Effect of CyberKnife radiotherapy on peripheral blood lymphocytes of liver cancer / 局解手术学杂志

Objective To explore the effects of different fractionation doses,fractionation methods,and other related parameters on the peripheral blood lymphocyte count of patients with liver cancer receiving CyberKnife radiotherapy.Methods The clinical data of 90 patients with liver cancer receiving CyberKnife radiotherapy in our hospital were retrospectively analyzed.The peripheral blood lymphocyte counts of patients 1 week before CyberKnife radiotherapy and 1 week,1 month and 3 months after treatment were determined.The effects of different prescribed doses,fractionation doses and numbers of fractionations on the peripheral blood lymphocyte count were analyzed.Results The peripheral blood lymphocyte counts of patients with different prescribed doses,fractionation doses and fractionation methods after CyberKnife treatment decreased to varying degrees compared with those 1 week before treatment(P<0.05).The peripheral blood lymphocyte counts of patients in the groups with≤5 fractionations and fractionation dose>7 Gy were significantly higher than those of patients in the groups with>5 fractionations and the fractionation dose≤7 Gy,respectively(P<0.05).There was no significant difference in peripheral blood lymphocyte counts between patients with different prescribed doses before and after CyberKnife treatment(P>0.05).Conclusion CyberKnife in the treatment of liver cancer with≤5 ractionations and a fractionation dose of>7 Gy is more beneficial to alleviate the decrease of lymphocyte count caused by Cyberknife treatment.

Treatment progress of pains caused by transcatheter arterial chemoembolization and hepatic arterial infusion chemotherapy in hepatocellular carcinoma / 局解手术学杂志

Conversion therapy such as transcatheter arterial chemoembolization(TACE)and hepatic arterial infusion chemotherapy(HAIC)is the main treatment method to transform unresectable advanced liver cancer into resectable liver cancer,which can not only effectively increase the survival rate of patients,but also provide patients with the opportunity of liver transplantation.However,pain is a major complication of TACE and HAIC in the treatment of liver cancer,and the incidence of abdominal pain after TACE is from 19.3%to 71.2%,and nearly 64.6%of patients have different degrees of pain during HAIC,which seriously affects the quality of life of patients and shortens their survival time.At present,the mechanism of pains caused by TACE and HAIC is not clear,and it may be related to local liver tissue swelling after embolic agents block the tumor blood supply artery,increased pressure in the liver tissue envelope or traction of the mass capsule,chemical stimulation of the hepatic artery by embolic agents and antineoplastic drugs,thrombosis adjacent to the normal organs,and visceral pain sensitization caused by intestinal ischemia.There are two main intervention measures for pain,one of which is lidocaine,opioids,non-steroidal anti-inflammatory drugs and glucocorticoids,and the other is wrist and ankle acupuncture and traditional Chinese medicine decoction,but their treatment effects are uneven.This article summarizes the status and treatment of pain caused by TACE and HAIC therapies for liver cancer,in order to provide reference for its clinical treatment.

Oncolytic spore eruption virus encoding IL-7 enhances killing activity of liver cancer by activating CD8+T cells / 中国免疫学杂志

Objective:To investigate whether IL-7-secreting oncolytic herpes simplex virus(HSV)could activate CD8+T cells and inhibit the growth of hepatocellular carcinoma.Methods:The expression of IL-7 was detected by Western blot.The in vitro cleavage of tumor cells by tumor oncolytic virus HSV and HSV-IL-7 were detected by crystal violet staining.The tumor inhibition ability of HSV-IL-7 and HSV were detected in subcutaneous transplanted tumor model.Levels of IL-7,IFN-γ and TNF-α in serum and tumor tissues were determined by ELISA.The infiltration of CD8+T cells in tumor tissues was detected by immunohistochemistry.Flow cytometry was used to detect Granzyme B secretion in CD8+T cells infiltrated by tumor.Results:Tumor cells infected with HSV-IL-7 expressed high level of IL-7.Both HSV and HSV-IL-7 can effectively lyse B16-F10,CT-26 and H22 tumor cell lines in a dose-dependent manner in vitro.HSV-IL-7 could significantly inhibit the growth of H22 hepatoma cells in vivo(P<0.01)and prolong the survival time of tumor-bearing mice(P<0.001).HSV-IL-7 could significantly increase the IL-7 content in tumor sites(P<0.000 1),and effectively increase the number of tumor infiltrating CD8+T cells(P<0.001).HSV-IL-7 significantly enhanced Granzyme B secretion of tumor-infiltrating CD8+T cells and IFN-γ and TNF-α in tumor tissues(P<0.000 1).Conclusion:HSV-IL-7 has well tumor inhibition activity in vivo and in vitro.It also can activate the anti-tumor activity of CD8+T cells in vivo by secreting IL-7,inhibit tumor growth and prolong the survival time of tumor-bearing mice.

Osteopontin activates the PI3K/AKT pathway by upregulating LGALS3BP in promotion of hepatoma cell migration / 中国比较医学杂志

Objective To investigate the effect and mechanism of osteopontin(OPN)in hepatoma cell migration through galectin-3 binding protein(LGALS3BP).Methods Human hepatoma cell lines SMMC-7721,SMMC-P(stably transfected with empty eukaryotic expression vectors),and SMMC-OPN(stably transfected with the OPN gene)were cultured.mRNA expression levels of OPN and LGALS3BP were measured by RT-qPCR.Western blot assays were used to analyze the relative protein expression of OPN and LGALS3BP and PI3K/AKT pathway.Wound healing assays were performed to explore the cell migration ability.After transfection with LGALS3BP-targeting small interfering RNA(si-LGALS3BP)or negative control small RNA(si-NC)into SMMC-OPN cells,cell migration and relative expression of PI3K/AKT pathway-related proteins were assessed.Results Compared with SMMC-7721 and SMMC-P,the migratory ability of SMMC-OPN cells was significantly reinforced,and expression of LGALS3BP was obviously upregulated at both mRNA and protein levels.Moreover,relative expression of p-PI3K/PI3K and p-AKT/AKT proteins was significantly increased.Wound healing assays showed that the si-LGALS3BP obviously suppressed the migratory ability of SMMC-OPN cells.Furthermore,relative expression of p-PI3K/PI3K and p-AKT/AKT proteins in SMMC-OPN cells was significantly decreased after transfection of si-LGALS3BP.Conclusions OPN activates the PI3K/AKT pathway by upregulating LGALS3BP expression to promote hepatoma cell migration.

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

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

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

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

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

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

Effect of Shipi Xiaoji Beverage（实脾消积饮）-containing Serum on Mitochondrial Dynamics Imbalance and Ferroptosis of Liver Cancer HepG2 Cells / 中医杂志

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.

The Effects of Huqi Zhengxiao Formula （槲芪癥消方） on the Survival Rate and Quality of Life of Patients of Stage Ⅲ Hepatitis B-Associated Primary Liver Cancer with Syndrome of Healthy Qi Deficiency， Toxic Stasis Accumulation After Transcatheter Arterial Chemoembolisation Treatment / 中医杂志

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.

Berbamine Hydrochloride Ameliorates Sorafenib Resistance by Regulating Autophagy and PI3K/Akt/mTOR Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects of berbamine hydrochloride on sorafenib resistance in hepatocellular carcinoma cells and the underlying mechanisms. MethodThe sorafenib-resistant cell line SMMC-7721/S was selected by the concentration increment method starting at 1.25 μmol·L-1 sorafenib. Both SMMC-7721 and SMMC-7721/S cells were treated with 0， 2.5， 5， 10， 15， 20 μmol·L-1 sorafenib， and the cell counting kit-8 （CCK-8） assay was employed to determine the half maximal inhibitory concentration （IC50） and calculate the resistance index （RI）. Western blot was conducted to compare the expression of proteins involved in autophagy and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway between SMMC-7721 and SMMC-7721/S cells. Furthermore， SMMC-7721/S cells were treated with 5 μmol·L-1 berbamine hydrochloride alone or in combination with 2.5， 5， 10 μmol·L-1 sorafenib， and the cell growth was assessed by the CCK-8 assay. In addition， SMMC-7721 and SMMC-7721/S cells were treated with 5 μmol·L-1 berbamine hydrochloride alone or in combination with 5 μmol·L-1 sorafenib， and the cell proliferation was examined by the colony formation assay. The immunofluorescence assays with Microtubule-associated protein 1 light chain 3 （LC3） and LysoTracker as probes were employed to assess the lysosomal acidification in SMMC-7721 cells treated with 5 μmol·L-1 berbamine hydrochloride or 0.1 μmol·L-1 autophagy inhibitor bafilomycin A1 （Baf）. Further， the expression of proteins involved in autophagy and PI3K/Akt/mTOR signaling pathway was determined by Western blot and compared between groups. ResultSorafenib showed the IC50 of 9.56 mol·L-1 （P<0.01） and 7.99 mol·L-1 for SMMC-7721/S and SMMC-7721 cells， respectively， at 24 h. The resistance index （RI） of SMMC-7721/S for sorafenib was 1.20 （P<0.01）， which indicated mild resistance. Compared with SMMC-7721 cells， SMMC-7721/S cells exhibited up-regulated expression of p-mTOR， p-Akt， and LC3Ⅱ， down-regulated expression of p62 protein （P<0.01）， and unchanged Akt protein level. CCK-8 and colony formation assays demonstrated that the combination of berbamine hydrochloride and sorafenib exhibited a synergistic effect （Q>1.15）， with berbamine hydrochloride partially reversing the resistance of liver cancer cells to sorafenib. The immunofluorescence detection of LC3 revealed that berbamine hydrochloride and Baf significantly increased LC3 in SMMC-7721 cells. The detection with LysoTracker as the probe showed that berbamine hydrochloride inhibited the acidity of lysosomes in SMMC-7721 cells （P<0.01）， indicating the suppression of autophagy. Berbamine hydrochloride further enhanced the downregulation of p-mTOR and p-Akt protein levels and did not change the Akt protein level in SMMC-7721 cells exposed to sorafenib. Berbamine hydrochloride inhibited the increase in p-mTOR expression， down-regulated the p-Akt protein level， and did not change the total Akt protein level in the SMMC-7721/S cells exposed to sorafenib. ConclusionBerbamine hydrochloride can ameliorate the resistance of liver cancer cells to sorafenib by inhibiting cellular autophagy and the PI3K/Akt/mTOR signaling pathway.

Clinical observation of camrelizumab combined with sorafenib in the treatment of advanced liver cancer / 中国药房

OBJECTIVE To observe the clinical efficacy and safety of camrelizumab combined with sorafenib in the treatment of advanced liver cancer. METHODS Sixty patients with advanced liver cancer who were treated in our hospital from March 2020 to November 2021 were selected as the study subjects， and then were randomly divided into study group and control group， with 30 cases in each group. The control group was treated with Sorafenib tosylate tablets orally （0.4 g，bid）， and the study group was additionally given Camrelizumab for injection intravenously （200 mg， every 3 weeks） based on the control group； for all patients， the treatment was stopped until disease progression or intolerable side effects occurred. The clinical efficacy， progression-free survival （PFS）， total survival （OS） and 1-year survival rate of the two groups were compared， and the incidence of adverse reactions in two groups， and immune-related adverse reactions in the study group during treatment were recorded. RESULTS The objective remission rate of the study group was significantly higher than the control group （36.7% vs. 13.3%， P＜0.05）， and the median OS and median PFS were significantly longer than the control group （OS： 12.6 months vs. 7.9 months； PFS： 8.2 months vs. 5.3 months， P＜0.05）. There was no significant difference in the 1-year survival rate and the incidence of elevated aspartate aminotransferase and alanine aminotransferase， rash or pruritus， anorexia， diarrhea， fatigue and hypertension between the two groups （P＞0.05）. The adverse events immune-related in the study group mainly included 21 cases of reactive capillary hyperplasia （70.0%）， 6 cases of hypothyroidism （20.0%）， and 1 case of immune-associated pneumonia （3.3%）， which were improved or tolerable after symptomatic treatment. CONCLUSIONS Camrelizumab combined with sorafenib in the treatment of advanced liver cancer can effectively control and delay the disease progression， prolong the survival period of patients， and the adverse reactions can be tolerated.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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