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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.
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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)
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ObjectiveTo explore the possible mechanism of Shipi Xiaoji Beverage （实脾消积饮） in treating primary liver cancer from the perspective of mitochondrial dynamics imbalance and ferroptosis. MethodsThe Shipi Xiaoji Beverage-containing serum was prepared， and liver cancer HepG2 cells were cultured in vitro. The blank group， control group， cisplatin group （10 µg/ml）， and 5%， 10%， and 15% medicated serum groups were set， with 4 duplicate holes in each group. After adding the corresponding medicinals to each group， the cell survival rate was calculated using the CCK-8 test after 24-hour culture at 37 ℃ with 5% CO2. Using transwell invasion assay， the number of cells that reached the upper chamber membrane through penetrating the Matrigel was calculated after culturing for 48 hours. The scratch migration rate was calculated after incubation for 24 h and 48 h in the scratch experiment， and the concentration of the medicated serum was screened for subsequent experiments. The control group， 10% medicated serum group （the screened concentration） and 10% medicated serum+Mdivi-1 group were set up. After culturing for 24 hours， the average fluorescence intensity of mitochondria and reactive oxygen species （ROS）， adenosine triphosphate （ATP） content and level were measured， and the protein expression of cytoplasmic and mitochondrial dynein-related protein 1 （Drp1） and mitochondrial phosphorylated dynamin-related protein 1 （p-Drp1） was detected. The control group， 10% medicated serum group， ferroptosis activator group （Erastin， 10 μmol/L） and 10% medicated serum+ferroptosis inhibitor group （fer-1，10 μmol/L） were set up， and after adding the corresponding medicinals to each group and culture for 24 hours， the intracellular glutathione （GSH）， malondialdehyde （MDA） content and ferrous ion level were detected， as well as the protein expression of solute carrier family 7 member 11 （SLC7A11） and glutathione peroxidase 4 （GPX4） in cells. ResultsCompared to those in the control group， the cell survival rate， invasion number， 24 h and 48 h scratch migration rate in all medicated serum groups and cisplatin group significantly decreased （P＜0.01）； as the concentration of medicated serum increased， the cell survival rate， invasion number and 48h scratch migration rate of each medicated serum group gradually decreased （P＜0.01）， and finally， 10% of Shipi Xiaoji Beverage-containing serum was selected for subsequent experimental concentration. Compared to the control group， the 10% medicated serum group had decreased average fluorescence intensity of mitochondria and ATP content and increased average fluorescence intensity of ROS （P＜0.05）； compared to the 10% medicated serum group， the 10% medicated serum+Mdivi-1 group had higher average fluorescence intensity of mitochondria and ATP content and lower average fluorescence intensity of ROS （P＜0.05 or P＜0.01）. Compared to those in the control group， GSH content and protein expression of SLC7A11 and GPX4 in other groups significantly decreased， while MDA content and ferrous ion level increased （P＜0.05 or P＜0.01）； compared to the ferroptosis activator group， the 10% medicated serum group and the 10% medicated serum+ferroptosis inhibitor group had decreased MDA content and ferrous ion level， and increased protein expression of SLC7A11 and GPX4 （P＜0.05 or P＜0.01）； the 10% medicated serum+ferroptosis inhibitor group had higher GSH level than the 10% medicated serum group （P＜0.01）. ConclusionShipi Xiaoji Beverage may inhibit the proliferation， infestation， migration of HepG2 cells by causing mitochondrial dynamics imbalance and inducing ferroptosis， thereby playing against liver cancer.
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ObjectiveTo observe the effects of Huqi Zhengxiao Formula （槲芪癥消方） on the survival rate and quality of life of patients with stage Ⅲ hepatitis B-associated primary liver cancer （PLC） with syndrome of healthy qi deficiency and toxic stasis accumulation after transcatheter arterial chemoembolisation （TACE） treatment. MethodsOne hundred and twenty-six patients with stage Ⅲ hepatitis B-associated PLC who were identified as syndrome of healthy qi deficiency and toxic stasis accumulation after TACE treatment were selected， and were randomly assigned to 63 cases each of the treatment group and the control group in a ratio of 1∶1 by using the random number table method； the control group was given symptomatic supportive treatments with western internal medicine， and the treatment group was given the addition of Huqi Zhengxiao Formula on the basis of the control group. All patients were treated for a period of 48 weeks， and were followed up at weeks 4， 8， 12， 24， 36， and 48 of the treatment process. The primary effectiveness index was the 1-year survival rate， and the secondary effectiveness index was the Karnofsky score and the traditional Chinese medicine （TCM） syndrome score. Survival analysis was performed using the Kaplan-meier method， and Log-rank test was used to compare the differences between the survival curves of each group. ResultsSix withdrawals in the treatment group and seven withdrawals in the control group， and finally 57 patients in the test group and 56 patients in the control group were included in the statistical analysis. The 1-year survival rate of patients in the treatment group was 56.1% （32/57）， which was higher than that of 33.9% （19/56） in the control group （P = 0.033）. The mean survival time was （275.30±15.50） days in the treatment group， higher than （227.16±17.11） days in the control group （P = 0.039）. Thirty-two patients in the treatment group and 19 patients in the control group completed the Karnofsky score and TCM symptom score at each time point. At weeks 4， 8， 12 and 36， the difference in the Karnofsky score between the two groups was not statistically significant （P＞0.05）； at weeks 24 and 48， the Karnofsky score in the treatment group was higher than that in the control group at the same time point （P＜0.05）； analysis of variance of repeated measurements found that the downward trend of the Karnofsky score in the treatment group was slower than that in the control group （F = 4.47， P = 0.037）. The difference between the TCM symptom scores of the two groups at each follow-up observation point was not statistically significant （P＞0.05）； there was a tendency for the TCM symptom scores of the two groups to increase， but the ANOVA of repeated measurements found that the difference between the two groups was not statistically significant either （F = 0.31， P = 0.58）. Concusion The oral administration of Huqi Zhengxiao Formula can improve the survival rate， prolong the survival time， and improve the quality of life of patients with stage Ⅲ hepatitis B-associated PLC with syndrome of healthy qi deficiency and toxic stasis accumulations after TACE treatment.
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ObjectiveTo observe the effect of the Fangfeng Tongshengsan on post-chemoembolization syndrome with primary liver cancer or postoperative liver metastases of colorectal cancer. MethodSeventy-two patients suffered from post-chemoembolization syndrome after transcatheter hepatic arterial chemoembolization were randomly divided into 2 groups， including a Fangfeng Tongshengsan group and a control group， with 36 patients in each group. The patients in Fangfeng Tongshengsan group orally took the decoction for consecutive 7 d. The patients in the control group were physically cooled down with alcohol rub bath and ice pack for consecutive 7 d. Furthermore， the difference of fever， Karnofsky performance status （KPS）， pain in the liver region， nausea vomiting， constipation， and liver function between these two groups were observed. ResultCompared with the control group， Fangfeng Tongshengsan significantly relieved fever， reduced the body temperature （P<0.05）， and shortened the duration of fever （P<0.05）， indicating that Fangfeng Tongshengsan remarkably improved the KPS （P<0.05）. Meanwhile， Fangfeng Tongshengsan obviously alleviated nausea， vomiting， and constipation status and shortened the duration time compared with the control group （P<0.05）. In addition， the parameters of liver function including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyl transpeptidase （GGT）， and total bilirubin （TBIL） were significantly decreased in the Fangfeng Tongshengsan group （P<0.05）， which indicated that Fangfeng Tongshengsan alleviated liver dysfunction of patients with post-chemoembolization syndrome. ConclusionFangfeng Tongshengsan can be used to treat post-chemoembolization syndrome with primary liver cancer and postoperative liver metastases of colorectal cancer.
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ObjectiveTo evaluate the efficacy and influencing factors of Biejiajianwan in the treatment of primary liver cancer based on real-world data of traditional Chinese medicine （TCM）. MethodClinical diagnosis and treatment data of patients with primary liver cancer admitted to five Grade-A tertiary hospitals in Henan Province from January 2015 to December 2020 were collected from the medical electronic database. The patients treated with Biejiajianwan for ≥30 days were assigned to the exposure group and those without treatment with Biejiajianwan or treated with Biejiajianwan for <30 days to the non-exposure group. The propensity score matching model was used to balance confounding factors between the two groups according to the 1∶1 genetic matching method. Kaplan-Meier method was used for survival analysis and survival curve plotting. Log-rank was used to test the difference in survival rate between the two groups. Univariate analysis of Biejiajianwan in the treatment of primary liver cancer was performed by Log-rank test combined with the Kaplan-Meier method. The factors with statistical significance （P<0.05） were combined with unbalanced factors by the propensity score matching model， and at the same time， clinical common sense and relevant prognostic factors by literature search were considered， which were subjected to multivariate analysis by Cox proportional hazards regression model. ResultA total of 2 207 electronic cases were collected，including 174 cases in the exposure group （Biejiajianwan group） and 2 033 cases in the non-exposure group. After propensity score matching， there were 174 cases in the exposure group and 174 cases in the non-exposure group. The Kaplan-Meier method was used for survival analysis on the matched data， and the Log-rank test results showed that the survival rate of patients with primary liver cancer in the Biejiajianwan group was higher than that in the control group （χ2=12.193， P<0.01）. Cox proportional hazards regression model analysis showed that the regression coefficient of Biejiajianwan was -0.916 4 with the hazard ratio （HR） ［95% confidence interval （CI）］=0.4 （0.239 5-0.668 0）， P<0.01， and the regression coefficient of radiofrequency ablation treatment was -0.976 5 with HR （95% CI）=0.376 6 （0.172 8-0.821 1， P<0.05）. Fibrinogen （FIB） abnormal regression coefficient was 0.481 4 with HR （95% CI）=1.618 4（1.022 0-2.562 9），P<0.05. ConclusionBiejiajianwan can prolong the survival period of patients with primary liver cancer. Radiofrequency ablation is an independent protective factor for Biejiajianwan in the treatment of primary liver cancer，while abnormal FIB are independent risk factors for Biejiajianwan in the treatment of primary liver cancer.
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@#Clinically， the recurrence and metastasis of liver cancer after local ablation therapy have been the main factors affecting the long-term survival of patients with liver cancer. As a new generation of composite cryoablation and thermal ablation system， Co-Ablation System creatively integrates the advantages of profound hypothermia cryoablation and thermal ablation， which can maximize the release of tumor antigen while completely destroying liver cancer in situ， thus， the purpose of controlling liver cancer recurrence and metastasis can be achieved. Co-Ablation System treatment is usually carried out through percutaneous puncture under ultrasound or CT guidance. The selection of local anesthesia or general anesthesia is based on the size and location of the liver cancer. Co-Ablation System treatment is mainly suitable for single tumor with diameter <5 cm and multiple tumors（≤3 tumor lesions） with a maximum diameter <3 cm. After ablation， protection of liver function and symptomatic treatment are employed according to patient’s condition. About one month after ablation， MRI or contrast-enhanced CT examination is performed to evaluate the therapeutic efficacy， then， the patients are followed up regularly. In order to standardize the application of Co-Ablation System in treating liver cancer， the Committee of Minimally Invasive Therapy in Oncology and the Committee of Ablation Therapy in Oncology， Chinese Anti-Cancer Association， have organized domestic experts engaged in liver cancer ablation therapy to make a professional and in-depth discussion and to compose this expert consensus on Co-Ablation System for the treatment of primary liver cancer.
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Primary liver cancer, especially hepatocellular carcinoma, poses a serious threat to the life and health of the Chinese people. Given the insidious onset of liver cancer, less than 30% of hepatocellular carcinoma patients are considered for radical treatment at the initial diagnosis. Systemic anti-tumor therapy plays an important role in the treatment of advanced hepatocellular carcinoma. Immunotherapy of hepatocellular carcinoma has developed rapidly, and an increasing number of immunotherapy drugs, which can better control the progress of hepatocellular carcinoma and prolong the survival of patients, have become first- and second-line treatment options. This article reviews briefly the progress of immunotherapy for hepatocellular carcinoma in recent years.
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Objective To explore the classification and characteristics of common syndromes of primary liver cancer and provide reference for clinical treatment.Methods Collect the four diagnostic information of patients with primary liver cancer from two top three TCM hospitals in Henan Province,and build a database.Using Lantern 5.0 software,based on two-step hidden tree analysis,a hidden structure model was constructed,and common syndromes of primary liver cancer were extracted through comprehensive clustering.SPSS 23.0 software was used for factor analysis and systematic cluster analysis to infer the potential syndromes.Combined with the results of different methods and professional knowledge,the syndrome classification of primary liver cancer was determined.Results A total of 1353 patients with 105 symptoms of primary liver cancer were included.59 symptoms with an analysis frequency≥40 were included to construct a hidden structure model,24 hidden variables were obtained,and 5 common syndromes were obtained by comprehensive clustering,namely,qi deficiency syndrome,liver depression and qi stagnation syndrome,blood stasis syndrome,water dampness stagnation syndrome,liver and gallbladder damp heat syndrome.20 common factors were obtained by factor analysis for symptoms with frequency>3%,and 8 common syndromes were inferred by cluster analysis with common factors.7 common syndromes and characteristics were finally determined by combining different methods and expertise.Conclusion The common syndromes of primary liver cancer are qi deficiency syndrome,liver depression and qi stagnation syndrome,blood stasis syndrome,water dampness stagnation syndrome,yin deficiency syndrome,liver and gallbladder damp heat syndrome,spleen deficiency and dampness stagnation syndrome.The results objectively reflect the actual situation of patients with primary liver cancer,and can provide reference for the treatment of primary liver cancer based on syndrome differentiation.
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Primary liver cancer(PLC)is one of the most common malignant tumors of digestive system in clinic.TCM plays an important role in the treatment of PLC.After sorting out the medical records and literatures related to the syndrome types of primary liver cancer in recent years,it was found that the syndrome type of qi stagnation and blood stasis was one of the important syndrome types of primary liver cancer.This article discusses and supplements the syndrome type of qi stagnation and blood stasis from the aspects of etiology and pathogenesis,proportion of syndrome types,staging of liver cancer,objective indicators of liver cancer,etc.It provides a new understanding for the treatment of primary liver cancer based on syndrome differentiation,so as to improve the clinical cure rate of liver cancer,alleviate the clinical symptoms of patients,improve the quality of life,and prolong the survival period.
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Objective The aim of this study was to identify macrophage related genes(MRGs)in liver cancer and construct a prognostic risk prediction model for liver cancer.Methods The liver cancer scRNA-seq data from the GEO database were down-loaded to identify genes specifically expressed in macrophages as MRGs.The GO and KEGG functional enrichment analyses on MRGs were conducted.In the TCGA-LIHC dataset of the TCGA database,multiple random sampling single factor Cox regression for single-factor Cox regression,LASSO regression,and multivariate Cox regression analyses were employed to identify MRGs for liver cancer prognosis prediction,and a liver cancer prognostic prediction model was constructed.Results The results obtained 8 major cell types,including those containing macrophages through clustering using scRNA-seq data from the GEO database.The proportion of macrophages in the immune microenvironment of liver cancer was significantly higher than that of normal tissues(P=0.016),and genes such as SPP1,RNASE1,and MMP9 were highly expressed.Multiple metabolic pathways,including purine metabolism,citric acid cycle,and drug metabolism cytochrome P450 were activated in liver cancer-associated macrophages.This study identified 777 MRGs from liver cancer scRNA-seq(LogFC＞0.25,P＜0.05),which mainly involved in functions such as actin binding and regula-tion of immune receptor activity.Seven MRGs,including ATP1B3,ATP6V0B,HBEGF,KLF2,NR1H3,RAB10,and SPP1 were select-ed from the 169 stable prognostic genes(P＜0.05)for the construction of the prognosis model.The AUC values for the 1,3,and 5-year survival outcomes of the model in the TCGA liver cancer cohort were 0.791,0.791,and 0.751,respectively.In the validation ICGC cohort,they were 0.614,0.682,and 0.688,respectively,demonstrating good predictive performance.In liver cancer patients with high prognosis risk scores,the expression of macrophages M0,neutrophils,and regulatory T cells was higher(P＜0.05),and im-munosuppression and immune activation coexisted.Conclusion Liver cancer MRGs can serve as potential biomarkers for predicting the prognosis of liver cancer patients.These liver cancer MRGs are mainly associated with actin binding,immune receptor activity,and infiltration of various immune cells.
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Throughout the 1 34-year development of hepatectomy,whether open,laparoscopic,or robotic,it has inherited an anatomical,empirical surgical approach based on morphology,which has not fundamentally changed the two-dimensional diagnosis and treatment of the disease.Over the last 20 years,the diagnosis and treatment of primary liver cancer have undergone profound changes with the advent and evolution of digital intelligent diagnosis and treatment technologies.Three-dimensional visualization techniques have allowed the pre-operative visualization of tumors and complex liver anatomy,changing the traditional two-dimensional diagnosis and treatment paradigm.The development of indocyanine green fluorescence imaging has enabled intraoperative visualization of tumor boundaries at the molecular and cellular levels.The application of augmented reality navigation technology has allowed the visualization of anatomical structures during surgery.Hepatectomy has transformed from traditional empirical surgery into modern intelligent navigation-based minimally invasive surgery,ushering in a new era of digital intelligent liver surgery.This review has summarized the most recent research progress of digital intelligent minimally invasive treatment of primary liver cancer.
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Primary liver cancer(PLC)is one of the most common malignant diseases with the highest incidence and mortality rate,which poses a serious threat to public health in China.Thus,it is crucial to realize the early and accurate diagnosis of PLC.In clinical practice,traditional imaging techniques can provide the morphological information of liver cancer tissues,but they still have some limitations.Multimodality imaging can provide more comprehensive diagnostic information by integrating the advantages of different imaging technologies.By using liver cancer-specific targeting probes,multimodality imaging technology can achieve higher sensitivity and specificity than traditional imaging techniques.It can not only help with the accurate diagnosis of liver cancer by providing the structural and functional information of PLC simultaneously,but also guide surgeons to make better intraoperative decisions for PLC patients by supporting real-time navigation imaging during surgery.Therefore,multimodality imaging is of great significance to the clinical diagnosis and treatment of PLC.This review mainly focuses on the multimodality imaging technology and specific targeting probes of PLC,and summarizes the current research progress in this field.
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ObjectiveTo explore the anti-tumor effect and mechanism of Shenqi Yiliu prescription in the intervention of pyroptosis. MethodTen male BALB/c mice were randomly selected and assigned to the blank group. The remaining 40 mice underwent the induction of the liver cancer xenograft model. After 5 days of modeling， 40 surviving mice were randomly divided into model group， cisplatin group ［2.5×10-3 g·kg-1·（3 d）-1］， Shenqi Yiliu prescription group （27 g·kg-1·d-1）， and a combination group （Shenqi Yiliu prescription group + cisplatin）. The mice in the blank group and the model group were treated with an equal volume of normal saline for 10 days. The general conditions of mice in each group were observed. After the intervention， the tumor weight of the mice was weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in tumor tissues. The levels of mouse liver function indicators， including alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were detected. The TdT-mediated dUTP-biotin nick end labeling （TUNEL） assay was used to detect DNA damage in mouse tumor tissue cells. Immunohistochemistry （IHC）， immunofluorescence （IF）， and Western blot were used to detect the protein expression levels of NOD-like receptor protein 3 （NLRP3）， cysteinyl aspartate-specific protease-1 （Caspase-1）， and gasdermin D （GSDMD） in tumor tissues. The levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in tumor tissues were detected by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the mice in the blank group， those in the model group were in a poor mental state， sleepy， and lazy， and their fur color was dull， with increased levels of serum ALT and AST in liver function tests （P<0.01）. Compared with the model group， the groups with drug intervention showed improved mental state， inhibited tumor growth to varying degrees， and decreased tumor weight， and the tumor inhibition rate in the combination group was the highest （P<0.01）. HE staining showed that the pathological and morphological lesions of the tumor tissues in the model group were significant， while those in all groups with drug intervention were improved to a certain extent. The karyolysis and nuclear rupture in the Shenqi Yiliu prescription group and the combination group were more significant. In the liver function test， the serum ALT and AST levels of mice in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the inflammatory factors IL-1β and IL-18 in each group with drug intervention decreased （P<0.05， P<0.01）. Among them， the declining trend of IL-1β and IL-18 in the Shenqi Yiliu prescription group was the most significant （P<0.01）. TUNEL staining showed that the positive TUNEL staining in each group with drug intervention decreased after intervention （P<0.05， P<0.01）， especially the cisplatin group and Shenqi Yiliu prescription group （P<0.01）. Western blot， IHC， and IF found that the protein expression levels of NLRP3， Caspase-1， and GSDMD in each group with drug intervention decreased （P<0.05， P<0.01）. Compared with the mice in the cisplatin group， those in the Shenqi Yiliu prescription group and the combination group had better mental state and regular tumor morphology， and the tumor weight of the mice in the combination group decreased （P<0.05）. The levels of ALT and AST in the Shenqi Yiliu prescription group decreased （P<0.05）， and the levels of IL-1β and IL-18 in the Shenqi Yiliu prescription group and the combination group decreased （P<0.05， P<0.01）， especially in the combination group （P<0.01）. The results of IHC showed that the expression of GSDMD protein in the tumor tissues of mice in the combination group was reduced （P<0.01）. IF detection showed that the expression of NLRP3 in the tumor tissues of the Shenqi Yiliu prescription group was reduced （P<0.01）. The results of Western blot showed that the expression level of NLRP3 protein in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the expression level of Caspase-1 protein in the combination group decreased （P<0.01）. The decrease in GSDMD protein expression was not significant， and the difference was not statistically significant. ConclusionShenqi Yiliu prescription combined with cisplatin has an obvious anti-tumor effect， which may be achieved by down-regulating the NLRP3/Caspase-1/GSDMD inflammatory pyroptosis pathway to inhibit cell pyroptosis， and relieve the inflammatory response in mice with liver cancer.
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Aim To investigate the mechanism of Qizhu anti-cancer prescription ( QZACP) inthe treatment of primary liver cancer using network pharmacology and molecular docking. Methods Drugs and primary liver cancer ( PLC) -related targets were found according to TCMSP database and disease databases such as GeneCard, the key chemical components and core targets were screened by Cytoscape 3. 9. 1 and String platform respectively, and a network relationship diagram of traditional Chinese medicine-active component-target was constructed by using Cytoscape 3.9. 1. GO functional analysis and KEGG pathway analysis were performed using DAVID platform, visualized by R 4. 1. 1 software, and finally the core clustered proteins were analyzed by CytoNCA plug-in to obtain the core action targets, and the core components and key targets were verified by using molecular docking technology and the pharmacodynamic mechanism of QZACP was further verified by animal experiments. Results The active ingredients of QZACP in the treatment of primary liver cancer may be quercetin, glycyrrhizin, Denudatin B, isoflavanone, sanguinarol, etc. ; the potential targets were STAT3, EGFR, AKT1 etc. ; the related pathways were mainly PI3K-Akt signaling pathway,MAPK signaling pathway,etc. ; molecular docking showed that the core compounds had better integrating conformation with the key targets. In addition, QZACP could inhibit the growth of tumor in nude mice and decrease the expression of STAT3, EGFR and AKT1. Conclusions Qizhu anti-cancer prescription may have some positive significance in the treatment of primary liver cancer, which may be related to the regulation of PI3K/Akt signaling pathway.
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AIM: To observe the clinical efficacy of Fuzheng Xiaoliu Granules in the treatment of stage II primary liver cancer and to explore its mechanism of action from the perspective of metabolomics. METHODS: Sixty patients with stage II primary liver cancer who achieved complete remission (CR) after comprehensive interventional therapy were randomly divided into treatment group and placebo group, with 30 patients in each group. They were treated for one year and observed for one year. The one-year recurrence rate, traditional chinese medicine (TCM) syndrome score, alpha-fetoprotein and child-pugh grade were compared between the two groups. The serum metabolites of the two groups before and after treatment were screened by ultra-high liquid chromatography-mass spectrometry technology, and the metabolic pathways and related biological pathways were analyzed. RESULTS: The one-year recurrence rate of the treatment group was significantly lower than that of the placebo group, and the overall improvement rate of TCM syndrome score was significantly better than that of the placebo group (P0.05). Metabolomics results showed that there were 39 and 33 different metabolites in the treatment group before and after treatment and in the two groups after treatment, respectively. After enrichment analysis and topological analysis of the different metabolites, it was found that Fuzheng Xiaoliu Granules could affect amino acid metabolism, fatty acid metabolism and purine metabolism and other metabolic pathways. Before and after treatment in the treatment group and after treatment in the two groups, there were the same differential metabolites and metabolic pathways in the two comparison results. The same differential metabolites with FOLD CHANGE>1 include Stearic acid, Hypoxanthine, Kynurenic acid, Arachidonic acid, and N-Arachidonoyl Dopamine. The same metabolic pathways with Impact>0.1 include Arachidonic acid metabolism and Histidine metabolism. CONCLUSION: Fuzheng xiaoliu granules can effectively reduce the recurrence rate of stage II liver cancer patients after comprehensive intervention and improve the TCM syndrome. It may inhibit the activation of PI3K/Akt and ERK signaling pathways by regulating the content of metabolites involved in metabolic pathways such as amino acids and fatty acids, thereby delaying tumor recurrence.
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Liver cancer is one of the most common cancers in China. In recent years, liver cancer tends to be treated with comprehensive therapies, including surgery, ablation, interventional embolization, radiotherapy, chemotherapy, targeted therapy, immunotherapy, and liver transplantation. At present, the low surgical resectionrate is one of the main factors affecting the prognosis of liver cancer patients. Preoperative neoadjuvant therapy or conversion therapy for liver cancer can maximize the rate of surgical resection and improve the prognosis. With the rapid development of radiotherapy and immunotherapy in the comprehensive treatment of liver cancer, it has been gradually confirmed that the unique effects of preoperative radiotherapy and immune therapy for liver cancer can improve the prognosis of the patients. Therefore, this paper reviewed the research progress in the preoperative radiotherapy and immunotherapy for liver cancer by searching relevant literature and reports at home and abroad.
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OBJECTIVE@#To assess the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on clinical outcomes of patients receiving anti-PD-1 immunotherapy for hepatocellular carcinoma.@*METHODS@#We conducted a retrospective study among 215 patients with primary liver cancer receiving immunotherapy between June, 2018 and October, 2020. The patients with balanced baseline characteristics were selected based on propensity matching scores, and among them 33 patients who used NSAIDs were matched at the ratio of 1∶3 with 78 patients who did not use NSAIDs. We compared the overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) between the two groups.@*RESULTS@#There was no significant difference in OS between the patients using NSAIDs (29.7%) and those who did not use NSAIDs (70.2%). Univariate and multivariate analyses did not show an a correlation of NSAIDs use with DCR (univariate analysis: OR=0.602, 95% CI: 0.299-1.213, P=0.156; multivariate analysis: OR=0.693, 95% CI: 0.330-1.458, P=0.334), PFS (univariate analysis: HR=1.230, 95% CI: 0.789-1.916, P=0.361; multivariate analysis: HR=1.151, 95% CI: 0.732-1.810, P=9.544), or OS (univariate analysis: HR=0.552, 95% CI: 0.208-1.463, P=0.232; multivariate analysis: HR=1.085, 95% CI: 0.685-1.717, P=0.729).@*CONCLUSION@#Our results show no favorable effect of NSAIDs on the efficacy of immunotherapy in patients with advanced primary liver cancer, but this finding still needs to be verified by future prospective studies of large cohorts.
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Humains , Anti-inflammatoires non stéroïdiens/usage thérapeutique , Immunothérapie/méthodes , Tumeurs du foie/traitement médicamenteux , Études prospectives , Études rétrospectivesRÉSUMÉ
Objective To analyze the relationship between hepatitis B virus genotyping and primary liver cancer (PHC) in Wuhan, and to provide a theoretical basis for the early prevention and diagnosis of PHC. Methods Patients with chronic hepatitis B (CHB) from Wuhan Sub-heart General Hospital for treatment from February 2020 to February 2021 were selected and divided into PHC group (182 cases) and control group (189 cases) according to whether they were complicated with primary liver cancer. 5ml of fasting elbow venous blood was taken from all subjects at admission. HBV genotyping was determined by real-time fluorescence quantitative PCR. The DNA of CHB virus was determined by fluorescence probe hybridization and PCR amplification, and genotyping and drug-resistant mutation points were detected according to the product sequencing analysis. Spearman linear correlation analysis was used to analyze the correlation between genotyping and mutation rate of PHC patients. Results The proportion of C genotype in PHC group was significantly higher than that in non-PHC group (P0.05). The proportion of HEPATITIS B virus mutation in PHC group (114/182) was significantly higher than that in control group (84/189) (χ2=12.331, P0.05). The proportion of HBV C mutant in PHC group was significantly higher than that in control group (P1=0.349, r2=0.305, P<0.05). Conclusion The HBV genotype of PHC patients is mainly TYPE C, and has a high mutation rate of C genotype. It can be used for diagnosis of PHC by detecting the genotyping of CHB and mutation rate of C genotype in clinic.
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Objective:To analyze the plasma levels of soluble immune checkpoint molecules in patients with primary liver cancer and their prognostic significance.Methods:The levels of sCD28, sCD80, sCD137, sCD27, sGITR, sTIM3, sCTLA4, sHVEM, IDO, sLAG3, sBTLA, sPD1, sPDL1 and sPDL2 in plasma samples of 58 patients with primary liver cancer and 30 healthy controls were detected by liquid chip technology and compared between different groups. The relationship between the plasma levels of soluble immune checkpoint molecules and tumor recurrence was analyzed.Results:The levels of sCD28 and sCD80 were higher in patients in Barcelona Clinic Liver Cancer (BCLC) stage 0/A and B than in healthy controls and patients in BCLC-C stage ( P<0.05). However, the levels of sCD27 and sHVEM in BCLC-C patients were significantly lower than those in BCLC-0/A and BCLC-B patients, and even lower than healthy control group. The levels of sCD137, IDO and sPD1 in BCLC-0/A and BCLC-B patients were higher than those in healthy controls. The levels of sPDL1 and sPDL2 in different BCLC stages were all higher than those in healthy controls, and maintained at high level in the three stages, but there was no significant difference between different stages. After 24 months of interventional treatment, the preoperative sCD28 level was lower in patients with recurrent tumor recurrence than in patients without recurrence ( t=2.843, P=0.007). The optimal cut-off value of sCD28 based on the receiver operating characteristic (ROC) curve for predicting tumor recurrence was 101.42 pg/ml and the area under the ROC curve was 0.771 (95%CI: 0.611-0.931) with a sensitivity of 0.889 and a specificity of 0.666. The cumulative recurrence rate in patients with high sCD28 level (≥101.41 pg/ml) was 57.9% at 24 months after surgery, which was lower than the rate (95.5%) in patients with low sCD28 level (<101.41 pg/ml). The difference in the cumulative recurrence rate between the two groups was statistically significant (χ 2=15.777, P=0.000). Conclusions:The expression patterns of soluble immune checkpoint molecules varied in patients at different stages of primary liver cancer, suggesting that there were differences in their immune status and sCD28 could be used as a prognostic marker for postoperative recurrence of liver cancer.