Intervention Mechanism of Biejiajian Wan on Primary Liver Cancer by Regulating lncRNA SNHG5/miRNA-26a-5p/GSK-3β Signal Axis / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Biejiajian Wan in the intervention of primary liver cancer based on long non-coding RNA SNHG5 （lncRNA SNHG5）/micro RNA-26a-5p （miRNA-26a-5p）/glycogen synthase kinase-3β （GSK-3β） signal axis. MethodDouble luciferase reporting assay was used to verify the targeted interaction between lncRNA SNHG5 and miRNA-26a-5p， miRNA-26a-5p， and GSK-3β in HepG2 cells. Nude-mouse transplanted tumor model of human HepG2 were established and randomly divided into model group， Biejiajian Wan low-dose group （0.5 g·kg-1）， medium-dose group （1.0 g·kg-1）， and high-dose group （2.0 g·kg-1）， and sorafenib group （100 mg·kg-1）， with 10 mice in each group. The mice were given intragastric administration of normal saline or drug for 28 days， and the tumor volume was measured at different time. Hematoxylin-eosin （HE） staining was used to observe the histological changes of tumors. The nucleic acid levels of lncRNA SNHG5， miRNA-26a-5p， GSK-3β， and β-catenin mPNA in tumor tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of GSK-3β and β-catenin in tumor tissue were detected by western blot. ResultCompared with the SNHG5-WT （wild type） + miRNA NC （negative control） group， the relative luciferase activities of the SNHG5-WT + miRNA-26a-5p mimic group were decreased （P<0.05）. Compared with the GSK-3β-WT + miRNA NC group， the relative luciferase activity of the GSK-3β-WT + miRNA-26a-5p mimic group was decreased （P<0.05）. Compared with the model group， the tumor volume of Biejiajian Wan low-dose， medium-dose， and high-dose groups was significantly decreased （P<0.05， P<0.01）. Compared with the model group， the cells in the tumor tissue of nude mice in each dose group of Biejiajian Wan were sparsely arranged with necrocytosis， which showed concentration-dependent changes. Compared with the model group， the expression levels of lncRNA SNHG5， GSK-3β， and β-catenin were decreased （P<0.05， P<0.01）， while the expression of miRNA-26a-5p was increased in each dose group of Biejiajian Wan （P<0.05， P<0.01）. Compared with the model group， the protein expression levels of GSK-3β and β-catenin were decreased in each dose group of Biejiajian Wan （P<0.05， P<0.01）. ConclusionBiejiajian Wan may affect the necrosis of liver cancer cells through lncRNA SNHG5/miRNA-26a-5p/GSK-3β signal axis and thus play an anti-tumor role. This research will provide more theoretical basis for the clinical application of Biejiajian Wan.

Epidemiological characteristics of childhood liver cancer in China in 2006-2017 / 公共卫生与预防医学

Objective To understand the epidemiological characteristics of liver cancer in Chinese children from 2006-2017, and to explore the correlation between hepatitis B and liver cancer in Children. Methods　The data of childhood liver cancer from 2006 to 2017 were collected from the Chinese Cancer Registry Annual Report. Joinpoint regression program was used to analyze the trends of standardized incidence. Analysis was conducted to determine the distributions of incidence by region, sex and age group. The data of hepatitis B were collected from China Public Health Science Data Center. Pearson correlation was used to explore the incidence correlation between hepatitis B and liver cancer. Results　From 2006 to 2017, the standardized incidence rate of childhood liver cancer in China showed a downward trend before 2010, and then remained relatively stable (AAPC=-5.09%，95%CI:-13.22%~3.80%，P=0.253). The standardized incidence rate of liver cancer showed a decreased trend in urban children (AAPC=-3.52%，95%CI:-6.82%~-0.10%，P=0.045), while the standardized incidence rate was on an upward trend in rural children (AAPC=4.95%，95%CI:1.40%~8.63%，P=0.011). The incidence rates of liver cancer were higher in urban children than in rural children (ｚ=-4.071， P<0.001), in boys than in girls (ｚ=-2.425， P=0.015), and in children of the 0~4 age group than in children of the 5~9 and 10~14 age groups (H=22.285, P<0.001). The incidence rates of both hepatitis B and liver cancer showed a downward trend from 2006 to 2017， and there was a significant correlation（r=0.775，95%CI:0.319~0.927，P=0.005). Conclusion From 2006 to 2017, the incidence of liver cancer in Chinese children showed a decreased trend with significant differences between urban-rural areas, both sexes and age groups. Boys in urban areas and children in the 0~4 years age group should be the key targets for prevention and control in the future.

Effects of colchicine via Hippo signaling pathway on mouse liver cancer and its mechanism research / 安徽医科大学学报

Objective To investigate the effect and mechanism of colchicine on mouse liver cancer via Hippo sig-naling pathway.Methods The 6-week-old male C57BL/6J mice were randomly divided into 3 groups:diethylni-trosamine(DEN)/carbon tetrachloride(CCl4)/ethanol(C2H5OH)induced mouse liver cancer model and col-chicine(0.1 mg/kg)intervention were established in control group,model group and colchicine group.From week 1st to week 2nd,the model group and the colchicine group were intraperitoneally injected with 1.0％DEN once a week.From week 3rd to week 7th,20％CCl4 dissolved in olive oil solution(5 ml/kg)was intragastric ad-ministration twice a week.From week 8th to week 18th,20％CC14 dissolved in olive oil solution(6 ml/kg)was intragastric twice a week.The colchicine group was given continuous intragastric administration for 20 weeks.The control group was given the corresponding solvent.Liver index,alanine aminotransferase(ALT)and aspartate ami-notransferase(AST)serum biochemical indexes were detected.Western blot and immunofluorescence were used to detect the expression levels of MST1,pYAP,YAP,pTAZ and TAZ proteins in liver tissues of mice in each group.Results The liver surface of mice in the control group was smooth and soft,while the liver of mice in the model group was rough and hard with granular nodules.The above lesions were significantly improved in the colchicine group.HE staining showed that the liver lobular structure of mice in the control group was normal,while the liver lobular structure of mice in the model group was disordered,with a small amount of fat droplets,extensive tissue necrosis,inflammatory cell infiltration,and fat vacuoles.The degree of liver lesions of mice after colchicine inter-vention was significantly reduced.The results of immunofluorescence and Western blot showed that compared with the control group,the protein expression levels of pYAP and pTAZ in liver tissue of model group mice were signifi-cantly decreased,while the protein expression levels of MST1,YAP and TAZ increased.After colchicine interven-tion,the protein expression levels of MST1,pYAP and pTAZ were significantly up-regulated,while the protein ex-pression levels of YAP and TAZ were down-regulated.Conclusion The therapeutic effect of colchicine on mouse liver cancer may be related to its activated Hippo signaling pathway.

The value of GNB4 and Riplet gene methylation detection in the diagnosis of primary liver cancer / 安徽医科大学学报

Objective To investigate the diagnostic efficacy and clinical value of GNB4 and Riplet gene methylation alone and in combination in the diagnosis of primary liver cancer.Methods A total of 313 patients were selected,including 78 patients with primary liver cancer,41 patients with other digestive system tumors,17 patients with non-digestive system tumors,20 patients with postoperative liver cancer,and 157 patients with benign liver disea-ses.The levels of GNB4 and Riplet gene methylation in plasma were detected using quantitative methylation-specific PCR(qMSP).Serum alpha-fetoprotein(AFP)levels were measured by direct chemiluminescence.Results The sensitivity and specificity of AFP in diagnosis were 51.3％and 94.3％,respectively;the sensitivity and specificity of GNB4 gene methylation in diagnosis were 83.3％and 99.4％,respectively;the sensitivity and specificity of Riplet gene methylation in diagnosis were 73.1％and 99.4％,respectively.The sensitivity and specificity of GNB4 and Riplet gene methylation combined diagnosis were 92.3％and 98.7％,respectively;the sensitivity and specificity of AFP,GNB4 and Riplet gene methylation combined diagnosis were 92.3％and 98.7％,respectively;the sensitivity and specificity of combined diagnosis including age and gender were 93.6％and 97.5％,respective-ly.Conclusion The sensitivity and specificity of AFP in the diagnosis of primary liver cancer are limited,while the methylation levels of GNB4 and Riplet genes are higher,and the sensitivity and specificity of their combined de-tection are higher than those of AFP.The sensitivity and specificity of AFP,GNB4 and Riplet gene methylation combined diagnosis are significantly higher than those of AFP,GNB4 and Riplet gene methylation alone.

Effect of apolipoprotein C1 expression on proliferation and apoptosis of human liver cancer HepG2 cells and its mechanism / 吉林大学学报(医学版)

Objective:To discuss the effect of apolipoprotein C1(APOC1)expression on the proliferation and apoptosis of the hepatocellular carcinoma cells,and to preliminarily clarify the related molecular mechanism.Methods:The expression level of APOC1 mRNA in hepatocellular carcinoma tissue and its relationship with the prognosis of the patient were analyzed by The Cancer Genome Atlas(TCGA)Database;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of APOC1 mRNA in different hepatocellular carcinoma cells;the human liver cancer HepG2 cells with low APOC1 expression were selected as the subjects.The HepG2 cells were transfected with pcDNA3.1-APOC1 plasmid to over-express APOC1(APOC1 over-expression group),and the HepG2 cells transfected with empty vector pcDNA3.1 were regarded as control group.MTS assay and 5-ethynyl-2'-deoxyuridine(EdU)staining were used to detect the proliferative activities and proliferation rates of the cells in two groups;Transwell chamber assay was used to detect the numbers of migration cells in two groups;flow cytometry and TUNEL assay were used to detect the percentages of the cells at different cell cycles and apoptotic rates in two groups;Western blotting method was used to detect the expression levels of extracellular regulated protein kinase(ERK),phosphorylated ERK(p-ERK),protein kinase B(AKT),phosphorylated AKT(p-AKT),B-cell lymphoma-2(Bcl-2),and cleaved cysteinyl aspartate specific proteinase-3(cleaved caspase-3)proteins in the cells in two groups.Results:The TCGA Database results showed that the expression level of APOC1 mRNA in hepatocellular carcinoma tissue was lower than that in normal liver tissue(P<0.05),and the patients with low expression of APOC1 mRNA had poor prognosis.The RT-qPCR results showed that the expression level of APOC1 mRNA in the HepG2 cells was the lowest,and the HepG2 cells were chosen for the subsequent research.Compared with control group,the proliferative activity and proliferation rate of the cells in APOC1 over-expression group were decreased(P<0.05 or P<0.01),the number of migration cells was decreased(P<0.01),and the percentage of the cells at S phase and the apoptotic rate were significantly increased(P<0.01).Compared with control group,the expression levels of p-ERK,p-AKT,and Bcl-2 proteins in the cells in APOC1 over-expression group were significantly decreased(P<0.05),and the expression level of cleaved caspase-3 protein was increased(P<0.01).Conclusion:High expression of APOC1 can inhibit the proliferation of the human liver cancer HepG2 cells and induce the apoptosis,and its mechanism may be related to inhibition of the expressions of p-ERK,p-AKT,Bcl-2 proteins and promotion of the expression of cleaved caspase-3 protein.

Clinical study of ICG-R15 combined with three-dimensional image reconstruction technology in preoperative evaluation of liver cancer / 重庆医学

Objective To explore the advantages of indocyanine green clearance rate at 15 min(ICG-R15)combined with three-dimensional image reconstruction technology in preoperativ evaluation of liver cancer,as well as its impact on the efficacy of liver resection surgery.Methods The data of the patients with liver cancer undergoing preoperative three-dimensional image reconstruction evaluation(experimental group,n=65)and traditional CT evaluation(control group,n=70)in the Jining Municipal First People's Hospital from January 2018 to January 2021 were retrospectively analyzed.All patients performed the ICG-R15 test be-fore operation.In the experimental group,45 cases adopted laparotomy and 20 cases adopted laparoscopic sur-gery,which in the control group had 50 cases and 20 cases,respectively.The data of preoperative laboratory tests,intraoperative related indicators and postoperative laboratory tests were collected in the two groups.The influences between the two kinds of evaluation modes on the effects of laparotomy and laparoscopic surgery in liver cancer were compared.Results In laparotomy,compared with the control group,the operation time and postoperative drainage tube extraction time in the experimental group were significantly shortened,the intrao-perative bleeding volume was significantly decreased,the incidence rate of postoperative complications,direct bilirubin and AST levers on 7 d after operation were significantly decreased(P＜0.05);there were no statis-tically significant differences in the intraoperative blood transfusion rate,postoperative hospitalization dura-tion,levels of total bilirubin,ALT and albumin and prothrombin time on 7 d after operation between the two groups(P＞0.05).In laparoscopic surgery,compared with the control group,the postoperative hospitalization duration and postoperative drainage tube extraction time in the experimental group were significantly short-ened,the levels of AST and ALT on 7 d after operation were significantly decreased(P＜0.05);there was no statistically significant difference in the other observation indicators between the two groups(P＞0.05);in the control group,3 cases were converted to laparotomy due to inability to excision during laparoscopic explo-ration.Compared with the control group,the accuracy rate of preoperative evaluation of the number of liver tumors and Couinaud segmentation localization(96.9％vs.85.7％)and preoperative evaluation of liver vas-cular variation(100.0％vs.53.8％)were increased in the experimental group,the percentage of the patients with actual resection range greater than preoperative prediction range was lower(7.7％vs.20.0％),and the differences were statistically significant(P＜0.05).There was no statistically significant difference in the accu-racy of preoperative evaluation of portal vein invasion between the two groups(P＞0.05).Conclusion ICG-R15 combined with three dimensional reconstruction technology in preoperatively assessing liver cancer has more advantages compared with combined traditional CT,moreover which is conducive to reduce intraoperative bleeding,shorten operation time and has the positive effect on the patients'prognosis.

A Review of Research Status for the Anti-tumor Mechanism of Shanxian Granule / 广州中医药大学学报

In this article,the mechanism of Shanxian Granule in inhibiting liver cancer,lung cancer,sarcoma,melanoma and other tumors was reviewed,with a view to providing a theoretical basis for the clinical research of Shanxian Granules in the treatment of malignant tumors.Shanxian Granule are the pure Chinese medicine preparation for counteracting malignant tumor developed by the Oncology Research Team of Shaanxi University of Chinese Medicine on the basis of the theory of traditional Chinese medicine syndrome differentiation and treatment combined with decades of clinical experience as well as the achievements of modern pharmacological research.Shanxian Granule are mainly composed of Crataegi Fructus,Agrimoniae Herba,Panacis Quinquefolii Radix,Curcumae Rhizoma,Testudinis Carapax et Plastrum,Trionycis Carapax,Corydalis Rhizoma,and Polyporus,and have the actions of benefiting qi and nourishing yin,supporting healthy-qi and cultivating the essence,activating blood and removing stasis,and eliminating swelling and counteracting cancer.The compatibility of Shanxian Granule embodies the principle of supporting healthy-qi but avoiding maintaining pathogens,and eliminating pathogens but avoiding injuring healthy-qi.The granules can effectively inhibit the growth and metastasis of liver cancer,lung cancer,sarcoma,melanoma and other tumors both in vivo and in vitro,alleviate the clinical symptoms of tumor patients,and improve their prognosis.The anti-tumor mechanism of Shanxian Granules is related to the enhancement of body immune function,inhibition of tumor cell proliferation,enhancement of tumor cell apoptosis,inhibition of tumor cell invasion and metastasis as well as the tumor angiogenesis.

Aucubin inhibits the proliferation of human hepatocellular carcinoma cells line HepG2 / 基础医学与临床

Objective To investigate the effects of aucubin(AU)on the proliferation,apoptosis,and cell cycle of human liver cancer cells line HepG2 and its mechanism of action.Methods HepG2 cells were cultured in vitro,CCK-8 method was applied to screen the optimal dosage concentration of AU.HepG2 cells were randomly grouped into a control group,an AU 12.5 mg/L group(AU L group),an AU 62.5 mg/L group(AU H group),and an AU H+Akt pathway agonist(SC79)group(AU H+SC79 group).The cell proliferation was observed in each group;5-Ethynyl-2′-deoxyuridine(EDU)method was applied to detect cell proliferation;Flow cytometry was applied to detect cell apoptosis and cell cycle;Western blot was applied to detect the expression levels of phosphorylated pro-tein kinase B(p-Akt),Akt,p-MDM2,MDM2,p-p53,and p53 proteins.Results AU concentrations of 12.5 and 62.5 mg/L were selected for subsequent experiments.Compared with 0 mg/L AU,the proliferation of 12.5 and 62.5 mg/L AU cells was obviously reduced(P＜0.05);Compared with the control group,the number of suspended and exfoliated cells in the AU L and AU H groups gradually increased.Cells shrunk and became round.The propor-tion of G0/G1 phase cells,the proportion of EDU positive staining cells increased and the expression level of p-Akt/Akt and p-MDM2/MDM2 proteins decreased.The proportions of S and G2/M phase cells,the rate of cell apoptosis,and the expression level of p-p53/p53 protein all increased(P＜0.05).Compared with the AU H group,the above changes in the AU H+SC79 group were recovered(P＜0.05).After AU treatment,the tumor vol-ume and weight of transplanted nude mice decreased.Conclusions AU may inhibit the proliferation of liver cancer cells,induce cell cycle arrest and apoptosis by regulating the Akt/MDM2/p53 signaling pathway.

Identification of the effect of cisplatin on the transcriptome of human hepatocellular carcinoma cell lines / 基础医学与临床

Objective To investigate the effect of cisplatin treatment on the transcriptional level of human liver cancer cells by conducting transcriptome sequencing analysis after treating human liver cancer cell lines with differ-ent concentrations of cisplatin(CDDP).Methods Liver cancer cell lines HepG2 and Huh7 were incubated with cisplatin at different final concentrations of 0,20,50,100 and 200 μmol/L.After 12 hours,cell viability,immuno-fluorescence and RNA-sequencing(RNA-seq)were performed.Differential gene expression analysis(DEG),KEGG pathway analysis,and protein-protein interaction network analysis were conducted.Results Cisplatin de-creased cell viability and increased DNA damage in HepG2,Huh7 cells.Among the genes regulated after cisplatin treatment at different concentrations,59 genes were commonly up-regulated in both HepG2 and Huh7 cells,while 81 genes were commonly down-regulated.The commonly upregulated genes were mainly enriched in cancer initiation and progression pathways.The 81 commonly down-regulated genes were mainly enriched in Rap1 signaling pathway,Ras signaling pathway,signaling pathways regulating pluripotency of stem cells,axon guidance,and cell adhesion-related pathways.Survival analysis of key nodes in the protein-protein interaction network of commonly up-regulated and downregulated genes revealed a significant correlation between high expression of Jun proto-oncogene,AP-1 transcription factor subunit(JUN)and prolonged patient survival and a significant correlation between low ex-pression of growth arrest and DNA damage inducible alpha(GADD45A)and prolonged patient survival.Conclu-sions The study revealed common transcriptional changes in liver cancer cells under cisplatin treatment.Differential expression of JUN and GADD45A is a potential core mechanism to explain drug resistance.This conclusion provides some important prognostic indicators for clinical treatment.

Different therapeutic methods combined with TACE for primary liver cancer complicated by upper gastrointestinal bleeding:evaluation of clinical efficacy / 介入放射学杂志

Objective To compare the clinical efficacy of three different therapies,including transjugular intrahepatic portosystemic shunt(TIPS)treatment,endoscopic treatment and medication treatment,combined with transhepatic arterial chemoembolization(TACE)in treating primary liver cancer complicated by portal hypertension and upper gastrointestinal bleeding.Methods A total of 105 patients with primary liver cancer associated with portal hypertension and upper gastrointestinal bleeding,who were admitted to the No.980 Hospital of PLA Joint Logistics Support Forces of China to receive treatment between January 2014 and June 2020,were enrolled in this study.According to the therapeutic scheme,the patients were divided into TIPS+TACE group(TIPS group,n=25),endoscopy+TACE group(endoscopy group,n=30),and medication+TACE group(medication group,n=50).The clinical efficacy,recurrence rate of bleeding,incidence of hepatic encephalopathy,and survival rate were compared between each other among the three groups.Results The differences in the postoperative 6-month,12-month and 24-month recurrence rates of bleeding between each other among the three groups were statistically significant(all P＜0.05).In TIPS group,the portal vein pressure decreased from preoperative(38.47±9.35)mmHg(1 mmHg=0.133 kPa)to postoperative(25.24±5.68)mmHg,the difference was statistically significant(P＜0.05).After treatment,the hemoglobin level in the three groups showed varying degrees of elevation,which in the TIPS group and endoscopy group were better than that in the medication group,the differences were statistically significant(P＜0.05).In all three groups,the differences in the recurrence rate of bleeding between postoperative 6-month value,12-month value and 24-month value were statistically significant(all P＜0.05).The postoperative 6-month,12-month and 24-month recurrence rates of bleeding in the TIPS group were lower than those in the endoscopy group and the medication group,and the differences were statistically significant(P＜0.05).The postoperative 12-month and 24-month recurrence rates of bleeding in the TIPS group were lower than those in the endoscopy group,and the differences were statistically significant(P＜0.05).The postoperative 12-month and 24-month recurrence rates of bleeding in the endoscopy group were lower than those in the medication group(P＜0.05),and the difference in the postoperative 6-month recurrence rate of bleeding between the two groups was not statistically significant(P＞0.05).The postoperative 6-month and 12-month incidences of hepatic encephalopathy in the TIPS group were higher than those in the endoscopy group and the medication group,the differences were statistically significant(P＜0.05),while the differences in the postoperative 6-month and 12-month incidences of hepatic encephalopathy between the endoscopy group and the medication group were not statistically significant(P＞0.05),and the differences in the postoperative 24-month incidence of hepatic encephalopathy between each other among the three groups were not statistically significant(P＞0.05).No statistically significant difference in the 6-month mortality existed between TIPS group and endoscopy group(P＞0.05),and the 6-month mortality of both TIPS group and endoscopy group was remarkably lower than that of the medication group(P＜0.05).The postoperative 12-month mortality and 24-month mortality in TIPS group were lower than those in the endoscopy group and the medication group,and the differences were statistically significant(P＜0.05),but the differences in the postoperative 12-month mortality and 24-month mortality between the endoscopy group and the medication group were not statistically significant(P＞0.05).Conclusion For primary liver cancer associated with portal hypertension and upper gastrointestinal bleeding,TIPS combined with TACE can effectively control tumor progression and prolong survival.(J Intervent Radiol,2024,32:33-37)

The current status of health literacy among caregivers of patients with liver cancer and analysis of its influencing factors / 介入放射学杂志

Objective To understand the current status of health literacy among caregivers of patients with liver cancer and its influencing factors so as to provide a basis for improving the level of health literacy among caregivers of patients with liver cancer.Methods Using convenience sampling method,the caregivers of the liver cancer patients,who were admitted to the Department of Interventional Radiology of a certain grade ⅢA hospital in Changsha City,Hunan Province of China between April and October of 2022 and who met the inclusion and exclusion criteria,were selected as the research objects.The general information questionnaire,Health Literacy of Caregivers Scale-Cancer(HLCS-C),and Simplified Coping Style Questionnaire(SCSQ)were used to conduct the survey.Multiple linear regression analysis was used to analyze the factors influencing the health literacy among caregivers of patients with liver cancer.Results A total of 204 valid questionnaires were collected.The score of health literacy of caregivers was(123.08±16.66)points.The results of multiple linear regression analysis showed that the residence location,the monthly income per capita of the family,the number of hospitalization times,the length of care,work/study status,and coping style were the main factors influencing the health literacy(P<0.001),which explained 81.9％of the total variance.Conclusion The health literacy among the caregivers of patients with liver cancer is at a moderate level.Clinical medical staff can implement individualized health education by evaluating caregivers with different characteristics,encourage caregivers to seek and grasp disease-related information,and help the caregivers to adopt positive coping styles,so as to improve their health literacy.

Risk Prediction of SBP in Patients with Primary Liver Cancer Complicated with Ascites / 昆明医科大学学报

Objective To explore the influencing factors of spontaneous bacterial peritonitis in patients with primary liver cancer complicated with ascites and establish a prediction model.Methods A total of 292 patients with primary liver cancer complicated with ascites who were hospitalized for the first time in the Third People's Hospital of Kunming from January 2012 to December 2021 were selected as the study objects.General data,etiological indicators,serological indicators and complications of these subjects were collected.Then they were divided into the infection group(n = 114)and the control group(n = 178)according to whether spontaneous bacterial peritonitis(SBP)was complicated.Univariate and multivariate logistic regression were used to analyze the influencing factors of SBP in patients with primary liver cancer complicated with ascites.Finally,ROC curves were constructed to more intuitively represent the individual and combined predictive value of these targets.Results Am-ong 292 hepatocellular carcinoma patients with ascites,there were 235 males(80.48%)and 57 females(19.52%),among which 114 patients with SBP were in the infection group and 178 patients without SBP were in the control group.The results of univariate analysis showed that compared with the control group,the levels of WBC,neutrophils,prothrombin time,total bilirubin,albumin,CD3,CD4,CD8,CD4/CD8 ratio,CD19 procalcitonin,serum amyloid A,hypersensitive C-reactive protein,sodium,chlorine,alcohol consumption,shock,hepatorenal syndrome,hepatic encephalopathy,massive ascites in the infection group had statistically significant difference(P<0.05).Multi-factor analysis revealed that CD8,CD4/CD8 ratio were protective factors for SBP in patients with liver cancer ascites,CD19,procalcitonin,serum amyloid A,and massive ascites were risk factors for SBP in patients with ascites.ROC curve construction showed that serum amyloid A,CD8,CD4/CD8 ratio,CD19,procalcitonin,massive ascites area under curve(AUC)of massive ascites were 0.724,0.637,0.653,0.820,0.705,0.686,respectively.Conclusion CD8,CD4/CD8 ratio,CD19,procalcitonin,serum amyloid A,and a large volume of ascites are significant factors contributing to the development of spontaneous bacterial peritonitis(SBP)in patients with hepatocellular carcinoma ascites.The predictive value of combination is substantial,demonstrating a level of accuracy in forecasting SBP occurrence

Study on the mechanism of fatty acid binding protein 5 binding Vimentin protein in the Hepatocellular Carcinoma cells / 实用医学杂志

Objective The aim of this study was to screen and verify the proteins interacting with Vimentin,investigate the regulatory relationship between FABP5 and candidate proteins,and further explore the mechanism of FABP5 in hepatocellular carcinoma.Methods Immunoprecipitation combined with tandem mass spectrometry(IP-MS)was used to screen the proteins that bind to FABP5.The binding relationship between FABP5 and candi-date interacting proteins was verified from the exogenous and endogenous levels by Co-immune precipitation assay(Co-IP).RT-qPCR,Western blot and immunofluorescence were used to observe the effect of knockdown FABP5 on the transcription and translation of Vimentin in HCC cells.The effect of overexpressing FABP5 on the cytoskeleton of HCC cell was observed by phalloidin staining.Results 336 potential target proteins that bind to FABP5 were identi-fied through IP-MS.Based on literature,five candidate proteins related to tumors were selected,namely PRDX1,PRSS3,PKM,HSP90AA1,and Vimentin.The binding relationship between FABP5 and Vimentin protein was con-firmed through both exogenous and endogenous Co-IP.Knockdown FABP5 has no significant effect on the expression of Vimentin mRNA,but it can inhibit the expression of Vimentin protein,and overexpression of FABP5 can affect the cytoskeleton of HCC cell.Conclusions FABP5 promotes the migration and invasion of HCC cells by the regula-tion of Vimentin and the influence of cytoskeletal remodeling,and thus it is expected to be a potential target for anti-HCC and provide new ideas for the treatment of HCC.

LINC00115 Targets miR-874-3p to Regulate the Biological Behavior and Paclitaxel Sensitivity of Liver Cancer Cells / 华中科技大学学报(医学版)

Objective To explore the effect of LINC00115 targeting miR-874-3p on the biological behavior and paclitaxel sensitivity of liver cancer cells.Methods The qRT-PCR was performed to detect the expression levels of LINC00115 and miR-874-3p in liver cancer tissues and cell lines.The si-NC,si-LINC00115,miR-NC,miR-874-3p,pcDNA,pcDNA-LINC00115,anti-miR-NC+si-LINC00115,anti-miR-874-3p+si-LINC00115 were transfected into liver cancer cells MHCC97H respective-ly.CCK-8 method was applied to assess cell viability and IC50 value to paclitaxel.Transwell assay was performed to detect cell migration and invasion.Dual luciferase reporter gene method was used to determine the relationship between LINC00115 and miR-874-3p.Results LINC00115 was highly expressed(P＜0.05),while miR-874-3p was lowly expressed(P＜0.05)in liver cancer tissues and cell lines.After downregulating LINC00115,the cell absorbance(A)value,the IC50 value to paclitaxel,migra-tion and invasion were significantly reduced(all P＜0.05),while miR-874-3p expression was significantly increased(P＜0.05).After upregulating miR-874-3p,the cell A value,IC50 value to paclitaxel,migration and invasion were significantly reduced(all P＜0.05).After upregulating LINC00115,miR-874-3p expression was decreased(P＜0.05).LINC00115 had a direct interaction with miR-874-3p.Downregulating miR-874-3p significantly reduced the effect of low LINC00115 expression on A value,IC50 value to paclitaxel,migration and invasion of liver cancer cells(all P＜0.05).Conclusion Downregulation of LINC00115 inhibits the prolifera-tion,migration and invasion of liver cancer cells to increase paclitaxel sensitivity by promoting miR-874-3p expression.

Best evidence of perioperative exercise interventions in patients with liver cancer / 现代临床护理

Objective To acquire,evaluate and integrate the best evidence of perioperative exercise interventions in patients with liver cancer and provide evidence-based references for clinical medical staff.Methods Following the"6S"Evidence Resource Pyramid model,literatures in perioperative exercise interventions published between January 2010 and June 2022 were retrieved from various databases,including BMJ Best Practice,UpToDate,Guidelines International Network,National Guideline Clearinghouse,National Institute for Health and Clinical Excellence,Scottish Intercollegiate Guidelines Network,Medlive,Cochrane Library,JBI,Web of Science,PubMed,Embase,CINAHL,CNKI,SinoMed,Wanfang Data,American Cancer Society,American College of Sports Medicine and International Liver Cancer Association from January 2010 to June 2022.Two researchers evaluated the quality of the retrieved literatures and extracted evidences that met the inclusion criteria.Results A total of 22 articles were included,yielding 26 pieces of evidence across seven themes:the necessity of exercise,evaluation before exercise,preoperative exercise program,postoperative exercise program,exercise monitoring,health education and effect evaluation.Conclusions This study provides a summary of the best evidence regarding perioperative exercise interventions in the patients with liver cancer.The findings offer valuable references for clinical healthcare providers to deliver evidence-based care for the patients with liver cancer.

Effects of dexmedetomidine combined with desflurane anesthesia on cerebral oxygen metabolism,sedation depth and cerebral function in patients undergoing liver cancer surgery / 新乡医学院学报

Objective To explore the effects of dexmedetomidine combined with desflurane anesthesia on cerebral oxygen metabolism,sedation depth and cerebral function in liver cancer patients undergoing partial hepatic lobectomy.Methods A total of 30 liver cancer patients undergoing partial hepatic lobectomy at the Affiliated Cancer Hospital of Zhengzhou University from March to September 2022 were selected as the research subjects,they were divided into control group(n=15)and observation group(n=15)according to different anesthesia methods.Patients in both groups underwent partial open hepatectomy,and they were given the same anesthesia induction method.The patients in the control group received desflurane for anesthesia mainte-nance,while patients in the observation group received dexmedetomidine combined with desflurane for anesthesia maintenance.The anesthesia recovery indexes including the postoperative recovery time,recovery time of spontaneous breathing,eye-opening time of patients between the two groups were compared.The arterial oxygen saturation(SaO2),cervical vein oxygen saturation(SjvO2),arterial partial pressure of oxygen(PaO2)and partial pressure of venous oxygen of patients were detected by blood gas analyzer before anesthesia induction(T0),at the completion of anesthesia induction(T,),at 10 minutes after hepatic portal occlusion(T2),after hepatic lobectomy(T3)and after surgery(T4),and arterio-venous oxygen content difference(AVDO2)and cerebral oxygen extraction rate(CEO2)were calculated.The sedation depth of patients was evaluated by bispectral index(BIS)and patient state index(PSI)at T0,T1,T2,T3 and T4.The cerebral function of patients was evaluated by the Glasgow-Pittsburgh cerebral performance category scale at 3 months after surgery.The incidence of postoperative adverse reactions of patients between the two groups was compared.Results The postoperative recovery time,recovery time of sponta-neous breathing and eye-opening time of patients in the observation group were significantly shorter than those in the control group(P＜0.05).There was no significant difference in SaO2 of patients between the two groups at different time points(P＞0.05).At T2 and T3,SjvO2,AVDO2 and CEO2 of patients in the observation group were significantly lower than those in the control group(P＜0.05),but there was no significant difference in SjvO2,AVDO2 and CEO2 of patients between the two groups at the other time points(P＞0.05).At T2,T3 and T4,BIS and PSI of patients in the observation group were significantly lower than those in the control group(P＜0.05),but there was no significant difference in BIS and PSI of patients between the two groups at T0 and T1(P＞0.05).In the control group,there were 11 patients with postoperative brain function in grade 1,3 patients in grade Ⅱ and 1 patient in grade Ⅲ;in the observation group,there were 12 patients in grade Ⅰ and 3 patients in gradeⅡ.There was no significant difference in postoperative grading of brain function between the two groups(x2=1.044,P＞0.05).There was no significant difference in the total incidence of postoperative adverse reactions between the control group and observation group[20.00％(3/15)vs 26.67％(4/15),x2=0.186,P＞0.05].Conclusion Dexmedetomidine combined with desflurane anesthesia can shorten anesthesia recovery time,improve anesthesia depth and reduce cerebral oxygen metabolism in patients undergoing liver cancer surgery,which has no effect on cerebral function,showing good safety.

Research progress in oncolytic virus and immunotherapy for liver cancer / 新乡医学院学报

Liver cancer is one of the most common cancers,and its common surgical treatment methods include tran-scatheter arterial chemoembolization,radiofrequency ablation,and liver transplantation surgery.However,the treatment effect of these surgeries on patients with mid-to late-stage liver cancer is not ideal.In recent years,with the continuous development of tumor gene therapy and tumor immunology,tumor treatment methods have transitioned from traditional models to targeted onco-lytic virus therapy.With the advantages of fast replication,the oncolytic virus can kill tumor cells without damaging other normal cells and realize the targeted treatment of liver cancer through mechanisms such as activating the immune system and improving the tumor microenvironment.In addition,immunotherapy can reduce tumor recurrence and metastasis,thereby exerting therapeutic effects on liver cancer.This article reviews the research progress of oncolytic virus and immunotherapy for liver cancer,aiming to provide a reference for the clinical treatment of liver cancer.

Assessment value of X-ray angiography in postoperative recurrence,curative effect and the reduction of the perfusion of liver tumor of interventional TACE for liver cancer / 中国医学装备

Objective:To investigate the assessment value of X-ray angiography in postoperative recurrence,curative effect and reduction of the perfusion of liver tumor of interventional transarterial chemoembolization(TACE)for liver cancer.Methods:A total of 59 patients with liver cancer who were treated in The Third the People's Hospital of Bengbu from January 2015 to December 2020 were selected.All patients underwent the examination of routine X-ray angiography one week before surgery and four weeks after surgery.The obtained image sequences were imported into the workstation equipped with imaging technology software of color coded digital subtraction angiography(ccDSA)to conduct analysis.The region of interest(ROI)was manually defined on the ccDSA images before and after TACE.And then,the time intensity curve was obtained,and the quantitative perfusion parameters included the time to peak(TTP),area under curve(AUC),maximum slope(MS)were exported from that.The receiver operating characteristics(ROC)curve was drawn,and the area under curve(AUC)of that was calculated to analyze the assessment efficacy of perfusion parameters on the postoperative recurrence,curative effect and reduction of the perfusion of liver tumor of TACE for liver cancer.Results:In the 59 patients who were included in the study,39 cases occurred postoperative recurrence and 20 cases did not occurred postoperative recurrence according to the definition of postoperative recurrence,and the perfusion TTP(7.38±1.22)s of patients with postoperative recurrence was significantly lower than that(9.03±1.01)s of patients without postoperative recurrence,and the difference of that between them was significant(t=5.198,P<0.05).The AUC and MS of patients with postoperative recurrence were significantly lower than those of patients without postoperative recurrence(t=2.868,31.499,P<0.05),respectively.There were not significant differences in TTP,AUC and MS between patients with and without postoperative recurrence before surgery(P>0.05).According to the determination criteria of curative effect,35 cases were effectiveness,and 24 cases were ineffectiveness,and the postoperative TTP(9.09±1.08)s of patients with effectiveness was significantly higher than that(7.84±2.07)s of patients without effectiveness(t=3.029,P<0.05),and AUC and MS of patients with effectiveness were significantly higher than those of patients without ineffectiveness(t=3.852,54.366,P<0.05),and there were not significant differences in preoperative TTP,AUC and MS between patients with and without effectiveness(P>0.05),and the values of TTP,AUC and MS of the group with effectiveness and group without effectiveness after surgery were significantly higher than those before surgery,and the differences of them between two groups were significant(t=3.029,3.852,54.366,P<0.05),respectively.According to the grading criteria of subjective angiographic endpoints(SACE),33 cases were grade Ⅲ,and 26 cases were grade Ⅳ,and there were not significant in TTP,AUC and MS between patients with grade Ⅲ and patients with grade IV(P>0.05).The postoperative TTP,AUC and MS of patients with grade Ⅳ were significantly lower than those of patients with grade Ⅲ(t=7.679,3.498,58.968,P<0.05),respectively.The sensitivities of TTP,AUC and MS were respectively 66.70%,89.70% and 59.00% in assessing postoperative recurrence of interventional TACE for liver cancer,and the specificities of them were respectively 55.00%,55.00% and 55.00%,and the AUC values of them were respectively 0.629(95% CI:0.478-0.779),0.827(95% CI:0.723-0.931)and 0.512(95% CI:0.356-0.667).The sensitivities of TTP,AUC and MS were respectively 64.10%,79.50% and 61.50% in assessing postoperatively curative effect of interventional TACE for liver cancer,and the specificities of them were respectively 55.00%,65.00% and 55.00%,and the AUC values of them were respectively 0.609(95% CI:0.462-0.756),0.808(95% CI:0.698-0.918)and 0.580(95% CI:0.413-0.747).The sensitivities of TTP,AUC and MS were respectively 69.20%,82.10% and 53.80% in assessing the postoperative reduction of the perfusion of liver tumor of interventional TACE for liver cancer,and the specificities of them were respectively 70.00%,75.00% and 55.00%,and the AUC values of them were respectively 0.745(95% CI:0.613-0.877),0.842(95% CI:0.724-0.960)and 0.507(95% CI:0.360-0.654).Conclusion:The TTP,AUC and MS of perfusion parameters that are obtained by ccDSA quantitative analysis for the data after X-ray angiography examination have a certain application value in assessing the postoperative recurrence,curative effect and the reduction of the perfusion of liver tumor of interventional TACE for liver cancer.

Value of serum AFP, CEA and CA19-9 detection in opportunistic screening for liver cancer in Chinese population: a meta-analysis / 中华健康管理学杂志

Objective:To evaluate the value of detection of serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in opportunistic screening of liver cancer in Chinese population with a meta-analysis.Methods:Literatures on combined screening of liver cancer by AFP, CEA and CA19-9 were retrieved from CNKI, Wanfang Database, Chongqing VIP database, PubMed, Embase and Cochrane Library from the establishment of the databases to June 2023. The Quality Assessment Tool of Diagnostic Accuracy Studies (QUADAS-2) was used to evaluate the quality of the literature. Stata 17.0 statistical software was used for meta-analysis, and Deeks funnel plot was used to analyze publication bias.Results:A total of 24 literatures met the inclusion criteria, including 1 471 patients with liver cancer and 2 150 controls. The overall sensitivity of AFP in liver cancer diagnosis (screening) was 0.71 (95% CI: 0.66-0.75), the total specificity was 0.86 (95% CI: 0.80-0.90), and the area under summary receiver operating characteristic (sROC) curve (AUC) was 0.82 (95% CI: 0.78-0.85). The total sensitivity of CEA in liver cancer diagnosis (screening) was 0.48 (95% CI: 0.40-0.56), the total specificity was 0.85 (95% CI: 0.79-0.89), and the AUC of sROC was 0.74 (95% CI: 0.70-0.77). The total sensitivity of CA19-9 in liver cancer diagnosis (screening) was 0.56 (95% CI: 0.50-0.61), the total specificity was 0.80 (95% CI: 0.73-0.85), and the AUC was 0.69 (95% CI: 0.65-0.73). AFP has the highest sensitivity and specificity among the three. The overall sensitivity of combined detection of AFP, CEA and CA19-9 for liver cancer diagnosis (screening) was increased to 0.89 (95% CI: 0.85-0.92), the overall specificity was 0.77 (95% CI: 0.70-0.82), and the AUC was 0.91 (95% CI: 0.88-0.93). No publication bias was found in either individual or combined test of the biomarkers. Conclusions:Detection of AFP alone has high sensitivity and specificity, and it is a tumor marker that can be used for the opportunistic screening of liver cancer. When combined tests of AFP, CEA and CA19-9 are used to screen liver cancer, the results should be interpreted more carefully.

Hydrangea serrata extract exerts tumor inhibitory activity against hepatocellular carcinoma HepG2 cells via inducing p27/CDK2-mediated cell cycle arrest and apoptosis

@#Objective: To examine the inhibitory effect of Hydrangea serrata extract against hepatocellular carcinoma HepG2 cells and its underlying mechanisms. Methods: The effects of Hydrangea serrata extract on growth inhibition of tumor cells and spheroids were assessed using MTT and 3D culture assays. Quantitative real-time PCR and Western blot analyses were employed to investigate the changes in mRNA and protein expression levels of molecules related to cell cycle and apoptosis. Results: Hydrangea serrata extract effectively inhibited the growth of both tumor cells and spheroids. The extract also significantly upregulated p27 mRNA expression and downregulated CDK2 mRNA expression, leading to cell cycle arrest. Moreover, increased BAX/ Bcl-2 ratio as well as caspase-9 and -3 were observed after treatment with Hydrangea serrata extract, indicating the induction of tumor cell apoptosis. Conclusions: Hydrangea serrata extract has the potential to alleviate tumors by effectively modulating cell-cycle-related gene expressions and inducing apoptosis, thereby inhibiting tumor growth.