Base Sequence ; Hepacivirus ; drug effects ; genetics ; Hepatitis C ; drug therapy ; virology ; Humans ; Molecular Sequence Data ; Oligonucleotides ; therapeutic use ; Phosphorothioate Oligonucleotides ; therapeutic use

In addition to the structural genes of the coronavirus genome, S, E, M, and N, there are several additional genes called "group-specific or accessory genes". Their gene products are designated as "accessory proteins", as reports to date make it clear that these proteins are not essential for virus replication in vitro. Nevertheless, many of these genes are still maintained in the virus genome under selective pressure, suggesting that they might play a very important role in the survival of the virus in the natural environment of the infected host. This review will summarize the research progress in the functions of coronavirus accessory genes.
Animals ; Coronavirus ; genetics ; metabolism ; Coronavirus Infections ; virology ; Humans ; Open Reading Frames ; Viral Proteins ; metabolism

Animals ; Autophagy ; Coronaviridae ; genetics ; pathogenicity ; physiology ; Coronaviridae Infections ; physiopathology ; virology ; Humans ; Virus Replication

Hepatitis C virus (HCV) accounts for the majority of cases of transfusion acquired hepatitis and may cause chronic hepatitis, cirrhosis and hepatocellular carcinoma. Currently, there is no vaccine against HCV and treatment is expensive and not always effective.The adaptive host immune response in viral clearance of HCV infection was described and the recent progress in vaccine development of HCV, focusing on the fields of DNA vaccine candidates, recombinant viral vectored vaccine candidates and combined (prime-boost) vaccine candidates were summarized. Some challenges and limitations of developing a HCV vaccine were also analysed. In summary, a promising approach of developing an experimental HCV vaccine to induce extremely potent and broad T-cell responses based on prime-boost strategy was presented.

Objective To determine the clinical value of EUS in combination with detection of CA19-9 and CA242 for early diagnosis of pancreatic cancer.Methods General features of high-risk group were determed by EUS and the plasma levels of CA19-9 and CA242 measured by ELISA.Results The serum level of CA19-9 was abnormal in 9.80% (10/102) and that of CA242 in 12.75% (13/102) of the patients.They were both abnormal in 7 cases.Of the 7 cases, 3 were found to suffer from pancreatic cancer by EUS, 1 had the tumor that had been clinically confirmed, 1 had posterior peritoneal tumor and 2 were normal.Among 102 cases detected by EUS, 2 showed low echo in pan-creatic head, 2 semi-cyst, 3 pancreatic cancer and proved by pathology.Accurate diagnotic rate, sensi-tivity and specificity were 90.20% (92/102), 50% (4/8) and 93.62% (88/94), respectively, for serum CA19-9.For the serum CA242, the 3 parameters were 87.25% (89/102), 50% (4/8) and 90.43% (85/94), respectively.For combination of both methods, they were 98.04% (100/102), 100%(8/8) and 97.87%(92/94), respectively.Accurate diagnostic rate of the latter was significantly higher than that of the former 2(P＜0.05).Concision Combination of EUS with detection of serum CA19-9 and CA242 is of great vlaue for early screening of pancreatic cancer.

Objective To investigate the immunogenicity and cross protective effects of two novel HCV DNA vaccines in a mice model.Methods Two self-replicating alphavirus vector-based HCV DNA vaccines, pSCK CE1E2Y and pSCK H155, were constructed based on the genes encoding the structural pro-teins (Core, E1 and E2) and structural and NS3 fusion proteins (Core, E1 , E2 and NS3) of a HCV strain isolated from a Chinese patient (genotype 1b, Hebei strain), respectively.Western blot analysis was per-formed to detect the expression of fusion antigens.The BALB/c mice were intradermally immunized with the recombinant DNA vaccines by using electroporation.The immune responses induced in mice and the cross protective effects of the recombinant DNA vaccines were evaluated.Results The DNA vaccines effectively expressed the target antigens in vitro.The antigen-specific antibody responses and specific T cell immune re-sponses were induced in mice by the immunization of replicative DNA vaccines.However, no effective cross protection was provided by either of the DNA vaccines in the surrogate challenge model based on a recombi-nant heterologous HCV (JFH1, 2a) vaccinia virus strain.Conclusion Although no effective cross protec-tion was observed, both of the two replicative DNA vaccines could induce strong humoral and cellular im-mune responses against multi-target antigens of HCV strains.This study has paved the way for further inves-tigation on the development of novel HCV vaccines.

Objective To evaluate the expression of macrophage migration inhibitor factor (MiF) and cyclinD1 in pancreatic carcinoma and their relationships with clinical pathology characteristics. Methods The expression of MIF and eyclinD1 in 89 carcinoma and 5 normal pancreatic tissues was detected with immunohis-tochemistry methods, and the relationships among MIF and cyclinD1 expression and clinicopathological factors were studied. Results The overexpression of MIF and cyclinD1 was found in 88.8%, and 50. 6% of pancre-atic carcinoma tissues respectively. The overexpression of MIF had a significant correlation with Ⅰ,Ⅱ,Ⅲ,Ⅳ tumor stage (69. 2%, 94. 7%, 96. 4%, 100%, P <0.05), while the positive expression rate of cyclinD1 only had a significant correlation with tumor stages Ⅲ,Ⅳ (33. 3%, 68. 8%, P <0. 05). Both of the two proteins had a correlative tendency with pathological grade and lymph node metastasis. The different expression of MIF between pancreatic carcinoma with and without liver metastasis had no statistical significance, (100% ,85.9%, P >0. 05)while there was a statistically significant difference about cyclinD1 (66. 7% ,46. 5% ,P <0. 05). A significant positive correlation was also found between MIF and cyclinD1 (P < 0. 05). Conclusion The ex-pression of MIF and CyclinD1 was higher in pancreatic cancer tissues than in normal tissue, and they may be associated with the malignant stage, tumor differentiation, local lymph node and liver metastasis of this tumor.

objective To explore the role of cytokines and dendritic cells (DCs) in rat high-risk corneal allograft survival pro- longed by superantigen Staphylococcal Enterotoxin B (SEB) and to compare the different effects between SEB and glucocorticoid. Design Experimental study.Participants Fisher 344 and Lewis rats.Methods The Fisher 344 and Lewis inbred rats were used for high-risk penetrating keratoplasty model.All of the Lewis rat recipients were divided into three groups by blinded fashion.GroupⅠand GroupⅡrats were injected intraperitoneally with 0.2ml saline buffer or SEB (75?g/ml) respectively at 4-day intervals on three occasions before transplantation.GroupⅢrats were injected subconjunctivally with 0.1ml dexamethasone (1mg/ml) daily from the first day after surgery for 2 weeks.The allograft survival was examined under slit-lamp.The concentration of interleukin IL-1?,IL-2,IL-4,IL-5,IL-6, IL-10,TNF-?in rat aqueous humor and peripheral blood were measured by liquichip and the cytokine and CD11c,CD80,MHC-Ⅱex- pression in corneal grafts were examined by immunohistochemestry staining.Main Octcome Measures Mean survival time of the allo- grafts,the level of cytokines in aqueous humor,peripheral blood and corneal grafts.Results Compared with group control,the grafts mean survival time was delayed about 3.8d in group SEB (P=0.00) and 7.1d in group dexamethasone(P=0.01).But there was no signifi- cant difference between group SEB and dexamethone (P=0.26).Liquichip test showed that the level of IL-1?in aqueous humor was re- duced and IL-4,IL-6 and IFN-?,ascended.Only IFN-?,and IL-6 could be found in peripheral blood,and the changing shift of them was similar to that in aqueous humor.The immunohistochemistry staining showed that the expression of IL-2 in rat corneal grafts was signif- icantly decreased but IL-4,IL-6 and IL-10 elevated.The expression of DCs in group SEB was similar to that in group control,which was elevated after keratoplasty,but the phenotype of DCs was not the same.There were predominantly mature DCs in group control while immature DCs in group SEB.Conclusions The immunological inhibiting effect of SEB is same to glucocorticoid,but the mecha- nism is different.SEB can modulate immune response,which might induce immune inhibition via the local production of cytokines and effect on DCs maturation involving corneal graft rejection prevention.

Objective To evaluate the treatment of current status and prognosis in childhood APL with APL2008 ,which was administrated since 2008 in our center .Methods A total of 43 children with newly diagnosed APL between 2008 to 2014 were studied retrospectively .Treatment options and current status were summarized from 28 patients who received APL2008 therapy . Results Studied 43 patients were at median age of 8 years and 4 months ,with 28 boys and 15 girls .The main clinical manifestations were infection ,anemia ,bleeding ,fever ,hepatomegaly ,splenomegaly and lymphadenopathy .The proportions of low ,intermediate and high risk groups were 27 .9% ,48 .8% and 23 .3% ,respectively .Eleven cases could be diagnosed as DIC .Bone marrow morphology showed abnormal elevation of promyelocyte .37 patients had distinctive immunophenotype such as frequent expression of CD33 , CD117 and MPO .PML/RARαfusion gene positive rate was 100% in 43 children and cytogenetic analysis were positive in 37 cases , of which specific genetic lesion in APL cells with t (15 ;17)(q22 ;q12) was found in 28 cases ,and karyotypes was found in 9 cases as infrequent chromosomal abnormalities .In 43 patients ,4 cases were early dead from intracranial hemorrhage at early stage ,and 11 cases were given up early .There were only 2 cases dead ,2 cases relapsed and 1 case lost among 28 APL children ,which enabled ef‐ficacy analysis possible .96 .4% of these 28 cases achieved HCR .The 2 year Kaplan Meier estimates of OS and EFS were 85 .9% ± 7 .6% and 80 .4% ± 8 .8% .But OS and EFS would be 94 .7% ± 5 .1% and 88 .9% ± 7 .4% if 3 patients who had non standard treat‐ment were excluded .Conclusion Childhood APL were characterized by anemia ,bleeding ,fever and infiltration .APL′s coincidence rate between PML/RARa fusion gene and morphology ,immunology and cytogenetics were 95 .3% ,90 .2% and 86 .5% ,respective‐ly .APL2008 significantly improved the prognosis of APL .

Objective To investigate the development strategy of novel T cell based vaccine against HCV infection.Methods BALB/c mice were primed with pSCK-based DNA vaccine and boosted with type 5 adenoviral vector-based vaccine, which expressed the structural proteins ( Core, E1 and E2) de-rived from a Chinese HCV patient (genotype 1b, Hebei strain).Enzyme linked immunospot assay (ELIS-POT) and intracellular cytokine staining ( ICS) were used to analyze the elicited antigen-specific immune re-sponses and the efficacy of cross-protection.Results Immunization of mice with the prime-boost vaccination strategy elicited stronger T cell immune responses against multiple HCV antigens than using the DNA vac-cines alone, especially the IFN-γ-secreting T cell responses against E1 protein as indicated by ELISPOT as-say.ICS data indicated that the prime-boost regimen elicited more TNF-α-producing CD4+and IFN-γ-produ-cing CD8+T cells against E1 protein and high levels of IFN-γ-producing CD4+and CD8+T cells against E2 protein in comparison with immunization with DNA vaccines.Moreover, the prime-boost vaccination was ca-pable of eliciting effective cross-protection in a surrogate challenge model based on a recombinant heterolo-gous HCV (JFH1, 2a) vaccinia virus.Conclusion The prime-boost vaccination using DNA and rAd5-based vaccine expressing HCV structural antigens induced significant cellular immune response and cross-protection in mice, suggesting the possibility of using it as a promising T cell based vaccine against HCV in-fection.