Epigenetics refers to steady phenotypic changes in gene expression without modifications in the genetic nucleotide sequence.Disorder of epigenetic mechanisms plays an important role in the occurrence and development of human malignant tumors including hepatocellular carcinoma.A large number of gene targets and pathways related to epigenetics were discovered.For instance,DNA methylation,histone modification and RNA regulator gene silencing were associated with the development of hepatocellular carcinoma.Exploring the abnormal epigenetics is of great significance for prevention and treatment of hepatocellular carcinoma.

The West Nile virus (WNV), a mosquito-borne arbovirus, is also a zoonotic pathogen first isolated in the 1930s in Africa, followed by the identification of the prevalence of febrile illness caused by West Nile virus infections. In 1999, the West Nile virus was first introduced into New York City of the United States, and caused the outbreak of viral encephalitis in adults. This marked the first reported outbreak of mass adult viral encephalitis caused by West Nile virus. Subsequently, West Nile virus and its infections in humans and animals spread rapidly throughout the United States, causing a worldwide sensation. West Nile virus is currently considered the most widely distributed emerging mosquito-borne arboviruses worldwide. Humans or animals infected by mosquito bites can develop symptoms such as fever, encephalitis (meningitis), and in rare cases, present with severe pancreatitis, hepatitis, myocarditis, miscarriage, or even death, posing a huge global public health burden. This review introduces China's progress in the isolation and identification of West Nile virus, the prevalence of adult viral encephalitis, and the field surveys and laboratory investigations of the coinfection of West Nile virus and typhoid bacteria, aiming to promote the research work and control and prevention of West Nile virus and its infection in China.

Objective To investigate the expression of Toll like receptor 2 (TLR2) in glioma and its relationship with the malignant biological behavior of glioma, so as to provide a new therapeutic target for glioma immunotherapy. Methods The tumor tissues of 90 glioma patients undergoing surgical excision were collected, of which WHO gradingⅠ-Ⅱgrade 39 cases,Ⅲgrade 24 cases,Ⅳgrade 24 cases. In addition, the normal brain tissues of 12 patients undergoing routine intracranial decompression were selected. The human glioma cell lines U87-MG, U251-MG and human astrocyte cell line HA were cultured. The expression levels of TLR2 mRNA and protein were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and Western Blot test. The correlation between TLR2 protein and different clinical pathological parameters was analyzed. Results The expression levels of TLR2 mRNA and protein in the glioma tissuesⅠ-Ⅱgrade,Ⅲgrade andⅣgrade were significantly higher than those in normal brain tissues (0.27 ± 0.09, 0.57 ± 0.12 and 0.96 ± 0.18 vs. 0.11 ± 0.05; 0.31 ± 0.05, 0.44 ± 0.05 and 0.71 ± 0.09 vs. 0.02 ± 0.01), there were statistical differences (P<0.05). In different grades of glioma tissues, there were statistical differences in the expression levels of TLR2 mRNA and protein (F = 205.9 and 194.9, P<0.05). The expression levels of TLR2 mRNA and protein in human malignant glioma cell lines U87-MG and U251-MG were significantly higher than those in human astrocyte cell line HA (1.000 ± 0.100 and 0.356 ± 0.060 vs. 0.245 ± 0.030, 0.720 ± 0.100 and 1.800 ± 0.150 vs. 0.004 ± 0.000), there were statistical differences (P<0.05). The expression of TLR2 protein was independent of age, sex and location(P>0.05), but was related to tumor diameter and WHO grading (P < 0.01). Conclusions TLR2 in different grade glioma tissues and glioma cell lines are expressed, and its expression level is associated with the malignant degree of glioma; TLR2 protein not only can be used as a biomarker of gliomas and prognosis, but also provide a new target for the treatment of glioma.

Abstract Fangjiomics is a promising paradigm that enhances research on multi-omics-based pharmacological mechanisms of Fangji from holistic and systematic perspective. We reviewed recent advances in Fangjiomics, focusing on database and analysis platform development, methodological innovations, and translational applications. Through the integration of Fangji and multi-omics data, multi-level system analysis approaches were developed, encompassing single-target analysis, signaling pathways, multi-targeted network and modules. Fangjiomics has emerged as a key strategy in various areas of Fangji research. To support the high quality development of Fangjiomics, we propose principles and perspectives from the integrated, macro-level, and practical viewpoints.

Objective To observe the impacts of the method of fortifying the spleen and supplementing Qi on the cellular immunity of chronic hepatitis B virus(HBV)carriers.Methods Asymptomatic HBV carriers group(ASC group,n=60)with HBV DNA positive were randomly divided into Fortifying the Spleen and Supplementing Qi decoction group(A group,n=30)and conventional treatment group(B group,n=30),the peripheral blood T lymphocyte subsets were detected with flow cytometey and compared with those of the healthy people(The normal control group,n=18).All the patients were treated,and 24 weeks after treatment the indexes were measured again.Results As compared with those of normal controls,the numbers of CD4+ T cells and CD8+ T cells were decreased significantly in HBV carriers(P＜0.01);There was a statistical significance between the values before and complete the treatment with the decoction of fortifying the spleen and supplementing Qi(P＜0.05 or P＜0.01),and compared with conventional treatment group,there Was a statistical significance(P＜0.05).Conclusion T-cell subset function was disturbed in the HBV carriers.The method of fortifying the spleen and supplementing Qi could improve the cellular immunity of carriers with chronic hepatitis B.

Objective: To elucidate the mechanism of epigallocatechin gallate (EGCG) mediated anti-HBV effect. Methods: The CCK-8 kit was used to test cell viability in response to EGCG treatment. For HBV DNA replication assay, purified HBV DNA was analyzed by real-time PCR assay. Western blotting was used to confirm HNF4α expression in response to EGCG or siRNA treatment. Results: Our result showed that, EGCG treatment significantly decreasee HBV DNA level both in vivo and in vitro without affecting cell viability. Curiously, we found that EGCG treatment downregulated HNF4α expression. Considering that HNF4α could restrain HBV replication, we knocked down HNF4α in HepG2.2.15 cells and found that the response of HBV replication to EGCG decreased obviously. Conclusions The above result suggest that HNF4α could be an important intracellular factor in EGCG mediated anti-HBV signaling pathway.

Abstract： Objective　To elucidate the antigenic antibody reaction of recombinant expression of non-structural protein 1 (NS1) of Japanese encephalitis (JE) virus with various mosquito-borne flaviviruses, including JE virus, and the antigenic antibody reaction of serum samples of patients infected with JE virus in acute stage. Methods　In this study, Escherichia coli prokaryotic expression vector (pET) system was used to recombinant express Japanese encephalitis virus NS1 gene. Western Blot assay was performed to detect the antibody responses of the recombinantly expressed protein against a variety of mosquito-transmitted flaviviruses, including JE virus, as well as antigen-antibody reactions of serum from patients with acute JE virus infection. Results　The NS1 gene expression product of JE virus (P3 strain) was in the form of an inclusion body, and the denatured and renatured expression product was displayed as a single band in the denatured gel (polyacrylamide gel electrophoresis, PAGE), with a molecular weight of about 45 000. The results of further antigen-antibody analysis showed that the antigen/antibody hybridization reaction of the expression product with polyclonal or monoclonal antibody of JE virus (mosquito isolates, encephalitis isolates) and serum samples of patients with acute JE virus infection could be completely consistent. The recombinant product showed negative antigen/antibody hybridization reactions with mosquito-transmitted flaviviruses, such as dengue virus and yellow fever virus polyclonal antibodies, but positive reactions with polyclonal antibodies to West Nile virus and Murray Valley encephalitis virus. Conclusions　In this study, the recombinant expression of the NS1 protein of JE virus was successfully obtained, and the antigen/antibody reaction between the recombinant protein and samples of patients infected with mosquito-borne flavivirus and JE virus was analyzed. The study results provide important basic data for elucidating the antigen-antibody reaction between the NS1 protein of JE virus and mosquito-borne flavivirus. The recombinant expression protein obtained in this study provides an important material basis for further research on the function of JE virus NS1 protein.

Myeloproliferative neoplasms (MPN) are a group of clonal disorders of hematopoietic stem cells, and JAK2 V617F gene mutation is the main basis for the diagnosis of MPN. Previous studies have shown that BCR-ABL fusion gene and JAK2 V617F gene mutation are mutually exclusive in MPN patients, but in recent years, patients with a double mutation of both genes are often reported. The article synthesizes the relevant domestic and foreign literature in recent years, and reviews the BCR-ABL fusion gene and JAK2 V617F mutation double-positive MPN.

Objective To investigate the relationship of skin-resident memory T cells (Trm cells) with the skin lesions in systemic lupus erythematosus (SLE) so as to deepen our understanding of the pathogenesis of skin lesions in SLE. Methods Peripheral blood and skin samples were collected from SLE patients and matched healthy volunteers. The percentages of effector memory T cells (Tem cells) and effcctor T cells (Teff cells) from peripheral blood were analyzed by flow cytometry. By using direct immunofluoresence, we detected the presence of immune complex,which deposited on the basement membrane of normal appearance skin from SLE patients or healthy individuals. Immunohistochemical staining was performed to detect the two characteristic surface markers of tissue-resident memory T lymphocytes,CD69 and CD103 and to analyze the expression of these T lymphocytes within skins from SLE patients or healthy volunteers. Data analysis was performed using t test. P<0.05 was considered statistically significant. Results As compared with control individuals,the proportions of CD4+Tem (12.6±3.4 vs 8.2±2.5,t=-3.15,P<0.05),CD4+Teff (2.5±1.5 vs 1.3± 0.8,t=-2.79,P<0.05)、CD8+Tem(15.3±3.6 vs 7.0±3.0,t=-6.22,P<0.05)and CD8+Teff cells(13.1±5.4 vs 3.7± 1.3,F=-7.36,P<0.05)in T cell subset were significantly increased. Also,the proportions of CD4+Tem(8.4±2.7 vs 5.8±2.0,t=-2.74,P<0.05),CD4+Teff (1.6±1.0 vs 0.8±0.5,t=-2.84,P<0.05),CD8+Tem (10.4±3.6 vs 5.3±2.4, t=-4.03, P<0.05) and CD8+Teff cells (8.2±4.1 vs 2.6±0.8, t=-6.15, P<0.05) in peripheral blood were increased as well. By direct immunofluorescence,we noticed the deposition of immunoglobulin IgA, IgM and complement C3 on the basement membrane zone of skins from SLE patients but not on heanlhy individuals. The amount of infiltrated lymphocytes in skin samples from SLE patients were significantly iecreased compared to that of healthy individuals,and the quantities of CD4, CD8 and CD103 positive T cells from SLE skin samples were all increased by various degrees than that of controls. Conclusion Skin-resident memory T cells may be involved in the pathogenesis of skin lesions in SLE.

Objective:This study contrasts the immune efficacy of the varicella zoster virus glycoprotein E (VZV gE)using Al/CpG combined adjuvants and AS01 adjuvant in BALB/c mice.Methods:BALB/c mice were immunized at 0 and 21 days respectively, and serum antibodies were detected using enzyme-linked immunosorbent assay. Detection of neutralizing antibodies in mouse serum using varicella zoster virus; enzyme-linked immunosorbent spot assay was used to detect cellular immune response.Results:Following two intramuscular immunizations, mice in the experimental groups (Shingrix, gE+ Al/CpG, and gE+ AS01) demonstrated elevated neutralizing antibody titers and an augmented count of lymphocytes releasing IFN-γ and IL-4. The gE+ Al/CpG group displayed the highest neutralizing antibody titer (1943), yet the AS01-adjuvanted groups (Shingrix and gE+ AS01) showed increased lymphocyte counts secreting IFN-γ and IL-4 compared to the Al/CpG group (gE+ Al/CpG). In comparison to the AS01 adjuvant, Al/CpG adjuvants triggered a humoral immune response favoring Th2 in mice. The proportions of CD4 + T and CD8 + T cells were not significantly different among the experimental groups. Conclusions:Al/CpG adjuvant combined with gE protein resulted in high neutralizing antibody titers, while the intensity of the induced cellular immune response was inferior to that of AS01 adjuvant.