In China,the vast majority of hepatocellular carcinoma(HCC) is the result of long-term development of hepatitis B and cirrhosis. Pathologically,HCC is characterized by rich blood supply and multicenter origin,with early invasion of small branches of portal vein and intrahepatic metastasis. Therefore,HCC is not only a local organ but also a systemic disease at the beginning of its occurrence. For this reason,in clinical treatment of HCC a comprehensive treatment scheme should be adopted,including local treatment(such as surgical resection,radiofrequency ablation,microwave ablation,chemical ablation and cryoablation et al),organ-level therapy(such as transcatheter arterial infusion chemotherapy and transcatheter arterial chemoembolization),and systemic therapy(such as immunotherapy,antiviral therapy and molecular targeted therapy et al). This consensus sets forth the minimally-invasive and multidisciplinary comprehensive diagnosis and treatment of HCC,focusing on the following eight aspects:(1) hepatic arteriography,hepatic arteriography CT(CTHA),arterioportal angiography CT(CTAP),lipiodol CT(Lp-CT),TACE-CT,which are helpful in finding the lesion and making precise staging;(2)TACE/ablation should be used as the first choice of treatment for early stage or small HCC;(3) infiltrating HCC should be regarded as an independent type;(4) minimally-invasive comprehensive treatment of metastatic lymph nodes;(5) multi-level subdivision of M-staging used for guiding individual treatment and predicting prognosis;(6) HCC with severe hepatic decompensation is a candidate criterion for liver transplantation;(7) promotion of bio-immunotherapy,traditional Chinese medicine therapy,antiviral therapy and social psychotherapy,which should be run through all stages of treatment;(8) implementation of multicenter randomized controlled trials of minimally-invasive therapy and surgery for early and middle stage HCC is recommended.

Objective To investigate the traditional Chinese medicine(TCM) syndrome characteristics of portal vein thrombosis(PVT) in patients with liver cirrhosis and related risk factors. Methods A total of 62 patients with liver cirrhosis and PVT who were hospitalized in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2015 to March 2019 were enrolled as PVT group,and 66 liver cirrhosis patients without PVT were enrolled as non-PVT group. Related clinical data were compared between the two groups. The independent samples 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,and the unconditional multivariate logistic regression was used for multivariate analysis. Results The univariate analysis showed that there were significant differences between the PVT group and the non-PVT group in the etiology of liver cirrhosis(χ2= 12. 902,P = 0. 036),alanine aminotransferase(Z =-2. 571,P =0. 010),aspartate aminotransferase(Z =-2. 801,P = 0. 005),cholinesterase(t =-2. 579,P = 0. 011),fibrinogen degradation product(Z=-4. 410,P < 0. 001),D-dimer(Z =-4. 888,P < 0. 001),percentage of neutrophils(Z =-3. 124,P = 0. 002),internal diameter of the main portal vein(t = 2. 572,P = 0. 012),blood flow velocity of the portal vein(t =-2. 441,P = 0. 016),diameter of the splenic vein(t = 3. 175,P = 0. 002),spleen thickness(t = 4. 575,P < 0. 001),spleen length(Z =-4. 028,P < 0. 001),and volume of peritoneal effusion(t = 2. 273,P = 0. 025). The logistic regression analysis showed that D-dimer(odds ratio [OR]= 2. 078,95% confidence interval [CI]: 1. 293-3. 339,P = 0. 003) and spleen length(OR = 1. 964,95% CI: 1. 228-3. 142,P = 0. 005) were independent risk factors for PVT in patients with liver cirrhosis. Fatigue(100%),splenomegaly(74. 19%),abdominal distension(46. 77%),severe esophagogastric varices(48. 29%),history of variceal bleeding(40. 32%),light-reddish tongue(43. 55%),and stringy/thready pulse(96. 77%) were the main characteristics of patients with liver cirrhosis and PVT,which were consistent with the manifestations of Qi deficiency and blood stasis syndrome. Conclusion An increase in D-dimer level and a long spleen length are independent risk factors for PVT in patients with liver cirrhosis,and the syndrome characteristics of such patients are consistent with the manifestations of Qi deficiency and blood stasis syndrome.

Objective To establish and validate a nomogram for overall survival(OS) of patients after hepatectomy for hepatocellular carcinoma(HCC). Methods A retrospective analysis was performed for the clinical data of 1013 patients who underwent hepatectomy for HCC in The Affiliated Tumor Hospital of Guangxi Medical University from February 2004 to October 2013. These patients were randomly divided into training cohort with 710 patients and validation cohort with 303 patients. For the training cohort,the Cox proportional hazards model was used to determine independent risk factors and a nomogram was established to predict 1-,3-,and 5-year survival rates. The performance of this nomogram was evaluated by internal verification within the training cohort and external verification of the validation cohort,as well as C-index,receiver operating characteristic(ROC) curve,and calibration curve. The independent samples t-test was used for comparison of continuous variables between groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical variables between groups. The Cox proportional hazards model was used for univariate and multivariate analyses. Results The 1-,3-,and 5-year OS rates in the training cohort were 0. 72,0. 48,and 0. 34,respectively,and those in the validation cohort were 0. 66,0. 45,0. 32,respectively. The univariate and multivariate analyses showed that age,number of tumors,tumor diameter,tumor capsule,vascular invasion,microsatellite lesion,aspartate aminotransferase(AST),and alpha-fetoprotein(AFP) were the influencing factors for OS in patients after hepatectomy for HCC(all P < 0. 05),and such factors were used to establish a nomogram model. In the training cohort,the C-index for predicting OS was 0. 748(95% confidence interval [CI]: 0. 712-0. 784); the calibration curve of 1-,3-,and 5-year survival rates showed that the predicted value of the nomogram was in good consistency with the actual values observed; this nomogram model had an area under the ROC curve of 0. 81(95% CI: 0. 76-0. 87),0. 82(95% CI: 0. 77-0. 88),and 0. 79(95% CI: 0. 71-0. 88),respectively,in predicting the 1-,3-,and 5-year survival rates. In the validation cohort,the C-index was 0. 712(95% CI: 0. 685-0. 739); the calibration curve of 1-,3-,and 5-year survival rates showed that the predicted value of the nomogram was in good consistency with the actual values observed; this nomogram model had an area under the ROC curve of 0. 75(95% CI: 0. 71-0. 79),0. 77(95%CI: 0. 73-0. 81),and 0. 74(95% CI: 0. 68-0. 80),respectively,in predicting the 1-,3-,and 5-year survival rates. Conclusion The nomogram established in this study can effectively predict OS in patients after hepatectomy for HCC.

Objective To investigate the effect of the liver-regulating and spleen-strengthening method on the expression of Toll-like receptor 4(TLR4) and occludin in the intestinal mucosal barrier of rats with nonalcoholic fatty liver disease(NAFLD) induced by high-fat and high-sugar diet. Methods A total of 50 male Sprague-Dawley rats were randomly divided into normal group,model group,liver-regulating and spleen-strengthening group,liver-regulating group,and spleen-strengthening group. A rat model of nonalcoholic steatohepatitis was established by high-fat and high-sugar diet for four weeks. The five groups were observed in terms of the degree of hepatic steatosis,the change in liver function,and the expression of the tight junction protein occludin in the intestinal mucosa and TLR4 in the intestinal epithelium. 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. Results Compared with the normal group,the model group showed hepatic steatosis and had significant increases in the serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST)(P<0. 05),as well as a reduction in the expression of the tight junction protein occludin in intestinal epithelial cells and an increase in the expression of TLR4 in the intestinal epithelium. Compared with the model group,the three treatment groups had a significant reduction in the degree of steatosis,a significant increase in the expression of occludin,and a significant reduction in the expression of TLR4 in the intestinal epithelium. Among the three treatment groups,the liver-regulating and spleen-strengthening group had the lowest degree of steatosis and significantly greater reductions in the serum levels of ALT and AST than the model group(P < 0. 05),as well as significantly greater changes in the expression of occludin and TLR4. Conclusion The liver-regulating and spleen-strengthening method can improve intestinal mucosal barrier function by increasing the expression of the tight junction protein occludin in intestinal epithelial cells and reducing the expressionof TLR4 in the intestine,with a better clinical effect than the liver-regulating method or the spleen-strengthening method alone.

Objective To investigate the effect of JNK1 gene silencing on the expression of high-molecular-weight adiponectin and related pathway molecules in adipose tissue of mice with nonalcoholic fatty liver disease(NAFLD). Methods A total of 20 C57 BL/6 mice were randomly divided into normal group,model control group,NAFLD group treated with shRNA-JNK1 lentivirus(JNK1 + NAF group),and NAFLD group treated with unrelated-sequence shRNA lentivirus(unrelated sequence + NAF group),with 5 mice in each group. Normal diet and high-fat diet were given for 3 months,and a mouse model of NAFLD was successfully established. The mice with NAFLD were given tail vein injection of shRNA-JNK1 lentivirus with the optimal interfering effect and unrelated-sequence shRNA lentivirus. After 5 days of feeding based on diet and lentivirus injection,HE staining was used to observe the pathological changes of liver tissue. ELISA was used to measure the serum level of high-molecular-weight adiponectin. Western blot was used to measure the expression of AMP-activated protein kinase(AMPK),phosphorylated AMPK(p-AMPK),high-molecular-weight adiponectin,and disulfide-bond-A oxidoreductase-like protein(DsbA-L) in epididymal fat pad. A one-way analysis of variance was used for comparison of continuous data between groups,and the least significant difference t-test was used for further comparison between two groups. Results HE staining showed that compared with the model control group,the JNK1 + NAF group had significant reductions in lipid droplet vacuoles,edema,and inflammation. The JNK1 + NAF group had a significantly lower liver steatosis score than the model control group and the unrelated sequence + NAF group(2. 267 ± 0. 704 vs 3. 800 ± 0. 414/3. 667 ± 0. 617,both P < 0. 05). ELISA showed that the JNK1 + NAF group had a significantly higher serum level of high-molecular-weight adiponectin than the model control group(294. 71 ± 102. 30 ng/ml vs 124. 06 ± 70. 58 ng/ml,P<0. 001). Western Blot showed that the JNK1 + NAF group had significantly higher expression levels of AMPK,p-AMPK,DsbA-L,andhigh-molecular-weight adiponectin than the model control group and the unrelated sequence + NAF group(all P < 0. 05). Conclusion JNK1 gene silencing can promote the expression of Dsb A-L and high-molecular-weight adiponectin in NAFLD mice,activate the AMPK pathway to regulate adiponectin multimerization,and thus improve fat deposition in NAFLD.

Objective To investigate the effect of rapamycin on the expression of the autophagy-related proteins Unc-51 like autophagy activating kinase 1(ULK1) and microtubule-associated protein 1 light chain 3(LC3) in hepatic ischemia-reperfusion injury and its significance. Methods A total of 30 rats were divided into experimental group,control group,and sham-operation group,with 10 rats in each group,and a rat model of hepatic ischemia-reperfusion injury was established. Samples were collected at 24 and 72 hours after surgery,and serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST),liver pathology,and mRNA and protein expression of ULK1 and LC3 were measured. 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. Results There were increases in the serum levels of ALT and AST and liver pathological structural damage at 24 hours after surgery(F = 1531. 83 and 1799. 97,P < 0. 05),and compared with the control group,the experimental group had significant reductions in the serum levels of ALT(354. 58 ± 28. 40 U/L vs 556. 15 ± 19. 32 U/L,P < 0. 05) and AST(384. 37 ± 8. 98 U/L vs 575. 96 ± 30. 21 U/L,P < 0. 05) and alleviation of liver pathological structural damage. At 72 hours after surgery,the experimental group had significantly lower serum levels of ALT and AST than the control group(ALT: 271. 81 ±8. 63 U/L vs 466. 33 ± 30. 00 U/L,P < 0. 05; AST: 358. 92 ± 13. 20 U/L vs 497. 05 ± 40. 14 U/L,P < 0. 05). Both the experimental group and the control group had significant reductions in the serum levels of ALT and AST from 24 to 72 hours after surgery(ALT: t = 8. 87、7. 92,AST: t = 5. 04、5. 34,both P < 0. 05). At 24 hours after surgery,the experimental group and the control group had significant increases in the mRNA and protein expression of ULK1 and LC3 compared with the sham-operation group(all P < 0. 05),and compared with the control group,the rapamycin intervention group had significant increases in the mRNA and protein expression of ULK1 and LC3(ULK1 mRNA: 13. 23 ± 6. 58 vs 4. 91 ± 1. 64,P < 0. 05; LC3 mRNA: 7. 82 ± 1. 65 vs 3. 70 ± 1. 10,P < 0. 05; ULK1 protein: 1. 62 ± 0. 19 vs 1. 17± 0. 33,P < 0. 05; LC3 protein: 1. 62 ± 0. 19 vs 0. 84 ± 0. 10,P < 0. 05). Compared with the control group at 72 hours after surgery,the rapamycin intervention group had significant increases in the mRNA and protein expression of ULK1 and LC3(ULK1 mRNA: 10. 58 ± 3. 31 vs 4. 83 ± 2. 66,P < 0. 05; LC3 mRNA: 6. 42 ± 1. 13 vs 2. 71 ± 0. 81,P < 0. 05; ULK1 protein: 1. 29 ± 0. 24 vs 0. 90 ± 0. 29,P < 0. 05;LC3 protein: 1. 40 ± 0. 73 vs 0. 64 ± 0. 08,P < 0. 05). There were significant reductions in the serum levels of ALT and AST from 24 to 72 hours after hepatic ischemia-reperfusion injury,with alleviation of liver pathological structural damage and reductions in the mRNA and protein expression of ULK1 and LC3(all P < 0. 05). Conclusion There are increases in the expression of ULK1 and LC3 after hepatic ischemia-reperfusion injury,and rapamycin may exert a protective effect on liver function by upregulating autophagy during liver ischemia-reperfusion injury.

Objective To systematically review the efficacy and safety of norepinephrine combined with albumin versus terlipressin combined with albumin in the treatment of type 1 hepatorenal syndrome(HRS1). Methods Pub Med,EMBASE,Medline,Cochrane Library,CNKI,Wanfang Data,and VIP were searched for comparative studies on norepinephrine combined with albumin versus terlipressin combined with albumin in the treatment of HRS1. Quality assessment was performed for articles. Related indicators were extracted,including hepatorenal syndrome(HRS) reversal rate,mortality rate,incidence of adverse events,mean arterial pressure,and renal function,and Review Manager 5. 3 was used for data analysis. The chi-square test was used to determine the heterogeneity between studies. Odds ratio(OR) was used for the analysis of dichotomous variables,weighted mean difference(WMD) was used for the analysis of continuous variables,and 95% confidence interval(CI) was calculated for these two types of variables. Results A total of 6 randomized controlled trials which met the inclusion criteria were included,with a total sample size of 298 patients(149 patients in the norepinephrine + albumin group and 149 in the terlipressin + albumin group). The meta-analysis showed that there were no significant differences between the two groups in HRS reversal rate(OR = 0. 95,95% CI: 0. 6-1. 49,P = 0. 81),mortality rate(OR = 0. 84,95% CI: 0. 51-1. 41,P = 0. 51),incidence rate of adverse events(OR =0. 42,95% CI: 0. 16-1. 07,P = 0. 07),mean arterial pressure(standardized mean difference = 0. 05,95% CI:-0. 92 to 1. 03,P = 0. 92),and renal function. Conclusion Norepinephrine combined with albumin has similar efficacy and safety as terlipressin combined with albumin in the treatment of HRS1,and terlipressin can be replaced by norepinephrine in clinical practice when necessary.

Objective To perform a transcriptomic study of Huh7 cells with low expression of Mindin,and to investigate the biological effects of Mindin. Methods The Mindin interference sequence was designed,synthesized,and introduced into Huh7 cells via the lentiviral vector GV248. Real-time quantitative PCR was used to measure the inhibitory effect on Mindin transcription level. Huh7 cells with low expression of Mindin were obtained and a transcriptomic study was performed for such cells and their control cells. Bioinformatics was used to analyze abnormally expressed genes,and pathway analysis was used to investigate the possible biological functions involving Mindin. The t-test was used for comparison of continuous data between groups. Results Compared with the control cells,Huh7 cells transfected with the lentivirus containing interference sequence had a knockdown efficiency of Mindin mRNA of 63. 8%(P = 0. 003). Huh7 cells with stable low expression of Mindin had a significantly higher cell migration rate than the control cells(3. 511 ± 0. 538 vs 1. 701 ± 0. 765,t =-3. 355,P = 0. 03). Compared with the control cells,Huh7 cells with low expression of Mindin had 2888 upregulated genes and 2516 downregulated genes. Gene ontology analysis and pathway analysis were performed for 895 differentially expressed genes with | log2 FC | > 2. 0 and P<0. 05. The pathway analysis showed that the top 10 biological functions involving Mindin were tumor signaling pathway,chemokine signaling pathway,systemic lupus erythematosus,glycerophospholipid metabolism,neuroactive ligand-receptor interaction,hypertrophic cardiomyopathy,glycerolipid metabolism,MAPK signaling pathway,complement and coagulation cascades,and basal cell carcinoma. Conclusion Huh7 cells with low expression of Mindin are successfully constructed. Mindin has wide biological functions including tumors,chemokines,and lipid metabolism.

Objective To investigate the safety and efficacy of splenectomy versus spleen-preservation surgery(endocystectomy or subtotal pericystectomy) in the treatment of primary splenic hydatid cysts,and to determine the optimal surgical procedure for this disease. Methods A retrospective analysis was performed for the clinical and pathological data of 29 patients with primary splenic hydatid cysts who were admitted to The First Affiliated Hospital of Xinjiang Medical University from April 2002 to June 2017 and underwent surgical treatment. According to the surgical procedure,the patients were divided into group A(splenectomy) and group B(endocystectomy or subtotal pericystectomy).The two groups were compared in terms of time of operation,intraoperative blood loss,time to first flatus after surgery,catheter indwelling time after surgery,length of postoperative hospital stay,hospital costs,residual complications,and recurrence. The t-test was used for comparison of continuous data between the two groups,and the chi-square test was used for comparison of categorical data between the two groups. Results Compared with group B,group A had a significantly longer time of operation(167. 50 ± 41. 85 min vs 125. 84 ± 28. 88 min,t = 3. 41,P = 0. 002) and a significantly higher intraoperative blood loss(189. 00 ± 50. 65 ml vs 113. 16 ± 59. 73 ml,t = 3. 15,P =0. 004). Group A had significantly longer catheter indwelling time after surgery and length of postoperative hospital stay than group B(catheter indwelling time: 5. 00 ± 2. 36 d vs 3. 16 ± 1. 34 d,t = 2. 70,P = 0. 012; length of postoperative hospital stay: 7. 90 ± 1. 91 d vs 5. 47 ±1. 61 d,t = 3. 42,P = 0. 004). There were no significant differences between the two groups in time to first flatus after surgery,hospital costs,and incidence rate of residual cavity effusion(all P > 0. 05). Conclusion Spleen-preserving surgery(endocystectomy and subtotal pericystectomy) is safer and more effective than splenectomy in the treatment of primary splenic hydatid cysts.

Objective To investigate the clinical effect and safety of robotic versus laparoscopic splenectomy in the treatment of nontraumatic splenic diseases. Methods According to the inclusion and exclusion criteria,PubMed,Web of Science,Embase,Cochrane Library,CBM,CNKI,Wanfang Data,and VIP were systematically searched for Chinese and English articles on the comparison of robotic splenectomy and laparoscopic splenectomy in the treatment of nontraumatic splenic diseases published up to March 2019. After quality assessment was performed for the articles included,RevMan 5. 0 provided by Cochrane Library was used for analysis. Mean difference(MD) and rate difference(RD) were used as the effect indicators for continuous variables and binary variables,and pooled value and 95% confidence interval(CI) were calculated. Results A total of 7 studies with 374 patients were included,with 160 patients in the robotic splenectomy group and214 in the laparoscopic splenectomy group. The results of the meta-analysis showed that compared with laparoscopic splenectomy,robotic splenectomy had significantly lower intraoperative blood loss(MD =-127. 14,95% CI:-199. 87 to 54. 42,P < 0. 01),rate of conversion to laparotomy(RD =-0. 06,95% CI:-0. 11 to 0. 01,P = 0. 02),and rate of postoperative complications(RD =-0. 10,95% CI:-0.20 to 0. 01,P = 0. 04). There were no significant differences in time of operation and length of hospital stay between the two surgical procedures(both P > 0. 05). Conclusion Based on current evidence,robotic splenectomy has better clinical effect and safety than laparoscopic splenectomy in some aspects in the treatment of nontraumatic splenic diseases,and more multicenter large-sample randomized controlled trials are needed in the future for verification.