Objective To explore the relationship of the preoperative serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST)ratio and imaging features to the prognosis of patients with hepatocellular carcinoma(HCC)after receiving transarterial chemoembolization(TACE),and to develop a nomogram model used for predicting the patient's overall survival(OS).Methods A total of 211 patients,who were diagnosed as HCC and were treated with TACE as the initial therapy at the Guangci Branch of the First Affiliated Hospital of Soochow University of China between July 2016 and July 2020,were enrolled in this study.The patients were randomly divided into the modeling group(n=139)and validation group(n=72).The receiver operating characteristic(ROC)curve was used to determine the optimal cutoff value of AST/ALT ratio.The univariate and multivariate Cox regression analyses were conducted in the modeling group to screen out the independent predictors affecting HCC patient's OS and to establish a prognostic model.Harrell consistency index(C-index)was used to evaluate the predictive ability of the nomogram model for OS in HCC patients,and the calibration curves were plotted to assess the predictive accuracy of the nomogram model.Results No statistically significant difference in the baseline feature distribution existed between the modeling group and validation group(P＞0.05).The median OS of the modeling group and validation group was 28.5 months(95％CI:22.1-34.9)and 25.1 months(95％CI:19.2-29.0)respectively,the difference was not statistically significant(x2=1.395,P=0.322).The optimal cutoff value of AST/ALT ratio for predicting OS was 1.10,and the area under curve(AUC)value was 0.674(95％CI:0.604-0.753).The Cox regression analysis indicated that the tumor number(HR=2.080,95％CI=1.245-3.475,P=0.005),tumor capsule(HR=1.771,95％CI=1.128-2.780,P=0.013),irregular marginal enhancement(HR=1.884,95％CI=1.190-2.984,P=0.007),and AST/ALT ratio(HR=2.450,95％CI=1.506-3.987,P＜0.01)were the independent prognostic factors for HCC patients receiving TACE treatment.Based on the above variables,a nomogram model for predicting OS was established,and the C-index values in the modeling group and validation group were 0.733(95％CI:0.650-0.826)and 0.770(95％CI:0.688-0.862)respectively.The calibration curves showed that no significant deviations existed between the predictive curves of the prognostic model and the ideal reference curves for one-,2-and 3-year OS.Conclusion The nomogram model,which is established based on the tumor number,imaging features and preoperative AST/ALT ratio,has an excellent value in predicting the prognosis of HCC patients treated with TACE.

Objective:To explore the occurrence of programmed cell death 1 receptor (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitor-related liver injury and the influencing factors in patients with extrahepatic primary tumors.Methods:The electronic medical records of patients with extrahepatic primary tumors who were treated with PD-1/PD-L1 inhibitors in Zhongshan Hospital, Fudan University from January to July 2021 were collected and retrospectively analyzed. Patients with PD-1/PD-L1 inhibitor-related liver injury were screened out, and the occurrence time, clinical type, and severity of liver injury were statistically recorded and analyzed. Patients were divided into liver injury group and non-liver injury group according to whether liver injury occurred. Clinical characteristics including age, gender, type of primary tumor, underlying disease, liver metastasis, regimen of PD-1/PD-L1 inhibitor therapy, combined medication, and baseline liver and renal function were compared between the 2 groups. The influencing factors of liver injury were analyzed by multivariate logistic regression method, and the odds ratio ( OR) and 95% confidence interval ( CI) were calculated. Results:A total of 386 patients were included in the analysis and 29 patients had PD-1/PD-L1 inhibitor-related liver injury, with an incidence of 7.5%. Of the 29 patients, 25 were male and 4 were female, aged from 19 to 90 years. PD-1/PD-L1 inhibitors used were sintilimab, nivolumab, teriprizumab, pembrolizumab, tislelizumab, atezolizumab, camrelizumab, and durvalumab in 7, 5, 5, 4, 3, 3, 1, and 1 patient, respectively. The median time from drug use to the occurrence of liver injury was 44 (24, 112) days. The liver injury were typed as hepatocellular injury in 8 patients, cholestatic liver injury in 17 patients, and mixed type in 4 patients, and the severity was grade 1 in 19 patients, grade 2 in 7 patients, and grade 3 in 3 patients. After diagnosis of liver injury, all 29 patients were given symptomatic treatments, of which 24 patients discontinued PD-1/PD-L1 inhibitors; 21 patients had recovered liver function after 6-71 days, and 8 developed chronic hepatitis. Multivariate logistic regression analysis showed that hepatitis virus infection ( OR=5.749, 95 %CI: 1.337-24.719, P=0.019), hypertension ( OR=5.345, 95 %CI: 2.034-14.047, P=0.001), and baseline alkaline phosphatase (ALP) ≥125 U/L ( OR=4.651, 95 %CI: 1.728-12.521, P=0.002) were independent risk factors for PD-1/PD-L1 inhibitor-related liver injury. Conclusions:Liver injury is a common adverse reaction of PD-1/PD-L1 inhibitors, and cholestatic liver injury is the most common clinical type. Patients with hepatitis virus infection, hypertension, and elevated baseline ALP are at high risk for developing PD-1/PD-L1 inhibitor-associated liver injury.

Objective:To explore the occurrence of programmed cell death 1 receptor (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitor-related liver injury and the influencing factors in patients with extrahepatic primary tumors.Methods:The electronic medical records of patients with extrahepatic primary tumors who were treated with PD-1/PD-L1 inhibitors in Zhongshan Hospital, Fudan University from January to July 2021 were collected and retrospectively analyzed. Patients with PD-1/PD-L1 inhibitor-related liver injury were screened out, and the occurrence time, clinical type, and severity of liver injury were statistically recorded and analyzed. Patients were divided into liver injury group and non-liver injury group according to whether liver injury occurred. Clinical characteristics including age, gender, type of primary tumor, underlying disease, liver metastasis, regimen of PD-1/PD-L1 inhibitor therapy, combined medication, and baseline liver and renal function were compared between the 2 groups. The influencing factors of liver injury were analyzed by multivariate logistic regression method, and the odds ratio ( OR) and 95% confidence interval ( CI) were calculated. Results:A total of 386 patients were included in the analysis and 29 patients had PD-1/PD-L1 inhibitor-related liver injury, with an incidence of 7.5%. Of the 29 patients, 25 were male and 4 were female, aged from 19 to 90 years. PD-1/PD-L1 inhibitors used were sintilimab, nivolumab, teriprizumab, pembrolizumab, tislelizumab, atezolizumab, camrelizumab, and durvalumab in 7, 5, 5, 4, 3, 3, 1, and 1 patient, respectively. The median time from drug use to the occurrence of liver injury was 44 (24, 112) days. The liver injury were typed as hepatocellular injury in 8 patients, cholestatic liver injury in 17 patients, and mixed type in 4 patients, and the severity was grade 1 in 19 patients, grade 2 in 7 patients, and grade 3 in 3 patients. After diagnosis of liver injury, all 29 patients were given symptomatic treatments, of which 24 patients discontinued PD-1/PD-L1 inhibitors; 21 patients had recovered liver function after 6-71 days, and 8 developed chronic hepatitis. Multivariate logistic regression analysis showed that hepatitis virus infection ( OR=5.749, 95 %CI: 1.337-24.719, P=0.019), hypertension ( OR=5.345, 95 %CI: 2.034-14.047, P=0.001), and baseline alkaline phosphatase (ALP) ≥125 U/L ( OR=4.651, 95 %CI: 1.728-12.521, P=0.002) were independent risk factors for PD-1/PD-L1 inhibitor-related liver injury. Conclusions:Liver injury is a common adverse reaction of PD-1/PD-L1 inhibitors, and cholestatic liver injury is the most common clinical type. Patients with hepatitis virus infection, hypertension, and elevated baseline ALP are at high risk for developing PD-1/PD-L1 inhibitor-associated liver injury.

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.

Objective: To evaluate Chinese clinical practice guideline/consensus for digestive diseases published in the past five years in order to recommend the high-quality guidelines and help with the promotion and implementation of them. Methods: From January 2013 to June 2018, the officially published Chinese practice guideline/consensus for digestive diseases were selected. The inclusion and exclusion criteria of the guideline/consensus was evaluated by "Evaluation Criteria for Chinese Clinical Practice Guidelines 2017(AGREE-China 2017)" . The guideline/consensus were independently scored by three evaluators and then calculated the average value. Descriptive analysis methods were used to analyze the Chinese clinical practice guideline/consensus for digestive diseases. Those with the total score more than 40.0 points were included in the recommended list. Results: A total of 119 officially published clinical practice guideline/consensus of digestive diseases were retrieved, and 74 clinical practice guideline/consensus for digestive diseases were included in the evaluation. Among them, 18 (24.3%, 18/74) scored over 60.0 points, 31 (41.9%, 31/74) scored between 40.0 and 59.9 points. Finally 48 guideline or consesus were selected for the recommended list 19 cases of esophagus and gastrointestinal diseases, 18 cases of liver diseases, five cases of biliary and pancreafic diseases, and six cases of digestive endoscopy. The three guideline/consensus with the high scores (> 80.0 points) were The Fifth Chinese National Consensus Report on the Maragement of Helicobacter pylori Infection, Consensus on the Diagnosis and Treatmeat of Cholestatic Liver Disease (2015) and Guidelines for the Prevention and Treatment of Chroaic Hepatitis B (2015 Update). The higher the score of the guideline/consensus, the more scientific and rigorous the method, and the clearer the evaluation of evidence grade and the description of the formation of recommendations. Compared with international standards of guideline/consensus development, there are still some problems in Chinese guidelines or consensus such as no explanation of retrieval strategy, no basis of evidence classification and no description of the formation process from evidence to recommendation. Conclusions The quality of Chinese clinical practice guideline/consensus for digestive diseases has been improved year by year. However the scientific aspects need to be further improved. AGREE-China which demonstrates good validity, realiability and practicability is easy and clear to use.

OBJECTIVETo investigate the influence of Dureping injection to the murinal celiac macrophage Ana-1 on TIR signal pathway.

METHODAna-1 cell line was infected by influenza virus FM1 strain and treated with the Dureping injection in different concentrations (10.1 mg x L(-1) group) for 12 h and 24 h. Then we collected the cells, extracted mRNA and measured the expressions of TLR7, MyD88, IRAK4, TRAF6 and NF-kappaB p65 respectively by RT-PCR.

RESULTDureping injection down-regulated the expression of TLR7, MyD88, IRAK4, TRAF6 and NF-kappaB p65 mRNA in Ana-1 cell line infected by influenza virus, in a dose-dependent manner significantly.

CONCLUSIONDureping injection has an obvious effect against influenza virus FM1 strain by regulating the TIR signal pathway.

Adaptor Proteins, Signal Transducing ; Animals ; Cells ; Cells, Cultured ; Epithelial Cells ; drug effects ; metabolism ; Interleukin-1 Receptor-Associated Kinases ; genetics ; Macrophages ; drug effects ; metabolism ; Mice ; Myeloid Differentiation Factor 88 ; genetics ; metabolism ; NF-kappa B ; metabolism ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; drug effects ; TNF Receptor-Associated Factor 6 ; drug effects ; genetics ; metabolism ; Transcription Factor RelA ; metabolism

Objective:To survey the effect of the Dureping Injection on the kinetic change of nitrous oxide(NO) in macrophage infected by the influenza virus FM1 strain.Methods:The murinal celiac macrophage(Ana-1) was infected by the virus,add the different concentration of the drug in the supernatant of the macrophage for 6 h,12 h,24 h and 36 h.The level of the NO in the supernatant was measured by the method of traditional Griess.Ana-1 cell line was infected by influenza virus FM1 strain,then treated with Dureping Injection 1 ?g/ml for 24 h.The cells were then collected,mRNA was extracted and the expression of NF-?B p65 was measured by RT-PCR;The nuclear protein was extracted and the expression of NF-?B p65 measured by Western blot.Results:60 ?g/ml,30 ?g/ml,10 ?g/ml and 1 ?g/ml group of Dureping Injection down-regulated amount of NO secreted by the Ana-1 cells infected by virus,and it was showed in dose relationship significantly;1 ?g/ml group of Dureping Injection down-regulated the expression of the NF-?B p65 mRNA and protein.Conclusion:Dureping Injection has an obvious effect against influenza virus FM1 strain by depressing the activity of NF-?B,which prevents the production of NO secreted by Ana-1 cells infected by the virus.