Surgical treatment is the most effective approach to achieving radical treatment and long-term survival of liver cancer. At present,most patients with intermediate and advanced liver cancer do not have the opportunity to receive radical surgery. The downstaging and conversion treatment strategies for intermediate and advanced liver cancer should be taken seriously in clinical practice to further improve treatment outcome. According to disease stage and conditions of patients with intermediate and advanced liver failure,multidisciplinary cooperation is needed to optimize downstaging and conversion treatment regimens,which may help inoperable patients to obtain the opportunity for surgical treatment. Palliative therapy can be changed to radical surgical resection,and patients who cannot undergo antitumor treatment can still receive palliative therapy. More patients with intermediate and advanced liver cancer are able to achieve a better clinical outcome,an improvement in prognosis,and long-term survival.

Surgery is the most important radical treatment for hepatocellular carcinoma( HCC),but less than 30% of HCC patients have the chance for radical surgery at initial diagnosis. How to transform unresectable tumor into the candidate of radical resection becomes an important way to improve the survival rate of HCC and has been a research hotspot in recent years. At present,comprehensive application of the therapies including hepatic artery catheterization,radiotherapy,and targeted therapy can achieve the downstaging of HCC,or portal vein embolization,liver partition,and portal vein ligation can rapidly increase residual liver volume; all these methods can realize successful conversion and help patients obtain the opportunity for radical resection. However,further exploration and studies are needed to investigate how to optimize a variety of treatment modes,standardize the multidisciplinary diagnosis and treatment of complex liver cancer,and improve the efficiency and safety of surgical resection.

The purpose of tumor staging is to guide treatment,and the treatment for a certain stage should be adjusted based on the changes in disease condition,in order to facilitate better control of tumor. Therefore,the treatment of liver cancer requires follow-up and re-staging to develop better treatment regimens for patients,especially the opportunity for cure. Surgical resection is not suitable for large hepatocellular carcinoma confined to the liver,and after embolization chemotherapy combined with radiotherapy for tumor regression and downstaging,some patients may undergo surgical resection,and the incurable tumor can thus be cured. For liver cancer patients with portal vein tumor thrombus,surgical resection can be performed after tumor thrombus is reduced by neoadjuvant radiotherapy,and the patients undergoing neoadjuvant radiotherapy have a significant increase in survival time than those not undergoing neoadjuvant radiotherapy. Large hepatocellular carcinoma can be downstaged to small hepatocellular carcinoma after multimodality therapy,and then stereotactic radiotherapy or radiofrequency ablation can help to achieve radical treatment. There is an increasing number of clinical reports of radiotherapy for liver cancer downstaging,with a gradual increase in evidence-based level,and thus it holds promise for clinical application.

Hepatocellular carcinoma with portal vein tumor thrombus has a high incidence rate and rapid progression,and there are limited therapies with a poor clinical effect. Although sorafenib is recommended as the sole therapy for such patients in foreign guidelines,studies have shown that some patients may achieve a better outcome via surgical treatment,especially those with tumor thrombus in the first-or second-order branches of the portal vein( type Ⅰ/Ⅱ thrombus according to Cheng's classification). However in clinical practice,a large proportion of patients cannot undergo radical resection due to extensive lesions,or there may be a high possibility of residual tumor thrombus after surgery due to the presence of tumor thrombus in the main portal vein( type Ⅲ according to Cheng's classification),and therefore,downstaging resection is needed to improve prognosis. Studies have shown that with the help of palliative therapies including neoadjuvant three-dimensional conformal radiotherapy,( 90) Y-loaded microsphere radioembolization,and hepatic arterial infusion chemotherapy,some patients may achieve regression or disappearance of portal vein tumor thrombus,tumor shrinkage,and disappearance of satellite lesions,which helps to achieve tumor downstaging,increase surgical resection rate,and prolong survival time. Multidisciplinary therapy is of vital importance in improving downstaging resection rate in patients with hepatocellular carcinoma and portal vein tumor thrombus.

Most patients with primary liver cancer in China are in the advanced stage at initial diagnosis and lose the opportunity for surgical treatment,and therefore,how to reduce advanced liver cancer to resectable liver cancer is a hot topic in clinical research in recent years.The key premise of successful conversion is to screen out the individuals who are suitable for conversion or may achieve successful conversion through comprehensive examination and necessary multidisciplinary consultation. This article introduces the conversion strategy and the antitumor strategy for liver cancer with lung metastasis,portal vein tumor thrombus,massive tumor dissemination,or multiple tumors,liver cancer with liver function decompensation,liver cancer with liver cancer dissemination and metastasis and an ECOG constitution score of >2,and liver cancer with a high HBV load,which has certain guiding significance in the downstaging conversion therapy for advanced liver cancer in clinical practice.

Interventional therapy has become an important palliative therapy for advanced liver cancer,and meanwhile,interventional therapy is playing an important role in the downstaging of liver cancer. Local interventional therapy can help patients meet the criteria for transplantation or resection by reducing tumor volume and number in patients with advanced liver cancer. Interventional downstaging techniques include transarterial chemotherapy,drug-eluting beads,transarterial radioembolization,and various ablation techniques( radiofrequency ablation,microwave ablation,cryoablation,and ethanol ablation). No consensus has been reached on the optimal interventional downstaging strategy,while high-level evidence-based clinical studies are needed to screen out the optimal candidates for different methods and evaluate the complexity,safety,and long-term efficacy of subsequent liver transplantation after interventional downstaging therapy,so as to improve the effect of interventional therapy in the downstaging of advanced liver cancer.

ObjectiveTo investigate the distribution characteristics of hepatitis C virus (HCV) genotypes in patients with hepatitis C in Guizhou, China, and to provide a basis for the prevention and individualized treatment of HCV infection. MethodsA total of 1211 HCV RNA-positive patients with hepatitis C who were treated in Guiyang Public Health Clinical Center from September 2011 to October 2018 were enrolled. PCR direct sequencing was performed to obtain HCV sequences, which were then compared with the known HCV sequences in GenBank to obtain HCV genotypes and subgenotypes. The association of genotype distribution with sex, age, ethnic group, region, and route of infection was analyzed. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsA total of 4 genotypes and 11 subgenotypes were detected among the 1211 individuals with HCV infection, with the main genotypes of 1b (26.84%), 3b (27.17%), and 6a (24.28%). There was a significant difference in the distribution of HCV genotypes between the male and female individuals (χ2=15.428, P=0.009); 29.34% of the male individuals had genotype 3b, and 32.21% of the female individuals had genotype 1b. There was a significant difference in the distribution of HCV genotypes between different age groups (χ2=67.439, P＜0.001); genotype 1b was the main genotype in the individuals aged ≤18 years (66.67%) or ≥60 years (58.93%), genotypes 3b and 6 were the main genotypes in the individuals aged 19-39 years (28.93% and 29.29%, respectively), and genotypes 1b, 3b, and 6 were the main genotypes in the individuals aged 40-59 years (29.54%, 27.33%, and 24.28%, respectively). There was a significant difference in the distribution of HCV genotypes between the individuals with different routes of infection (χ2=153.916, P＜0.001); the most common route of infection was intravenous drug addiction (57.97%), followed by sexual contact (8.42%) and invasive cosmetic surgery (8.42%); genotype 3b was the main genotype in the individuals with intravenous drug addiction (31.48%) or invasive cosmetic surgery (32.35%), and genotype 6 was the main genotype in the individuals with sexual contact (36.27%). There was no significant difference in the distribution of HCV genotypes between the individuals in different ethnic groups or from different regions of Guizhou (both P＞0.05). ConclusionThe distribution of HCV genotypes is diverse in Guizhou, and HCV strains with genotypes 3b, 1b, and 6a are the main epidemic strains. Several rare subgenotypes of HCV genotype 6 are observed. There is a significant difference in the distribution of HCV genotypes between the individuals with different ages, sexes, or routes of infection.

Objective To investigate the association between the change in liver stiffness measurement( LSM) and the histological outcome of liver fibrosis in patients with chronic hepatitis B( CHB) during antiviral therapy. Methods In a prospective cohort of CHB patients receiving entecavir-based therapy( from July 2013 to September 2015),HBV DNA,liver function,and LSM were measured at baseline and every 6 months during treatment. According to a more stringent criteria for the change in Ishak score after treatment,the patients were divided into definite regression group( a reduction of ≥2 in Ishak score),indeterminate group( a reduction of 0-1 in Ishak score),and progression group( an increase of > 1 in Ishak score). A one-way analysis of variance was used for comparison between multiple groups. The piecewise linear mixed-effects model was used to evaluate the dynamic changes of LSM and its association with the histological outcome of liver fibrosis. The t-test was used for comparison of slope between groups. Results A total of 239 CHB patients were enrolled,and after1. 5 years of entecavir treatment,18 patients( 7. 5%) achieved the histological outcome of definite regression of liver fibrosis,196( 82. 0%)achieved indeterminate regression,and 25( 10. 5%) experienced progression. The rate of reduction in LSM within the first half year of antiviral therapy was-36. 3% in the definite regression group( 95% confidence interval [CI]:-52. 8% to-19. 7%),-23. 7% in the indeterminate group( 95% CI:-29. 7% to-17. 8%),and-12. 6%( 95% CI:-31. 0% to 5. 9%) in the progression group. In the definite regression group and the indeterminate group,the rate of reduction in LSM in the first 6 months of treatment was significantly higher than that thereafter( both P < 0. 05). Conclusion The rate of reduction in LSM is associated with the histological outcome of liver fibrosis within the first 6 months of antiviral therapy. The patients with > 30% reduction in LSM after the first 6 months of antiviral therapy tend to have a higher probability of definite regression of liver fibrosis.

Objective To investigate the anti-liver fibrosis effect and mechanism of action of Kangxian Ruangan prescription based on hepatic sinusoidal capillarization. Methods A total of 16 male Wistar rats were divided into Kangxian Ruangan prescription group and control group,with 8 rats in each group. The rats in the Kangxian Ruangan prescription group were given crude drug 40 g/kg body weight by gavage,and those in the control group were given normal saline by gavage. Serum containing Kangxian Ruangan prescription was prepared,and then primary liver sinusoidal endothelial cells were treated with the serum containing Kangxian Ruangan prescription or the control serum. Western blot was used to measure the protein expression of the vascular endothelial markers cluster of differentiation 31( CD31) and von Willebrand factor( vWF),and immunocytochemistry was used to measure the expression of CD31 and vWF in cells. Scanning electron microscopy was used to observe the change in the fenestrae of liver sinusoidal endothelial cells. The t-test was used for comparison of continuous data between two groups. Results Kangxian Ruangan prescription had no marked influence on the morphology of liver sinusoidal endothelial cells. The liver sinusoidal endothelial cells in the control group had a small number of narrow fenestrae with an occluded structure,while those in the Kangxian Ruangan prescription group had an increased number of large fenestrae with a clear structure. The results of immunocytochemistry showed that compared with the control group,the Kangxian Ruangan prescription group had significant reductions in the expression of CD31( 0. 069 ± 0. 015 vs 0. 115 ± 0. 011,t = 4. 257,P < 0. 05) and vWF( 0. 092 ± 0. 009 vs 0. 132 ± 0. 014,t = 4. 274,P < 0. 05). The results of Western blot showed that compared with the control group,the Kangxian Ruangan prescription group had significant reductions in the protein expression of CD31( 0. 334 ± 0. 029 vs 0. 448 ± 0. 013,t = 6. 245,P < 0. 01) and vWF( 0. 560 ± 0. 047 vs0. 709 ± 0. 045,t = 3. 966,P < 0. 05). Conclusion Kangxian Ruangan prescription can significantly resist hepatic sinusoid capillarization and thus prevent the progression of liver fibrosis.

Objective To investigate glucose metabolism and insulin secretion in patients with chronic hepatitis B( CHB) of different Child-Pugh grades and liver cirrhosis and their association with inflammatory response. Methods A total of 147 patients with CHB and liver cirrhosis who were admitted to Guangzhou Red Cross Hospital from January 2013 to January 2018 were enrolled,and 65 healthy individuals who underwent physical examination in our hospital during the same period of time were enrolled as control group. The clinical data within 12 hours after admission were collected,including age,sex,body mass index,systolic pressure,diastolic pressure,HBV DNA load,total cholesterol,triglyceride,low-density lipoprotein,high-density lipoprotein,alanine aminotransferase,aspartate aminotransferase,tumor necrosis factor α( TNFα),neutrophil-lymphocyte ratio( NLR),fasting blood glucose,plasma insulin,C-peptide level,homeostasis model assessment of insulin resistance( HOMA-IR),and insulin secretion function. Blood glucose,insulin,and C-peptide were recorded at 2 hours after oral glucose tolerance test( OGTT). The chi-square test was used for comparison of categorical data between two groups; the t-test was used for comparison of continuous data between two groups; the Kruskal-Wallis H test was used for comparison of ranked data between multiple groups and further comparison between two groups. A Pearson correlation analysis was used to investigate correlation.Results Compared with the control group,the patients with CHB and liver cirrhosis had significantly higher TNFα,interleukin-6( IL-6),NLR,insulin,and HOMA-IR( all P < 0. 05) and significantly lower insulin secretion function( P < 0. 05). The 147 patients with CHB and liver cirrhosis were divided into Child-Pugh A,B,and C groups according to Child-Pugh grade,and there were significant differences in TNFα,IL-6,NLR,insulin,HOMA-IR,and insulin secretion function between these three groups( all P < 0. 05). Compared with the control group,the patients with CHB and liver cirrhosis had significantly higher blood glucose,insulin,C-peptide,NLR,TNFα,and IL-6 at 2 hours after OGTT( all P < 0. 05); there were significant differences in blood glucose,insulin,NLR,TNFα,and IL-6 at 2 hours after OGTT between the three groups with different Child-Pugh grades( all P < 0. 05). Child-Pugh score was positively correlated with NLR and blood glucose and insulin at 2 hours after OGTT( r = 0. 678,0. 451,and 0. 644,all P < 0. 001),and NLR was positively correlated with blood glucose and insulin at 2 hours after OGTT( r = 0. 408 and 0. 795,both P < 0. 001). Conclusion There is a certain degree of abnormal glucose metabolism and insulin resistance in CHB patients with liver cirrhosis,and the severities of abnormal glucose metabolism and insulin resistance increase with the increase in liver injury,while inflammation may mediate the association between them.

Objective To investigate the causes of hypoglycemia and the features of clinical indices in patients with liver cirrhosis and diabetes mellitus. Methods A total of 50 patients with liver cirrhosis and diabetes mellitus who were admitted to Beijing YouAn Hospital,Capital Medical University,from January 2017 to June 2019 were enrolled as subjects,among whom 25 patients with one hypoglycemic event were enrolled as experimental group and 25 patients without hypoglycemia were enrolled as control group. Hepatic and renal function,fasting blood glucose,glycosylated hemoglobin,and Child-Pugh class were evaluated for both groups,and the time period and possible causes of hypoglycemia were analyzed. The independent samples 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. Results Compared with the control group,the experimental group had significantly lower levels of fasting blood glucose [6. 10( 3. 45 ～ 8. 96) mmol/L vs 8. 12( 6. 18 ～12. 59) mmol/L,Z =-2. 687,P = 0. 007],cholinesterase [3009. 00( 1788. 50 ～ 4439. 50) U/L vs 4936. 00( 4051. 00 ～ 6740. 50) U/L,Z =-3. 095,P = 0. 002),albumin( 32. 02 ± 7. 07 g/L vs 35. 89 ± 5. 49 g/L,t = 2. 161,P = 0. 036),and glycosylated hemoglobin( 6. 97± 1. 64 mmol/L vs 8. 04 ± 1. 78 mmol/L,t = 2. 047,P = 0. 047). Among the patients in the experimental group,36% had Child-Pugh class B cirrhosis and 36% had Child-Pugh class C cirrhosis,and among the patients in the control group,56% had Child-Pugh class A cirrhosis and 40% had Child-Pugh class B cirrhosis; there was a significant difference in Child-Pugh class between the two groups( χ2=8. 786,P = 0. 012). Most of the patients with liver cirrhosis and diabetes mellitus experienced hypoglycemia in the fasting state in the morning and in the daytime,with the main causes of excessive insulin( 44%) and insufficient food intake or calorie supplementation( 40%),and some patients experienced fasting asymptomatic hypoglycemia( 16%). Conclusion Blood glucose monitoring and management should be taken seriously for patients with liver cirrhosis and diabetes mellitus in clinical practice,in order to reduce the occurrence of hypoglycemia.

Objective To investigate the characteristics of flora microbiota before and after transjugular intrahepatic portosystemic shunt( TIPS) in patients with liver cirrhosis. Methods A total of 18 patients with liver cirrhosis who were hospitalized and underwent TIPS in Department of Gastroenterology,The Affiliated Hospital of Southwest Medical University,from July 2018 to July 2019 were enrolled. Fecal samples were collected from 18 patients before surgery,6 fecal samples were collected at 1 month after surgery,and 9 were collected at 3 months after surgery. The results of liver function and coagulation were collected before and after surgery. Fecal samples were analyzed by the 16 S rRNA high-throughput sequencing method,and the DADA2 method recommended by QIIME2 was used in the bioinformatics analysis. The intestinal flora was analyzed in terms of the generated amplified characteristic sequence,and the multiple hypothesis tests of LEfSe,SPSS( Alpha analysis),PERMANOVA( Beta analysis),and Pheatmap were used for analysis. For normally distributed continuous data,intergroup comparison of parameters at different time points was made by a repeated measures analysis of variance. For non-normally distributed continuous data,intergroup comparison of parameters at different time points was made using a generalized estimating equation,and further pairwise comparison was made using the Bonferroni method. Results There were significant differences in total bilirubin and total bile acid between groups before TIPS and during the three periods of time after TIPS( F = 8. 201 and 39. 482,P = 0. 001 and P < 0. 001).At 1 month after surgery,Beta diversity changes were observed in fecal samples( F = 2. 603,P = 0. 02),while there was no significant difference in Alpha diversity of the fecal samples between the three periods of time( P > 0. 05). At the genus level,portal venous pressure before TIPS was negatively correlated with Bifidobacterium,Collinsella,and Ruminococcus( r =-0. 35,-0. 38,and-0. 34,P = 0. 04,0. 02,and 0. 04) and was positively correlated with Boletus( r = 0. 41,P = 0. 015). Other indices were also correlated with different components of the intestinal flora( P < 0. 05). Conclusion There is a correlation between clinical indices and intestinal flora before TIPS. The composition of intestinal flora changes after TIPS,with a significant difference at the genus level.

Objective To investigate the prognostic and risk factors for cirrhotic patients undergoing recanalization due to shunt dysfunction after transjugular intrahepatic portosystemic shunt( TIPS). Methods A retrospective analysis was performed for the clinical data of 69 cirrhotic patients who were admitted to Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2013 to February2019 and underwent TIPS due to esophagogastric variceal bleeding and recanalization due to shunt dysfunction after TIPS. Related clinical data included preoperative,intraoperative,and postoperative data of TIPS and recanalization,stent parameters,hepatic venous pressure gradient,site of puncture of the portal vein,and laboratory markers. The Kaplan-Meier curve was used to evaluate the cumulative rate of shunt dysfunction and cumulative survival rate after recanalization,and the log-rank test was used for comparison of cumulative patency rate between two groups. The Cox regression model was used to investigate the influencing factors for secondary shunt dysfunction and survival after recanalization. Results Of all patients undergoing recanalization,28( 40. 6%) experienced secondary shunt dysfunction and 15( 21. 7%) died. The median time to secondary shunt dysfunction was 11. 3 months. The 1-,2-,3-,and 5-year cumulative incidence rates of secondary shunt dysfunction were 29. 8%,41. 6%,48. 0%,and 52. 7%,respectively,and the 1-,2-,3-,and 5-year cumulative survival rates were 96. 9%,94. 8%,83. 0%,and 62. 6%,respectively. There was a significant difference in cumulative patency rate between the patients undergoing balloon dilatation of stent alone and those undergoing stent implantation( χ2= 9. 494,P = 0. 009).Child-Turcotte-Pugh( CTP) grade before first TIPS,stent diameter for first surgery,and international normalized ratio( INR) and prothrombin time( PT) before recanalization were associated with secondary shunt dysfunction( all P < 0. 05),and an increase in INR before recanalization was an independent risk factor for secondary shunt dysfunction( hazard ratio [HR]= 4. 398,95% confidence interval [CI]:1. 848-10. 467,P = 0. 001),while stent implantation during recanalization was an independent protective predictor against secondary shunt dysfunction( HR = 0. 370,95% CI: 0. 194-0. 704,P = 0. 002). CTP grade before first TIPS and Model for End-Stage Liver Disease( MELD) score were associated with patients' survival after recanalization( both P < 0. 05),and an increase in MELD score was the only independent risk factor for death after recanalization( HR = 1. 293,95% CI: 1. 054-1. 627,P = 0. 026). Conclusion For patients undergoing recanalization due to shunt dysfunction after TIPS,stent implantation during recanalization is a reasonable choice,while an increase in MELD score is associated with poor prognosis of patients.

Objective To investigate the risk factors for hepatic encephalopathy( HE) after emergency transjugular intrahepatic portosystemic shunt( TIPS) for patients with acute esophagogastric variceal bleeding( EVB) based on an analysis of clinical outcomes. Methods A retrospective analysis was performed for the clinical data of 93 patients with decompensated liver cirrhosis and acute EVB who failed endoscopy or medication and then underwent TIPS with a covered stent within 72 hours in The First Affiliated Hospital of Soochow University from January 2013 to December 2018. According to the presence or absence of HE after surgery,they were divided into HE group with 36 patients and non-HE group with 57 patients. Preoperative clinical data were collected,including sex,age,etiology,comorbidities,and blood biochemical parameters [white blood cell count( WBC),platelet count( PLT),hematocrit( Hct),total bilirubin( TBil),aspartate aminotransferase( AST),albumin( Alb),serum creatinine( SCr),and prothrombin time( PT) ],and the measured values were used to calculate Model for End-Stage Liver Disease( MELD) score. Wedged hepatic venous pressure( WHVP) and free hepatic venous pressure( FHVP) were measured and recorded before TIPS stent implantation,and hepatic venous pressure gradient( HVPG) was the difference between WHVP and FHVP. The t-test or the Mann-Whitney U test was used for comparison between two groups,and the chi-square test was used for comparison of categorical data between two groups. A binary logistic regression analysis was used to identify the risk factors for the prognosis of patients after TIPS. Results The incidence rate of postoperative HE was 38. 710%. There were significant differences between the two groups in preoperative MELD score( 13. 000 ± 3. 189 vs 11. 684 ± 2. 068,t = 2. 068,P = 0. 043) and HVPG( 24. 908 ±5. 317 mm Hg vs 22. 597 ± 4. 928 mm Hg,t = 2. 100,P = 0. 039). Based on the results of HE grading,17 patients( 47. 222%) had grade0-1 HE,9( 25. 000%) had grade 2 HE,6( 16. 667%) had grade 3 HE,and 4( 11. 111%) had grade 4 HE. The stepwise logistic regression analysis showed that MELD score( odds ratio [OR]= 0. 803,95% confidence interval [CI]: 0. 679-0. 948,P = 0. 010) and HVPG( OR = 0. 896,95% CI: 0. 816-0. 984,P = 0. 022) were independent risk factors for HE after TIPS. Conclusion There is a high incidence rate of HE after emergency TIPS for acute EVB,and preoperative MELD score and HVPG can predict the risk of HE after TIPS.

Objective To investigate the influence of ideal cardiovascular health behaviors and factors on the onset of primary liver cancer in northern China. Methods A prospective cohort study was conducted for 95 055 on-the-job or retired employees of Kailuan Group who underwent physical examination from July 2006 to June 2007,and related data were collected. They were followed up to observe the onset of primary liver cancer. According to the cardiovascular health score( CHS),the subjects were divided into first quartile group with 27 143 subjects( CHS≤7),second quartile group with 35 488 subjects( 7 < CHS≤9),and third quartile group with 32 424 subjects( 9 < CHS≤14),and the person-year incidence rate was calculated. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between multiple groups. The chi-square test was used for comparison of categorical data between groups. The life-table method was used to calculate the cumulative incidence rate of primary liver cancer,and the log-rank test was used for comparison of cumulative incidence rate between groups. The Cox proportional hazards model was used to analyze the influence of ideal cardiovascular health behaviors and factors on the onset of primary liver cancer. Results There were significant differences between the three groups in age,male/female ratio,body mass index,total cholesterol,fasting blood glucose,alanine aminotransferase,hypersensitive C-reactive protein,drinking,family income,educational level,fatty liver disease,family history of cancer,and proportion of subjects with ideal smoking,ideal physical exercise,ideal body mass index,ideal blood pressure,ideal total cholesterol,ideal blood glucose,and ideal diet ratio( all P < 0. 05). The mean follow-up time was 11. 49 ± 1. 86 years,and a total of 387 cases of primary liver cancer were observed,among whom there were 360 male and 27 female patients. The person-year incidence rates of the three groups were 4. 11/10 000 person-years,3. 78/10 000 person-years,and 2. 84/10 000 person-years,respectively. The 10-year cumulative incidence rates of the three groups were 4. 43‰,3. 61‰,and 2. 84‰,respectively,and there was a significant difference in the cumulative incidence rate between the three groups( χ2= 8. 29,P =0. 016). The Cox proportional hazards model showed that after adjustment for confounding factors( age,sex,alanine aminotransferase,hypersensitive C-reactive protein,drinking,family income,educational level,positive HBs Ag,liver cirrhosis,fatty liver disease,and family history of cancer),compared with the first quartile group,the second quartile group had a hazard ratio( HR) of 0. 87( 95% confidence interval [CI]: 0. 67-1. 13) and the third quartile group had an HR of 0. 74( 95% CI: 0. 56-0. 98)( P for trend < 0. 05). Conclusion The higher scores of ideal cardiovascular health behaviors and factors play a protective role in the onset of primary liver cancer,and the risk of primary liver cancer decreases with the increase in cardiovascular score.

Objective To investigate the expression of CD90 in human intrahepatic cholangiocellular carcinoma and its association with lymph node metastasis and poor prognosis. Methods A total of 49 samples of intrahepatic cholangiocellular carcinoma tissue and 49 samples of adjacent tissue were collected after surgical resection in The Affiliated Hospital of Chengde Medical College from March 2013 to March2016,and 40 normal liver tissue samples were selected as control. Immunohistochemistry was used to measure the expression of CD90 in each sample,and its association with clinical indices,survival,and prognosis of patients with intrahepatic cholangiocellular carcinoma was analyzed. The t-test was used for comparison of continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups,the Kruskal-Wallis H test was used for comparison between three groups and further comparison between two groups. The Kaplan-Meier curve was used to analyze postoperative recurrence and survival,and the log-rank test was used for comparison. Results The moderately positive expression rate of CD90 was 65. 31% in intrahepatic cholangiocellular carcinoma tissue,30. 61%in adjacent normal tissue,and 0% in normal liver tissue,suggesting that the intrahepatic cholangiocellular carcinoma tissue had a significantly higher moderately positive expression rate of CD90 than adjacent normal tissue and normal liver tissue( P < 0. 05). The expression of CD90 was associated with TNM stage and hilar lymph node metastasis in the patients with intrahepatic cholangiocellular carcinoma( χ2=12. 837 and 17. 824,both P < 0. 001). The patients with negative/weakly positive expression of CD90 had significantly higher relapse-free survival rate and overall survival rate after surgery than those with moderately/strongly positive expression( χ2= 3. 845 and 4. 152,P =0. 025 and 0. 021). Conclusion CD90 is highly expressed in human intrahepatic cholangiocellular carcinoma tissue,which is associated with hilar lymph node metastasis and poor prognosis and plays an important role in tumor development,progression,and metastasis.

Objective To investigate the short-and long-term effects of radiofrequency ablation( RA) versus minimally invasive hepatectomy( MIH) in the treatment of small hepatocellular carcinoma( SHCC). Methods PubMed,Web of Science,Embase,Cochrane Library,CBM,CNKI,Wanfang Data,and VIP were searched for Chinese and English articles on RA versus MIH in the treatment of s HCC published up to August 2019. Quality assessment was performed for the articles included,and RevMan 5. 1 was used for analysis. Results A total of 7 studies with 737 patients were included after screening,and there were 393 patients in RA group and 344 patients in MIH group.Compared with the MIH group,the RA group had significantly shorter time of operation( mean difference [MD]=-206. 57,95% confidence interval [CI]:-387. 28 to-25. 86,P = 0. 03) and length of hospital stay( MD =-4. 02,95% CI:-4. 94 to-3. 10,P <0. 01),as well as a significantly lower overall incidence rate of postoperative complications( odds ratio [OR] = 0. 31,95% CI: 0. 20-0. 47,P < 0. 01). Compared with the RA group,the MIH group had significantly higher 3-year overall survival rate( OR = 0. 55,95% CI:0. 36-0. 84,P < 0. 01),1-year disease-free survival rate( OR = 0. 63,95% CI: 0. 41-0. 98,P = 0. 04),and 3-year disease-free survival rate( OR = 0. 51,95% CI: 0. 34-0. 74,P < 0. 01),as well as a significantly lower local recurrence rate after surgery( OR =1. 87,95% CI: 1. 31-2. 68,P < 0. 01). Conclusion In the treatment of s HCC,RA has good short-term effect,good safety,and poor long-term effect,while MIH has good long-term effect and poor short-term effect.

Objective To investigate the efficacy and safety of Kanglaite injection( KLT) combined with transarterial chemoembolization( TACE) in the treatment of advanced liver cancer through a Meta-analysis. Methods CNKI,Wanfang Data,VIP,CBM,PubMed,Cochrane Library,and Embase were searched for clinical studies on KLT combined with TACE in the treatment of advanced liver cancer published up to October 2019. The patients in the experimental group were given KLT combined with TACE,while those in the control group were given TACE alone. Data extraction and quality assessment were performed for the articles included in the analysis,and RevMan 5. 3 was used for Meta-analysis. The chi-square test was used to evaluate heterogeneity between studies; odds ratio( OR) and 95% confidence interval( CI) were used to evaluate outcome measures; funnel plots were used to evaluate publication bias. Results A total of 16 articles which met the inclusion criteria were included,with a total of 1131 patients( 558 patients in the experimental group and 573 in the control group). Compared with the control group,the experimental group had significant increases in tumor response rate( OR = 2. 85,95% CI:2. 17-3. 76,P < 0. 001),disease control rate( OR = 2. 58,95% CI: 1. 57-4. 24,P < 0. 001),and Karnofsky Performance Scale score for quality of life( OR = 3. 54,95% CI: 2. 48-5. 06,P < 0. 001),as well as significant improvements in clinical symptoms( OR = 3. 71,95% CI: 1. 55-8. 89,P = 0. 003) and alpha-fetoprotein level( OR = 2. 57,95% CI: 1. 41-4. 68,P = 0. 002). In addition,the experimental group had a significantly lower incidence rate of bone marrow suppression than the control group( leukocyte reduction: OR = 0. 39,95% CI: 0. 23-0. 66,P < 0. 001; thrombocytopenia: OR = 0. 22,95% CI: 0. 12-0. 42,P < 0. 001). Conclusion In the treatment of advanced liver cancer,KLT combined with TACE results in a high response rate and good quality of life and can reduce the incidence rate of toxic and side effects including bone marrow suppression due to chemotherapy.

Objective To investigate whether the reference intervals for serum alpha-fetoprotein( AFP) and carcinoembryonic antigen( CEA) in WS/T 645. 2-2018 are applicable to the adults in Changchun,China. Methods According to the validation method for the reference intervals in WS/T 645. 2-2018,5420 subjects,aged from 20-79 years,who underwent physical examination from January 2016 to April 2019 were enrolled and divided into 12 subgroups based on age and sex. Each subgroup was analyzed in terms of whether more than90% of the measured values fell into the reference intervals,and the changing trend of AFP and CEA with age and sex was analyzed. The Mann-Whitney U test was used for comparison between two groups. Results More than 90% of the measured values of serum AFP and CEA fell into the reference intervals,which passed the validation test. There was a significant difference in serum AFP between male and female subjects aged 30-39 years( Z =-4. 51,P < 0. 05),and there was a significant difference in serum CEA between male and female subjects aged 20-29,30-39,40-49,50-59,and 60-69 years( Z =-13. 45,-18. 15,-17. 34,-10. 82,and-3. 65,all P <0. 05). Serum AFP increased slowly with age in female subjects aged 20-69 years and decreased with age in male and female subjects aged70-79 years. Serum CEA increased with age in male and female subjects aged 20-79 years,and male subjects had a higher measured value than female subjects. Conclusion Reference intervals for serum AFP and CEA in WS/T 645. 2-2018 issued by National Health Commission are applicable to the adults in Changchun.

Objective To investigate the expression of proteasome subunit beta type 4( PSMB4) in hepatocellular carcinoma( HCC) tissue and normal liver tissue and its significance in clinical prognosis. Methods Eight fresh HCC tissue specimens were collected from the patients who underwent surgical treatment in Affiliated Hospital of Nantong University from January to October,2017,and Western Blot was used to measure the protein expression of PSMB4 in HCC tissue and the corresponding adjacent tissue. A total of 105 paraffin-embedded HCC tissue specimens and 25 paraffin-embedded normal liver tissue specimens,which were preserved in Affiliated Hospital of Nantong University from January 2009 and October 2012,were collected,and immunohistochemistry was used to measure the expression of PSMB4.According to the expression of PSMB4,105 HCC patients were divided into high PSMB4 expression group with 57 patients and low PSMB4 expression group with 48 patients. The independent samples t-test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups. The Cox proportional-hazards regression model and the Kaplan-Meier survival curves were used to analyze the clinicopathological features and prognosis of the patients in the two groups. Results There were significant differences between the two groups in hepatitis B virus infection,maximum tumor diameter,degree of tumor differentiation,and TNM stage( χ2= 22. 482,8. 219,14. 964,and 6. 587,all P < 0. 05). Among the 105 HCC patients,57( 54. 29%) had high PSMB4 expression and 48( 45. 71%) had low PSMB4 expression,while among the 25 normal liver tissue specimens,8( 32%) had high PSMB4 expression and 17( 68%) had low PSMB4 expression or no PSMB4 expression,and there was a significant difference in PSMB4 expression between the two groups( χ2= 4. 011,P < 0. 05). PSMB4 staining was mainly distributed in the cytoplasm and nucleus,with an appearance of brown or brownish yellow particles. Among the 8 fresh HCC tissue specimens,7 specimens had significantly higher protein expression of PSMB4 than the corresponding adjacent tissue specimens( all P < 0. 05). The patients' 5-year survival was associated with tumor size( P = 0. 01),metastasis( P < 0. 001),degree of tumor differentiation( P = 0. 01),TNM stage( P = 0,003),and PSMB4 expression( P <0. 001),among which metastasis( hazard ratio [HR]= 11. 375,95% confidence interval[CI]: 4. 911-26. 348,P < 0. 001) and high PSMB4 expression( HR = 6. 834,95% CI: 2. 939-15. 889,P < 0. 001) were independent risk factors in HCC patients. The high PSMB4 expression group had a significantly lower 5-year survival rate than the low PSMB4 expression group( 27. 6% vs 79. 2%,χ2= 22. 96,P <0. 05). Conclusion There is an increase in the expression of PSMB4 in HCC tissue,and high expression of PSMB4 is an independent risk factor for poor prognosis in HCC patients,suggesting that PSMB4 may serve as a potential prognostic marker or a potential target for treatment.

Objective To construct pCTHRC1-IRES2-EGFP eukaryotic expression vector,and to investigate the association between collagen triple helix repeat containing 1( CTHRC1) gene and miR-30 b. Methods Specific primers were designed and PCR was used for the amplification and synthesis of the sequence of CTHRC1 CDS + 3 'UTR region,which was then cloned into the pIRES2-EGFP eukaryotic expression vector to obtain the p CTHRC1-IRES2-EGFP eukaryotic expression vector. Nhe I/Xho I double enzyme electrophoresis and sequencing were used for identification,and the lipofection method was used to evaluate the transfection efficiency of Huh7 and HepG2 cells.After miR-30 b mimic,control,p CTHRC1-IRES2-EGFP plasmid,and pIRES2-EGFP plasmid were transfected into 293 T cells,Western Blot and quantitative real-time PCR were used to measure the protein expression of CTHRC1 and the expression of miR-30 b at 48 hours after transfection. The association between CTHRC1 gene and miR-30 b was analyzed. The independent samples t-test was used for comparison between two groups. Results Nhe I/Xho I double enzyme digestion was performed for the p CTHRC1-IRES2-EGFP eukaryotic expression vector,and two fragments with a length of 5300 bp and 1100 bp were obtained,which was consistent with the expected results;the sequencing results also showed that the sequence was exactly the same as that published in GeneBank,suggesting that the pCTHRC1-IRES2-EGFP eukaryotic expression vector was constructed successfully. In the transfection of Huh7 and HepG2 cells,2 μg p CTHRC1-IRES2-EGFP plasmid had a transfection efficiency of 90% and 89%,respectively,while 4 μg p CTHRC1-IRES2-EGFP plasmid had a transfection efficiency of 85% and 83%,respectively. In 293 T cells,the expression of CTHRC1 decreased to the miR-30 b group( P <0. 05). The expression of miR-30 b decreased in the group with overexpressed CTHRC1( P < 0. 05). Conclusion The eukaryotic expression vector of pCTHRC1-IRES2-EGFP is successfully constructed,and the expression of CTHRC1 is negatively correlated with the expression of miR-30 b in 293 T cells.

Objective To investigate the effect of NOR1 gene knockout on the growth of nude mice xenograft tumor of human liver cancer,the survival rate of nude mice,and organ damage in nude mice. Methods A total of 30 specific pathogen-free male BALB/C nude mice were randomly divided into control group,Scramble group,and siNOR1 group,with 10 mice in each group. The negative control plasmid( Scramble) and siNOR1 plasmid were transfected into HepG2 cells,and then the HepG2 cells were inoculated into nude mice to establish a nude mouse model of xenograft tumor. The volume and weight of nude mice xenograft tumor were measured every 5 days for 30 consecutive days. Immunohistochemistry was used to measure the expression of Ki-67,caspase-3,Notch,and NOR1,and Western Blot was used to measure the protein expression of Survivin,Notch1,NICD,Hes1,and Hey1. HE staining was used to observe the degree of pathological injury in the liver,the kidney,the lungs,and the brain. A one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups. The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival rates. Results Compared with the control group since day 20 of modeling,the siNOR1 group had a significantly lower volume of xenograft tumor on days 20,25,and 30( day 20: 149. 6. 16 ± 60. 05 mm3 vs 418. 71 ± 78. 24 mm3,P < 0. 05; day 25: 239. 83 ± 100. 51 mm3 vs 864. 22 ± 125. 66 mm3,P < 0. 05; day 30: 446. 54 ± 147. 09 mm3 vs1468. 45 ± 199. 78 mm3,all P < 0. 05). The xenograft tumor was collected on day 30,and compared with the control group,the siNOR1 group had a significantly lower weight of xenograft tumor( 0. 12 ± 0. 04 g vs 0. 45 ± 0. 07 g,P < 0. 05). Compared with the control group,the siNOR1 group had significantly lower expression of Ki-67,Notch,and NOR1 in xenograft tumor tissue( Ki-67: 11. 51% ± 5. 09% vs48. 98% ± 9. 75%,P < 0. 05; Notch: 18. 75% ± 4. 61% vs 62. 51% ± 9. 26%,P < 0. 05; NOR1: 16. 57% ± 3. 76% vs 76. 33% ±8. 31%,P < 0. 05),as well as significantly higher expression of caspase-3( 38. 03% ± 9. 28% vs 6. 39% ± 4. 67%,P < 0. 05). The siNOR1 group had a significantly higher 30-day survival rate than the control group( 77. 66% ± 6. 75% vs 25. 32% ± 4. 63%,χ2= 6. 897,P < 0. 05). Western blot showed that compared with the control group,the si NOR1 group had significantly lower protein expression of Survivin( 0. 02 ± 0. 01 vs 0. 34 ± 0. 06,P < 0. 05),Notch1( 0. 03 ± 0. 01 vs 0. 16 ± 0. 03,P < 0. 05),NICD( 0. 04 ± 0. 02 vs 0. 26 ± 0. 05,P < 0. 05),Hes1( 0. 06 ± 0. 02 vs 0. 35 ± 0. 04,P < 0. 05),and Hey1( 0. 05 ± 0. 02 vs 0. 29 ± 0. 06,P < 0. 05). The si NOR1 group had a significant improvement in organ damage. Conclusion NOR1 gene knockout inhibits the growth of nude mice xenograft tumor of human liver cancer,improve the survival rate of model nude mice,and alleviate the damage of the liver,the kidney,the lungs,and the brain in model nude mice,possibly by inhibiting the activity of the Notch signaling pathway.

Objective To investigate the composition and changing trend of the etiologies of liver failure in Shaanxi Province,China.Methods A retrospective analysis was performed for the clinical data of 975 patients with liver failure who were hospitalized in The First Affiliated Hospital of Xi'an Jiaotong University from January 2008 to December 2017. According to the clinical type of liver failure,the patients were divided into acute liver failure( ALF) group with 115 patients,subacute liver failure( SALF) group with 165 patients,and acute-on-chronic liver failure( ACLF) group with 695 patients. A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the t-test was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups. Results Drug was the primary cause of ALF( 25. 22%,29/115),followed by hepatitis B virus( HBV) infection( 21. 74%,25/115); HBV infection was the primary cause of SALF( 35. 15%,58/165),followed by drug( 27. 27%,45/165); HBV infection was the primary cause of ACLF( 87. 19%,606/695),followed by alcohol( 3. 45%,24/695). The main age distribution of patients with liver failure due to HBV infection,alcohol,and drug was 20-60 years( 595/689),30-40 years( 22/32),and30-70 years( 67/89),respectively. There was a significant reduction in the proportion of patients with HBV-related liver failure in the recent 5 years( 61. 52% vs 81. 33%,χ2= 45. 87,P < 0. 001),while there were significant increases in the proportion of patients with drug-induced liver failure( 13. 14% vs 4. 44%,χ2= 22. 10,P < 0. 001) and alcoholic liver failure( 4. 76% vs 1. 56%,χ2= 7. 85,P =0. 005). Further analysis showed that the age of onset of HBV-related liver failure in the recent 5 years was significantly higher than that in the first 5 years( 45. 3 ± 13. 0 vs 42. 5 ± 12. 9,t =-2. 567,P = 0. 011). Conclusion Management of chronic HBV infection is still an important link in the control of liver failure,and meanwhile,the prevention and treatment of drug-induced and alcoholic liver diseases should be strengthened. More attention should be paid to the treatment of elderly patients with liver failure.

Objective To investigate the expression of the long non-coding RNA( lncRNA) EXOC7 in serum and liver biopsy tissue of patients with nonalcoholic fatty liver( NAFLD) and its clinical significance. Methods A total of 120 patients who underwent liver biopsy in The Affiliated Hospital of Southwest Medical University from January 1,2013 to December 31,2018 and were diagnosed with NAFLD based on imaging and histopathology were enrolled,among whom 47 had nonalcoholic fatty liver( NAFL) and 73 had nonalcoholic steatohepatitis( NASH). A total of 50 liver disease patients without steatosis or steatohepatitis were enrolled as control group. Real-time PCR was used to measure the expression of lncRNA EXOC7 in liver tissue and serum. The t-test was used for comparison of continuous data between two groups; an analysis of variance was used for comparison between multiple groups,and the SNK-q test was used for further comparison between two groups. A chi-square test was used for comparison of categorical data between groups. A Pearson correlation analysis was used to investigate the correlation between lncRNA EXOC7 and biochemical parameters. The receiver operating characteristic( ROC) curve was plotted to investigate the diagnostic value of lncRNA EXOC7. Results Compared with the control group,the patients with NAFL or NASH had significant increases in the expression of lncRNA EXOC7 in liver tissue and serum( all P < 0. 05),and the level of such expression increased with the aggravation of hepatic steatosis and inflammation( F = 19. 96,P < 0. 05). The correlation analysis showed that the expression of lncRNA EXOC7 was positively correlated with total triglyceride and low-density lipoprotein cholesterol( r = 0. 785 and r = 0. 847,both P < 0. 001) and was negatively correlated with high-density lipoprotein cholesterol and insulin sensitivity index( r =-0. 726 and-0. 709,both P < 0. 001). LncRNA EXOC7 had an area under the ROC curve of 0. 812( 95% confidence interval: 0. 599-0. 915,P < 0. 001),a sensitivity of85. 42%,and a specificity of 81. 17% in the diagnosis of NAFLD. Conclusion LncRNA EXOC7 is highly expressed in patients with NAFLD,and the expression of lncRNA EXOC7 increases with the aggravation of hepatic steatosis and inflammation,suggesting that lncRNA EXOC7 may be a potential new target for the prevention and treatment of NAFLD.

Objective To investigate the clinical features of patients with acute pancreatitis versus hyperamylasemia after endoscopic retrograde cholangiopancreatography( ERCP) and related influencing factors,and to provide a basis for preventing disease progression. Methods A retrospective analysis was performed for the clinical data of 117 patients who underwent ERCP in Renmin Hospital of Wuhan University from January 2017 to August 2019,and all patients were given the preventive use of diclofenac sodium suppository before surgery. After surgery,77 patients developed hyperamylasemia and 40 developed acute pancreatitis,and the two groups were compared in terms of clinical features and influencing factors. The t-test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test 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 two groups; a multivariate logistic regression analysis was used to investigate the independent risk factors for post-ERCP pancreatitis( PEP). Results There were significant differences between the two groups in preoperative levels of alkaline phosphatase( ALP)( Z =-2. 518,P = 0. 012),gamma-glutamyl transpeptidase( Z =-2. 313,P = 0. 021),total bilirubin( TBil)( Z =-2. 978,P = 0. 003),and direct bilirubin( Z =-3. 069,P = 0. 002) and presence or absence of guide wire insertion into the pancreatic duct during surgery( χ2= 4. 176,P = 0. 041). Further logistic regression analysis showed that the number of times of guide wire insertion into the pancreatic duct ≥3( odds ratio [OR]= 2. 469,95% confidence interval [CI]: 1. 199-5. 188,P = 0. 047),ALP< 125 U/L( OR = 5. 499,95% CI: 1. 452-18. 830,P = 0. 012),and TBil < 22 umol/L( OR = 4. 249,95% CI: 1. 023-17. 648,P =0. 046) were independent risk factors for PEP. Conclusion Although patients are given the preventive use of diclofenac sodium suppository before surgery,the patients with normal levels of ALP and TBil before surgery and repeated guide wire insertion into the pancreatic duct during surgery are more likely to develop PEP,which should be taken seriously by surgeons. Early intervention measures before and after surgery based on patients' conditions can reduce the progression of post-ERCP hyperamylasemia to PEP,reduce the development of moderate-to-severe PEP,and improve patients' prognosis.

Objective To investigate the clinical features of patients with pancreatic neuroendocrine tumor( PNET) and the influencing factors for prognosis. Methods A retrospective analysis was performed for the clinical data of 54 patients with pathologically confirmed PNET in The First Affiliated People's Hospital of Shanghai Jiao Tong University from March 2012 to April 2019,and clinical,pathological,and imaging features and prognosis were analyzed. The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison between groups.Results Among the 54 patients,there were 19 male patients( 35. 2%) and 35 female patients( 64. 8%). Of all patients,47( 87. 0%)had non-functional tumors and 7( 13. 0%) had functional tumors. There were 17 patients( 31. 5%) with TNM stage Ⅰ tumor,26 patients( 48. 1%) with stage Ⅱ tumor,9 patients( 16. 7%) with stage Ⅲ tumor,and 2 patients( 3. 7%) with stage Ⅳ tumor. According to the World Health Organization pathological grade,24 patients( 46. 2%) had G1 tumor,22( 42. 3%) had G2 tumor,and 6( 11. 5%) had G3 tumor. The patients with unclear boundary of tumor on CT( χ2= 8. 250,P = 0. 010) and MRI( χ2= 6. 048,P = 0. 031) tended to have higher postoperative recurrence rate and mortality rate. Overall survival time ranged from 1 to 86 months,with a 5-year survival rate of92. 0% and a disease-free survival time of 1-71 months. The univariate analysis showed that TNM stage( χ2= 9. 572,P = 0. 023),pathological grade( χ2= 7. 506,P = 0. 023),surgical margin invasion( χ2= 15. 123,P < 0. 001),lymph node metastasis( χ2= 4. 716,P =0. 030),and distant metastasis( χ2= 5. 534,P = 0. 019) were associated with overall survival time in the patients with PNET. Conclusion PNET patients with unclear tumor boundary on CT and MRI tend to have poor prognosis. TNM stage,pathological grade,surgical margin invasion,lymph node metastasis,and distant metastasis are closely associated with the prognosis of patients with PNET.

HBeAg seroconversion is an important process during antiviral therapy for patients with HBeAg-positive chronic hepatitis B( CHB),while the first-line antiviral drugs,such as entecavir and tenofovir disoproxil fumarate,tend to have low HBeAg clearance rate and/or seroconversion rate,and at present,there is still a lack of effective radical treatment regimens. Latest studies have shown that fecal microbial transplantation( FMT) can induce HBeAg clearance in HBeAg-positive CHB patients receiving long-term antiviral therapy.This article reviews the research advances in the role of FMT in inducing HBeAg clearance in HBeAg-positive CHB patients and points out that FMT may become a new treatment regimen for HBeAg-positive CHB patients.

Liver cirrhosis can lead to continuous pathological elevation of portal venous pressure,resulting in various complications such as esophageal and gastric varices,ascites,hepatic encephalopathy,and secondary circulatory dysfunction. Multimodality therapy is the main treatment method for portal hypertension,among which surgical treatment is mainly used to control and prevent massive esophagogastric variceal bleeding. Currently,interventional therapy and liver transplantation have gradually become a routine method for surgical intervention and can significantly improve patients' quality of life,but devascularization and shunt are still the mainstream surgical procedures. Each surgical strategy for cirrhotic portal hypertension has its own characteristics. It will be a trend in the future to evaluate patients' general conditions and clinical features and select individualized treatment regimens to achieve the best treatment outcome.

Liver transplantation is an effective method for the treatment of hepatocellular carcinoma( HCC). In order to reduce the high recurrence rate of tumor after liver transplantation for HCC,some scholars put forward the famous Milan criteria. Since the Milan criteria are too strict,some HCC patients with relatively“good biological behavior”and large lesions or multiple nodules are excluded from the waiting list for liver transplantation,and thus a large number of“expanded versions of the Milan criteria”appeared around the world. As for the histopathology of HCC,microvascular invasion( MVI) and poorly differentiated tumor tissue are significantly associated with the high recurrence rate after liver transplantation for HCC. This article reviews and summarizes the articles on the application of18F-FDG PET/CT in liver transplantation for HCC in China and foreign countries and points out that the uptake of18F-FDG in HCC lesions reflects the difference in the biological behavior( i. e.,invasion) of tumor tissue. The intense uptake of18F-FDG is positively correlated with MVI and poor differentiation of HCC. In addition,18F-FDG can detect extrahepatic metastatic lesions sensitively and accurately. Preoperative18F-FDG PET/CT findings have a high value in predicting the prognosis of liver transplantation for HCC,and it is a trend to incorporate such findings into the criteria for liver transplantation in HCC. It is also expected to unify the various expanded versions of the Milan criteria. The new criteria for liver transplantation may be defined as follows: the Milan criteria should be followed in general; as for the patients who do not meet the Milan criteria,liver transplantation can be performed for those who have lesions with negative18F-FDG PET/CT results,without the involvement of major blood vessels or extrahepatic metastasis.

Hepatocellular carcinoma( HCC) is a primary malignant tumor of the liver and has a complex pathogenesis. At present,the oxidative stress theory is one of the many important theories for the mechanism of the development and progression of this disease. Autophagy is an important way for cells to clear misfolded proteins or damaged organelles and maintain homeostasis of the internal environment. An increasing number of evidence has shown that autophagy plays an important role in liver fibrosis and HCC and is closely associated with oxidative stress. With reference to the latest research findings around the world,this article analyzes the interaction between autophagy and oxidative stress in the pathogenesis of HCC from the aspect of their relationship with HCC. It is pointed out that the molecular mechanism by which autophagy regulates oxidative stress in the development of HCC may become a research hotspot in the future; it may provide a new means for the early diagnosis and treatment of HCC to activate or block a key pathway through which autophagy regulates oxidative stress.

Liquid biopsy is a new noninvasive detection method and is also the main molecular detection method to guide the application of precision medicine. Liquid biopsy mainly includes the measurement of circulating free DNA( cf-DNA),circulating tumor cells,and exosomes,and in particular,cf-DNA is becoming a valuable molecular detection tool,especially in the early detection and diagnosis of liver cancer and parasitic infections involving the liver. This article reviews the clinical application of cf-DNA in liver cancer and liver-related parasitic diseases.

The prevalence rate of nonalcoholic fatty liver disease( NAFLD) is increasing year by year,and at present,it has become one of the most common chronic liver diseases in adults in China. NAFLD can progress from nonalcoholic fatty degeneration of the liver to nonalcoholic steatohepatitis,liver cirrhosis,hepatocellular carcinoma,NAFLD-associated cardiovascular events,and death. This article reviews the risk factors for the development of NAFLD and the progression of NAFLD to major diseases such as liver fibrosis,liver cirrhosis,liver cancer,related cardiovascular events,and death,in order to further explore the mechanism of the development and progression of NAFLD,reduce the prevalence rate of NAFLD,slow down the progression of NAFLD,reduce the mortality rate of related diseases,and achieve better prevention and treatment.

The incidence rate of nonalcoholic fatty liver disease( NAFLD) keeps increasing year by year,making NAFLD one of the most common liver diseases in the world. Reasonable diet and exercise are currently recognized as the most crucial step in the treatment of NAFLD and are the cornerstone of the management of NAFLD patients. However,diet and exercise regimens vary across countries,regions,and societies due to various objective reasons. This article reviews the diet and exercise regimens for NAFLD patients reported in different countries,regions,and literatures in recent years,in order to provide a basis for clinicians to guide NAFLD patients to develop reasonable diet and exercise strategies.

At present,ursodeoxycholic acid( UDCA) and obeticholic acid( OCA) are approved by FDA for the treatment of primary biliary cholangitis( PBC). New drugs are urgently needed for the patients who have inadequate response to UDCA or cannot tolerate pruritus,a common side effect of OCA. In recent years,a large number of basic experiments and clinical studies have shown that fibrates have a good clinical effect in the treatment of PBC. This article reviews the advances in the mechanism and clinical application of fibrates in the treatment of PBC.

Primary biliary cholangitis( PBC) is an autoimmune liver disease characterized by nonsuppurative inflammation of the small-and medium-sized bile ducts in the liver. The pathogenesis of PBC remains unclear,and immunoregulation may play a critical role. As the important components of the immune system,cytokines may be involved in the pathogenesis of PBC. This article reviews related research advances in recent years,including the roles of pro-inflammatory cytokines( interleukin-12,interleukin-17,interleukin-9,interleukin-8,tumor necrosis factor-α,and interleukin-6),the anti-inflammatory cytokine interleukin-10,and their signaling pathways in PBC,so as to deepen the understanding of the pathogenesis of PBC and explore new treatment methods.

Liver macrophages are in a dynamic equilibrium of immune tolerance and immune response after continuous antigen stimulation.The immune response of liver macrophages to external antigen is closely associated with the immune homeostasis of the liver. This article reviews the association between the programmed necrosis pathway and the apoptotic pathway and elaborates on the important role of the activity of IKK complex in the interactive regulation of the programmed necrosis and apoptotic pathways. Further studies are needed to clarify the role of programmed necrosis in the response of liver macrophages to extrahepatic antigens.

Silent information regulators are a family of highly conserved nicotinamide adenine dinucleotide( NAD+)-dependent deacetylases and has seven members( Sirt1-7). Silent information regulator 4( Sirt4),localized in the mitochondria,possesses the activity of deacetylase,ADP-ribosyltransferase,NAD+-dependent lipoamidase,and deacylase,participates in post-translational modification of mitochondrial proteins,and regulates multiple metabolic processes. Since metabolic dysfunction is closely associated with liver diseases,the role and regulatory mechanism of Sirt4 in liver diseases has attracted more and more attention. This article elaborates on the role of Sirt4 in viral hepatitis,nonalcoholic fatty liver disease,liver fibrosis,and hepatocellular carcinoma,in order to provide new perspectives for the prevention and treatment of these liver diseases.

Tumor necrosis factor-alpha-induced protein 8-like 2( TIPE2) can negatively regulate innate immunity and adaptive immunity and participate in the development and progression of various liver diseases,such as hepatitis,liver cirrhosis,and hepatocellular carcinoma,by affecting a variety of signaling pathways. This article summarizes the current research on the involvement of TIPE2 in the pathogenesis of different liver diseases and points out that TIPE2 may become a new target for the treatment of liver diseases.

Endoplasmic reticulum stress( ERS) manifests as the aggregation of misfolded and unfolded proteins in the endoplasmic reticulum lumen and disorder of calcium balance and can activate the signaling pathways involved in unfolded protein response,endoplasmic reticulum overload reaction,and sterol regulatory cascade response. ERS can not only exert a protective effect by inducing the expression of endoplasmic reticulum molecular chaperones such as glucose-regulated protein 78 and glucose-regulated protein 94,but also induce cell apoptosis.At present,there is still no systematic understanding of ERS involvement in the development and progression of liver diseases. This article summarizes the research advances in ERS-related signaling pathways and related liver diseases and elaborates on the role of ERS-mediated cell apoptosis in liver diseases. The intervention of ERS signaling pathways may provide a reference for the research and treatment of liver diseases in the future.

The Oddi sphincter has a delicate structure,and the integrity of its function has an irreplaceable role in preventing retrograde infection due to the reflux of duodenal contents and bacteria and maintaining the balance of physiological environment inside and outside the liver,the pancreas,and the gallbladder. Endoscopic sphincterotomy impairs the integrity of the Oddi sphincter,and such negative effects have received more and more attention. This article reviews the research advances in the impairment of Oddi sphincter function caused by endoscopic sphincterotomy and points out that clinicians should understand and attach importance to such impairment,perform a comprehensive analysis from various aspects,and develop reasonable diagnosis and treatment regimens based on patient's own conditions.

Hilar cholangiocarcinoma( HCCA) is a malignant tumor arising from the epithelium of the bile duct,which involves the common hepatic duct,the left and right hepatic ducts,and the confluence areas of these bile ducts. HCCA has an insidious onset and most patients are in the advanced stage when jaundice is observed,and therefore it is considered a difficult issue in the field of surgery. Radical resection is the optimal method for the treatment of HCCA and has great influence on recurrence rate of tumor and patients' survival time. Therefore,preoperative evaluation of tumor resectability is an important step of HCCA treatment. At present,there are eight main methods for HCCA staging and typing,i. e.,Bismuth-Corlette classification system,modified T staging system,TNM staging system,JSBS staging system,Gazzaniga staging system,International Cholangiocarcinoma Group staging system,Mayo staging system,and Blechacz staging system. Each staging and typing system has its own advantages and disadvantages in clinical practice. This article reviews the staging and typing methods for HCCA,with a focus on the clinical value of each staging and typing system in preoperative evaluation of radical resection and prognosis.

Intraductal papillary neoplasm of the bile duct( IPNB) is a rare type of bile duct tumors with different classification criteria and has a better prognosis than cholangiocarcinoma. Clinicians lack the awareness of this disease due to its low incidence rate. This article reviews recent research advances in the etiology and pathogenesis,pathological characteristics,clinical features,differential diagnosis,treatment and prognosis of IPNB,in order to improve the clinical diagnosis and treatment of IPNB.