Pancreatic diseases mainly include acute pancreatitis,chronic pancreatitis,pancreatic cancer,and pancreatic cysts and greatly threaten human health,and the incidence rates of pancreatic diseases are increasing around the world.Early diagnosis and intervention and delaying severe exacerbation,chronicity,and malignant transformation of disease are the focus of clinical management of pancreatic diseases.In recent years,the development of endoscopic retrograde cholangiopancreatography,ultrasound endoscopy,and related technologies have greatly improved the diagnostic efficiency of pancreatic diseases.By using the natural cavity of the human body,endoscopic intervention reduces the unnecessary damage to the surrounding tissue and has partially replaced surgery to become the first choice for treatment.However,pancreatic diseases have complex conditions,and the problems in endoscopic diagnosis and treatment and intervention timing have not been solved and thus remain the hotspots and difficulties in current research.This article reviews the difficulties and research advances in endoscopic diagnosis and treatment of major pancreatic diseases.

Since more than 30 years ago,endoscopic retrograde cholangiopancreatography and papillary myotomy have been used to remove the cause of acute biliary pancreatitis.In the past 10 years,minimally invasive endoscopic technology has developed rapidly and has been widely used in the treatment of late complications of acute pancreatitis,such as infectious pancreatic necrosis,pancreatic pseudocyst,disconnected pancreatic duct syndrome,and gastrointestinal fistula.This article focuses on the advances in the application of endoscopy in the treatment of acute pancreatitis.

Chronic pancreatitis is a disease of progressive fibrosis in pancreatic tissue,with the characteristic pathological changes of pancreatic duct stones and main pancreatic duct stenosis,some patients may frequently experience pancreatic abdominal pain or acute pancreatitis or develop the complications such as pancreatic pseudocyst and biliary stricture.Endoscopic therapy is the first-line treatment of chronic pancreatitis and has a good clinical effect in the treatment of pancreatic duct stones,main pancreatic duct stenosis,abdominal pain,and complications.With the development of technology,the complications of endoscopic therapy will be further reduced,and patients' treatment outcome will be further improved.Endoscopic therapy may bring more benefits to patients with chronic pancreatitis.

The diagnostic rate of pancreatic cystic lesions(PCLs) is increasing year by year with the development of radiological techniques.PCLs are a group of heterogeneous diseases,mainly including intraductal papillary mucinous neoplasms,mucinous cystic neoplasm,serous cystic neoplasm,and other rare cystic lesions,and different types of pancreatic cystic neoplasms have different biological behaviors and rates of malignant transformation.A precise diagnosis of patients with pancreatic cystic neoplasms helps to select surgical treatment for some patients and perform follow-up observation for other patients.Endoscopic ultrasound and endoscopic ultrasound-guided fine-needle aspiration play an important role in the diagnosis and differential diagnosis of PCLs.Endoscopic ultrasound-guided ablation therapy for PCLs is still in the early stage although it has been performed for more than a decade;however,it is safe and effective and can be used as an substitutive therapy for surgical operation,and therefore,it holds promise for clinical application.

Space-occupying lesions in the pancreas have complex etiologies,various types,and different treatment methods,and the diagnosis and differential diagnosis of such lesions have always been a difficult issue in clinical practice.Endoscopic ultrasound(EUS) is a relatively sensitive and effective method for space-occupying lesions in the pancreas.This article reviews the advances in the value of EUS in the diagnosis of space-occupying lesions in the pancreas,introduces the efficiency of EUS in common space-occupying lesions in the pancreas,and elaborates on the latest advances in EUS-guided fine-needle aspiration and other related techniques in the diagnosis of space-occupying lesions in the pancreas.

Pancreatic cancer is a gastrointestinal tumor with a high degree of malignancy.It is difficult to treat and often has poor prognosis,and therefore,it has always been a clinical challenge.Endoscopic ultrasound-guided interstitial implantation of radioactive seeds and gold fiducial markers are both innovative techniques which combine interventional ultrasonography and radiotherapy and are used for the treatment of pancreatic cancer to realize the concentrated radioactive treatment of pancreatic tumors.This article reviews the advances in the application and research of these two techniques,hoping that more studies can be conducted in the future to help it play a greater role in the treatment of pancreatic cancer.

ObjectiveTo investigate the value of baseline HBsAg quantification in predicting HBsAg clearance in pegylated interferon α-2b (PEG-INFα-2b)-treated chronic hepatitis B (CHB) patients with a low level of HBsAg. MethodsA retrospective analysis was performed for 51 HBeAg-negative CHB patients who achieved HBV DNA ＜20 IU/ml after nucleos(t)ide analogue (NA) treatment, had a normal level of alanine aminotransferase (ALT) and an HBsAg quantification of ＞0.05 IU/ml and ＜1500 IU/ml, and received sequential PEG-INFα-2b treatment in Hepatobiliary Hospital of Jilin from March 2016 to September 2018. The clinical data of serum HBsAg quantification, anti-HBs quantification, HBV DNA quantification, and ALT level were collected at baseline and at weeks 12, 24, 36, and 48 of treatment. At week 48 of treatment, 19 patients with HBsAg clearance were enrolled as response group, and 32 patients without HBsAg clearance were enrolled as non-response group. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the receiver operating characteristic (ROC) curve was used to analyze the value of baseline HBsAg quantification in predicting HBsAg clearance at week 48 of treatment. ResultsAt week 48 of treatment, 19 patients (37.25%) achieved HBsAg clearance, among whom 7 (7/19, 36.84%) had a baseline HBsAg quantitation of ≤10 IU/ml, 9 (9/19, 47.37%) had a baseline HBsAg quantitation of ＞10 IU/ml and ≤100 IU/ ml, 1 had a baseline HBsAg quantitation of ＞100 IU/ml and ≤500 IU/ml, 1 had a baseline HBsAg quantitation of ＞500 IU/ml and ≤1000 IU/ml, and 1 had a baseline HBsAg quantitation of ＞1000 IU/ml and ≤1500 IU/ml; 8 patients (15.69%) achieved HBsAg seroconversion, among whom 4 had an anti-HBs level of ＞10 IU/L and ≤100 IU/L, 3 had an anti-HBs level of ＞100 IU/L and ≤500 IU/L, and 1 had 500 IU/L. The response group had a significantly lower baseline HBsAg quantitation than the non-response group ［16.38 (2.25-61.62) IU/ml vs 363.73 (110.14-927.72) IU/ml, Z=-4.442, P＜0.001］. At weeks 12 and 24 of treatment, both groups had an increase in serum ALT level, and there was a significant difference between the response group and the non-response group ［week 12: 82.00 (55.00-123.00) U/L vs 49.00 (34.00-65.00) U/L, Z=-2.286, P=0.005; week 24: 78.00 (46.00-88.00) U/L vs 48.08 (29.79-71.75) U/L, Z=-2.617, P=0.009］. At weeks 12 and 24 of treatment, the response group had a significantly greater reduction in HBsAg than the non-response group ［week 12: 91.77% (49.62%-99.28%) vs 44.03% (15.75%-68.90%), Z=-3.312, P=0.001; week 24: 99.00% (98.00%-100.00%) vs 77.94% (37.02%-89.60%), Z=-5.100, P＜0.001］. The patients were followed up for 24 weeks after drug withdrawal, and the results showed that all 19 patients with HBsAg clearance achieved sustained response and 7 patients achieved HBsAg seroconversion. The ROC curve analysis showed that baseline HBsAg quantification predicted HBsAg clearance rate at week 48 of treatment, with an optimal predictive value of 86.36 IU/ml, an area under the ROC curve of 0.875 (95% confidence interval: 0.764-0.986), a sensitivity of 84.4%, and a specificity of 84.2%. The positive predictive value and negative predictive value were 84.21% and 84.37%, respectively. ConclusionIn CHB patients with a low level of HBsAg (≤100 IU/ml) treated by NAs, sequential PEG-INFα-2b treatment can significantly improve HBsAg clearance and seroconversion and help with HBsAg clearance at week 48 of treatment especially in those with a significant reduction in HBsAg and a significant increase in ALT in the early stage of treatment. Baseline HBsAg quantification ＜86.36 IU/ml can predict HBsAg clearance at week 48 of treatment.

Objective To investigate the expression of phosphoinositide 3-kinase(PI3 K),mammalian target of rapamycin(m TOR),70-k Da ribosomal protein S6 kinase(p70 S6 K),and interferon-α(IFNα) in umbilical cord blood plasmacytoid dendritic cells(p DCs)in parturients in the immune tolerance stage of hepatitis B virus(HBV) infection versus normal parturients.Methods A total of 20 parturients in the immune tolerance stage of HBV infection and 10 normal parturients who were hospitalized in Inpatient Department of Obstetrics in The First Affiliated Hospital of Hunan University of Chinese Medicine from October 2017 to January 2020 were enrolled as hepatitis B group and normal group,respectively.Umbilical cord blood pDCs were isolated and cultured,and CpG-A was added on day 7.The cells and the supernatant were collected after 24 hours;real-time PCR was used to measure the mRNA expression of PI3 K,m TOR,and p70 S6 K,Western Blot was used to measure the protein expression of PI3 K,m TOR,and p70 S6 K,and ELISA was used to measure the level of IFNα in the supernatant of p DCs.The two-independent-samples t-test was used for comparison of continuous data between the two groups.Results Compared with the normal group,the hepatitis B group had significantly lower mRNA and protein expression of PI3 K,m TOR,and p70 S6 K in umbilical cord blood p DCs(mRNA expression:t=-81.04,-63.07,and-34.55,all P<0.001;protein expression:t=-8.13,-7.75,and-6.71,all P<0.001).The hepatitis B group had significantly lower expression of IFNα in the supernatant of umbilical cord blood p DCs than the normal group(t=-15.88,P<0.05).Conclusion Parturients in the immune tolerance stage of HBV infection have reductions in the mRNA and protein expression of PI3 K,m TOR,and p70 S6 K and the level of IFNα in umbilical cord blood pDCs,suggesting that pDC function is inhibited.

Objective To investigate the efficiency of transient elastography(TE) in the diagnosis of liver fibrosis in patients with human immunodeficiency virus(HIV)/hepatitis C virus(HCV) co-infection.Methods The patients with HIV/HCV co-infection who were hospitalized in The Sixth People's Hospital of Xinjiang Uygur Autonomous Region from January 2013 to December 2018 were enrolled and related indices were collected,including routine blood test results,liver function,renal function,coagulation,biochemical parameters for liver fibrosis,and viral load of HIV and HCV.Noninvasive models for liver fibrosis [aspartate aminotransferase-to-platelet ratio index(APRI) and fibrosis-4(FIB-4) ]were calculated,and liver biopsy was performed for all patients.TE was performed within 3 days before biopsy,and the results were expressed as liver stiffness measurement(LSM).A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison between multiple groups;a Spearman correlation analysis was used to investigate the correlation of LSM,APRI,FIB-4,biochemical parameters for liver fibrosis,HCV RNA quantification,and liver biopsy results with the stage of liver fibrosis;the receiver operating characteristic(ROC) curve was used to evaluate the efficiency and cut-off value of LSM in determining the stage of liver fibrosis.Results A total of 76 patients with chronic HCV/HIV co-infection who underwent liver biopsy and were diagnosed with liver fibrosis were enrolled.The correlation analysis showed that LSM had the best correlation with the stage of liver fibrosis(r=0.526,P<0.001)and had a better correlation than APRI(r=0.403,P<0.001) and FIB-4(r=0.441,P<0.001),and among the biochemical parameters for liver fibrosis,only type IV collagen was correlated with the stage of liver fibrosis(r=0.339,P<0.05).HCV RNA quantification had no correlation with the stage of liver fibrosis.For marked liver fibrosis,LSM had an area under the ROC curve of 0.809,0.929,and0.906,respectively,in the diagnosis of S2,S3,and S4 liver fibrosis at the optimal cut-off values of 11.6 k Pa,12.7 k Pa,and 14.5 k Pa,respectively.Conclusion TE can accurately determine the stage of liver fibrosis in patients with HCV/HIV co-infection,which might help to avoid liver biopsy and provide a more reliable basis for developing antiviral regimen and judging the progression of liver fibrosis,and therefore,it holds promise for clinical application.

ObjectiveTo investigate the expression profiles of sphingolipids in peripheral serum in patients with hepatitis B/C cirrhosis and those with non-viral hepatitis-related cirrhosis. MethodsA total of 104 patients with liver cirrhosis who were admitted to Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, from July 2014 to May 2015 were enrolled as subjects, and finally 97 patients with liver cirrhosis were enrolled, among whom there were 66 patients (68.04%) with hepatitis B/C cirrhosis and 31 patients (31.96%) with non-viral hepatitis-related cirrhosis. High-performance liquid chromatography-mass spectrometry was used to measure the expression of 57 sphingolipids in peripheral serum. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The variables with statistical significance in the univariate analysis were included in the multivariate analysis. ResultsThere were no significant differences between the two groups in age, proportion of male patients, total bilirubin, direct bilirubin, and gamma-glutamyl transpeptidase (all P＞0.05). As for the 57 sphingolipids in peripheral serum,  compared with the non-viral hepatitis-related cirrhosis group, the viral hepatitis-related cirrhosis group had significantly higher expression of Cer(d18∶1/12∶0) ［168.61 (16854-168.88) pmol/0.1 ml vs 168.53 (168.48-168.63) pmol/0.1 ml, Z=-2.54, P＜0.05］, HexCer (d18∶1/14∶1) ［213.93 (211.15-218.92) pmol/0.1 ml vs 212.26 (209.90-214.64) pmol/0.1 ml, Z=-2.03, P＜0.05］, and dhCer(d18∶0/24∶1)-1-P ［60.07 (59.40-61.23) pmol/0.1 ml vs 59.42 (59.28-59.87) pmol/0.1 ml, Z=-2.32, P＜0.05］. The logistic regression analysis revealed that high expression of dhCer(d18∶0/24∶1)-1-P was independently associated with hepatitis B/C cirrhosis (odds ratio=111, 95% confidence interval: 1.004-1.225, P=0.042). The subgroup analysis of the patients with viral hepatitis-associated cirrhosis showed that there were no significant differences between the patients with hepatitis B cirrhosis and those with hepatitis C cirrhosis in the expression of Cer(d18∶1/12∶0), HexCer (d18∶1/14∶1), and dhCer(d18∶0/24∶1)-1-P (Z=-0.563, -0.610, and -0.579, all P＞0.05). ConclusionThe sphingolipid dhCer (d18∶0/24∶1)-1-P in peripheral serum is closely associated with hepatitis B/C cirrhosis and may help to understand the features of viral hepatitis-related cirrhosis from the perspective of sphingolipids.

ObjectiveTo investigate the clinical value of routine liver fibrosis markers in the noninvasive diagnosis of high-risk gastroesophageal varices (HRGOV) in patients with liver cirrhosis. MethodsA total of 165 patients with liver cirrhosis who underwent gastroscopy and routine laboratory examinations in Nanfang Hospital, Southern Medical University, from January to December 2018 were enrolled, and the presence or absence of HRGOV was determined based on the gold standard of gastroscopy with reference to Child-Pugh score. 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. The area under the receiver operating characteristic curve (AUC) was calculated and compared, and likelihood ratio was used to confirm diagnosis and exclude cut-off values. ResultsOf all 165 patients, 83 (50.3%) patients were diagnosed with HRGOV. There were significant differences between the HRGOV group and the non-HRGOV group in albumin (t=-5.118, P＜0.001), platelet count (Z=-5.409，P＜0.001), proportion of male patients (χ2=3.883, P=0.049), prothrombin time (Z=-4.433, P＜0.001), prothrombin time activity (Z=-4.447, P＜0.001), international normalized ratio (Z=-4.426, P＜0.001), white blood cell count (Z=-2.371, P=0.018), spleen thickness (Z=-6.296, P＜0.001), aspartate aminotransferase-to-platelet ratio index (APRI) (Z=-3.409, P=0.001), fibrosis index based on four factors (FIB-4) (Z=-4.494, P＜0.001), gamma-glutamyl transpeptidase-to-platelet ratio (GPR) (Z=-2.377, P=0.017), red blood cell distribution width-to-platelet ratio (RPR) (Z=-5.345, P＜0.001), Easy Liver Fibrosis Test (eLIFT)(t=3.170, P=0.002), gastroscopic grade (χ2=131.714, P＜0001), and Child-Pugh class (χ2=30.663, P＜0.001). Spleen thickness on ultrasound, platelet count, RPR, FIB-4, APRI, eLIFT, and GPR had an AUC of 0.785, 0.747, 0.744, 0.703, 0.652, 0.622, and 0.606, respectively, in the diagnosis of HRGOV, and there was no significant difference between the models with an AUC of ＞0.7 (P＞0.05). With spleen thickness ＜29.5 mm for exclusion and spleen thickness ≥53.0 mm for confirmed diagnosis, 51 patients (30.9%) had no need to undergo gastroscopy, with a diagnostic accuracy of 94.1%; with RPR ＜0.067 for exclusion and RPR ≥0.480 for confirmed diagnosis, 19 patients (115%) had no need to undergo gastroscopy, with a diagnostic accuracy of 89.5%. Spleen thickness followed by RPR was used to confirm the presence or absence of HRGOV in 63 patients (38.2%) and achieved a diagnostic accuracy of 92.1%. ConclusionSpleen thickness, RPR, platelet count, and FIB-4 had moderate efficiency in the diagnosis of HRGOV, among which spleen thickness has the highest diagnostic efficiency, followed by RPR, platelet count, and FIB-4. Spleen thickness followed by RPR can be used for the screening for HRGOV in liver cirrhosis patients, helping some patients avoid gastroscopy.

ObjectiveTo investigate the clinical manifestations, emergency endoscopic diagnosis and treatment, and prognosis of rebleeding after different secondary prevention measures for esophagogastric variceal bleeding in cirrhotic portal hypertension. MethodsA retrospective analysis was performed for the clinical data of 254 patients with rebleeding after secondary prevention (endoscopic therapy, surgical treatment, or interventional prevention) for esophagogastric variceal bleeding who underwent emergency endoscopic diagnosis and treatment in The Fifth Medical Center of Chinese PLA General Hospital from January 2018 to April 2019, and 419 patients who received medication alone for the prevention of rebleeding during the same period of time were enrolled as controls. Clinical features were observed and compared between groups. An analysis of variance was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis H test was used for comparison of continuous data with heterogeneity of variance between groups. The least significant difference Bonferroni test was used for further comparison between two groups. The chi-square test  was used for comparison of categorical data between groups. ResultsAmong the 254 patients with rebleeding after secondary prevention, 144 (56.69%) received endoscopic prevention, 40 (15.75%) received surgical prevention, 33 (12.99%) received interventional prevention, and 37(14.57%) received prevention with endoscopy combined with other prevention measures. As for the time from last prevention to bleeding, 57.50% in the surgical prevention group had a time of more than 5 years, and 69.70% in the interventional prevention group experienced bleeding within 1 year after transjugular intrahepatic portosystemic shunt; 40.28% in the endoscopic prevention group and 35.14% in the combined prevention group experienced rebleeding within 1 year after prevention ended. During rebleeding, the interventional prevention group and the combined prevention group had a significantly higher incidence rate of hepatic encephalopathy than the other groups (all P＜0.001), and the interventional prevention group had significantly better controlled ascites than the other groups (all P＜0.05). There were significant differences in various clinical indices between these groups during rebleeding (all P＜0.001), and the endoscopic prevention group had significantly higher levels of hemoglobin and albumin than the surgical prevention group (P＜0.001 and P=0.001) and the medication prevention group (P=0.001 and P＜0.001). The surgical prevention group had a significantly higher platelet count than the interventional prevention group (P=0.037), the combined prevention group (P＜0.001), and the medication prevention group (P=0.012). The medication prevention group had a significantly higher level of bilirubin than the endoscopic prevention group (P=0.037), the interventional prevention group (P=0.025), and the combined prevention group (P＜0.001); the surgical prevention group had a significantly higher level of creatinine than the other four groups (all P＜0.05); the combined prevention group had significantly better coagulation parameters prothrombin time and international normalized ratio than the medication prevention group (both P=0.002). The medication prevention group had a significantly higher proportion of patients with active bleeding than the endoscopic prevention group (P＜0.001), the interventional prevention group (P=0.004), and the combined prevention group (P=0.008). The surgical prevention group and the medication prevention group had a significantly higher proportion of patients with esophageal variceal bleeding than the other groups (all P＜0.05), and the interventional prevention group had a significantly higher proportion of patients with peptic ulcer and bleeding than the other four groups (all P＜0.05). The medication prevention group had significantly higher dissatisfaction rate and failure rate of endoscopic treatment than the endoscopic prevention group (P＜0.001), the interventional prevention group (P=0.007), and the combined prevention group (P＜0.001). The medication prevention group had significantly higher rebleeding rate and mortality rate within 42 days than the other four groups (all P＜0.05). Conclusion Compared with medication prevention alone, interventional prevention, endoscopic prevention, or combined secondary prevention can significantly alleviate the degree of esophagogastric variceal rebleeding, improve the hemostatic rate of emergency endoscopy, and significantly reduce rebleeding rate and mortality rate within 42 days. The clinical features of rebleeding after different secondary prevention measures should be considered to perform individualized treatment of patients with rebleeding after secondary prevention for esophagogastric variceal bleeding.

ObjectiveTo investigate the association between transversal psoas thickness index (TPTI) and nutritional risk in patients with liver cirrhosis or hepatocellular carcinoma (HCC). MethodsThe patients with liver cirrhosis or HCC who were admitted to Tianjin Third Central Hospital from January 2018 to January 2019 and underwent abdominal CT examination were enrolled, and according to the inclusion and exclusion criteria, the patients were screened and divided into liver cirrhosis group and HCC group. The patients with liver cirrhosis or HCC were divided into nutritional risk group and non-nutritional risk group according to the results of Nutritional Risk Screening 2002. Related clinical data, including body height, body weight, liver function, and TPTI were collected. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test and the trend chi-square test were used for comparison of categorical data between two groups. A logistic regression analysis was used to analyze the factors for nutritional risk in patients with liver cirrhosis or HCC. ResultsA total of 151 patients were enrolled in this study, with 95 patients in the liver cirrhosis group and 56 patients in the HCC group. The incidence rates of nutritional risk in patients with Child-Pugh class A/B/C liver cirrhosis were 61.2%, 80.6%, and 86.7%, respectively, and those in patients with Child-Pugh A/B/C HCC were 44.4%, 84.6%, and 85.7%, respectively. The trend chi-square test and the Spearman correlation analysis showed that the incidence rate of nutritional risk tended to increase with the reduction in liver function reserve in patients with liver cirrhosis or HCC (χ2=5.051, P=0.025; r=0.388, P=0.003). For the patients with liver cirrhosis or HCC, the nutritional risk group had a significantly lower TPTI than the non-nutritional risk group (both P＜0.05). For the patients in the liver cirrhosis group, after adjustment for albumin level in the logistic regression model, the higher the TPTI value, the lower the possibility of nutritional risk in patients (odds ratio=0.766, 95% confidence interval: 0.642-0.915). ConclusionThe incidence rate of nutritional risk in patients with liver cirrhosis or HCC tends to increase with the reduction in liver function reserve. For patients with liver cirrhosis, the higher the TPTI value, the lower the possibility of nutritional risk; for patients with HCC, those with nutritional risk have a lower TPTI value.

Objective To investigate the value of microvascular invasion(MVI) grade versus TNM stage and Barcelona Clinic Liver Cancer(BCLC) stage in predicting the early recurrence of hepatocellular carcinoma(HCC) after radical hepatectomy and the clinical value of MVI grade through a retrospective analysis of the prognosis of patients after HCC surgery.Methods A total of 100 HCC patients who underwent radical hepatectomy in Department of Hepatobiliary Surgery,The Second Affiliated Hospital of Kunming Medical University,from December2015 to December 2017 were enrolled,and according to the results of the 2-year follow-up,these patients were divided into recurrence group with 49 patients and non-recurrence group with 51 patients.Laboratory markers and MVI grade were compared between the two groups,and MVI grade,TNM stage,and BCLC stage were compared in terms of their value in predicting 2-year recurrence-free survival(RFS) after surgery.The t-test was used for comparison of normally distributed continuous data between groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups;the chi-square test was used for comparison of non-ranked data between two groups,and the Mann-Whitney U test was used for comparison of ranked data between groups;the Kruskal-Wallis H test was used for comparison between three groups,and the Bonferroni method was used for further comparison between two groups.The Kaplan-Meier method was used to plot survival curves,and the log-rank test was used for survival analysis.The consistency index calculated by RMS package was used to compare the predictive value of clinicopathological staging systems.Results Compared with the non-recurrence group,the recurrence group had significantly higher alpha-fetoprotein level(Z=0.099,P<0.05) and proportion of patients with MVI(Z=-2.651,P=0.008).After 2 years of follow-up,there were 47 patients in M0 group,34 in M1 group,and 19 in M2 group;18 patients in the M0 group(38.3%),16 in the M1 group(47.1%),and 15 in the M2 group(78.9%) experienced recurrence,and there was a significant difference in recurrence between the three groups(H=8.934,P=0.011);further comparison between two groups showed that the M2 group had a significantly higher number of patients with recurrence than the M0 group and the M1 group(P<0.05).The cumulative recurrence rate was 41.9% in the M0 + M1 group and 78.9% in the M2 group,and there was a significant difference between these two groups(χ2=11.445,P<0.001);the M2 group had a significantly lower 2-year RFS rate than the M0 + M1 group.As for BCLC stage,the cumulative recurrence rate was 36.2% in the patients with early-stage(stage 0 + stage 1) HCC and 66.7% in those with middle-and late-stage(stage 2 + stage 3) HCC,and there was a significant difference between the two groups(χ2=5.047,P=0.012);the middle-and late-stage group had a significantly lower 2-year RFS rate than the early-stage group.As for TNM stage,the cumulative recurrence rate was 24.5% in the patients with stage Ⅰ HCC and 72.5% in those with stage Ⅱ + Ⅲ HCC,and there was a significant difference between the two groups(χ2=17.223,P<0.001);the stage Ⅱ + Ⅲ group had a significantly lower 2-year RFS rate than the stage I group.TNM stage had the highest value in predicting 2-year RFS,while MVI and BCLC stage had a similar predictive value(consistency index:0.659 vs 0.598 vs 0.600).Conclusion Compared with MVI patients with no risk or low risk,patients with high-risk MVI have a significantly higher probability of early recurrence,and thus MVI may become an evaluation target for postoperative treatment.

Objective To investigate whether local treatment based on limited segmental resection can improve the prognosis of colorectal liver oligometastases(CRLOM) compared with other non-surgical treatment method,as well as the individualized regimen of this treatment method.Methods A retrospective analysis was performed for the clinical data of 74 CRLOM patients who underwent local treatment in The First Affiliated Hospital of Kunming Medical University from January 2012 to December 2018,and according to the treatment method,they were divided into surgical group with 39 patients and non-surgical group with 35 patients.Treatment regimen and complications were compared between the two groups.The t-test or the Mann-Whitney U test was used for comparison of continuous data between groups;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 to plot survival curves and calculate median disease-free survival(DFS) time and overall survival(OS) time,and the log-rank test was used for survival analysis.Results Among the 39 patients in the surgical group,23 underwent laparotomy and 16 underwent laparoscopy;as for the surgical procedure,11 underwent limited segmental/subsegmental resection alone,21 underwent limited segmental/subsegmental resection combined with wedge resection of small lesions,and 7 underwent limited segmental/subsegmental resection combined with radiofrequency ablation(RFA);5 patients experienced postoperative complications,with bleeding in 1 patient,biliary fistula in 1 patient,and pleural effusion in 3 patients.Among the 35 patients in the non-surgical group,18 underwent ultrasound-or CT-guided RFA combined with transarterial chemoembolization(TACE),5 underwent TACE alone,9 underwent RFA,and 3 underwent stereotactic body radiotherapy;as for postoperative complications,1 patient experienced liver abscess after TACE,and 1 experienced pneumothorax after RFA.No patient died within 30 days after treatment.The surgical group had a DFS time of 38 months(95% confidence interval [CI]:31.3-44.9)and an OS time of 27 months(95% CI:19.9-34.0),and the non-surgical group had a DFS time of 64 months(95% CI:57.6-70.1)and an OS time of 43 months(95% CI:36.2-50.0),with significant differences between the two groups(χ2=6.072 and 11.685,P=0.014 and 0.001).The surgical group had a 1-year survival rate of 92.3% and a 5-year survival rate of 41.0%,while the non-surgical group had a 1-year survival rate of 82.8% and a 5-year survival rate of 14.3%.Conclusion Compared with non-local surgical treatment,local treatment based on limited segmental resection can significantly improve the prognosis of CRLOM in patients with colorectal cancer.The surgical procedure should be individualized according to lesion characteristics.

Objective To investigate the expression and clinical significance of serum exosomal microRNA(miRNA)-221-3 p in hepatocellular carcinoma(HCC).Methods A total of 66 patients who underwent surgery in Nanjing Drum Tower Hospital,Nanjing University Medical School,from February 2010 to December 2014 and were diagnosed with HCC were enrolled as HCC group,and 25 individuals who underwent physical examination in our hospital during the same period of time were enrolled as control group.The exosome extraction kit was used to isolate the exosomes in serum;Western blotting was used to measure the expression of exosome markers;a transmission electron microscope was used to observe the morphology of serum exosomes;quantitative real-time PCR was used to measure the expression of serum exosomal miRNA-221-3 p.The Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.The Kaplan-Meier method and the log-rank test were used to analyze the association of the expression of serum exosomal miRNA-221-3 p with prognosis,and the Cox proportional hazards regression model was used to analyze the influencing factors for prognosis.Results Serum exosomes were small membranous vesicles with a diameter of about 40-100 nm,and HSP70,Alix,and CD63 were expressed in the exosomes.The HCC group had significantly higher expression of serum exosomal miRNA-221-3 p than the control group(U=354.00,P<0.001).In the patients with HCC,the high expression of serum exosomal miRNA-221-3 p was associated with tumor size(χ2=6.016,P=0.014),capsular invasion(χ2=7.580,P=0.006),and TNM stage(χ2=6.340,P=0.012).In addition,the HCC patients with high expression of serum exosomal miRNA-221-3 p had a significantly lower overall survival rate than those with low expression(χ2=17.105,P<0.001).The multivariate analysis showed that the expression of serum exosomal miRNA-221-3 p(hazard ratio [HR]=2.434,95% confidence interval [CI]:1.178-5.027,P=0.016)and tumor stage(HR=2.653,95% CI:1.222-5.760,P=0.014) were independent risk factors for the prognosis of patients with HCC.Conclusion There is a significant increase in the expression of serum exosomal miRNA-221-3 p in HCC patients,which provides a reference for the diagnosis and prognostic evaluation of HCC.

Objective To investigate the constituent ratio and changing trend of four common types of non-infectious liver diseases in our hospital from 2002 to 2018.Methods Medical records were collected from 37 973 patients with non-infectious liver diseases who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from 2002 to 2018,and according to the first diagnosis listed in the first page of discharge medical records,14 971 patients had alcoholic liver disease,11 406 had drug-induced liver injury,1776 had nonalcoholic fatty liver disease,and 9820 had autoimmune liver diseases.The distribution characteristics of age and sex and the changing trend were analyzed.The chi-square test was used for comparison of categorical data between groups.Results The patients with drug-induced liver injury accounted for 30.04% of the patients with common non-infectious liver diseases,and it ranked only second to alcoholic liver diseases in all four types.The proportion of patients with drug-induced liver injury among the hospitalized patients with liver diseases tended to increase before 2011,and this constituent ratio showed a trend of transient reduction after 2012.There was a significant difference in sex distribution between the patients with different ages(χ2=113.087,P<0.05).The age of onset was mainly 40-49 years in male patients and50-59 years in female patients.There were significant differences in the age distribution of drug-induced liver injury between the male and female patients hospitalized in different years(χ2=369.252 and 663.490,both P<0.05).There was no significant change in the range of peak age of onset in male patients,while in female patients,the range of peak age of onset showed an aging trend from 40-49 years to50-59 years in the recent 6 years.Conclusion Drug-induced liver injury has become a major part of non-infectious liver disease and often occurs in middle-aged and elderly women.The prevention,control,diagnosis,and treatment of drug-induced liver injury should be taken seriously,especially medication guide and education for middle-aged and elderly women,and it is recommended to strengthen the monitoring of liver function during medication.

ObjectiveTo investigate the clinical effect and safety of robot-assisted laparoscopic hepatectomy (RALH) versus open hepatectomy (OH) in the treatment of liver diseases. MethodsWeb of Science, PubMed, Cochrane Library, Embase, CNKI, CBM, VIP, and Wanfang Data were searched for Chinese and English articles on RALH versus OH in the treatment of liver diseases published up to February 2020. The quality of the articles included was assessed, and RevMan 5.1 was used to perform the meta-analysis. ResultsSeven studies were included, with a total of 754 patients (328 patients in the RALH group and 426 in the OH group). The meta-analysis showed that compared with the OH group, the RALH group had a significantly longer time of operation (mean difference ［MD］=59.41, 95% confidence interval ［CI］: 9.74-109.08, P=0.02), significantly higher blood transfusion rate (relative risk ［RR］=2.24, 95%CI: 1.04-4.82, P=0.04) and rate of hepatic portal occlusion (RR=2.27, 95%CI: 1.37-3.75, P=0.001), a significantly shorter length of hospital stay (MD=-3.87, 95%CI: -5.63 to -2.12,P＜0.001), and significantly lower overall incidence rate of postoperative complications (RR=0.58, 95%CI: 0.41-0.81, P=0.001) and incidence rates of major postoperative complications (RR=0.45, 95%CI: 0.22-0.91, P=0.03). There was no significant difference in intraoperative blood loss between the two groups (P＞0.05). ConclusionFor hepatectomy, RALF can shorten the length of hospital stay and reduce postoperative complications, creating conditions for minimally invasive hepatectomy and rapid recovery.

Objective To investigate the protective effect of urolithin A(Uro-A) against hepatic ischemia-reperfusion injury(HIRI) in rats.Methods A total of 40 Sprague-Dawley rats were randomly divided into sham-operation group,model group,low-dose Uro-A(1 mg/kg) group,and high-dose Uro-A(3 mg/kg) group,with 10 rats in each group.Before modeling,the rats in the low-and high-dose Uro-A groups were given the drug by gavage once a day for 5 consecutive days.The model was established after anesthesia,and the serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and lactate dehydrogenase(LDH) were measured at 6 hours after the recovery of blood flow.ELISA was used to measure the content of superoxide dismutase(SOD),malondialdehyde(MDA),catalase(CAT),interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α) in the liver,and liver pathological injury and hepatocyte apoptosis were evaluated.Western blot was used to measure the expression of the endoplasmic reticulum chaperone glucose-regulated protein 78(GRP78),the downstream transcription factor CHOP,and the apoptosis protein caspase-12 in the liver.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the model group,the high-dose Uro-A group had significantly lower levels of ALT,AST,LDH,MDA,CAT,IL-1β,IL-6,TNF-α,CHOP,GRP78,and caspase-12 and apoptosis rate and a significantly higher content of SOD(all P<0.05).The model group had severe damage of liver structure,with a positive rate of 90%,while the high-dose Uro-A group had intact liver structure without obvious tissue proliferation or inflammatory cell proliferation,with a negative rate of 80%.Compared with the high-dose Uro-A group,the low-dose Uro-A group had significant increases in the levels of ALT,AST,and LDH and apoptosis rate(all P<0.05).Conclusion Uro-A pretreatment can alleviate liver ischemia-reperfusion injury in rats and reduce oxidative damage and the release of inflammatory factors,possibly by inhibiting the endoplasmic reticulum stress pathways and reducing hepatocyte apoptosis.

Objective To investigate the correlation of signal intensity on Gd-EOB-DTPA-enhanced magnetic resonance imaging(MRI) with the expression of organic anion transport polypeptide 1(OATP1) and multidrug resistance-associated protein 2(MRP2) on the surface of hepatocyte membrane.Methods A total of 16 healthy adult male beagle dogs were randomly divided into control group and acute liver failure group,with 8 dogs in each group.Gd-EOB-DTPA-enhanced MRI was performed for the dogs in the acute liver failure group at 24 hours after modeling to measure the signal intensity of different signal areas of liver parenchyma and the percentage of enhancement slope in the first-pass rapid rise period,and according to the MRI images of the hepatocyte phase(20 minutes after the injection of Gd-EOB-DTPA),the high-,medium-,and low-signal areas were selected for liver biopsy.Gd-EOB-DTPA-enhanced MRI was performed for the dogs in the control group after the injection of an equal volume of normal saline using the method,and liver biopsy was performed in the corresponding area.Western blot was used to measure the expression of the Gd-EOB-DTPA uptake protein OATP1 and its excretion protein MRP2 in liver tissue.An analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups;the independent samples t-test was used for comparison of the protein expression of OATP1 and MRP2 in the same signal area between groups.A Pearson correlation analysis was used to investigate the correlation between protein expression levels and signal intensity.Results The Gd-EOB-DTPA-enhanced MRI images of the beagle dogs with acute liver failure showed a significant difference in signal between the high-,medium-,and low-signal areas during hepatocyte phase,and there were also significant differences in the corresponding SIbase value,SIst value,and percentage of enhancement slope during the first-pass rapid rise period(F=70.70,55.12,and 19.82,all P<0.001).In the acute liver failure group,there were significant differences in the expression of OATP1 and MRP2 in liver tissue between different signal areas(F=7.508 and 6.212,both P<0.01),and compared with the control group,the acute liver failure group had a significant reduction in the expression of OATP1 in the medium-and low-signal areas(t=3.301 and 3.641,both P<0.05),which was consistent with the trend of signal reduction in hepatocyte phase;the reduction in the low-signal area was significantly greater than that in the high-signal area(t=3.436,P<0.05) and the medium-signal area(t=2.378,P<0.05).Compared with the control group,the acute liver failure group had a significant increase in the expression of MRP2 in the high-,medium-,and low-signal areas,with a tendency to increase from the high-signal area to the medium-signal area and low-signal area(t=-7.236,-8.130,and-9.614,all P<0.05).Conclusion The expression levels of OATP1 and MRP2 on the surface of hepatocyte membrane are correlated with the degree of enhancement of liver parenchyma in the hepatocyte phase of Gd-EOB-DTPA-enhanced MRI,which provides a certain basis for the segmental assessment of hepatocyte function.

Objective To investigate the clinical features of acute pancreatitis(AP) with metabolic syndrome(MS) and the influencing factors for prognosis.Methods A retrospective analysis was performed for the clinical data of 590 patients with AP who were admitted to The Affiliated Hospital of Southwest Medical University from January 2013 to January 2019,and according the presence or absence of MS,they were divided into MS group with 178 patients and non-MS group with 412 patients and basic clinical features were compared between the two groups.According to the severity of AP,they were divided into mild acute pancreatitis(MAP) group with 317 patients,moderate-severe acute pancreatitis(MSAP) group with 171 patients,and severe acute pancreatitis(SAP) group with 102 patients,and the component indicators of MS were compared between the three groups.The t-test was used for comparison of normally distributed continuous data between two groups,and a one-way analysis of variance was used for comparison between multiple groups;the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups,and the Kruskal-Wallis H test was used for comparison between multiple groups;Bonferroni correction was used for further comparison between two groups.The chi-square test was used for comparison of categorical data between groups;the trend chi-square test was used for comparison of one-way ordinal categorical data,and the Goodman-Kruskal Gamma analysis was used for two-way ordinal categorical data.An ordinal logistic regression analysis was used to investigate the correlation between body mass index(BMI) and severity of AP,and a binary logistic regression analysis was used to investigate the correlation between MS and severity of AP.Results The most common causes of MS with AP were hyperlipidemia(48.3%) and biliary disease(24.7%).The patients with SAP were more likely to have MS(χ2=141.519,P<0.001),and the patients with AP and MS tended to have a significantly higher clinical system score,significantly more local and systemic complications,significantly longer hospital stays,a significantly higher ICU admission rate,and a significantly higher mortality rate(all P<0.05).The severity of AP increased with the increase in MS components(overweight,hypertension,diabetes,and dyslipidemia),(G=0.540,P<0.001).There were significant differences between the MAP,MSAP,and SAP groups in BMI(F=9.291,P<0.001) and high-density lipoprotein cholesterol(HDL-C)(χ2=40.351,P<0.001),and the SAP group had significantly higher BMI and significantly lower HDL-C than the MAP group and the MSAP group(all P<0.05).The ordinal logistic regression analysis showed that BMI was an independent risk factor for the progression of AP(odds ratio [OR]=1.091,95% confidence interval [CI]:1.041-1.143,P<0.001).Binary logistic regression models were established based on the severity of AP,with MAP group versus non-MAP group as model 1 and SAP group versus non-SAP group as model 2.The results showed that in model 1,the incidence rate of non-MAP was 5.867 times that of MAP in patients with MS(OR=5.867,95% CI:3.072-11.207,P<0.001),and in model 2,the incidence rate of SAP was 7.214 times that of non-SAP(OR=7.214,95% CI:3.018-17.244,P<0.001).Both model 1 and model 2 showed that HDL-C was a protective factor against the progression of AP(model 1:OR=0.593,95% CI:0.387-0.910,P=0.017;model 2:OR=0.314,95% CI:0.160-0.614,P=0.001).Conclusion AP with MS on admission may suggest poor prognosis,and BMI and HDL-C are closely associated with disease progression.

Objective To analyze the articles on endoscopic retrograde cholangiopancreatography(ERCP),an important method for minimally invasive treatment of biliary and pancreatic diseases,published worldwide,and to investigate the status,hotspots,and development trends in this field.Methods The web of science core collection database in Web of Science platform was selected to search by the subject words“TS=(Cholangiopancreatography,Endoscopic Retrograde) ”,for the articles published from January 1,2015 to December 31,2019,and the literature type was selected as“article”.CiteSpace 5.6.R2(64-bit) was used to analyze the authors,key words,institutions,countries(regions),and references and plot visualized maps.Results A total of 1535 articles on ERCP were included.The analysis showed that Hiroyuki Isayama had the highest number of published articles,followed by Yousuke Nakai and Takeshi Ogura,and University of Tokyo had the highest number of published articles,followed by Shanghai Jiao Tong University and University of Ulsan College of Medicine.Moreover,the US,Japan,and China were the top three countries from the aspect of the number of published articles in the recent 5 years,and ERCP,complication,and risk factor were the key words with the highest frequency in the recent 5 years.The most frequently cited articles mainly focused on the complications of ERCP and related consensus or guidelines.Conclusion The main research hotspots and trends in the field of ERCP are related factors and clinical prevention of ERCP-related complications.

Objective To investigate the clinical effect of the artery-first approach versus the traditional approach for pancreaticoduodenectomy.Methods PubMed,Embase,Cochrane Library,Wanfang Data,CNKI,and VIP were searched for randomized controlled trials(RCTs) and non-RCTs on the artery-first approach versus the traditional approach for pancreaticoduodenectomy published from January1,2003 to January 31,2020,and the articles were screened according to inclusion and exclusion criteria.RevMan5.3 software was used to perform the meta-analysis.Mean difference and odds ratio(OR) were used to analyze continuous variables and binary variables,95%confidence interval(CI) was calculated for each variable.The fixed effects model was used for unobserved heterogeneity,and the random effects model was used for significant heterogeneity.Funnel plots were used to evaluate the absence or presence of publication bias.Results A total of 18 articles were included.The results of the meta-analysis showed that compared with pancreaticoduodenectomy with the traditional approach,pancreaticoduodenectomy with the artery-first approach reduced pancreatic fistula(OR=0.68,95% CI:0.48-0.94,P<0.05),delayed gastric emptying after surgery(OR=0.51,95% CI:0.35-0.73,P<0.05),postoperative abdominal infection(OR=0.50,95% CI:0.30-0.84,P<0.05),local recurrence(OR=0.36,95% CI:0.20-0.65,P<0.05),and incidence rate of blood transfusion(OR=0.20,95% CI:0.07-0.59,P<0.05) and increased R0 resection rate(OR=3.04,95% CI:1.86-4.99,P<0.05).Symmetric funnel plots were observed for the incidence rates of pancreatic fistula and delayed gastric emptying after surgery,suggesting that publication bias of the articles included had little influence on the results of this study.Conclusion The artery-first approach is as safe and feasible as the traditional approach for pancreaticoduodenectomy,and the artery-first approach is superior to the traditional approach in reducing some important postoperative complications and increasing R0 resection rate.Therefore,the artery-first approach holds promise for clinical application.

Objective To investigate the safety and clinical effect of pancreaticoduodenectomy with total mesopancreas excision(TMpE)versus traditional pancreaticoduodenectomy(PD) in the treatment of pancreatic head carcinoma and periampullary cancer.Methods PubMed,Web of Science,Cochrane Library,CBM,CNKI,Wanfang Data,and VIP were searched for the Chinese and English articles on the clinical effect of TMpE and PD in the treatment of pancreatic head carcinoma and periampullary cancer published from January 2007 to February 2020.Quality assessment was performed for the articles included,and Revman 5.3 software was used to perform the Meta-analysis.Results Five retrospective cohort studies were included after screening,with a total of 358 patients,among whom 188 underwent TMpE and 170 underwent PD.The results of the meta-analysis showed that compared with the PD group,the TMpE group had a significant increase in the incidence rate of pancreatic fistula(odds ratio [OR]=1.69,95% confidence interval [CI]:1.03-2.78,P=0.04),while there was no significant difference in the incidence rate of postoperative complications between the two groups(OR=1.51,95% CI:0.76-2.98,P=0.24).In addition,TMpE improved R0 resection rate(OR=2.89,95% CI:1.30-6.43,P=0.009),number of dissected lymph nodes(mean difference [MD]=5.14,95% CI:4.16-6.13,P<0.001),and 1-year survival rate after surgery(OR=2.60,95% CI:1.45-4.69,P=0.001),without increasing the time of operation(MD=7.74,95% CI:-42.84 to 58.33,P=0.76),intraoperative blood loss(MD=-45.89,95% CI:-198.19 to 106.41,P=0.55),and the length of postoperative hospital stay(MD=-4.62,95% CI:-16.60 to 7.36,P=0.45).Conclusion TMpE is safe and feasible in the treatment of pancreatic head carcinoma and periampullary cancer and has the advantages of high R0 resection rate and 1-year survival rate after surgery,and therefore,it may become a preferred treatment method for pancreatic head carcinoma and periampullary cancer.

Chronic hepatitis B virus(HBV) infection and end-stage liver disease caused by such infection pose a serious threat to the health of Chinese citizens.The presence of HBV ccc DNA is the main reason for the difficulties in the treatment of chronic hepatitis B and recurrence after drug withdrawal.HBV RNA,as a new serum marker,is produced by ccc DNA transcription,and theoretically,it can reflect the level and transcriptional activity of ccc DNA in hepatocytes.This article mainly introduces the formation of serum HBV RNA and analyzes its significance in evaluating the activity or status of ccc DNA in liver tissue and predicting patients' response during antiviral therapy and after drug withdrawal.Moreover,it is pointed out that further large-scale clinical studies are needed to verify and improve the clinical significance of serum HBV RNA measurement,so as to further optimize the regimens of antiviral therapy and guide the precision treatment of patients.

Esophageal varices(EV) are the most common complication in patients with liver cirrhosis.Although achievements have been made in the development of endoscopy and other hemostatic techniques,the 6-week mortality rate is still as high as 16%-26% in patients with esophageal variceal bleeding,and therefore,early diagnosis of EV,especially high-risk EV,is of great importance.At present,gastroscopy is the gold standard for the diagnosis of EV,but its clinical application is limited by invasiveness,high cost,and patient discomfort.In recent years,several noninvasive tests have been proposed for the diagnosis of EV,among which the original Baveno VI criteria and its expanded criteria are the most commonly used ones.This article summarizes and reviews the advances in serological marker,ultrasound,CT,MRI,elastography,capsule endoscopy,and ultrathin endoscopy in the noninvasive diagnosis of EV and emphasizes the development of simple noninvasive technology,so as to provide help for the early diagnosis of EV.

Great achievements have been made in the treatment of liver cancer in recent years.Inflammation plays an important role in the development and progression of liver cancer,while aspirin can exert an anti-inflammatory effect.Basic and clinical studies have found that aspirin can inhibit the development and progression of liver cancer,assist in the comprehensive treatment of liver cancer,and exert an anticancer effect together with other drugs.Aspirin has low costs and is easy to access,and its potential in the adjuvant therapy for liver cancer has attracted great attention;however,there are still many problems and confusions in the application of aspirin in clinical practice.This article summarizes and reviews the recent research advances in aspirin in the prevention and treatment of liver cancer,the problems faced at present,and the future development direction,in order to improve the understanding of this field and lay a foundation for clinical application in the real world in the future.

The mortality rate of liver cancer patients in China is increasing constantly,which greatly threatens human health,and therefore,it is urgent to explore more effective treatment methods to prolong the survival time of patients.Because of its special physiological structure,the liver plays an immunoregulatory role,and thus immunotherapy for liver cancer gradually shows its clinical advantages and has become the fourth-generation therapy for liver cancer after surgical resection,chemotherapy,and radiotherapy.Adoptive cell transfer immunotherapy has been developed rapidly in the treatment of hepatocellular carcinoma(HCC) in recent years.CIK,NK,DC-CIK,TIL,and CAR-T cells are immune cells used for adoptive cell transfer immunotherapy.This article briefly summarizes the research advances in these immune cells in the treatment of HCC.

At present,there are various treatment methods for hepatocellular carcinoma(HCC),including surgical treatment,interventional treatment,and immunotherapy,and even so,the five-year survival rate of HCC patients is only 12.5%.Influencing factors for the prognosis of HCC have always been the focus of research.With the in-depth research on programmed cell death protein 1(PD-1) inhibitors in the treatment of HCC in recent years,the role of programmed cell death ligand 1(PD-L1) and soluble programmed cell death ligand 1(s PD-L1),as the ligands of PD-1,in immune escape and their value in predicting prognosis have attracted more and more attention.This article elaborates on the current controversies,consensus,and advances in PD-L1 and s PD-L1 as immune markers in evaluating the prognosis of HCC.

The mortality rate of hepatocellular carcinoma(HCC) remains high,and although there have been several treatment methods,HCC patients still have poor treatment outcome and prognosis in clinical practice.Therefore,it is necessary to find a new drug for the treatment of HCC to improve patients' survival rate.This article introduces a new antitumor drug,galangin,which can exert an antitumor effect by inhibiting cell proliferation,promoting apoptosis,inducing autophagy,and inhibiting metastasis.In addition,galangin can also inhibit angiogenesis in liver cancer,reverse multidrug resistance,and enhance the synergistic effect between drugs.Therefore,galangin is believed to have a promising future in clinical practice,and it is expected that more studies will focus on the anti-hepatoma cell mechanism of galangin to provide a scientific basis for the clinical translation of galangin.

Cholangiocellular carcinoma(CCA) is a malignant tumor derived from the biliary epithelium,with a lack of effective therapeutic drugs and poor prognosis.Studies have shown that the development and progression of CCA are closely associated with angiogenesis,and a variety of angiogenic factors,including vascular endothelial growth factor(VEGF) and its receptor VEGFR,can regulate angiogenesis in CCA,participate in the development and progression of CCA,and affect its prognosis.Therefore,anti-angiogenic drugs targeting VEGF/VEGFR,such as monoclonal antibodies and small-molecule inhibitors,have gradually become research hotspots for the treatment of CCA.This article reviews the role of the VEGF/VEGFR pathways in the clinical features and prognosis of CCA,the advances in anti-angiogenic therapy for CCA,and related studies on drug resistance.

Radical hepatectomy and liver transplantation are the best choices to improve the long-term prognosis of patients with primary liver cancer;however,most of the patients in China have lost the opportunity for surgical treatment at the time of confirmed diagnosis.Therefore,conversion therapy has become a research hotspot in improving the survival rate of patients with advanced liver cancer.This article briefly describes the evaluation of conversion therapy for liver cancer and summarizes the current conversion treatment regimens for unresectable liver cancer.With the deepening of the understanding of primary liver cancer and individualized treatment,the group of precise treatment combined with multidisciplinary diagnosis and treatment develops the regimens for individualized conversion therapy,which is considered to effectively improve the surgical resection rate,treatment outcome,and long-term prognosis of patients with advanced liver cancer.

The development and progression of nonalcoholic fatty liver disease(NAFLD) have complex potential mechanisms.The traditional“two-hit”pathophysiological theory has been challenged,and in recent years,an increasing number of studies have been performed to investigate the interaction between insulin resistance,adipokines,and other unknown pathogenic factors in various organs.This article summarizes the factors of the liver,intestinal tract,hypothalamus,and extracellular cysts,as well as genetic factors,with an emphasis on the synergistic mechanism of action of the liver and extrahepatic organs in the pathogenesis of NAFLD,in order to provide a reference for obtaining new insights into NAFLD regulatory network and determining new targets for the prevention and treatment of NAFLD.

The incidence rate of nonalcoholic fatty liver disease(NAFLD) is increasing year by year and NAFLD has become one of the most common liver diseases in the world.Metabolomics follows the research thoughts of genomics and proteomics and conducts a quantitative analysis of all metabolites in organisms to explore the association between metabolites and physiological and pathological changes,which provides a new way for studying the traditional Chinese medicine diagnosis and treatment of NAFLD.This article summarizes the research advances in metabolomics and traditional Chinese medicine syndromes in NAFLD,so as to provide new thoughts and methods for further exploration of NAFLD.

Drug-induced liver injury(DILI) refers to liver injury caused by one or more drugs or their metabolites after use.Due to the various types of drugs and large differences between individuals,there are many difficulties in the clinical diagnosis of DILI,and the search for new biomarkers has become a research hotspot.Related studies have shown that cytokines play a key role in DILI,especially idiosyncratic DILI.This article outlines the role of different cytokines in DILI and their value in predicting the severity and evaluating prognosis of DILI.It is pointed out that cytokines have a broad application prospect as biomarkers for DILI.

Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 has become a serious threat to global public health security.Besides lung diseases,severe cases are also accompanied by varying degrees of liver injury.Previous studies have shown that patients infected with severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus may also suffer from liver injury,which is closely associated with disease severity.This article elaborates on the clinical features and pathogenesis of liver injury caused by these three types of highly pathogenic human coronavirus,in order to help clinicians better understand this disease and make accurate decisions.

Hypoxic microenvironment is a common phenomenon of liver diseases and runs through the whole process of the development and progression of liver diseases.In recent years,the research on liver fibrosis and hypoxic microenvironment of hepatocellular carcinoma has attracted more and more attention.Hypoxia-inducible factor(HIF) is the most important hypoxic stress factor found at present.This article reviews the characteristics of hypoxic microenvironment in the liver and liver diseases and further elaborates on the association of HIF overexpression with hepatocyte damage,formation of fibrosis,and malignant transformation of hepatocytes.

Liver regeneration is an important response after liver injury and necrosis to maintain liver volume and function,with the involvement of various factors and signaling pathways.This process has three main stages,i.e.,the initial stage of mitosis triggered by certain factors,the proliferation stage of promoting hepatocytes to enter the cell cycle,and the termination stage of promoting liver cells to reach a certain number and the recovery of liver mass.This article introduces various factors and multiple cellular signaling pathways that promote the differentiation of liver stem cells into liver cells to restore liver volume and function and summarizes the previous research findings of our group that alpha-fetoprotein is an important serum marker for liver regeneration after liver failure.The analysis shows that in-depth studies of the occurrence and clinical application of liver regeneration will help to improve the understanding of liver regeneration,better predict the prognosis of acute and chronic liver diseases,and provide new ideas and methods for the clinical diagnosis and treatment of various advanced liver diseases.

MicroRNAs(miRNAs) are endogenous non-coding small molecular RNAs that widely exist in eukaryotes,and mature miRNAs are composed of 20-25 nucleotide sequences.With the deepening of the research on miRNAs in recent years,it has been found that miRNAs play an important role in the development,progression,prognosis,chemotherapy resistance,and early diagnosis of gallbladder carcinoma.This article reviews the research advances in the role of miRNAs in gallbladder carcinoma.

Acute pancreatitis(AP) is a common gastrointestinal disease and may lead to local complications and even multiple organ failure,and the pathogenesis of AP involves self-digestion of trypsin,inflammatory response,and microcirculation disturbance.This article introduces the role of pyroptosis in the pathogenesis of AP and briefly describes the activation pathway of pyroptosis,inflammasome,and the mechanism of action of effector molecules in inducing damage to the pancreas and extra-pancreatic organs.It is believed that the regulation of pyroptosis plays an important role in the pathogenesis of AP,which provides new ideas for the prevention and treatment of AP.

Severe acute pancreatitis(SAP) is a common critical disease of the digestive system with rapid progression,multiple clinical outcomes,and high mortality rate.With the development of minimally invasive technology,the surgical intervention strategies for SAP have changed greatly,and the mode of surgical intervention is developing towards minimal invasiveness,multidisciplinary cooperation,and individualization.At present,the treatment concepts of“step-up approach”and delayed intervention have been widely accepted by clinicians.Accurately grasping the indications for surgical intervention,emphasizing the timing of surgical intervention,and selecting a reasonable mode of surgical intervention have become the key to successful surgical intervention for SAP in clinical practice.Emphasis on the principles of multidisciplinary cooperation and individualization and a correct understanding of the role and status of surgical intervention may help to further improve the overall cure rate of SAP patients.