Evaluation of combined detection of nuclear factor erythroid 2-related factor 2 and glutathione peroxidase 4 in primary hepatic carcinoma and preliminary exploration of pathogenesis

This study aims to analyze the clinical significance and mechanism of nuclear factor erythroid 2-related factor 2(NRF2)and glutathione peroxidase 4(GPX4)in primary hepatic carcinoma(PHC).Methods:The expression of NRF2 and GPX4 in peripheral blood of patients with PHC was determined to analyze the diagnostic value of the two combined for PHC.The prognostic significance of NRF2 and GPX4 was evaluated by 3-year followup.Human liver epithelial cells THLE-2 and human hepatocellular carcinoma cells HepG2 were purchased,and the expression of NRF2 and GPX4 in the cells was determined.NRF2 and GPX4 aberrant expression vectors were constructed and transfected into HepG2,and changes in cell proliferation and invasion capabilities were observed.Results:The expression of NRF2 and GPX4 in patients with PHC was higher than that in patients with LC or VH(p<0.05),and the two indicators combined was excellent in diagnosing PHC.Moreover,patients with high expression of NRF2 and GPX4 had a higher risk of death(p<0.05).In in vitro experiments,both NRF2 and GPX4 expression was elevated in HepG2(p<0.05).HepG2 activity was enhanced by increasing the expression of the two,vice versa(p<0.05).Conclusion:NRF2 and GPX4 combined is excellent in diagnosing PHC,and promotes the malignant development of PHC.

Development and validation of a postoperative pulmonary infection prediction model for patients with primary hepatic carcinoma

BACKGROUND There are factors that significantly increase the risk of postoperative pulmonary infections in patients with primary hepatic carcinoma(PHC).Previous reports have shown that over 10%of patients with PHC experience postoperative pulmonary infections.Thus,it is crucial to prioritize the prevention and treatment of postoperative pulmonary infections in patients with PHC.AIM To identify the risk factors for postoperative pulmonary infection in patients with PHC and develop a prediction model to aid in postoperative management.METHODS We retrospectively collected data from 505 patients who underwent hepatobiliary surgery between January 2015 and February 2023 in the Department of Hepatobiliary and Pancreaticospleen Surgery.Radiomics data were selected for statistical analysis,and clinical pathological parameters and imaging data were included in the screening database as candidate predictive variables.We then developed a pulmonary infection prediction model using three different models:An artificial neural network model;a random forest model;and a generalized linear regression model.Finally,we evaluated the accuracy and robustness of the prediction model using the receiver operating characteristic curve and decision curve analyses.RESULTS Among the 505 patients,86 developed a postoperative pulmonary infection,resulting in an incidence rate of 17.03%.Based on the gray-level co-occurrence matrix,we identified 14 categories of radiomic data for variable screening of pulmonary infection prediction models.Among these,energy,contrast,the sum of squares(SOS),the inverse difference(IND),mean sum(MES),sum variance(SUV),sum entropy(SUE),and entropy were independent risk factors for pulmonary infection after hepatectomy and were listed as candidate variables of machine learning prediction models.The random forest model algorithm,in combination with IND,SOS,MES,SUE,SUV,and entropy,demonstrated the highest prediction efficiency in both the training and internal verification sets,with areas under the curve of 0.823 and 0.801 and a 95%confidence interval of 0.766-0.880 and 0.744-0.858,respectively.The other two types of prediction models had prediction efficiencies between areas under the curve of 0.734 and 0.815 and 95%confidence intervals of 0.677-0.791 and 0.766-0.864,respectively.CONCLUSION Postoperative pulmonary infection in patients undergoing hepatectomy may be related to risk factors such as IND,SOS,MES,SUE,SUV,energy,and entropy.The prediction model in this study based on diffusion-weighted images,especially the random forest model algorithm,can better predict and estimate the risk of pulmonary infection in patients undergoing hepatectomy,providing valuable guidance for postoperative management.

Percutaneous microwave ablation and transcatheter arterial chemoembolization for serum tumor markers and prognostics of middle-late primary hepatic carcinoma

BACKGROUND Primary hepatic carcinoma(PHC)has an insidious onset and is usually diagnosed in the middle and late stages.Although transcatheter arterial chemoembolization(TACE)is the preferred option for treating middle-and advanced-stage PHC,it has limited efficacy in killing tumor cells and poor long-term efficacy.TACE plus percutaneous microwave coagulation therapy(PMCT)is more effective than interventional therapy alone and can improve survival time.However,there are few reports on the effects of TACE and PMCT on serum marker levels and the prognosis of patients with advanced PHC.AIM To investigate the effect of PMCT+TACE on serum tumor markers and the prognosis of middle-late PHC.METHODS This retrospective study included 150 patients with middle-late PHC admitted to Zhongshan People’s Hospital between March 2018 and February 2021.Patients were divided into a single group(treated with TACE,n=75)and a combined group(treated with TACE+PMCT,n=75).Before and after treatment,the clinical efficacy and serum tumor marker levels[carbohydrate antigen 19-9(CA19-9),alpha-fetoprotein(AFP),and carcinoembryonic antigen(CEA)]of both groups were observed.The 1-year survival rates and prognostic factors of the two groups were analyzed.RESULTS The combined group had 21 and 35 cases of complete remission(CR)and partial remission(PR),respectively.The single group had 13 and 25 cases of CR and PR,decreased,with the decrease in the combined group being more significant(P<0.05).The 1-year survival rate of the combined group(80.00%)was higher than that of the single group(60.00%)(P<0.05).The average survival time within 1 year in the combined group was 299.38±61.13 d,longer than that in the single group(214.41±72.97 d,P<0.05).COX analysis revealed that tumor diameter,tumor number,and the treatment method were prognostic factors for patients with middle-late PHC(P<0.05).CONCLUSION TACE+PMCT is effective in treating patients with mid-late PHC.It reduces the levels of tumor markers,prolongs survival,and improves prognosis.

EXPRESSION OF PRE-S_1 AND PRE-S_2 ANTIGENS OF HEPATITIS B VIRUS AND THEIR SIGNIFICANCE IN HUMAN PRIMARY HEPATIC CARCINOMA

The specimens of 135 cases of primary hepatic carcinoma were obtained from the Pathological Laboratory of the First Affiliated Hospital of the Fourth Military Medical University, Xi' an, PRC. Ten percent formalin-fixed and paraffin- embedded sections were stained by HE and by ABC and PAP immunohistochemical methods. Positive rates of pre- S1 and pre- S2 antigens in cancerous tissue were 22. 2% and 20. 0%, respectively, while those in surrounding hepatic tissue were 60.6% and 59.6%, separately. The pre- S1 and pre- S2 antigens were found to coexist In 16. 3% of cancerous tissue and in 55. 6% of surrounding hepatic tissue. In all the 135 cases of hepatic carcinoma, the cancerous tissue showed positive HBsAg in 16. 3%, HBxAg in 55. 6% and HBcAg in 8. 9%; in the surrounding hepatic tissue, positive HBsAg was 59.6%, HBxAg 78.8% and HBcAg 24.2%. The results of this study suggestes that positive rates of pre- S1 and pre-S2 antigens in cancerous tissue were slightly higher than that of HBsAg, but markedly lower than that of HBxAg. The positive rate of pre-S1 and pre- S2 antigens in surrounding hepatic tissue was nearly the same as HBsAg, but slightly lower than that of HBxAg. Antigens of pre-S1 and pre-S2 are the new markers of HBV infection. The same as other antigens, they may play an important role in the development of hepatic carcinoma. The mechanism of their effect will be further investigated,

DIAGNOSTIC SIGNIFICANCE OF α_1-ANTITRYSIN IN PRIMARY HEPATIC CARCINOMA - AN APPRAISAL OF MONOCLONAL ANTIBODY-RATE NEPHELOMETRY

Using hybridoma technique, we prepared the monoclonal antibody against a1-AT and combined it with Immuno-Chemical Monitor System-(ICS)-rate nephelemetry to determine the serum a1-AT concentration of 50 health adults, 49 patients with primary hepatic carcinoma (PHC) and 52 with benign liver diseases, respectively. Serum a1-AT levels were significantly higher in patients with PHC than in normal adults (P<0.001). Elevated levels of a1-AT were found in 43% of patients with PHC. No difference was found in a1-AT between patients with benigh liver diseases and health adults (P>0.05). The results indicated that a1-AT is one of the serum markers useful for diagnosing PHC. It is hopeful by using the monoclonal antibody against a1-AT as a new reagent to examine a1-AT on the molocular cytological level.

IMMUNOHISTOCHEMICAL STUDY ON X ANTIGEN OF HBV (HBxAg) IN PRIMARY HEPATIC CARCINOMA

The specimens were from 110 patients with primary hepatic carcinoma. The formalin- fixed and paraffin-embedded sections were stained for HBxAg by ABC method and for HBsAg and HBcAg by PAP method. Of the 110 cases, 64 (58. 2%) showed HBxAg-positive reaction in tumor tissue, and 63 (78. 8%) of 80 cases displayed positive HBxAg in surrounding non-cancerous hepatic tissue. Among the 64 cases with positive HBxAg in tumor tissue, 15 (23. 4%) were associated with HBsAg and/or HBcAg, while in the 63 cases with positive HBxAg in non-tumor tissue, 45(71. 4%) were accompanied with HBsAg and/or HBcAg. These findings suggest a dose relationship between prlmay hepatic carcinoma and HBV infection. The high detection rate of HBxAg Indicates a very active expression of the Integrated HBV- DNA genome in the host cells. However, the action of HBxAg in pathogenesis of hepatocellular carcinoma remains to be further investigated.

STUDY ON THE RFLPs AND AMPLICATION AND REARRANGEMENT OF THE TRANSFORMING GENES IN PRIMARY HEPATIC CARCINOMA, GASTRIC CARCINOMA AND BRAIN TUMOR WITH SIX HUMAN ONCOGENE PROBES

By using c-Ha-ras-1, N-ras Wigler (left sequence) and P52C.(right sequence), c-sis, v-erbB, c-myc and v-fos oncogenes as probes, restriction fragment length polymorphisms (RFLPs) of tumor tissue DNAs of 95 patients with gastric carcinoma, primary hepatic carcinoma and brain tumor, and those of 90 normal individuals were studied with the techniques of Southern blot and dot blot. Gene amplification and recombination were also examined in some tumors simultaneously. Some alleles of oncogene are reported in Chinese population for the first time. Moreover, the characteristic frequency of some "rare" alleles and genotypes occurred in some tumor samples is significantly higher than that occured in normal individuals. Pedigree analysis for 2 patients showed that some "rare" alleles are also abandant. Besides, gene amplification and recombination were found in some tumors.

Clinical Study on TACE Combined with Elemene Injection and Cinobufagin Injection Respectively for Middle and Advanced Primary Hepatic Carcinoma

Objective: To observe and compare the differences in the clinical effect and the incidences of adverse reactions oftranscatheter arterial chemoembolization(TACE) combined with elemene injection and cinobufagin injection respectively for middleand advanced primary hepatic carcinoma. Methods: A total of 104 cases of patients with middle and advanced primary hepaticcarcinoma who were treated in the oncology department from August 2018 to January 2020 were included as the study objects, andwere randomly divided into two groups according to different treatment regimens, 52 cases in each group. Both groups were treatedwith TACE once;the cinobufagin injection group was given intravenous infusion with 500 mL of 5% glucose injection and 10 mLof cinobufagin injection once a day. The elemene injection group was given intravenous infusion with elemene injection of 0.4 geach time and once a day. Both groups were treated for two courses, 15 days of continuous treatment with a rest of 15 days beingone course. The clinical effect, the changes in the indexes of liver function including alanine amino transferase(ALT), aspartatetransaminase(AST) and total bilirubin(TBil), the scores of alpha-fetoprotein(AFP) and Karnofsky (KPS) and tumor volumes aswell as the difference in the incidences of adverse reactions between the two groups were observed and compared. Results: Thetotal clinical effective rate was 88.46% in the elemene injection group and 71.15% in the cinobufagin injection group, and thedifference was significant(P<0.05). After treatment, the levels of ALT, AST and TBil in serum in the two groups were significantlydecreased when compared with those before treatment, differences being significant(P<0.05). There was no significant differencebeing found in the comparison of the levels of ALT, AST and TBil in serum between the two groups (P>0.05). After treatment, thedecrease of AFP, tumor volume and the increase of KPS scores in the elemene injection group were significantly more than thosein the cinobufagin injection group, differences being significant (P<0.01). During treatment, there was no significant differencebeing found in the comparison of the total incidences of adverse reactions between the two groups(P>0.05). The adverse reactionsin the cinobufagin injection group were mainly nausea and vomiting, with higher incidence than that in the elemene injection group,the difference being significant (P<0.05). The adverse reactions in the elemene injection group were mainly pain at the injectionsite, with higher incidence than that in the cinobufagin injection group, the difference being significant (P<0.05). Conclusion: Thetherapy of elemene injection combined with TACE for middle and advanced primary hepatic carcinoma has better clinical effect thanthat of cinobufagin injection, but the occ.

Short-term Effect of Combined Therapy with Jinlong Capsule(金龙胶囊)and Transcatheter Arterial Chemoembolization on Patients with Primary Hepatic Carcinoma and Its Influence on Serum Osteopontin Expression

Objective：To observe the clinical combination effect of Jinlong Capsule（金龙胶囊,JLC） and transcatheter arterial chemoembolization（TACE） on the patients with primary hepatic carcinoma（PHC） and JLC＇s influence on serum osteopontin（OPN） expression and elucidate the correlation between the serum OPN level and curative effect of JLC and TACE.Methods：A total of 98 patients with PHC were observed in a randomized controlled trial（RCT）.They were assigned to the Chinese medicine（CM） group（53 patients who were treated with TACE and JLC） and the intervention group（45 patients who were treated with TACE only）.The serum OPN levels were measured before and after treatment by quantitative sandwich enzyme-linked immunosorbent assay（ELISA）.Forty healthy people were assigned to the control group.The clinical efficacy was observed and Karnofsky score（KPS） was graded.Results：The clinical efficacy of the CM group（60.38%） was better than that of the intervention group（40.00%）,and the KPS（84.35±12.19） was higher than the intervention group（69.86±11.58）（P〈0.05）.The serum OPN levels before and after treatment in the patients with PHC were significantly elevated compared with those in the control group（P〈0.01）.After treatment,the OPN levels in CM group（117.69±78.50） were significantly lower compared with those in intervention group（151.09±83.90,P〈0.05）.The OPN levels of responders were remarkably lowered than the non-responders after treatment,and the level of OPN in the CM group was lower than the intervention group（P〈0.05）.Conclusions：The short-term clinical efficacy and the quality of life of patients with PHC can be improved by combining JLC with TACE.The serum OPN levels in PHC patients can reflect the curative effect of treatment and the prognosis of the disease.

Effect of traditional Chinese medicine combined with Western therapy on primary hepatic carcinoma： a systematic review with meta-analysis

Primary hepatic carcinoma （PHC） is a common malignant tumor in China. Cancer is comprehensively treated with various therapeutic regimes, including traditional Chinese medicine （TCM）. TCM has been widely used to improve the quality of fife, delay the time of cancer progression, and prolong the median survival time. This systematic review with meta-analysis aimed to assess the effect of TCM combined with Western therapy on primary hepatic carcinoma. A comprehensive literature search was conducted in six databases, including CNKI, VIP, Wan-Fang Database, CBM, PubMed, and Cochrane library. A total of 44 randomized controlled trials （RCTs） involving 3429 participants suffering from PHC were selected. Meta-analysis results indicated that the overall effect of TCM and Western integrative treatment on PHC was higher than that of Western intervention alone, which can postpone tumor recurrence and metastasis and prolong the overall survival time of patients with PHC. Although the obtained evidence remained weak because of the poor methodological quality of the included studies, this review provided relevant data supporting the efficacy and safety of TCM combined with Western therapies. In future research, individual RCT studies should incorporate accepted standards for trial design and reporting, proper outcome indicators according to international standards, blinding in allocation concealment, and valid follow-up periods.

Relationship between Abnormal Characteristics of Sublingual Collateral and Portal Vein Hemodynamic Changes in Patients with Primary Hepatic Carcinoma

Objective： To investigate the relationship between the abnormal characteristics of sublingual collateral （SC） and portal vein hemodynamic changes in patients with primary hepatic carcinoma （PHC）. Methods： A total of 123 patients of PHC with abnormal SC were enrolled. The SC characteristics were classified and evaluated. The principal components （PC） of SC extracted from them by principal component analysis and the relationship between PC and the dynamic changes of portal vein flow were analyzed by correlation analysis. Results： Three groups of PC were extracted, namely PC-1 （length, width, presentation type of visualization）, PC-2 （circuitous, vesicular change）, and PC-3 （color, collateral hemostasis, petechiae, ecchymosis）. Their total accumulative contribution degree reached 56.803%. Correlation analysis shows that PC-1 was significantly positively correlated with the hemodynamic parameters of the portal vein （P〈0.01）, while PC-2 and PC-3 were not （P〉0.05）. Conclusion： Length, width and presentation type of SC could be used for predicting the changes of portal venous pressure in PHC patients.

Predominant expression of Th1-type cytokines in primary hepatic cancer and adjacent liver tissues

BACKGROUND: Research has revealed a shift towards Th2 in many types of malignant tumor, but the state of Th1/Th2 is not clear in patients with primary hepatic cancer (PHC). This study was designed to determine the expression of Th1- versus Th2-type cytokines in primary hepatic cancer and the adjacent liver tissue in order to provide evidence for treatment of the Th1/Th2 shift. METHODS: Samples were collected from 11 patients with PHC. The gene expression of Th1/Th2 cytokines was detected by reverse transcriptase polymerase chain reaction (RT-PCR) using IFN-gamma and IL-2 as Th1-type cytokine genes, and IL-4 and IL-10 as Th2-type cytokine genes. RESULTS: Th1-type cytokines were expressed in 7/11 PHCs and 9/11 adjacent liver tissues, while Th0 type cytokines occurred in 4/11 PHCs and 2/11 adjacent liver tissues. CONCLUSION: Th1-type cytokines are expressed predominantly in primary hepatic cancer and the adjacent liver tissue.

The Effect Observation of TACE Combinated with the Lobaplatin for Hepatocellular Carcinoma

Objective To observe the effect and safety of lobaplatin combinated floxuridine/pirarubicin in transcatheter hepatic arterial chemoembolization(TACE) of unresectable primary liver cancer. Methods TACE combinated with the lobaplatinbased chemotherapy regimen was used to treat 34 unresectable primary liver cancer patients. The DSA/MRI/CT/blood routine examinations were used to evaluate the short term activity and toxicity after 4-5 weeks, the process was repeated if necessary. The results were observed. Results Among the 34 cases, 1 case(2.9%) showed a complete response, 21 cases(61.7%) showed a partial response, 8 cases(23.5%) showed stable disease, and 4 cases showed progressive disease, with a total effective rate of 67.6%. The content of AFP dropped by over 50% in 20 cases(58.8%). The rate of recovery was hepatalgia(88.2%),ascites(47.1%),appetite(55.9%), Performance Status(30.4%). The median follow-up time(MFT)was 281day(s63-558 days),The median pro-gression-free survival was 118.5 days(95%,CI:88.8-148.2days). Adverse reaction(sIIIIV grade)were less commom, Only 4 cases of vomiting and 2 cases of thrombocytopenia(III grade) were observed. Conclusion Lobaplatin-based TACE is an effective and safe treatment for primary liver cancer.

Study on the role of autophagy in the occurrence and development of liver diseases

Autophagy is a process of lysosome degradation,which plays an important role in maintaining cell homeostasis and organ integrity through the degradation of misfolded proteins,removal of damaged organelles and excess lipids,which is one of the research hotspots in recent years.Liver disease often develops into chronic disease with high mortality,which seriously affects the life safety and quality of life of patients.Studies have shown that autophagy participates in the processes of cellular immunity and oxidative stress,plays an important role in a variety of liver diseases,has the characteristics of two-way regulation,and moderate autophagy has a protective effect.Excessive or dysfunctional autophagy can promote cell death and lead to the occurrence and development of the disease.at present,regulating autophagy is considered as a potential treatment.Based on chronic viral hepatitis,liver fibrosis,non-alcoholic fatty liver disease,acute liver failure and primary liver cancer,this paper reviews the functional characteristics and regulatory mechanism of autophagy in liver diseases.to explore new therapeutic targets for liver diseases,in order to provide new ideas and basis for clinical diagnosis and treatment.