MLN NK cells (P?<?0.05). Furthermore, intracellular cytokine staining revealed that expression of IL-4 and IL-17 were significantly enhanced in both the NK and NKT cells of infected mice after phorbol 12-myristate 13-acetate (PMA) and ionomycin stimulation (P?<?0.05). Taken together, these results indicated that infection-induced MLN NK and NKT cells might play roles in modulating the classical T cell response. Finally, our results indicated that the expression of CD94 was decreased in NK cells, suggesting that the downregulation of CD94 expression might served as a mechanism in NK cell activation.     

Edwardsiella tarda-Induced Cytotoxicity Depends on Its Type III Secretion System and Flagellin

Many Gram-negative bacteria utilize a type III secretion system (T3SS) to translocate virulence proteins into host cells to cause diseases. In responding to infection, macrophages detect some of the translocated proteins to activate caspase-1-mediated cell death, called pyroptosis, and secretion of proinflammatory cytokines to control the infection. Edwardsiella tarda is a Gram-negative enteric pathogen that causes hemorrhagic septicemia in fish and both gastrointestinal and extraintestinal infections in humans. In this study, we report that the T3SS of E. tarda facilitates its survival and replication in murine bone marrow-derived macrophages, and E. tarda infection triggers pyroptosis of infected macrophages from mice and fish and increased secretion of the cytokine interleukin 1β in a T3SS-dependent manner. Deletion of the flagellin gene fliC of E. tarda results in decreased cytotoxicity for infected macrophages and does not attenuate its virulence in a fish model of infection, whereas upregulated expression of FliC in the fliC mutant strain reduces its virulence. We propose that the host controls E. tarda infection partially by detecting FliC translocated by the T3SS, whereas the bacteria downregulate the expression of FliC to evade innate immunity.     

Immunogenicity of recombinant human bocavirus‐1,2 VP2 gene virus‐like particles in mice

Human bocavirus (HBoV), a recently identified pathogen with a worldwide distribution is closely related to paediatric acute respiratory infection and gastroenteritis. The present study was performed to evaluate the immunogenicity of HBoV1 and HBoV2 virus‐like particles (VLPs) as vaccine candidates in mice. Both HBoV1 and HBoV2 VLPs were expressed in the bacmid virus–SF9 cell system. Mice were inoculated three times at 3‐week intervals with HBoV VLPs at one dose intramuscular (i.m.) or intradermal (i.d.) with or without the addition of the alum adjuvant. ELISA was used to detected antibody, and ELISPOT was used to test cellular immune responses. HBoV‐specific IgG antibodies were induced and alum adjuvant improved the antibody titres and avidity, while the inoculation pathway had no influence. T helper type 1/ type 2 immune responses were balanced induced by HBoV1 VLPs but not HBoV2 VLPs. Serum IgG antibody cross‐reactivity rates of the two subtypes were similar, but cross‐reactions of HBoV1 immunization groups were higher. The single i.m. group had more interferon‐γ‐secreting splenocytes. These data indicate that HBoV VP2 VLPs have good immunogenicity with induction of strong humoral and cellular immune responses, and they may be potential candidate vaccines for HBoV infection.     

‘Default’ generated neonatal regulatory T cells are hypomethylated at conserved non‐coding sequence 2 and promote long‐term cardiac allograft survival

Regulatory T (Treg) cells play an important role in the maintenance of immune self-tolerance and homeostasis. We previously reported that neonatal CD4⁺ T cells have an intrinsic ‘default’ mechanism to become Treg (neoTreg) cells in response to T-cell receptor (TCR) stimulation. However, the underlying mechanisms are unclear and the effects of neoTreg cells on regulating immune responses remain unknown. Due to their involvement in Foxp3 regulation, we examined the role of DNA methyltransferase 1 (DNMT1) and DNMT3b during the induction of neoTreg cells in the Foxp3^gfp mice. The function of neoTreg cells was assessed in an acute allograft rejection model established in RAG2^−/− mice with allograft cardiac transplantation and transferred with syngeneic CD4⁺ effector T cells. Following ex vivo TCR stimulation, the DNMT activity was increased threefold in adult CD4⁺ T cells, but not significantly increased in neonatal cells. However, adoptively transferred neoTreg cells significantly prolonged cardiac allograft survival (mean survival time 47 days, P < 0·001) and maintained Foxp3 expression similar to natural Treg cells. The neoTreg cells were hypomethylated at the conserved non-coding DNA sequence 2 locus of Foxp3 compared with adult Treg cells. The DNMT antagonist 5-aza-2′-deoxycytidine (5-Aza) induced increased Foxp3 expression in mature CD4⁺ T cells. 5-Aza-inducible Treg cells combined with continuous 5-Aza treatment prolonged graft survival. These results indicate that the ‘default’ pathway of neoTreg cell differentiation is associated with reduced DNMT1 and DNMT3b response to TCR stimulus. The neoTreg cells may be a strategy to alleviate acute allograft rejection.     

Temporal features of elevated hair cortisol among earthquake survivors

This study aimed to determine the effect on hair cortisol level of a chronic stress response from the Wenchuan earthquake, and to explore the temporal features of elevated hair cortisol. We recruited two cohorts of earthquake survivors: cohort A consisted of 12 male adults and 8 females and cohort B of 20 male adolescents, with 23 and 29 participants as controls, respectively. Their hair samples closest to the scalp were assayed with mass spectrometry to determine cortisol content. Results revealed that hair cortisol content in survivors of cohort A was significantly higher than in the control. For survivors of cohort B, hair cortisol levels increased 6 and 22 weeks after the earthquake and decreased 43 weeks after the outburst. In conclusion, the chronic stress response elicited by the earthquake resulted in elevated hair cortisol. Timing since the earthquake outburst played an important role in the long‐term response of the HPA axis to a major acute stressor.     

Serum tissue polypeptide-specific antigen is an independent predictor in breast cancer

Tissue polypeptide-specific antigen (TPS) is a tumor proliferative marker associated with cytokeratin 18. The aim of the study was to investigate the potential relationship between the preoperative serum TPS levels and the outcome in Chinese breast cancer patients. 975 consecutive female patients, affected by invasive breast cancer under investigation from January 2005 to December 2011, had their TPS levels measured with a one-step solid phase radiometric sandwich assay detecting the M3 epitope on cytokeratin 18 fragments. The cut-off value was 80 U/L. The average age diagnosed with breast cancer was 48, ranging from 23 to 71. About 19% (185) patients displayed an elevated preoperative TPS level (>80 U/L) associated with older age (>45), advanced cancer stage, larger tumor size (>2 cm), axillary lymph node metastasis, negative progesterone receptor status, and positive HER2 status. In addition, preoperative TPS levels were also significantly connected with recurrence (p < 0.05), particularly distant metastasis and visceral metastasis. The mean preoperative TPS level was 68.4 ± 116.43 U/L (range 0–1839 U/L). In multivariate analysis, high preoperative TPS level was recognized as an independent prognostic factor for disease-free survival (p < 0.001 and overall survival (p = 0.023). From these results we conclude that the serum preoperative TPS level may be a valuable and independent marker for breast cancer.     

Syntheses,structures, and magnetic properties of mixed-ligand complexes based on 3,6-bis(benzimidazol-1-yl)pyridazine

Six new metal–organic coordination polymers (CPs) [Ni(L)(2,5-TDC)(H₂O)]_n(1), [Ni(L)(1,3-BDC)(H₂O)]_n (2), [Ni(L)(1,4-BDC)(H₂O)]_n (3), [Mn(L)(2,5-TDC)(H₂O)]_n (4), [Mn(L)(2,6-PYDC)(H₂O)]_n (5) and [Mn(L)(1,4-NDC)]_n (6) were achieved by reactions of the corresponding metal salt with mixed organic ligands (L = 3,6-bis(benzimidazol-1-yl)pyridazine, 2,5-H₂TDC = thiophene-2,5-dicarboxylic acid, 1,3-H₂BDC = isophthalic acid, 1,4-H₂BDC = terephthalic acid, 2,6-H₂PYDC = pyridine-2,6-dicarboxylic acid, 1,4-H₂NDC = naphthalene-1,4-dicarboxylic acid) under solvothermal condition. CPs 1–6 were characterized by single-crystal X-ray diffraction, IR, TG, XRD and elemental analyses. Their structures range from the intricate 3D CPs 1, 3, 4 and 6 to the 2D coordination polymer 2 and the infinite 1D chain 5. The CPs 1–4 and 6 underlying networks were classified from the topological viewpoint, disclosing the distinct sql (in 1), pcu (in 3 and 6), new topology (in 2), and dia (in 4) topological nets. Moreover, analysis of thermal stability shows that they had good thermal stability. Finally, magnetic properties of CPs 1–6 have been studied, the results showed that complex 2 had ferromagnetic coupling and complexes 1, 3–6 were antiferromagnetic.

Six new metal–organic coordination polymers were prepared by reactions of the corresponding metal salt with mixed organic ligands under solvothermal conditions. The compounds were structurally, magnetically and catalytically characterized.