The clinical outcome of hepatitis B virus(HBV) infection mostly depends on the interaction between HBV and host immune system. Although there are still no drugs for the radical treatment of hepatitis B at present, more and more studies have found that functional cure, characterized by persistent negative conversion of HBsAg and HBV DNA in serum, has become an achievable goal for the treatment of chronic hepatitis B. Meanwhile, immunoregulatory therapy based on a new understanding of the mechanism of immune control of HBV infection has been used as one of the important strategies for functional cure of chronic hepatitis B. This article elaborates on the immune control of HBV infection and the advances and challenges of its application in the research on the strategies for functional cure.

The liver has a unique immune microenvironment, and the intrinsic antigen-presenting cells in the liver interact with each other and form a network to accurately regulate the homeostasis between liver immune tolerance and immune response. During hepatitis B virus(HBV) infection, on the one hand, the intrahepatic intrinsic antigen-presenting cells induce immune tolerance to help the virus escape immune clearance and thus result in persistent infection; on the other hand, the maturation and activation of the intrahepatic intrinsic antigen-presenting cells can also mediate effective anti-HBV immune response to achieve virus clearance. This article elaborates on the research advances in the role and mechanism of action of intrahepatic intrinsic antigen-presenting cells in regulating immune response against HBV infection.

Host innate and adaptive immune responses are essential for the clearance of hepatitis B virus(HBV). Patients with chronic HBV infection have defects in innate and specific immune responses against HBV, which cannot effectively eliminate the virus and may result in persistent virus replication and liver inflammation. In addition to direct inhibition of HBV, treatment strategies targeting host immunity,such as stimulating or restoring antiviral immunity, are also important methods to achieve functional cure in patients with chronic hepatitis B.The liver is the target organ for HBV infection, and therefore, the research on the impact of HBV infection on intrahepatic immune microenvironment has become a hotspot for the research and development of new drugs that regulate the antiviral immune response against HBV in the liver. This article reviews the recent research advances in innate immune response associated with HBV infection and the new strategies to activate intrahepatic innate immune response and achieve the cure of hepatitis B.

Functional cure of chronic hepatitis B(CHB) marks sustained virological inhibition and immunological control and is the ideal treatment goal recommended by the latest guidelines for the prevention and treatment of CHB in China and foreign countries. CHB patients can achieve virological inhibition with the help of long-term direct antiviral therapy, and only a small number of patients can achieve functional cure, suggesting that there is an urgent need for the combination of direct antiviral therapy and immunotherapy. At present, the best treatment strategy is targeted precise clearance of HBV-infected hepatocytes to reduce liver injury, which depends on HBV-specific immune cells in the liver. Therefore, restoring or enhancing the function of HBV-specific T cells and B cells is the key strategy for functional cure of CHB.

Hepatitis B virus(HBV)-specific T cells in patients with chronic HBV infection are currently acknowledged as exhausted T cells. This article summarizes previous studies which support this hypothesis and then points out several inconsistencies between this hypothesis and clinical observation. Based on recent research findings, it is pointed out that in patients with chronic HBV infection, HBV-specific T cells might be dominated by silenced, early-differentiated progenitor T cells. Also, this article analyzes the possible causes of the silenced status of those T cells.

It is known that hepatitis B virus(HBV) covalently closed circular DNA(cccDNA) persists in the nucleus of infected hepatocytes in the form of minichromosome and is difficult to target and eliminate. Studies on the mechanisms and strategies for persistent silencing or elimination of HBV cccDNA are the focus achieving for “functional cure” of chronic hepatitis B. This article introduces the current knowledge on the basic biological features of cccDNA, regulatory mechanisms of transcription and metabolism, and related host factors, with a focus on the potential pathways and strategies for cccDNA silencing or elimination.

In June 2017, the National Health and Family Planning Commission of the People's Republic of China issued the Guidelines for diagnosis and treatment of primary liver cancer in China(2017 edition), which is of great significance as it provides recommendations on the diagnosis, staging, and treatment of liver cancer. Since then, more and more high-level evidence in accordance with the principles of evidence-based medicine has appeared in research on primary liver cancer around the world, so the National Health Commission of the People's Republic of China revised the 2017 edition of the Guidelines and issued the Guidelines for diagnosis and treatment of primary liver cancer in China(2019 edition). This article interprets the updated key points of the new edition of the Guidelines to better guide clinical treatment.

During the severe epidemic of coronavirus disease 2019(COVID-19) in China, some patients with chronic viral hepatitis have difficulties in attending the hospital and getting medical treatment. This article introduces the management strategies for patients with chronic viral hepatitis in medical institutions, including long prescription to improve patients' compliance, long-distance online outpatient service,participation of community health service centers in management, medication guidance for patients by pharmacists, and nurses' participation in improving patients' self-management ability. At the same time, patients should also strengthen the self-management of life style and take protective measures when going out. With the efforts of both doctors and patients, proper management of patients with chronic viral hepatitis will be achieved during this special period.

At present, coronavirus disease 2019(COVID-19) caused by 2019 novel coronavirus(2019-nCoV) infection has spread rapidly in China and more than 70 countries around the world and thus become a public health event of international concern. In addition to fever and respiratory symptoms, varying degrees of liver injury is also observed after 2019-nCoV infection. This article reviews the clinical features, pathology, pathogenic mechanism, and therapeutic strategies of liver injury associated with COVID-19, hoping to provide a reference for clinical decision-making on the prevention and treatment of COVID-19.

Objective To investigate value of combined measurement of serum hepatitis B virus(HBV) covalently closed circular DNA(cccDNA), HBsAg, and HBV pregenomic RNA(pgRNA) in predicting the treatment outcome of HBeAg-positive chronic hepatitis B(CHB) patients treated with entecavir(ETV).Methods A total of 87 HBeAg-positive CHB patients who were diagnosed and treated inThe Second Affiliated Hospital of Suzhou University from May 2015 to May 2017 were enrolled. All patients were treated with ETV for 48 weeks, and the serum levels of HBV cccDNA, HBsAg, and HBV pgRNA were measured at baseline and at weeks 12, 24, and 48 of treat-ment. Thet-test was used for comparison of normally distributed continuous data between groups, and the Mann-WhitneyUtest was usedfor comparison of non-normally distributed continuous data between groups. The chi-square test was used for comparison of categorical da-ta between groups, and the Mann-WhitneyUtest was used for comparison of ranked data between groups. A Pearson correlation analysiswas performed to determine the correlation of liver HBV cccDNA with serum HBsAg and HBV pgRNA. A multivariate logistic regression analysis was used to investigate the predictive factors for complete response, and the receiver operating characteristic(ROC) curve was usedto evaluate the value of serum HBV cccDNA, HBsAg, and HBV pgRNA measured alone or in combination in predicting complete response.Results Of all 87 HBeAg-positive CHB patients after 48 weeks of ETV treatment, 38 achieved complete response and 49 did not achievecomplete response. Compared with the non-complete response group, the complete response group had significant reductions in the levels ofHBV cccDNA at baseline and at weeks 24 and 48 of treatment(Z =-2. 452,-2. 518, and-2. 266, allP< 0. 001), HBsAg at baselineand at weeks 12, 24, and 48 of treatment(Z=-2. 431,-2. 750,-2. 386, and-2. 536, allP< 0. 001), and HBV pgRNA at weeks12, 24, and 48 of treatment(Z=-2. 674,-2. 503, and-2. 528, allP< 0. 001). Compared with the non-complete response group,the complete response group had significantly greater reductions in HBV cccDNA at week 24 of treatment, HBsAg at week 12 of treatment,and HBV pgRNA at week 12 of treatment(Z=-2. 352,-2. 566, and-2. 389,P= 0. 006, 0. 001, and 0. 004). Serum HBsAg andHBV pgRNA were positively correlated with HBV cccDNA in liver tissue(r= 0. 553 and 0. 757, bothP< 0. 001). The levels of HBVcccDNA at week 24 of treatment(odds ratio [OR] = 6. 248, 95% confidence interval [CI]: 1. 574-14. 262,P< 0. 05), HBsAg at week12 of treatment(OR = 5. 452, 95% CI: 2. 048-16. 888,P< 0. 05), and HBV pgRNA at week 12 of treatment(OR = 5. 670, 95% CI:1. 201-16. 183,P< 0. 05) were predictive factors for complete response. As for the area under the ROC curve(AUC), HBV cccDNA,HBsAg, or HBV pgRNA measured alone had a significantly lower AUC than the combined measurement of the three indices(0. 845/0. 741/0. 773 vs 0. 913, allP< 0. 001), and the patients with a value of < 9. 7 could achieve complete response at week 48 of treatment.Conclusion Combined measurement of serum HBV cccDNA, HBsAg, and HBV pgRNA has a good value in predicting the treatment outcome ofHBeAg-positive CHB patients treated with ETV.

Objective To investigate the genotype distribution of chronic hepatitis B virus(HBV) infection patients with different disease spectrums in Sichuan, China, as well as the association of genotypes with cellular immunity and coagulation function.Methods A total of543 patients with chronic HBV infection who were hospitalized in Chengdu Public Health Medical Center from January 2015 to June 2017 were enrolled, among whom there were 31 chronic HBV carriers, 285 patients with chronic hepatitis B(CHB), 77 patients with severe hepatitis B, 81 patients with hepatitis B cirrhosis, and 69 patients with hepatocellular carcinoma(HCC). Blood samples were collected; gene microarray was used to determine the genotypes of HBV DNA, and T lymphocyte subsets and coagulation function were measured. An analysis of variance was used for comparison of continuous data between multiple groups, and the SNK-qtest was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups.Results Among the 543 patients with chronic HBV infection, 400(73.66%) had type B infection, 123(22.65%) had type C infection, 10(1.84%) had mixed type B and C infection, and 10(1.84%) had mixed type C and D infection. There were no significant differences in the distribution of HBV genotypes,prothrombin time, and prothrombin activity in different disease spectrums between the patients with type B infection and those with type C infection(allP> 0. 05). According to the results of T lymphocyte subsets, in the severe hepatitis B group, the patients with type C infection had higher percentages of CD3+and CD3+CD4+T cells than those with type B infection; in the chronic hepatitis B group, the patients with type C infection had a higher percentage of CD3+CD8+T cells than those with type B infection; in the chronic HBV carrier group, severe hepatitis B group, and hepatitis B cirrhosis group, the patients with type C infection had a higher CD4+/CD8+ratio than those with type B infection; in the hepatitis B cirrhosis group, the patients with type C infection had lower percentages of CD3+, CD3+CD4+, and CD3+CD8+T cells than those with type B infection; in the HCC group, the patients with type C infection had lower percentages of CD3+, CD3+CD4+, and CD3+CD8+T cells and a lower CD4+/CD8+ratio than those with type B infection, with significant differences in the percentages of CD3+CD4+T cells(t =2.078,P= 0. 041) and CD3+CD8+T cells(t =6.672,P< 0. 001) between the patients with type C in-fection and those with type B infection in the hepatitis B cirrhosis group.Conclusion Types B and C are the main genotypes of chronicHBV infection in different disease spectrums in Sichuan, with type B more commonly seen than type C, and there is no difference in the dis-tribution of HBV genotypes between patients with different disease spectrums. Disorder of cellular immune function is observed in patientswith chronic HBV infection, with different immune disorders in different stages of infection, and the genotype of infection is not associatedwith coagulation function and cellular immune function.

Objective To investigate the association between T-lymphocyte phenotype and immune status in chronic hepatitis B(CHB)and its application value.Methods A total of 77 CHB patients who attended The First Hospital of Lanzhou University from January 2015 to May 2019 were enrolled, and according to the status of HBeAg and the serum levels of alanine aminotransferase(ALT), HBsAg, and HBV DNA, they were divided into immune tolerance group and non-immune tolerance group. The laboratory results of T-lymphocyte phenotype, HBV serological test, HBV DNA load, routine blood test, and liver function were obtained, and aspartate aminotransferase-to-platelet ratio index(APRI) and fibrosis-4(FIB-4) were calculated. Thettest was used for comparison of normally distributed continuous data between two groups; and the Mann-WhitneyUtest was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups. Spearman correlation analysis was used to test the correlation effect between the two variables. The diagnostic efficacy of Treg, CD8+PD-1+T lymphocyte percentage and CD8+CD45 RO+T lymphocyte percentage were evaluated by AUC.Results Compared with the non-immune tolerance group, the immune tolerance group had significantly higher percentages of Treg and CD8+PD-1+T cells(U= 12. 0 and 59. 0,P< 0. 001,P= 0 013) and significantly lower percentages of CD3+CD8+T cells and CD8+CD45 RO+T cells(U= 50. 0 and 38. 5, bothP< 0. 05). Compared with the high HBV DNA load group, the low HBV DNA load group had significantly lower percentages of Treg and CD8+PD-1+T cells(U= 178 5 and 255.0,P= 0. 003 and 0. 018) and significantly higher percentages of CD3+T cells and CD8+CD45 RO+T cells(U= 104. 0 and1495,P= 0. 033 and 0. 025). APRI was negatively correlated with the percentage of Treg(r=-0. 379,P= 0. 013), and FIB-4 was negatively correlated with the percentages of CD3+CD4+, CD3+CD8+, CD4+CD45 RO+, and CD8+CD45 RO+T cells(r=-0. 259,-0. 275,-0. 233, and-0. 229,P= 0. 023, 0. 016, 0. 041, and 0. 045). Treg, CD8+PD-1+T cells, and CD8+CD45 RO+T cellshad an area under the ROC curve of 0. 793(95% confidence interval [CI]: 0. 651-0. 936), 0. 802(95% CI: 0. 678-0. 927), and0. 816(95% CI: 0. 706-0. 927), respectively, in evaluating immune status.Conclusion There are various T-lymphocyte phenotypesin patients with chronic HBV infection, and different T lymphocytes have different abilities to eliminate HBV. Detection of T-lymphocytephenotype helps to understand the immune status and adjust the immune function in CHB patients and can provide a reference for the func-tional cure of CHB patients.

Objective To investigate the effect of microRNA-18 a(miRNA-18 a) on the regulatory immune function in patients withchronic hepatitis B(CHB) through the PPARα/γ signaling pathway.Methods A total of 98 CHB patients and 96 patients without hepatitisB, who were treated in Air Force Special Medical Center(formerly known as General Air Force Hospital, PLA) from April 2017 to October2018, were enrolled as experimental group and control group, respectively. There were no significant differences in age and sex between thetwo groups(P> 0. 05). RT-PCR was used to measure the relative mRNA expression of miRNA-18 a in serum; flow cytometry was usedto measure the expression of miRNA-18 a in peripheral blood mononuclear cells(PBMCs); ELISA was used to observe the effect of miRNA-18 a on the frequency of CD4+CD25+regulatory T(Treg) cells; Western blot was used to measure the expression of proteins associatedwith the PPARα/γ signaling pathway. PBMCs were further divided into si-miRNA-18 a inhibitor group(transfected with si-miRNA-18 a inhibitor) and si-miRNA-18 a normal control group(transfected with si-miRNA-18 a plasmid); flow cytometry was used to investi-gate the effect of miRNA-18 a inhibition on the frequency of CD4+CD25+Treg cells, and Western blot was used to measure the expressionof proteins associated with the PPARα/γ signaling pathway. Thet-test was used for comparison of normally distributed continuous data between two groups, and a Pearson correlation analysis was performed to investigate the correlation between miRNA-18 a expression and pro-teins associated with the PPARα/γ signaling pathway.Results Compared with the control group, the experimental group had significantlyupregulated mRNA expression of miRNA-18 a in serum and liver tissue(t= 9. 634 and 9. 863, bothP< 0. 01). The experimental grouphad a significantly higher frequency of CD4+CD25+Treg cells than the control group(t =9.854,P< 0. 01). Compared with the controlgroup, the experimental group had significantly upregulated levels of interferon-γ and interlukin-9(t =8. 235 and 8. 382, bothP<0. 05). Compared with the control group, the experimental group had significantly upregulated expression of PPARα and PPARγ （t =4. 229 and 3. 545, bothP< 0. 05). Compared with the si-miRNA-18 a normal control group, the si-miRNA-18 a inhibitor group had a signifi-cantly lower percentage of peripheral blood CD4+CD25+Treg cells among CD4+T cells(t =3.968,P< 0. 01). Compared with the si-miRNA-18 a normal control group, the si-miRNA-18 a inhibitor group had significantly lower expression of PPARα and PPARγ （t =5. 023 and 4. 983, bothP< 0. 05). miRNA-18 a was positively correlated with the protein expression of PPARα and PPARγ in thePPARα/γ signaling pathway(r= 0. 701 and 0. 682, bothP< 0. 05).Conclusion miRNA-18 a may affect the regulatory immune functionin CHB patients by activating the PPARα/γ signaling pathway and thus upregulate the frequency of cell surface factors and cytokine secretionlevels associated with immune function.

Objective To investigate the value of globulin-platelet(GP) model in the diagnosis of liver fibrosis in patients with chronic hepatitis B virus(HBV) infection and alanine aminotransferase(ALT)<2 ×upper limit of normal(ULN).Methods A retrospective analysis was performed for the clinical data of 659 patients with chronic HBV infection who underwent liver biopsy in The Second Affiliated Hospital of Anhui Medical University from January 2010 to December 2018 and had an ALT level of <2 ×ULN. Based on the results of liver biopsy, the patients were divided into marked liver fibrosis(S≥2) group, severe liver fibrosis(S≥3) group, and liver cirrhosis(S4)group. The levels of globulin and platelets were measured to calculate the value of GP model, the receiver operating characteristic(ROC)curve was used to evaluate the clinical value of GP model in the diagnosis of liver fibrosis, and the GP model was compared with aspartate aminotransferase to platelet ratio index(APRI) and fibrosis-4(FIB-4). An analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the Kruskal-WallisHtest was used for comparison of non-normally distributed continuous data between multiple groups; the chi-square test was used for comparison of categorical data between multiple groups; a Spearman correlation analysis was used to investigate the correlation between noninvasive models and liver fibrosis stage.Results There was a significant difference in the value of GP model between the patients with different degrees of liver fibrosis (χ2= 126. 960,P< 0. 001). The value of GP model gradually increased with the aggravation of liver fibrosis, suggesting that the value of GP model was positively correlated with the degree of liver fibrosis(r =0.401,P< 0. 01). Globulin, APRI score, and FIB-4 index were positively correlated with the degree of liver fibrosis(r =0. 125, 0. 452, and 0. 414, allP<0. 01), and platelet was negatively correlated with the degree of liver fibrosis(r =-0.390,P<0. .="" gp="" model="" had="" similar="" areas="" under="" the="" roc="" curve="" to="" apri="" score="" and="" fib-4="" index="" in="" diagnosis="" of="" marked="" liver="" severe="" 0.834="" vs="" 0.824="" allp="">0. 05).Conclusion For patients with chronic HBV infection and ALT < 2 × ULN, GP model is a simple and accurate noninvasive assessment model forliver fibrosis, with a similar clinical value to APRI score and FIB-4 index.

Objective To investigate the influence of different virologic responses on long-term survival rate and incidence rate of liver cancer in patients with decompensated hepatitis B cirrhosis.Methods A total of 378 patients with decompensated hepatitis B cirrhosis who were admitted to The Affiliated Hospital of Xuzhou Medical University from September 2010 to September 2016 were enrolled, and according to whether HBV DNA was continuously undetectable during antiviral therapy, they were divided into sustained virologic response group with 243 patients and non-sustained virologic response group with 135 patients. The patients were stratified according to the application of different antiviral drugs. Baseline data were recorded and the patients were followed up to the occurrence of end events or study endpoint to record death and hepatocellular carcinoma(HCC). The independent samplest-test was used for comparison of normally distributed continuous data between two groups, and the Mann-WhitneyUtest was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used to compare survival rates between groups.Results Compared with the non-sustained virologic response group, the sustained virologic response group had a significantly lower 5-year cumulative incidence rate of HCC(7.4% vs19.3%,χ2 =10.627,P= 0. 001) and a significantly higher 5-year transplant-free survival rate(93. 4% vs 80. 7%,χ2 =12.594,P<0.001). For the sustained virologic response group, there were no significant differences between the entecavir group and the non-entecavir group in the 5-year transplant-free survival rate(94.7% vs 90.2%,χ2 =1.122,P= 0. 290) and the 5-year cumulative incidence rate of liver cancer(6.4 % vs 9.7%,χ2 =0.552,P= 0. 458). For the non-sustained viral response group, there were also no significant differences between the entecavir group and the non-entecavir group in the 5-year transplant-free survival rate(78. 4% vs 82. 8%,χ2 =1.526,P= 0. 217) and the 5-year cumulative incidence rate of liver cancer(21. 5% vs 17. 1%,χ2 =1.844,P= 0. 174).Conclusion Antiviral therapy can improve the prognosis of patients with decompensated hepatitis B cirrhosis, and sustained virologic response can reduce the incidence rate of liver cancer and prolong survival time.

Objective To investigate the effect of hepatocyte transplantation(HCT) in the treatment of rats with liver cirrhosis and small-for-size syndrome(SFSS).Methods A total of 40 male Sprague-Dawley rats were given subcutaneous injection of carbon tetrachloride and oral administration of alcohol to establish a rat model of liver cirrhosis, among which 30 were randomly selected and divided into group A(hepatocyte transplantation on day 3 before surgery), group B(hepatocyte transplantation during surgery), and group C(no hepatocyte transplantation), with 10 rats in each group. All rats were given the resection of 70% of the liver, and the groups were compared in terms of survival rate, blood biochemistry at different time points, and change in liver pathological section based on HE staining. An analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant differencet-test(for data with homogeneity of variance) or the Games-Howell test(for data with heterogeneity of variance) was used for further comparison between two groups; the log-rank test was used for comparison of survival rate.Results Group A had a significantly higher postoperative survival rate than groups B and C [90%(9/10) vs 50%(5/10) and 30%(3/10）,χ2= 6. 440,P= 0. 04]. For groups A, B, and C at/L,904.6 ±35.6 U respectively(F =6.808,P=0. 007), the meal level of aspartate aminotransferase(AST) was 896. 3 ± 44. 7 U/L, 923. 8 ± 31. 6 U/L, and950.0 ±16.3 U/L, respectively(F= 3. 666,P= 0. 047), and the mean level of albumin(Alb) was 25. 6 ± 0. 5 g/L, 24. 8 ± 0. 6 g/L,and 23.4 ±0.4 g/L, respectively(F =26.577,P< 0. 001); group A tended to have better recovery than groups B and C, while some/L,128.2 ±20.7 U/L, and 150.5 ±14.8 U/L, respectively(F =13.816,P= 0. 001), the mean level of AST was 108. 7 ± 10. 8 U/L, 142 0±14.1 U/L, and 161.0 ±21.2 U/L, respectively(F =17.220,P< 0. 001), and the mean level of Alb was 29. 1 ± 0. 6 g/L, 28. 0 ± 0 2 g/L, and 27.0 ±0.2 g/L, respectively(F =15.629,P= 0. 001), with significant differences between the three groups. At 72 hours after surgery, liver histopathological examination showed disappearance of hepatic cord, massive hepatocyte necrosis, and inflammatory cell infil-tration in group C, while group A only had balloon-like lesions, punctate cell necrosis, and a small amount of inflammatory cell infiltra-tion.Conclusion Hepatocyte transplantation can effectively promote liver function recovery and improve survival rate of rats with liver cir-rhosis and SFSS, and its therapeutic effect is associated with the time point of transplantation.

Objective To investigate the changes in the diversity and structure of intestinal flora in patients with primary liver cancer after transcatheter arterial chemoembolization(TACE).Methods A total of 65 patients with primary liver cancer(among whom 20 received TACE) who were treated in The Affiliated Tumor Hospital of Guangxi Medical University from September 2018 to January 2019 were enrolled,and 27 individuals who underwent physical examination were enrolled as healthy group. High-throughput 16 S rDNA sequencing was used to analyze the structure of fecal bacterial communities, and Anosim, LEfSe software, and R language stats package were used to analyze the differences in the relative abundance, diversity, community, and evolutionary branching of intestinal flora between groups. Thet-test was used for comparison of normally distributed continuous data with homogeneity of variance between groups, and the Kruskal-WallisUtest was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The Spearman rank correlation test was used for correlation analysis.Results At the phylum level, the dominant bacteria were Bacteroidetes and Firmicutes in each group, which accounted for > 90% in the healthy group and > 80% in the primaryliver cancer group and the TACE treatment group. Bacteroidetes accounted for 48. 44%, 44. 96%, and 48. 60%, respectively, in thehealthy group, the primary liver cancer group, and the TACE treatment group, and Firmicutes accounted for 47. 09%, 38. 15%, and33. 93%, respectively, in the three groups, suggesting that the primary liver cancer group had significantly lower relative abundance ofBacteroidetes and Firmicutes than the healthy group; in addition, the primary liver cancer group and the TACE treatment group had signifi-cantly higher relative abundance of Proteobacteria and Fusobacteria than the healthy group; although there were changes in the other phyla ofbacteria, these bacteria accounted for < 0. 5%. Compared with the primary liver cancer group, the healthy group had significantly higher a-bundance and ACE value of observed species(abundance: 264 ± 47 vs 230 ± 64,t =2.499,P= 0. 014; ACE value: 284. 11 ± 50. 82 vs252. 96 ± 67. 58,t =2.158,P= 0. 034). The rank between the primary liver cancer group and the healthy group was higher than that ineach of the two groups(R > 0), so the difference in the structure of intestinal flora between the two groups was significantly greater than thatwithin each of the two groups(P< 0. 05). The rank between the pre-TACE group and the post-TACE group was lower than that in thepre-TACE group(R < 0), so the difference in the structure of intestinal flora within the pre-TACE group and the post-TACE group wasgreater than that between the two groups(P> 0. 05). In the patients with primary liver cancer, intestinal opportunistic pathogens were cor-related with Child-Turcotte-Pugh(CTP) score, total bilirubin(TBil), alanine aminotransferase(ALT), and aspartate aminotransferase(AST)(r= 0. 245, 0. 421, 0. 327, and 0. 446,P =0. 049,P< 0. 001,P =0. 008, andP< 0. 001), and potential probiotics were corre-lated with CTP score, TBil, albumin, ALT, and AST(r=-0. 314,-0. 490, 0. 285,-0. 374, and-0. 528,P= 0. 011,P <0.001,P=0.022,P= 0. 002, andP< 0. 001). The abundance of the opportunistic pathogens among the differentially expressed bacteria increasedwith the increase in Child-Pugh class for liver function, and the patients with class C liver function had higher abundance than those withclass A or B liver function(Z =4. 301 and 4. 063,P =0. 038 and 0. 044). The relative abundance of potential probiotics tended to decreasewith the increase in Child-Pugh class for liver function, and the patients with class C liver function had lower abundance than those withclass A liver function(Z =3.882,P= 0. 049).Conclusion There are differences in the diversity and structure of intestinal flora betweenpatients with primary liver cancer and healthy individuals, and the patients with primary liver cancer have similar intestinal flora before andafter TACE, suggesting that TACE has little influence on intestinal flora. Intestinal dysbacteriosis is associated with the clinical classificationof primary liver cancer, and the degree of intestinal dysbacteriosis increases with the increase in Child-Pugh class for liver function, with areduction in potential probiotics and an increase in opportunistic pathogens.

Objective To investigate the expression and clinical value of coiled-coil domain-containing protein 34(CCDC34) in hepatocellular carcinoma(HCC), and to predict the role of CCDC34 in the development and progression of HCC.Methods The datasets of HCC were downloaded from The Cancer Genome Atlas(TCGA) to obtain the expression profile and clinical information of the CCDC34 gene. The bioinformatics method was used to analyze the expression of CCDC34 in HCC, its correlation with clinicopathological parameters, and its influence on prognosis. The gene set enrichment analysis(GSEA) was used to predict the possible pathways regulated by the CCDC34 gene in HCC. The independent samplest-test and the pairedt-test were used for comparison of continuous data between two groups; the Kaplan-Meier method and the log-rank test were used for survival analysis; the Cox proportional-hazards regression model analysis was used to investigate the influencing factors for prognosis.P< 0. 01 was the standard for judging significant enrichment in GSEA, and the false discovery rate was <0.05.Results In TCGA database, CCDC34 was highly expressed in tumor tissue, and there was a significant difference in the expression of CCDC34 between patients with different TNM stages and tumor grades(t =2. 118 and 3. 622,P= 0. 035 andP< 0. 001). The patients with high expression of CCDC34 had a significantly shorter overall survival time than those with low expression （χ2 =21.716,P<05). The multivariate Cox regression analysis showed that the expression of CCDC34(HR =2. 287,95%CI:1. 312-3. 987)and TNM stage(HR =1.943,95%CI:1.101-3.429) were independent risk factors for the overall survival time of patients with HCC(allP< 0. 05).The enrichment of 8 pathway gene sets, including base excision repair and spliceosome, was observed in the samples with high expression of CCDC34(P< 0. 01, FDR < 0. 05).Conclusion CCDC34 may play a vital role in the development and progression of HCC and thus become a new prognostic indicator and a potential therapeutic target.

Objective To investigate the efficacy and safety of regional citrate anticoagulation(RCA) in patients with severe liver diseasesand acute kidney injury(AKI) receiving continuous renal replacement therapy(CRRT).Methods A retrospective analysis was performedfor the medical records and first-time CRRT data of 175 liver disease patients with AKI(liver disease group) and 285 non-liver diseasepatients with AKI(non-liver disease group) who underwent RCA-CRRT in Beijing You' an Hospital and Beijing Friendship Hospital,Capital Medical University, from January 2016 to March 2019. The two groups were compared in terms of the changes in hepatic and renalfunction markers, blood gas parameters, lactic acid, ionized calcium(iCa2+), and total calcium(tCa2+) after treatment, as well as themean operation life of filter and adverse reactions. The pairedt-test or the independent samplest-test was used for comparison of normallydistributed continuous data between two groups, and the Mann-WhitneyUtest was used for comparison of non-normally distributed contin-uous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier sur-vival curve was used to analyze the operation life of filter in the two groups, and the log-rank test was used for comparison.Results BeforeCRRT, the level of ALT、AST、TBil、BUN in liver disease group were significantly higher than those in non-liver disease group(allP<0. 05). After treatment, iCa2+, tCa2+, pH value, and base excess basically returned to normal, and there were significant differences inthe same group before and after treatment(allP< 0. 05). Compared with the non-liver disease group, the liver disease group had a signifi-cantly higher incidence rate of citrate accumulation(tCa2+/iCa2+>2. 5) during treatment(12% vs 2. 2%,χ2 =18.65,P< 0. 001).There was no significant difference in the mean operation life of filter between the liver disease group and the non-liver disease group(32. 20 ± 24. 99 h vs 32. 96 ± 18. 93 h,t =0.346,P> 0. 05) and there was also no significant difference in the 48-hour survival rate withfilter between the two groups(28. 1% vs 26. 9%,χ2 =1.356,P= 0. 381). No adverse reaction associated with citrate accumulation wasobserved.Conclusion In patients with severe liver diseases, although RCA used in CRRT may induce a high incidence rate of citrate accu-mulation, it can achieve a satisfactory anticoagulant effect and is relatively safe.

Objective To investigate the pathological and biochemical features of each pathological subtype of bile duct injury type of drug-induced liver injury(DILI), and to verify the value and significance of pathological classification of DILI.Methods A retrospective analysis was performed for the clinical data of 112 patients with bile duct injury type of DILI who were admitted to Shijiazhuang Fifth Hospital from January 2006 to January 2016 and China-Japan Friendship Hospital from October 2003 to June 2014. According to the pathological subtype, the patients were divided into mixed hepatitis group with 40 patients, cholestatic hepatitis group with 40 patients, and simple cholestasis group with 32 patients, and the three groups were compared in terms of types of drugs used, course of disease, R value, and peak values,changing trend, time to peak, and recovery time of liver biochemical indices. The independent-samples Kruskal-WallisHtest was used for comparison of continuous data between multiple groups, and the Mann-WhitneyUtest was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups.Results Among the drugs inducing DILI, traditional Chinese medicine and Western medicine each accounted for half of the cases of bile duct injury type of DILI. Traditional Chinese medicine mainly included the drugs for osteoarthropathy, intervertebral disc bulge, alopecia, calculus-removing and cholagogic treatment,Yang-tonifying therapy, and skin diseases; 26 patients(65%) in the cholestatic hepatitis group had DILI caused by traditional Chinese medicine, while 16 patients(40%) in the mixed hepatitis group and 13(40.6%) in the simple cholestasis group had such DILI. Antibiotics and antipyretic and analgesic drugs were the most common Western medicines for DILI. The mixed hepatitis group had the highest peak values of ALT and AST and R value, followed by the cholestatic hepatitis group and the simple hepatitis group （χ2 =54. 77, 44. 21, and5195, allP< 0. 001), and there were no significant differences in the peak values of the other liver biochemical parameters between the three groups(allP> 0. 05). In the mixed hepatitis group and the cholestatic hepatitis group, the time to peak of TBil was longer than that of ALT. There were no significant differences in course of disease, time to peak of liver biochemical parameters, and recovery time between the three groups(allP> 0. 05).Conclusion Each subtype of bile duct injury type of DILI has unique clinical and biochemical features,and an understanding of such features may help to accurately judge clinical typing, pathological changes of targets, and degree of injury.

Objective To investigate the clinical features of patients with sepsis-induced cholestatic jaundice and the risk factors for death.Methods A retrospective analysis was performed for the clinical data of 139 patients with sepsis-induced cholestatic jaundice who were admitted to Surgical Intensive Care Unit, Critical Care Medicine Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, from August 2011 to August 2019, and the patients were divided into survival group with 62 patients and death groupwith 77 patients. Age, sex, Acute Physiology and Chronic Health Evaluation II(APACHEII) score, and infection sites were recorded; re-lated laboratory data at five time points were recorded, including total bilirubin(TBil), direct bilirubin(DBil), indirect bilirubin(IBil),prothrombin time(PT), international normalized ratio(INR), aspartate aminotransferase(AST), alanine aminotransferase(ALT), whiteblood cell count(WBC), neutrophils(NEU), procalcitonin(PCT), and lactic acid(Lac); the peak values of TBil, DBil, and IBil werealso recorded, as well as duration of use of vasoactive agent, duration of mechanical ventilation, number of times of artificial liver plasma ex-change, length of stay in the intensive care unit(ICU), Child-Pugh class, and jaundice grade. The independent samplest-test was usedfor comparison of normally distributed continuous data with homogeneity of variance between groups, and the Mann-WhitneyUtest wasused for comparison of non-normally distributed continuous data with heterogeneity of variance between groups; the chi-square test wasused for comparison of categorical data between groups; a binary logistic regression analysis was used to investigate the risk factors for death.Results The mortality rate of patients with sepsis-induced cholestatic jaundice was 55. 4%. Compared with the death group, the survivalgroup had significantly lower levels of TBil, DBil, and IBil on days 14, 21, and 28 and significantly lower peak values of TBil, DBil, andIBil(TBil:Z=-3. 230,-8. 197, and-9. 281,t=-5. 371, allP< 0. 01; DBil:Z=-4. 708,-8. 633,-9. 579, and-8. 238,P< 0. 01; IBil:Z=-2. 402,-6. 522,-8. 113, and-5. 300, allP< 0. 01). The survival group had a higher proportion of patients withmoderate jaundice, while the death group had a higher proportion of patients with severe jaundice （χ2 =57.633,P< 0. 01). Compared withthe death group, the survival group had significantly lower PT and INR at all time points(at diagnosis and on days 7, 14, 21, and 28)(PT:Z=-3. 173,-3. 467,-2. 660,-2. 261, and-3. 120, allP< 0. 05; INR:Z=-3. 141,-2. 754,-3. 230,-2. 560, and-3. 229, allP< 0. 05) and significantly lower levels of AST on days 7, 14, 21, and 28(Z=-2. 484,-3. 200,-3. 298, and-4. 277, allP< 0. 05) and ALT on days 14, 21, and 28(Z=-2. 635,-2. 667, and-4. 656, allP< 0. 01). Compared with thedeath group, the survival group had significantly lower levels of WBC and NEU on days 7, 14, and 21(WBC:Z=-3. 229,-2. 987, and-4. 537, allP< 0. 01; NEU:t =-3.332,Z=-3. 107 and-4. 485, allP< 0. 01), as well as significantly lower PCT at diagnosis andon days 14, 21, and 28(Z =-4. 844,-2. 215,-2. 869, and-7. 442, allP< 0. 05) and Lac at all time points(at diagnosis and ondays 7, 14, 21, and 28)(Z=-4. 316,-2. 913,-3. 068,-8. 578, and-9. 341, allP< 0. 01). Compared with the death group, thesurvival group had significantly shorter duration of use of vasoactive agent(Z=-6. 421,P< 0. 01), duration of mechanical ventilation(Z =-2.005,P< 0. 05), duration of artificial liver(Z =-4.822,P< 0. 01), and length of stay in the ICU(t =-3.005,P< 0. 01).TBil(odds ratio [OR] = 0. 959, 95% confidence interval [ CI]: 0. 929-0. 991,P< 0. 05), DBil( OR = 1. 056, 95% CI: 1. 009-1. 105,P< 0. 05), IBil(OR = 1. 071, 95% CI: 1. 006-1. 140,P< 0. 05), WBC on day 7(OR = 31. 365, 95% CI: 2. 878-41. 761,P< 0. 05), WBC on day 14(OR = 5. 859, 95% CI: 1. 073-31. 999,P< 0. 05), NEU on day 7(OR = 0. 007, 95% CI: 0. 003-0. 409,P< 0. 05), NEU on day 14(OR = 0. 132, 95% CI: 0. 023-0. 765,P< 0. 05), PCT at diagnosis(OR = 1. 062, 95% CI: 1. 017-1. 110,P< 0. 05), PCT on day 7(OR = 0. 920, 95% CI: 0. 855-0. 990,P< 0. 05), PCT on day 28(OR = 12. 711, 95% CI: 3. 532-45. 745,P< 0. 05), duration of use of vasoactive agent(OR =1. 657, 95% CI: 1. 337-2. 053,P<0. 05), duration of mechanical ventilation(OR =0. 783, 95% CI: 0. 634-0. 967,P<0. 05), and duration of artificial liver(OR =1. 534, 95% CI: 1. 065-2. 208,P<0. 05) were independ-ent risk factors for death in patients with sepsis-induced cholestatic jaundice.Conclusion Patients with sepsis-induced cholestatic jaundicehave a high mortality rate. The survival group has significantly lower levels and peak values of bilirubin than the death group in the middle andlate stages of the disease, and there is a higher proportion of patients with moderate jaundice in the survival group and a higher proportion of pa-tients with severe jaundice in the death group. Compared with the death group, the survival group has significantly lower degree of coagulationdisorder, levels of AST and ALT, infection indices WBC, NEU, and PCT, and perfusion index Lac. Compared with the death group, the sur-vival group has significantly better duration of use of vasoactive agent, duration of artificial liver support, duration of mechanical ventilation,and length of stay in the ICU. Bilirubin levels, infection indices WBC, NEU, and PCT, vasoactive agent, duration of mechanical ventilation,and duration of artificial liver support are independent risk factors for death in patients with sepsis-induced cholestatic jaundice.

Objective To investigate the serotype and virulence genes of Klebsiella pneumoniae capsule for in-hospital liver abscess, as well as the homology of these strains.Methods A total of 26 non-repetitive strains of Klebsiella pneumoniae isolated from the patients with liver abscess in The First Affiliated Hospital of Jiamusi University from October 2018 to October 2019 were collected. These strains were identified to be Klebsiella pneumonia by Vitek-2 Compact automatic microbiological analyzer. The string test was performed for these strains; PCR was used to determine the major capsular serotypes and related virulence genes; multi-locus sequence typing was used to analyze the homology of the strains. The Fisher's exact test was used for comparison of categorical data between groups.Results The positive rate of all 26 strains of Klebsiella pneumoniae was 100% in the string test, with 17 strains of K1 type,5 strains of K2 type,1 strain of K5 type,1 strain of K57 type,and 2 strains with unknown serotype. The virulence genes rmpA, aero, and ureA had a positive rate of 100%(26/26); uge and mrkD had a positive rate of 96.2%(25/26); fimH had a positive rate of 80.8%(21/26); iucB had a positive rate of 73.1%(19/26); wcaG, magA,and kfu had a positive rate of 65.4%(17/26); allS had a positive rate of 61.5%(16/26); kpn had a positive rate of 30.8%(8/26); iroNB had a positive rate of 7.7%(2/26). The cf29 a gene was not detected; wcaG, magA, and allS were only detected in K1 serotype; uge was not detected in K57 serotype. Multi-locus sequence typing found 17 trains with ST23 type, 3 strains with ST86 type, 2 strains with ST65 type, 2 strains with ST1934 type,1 strain with ST485 type, and 1 strain with ST592 type.Conclusion K1 and K2 serotypes are the main serotypes in the strains in this experiment, and ST23 type is the main sequence type for infection in our hospital.

Objective To investigate the protective effect of apigenin against H2O2-induced injury in human hepatocytes(L02).Methods L02 cells were treated with H2O2 to establish a model of oxidative injury. CCK-8 assay was used to measure cell viability; DCFH-DA was used to measure the production of reactive oxygen species(ROS) in cells; test kits were used to measure the activities of lactate de-hydrogenase(LDH), malondialdehyde(MDA), and superoxide dismutase(SOD) in cell supernatant; Hoechst staining was performed toobserve cell apoptosis, and a test kit was used to observe the activity of caspase-3. A one-way analysis of variance was used for compari-son of continuous data between multiple groups, and the LSD-ttest was used for further comparison between two groups.Results Apige-nin at a concentration of ≥20 μmol/L significantly inhibited the proliferation of L02 cells(P< 0. 01). Compared with the cells in the blankcontrol group, the cells treated with H2O2 at a concentration of ≥500 μmol/L had a significant reduction in cell viability(P< 0. 001), andtherefore, 500 μmol/L was determined as the optimal concentration for modeling. There was a significant difference in cell viability betweenthe model group and the blank control group(P< 0. 01), and compared with the model group, the 5 and 10 μmol/L apigenin groups had asignificant increase in cell viability(P< 0. 01). The cells in the blank control group had good morphology, while those in the model groupwere contracted and round-shaped and had marked rupture and deformity, and compared with the model group, the 5 μmol/L apigenin group showed significant improvement with a reduction in ruptured and round-shaped cells. There was a significant difference in fluores-cence intensity between the blank control group, the model group, and the 5 μmol/L apigenin group(1. 00 ± 0. 26 vs 32. 94 ± 1. 29 vs13. 49 ± 1. 23,F= 1. 10,P< 0. 001), and the model group had a significantly higher fluorescence intensity than the blank control group(P< 0. 001). Compared with the model group, the 5 μmol/L apigenin group had a significant reduction in H2O2-induced ROS(P<0. 001). Compared with the control group, the model group had significant increases in the levels of LDH and MDA and a significant reduc-tion in the level of SOD(F= 3. 21, 2. 03, and 3. 32, allP< 0. 05), and compared with the model group, the 5 μmol/L apigenin group hadsignificant reductions in the levels of LDH and MDA and a significant increase in the level of SOD(allP< 0. 05). There was a significantdifference in cell apoptosis rate between the blank control group, the model group, and the 5 μmol/L apigenin group(7. 54% ± 0. 52% vs39. 77% ± 3. 44% vs 14. 40% ± 0. 79%,F =9.439,P< 0. 01], and the model group had a significantly higher cell apoptosis rate than thecontrol group(P< 0. 01); the cells treated with apigenin had a significantly lower apoptosis rate than those in the model group(P< 0. 01).There was a significant difference in the activity of caspase-3 between the blank control group, the model group, and the 5 μmol/L apigeningroup(4. 38 ±0. 59 U/mg vs 16. 44 ±1. 13 U/mg vs 10. 60 ± 1. 04 U/mg,F =1.17,P< 0. 05), and the model group had a significantlyhigher activity of caspase-3 than the blank control group(P< 0. 05); compared with the cells in the model group, the cells treated withapigenin had a significant reduction in the activity of caspase-3(P< 0. 05).Conclusion Apigenin may exert a protective effect againstH2O2-induced injury in L02 cells by eliminating ROS and reducing caspase-3 activity.

Objective To investigate the influencing factors for stent obstruction after endoscopic retrograde biliary drainage(ERBD) forrefractory common bile duct stones.Methods A total of 126 patients who underwent ERBD for refractory common bile duct stones inRenmin Hospital of Wuhan University from January 2014 to May 2019 and were readmitted for stent removal at 6 months after surgery wereenrolled, and according to the condition of stent removal, they were divided into obstruction group and unobstructed group. General data andrelated indices were compared between the two groups. The independent samplest-test was used for comparison of normally distributed con-tinuous data between groups, and the Mann-WhitneyUtest was used for comparison of non-normally distributed continuous data betweengroups; the chi-square test was used for comparison of categorical data between groups; a multivariate logistic regression analysis was usedto investigate the influencing factors for stent obstruction after surgery.Results Among the 126 patients, 28 were found to have stent ob-struction during removal, with a stent obstruction rate of 22. 2%. The univariate analysis showed that there were significant differences be-tween the two groups in white blood cell count(WBC), percentage of neutrophils(Neu%), alkaline phosphatase(ALP), gamma-glu-tamyl transpeptidase, leucine aminopeptidase, endoscopic sphincterotomy(EST), infection, aspirin, and stent type(allP< 0. 05). Themultivariate logistic regression analysis showed that WBC[OR(95% CI):1. 232(1. 033-1. 470)], Neu% [OR(95% CI):1. 263(1. 021-1. 562)], ALP[OR(95% CI):1. 013(1. 004-1. 022)], EST[ OR(95% CI):5. 890(1. 114-31. 139)], infection[ OR(95% CI):17. 317(1. 349-222. 349)], and stent type[OR(95% CI):0. 144(0. 022-0. 937)] were independent influencing factors for postopera-tive stent occlusion(allP< 0. 05).Conclusion Patients with elevated WBC/Neu%/ALP, intraoperative EST, and preoperative secondaryinfection have a high risk of postoperative stent obstruction, and close follow-up and early prevention should be performed for such patients.The double pigtail stent can effectively reduce the rate of postoperative stent obstruction.

Objective To screen out the key intergenic long non-coding RNAs(lncRNAs) in cholangiocarcinoma(CCA) and their association with patient prognosis.Methods CCA expression and clinical data were obtained from The Cancer Genome Atlas(TCGA). High-throughput gene expression data in GSE107943 dataset were obtained from the Gene Expression Omnibus(GEO). R software was used to analyze differentially expressed genes and determine significantly differentially expressed lncRNAs between tumor and normal samples, and the key lncRNAs were screened out. The receiver operating characteristic(ROC) curve was used to analyze the value of gene expression in the diagnosis of CCA; the Kaplan-Meier survival curves were used to analyze prognosis; Gene Set Enrichment Analysis(GSEA) was used to investigate significantly enriched pathways; quantitative real-time PCR was used to verify gene expression in clinical samples.Results A total of 451 upregulated lncRNAs and 154 downregulated lncRNAs in both TCGA and GSE107943 dataset were screened out. The lncRNA RP11-488 L18.10 in TCGA and GSE107943 dataset was highly abundant in tumor tissue. Based on TCGA and GSE107943 dataset, the ROC curve analysis of the association between lncRNA RP11-488 L18.10 expression and CCA showed that the expression of lncRNA RP11-488 L18.10 had an area under the ROC curve of 1 in TCGA(P< 0. 000 1) and 0. 9469 in GSE107943(P< 0. 000 1). In TCGA, the high expression of lncRNA RP11-488 L18.10 significantly predicted overall survival rate(P= 0. 016) and recurrence-free survival rate(P= 0. 017) in patients with CCA; in GSE107943, the high expression of lncRNA RP11-488 L18. 10 significantly predicted overall survival rate(P= 0. 023) and recurrence-free survival rate(P= 0. 005) in patients with CCA. LncRNA RP11-488 L18. 10 was significantly positively correlated with MCM2. Compared with the adjacent tissue, CCA tissue had high expression of lncRNA RP11-488 L18.10(P= 0.010) and MCM2(P= 0. 023).Conclusion LncRNA RP11-488 L18. 10 is closely associated with the development and prognosis of CCA and thus may become a target for the diagnosis and treatment of CCA.

Objective To investigate the association of nonalcoholic fatty liver disease( NAFLD) with the severity of acute pancreatitis(AP).Methods A total of 398 patients with AP who were admitted to The Affiliated Hospital of Southwest Medical University from January to August 2019 were enrolled, among whom there were 197 patients with mild acute pancreatitis(MAP), 151 patients with moderate-severe acute pancreatitis(MSAP), and 50 patients with severe acute pancreatitis(SAP). According to the presence or absence of NAFLD,these patients were divided into NAFLD group with 206 patients and non-NAFLD group with 192 patients. The two groups were compared in terms of the clinical features and prognosis, including baseline data, serological markers, etiology, complications, commonly used AP scores, length of hospital stay, and mortality rate. Thet-test or the Mann-WhitneyUtest was used for comparison of continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups; a logistic regression analysis was performed with the development of MSAP as the endpoint.Results There were significant differences between the two groups in age, proportion of male patients, body mass index, total cholesterol, triglyceride, Na+, white blood cell count, neutrophil count, blood glucose, and serum creatinine(allP< 0. 05), and compared with the non-NAFLD group, the NAFLD group tended to have a higher proportion of patients with abnormal glucose metabolism or abnormal lipid metabolism(P< 0. 05). There was a significant difference in etiological composition between the two groups(P< 0. 001), with the main etiology of hyperlipidemia in the NAFLD group1%) and biliary disease in the non-NAFLD group(57.8%). Compared with the non-NAFLD group, the NAFLD group had significantly higher proportion of patients with MSAP, RANSON score, and Balthazar score(allP< 0. 05), as well as significantly higher incidence rates of systemic inflammatory response syndrome(SIRS)(P< 0. 001), acute peripancreatic fluid collection （χ2 =15.820,P<0001), 2="6." and="" acute="" necrotic="" collection="" 0.="" .="" compared="" with="" the="" non-nafld="" nafld="" had="" a="" significantly="" higher="" risk="" of="" 30.="" vs="" 19.="" p="" incidence="" rate="" multiple="" organ="" 12.="" vs8.="">0. 05) and mortality rate(3. 4% vs 1. 2%,P> 0. 05). NAFLD, abnormal glucose metabolism, and lymphocyte count were in-dependent risk factors for MSAP(allP< 0. 05).Conclusion AP patients with NAFLD tend to develop SIRS and local complications of thepancreas and have a high disease grade, a poor prognosis, and a high risk of recurrence.

Objective To systematically evaluate the clinical effect of epidermal growth factor receptor( EGFR)-targeted agents in the treatment of advanced pancreatic cancer.Methods EMbase, PubMed, Cochrane Library, Clinical Trials, CNKI, Wanfang Data, and VIP were searched for randomized controlled trials(RCTs) of EGFR-targeted therapies for advanced pancreatic cancer. Eligible RCTs were screened out based on quality and related criteria, and RevMan 5.3 and STATA 12.0 were used to perform the meta-analysis.Results A total of 8 RCTs were included, with 2382 patients in total. The results of the meta-analysis showed that compared with the control group,the experimental group had no increases in overall survival time(hazard ratio [HR] =0.86, 95% confidence interval [CI]: 0.74-1.02,P> 0. 05) and objective response rate(risk ratio [RR] = 1. 00, 95% CI: 0. 76-1. 32,P> 0. 05), but had significant increases in progression-free survival time(HR =0.78, 95%CI: 0.62-0.98,P< 0. 05) and disease control rate(RR = 1. 22, 95% CI: 1. 04-1. 43,P< 0. 05). The subgroup analysis showed that after the source of heterogeneity was identified and the studies with high heterogeneity were excluded, the experimental group had a significant increase in overall survival time(HR =0. 85, 95%CI: 0. 77-0. 94,P< 0. 05), and the patients with rash appeared to be more sensitive to the therapies(HR =0.70, 95%CI: 0.54-0.92,P< 0. 05).Conclusion For patients with advanced pancreatic cancer, EGFR-targeted therapies can effectively prolong overall survival time and improve quality of life.

Objective To investigate the features and clinical data of different pathological types of Vater ampullary adenocarcinoma and the influencing factors for prognosis, and to improve the prognostic evaluation and treatment outcome of Vater ampullary adenocarcinoma after surgery.Methods A retrospective analysis was performed for the clinical data of 65 patients with Vater ampullary adenocarcinoma who were admitted to Nanjing First Hospital, namely Nanjing Hospital Affiliated to Nanjing Medical University, from January 2010 to January 2017,and the patients were divided into intestinal-type group, pancreaticobiliary-type group, and mixed-type group according to the results of HE staining. Immunohistochemistry was used to measure the expression of the tumor protein markers MUC1, MUC2, CK7, CK20, and CDX2 in the cancer tissue of various subtypes, and related clinical data and prognosis were compared and analyzed. The chi-square test was used for comparison of categorical data between groups; an analysis of variance was used for comparison of continuous data between groups; the Kaplan-Meier method was used to plot survival curves and calculate survival rates.Results Of all patients, 20 had intestinal type, 34 had pancreaticobiliary type, and 11 had mixed type. The results of immunohistochemistry showed that the intestinal-type group/5500% vs 2.94%/0/14.71%,χ2= 49. 916, 42. 178, and 9. 806, allP< 0. 01), and compared with the intestinal-type group, the pancreaticobiliary-type group had significantly higher positive rates of CK7(97. 06% vs 20. 00%, χ2 =34.665,P< 0. 01) and MUC1(94.12% vs 5.00%,χ2 =42.082,P< 0. 01). The patients in the mixed-type group often had co-expression of various tumor markers,and there were no significant differences in the positive expression of such markers between this group and the other two groups(allP>05). The comparison of clinical data between the three groups showed that there were no significant differences in age, sex, tumor tissue diameter, degree of tumor differentiation, and TNM stage between the patients with different subtypes(allP> 0. 05). The prognostic analysis showed that the median survival time after surgery in the three groups was 64. 00 months, 49. 50 months, and 56. 00 months, respective-ly. The results of comparison between groups showed that the intestinal-type group had significantly higher 5-year survival rate and 5-year disease-free survival rate than the pancreaticobiliary-type group(5-year survival rate: 60. 00% vs 32. 35%,χ2= 5. 206,P=0. 023; 5-year disease-free survival rate: 55. 00% vs 23. 53%,χ2 =6.140,P= 0. 013), and the mixed-type group had lower 5-yearsurvival rate and 5-year disease-free survival rate than the intestinal-type group but higher 5-year survival rate and 5-year disease-free survival rate than the pancreaticobiliary-type group(allP> 0. 05).Conclusion Different pathological subtypes of Vater ampullaryadenocarcinoma have different features of the expression of MUC1, MUC2, CK7, CK20, and CDX2, and combined measurement of thesefive tumor protein markers can better identify the pathological type of Vater ampullary adenocarcinoma and thus assist in prognostic evaluationand postoperative treatment.

Patients with chronic hepatitis B virus(HBV) infection with immune control generally have no or little liver damage, with a low incidence rate of adverse events, and spontaneous HBsAg seroclearance may occur in some patients. Most scholars do not recommend antiviral therapy for such patients in China and foreign countries. However, with the gradual aging of chronic HBV infection, patients with immune control are also faced with disease progression and the development of liver cirrhosis or liver cancer. This article introduces the clinical significance of appropriate timing of antiviral therapy for the prognosis of patients with chronic HBV infection with immune control.

Hepatic fibrosis is a reversible pathological reaction of the liver during the self-repair of various chronic liver injuries and can progress to liver cirrhosis and liver cancer. Pyroptosis is a new type of programmed cell death different from apoptosis and necrosis and is closely associated with the pathogenesis of hepatic fibrosis. This article reviews the latest research advances in the definition of pyroptosis,related activation pathways, and its role in hepatic stellate cells, hepatic parenchymal cells, Kupffer cells, and eosinophils, and it is pointed out that pyroptosis can induce liver inflammation, excessively activate hepatic stellate cells, and promote the development and progression of hepatic fibrosis, in order to provide new ideas and potential targets for clinical diagnosis and treatment.

Liver fibrosis is a chronic liver injury caused by various etiologies and a complex pathological change with the activation of hepatic stellate cells as the central link, and various signaling pathways are involved in the regulation of such complex lesions. It has the dual nature of repair and damage and may eventually progress to liver cirrhosis, liver failure, and even liver cancer. In recent years, rapid progress has been made in the basic research on the cell signal transduction pathways associated with liver fibrosis, and some achievements have been made in the research on the treatment strategy of liver fibrosis. This article briefly reviews the cell signaling pathways associated with the de-/STAT signaling pathway, the NF-κB signaling pathway, the MAPK signaling pathway, the Smad signaling pathway, the Wnt signaling pathway, the Hedgehog signaling pathway, and the Notch signaling pathway,and also introduces the potential therapeutic strategies for liver fibrosis at present.

Homocysteine(Hcy) has attracted more and more attention in the medical field since it was found to be closely associated with cardiovascular and cerebrovascular diseases, hypertension, diabetes, kidney diseases, skeletal system diseases, and even mental illnesses.In recent years, the application of Hcy in patients with liver fibrosis and liver cirrhosis has been taken more seriously by clinicians and researchers. This article reviews the recent research advances in the metabolic mechanism and pathophysiologic significance of Hcy in China and foreign countries and highlights the association of Hcy with liver fibrosis and liver cirrhosis and its possible mechanism.

As the prevalence rate of drug-induced liver injury increases year by year, the pathogenesis of drug-induced liver injury has become the focus of attention. As a large family, CYP450 enzymes participate in almost all oxidative metabolic reactions of drugs in the human liver. Recent studies have shown that CYP450 enzyme gene polymorphisms lead to the differences in pharmacodynamics between individuals, and therefore, exploring the role of CYP450 enzyme gene polymorphisms in drug-induced liver injury may promote the understanding of the pathogenesis of drug-induced liver injury. This article reviews the CYP450 enzyme polymorphisms that have been found to be associated with drug-induced liver injury.

The incidence rate of nonalcoholic fatty liver disease(NAFLD) is continuously increasing in the world, and NAFLD is a major cause of chronic liver disease in developed countries such as the United States and may become the most common chronic liver disease in China in the future. NAFLD is often observed in the obese population; however, it is also commonly seen in lean individuals. This article summarizes the latest studies on lean NAFLD and elaborates on the following pathogeneses of this disease: the change in single nucleotide polymorphism is one of the predisposing factors for NAFLD in the lean population; the change of gut microbiota and sarcopenia may induce a variety of metabolic disorders including hyperlipidemia, hyperuricemia, insulin resistance, and iron metabolic disorders, and such metabolic disorders may promote the development of NAFLD; in addition, unhealthy dietary habits and lifestyle may contribute to the accumulation of fat and increase the burden of the liver. The combined effect of these factors eventually lead to the development of NAFLD, but further studies are still needed to clarify the pathogenesis of lean NAFLD.

The incidence rate of nonalcoholic fatty liver disease(NAFLD) is gradually increasing in recent years, and the treatment of NAFLD is unsatisfactory due to the failure in lifestyle adjustment and a lack of effective drugs. Farnesoid X receptor(FXR), as the main bile acid receptor, may affect NAFLD by participating in glucose and fat metabolism, and intestinal FXR(iFXR) acts on the intestinal tract alone and may thus avoid the side effects of systemic release. Therefore, it may have potential value in the treatment of NAFLD, but there are also certain controversies. This article reviews the research advances in the role of iFXR in NAFLD.

Primary biliary cholangitis(PBC) is an autoimmune cholestatic liver disease with unknown etiology. Liver biopsy is an important diagnostic tool, but its clinical application is limited due to its invasiveness. Autoantibodies have special diagnostic and prognostic value for PBC, especially anti-mitochondrial antibodies and antinuclear antibodies, and each antibody has unique clinical significance. This article reviews the diagnostic and prognostic significance of autoantibodies associated with PBC and related research advances.

Primary biliary cholangitis(PBC) is an chronic progressive intrahepatic cholestasis autoimmune liver disease with unknown causes, and at present, the etiology and pathogenesis of PBC remain unclear. Nuclear receptor is a ligand-dependent transcription factor superfamily that regulates cell growth and differentiation by establishing a relationship between signal molecules and transcriptional responses.The human nuclear receptor family consists of 48 members, including peroxisome proliferator-activated receptors, pregnane X receptor,constitutive androstane receptor, liver X receptors, farnesoid X receptor, vitamin D receptor, and glucocorticoid receptor, which have attracted wide attention. These nuclear receptors regulate the key enzymes and transporter genes of bile acid metabolism at the transcriptional level and thus regulate the level of bile acid in the body and participate in inflammatory response. Bile acid metabolism disorder and persistent inflammation may be the key factors for the development and progression of PBC. This article reviews the research advances in nuclear receptors in the development and progression of PBC, in order to provide a theoretical basis for exploring the pathogenesis of PBC and new therapeutic targets.

The incidence rate of primary liver cancer continues to increase around the world, with a younger age of onset and poorer prognosis. As the most classic regulator of cell polarity and density, mechanical signal transduction, cell proliferation, and organ development, the Hippo pathway can promote the development and progression of various cancers including primary liver cancer. YAP, a classic nuclear effector of the Hippo pathway, is significantly upregulated in primary liver cancer and promotes the development of drug resistance. This article aims to investigate the association of the dysregulation of the Hippo signaling pathway with the development and progression of primary liver cancer and analyzes the mechanism of action of the Hippo signaling pathway in the drug resistance of primary liver cancer as an early event of the development of primary liver cancer, which is of great significance for exploring new treatment strategies for primary liver cancer.

As the first-line drug for the treatment of primary liver cancer, sorafenib has been widely used in clinical practice, but its drug resistance and toxic and side effects have become increasingly apparent, along with limited efficacy. In recent years, the research on regorafenib for the treatment of hepatocellular carcinoma(HCC) has gradually become a hotspot. The RESORCE trial has shown that regorafenib can significantly extend the overall survival time of patients with failed sorafenib treatment to 10.6 months, and regorafenib was approved as a second-line drug for advanced HCC by Food and Drug Administration in 2017. This article reviews the molecular mechanism, efficacy evaluation, combination therapy, and criteria for patient selection in the treatment of HCC with regorafenib, so as to provide a direction for further research in the future.

The prognosis of hepatocellular carcinoma(HCC) is closely associated microvascular invasion(MVI), and in recent years, more and more clinical studies have been conducted on MVI, but there are few articles on the development of basic pathology and related controversies. As the basis of clinical research, it is of great significance to understand the definition of MVI and the controversy over pathological grading. With reference to related articles, this article reviews the development history of the definition of MVI, analyzes the current status of the research on the criteria for pathological grading of MVI, and assesses the value of different criteria in predicting postoperative recurrence of HCC, so as to provide a reference for the clinical research on MVI.

Although hepatocellular carcinoma(HCC) is treated with a combination of multiple disciplines and methods, there are still a large number of patients with poor prognosis. Current studies have shown that microvascular invasion(MVI) is one of the important factors for poor prognosis of HCC, but MVI can only be confirmed by postoperative pathology. This article analyzes and summarizes the factors and treatment measures for MVI in recent years, so as to better understand the research advances in MVI.

Laparoscopic cholecystectomy is considered the gold standard for the treatment of symptomatic cholecystolithiasis and has become one of the typical representatives of minimally invasive surgery. This article briefly introduces the contraindication and indication for laparoscopic cholecystectomy, commonly used surgical procedures, and possible complications and related treatment methods, emphasizes the improvement of surgical procedure and the development of new equipment for cholecystectomy, and points out the current status, problems, and development trend of laparoscopic cholecystectomy, in order to provide a reference for better application of laparoscopic cholecystectomy in clinical practice.