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.

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.

Correlation between blood circulation grading and angiogenesis using ultrasonic contrast of rabbit VX2 hepatic carcinoma

Objective: To build the rabbit model of VX2 hepatic carcinoma, examine the tumor body using the ultrasonic contrast and study the correlation between the blood circulation grading and angiogenesis. Methods: The VX2 tumor strain was prepared in the lateral muscle of the hind legs of 40 male New Zealand rabbits (which were purchased from Nanjing Senbao Biotech Co., Ltd.). The tumor block was embedded in the center of left liver lobe directly to build the rabbit model of VX2 hepatic carcinoma. The ultrasonic contrast was performed 14 d after implanting the tumor body. The semi-quantitative classification (0-IV level) was taken according to the blood flow of tumor vessel. Animals were executed using the air embolism method. The liver was separated to extract RNA and total protein respectively. The real-time PCR and western blotting method were employed to detect the expression of angiogenesis-related factors of VEGF, bFGF and TNP-alpha, while the ultrasonic contrast to detect the correlation with blood circulation grading. The Pearson product moment correlation coefficient was used to measure the linear relationship between these two variables and analyze the correlation between the blood circulation grading and angiogenesis using the ultrasonic contrast. Results: Thirty-three rabbits had the successful model of VX2 hepatic carcinoma. The blood circulation grading by ultrasonic contrast was: 2 cases at level 0 (6.60%), 5 cases at level I (16.7%), 12 cases at level 11 (40.0%), 6 cases at level III (20.0%) (local dense or clustered blood flow) and 5 cases at level IV (16.7%). The results showed that there was positive correlation between three angiogenesis-related factors and the blood circulation grading. The correlation coefficient between three angiogenesis-related factors and the blood circulation grading was over 0.9, which indicated the relatively high correlation. Conclusions: The ultrasound blood circulation grading for the hepatic carcinoma can clearly reflect the changes of blood vessel, which will be of critical significance for the early diagnosis of hepatic carcinoma and clinical evaluation of angiogenesis indicators.

Using SELDI-TOF-MS technology for screening serum markers of hepatic carcinoma in rats

Objective： To identify potential serum markers of hepatic carcinoma in rats through Surface-Enhanced Laser Desorption Ionization-Time of Flight-Mass Spectrometry（SELDI-TOF-MS） Technology. Methods： A rat model of hepatic carcinoma was established. The serum samples of hepatic carcinoma and normal rats were analyzed via SELDI-TOF-MS Technology. The changes of the serum protein fingerprint patterns were observed between the experimental group of hepatic carcinoma and the controls. The analysis was conducted by statistical software-Biomarker Wizard. Results： Fifty-six protein peaks in the serums were found. Within m/z 0-20 000, the protein peaks of rrdz 1158, 8 835 and 15 302 of hepatic carcinoma serums were obviously higher in the rat models compared with those in the controls（P 〈 0.01）. Conclusion： Three peaks were considered as potential biomarkers according to the serum protein fingerprint patterns of the hepatic carcinoma group and the control group.

The expression of TGF-β_1,ADAM12 and HB-EGF in primary hepatic carcinoma

Objective: To detect the expression and location of TGF-β1, ADAM12 and HB-EGF in primary hepatic carcinoma and study their effect on the growth and metastasis of hepatoma carcinoma cell. Methods: TGF-β1, ADAM12 and HB-EGF were detected by RT-PCR and immunohistochemistry in 30 cases of hepatic carcinoma tissues, 30 cases of adjacent carci- noma tissues and 5 cases of normal hepatic tissues. Results: RT-PCR analyses showed that the mRNA expression of TGF-β1, ADAM12 and HB-EGF were markedly increased in each hepatic carcinoma tissue compared with its adjacent tissue (P < 0.01), but no signal was detected in normal hepatic tissue. Immunohistochemistry showed the same outcome on the expression of above three factors in hepatic tissues as RT-PCR. Proteins location analyses showed the proteins of TGF-β1, ADAM12 and HB-EGF all distributed in the stroma of hepatic carcinoma tissues. The positive correlation was found between TGF-β1 and ADAM12 (r = 0.6137, P < 0.05), as well as ADAM12 and HB-EGF (r = 0.5763, P < 0.05). The protein expression of TGF-β1, ADAM12 and HB-EGF were correlated with the size of tumors, degree of differentiation of hepatoma carcinoma cells, portal vein thrombus and the metastasis of absorbent glands, especially with hepatic cirrhosis caused by hepatitis B virus. Conclu- sion: TGF-β1, ADAM12 and HB-EGF possibly play an important role in the process of growth, invasion and metastasis of hepatoma carcinoma cell, meanwhile, the above three factors may collectively participate in the transition from hepatic cirrhosis caused by hepatitis B virus to hepatocellular carcinoma.

Cerebral lipiodol embolism after transarterial chemoembolization for hepatic carcinoma:A case report

We report a case of cerebral lipiodol embolism(CLE) after transarterial chemoembolization(TACE) for unresectable hepatic carcinoma(HCC).A 54-year-old man with unresectable HCC underwent TACE via the right hepatic artery and right inferior phrenic artery using a mixture of 40 mg pirarubicin and 30 mL lipiodol.His level of consciousness deteriorated after TACE,and non-contrast computed tomography revealed a CLE.The cerebral conditions improved after supportive therapy.The complication might have been due to hepatic arterio-pulmonary vein shunt caused by direct invasion of the tumor.Even though CLE is an uncommon complication of TACE,we should be aware of these rare complications in patients with high risk factors.

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,

An Intelligent Prediction Model for Target Protein Identification in Hepatic Carcinoma Using Novel Graph Theory and ANN Model

Hepatocellular carcinoma(HCC)is one major cause of cancer-related mortality around the world.However,at advanced stages of HCC,systematic treatment options are currently limited.As a result,new pharmacological targetsmust be discovered regularly,and then tailored medicines against HCC must be developed.In this research,we used biomarkers of HCC to collect the protein interaction network related to HCC.Initially,DC(Degree Centrality)was employed to assess the importance of each protein.Then an improved Graph Coloring algorithm was used to rank the target proteins according to the interaction with the primary target protein after assessing the top ranked proteins related to HCC.Finally,physio-chemical proteins are used to evaluate the outcome of the top ranked proteins.The proposed graph theory and machine learning techniques have been compared with six existing methods.In the proposed approach,16 proteins have been identified as potential therapeutic drug targets for Hepatic Carcinoma.It is observable that the proposed method gives remarkable performance than the existing centrality measures in terms of Accuracy,Precision,Recall,Sensitivity,Specificity and F-measure.

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.

COLOR FLOW IMAGING OF HEPATIC CARCINOMA

Color flow imaging(CFI)ultrasound technique can discover the tumor vascularity and superimposed it to convontional B-mode ultrasonogram in real-time. The flow velocity on spectral Doppler sonogram can be measured by setting the sample volume to any selected site.One hundred and thirty-six patients with solid hepatic space-occupied lesions had been admitted and 113 cases were confirmed by operation and pathology,23 patients were strongly suspected by hepatic angiography (HAA).Ninety nine patients with 109 nodules were finally diagnosed as hepatic cellular carcinoma(HCC).According to color flow distribution pattern,3 kinds of color configuation had been nominated.Tumor vascularity discovered by CFI,especially the arterial blood flow was easy to be recognized,and its emerge rate was quite different between HCC group(94.5%)and hemangioma(HCH)group(17.07%)(P<0.01).Spectral Doppler studies were also carried out in these cases and the detectability of arterial flow in HCC group(95.41%)was much higher than that to HCH group (21. 95%) (P<0. 005).Resistant index(RI)and pulsatile index(PI)could be used to differentiate HCC (>0. 50 and >0.80 respectively)from HCH (P<0.001 and P<0.001 respectively).Arterial-portal(A-P) shunt could also be detected by CFI and spectral Doppler(mostly its Vmax>0.6m/s).The detection rate of A-P shunt was 64% in HCC group,but no case could be detected in HCH group.

THE CHANGES OF PERIPHERAL BLOOD T LYMPHOCYTE SUBSETS IN PATIENTS WITH PRIMARY HEPATIC CARCINOMA BOTH PRE-TACE AND POST-TACE

Objective To observe the variations of the cellular immunological function in patients with primary hepatic carcinoma both pre-TACE(transcatheter arterial chemoembolization,TACE).Methods T lymphocyte subset CD4,CD8 and CD4/CD7 ratio in 45 patients with primary hepatic carcinoma both pre-TACE and post-TACE were measured by flow Cytometer,and compared with the result of T lymphocyte subset in 19 healthy people as normal control samples.Results The CD4 and CD4/CD8 ratio in patients with primary hepatic carcinoma were significantly lower than those in normal control(P<0.05),while CD8 higher(P<0.05);The CD4 and CD4/CD8 ratio in patients with primary hepatic carcinoma were much more lower after TACE than those before TACE(P<0.05),while CD8 was higher but had no significant difference(P>0.05).Conclusion The cellular immunological function in patients with primary hepatic carcinoma decreased and is much more lower after TACE.

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.

Intraoperative ultrasonography during radiofrequency ablation for hepatic carcinoma

Objective： To explore the feasibility and efficiency of intraoperative ultrasonography （IOUS） in the cool-tip ra- diofrequency ablation （RFA） of hepatic carcinoma. Methods： Thirty-one patients of hepatic carcinoma were enrolled in this study. In the process of open-surgical cool-tip radiofrequency ablations, IOUS was applied to assess the hepatic lesions, guide and monitor the process of RFA in real-time. Results： Under the guidance of intraoperative ultrasonography, the open surgical RFA in all patients proceed smoothly. Seven additional hepatic lesions were found that were not detected in preoperative imaging. A false positive focal lesion reported by preoperative MRI was accurately ruled out by IOUS. Conclusion： Intraoperative ultrasonography is superior to ordinary imaging techniques in finding missed lesions, avoiding complications such as injuries of bile ducts and vessels. Monitoring the real-time RFA process thereby obviously optimizing the treatment of hepatic carcinoma.

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.

Nanotechnology-based combinational strategies toward the regulation of myofibroblasts and diseased microenvironment in liver fibrosis and hepatic carcinoma

Liver fibrosis and hepatic carcinoma(HCC)pose a huge challenge worldwide due to the lack of effective treatment options for end-stage liver diseases.According to their functions and roles,hepatic myofibroblasts mainly include nontumoral fibroblasts(mainly activated hepatic stellate cells(HSCs)),which are involved in the wound-healing process of liver fibrosis,and cancer-associated fibroblasts(CAFs)in hepatic HCC.HSCs play a significant role in regulating extracellular matrix(ECM)deposition in progressive liver fibrosis.CAFs can be derived from activated HSCs and differentiate into ECM-producing myofibroblasts.Moreover,growing evidence shows that CAFs are the primary regulators of the HCC microenvironment,releasing growth factors and cytokines and suppressing the antitumor immune response.Combined therapeutic strategies show reduced drug resistance and side effects.Nanotechnology-based combined strategies aim to improve the delivery efficiency of various therapeutic agents with reduced toxicity via multiple mechanisms.In this review,we will discuss recent developments in combinational strategies based on nanotechnology that regulate myofibroblasts and the diseased microenvironment for liver fibrosis and HCC treatment.We will also identify the major challenges that the field is facing and offer some insights for future drug discovery.

Anti-hepatic carcinoma mechanisms of calycosin through targeting ferroptosis

Background Ferroptosis,a pathologic state induced by lipid-driven oxidative stress,is associated with the development of human cancers.Calycosin,a natural compound with antioxidant and anti-inflammatory activities,has promising antitumor effects.However,the ferroptosis-related mechanism of calycosin in the treatment of hepatic carcinoma has not been reported.Methods This study applied network pharmacology and bioinformatic approaches(including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis)to investigate the pharmacologic targets and mechanism of action of calycosin in the treatment of hepatic carcinoma through targeting ferroptosis.By searching online databases including The Cancer Genome Atlas,FerrDb,GeneCards,SwissTargetPrediction,SuperPred,BindingDB,TargetNet,BATMAN-TCM,and Drugbank,we identified 13 ferroptosis-related putative target genes of calycosin against hepatic carcinoma including IL-6,PTGS2,SRC,HRAS,NQO1,NOX4,PGK1,G6PD,GPI,MIF,NOS2,ALDOA,and SQSTM1.Results Molecular docking analysis revealed that calycosin potentially binded directly with the target proteins IL-6,PTGS2,and SRC.Functional enrichment analysis of these proteins indicated that they were involved in gluconeogenesis and apoptosis through regulation of ERK1,ERK2,and MAPK activities(P<0.05).Conclusion Calycosin exerts antitumor effects in hepatic carcinoma by targeting ferroptosis through regulation of IL-6,PTGS2,and SRC.

Splicing factor proline and glutamine-rich is a prognostic biomarker and correlated with clinical pathologic features and immune infiltrates in hepatocellular carcinoma

Background:Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related deaths globally.Splicing factor proline and glutamine-rich(SFPQ)is a multifunctional protein that controls various biological functions.As a potential therapeutic target and a promising prognostic indicator,the potential effects and processes of SFPQ in HCC require further investigation.Methods:The RNA sequencing data were obtained from the Gene Expression Omnibus,International Cancer Genome Consortium,and The Cancer Genome Atlas databases to analyze SFPQ expression and differentially expressed genes(DEGs).We utilized the LinkedOmics database to identify co-expressed genes.A Venn diagram was constructed to determine the overlapping genes between the DEGs and the co-expressed genes.Functional enrichment analysis was performed on the overlapping genes and DEGs.Furthermore,our study involved functional enrichment analysis,a protein-protein interaction network analysis,and an analysis of immune cell infiltration.The cBioPortal and Tumor Immune Single-cell Hub were utilized to investigate the genetic alterations of SFPQ and the single-cell transcriptome visualization of the tumor microenvironment.A ceRNA network was established with the assistance of the ENCORI website.Finally,we elucidated the clinical significance of SFPQ in HCC by employing Kaplan-Meier survival analysis,univariate and multivariate Cox regression,and prognostic nomogram models.Results:The expression of SFPQ in HCC tissues was significantly elevated compared to normal tissues.GSEA results indicated that increased expression of SFPQ was associated with pathways related to HCC.The ceRNA network,including SFPQ,hsa-miR-101-3p,AC023043.4,AC124798.1,AC145207.5,and GSEC,was constructed with the assistance of ENCORI.High SFPQ expression was related to a poor prognosis in HCC and its subtypes.Univariate and multivariate Cox regression analysis showed that elevated SFPQ expression is an independent predictive factor.Conclusions:The overexpression of SFPQ may serve as a potential prognostic biomarker,indicating a poor prognosis in HCC.

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.