[Study on F9 gene expression downregulation and its clinical value in hepatocellular carcinoma].

Objective: To analyze the expression levels of the F9 gene and F9 protein in hepatocellular carcinoma by combining multiple gene chip data, real-time fluorescence quantitative PCR (RT qPCR), and immunohistochemistry. Additionally, explore their correlation with the occurrence and development of hepatocellular carcinoma, as well as with various clinical indicators and prognosis. Methods: The mRNA microarray dataset from the GEO database was analyzed to identify the F9 gene with significant expression differences associated with hepatocellular carcinoma. Liver cancer and adjacent tissues were collected from 18 cases of hepatocellular carcinoma. RT-qPCR method was used to detect the F9 gene expression level. Immunohistochemistry was used to detect the F9 protein level. Combined with the TCGA database information, the correlation between F9 gene expression level and prognostic and clinicopathological parameters was analyzed. The biological function of F9 co-expressed genes associated with hepatocellular carcinoma was analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Statistical analysis was performed using Graphpad Prism software. Results: Meta-analysis results showed that the expression of the F9 gene was lower in HCC tissues than in non-cancerous tissues. Immunohistochemistry results were basically consistent with those of RT-qPCR. The data obtained from TCGA showed that the F9 gene had lower expression values in stages III-IV, T3-T4, and patients with vascular invasion. A total of 127 genes were selected for bioinformatics analysis as co-expressed genes of F9, which were highly enriched in redox processes and metabolic pathways. Conclusion: This study validates that the F9 gene and F9 protein are lower in HCC. The down-regulation of the F9 gene predicts adverse outcomes, which may provide a new therapeutic target for HCC.

[The clinical value of von Willebrand factor and VITRO score in evaluating disease progression in patients with HBV infection].

Objective: To explore the clinical value of von Willebrand Factor (vWF) and VITRO score (vWF:Ag/platelet count) in assessing disease progression in patients with HBV infection. Methods: Randomly collect relevant clinical data of 308 patients with HBV infection (including 154 cases of chronic hepatitis B, 66 cases of hepatitis B cirrhosis in compensatory period, 88 cases of hepatitis B cirrhosis in decompensated period) from December 1, 2018 to January 5, 2021 in the Second Affiliated Hospital of Chongqing Medical University. The vWF values are measured by a uniform optical method, and all data are included using a uniform standard. Analyze the difference and significance of plasma vWF level and VITRO score in chronic hepatitis B, hepatitis B cirrhosis in the compensatory phase and decompensated phase. Results: The plasma vWF level and VITRO score of the chronic hepatitis B group were (139.47±76.44) and (0.86±0.8), respectively, and the hepatitis B cirrhosis compensated group was (164.95±67.12 and 1.44±1.14), respectively. Hepatitis cirrhosis decompensated group were (317.48±103.32 and 6.81±4.98), respectively; plasma vWF level and VITRO score increased with the progression of HBV infection, and the difference was statistically significant (F=133.669,P=0.000F=137.598,P=0.000).The plasma vWF level and VITRO score in patients with hepatitis B cirrhosis were (185.65±85.07 and 2.3±2.37) in the Child-Pugh A group, (304.74±105.81 and 6.37±5.19) in the B grade group, and (369.48±73.238.28±5.38) in the C grade group; plasma vWF level and VITRO score in patients with hepatitis B cirrhosis increased with the increase of Child-Pugh grade, and the difference was statistically significant (F=60.236, P=0.000F=32.854, P=0.000). The area under the curve (AUC) of plasma vWF level and VITRO score for diagnosing the decompensated stage of hepatitis B cirrhosis were 0.897 [95% confidence interval (CI): 0.855-0.940, P＜0.01], 0.949 [95% CI: 0.916-0.982, P＜0.01). When the vWF level and VITRO score were taken as cut-off values of 238.5% and 1.65, respectively, the sensitivity of diagnosing the decompensated stage of hepatitis B cirrhosis was 79.5% and 94.3%, the specificity was 92.3% and 87.7%, and the positive predictive value was 80.5% and 94.3%, the negative predictive value was 91.9% and 97.5%, and the diagnostic accuracy was 88.6% and 89.3%. Among the patients with decompensated hepatitis B cirrhosis, the level of vWF in the group with gastrointestinal bleeding (367.24±68.29)% was significantly higher than that in the group without gastrointestinal bleeding (286.15±109.69)%, and the difference was statistically significant (P＜0.001) The VITRO score of the group with gastrointestinal bleeding (9.12±5.4) was significantly higher than that of the group without gastrointestinal bleeding (5.36±4.13), and the difference was statistically significant (P＜0.01). The vWF level in the spontaneous peritonitis group was (341.73±87.92)% higher than that in the non-spontaneous peritonitis group (296.32±111.74)%, and the difference was statistically significant (P＜0.05). There was no statistical difference in VITRO score between the two groups. significance. Conclusion: Plasma vWF level and VITRO score can evaluate the progression of liver disease and the degree of decompensation of liver cirrhosis in patients with HBV infection, and have a predictive effect on various complications after decompensation of liver cirrhosis, and have certain guiding significance for early intervention measures.

Protective effect of dexmedetomidine on neuronal hypoxic injury through inhibition of miR-134.

OBJECTIVE: To explore the mechanism of dexmedetomidine (DEX)-mediated miR-134 inhibition in hypoxia-induced damage in PC12 cells. METHODS: Hydrogen peroxide (H2O2)-stimulated PC12 cells were divided into control, H2O2, DEX + H2O2, miR-NC/inhibitor + H2O2, and miR-NC/ mimic + DEX + H2O2 groups. Cell viability and apoptosis were assessed by the 3-(4,5-dimethylthiazol(-2-y1)-2,5-diphenytetrazolium bromide (MTT) assay and Annexin V-FITC/PI staining, while gene and protein expression levels were detected by qRT-PCR and western blotting. Reactive oxygen species (ROS) levels were tested by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining, and malondialdehyde (MDA) content was determined with a detection kit. RESULTS: DEX treatment decreased H2O2-elevated miR-134 expression. H2O2-induced PC12 cell damage was improved by DEX and miR-134 inhibitor; additionally, cell viability was increased, while cell apoptosis was reduced. In addition, both DEX and miR-134 inhibitor reduced the upregulated expression of cleaved caspase-3 and increased the downregulated expression of Bcl-2 in H2O2-induced PC12 cells. However, compared to that in the DEX + H2O2 group, cell viability in the mimic + DEX + H2O2 group was decreased, and the apoptotic rate was elevated with increased cleaved caspase-3 and decreased Bcl-2 expression. Inflammation and oxidative stress were increased in H2O2-induced PC12 cells but improved with DEX or miR-134 inhibitor treatment. However, this improvement of H2O2-induced inflammation and oxidative stress induced by DEX in PC12 cells could be reversed by the miR-134 mimic. CONCLUSION: DEX exerts protective effects to promote viability and reduce cell apoptosis, inflammation, and oxidative stress in H2O2-induced PC12 cells by inhibiting the expression of miR-134.

[Very low-level viremia: new clinical attention-requiring problem during the course of anti-hepatitis B virus treatment].

Clinical studies have validated low-level viremia is associated with a variety of adverse outcomes in patients with chronic hepatitis B during the course of receiving nucleos(t)ide analogue antiviral therapy. With the advancement of PCR technology, the high sensitivity PCR detection of HBV DNA can reach the lower limit of detection of < 5-10 IU/mL. The standard criterion for judging among patients who have achieved complete virological response is HBV DNA levels < 20 IU/ml. The use of highly sensitive PCR tests can detect very low-level viremia (HBV DNA < 20 IU/ml, but > 5-10 IU/mL) in some patients. However, there are currently fewer relevant studies, and more research data needs to be accumulated to answer this clinical question of whether long-term very low-level viremia affects the clinical outcome of patients with chronic hepatitis B.

[Preliminary study on the effect of B7H3 interaction with fibronectin on apoptosis of human chronic myeloid leukemia cells].

Objective: To explore the effect of the interaction between B7H3 and fibronectin (FN) on the apoptosis of human chronic myeloid leukemia K562 cells. Methods: The expression of B7H3 molecules in K562 cells was detected using flow cytometry and B7H3 overexpressing cells were constructed. The interaction between B7H3 and FN was detected using the co-immunoprecipitation technology. After adding exogenous FN, cell experiments were performed to detect changes in adhesion and cell apoptosis. The changes in apoptosis-related proteins and PI3K/AKT signaling pathway were detected using Western blot. Results: The expression of B7H3 was low in K562, and the cell line K562 OE (overexpression) -B7H3 and the control cell line K562 NC (negative control) -B7H3 were obtained after lentivirus transfection. There is an interaction between B7H3 and FN (P=0.036) , and this interaction promoted cell adhesion (P<0.05) , inhibited cell apoptosis (P<0.05) , and activated the PI3K/AKT signaling pathway (P<0.05) . Conclusion: B7H3 interacts with FN to promote cell adhesion and may inhibit K562 cell apoptosis by activating the PI3K/AKT signaling pathway.

[Association between the morphology of the implanted atrial septal defect occluding umbrella and postoperative headache].

Objective: To explore whether the atrial septal defect(ASD) size, the type of occlusion umbrella selected, and the morphological changes after release of occlusion umbrella affect the headache symptoms of ASD patients after operation. Methods: A total of 567 ASD ptients, who underwent successful implantion with a single occlude from January 2014 to December 2017 in General Hospital of Northern Theater Command were enrolled. The patients were divided into symptomatic group and asymptomatic group according to the presence or absence of headache symptoms after occlusion. X-ray catheter calibration method was used to measure the diameter(d), thickness（L）, maximum diameter of the left umbrella surface after release(D2) and the value of i (i = D2/L). Risk factors related to headache were analyzed by multivariate logistic regression analysis. linear regression analysis was used to detect the relationship between the type of occluder umbrella and ASD diameter in asymptomatic group. Results: A total of 567 patients with one occluder umbrella were included, and 148(26.1%) cases were male. The age was (34.4±19.4) years old. The follow-up time was (12.7±2.8) months. There were 51 cases in the symptomatic group and 516 cases in the asymptomatic group. In 29 patients who were treated by extending the course or increasing the dose of aspirin, the symptoms disappeared or improved. There was no significant difference in the maximum ASD diameter (TTE measured) and the size of occluder between the symptomatic group and asymptomatic group(both P>0.05). The value of d ((19.80±6.67)mm vs.(17.40±7.28) mm, P=0.041) D2 ((43.29±7.41）mm vs. (39.20±9.59)mm， P=0.013)and L((13.06±3.72)mm vs. (10.19±2.90) mm，P=0.025) of the symptomatic group were all higher than that of the asymptomatic group，while the i value was smaller((3.54±0.88）vs.(3.99±0.93)，P=0.010）. The results of multivariate logistic regression analysis showed that the value of L(OR=1.286，95%CI 1.176-1.406, P=0.002) and the value of i(OR=0.916，95%CI 0.867-0.968, P<0.001) were independent factors of headache symptoms in patients after ASD occlusion, while the value of d and the value of D2 were not independent factors (both P>0.05). Linear equations obtained from asymptomatic patients showed the size of occluder =1.121×the maximum ASD diameter of TTE measured +6.414. Conclusions: There is no correlation between the symptoms with the expanded diameter and the maximum diameter of left umbrella's surface after released. The Postoperative discomfort symptoms is significantly correlated to the thickness of the occluder and the value of i. It is suggested that headache could be induced by the oversized occlude, thus choosing the appropriate size of the occluder is essential to reduce the occurrence of postoperative headache symptoms. Increasing the size of occluder because of worrying about the abscission and removal of the occlude is unreasonable. The antiplatelet therapy should also be strengthened to reduce the occurrence of symptoms and improve the symptoms of the patients if the occluder's size is too large. This regression equation (The size of occluder =1.121 × the maximum ASD diameter of TTE measured +6.414) could be used as a reference for the suitable selection of ASD occluder.

Protective effect of remifentanil on myocardial ischemia-reperfusion injury through Fas apoptosis signaling pathway.

OBJECTIVE: The aim of this study was to investigate the protective effect of remifentanil (RFT) on myocardial ischemia-reperfusion (IR) injury through Fas apoptosis signaling pathway. MATERIALS AND METHODS: A total of 36 Sprague-Dawley (SD) rats were randomly divided into 3 groups, including the sham operation (Sham) group, IR model (IR) group and RFT pretreatment (RFT) group, with 12 rats in each group. Myocardial tissues of rats in each group were collected. Hematoxylin and eosin (H&E) staining was used to examine the pathological differences of the myocardium in the three groups. The levels of lactate dehydrogenase (LDH), creatine kinase (CK), superoxide dismutase (SOD) and malondialdehyde (MDA) in the serum of rats in each group were detected by enzyme-linked immunosorbent assay (ELISA). Meanwhile, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was adopted to detect the apoptosis level of myocardial cells in each group. Furthermore, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting were applied to measure the mRNA and protein expression levels of Fas and its pathway indexes, respectively. RESULTS: Compared with the Sham group, LDH and CK activities and MDA level in the IR group were significantly increased, whereas the level of SOD was remarkably decreased (p<0.05). Compared with the IR group, RFT pretreatment could significantly reduce the release of LDH and CK-muscle/brain (CK-MB), increase SOD level and decrease MDA level (p<0.05). TUNEL results manifested that the apoptosis rate of myocardial cells in the IR group was markedly increased than that of the Sham group (p<0.05). Meanwhile, the apoptosis rate of myocardial cells in the RFT group was notably decreased when compared with that of the IR group (p<0.05). ELISA results demonstrated that the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) proteins in the RTF group were significantly lower than those of the IR group (p<0.05). RT-PCR and Western blotting results indicated that the expressions of Fas, Fas ligand (FasL), and Fas-associated protein with death domain (FADD) in IR and RFT groups were significantly higher than those of the Sham group (p<0.05). However, RTF pretreatment could markedly reduce the levels of Fas, FasL, and FADD (p<0.05). CONCLUSIONS: RFT can reduce the apoptosis of myocardial cells as well as IR-induced oxidative stress and inflammation by inhibiting the Fas/FasL signal transduction pathway.

[Changes in natural killer cell subsets marked with CD27 and CD11b for HBV carrier mice].

Objective: To evaluate the changes in natural killer cell subsets marked with CD27 and CD11b for HBV carrier mice. Methods: The pAAV-HBVl.2 plasmid was injected into the tail vein of C57BL/6 mice by hydrodynamic injection method to construct HBV-carrier model group and empty vector as the control group. Liver function and virological examination at different time points were used to judge the construction of HBV- plasmid carrier animal model. Flow cytometry was used to detect the frequency of NK cells and CD11b combined with CD27 NK cell subsets in spleen and liver. GraphPad Prism software was used for statistical analysis. Results: HBV-carrier mouse model was successfully constructed. There were no statistically significant difference in NK cell frequencies between spleen and liver of HBV carrier mice (P> 0.05), compared to control group. NK cells were divided into four subsets with in combination to CD27 and CD11b: CD11b(+)CD27(-)(CD11b(+)SP), CD11b(+)CD27(+)(DP), CD11b(-)CD27(+)(CD27(+)SP) and CD11b-CD27-(DN). Furthermore, the spleen of HBV-carrier mice had no statistically significant difference (P> 0.05) with the frequency of the four NK-cell subsets. The frequency of DN NK cell subsets was significantly increased in the liver of HBV carrier mice than control group (P< 0.001); however, the frequency of CD11b(+)SP cell subsets was significantly decreased (P < 0.05).There were no statistical significance in the frequency comparison between NK subgroups of DP and CD27(+)SP NK cell subsets (P> 0.05). Conclusion: HBV-carrier mice with abnormal distribution of hepatic NK cell subsets significantly increased and decreased the frequency of DN NK cell subsets and CD11b(+)SP cell subsets.

[Dysplastic nodules and precancerous lesions of liver cancer].

Liver cancer (HCC) holds third position for cause of cancer-related death worldwide. Therefore, it is urgent to explore new strategies for the diagnosis and treatment of liver cancer. Illustrating the successful experience of other tumors on precancerous lesions, this paper puts forward the idea of advance strategy for the diagnosis and treatment through dysplastic nodules, especially high-grade dysplastic nodules, which can reduce or delay the carcinogenesis of some patients with cirrhosis. It is hoped that this measure might improve the present situation of diagnosis and treatment of liver cancer in coming days in China.

[Combined anluohuaxianwan and entecavir treatment significantly improve the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection].

Objective: To explore the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection who received entecavir alone or in combination with anluohuaxianwan for 78 weeks. Methods: Patients with chronic HBV infection were randomly treated with entecavir alone or in combination with anluohuaxian for 78 weeks. Ishak fibrosis score was used for blind interpretation of liver biopsy specimens. The improvement in liver fibrosis condition before and after the treatment was compared. Student's t test and non-parametric test (Mann-Whitney U-Test and Kruskal-Wallis test) were used to analyze the measurement data. The categorical variables were analyzed by Chi-square test method and Spearman's rank correlation coefficient was used to test bivariate associations. Results: Liver fibrosis improvement rate after 78 weeks of treatment was 36.53% (80/219) and the progression rate was 23.29% (51/219). The improvement of liver fibrosis was associated to the degree of baseline fibrosis and treatment methods (P < 0.05). The improvement rate of hepatic fibrosis in patients treated with anluohuaxianwan combined with entecavir at baseline F < 3 (54.74%, 52/95) was significantly higher than that in patients treated only with entecavir (33.33%, 16/48), P = 0.016 and the progression rate of hepatic fibrosis (13.68%, 13/95) was lower than that in patients treated alone (18.75%, 9/48), P = 0.466. In patients with baseline F < 3, the proportion of patients with improved and stable liver fibrosis in the combined treatment group (68.1%, 32/47) was higher than that in the treatment group alone (51.7%, 15/29). Conclusion: Combined anluohuaxianwan and entecavir treatment can significantly improve the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection. Furthermore, it has the tendency to improve the stability rate and reduce the rate of progression of liver fibrosis.

[Optimal cessation period of anti-HBV therapy to block mother-to-child transmission].

Hepatitis B virus (HBV) carrier woman of childbearing age with high viral load is an important source of vertical transmission of hepatitis b virus from mother-to-child in China. Routine blockade with immunoglobulin combined with hepatitis B vaccine is used for neonates born to pregnant women with high viral load of hepatitis B virus, but in some cases, immunoprophylaxis fails. The main application of antiviral drugs in pregnancy is to reduce the serum viral load, thereby significantly improve the blocking rate of vertical transmission between mother and infant. Current evidence suggested that if the maternal age is less than 30 years old, with no obvious liver fibrosis or cirrhosis and there is no increase in ALT level >2ULN( upper limit of normal) during the treatment, the treatment with antiviral drugs can be stopped after delivery immediately. Additionally, ALT level should be examined at 4, 12 and 24 weeks after stopping the drug. Antiviral therapy for the occurrence of hepatitis attack should be given if criteria for HBV treatment are met.

miR-375 inhibits the proliferation and invasion of glioblastoma by regulating Wnt5a.

The aberrant expression of microRNA-375 (miR-375) has been proved to be associated with carcinogenesis. However, the role of miR-375 in glioblastoma (GBM) remains unknown. The aim of this study was to investigate biological functions and its molecular mechanisms of miR-375 in GBM cells. In this study, real-time PCR results showed that the level of miR-375 expression in GBM tissues and GBM cell lines (U87 and U251) was decreased. Using MTT assay, Transwell migration and invasion assay, we demonstrated that miR-375 overexpression significantly suppress cell proliferation, cell migration and cell invasion capacity in U87 and U251 cells. However, downregulation of miR-375 had reverse effects on cell proliferation, migration and invasion. Targeting association analysis, dual luciferase assay, RT-PCR and western blot analysis results confirmed that miR-375 could target the 3'UTR of Wnt5a mRNA and regulated its protein expression. Further studies also find overexpression of Wnt5a could significantly reverse miR-375-mediated proliferation, migration and invasion on U87 and U251 cells. Therefore, we concluded that miR-375 inhibited the proliferation and invasion of GBM by regulating Wnt5a and might be a possible therapeutic agent for GBM.

[Clinical advances in targeted therapy and immunotherapy for hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) has a high incidence and mortality rate in China, and is the worst-than-expected cancer management disease in all provinces of the country. In recent years, systemic drug therapy for HCC has developed rapidly, especially molecular targeted drugs and immune checkpoint blocker being the most prominent. Molecular targeted drugs and immune checkpoint blocker have achieved some progress in the treatment of advanced HCC, but they still have many problems and challenges. This paper briefly introduces the latest advances of drug therapy for advanced HCC.

[Genetic characteristics of hemagglutinin and neuraminidase of avian influenza A (H7N9) virus in Guizhou province, 2014-2017].

Objective: To understand the molecular characteristics of hemagglutinin (HA) and neuraminidase (NA) as well as the disease risk of influenza virus A H7N9 in Guizhou province. Methods: RNAs were extracted and sequenced from HA and NA genes of H7N9 virus strains obtained from 18 cases of human infection with H7N9 virus and 6 environmental swabs in Guizhou province during 2014-2017. Then the variation and the genetic evolution of the virus were analyzed by using a series of bioinformatics software package. Results: Homology analysis of HA and NA genes revealed that 2 strains detected during 2014-2015 shared 98.8%-99.2% and 99.2% similarities with vaccine strains A/Shanghai/2/2013 and A/Anhui/1/2013 recommended by WHO, respectively. Two strains detected in 2016 and 14 strains detected in 2017 shared 98.2%-99.3% and 97.6%-98.8% similarities with vaccine strain A/Hunan/02650/2016, respectively. Other 6 stains detected in 2017 shared 99.1%-99.4% and 98.9%-99.3% similarities with strain A/Guangdong/17SF003/2016, respectively. Phylogenetic analysis showed that all the strains were directly evolved in the Yangtze River Delta evolution branch, but they were derived from different small branch. PEVPKRKRTAR↓GLF was found in 6 of 24 strains cleavage site sequences of HA protein, indicating the characteristic of highly pathogenic avian influenza virus. Mutations A134V, G186V and Q226L at the receptor binding sites were found in the HA. All the strains had a stalk deletion of 5 amino acid residue "QISNT" in NA protein, and drug resistance mutation R294K occurred in strain A/Guizhou-Danzhai/18980/2017. In addition, potential glycosylation motifs mutations NCS42NCT were found in the NA of 9 of 24 strains. Conclusions: HA and NA genes of avian influenza A (H7N9) virus showed genetic divergence in Guizhou province during 2014-2017. The mutations of key sites might enhance the virulence of the virus, human beings are more susceptible to it. Hence, the risk of infection is increasing.

[Plasma exchange combined with double plasma absorption therapy improve the prognosis of acute-on-chronic liver failure].

Objective: To compare the efficacy and safety of plasma exchange (PE) combined with double plasma absorption and simple PE in the treatment of acute-on-chronic liver failure. Methods: We retrospectively analyzed 251 cases of acute-on-chronic liver failure treated with artificial liver treatment since January 2015. Changes in clinical manifestations, laboratory tests, and complications of the patients before and after different modes of treatment were compared and short-term efficacy was tracked. In accordance with different data, t-test, Pearson's chi-squared test and Fisher's exact test were used for statistical analysis. Results: The effectiveness of low-volume PE combined with double plasma molecular adsorption system (DPMAS) and equal amount of PE combined with DPMAS was significantly better than simple PE (83.7%, 84.05% and 82.15 vs 55.6%, P < 0.05) in early stage of liver failure. In late-stage of liver failure, there was no significant difference in the treatment efficiency of each group (P > 0.05). Bilirubin and bile acid levels were significantly decreased in combined treatment groups than that to simple PE group (P < 0.05). PTA and albumin improvement rate of DPMAS PE groups were significantly lower than that of simple PE group (P < 0.05). There was no statistical difference in adverse reactions between each group. Conclusion: PE combined with DPMAS improves the treatment efficiency of early hepatic failure and decrease dosage of plasma when compared with simple PE. A beforehand DPMAS treatment after PE treatment can improve the adverse effects of DPMAS on blood coagulation function and albumin levels.

[HBsAg loss with Pegylated-interferon alfa-2a in hepatitis B patients with partial response to nucleos(t)-ide analog: new switch study].

Objective: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA. Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281. Results: At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss. Conclusion: Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

[Reduced frequency of natural killer cell on siglec-7(+) is associated with progression of hepatitis B virus-related cirrhosis].

Objective: To explore the relationship between sialic-acid-binding immunoglobulin-like lectin 7 (Siglec-7) expressed on NK cells and hepatitis B virus-related cirrhosis. Methods: Peripheral venous blood samples were collected from 23 healthy controls and 31 patients with hepatitis B virus-related cirrhosis (Child-Pugh A, n = 7; Child-Pugh B, n = 12; Child-Pugh C, n = 12). Peripheral blood mononuclear cells (PBMCs) were obtained by using Ficoll-Hypaque density gradient centrifugation and the expression of Siglec-7 and NK cells phenotype and their subpopulations were detected by flow cytometry. Comparisons between various groups were performed using t -test, one-way analysis of variance (ANOVA), and correlations between variables were analyzed using Pearson's-correlation coefficient. Results: (1) There was no significant difference in the percentage of NK cells and in their subpopulations with HBV-related cirrhosis and healthy controls. (2) Siglec-7 expression on NK cells in patients with HBV-related cirrhosis(62.44±13.45%)was significantly down-regulated than that to healthy controls(75.39±12.19%)while the frequency of Siglec-7(+) NK cells were negatively correlated with Child-Pugh score. (3) Subpopulation analysis showed that Siglec-7 expression on CD56(bright)CD16(-)NK cells(66.99±15.93%)was significantly lower than CD56(dim)CD16(+)NK cells(76.54±13.9%) in HBV-related cirrhosis. However, the expression of Siglec-7 in healthy controls showed no difference in these two NK cell subsets. (4) Phenotypic analysis showed that Siglec-7(+) NK cells express higher levels of activating receptor CD16, CD38, NKp46 and lower levels of inhibitory receptor CD158b. Indeed, the frequency of CD16 and CD38 on Siglec-7(+) NK cells in HBV-related cirrhosis was lower than that in healthy controls. Conclusion: The disease progression in patients with hepatitis B virus-related cirrhosis is associated to decreased frequencies of Siglec-7(+)NK cells.

[Dynamic analysis of the academic influence in Chinese Journal of Hepatology from 2010 to 2016].

Objective: To dynamically analyze the discipline status, influence factors and key issues of Chinese Journal of Hepatology from 2010 to 2016 and explore the development rules of citation indexes. Methods: We collected information published by the China Institute of Scientific and Technological Information [China Science and Technology Journal Citation Report (Core Edition)] and Wanfang Database Periodicals statistical analysis platform from 2010 to 2016. A bibliometric analyses on article volume, citation frequency, citation rate, h-index, ratio of fund-aided papers, periodical influence, key number published period, number of relevant articles, and so on were analyzed for annual's impact factor. Results: According to the data released by the China Institute of Science and Technology Information, from 2010 to 2011, the impact factor of Chinese Journal of Hepatology was at leading level in the field of internal medicine and ranked sixth in the Journal of Internal Medicine. From 2012 to 2016, the overall comprehensive assessment score and citation frequency score of Chinese Journal of Hepatology were ranked first in the Journal of Gastroenterology. Core impact factors kept the discipline ahead. Indexes such as immediacy index, h- index, cited half-life and all other indicators were increased. Citation rate was >90% and cited issue number had greatly increased. Conclusion: Chinese Journal of Hepatology has a leading position in the Journal of Gastroenterology and credited by inland readers and authors of digestive and infectious fields. It has played a positive role in promoting the development of the discipline.