Chronic hepatitis B virus (HBV) infection is a major cause of viral hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). From chronic HBV infection to HCC, most patients go through the stages of chronic hepatitis, liver cirrhosis, and HCC. During this long process, the ongoing integration of HBV DNA into host DNA increases the risk of HCC, and the death and compensatory proliferation of hepatocytes caused by persistent liver inflammation may promote the accumulation of oncogenic mutations and finally lead to the malignant transformation of hepatocytes. Currently, nucleos(t)ide analogues are widely used anti-HBV drugs, which controls infection by inhibiting HBV replication and can thus effectively slow down disease progression and end-stage liver disease; however, anti-HBV therapy often starts late and has a relatively low treatment rate, and there is still a tendency of increase in the incidence rate of HBV-related HCC. Therefore, how to improve current antiviral strategies to further reduce the risk of HBV-related end-stage liver disease including HCC has become a hotspot in clinical practice. This article summarizes the previous studies supporting the expansion of antiviral therapy and suggests that antiviral therapy should be initiated as early as possible to inhibit viral replication and the sequential events of HBV DNA integration and ultimately reduce the risk of HCC in patients with chronic HBV infection.

Objective To investigate the ability of combined baseline serum markers, i.e., HBV DNA, HBV RNA, HBsAg, and HBcrAg, to predict HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) treated by nucleos(t)ide analogues. Methods A retrospective analysis was performed for 83 HBeAg-positive patients selected as subjects from the prospective CHB follow-up cohort established by Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, from June 2007 to July 2008, and the baseline serum levels of HBV DNA, HBV RNA, HBsAg, and HBcrAg were analyzed. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman method was used for correlation analysis. A Cox regression model was established to calculate HBeAg seroconversion prediction score, and the time-dependent receiver operating characteristic curve was used to evaluate the ability of combined markers in predicting HBeAg seroconversion. The Kaplan-Meier method was used to calculate cumulative seroconversion rate in each group, and the Log-rank test was used for comparison between groups. Results For the 83 HBeAg-positive patients, the median follow-up time was 108 months, and 44.58%(37/83) of these patients achieved HBeAg seroconversion. Compared with the non-seroconversion group, the HBeAg seroconversion group had significantly lower baseline serum levels of HBV DNA [6.23(1.99-9.28) log 10 IU/mL vs 7.69(2.05-8.96) log 10 IU/mL, Z =-2.345, P =0.019] and HBV RNA [4.81(1.40-7.53) log 10 copies/mL vs 6.22(2.00-8.49) log 10 copies/mL, Z =-1.702, P =0.010], and there were no significant differences in the levels of HBsAg and HBcrAg between the two groups ( P > 0.05). The Cox regression equation constructed based on the above serum markers showed a median score of 0.95(range 0.37-3.45) for predicting HBeAg seroconversion. In the total population, the combined score was negatively correlated with HBsAg, HBV DNA, HBV RNA, and HBcrAg ( r =-0.697, -0.787, -0.990, and -0.819, all P < 0.001). Based on the median prediction score, the patients were divided into high HBeAg seroconversion group and low HBeAg seroconversion group; as for the prediction of HBeAg seroconversion rate at 36, 60, and 84 months, the high HBeAg seroconversion group had a seroconversion rate of 43.90%, 51.20%, and 63.10%, respectively, while the low HBeAg seroconversion group had a seroconversion rate of 9.60%, 17.00%, and 19.8%, respectively, and there was a significant difference between the two groups ( χ 2 =11.6, P < 0.001). Conclusion The combined prediction score based on baseline serum HBV markers can predict HBeAg seroconversion in CHB patients treated by nucleos(t)ide analogues.

Objective: To explore the diagnostic value and model of serum Golgi protein 73 (GP73) in patients with hepatitis C cirrhosis. Methods: 271 cases with chronic hepatitis C virus infection who were treated in the Fifth Medical Center of PLA General Hospital from January 2010 to December 2017 were retrospectively collected as the research objects, including 126 cases with hepatitis and 145 cases with liver cirrhosis. Serum GP73 and liver stiffness measurement (LSM) based on transient elastography test were performed in all patients. Simultaneously, blood routine, liver function, coagulation function and other related indicators were collected. GP73 diagnostic efficiency for liver cirrhosis was evaluated by receiver operating characteristic curve (ROC). GP73 diagnostic value was clarified after comparison with aspartate aminotransferase/platelet ratio index (APRI), FIB-4 index (FIB-4) and LSM. Compensated hepatitis C virus-related cirrhosis diagnostic model based on serological index was established by logistic regression analysis. Results: The area under the receiver operating characteristic curve (AUC) of GP73, LSM, FIB-4 and APRI in the diagnosis of compensated hepatitis C virus-related cirrhosis were 0.923, 0.839, 0.836 and 0.800 respectively, and GP73 had the best diagnostic efficiency (P <0.001). LSM and GP73 combined use had improved the diagnostic sensitivity of cirrhosis to 97.24%. Multivariate logistic regression analysis revealed that GP73, age, and platelets were independent predictors of cirrhosis.Compensated hepatitis C virus-related cirrhosis diagnostic model (GAP) was established based on the result: LogitP=1/[1+exp(6.145+0.013×platelet-0.059×age-0.059×GP73)].AUC model for diagnosing compensated liver cirrhosis was 0.944, and the optimal cut-off value was 0.56, with sensitivity and specificity of 84.03% and 92.06%, respectively, and the diagnostic efficiency of this model was better than that of APRI, FIB-4, LSM and GP73 alone (P<0.05). Conclusion: GP73 is a reliable serum biomarker for the diagnosis of compensated hepatitis C virus-related cirrhosis. The GAP diagnostic model based on GP73, platelet count, and age can further improve the diagnostic efficiency and help to diagnose patients with compensated hepatitis C virus-related cirrhosis.
Aspartate Aminotransferases ; Biomarkers ; Fibrosis ; Hepatitis C ; Hepatitis C, Chronic/complications* ; Humans ; Infant, Newborn ; Liver/pathology* ; Liver Cirrhosis/pathology* ; Polyesters ; ROC Curve ; Retrospective Studies

ObjectiveTo investigate the effect of AU-rich element RNA-binding factor 1 (AUF1) on glypican 3 (GPC3) in hepatocellular carcinoma (HCC) and its possible mechanism. MethodsTCGA-HCC gene expression data were downloaded from Broad Institute Genome Data Analysis Center, and finally 371 HCC tissue samples with different etiologies and 50 adjacent tissue samples were included; LCI-HCC gene expression data were downloaded from GSE14520, and 214 patients with hepatitis B-associated HCC who had follow-up data were enrolled. A total of 35 primary liver cancer samples and corresponding adjacent tissue samples were collected from HCC patients who underwent radical surgery in Henan Provincial Cancer Hospital from 2009 to 2013. Immunohistochemistry was used to measure the protein expression of GPC3 and AUF1 in HCC tissue; Western Blot and qRT-PCR were used to measure the expression of GPC3 after AUF1 knockdown or overexpression in hepatoma cell lines; RNA-binding protein immunoprecipitation and RNA turnover assay were used to investigate the potential mechanism of AUF1 in regulating the expression of GPC3. The t-test was used for comparison of quantitative data between two groups, and the chi-square test was used for comparison of rates between two groups; the Kaplan-Meier method was used for survival analysis after surgery, and the log-rank test was used for comparison of survival rates. ResultsIn TCGA and LCI databases, the expression of GPC3 in HCC tissue was significantly higher than that in adjacent tissue (P＜0.05), and in TCGA database, the high expression of GPC3 was associated with the poor prognosis of HCC patients (P＜0.05). Immunohistochemistry showed that both GPC3 and AUF1 proteins are highly expressed in HCC tissue, with a positive expression rate of 77.1% (27/35) and 74.3% (26/35), respectively. In vitro experiment showed that AUF1 knockdown significantly reduced the expression of GPC3 in HepG2 and Huh-7 cells (P＜0.05), while AUF1 overexpression significantly increased the expression of GPC3 (P＜0.05). AUF1 protein could bind to GPC3 mRNA, and AUF1 knockdown reduced the stability of GPC3 mRNA. ConclusionAUF1 is an important post-transcriptional regulator of the GPC3 gene, and the abnormal high expression of AUF1 and GPC3 may be involved in the development and progression of HCC.

Neutrophil extracellular traps (NETs) are fibrous structures released by neutrophils and the formation process is called NETosis. NETs participate in the host innate immunity. Recent research has found that NETs is a double-edged sword. Under normal conditions, the formation of NETs can play a role in clearing pathogens and maintain the host homeostasis. However, when NETs are overproduced or not cleared in time, they can take part in the pathogenesis of many diseases. This article reviewed the formation of NETs, the mechanisms involved in NETosis and the role of NETs in the secretion of multiple cytokines in different diseases.

Objective:To learn the application of nosocomial infection prevention and control measures as stipulated in COVID-19 emergency plans by medical institutions at all levels in the region, for the purpose of strengthening epidemic prevention and control.Methods:During March 12-13, 2020, customized questionnaires were used to learn from 186 hospitals and medical institutions regarding the basics of their nosocomial prevention management departments, emergency plan application and revisions made. Comparison of the ratios or constituent ratios were tested with χ2 test, while the continuous variables analysis between groups was verified with one-way ANOVA. Results:77.53% of the medical institutions had set up independent nosocomial infection management departments, and 87.30% of the institutions were qualified. 80% of the medical institutions had in place emergency plans for respiratory infectious diseases, but 98.05% of them had revised their plans during the pandemic, with an average of 10.85 newly added and revised provisions. Only 30.11% of emergency planed provide for clearly graded early warning.Conclusions:Efforts should be upgraded to develop an emergency prevention and control system for infection prevention and control in epidemics, and improve technical support for infection prevention and control in the system; to strengthen the clearly-graded early warning and graded responses in a scientific manner; and conduct regular drills, revise plan to ensure its applicability.

Objective:To investigate the clinical and diagnostic value of liver stiffness measurement (LSM) for the evaluation and comparison of aspartate aminotransferas/platelet ratio index (APRI), fibrosis 4 indexes (FIB-4) and NAFLD fibrosis score (NFS) with liver fibrosis staging in relation to nonalcoholic fatty liver disease (NAFLD).Methods:103 cases with NAFLD who met the inclusion criteria confirmed by liver biopsy were selected for retrospective analysis. The results of serological tests and LSM were recorded. The APRI, FIB-4 and NFS were calculated. The accuracy and applicability of four liver fibrosis models in the diagnosis of liver fibrosis in NAFLD patients were compared with the receiver operating characteristic curve (ROC), and the diagnostic cut-off value of LSM was established.Results:Varying degrees of LSM, APRI, FIB-4 and NFS had shown positive correlations with the increasing degree of liver fibrosis. Among them, LSM was positively correlated with the degree of liver fibrosis, and the correlation coefficient was r = 0.727, P < 0.0001. Consistent with this, the area under the receiver operating characteristic curve, sensitivity, and specificity of LSM diagnosis of liver fibrosis in different stages was significantly higher than APRI, FIB-4 and NFS. Area under receiver operating characteristic curve of LSM was 0.862 and 0.928 for significant liver fibrosis ( f ≥ 2), and advanced liver fibrosis ( f ≥ 3). Conclusion:LSM has a good diagnostic exclusion value for NAFLD-induced fibrosis, and its sensitivity and specificity are better than APRI, FIB-4 and NFS.

Objective To study the mitochondrial DNA mutation in patients with primary multiple myeloma. Methods The mitochondrial DNA of 5 patients with primary multiple myeloma in the First Hospital of Qinhuangdao from February to June 2017 were amplified by polymerase chain reaction (PCR) and sequenced directly, and the results were compared with revised Cambridge Reference Sequence (rCRS) and Human Mitochondrial Gene Database (mtDB) database. Results There were 42 mutation genes, with 52.38％(22/42) mutation genes in D-loop region, 9.52％(4/42) mutation genes in ND4L region, 2.38％(1/42) mutation genes in ND5 region, 26.19％ (11/42) mutation genes in Cytb region, 7.14％ (3/42) mutation genes in ND1 region, and 4.76％ (2/42) mutation genes in COⅡ region. Conclusion There is a high mitochondrial DNA mutation rate in patients with primary multiple myeloma.

Objective To investigate the mutation of mitochondrial genome in lymphoma. Methods The peripheral blood or borrow fluid 2 ml from 14 lymphoma patients in the First Hospital of Qinhuangdao between May 2016 and July 2017 were collected. Polymerase chain reaction (PCR) was used to amplify and sequence mitochondrial DNA, and the results were compared with the revised Cambridge reference sequence (rCRS) and human mitochondrial genome database (mtDB), and then the mutation was also analyzed. Results There were 118 mutation genes, including 57.63％ (68/118) in D-loop region, 18.64％ (22/118) in NADH dehydrogenase 5 (ND5) region, 13.56％(16/118) in cytochrome b oxidase (CbO) region, 5.08％(6/118) in ND1 region, 3.39％ (4/118) in cytochrome oxidase (COⅡ) region, 1.69％ (2/118) in ND4 region. Conclusion Mitochondrial DNA mutation in lymphoma has a high mutation rate.

Objective To study the mitochondrial DNA mutation in leukemia.Methods Mitochondrial DNA of 16 leukemia patients in First Hospital of Qinhuangdao from February to June 2017 were amplified and sequenced by using polymerase chain reaction (PCR).The result was compared with revised Cambridge reference sequence (rCRS) and human mitochondrial genome database (mtDB),and the mutation was also analyzed.Results There were 106 mutation genes in total,including 47.17 ％ (50/106) in D-loop region,2.83 ％ (3/106) in ND4 region,17.92 ％ (19/106) in ND5 region,22.64 ％ (24/106) in Cytb region,7.55 ％ (8/106) in ND1 region,1.89 ％ (2/106) in Co Ⅱ region.Conclusion There is a high mitochondrial DNA mutation rate in leukemia patients.