1.Risk factors for concurrent hepatic hydrothorax before intervention in primary liver cancer and construction of a nomogram prediction model
Yuanzhen WANG ; Renhai TIAN ; Yingyuan ZHANG ; Danqing XU ; Lixian CHANG ; Chunyun LIU ; Li LIU
Journal of Clinical Hepatology 2025;41(1):75-83
ObjectiveTo investigate the influencing factors for hepatic hydrothorax (HH) before intervention for primary hepatic carcinoma (PHC), and to construct and assess the nomogram risk prediction model. MethodsA retrospective analysis was performed for the clinical data of 353 hospitalized patients who attended the Third People’s Hospital of Kunming for the first time from October 2012 to October 2021 and there diagnosed with PHC, and according to the presence or absence of HH, they were divided into HH group with 153 patients and non-HH group with 200 patients. General data and the data of initial clinical testing after admission were collected from all PHC patients. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. After the multicollinearity test was performed for the variables with statistical significance determined by the univariate analysis, the multivariate Logistic regression analysis was used to identify independent influencing factors. The “rms” software package was used to construct a nomogram risk prediction model, and the Hosmer-Lemeshow test and the receiver operating characteristic (ROC) curve were used to assess the risk prediction model; the “Calibration Curves” software package was used to plot the calibration curve, and the “rmda” software package was used to plot the clinical decision curve and the clinical impact curve. ResultsAmong the 353 patients with PHC, there were 153 patients with HH, with a prevalence rate of 43.34%. Child-Pugh class B (odds ratio [OR]=2.652, 95% confidence interval [CI]: 1.050 — 6.698, P=0.039), Child-Pugh class C (OR=7.963, 95%CI: 1.046 — 60.632, P=0.045), total protein (OR=0.947, 95%CI: 0.914 — 0.981, P=0.003), high-sensitivity C-reactive protein (OR=1.007, 95%CI: 1.001 — 1.014, P=0.025), and interleukin-2 (OR=0.801, 95%CI: 0.653 — 0.981, P=0.032) were independent influencing factors for HH before PHC intervention, and a nomogram risk prediction model was established based on these factors. The Hosmer-Lemeshow test showed that the model had a good degree of fitting (χ2=5.006, P=0.757), with an area under the ROC curve of 0.752 (95%CI: 0.701 — 0.803), a sensitivity of 78.40%, and a specificity of 63.50%. The calibration curve showed that the model had good consistency in predicting HH before PHC intervention, and the clinical decision curve and the clinical impact curve showed that the model had good clinical practicability within a certain threshold range. ConclusionChild-Pugh class, total protein, interleukin-2, and high-sensitivity C-reactive protein are independent influencing factors for developing HH before PHC intervention, and the nomogram model established based on these factors can effectively predict the risk of developing HH.
2.Value of FibroScan, gamma-glutamyl transpeptidase-to-platelet ratio, S index, interleukin-6, and tumor necrosis factor-α in the diagnosis of HBeAg-positive chronic hepatitis B liver fibrosis
Yingyuan ZHANG ; Danqing XU ; Huan MU ; Chunyan MOU ; Lixian CHANG ; Yuanzhen WANG ; Hongyan WEI ; Li LIU ; Weikun LI ; Chunyun LIU
Journal of Clinical Hepatology 2025;41(4):670-676
ObjectiveTo investigate the value of noninvasive imaging detection (FibroScan), two serological models of gamma-glutamyl transpeptidase-to-platelet ratio (GPR) score and S index, and two inflammatory factors of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in predicting liver fibrosis in patients with HBeAg-positive chronic hepatitis B (CHB), as well as the consistency of liver biopsy in pathological staging, and to provide early warning for early intervention of CHB. MethodsA retrospective analysis was performed for 131 HBeAg-positive CHB patients who underwent liver biopsy in The Third People’s Hospital of Kunming from January 2019 to December 2023. The results of liver biopsy were collected from all patients, and related examinations were performed before liver biopsy, including total bilirubin, alanine aminotransferase, platelet count, gamma-glutamyl transpeptidase, albumin, IL-6, TNF-α, liver stiffness measurement (LSM), and abdominal ultrasound. An analysis of variance was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. A Kappa analysis was used to investigate the consistency between LSM noninvasive histological staging and pathological staging based on liver biopsy, and the Spearman analysis was used to investigate the correlation between each variable and FibroScan in the diagnosis of liver fibrosis stage. The Logistic regression analysis was used to construct joint predictive factors. The receiver operating characteristic (ROC) curve was used to evaluate the value of each indicator alone and the joint predictive model in the diagnosis of liver fibrosis, and the Delong test was used for comparison of the area under the ROC curve (AUC). ResultsIn the consistency check, inflammation degree based on liver biopsy had a Kappa value of 0.807 (P<0.001), and liver fibrosis degree based on liver biopsy had a Kappa value of 0.827 (P<0.001), suggesting that FibroScan noninvasive histological staging and liver biopsy showed good consistency in assessing inflammation degree and liver fibrosis stage. Age was positively correlated with LSM, GPR score, S index, IL-6, and TNF-α (all P<0.05), and GPR score, S index, IL-6, and TNF-α were positively correlated with LSM (all P<0.05). GPR score, S index, IL-6, and TNF-α were all independent risk factors for diagnosing significant liver fibrosis (≥S2) and progressive liver fibrosis (≥S3) (all P<0.05). As for each indicator alone, GPR score had the highest value in the diagnosis of significant liver fibrosis (≥S2), followed by S index, IL-6, and TNF-α, while S index had the highest value in the diagnosis of progressive liver fibrosis (≥S3), followed by GPR score, TNF-α, and IL-6. The joint model had a higher predictive value than each indicator alone (all P<0.05). ConclusionThere is a good consistency between FibroScan noninvasive histological staging and pathological staging based on liver biopsy. GPR score, S index, IL-6, and TNF-α are independent risk factors for evaluating different degree of liver fibrosis in CHB, and the combined prediction model established by them can better diagnose liver fibrosis.
3.Value of albumin-bilirubin, easy albumin-bilirubin, and platelet-albumin-bilirubin scores in predicting the prognosis of patients with HCV-associated hepatocellular carcinoma
Huan MU ; Yingyuan ZHANG ; Danqing XU ; Yuanqiang HE ; Chunyan MOU ; Chunyun LIU ; Li LIU
Journal of Clinical Hepatology 2025;41(5):921-926
ObjectiveTo investigate the value of albumin-bilirubin (ALBI), easy albumin-bilirubin (EZ-ALBI), and platelet-albumin-bilirubin (PALBI) scores in predicting 2-year survival in patients with HCV-associated hepatocellular carcinoma (HCV-HCC). MethodsA retrospective analysis was performed for the clinical data of 174 patients with HCV-HCC who were admitted to The Third People’s Hospital of Kunming from January 2020 to January 2022, and the patients were followed up till 2 years after admission. According to the follow-up results, the patients were divided into survival group with 95 patients and death group with 79 patients. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate the influencing factors for the survival of HCV-HCC patients. The Kaplan-Meier method was used to plot survival curves and analyze the 2-year survival rate of HCV-HCC patients with different EZ-ALBI grades, and the log-rank test was used for comparison between groups. ResultsThere were significant differences between the survival group and the death group in platelet count, aspartate aminotransferase (AST), total bilirubin, albumin (Alb), alpha-fetoprotein (AFP), prealbumin, prothrombin time, international normalized ratio, PALBI score, ALBI score, EZ-ALBI score, Model for End-Stage Liver Disease (MELD) score, HCV genotype, peritoneal effusion, and vascular invasion (all P<0.05). The univariate Cox regression analysis showed that AST, Alb, AFP, ALBI score, EZ-ALBI score, PALBI score, MELD score, Barcelona Clinic Liver Cancer Staging, and peritoneal effusion were influencing factors for the survival of patients (all P<0.05), and the multivariate Cox regression analysis showed that EZ-ALBI score (hazard ratio [HR]=1.850, 95% confidence interval [CI]: 1.054 — 3.247, P=0.032) and peritoneal effusion (HR=1.993, 95%CI: 1.030 — 3.858, P=0.041) were independent risk factors for the survival of HCV-HCC patients. The survival curve analysis showed that the patients with EZ-ALBI grade 1/2/3 had a 2-year survival rate of 90.9%, 60.2%, and 32.2%, respectively, and there was a significant difference in cumulative survival rate between the patients with different EZ-ALBI grades (χ2=26.294, P<0.001). ConclusionEZ-ALBI score and the presence or absence of peritoneal effusion can be used as predictors of the survival of HCV-HCC patients.
4.Efficacy and safety of coblopasvir hydrochloride combined with sofosbuvir in treatment of patients with genotype 3 hepatitis C virus infection
Yingyuan ZHANG ; Huan MU ; Danqing XU ; Chunyan MOU ; Yuanzhen WANG ; Chunyun LIU ; Weikun LI ; Li LIU
Journal of Clinical Hepatology 2025;41(6):1075-1082
ObjectiveTo investigate the efficacy and safety of the direct-acting antiviral agents coblopasvir hydrochloride/sofosbuvir (CLP/SOF) regimen used alone or in combination with ribavirin (RBV) in the treatment of patients with genotype 3 hepatitis C virus (HCV) infection in terms of virologic response rate, liver function recovery, improvement in liver stiffness measurement (LSM), and adverse drug reactions, and to provide a reference for clinical medication. MethodsA total of 98 patients with genotype 3 HCV infection who attended The Third People’s Hospital of Kunming from January 2022 to December 2023 were enrolled, and according to the treatment method, the patients were divided into CLP/SOF+RBV treatment group with 55 patients and CLP/SOF treatment group with 43 patients. The patients were observed in terms of rapid virologic response at week 4 (RVR4), sustained virologic response (SVR), previous treatment experience, underlying diseases, laboratory and imaging indicators, and adverse reactions during treatment. The course of treatment was 12 weeks, and the patients were followed up for 12 weeks after drug withdrawal. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the Friedman test was used for comparison within each group at different time points, and the Bonferroni method was used for further comparison and correction of P value; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for SVR12. ResultsBefore treatment, there were significant differences between the CLP/SOF+RBV treatment group and the CLP/SOF treatment group in terms of LSM, total bilirubin (TBil), gamma-glutamyl transpeptidase (GGT), HCV genotype, and the presence or absence of liver cirrhosis and compensation (all P<0.05). The 98 patients with genotype 3 HCV infection had an RVR4 rate of 81.6% and an SVR12 rate of 93.9%. The patients with genotype 3a HCV infection had an RVR4 rate of 84.44% and an SVR12 rate of 97.78%, while the patients with genotype 3b HCV infection had an RVR4 rate of 79.25% and an SVR12 rate of 90.57%. There were significant differences in RVR4 and SVR12 rates between the patients without hepatocellular carcinoma and those with hepatocellular carcinoma, there was a significant difference in RVR4 rate between the patients without HIV infection and those with HIV infection, and there was a significant difference in SVR12 rate between the previously untreated patients and the treatment-experienced patients (all P<0.05). The univariate Logistic regression analysis showed that treatment history, hypertension, hepatocellular carcinoma, ascites, albumin (Alb), and platelet count were influencing factors for SVR12 (all P<0.05), and the multivariate Logistic regression analysis showed that hepatocellular carcinoma (odds ratio=0.034, 95% confidence interval: 0.002 — 0.666, P=0.026) was an independent influencing factor for SVR12. After treatment with CLP/SOF combined with RBV or CLP/SOF alone, the patients with genotype 3 HCV infection showed gradual reductions in the liver function parameters of TBil, GGT, and alanine aminotransferase (all P<0.05) and a gradual increase in the level of Alb (P<0.05). As for renal function, there were no significant changes in blood urea nitrogen and creatinine after treatment (P>0.05). For the patients with or without liver cirrhosis, there was a significant reduction in LSM from baseline after treatment for 12 weeks (P<0.05). Among the 98 patients with genotype 3 HCV infection, 9 tested positive for HCV-RNA at 12 weeks after treatment, 2 showed no response during treatment, 4 showed virologic breakthrough, and 3 experienced recurrence. The overall incidence rate of adverse events during treatment was 17.35% for all patients. ConclusionCLP/SOF alone or in combination with RBV has a relatively high SVR rate in the treatment of genotype 3 HCV infection, with good tolerability and safety in patients during treatment, and therefore, it holds promise for clinical application.
5.Risk Prediction of SBP in Patients with Primary Liver Cancer Complicated with Ascites
Hongyan WEI ; Yuanzhen WANG ; Lixian CHANG ; Huan MU ; Chunyun LIU ; Li LIU
Journal of Kunming Medical University 2024;45(3):133-140
Objective To explore the influencing factors of spontaneous bacterial peritonitis in patients with primary liver cancer complicated with ascites and establish a prediction model.Methods A total of 292 patients with primary liver cancer complicated with ascites who were hospitalized for the first time in the Third People's Hospital of Kunming from January 2012 to December 2021 were selected as the study objects.General data,etiological indicators,serological indicators and complications of these subjects were collected.Then they were divided into the infection group(n = 114)and the control group(n = 178)according to whether spontaneous bacterial peritonitis(SBP)was complicated.Univariate and multivariate logistic regression were used to analyze the influencing factors of SBP in patients with primary liver cancer complicated with ascites.Finally,ROC curves were constructed to more intuitively represent the individual and combined predictive value of these targets.Results Am-ong 292 hepatocellular carcinoma patients with ascites,there were 235 males(80.48%)and 57 females(19.52%),among which 114 patients with SBP were in the infection group and 178 patients without SBP were in the control group.The results of univariate analysis showed that compared with the control group,the levels of WBC,neutrophils,prothrombin time,total bilirubin,albumin,CD3,CD4,CD8,CD4/CD8 ratio,CD19 procalcitonin,serum amyloid A,hypersensitive C-reactive protein,sodium,chlorine,alcohol consumption,shock,hepatorenal syndrome,hepatic encephalopathy,massive ascites in the infection group had statistically significant difference(P<0.05).Multi-factor analysis revealed that CD8,CD4/CD8 ratio were protective factors for SBP in patients with liver cancer ascites,CD19,procalcitonin,serum amyloid A,and massive ascites were risk factors for SBP in patients with ascites.ROC curve construction showed that serum amyloid A,CD8,CD4/CD8 ratio,CD19,procalcitonin,massive ascites area under curve(AUC)of massive ascites were 0.724,0.637,0.653,0.820,0.705,0.686,respectively.Conclusion CD8,CD4/CD8 ratio,CD19,procalcitonin,serum amyloid A,and a large volume of ascites are significant factors contributing to the development of spontaneous bacterial peritonitis(SBP)in patients with hepatocellular carcinoma ascites.The predictive value of combination is substantial,demonstrating a level of accuracy in forecasting SBP occurrence
6.The effects of cannabidiol on the expression of NLRP3 inflammasome following multiple cerebral concussions in rats
Chunze YU ; Lifang YANG ; Zhaoda DUAN ; Yujia YANG ; Chunyun WU ; Jianyun YU ; Li YANG
Chinese Journal of Neuroanatomy 2024;40(1):98-104
Objective:To investigate the effects of cannabidiol(CBD)on the NOD-like receptor protein 3(NLRP3)inflammasome in the brains of rats with multiple cerebral concussions(MCC).Methods:Rats were subjec-ted to the MCC model and divided into Sham,MCC,vehicle(MCC+TW),CBD-L(10 mg/kg),and CBD-H(40 mg/kg)groups.Immunofluorescence double staining was used to observe changes in NLRP3 and microglial cells in the brain,and Western Blot was performed to detect the expression changes of the NLRP3 inflammasome.Results:A sig-nificant increase in lectin-positive microglial cells of the cortex with enlarged cell bodies and elevated immunofluores-cence intensity of NLRP3 in the activated microglial cells was revealed by immunofluorescence double staining following MCC(P<0.05).The immunofluorescence intensity of NLRP3 in the activated microglial cells was downregulated by the administration of CBD,with a more pronounced effect observed in the CBD-H group compared to the CBD-L group(P<0.05).The expression of NLRP3,caspase-1,and apoptosis-associated speck-like protein(ASC)in the cortex,hippocampus,and basal ganglia of rats following MCC was significantly increased,as shown by Western Blot analysis(P<0.05),and cortical areas are more elevated.The expression of these proteins in different brain regions was reduced by CBD-10 and CBD-40 intervention(P<0.05).Conclusion:Cannabidiol can reduce the inflammatory response of multiple cerebral concussions rats through NLRP3 inflammasome and protect nerve tissue.
7.Detection characteristics of the virus during school influenza outbreaks in Linyi City
Chinese Journal of School Health 2024;45(5):723-726
Objective:
To analyze the characteristics of influenza virus detection in an influenza outbreak in schools, so as to provide a strategic basis for the treatment of influenza outbreaks in schools.
Methods:
A total of 1 702 samples were collected from 52 school influenza outbreaks reported in Linyi City in 2021-2022. The samples were divided into 3 types according to different symptoms during the management of the epidemic [group A:influenzalike illness (ILI) group; group B:mild illness group; group C:close contacts group]. Rt-PCR was used to detect influenza virus nucleic acid in the collected samples. The detection rate of influenza virus in the outbreaks was analyzed by χ2 test.
Results:
In total, 1 071 samples (62.93%) tested positive for influenza virus nucleic acid. Among them, 610 out of 726 samples (84.02%) were detected in group A, while 331 out of 634 samples (52.21%) were detected in group B. In group C, 130 out of 342 samples (38.01%) tested positive. The differences were statistically significant (χ2=260.71, P<0.01). In group A, males had a detection rate of 80.83% for influenza virus nucleic acid, compared to 91.36% for females. For group B, the rates were 53.31% for males and 50.87% for females. In group C, males had a rate of 30.72%, while females had a rate of 43.92%. Statistical significance for gender differences was observed only in groups A and C (χ2=12.67, 6.25, P<0.05). According to the days of onset, the detection rates of influenza virus nucleic acid among patients with onset 0-6 days were 56.30%, 74.49%, 89.35%, 86.23%, 69.67%, 62.75%, 34.33%, respectively, and the difference was statistically significant (χ2=128.27, P<0.01).
Conclusions
Mild cases and close contacts are likely key factors contributing to the prolonged emergence of new cases within classrooms during school influenza outbreaks. The progression of influenza symptoms is related to the risk of transmission.
8.Cold and Heat in Acute Coronary Syndrome: A Review
Xuejiao WANG ; Zhen SHAO ; Chao MENG ; Chunyun JIANG ; Hengwen CHEN ; Jun LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):246-252
Cold and heat belong to the eight-principal syndrome differentiation of traditional Chinese medicine, which can reflect the rise and fall of Yin and Yang in the body and the Yin and Yang nature of the disease. At present, traditional Chinese medicine has an inconsistent understanding of cold and heat in acute coronary syndrome. The emphasis on pathogenic factors of cold and heat is biased, and the elements of cold and heat syndrome are not fully reflected in the scale. Therefore, the literature has been reviewed from the perspectives of etiology, pathogenesis, symptom elements, and test signs with drugs. From the perspective of etiology, both cold evil and heat evil can increase the risk of acute coronary syndrome. It was previously believed that acute coronary syndrome occurs frequently in cold climates such as winter and spring. Based on this understanding, hot weather can also induce acute coronary syndrome, and different temperatures have different effects on patients of different ages and with different underlying diseases. In addition, artificial pathogenic factors such as excessive consumption of cold food and refrigeration air conditioners were added. From the perspective of pathogenesis, on the basis of the traditional ''asthenia in origin and asthenia in superficiality'' and ''phlegm stagnation'', it is found that Yin-cold and fire-heat can both cause paralysis of the heart chakra and pain induced by the blockage. The pathogenesis of acute coronary syndrome characterized by heat stagnation and coldness featuring heartburn should be distinguished from gastroesophageal reflux disease. Moreover, the pathogenesis of Yin cold coagulation and pulse stagnation and wind obstruction are different. The acute coronary syndrome is in line with the wind characteristics of frequent changes and can be treated with wind medicine. From the perspective of syndrome elements, the syndrome elements such as cold condensation, heat accumulation, and toxicity are analyzed, and the use of basic syndrome elements and their combination forms facilitates clinical and scientific research. In addition, according to the test sign with the drug, it can be seen that the attributes of cold and heat of traditional Chinese medicine prescriptions for acute coronary syndrome can be explained according to the temperature-sensitive transient receptor potential (TRP) ion channel, thus proving the pathogenesis of cold and heat of acute coronary syndrome.
9.Efficacy and safety of sofosbuvir/velpatasvir alone or in combination with ribavirin in treatment of patients with genotype 3B HCV/HIV infection
Li LIU ; Lixian CHANG ; Zhiyong CHEN ; Junyi LI ; Chunyun LIU
Journal of Clinical Hepatology 2024;40(2):271-277
ObjectiveTo investigate the efficacy and safety of sofosbuvir/velpatasvir alone or in combination with ribavirin in Chinese patients with genotype 3B HCV/HIV infection. MethodsA total of 299 patients with genotype 3B HCV/HIV infection who attended The Third People’s Hospital of Kunming from January 2017 to December 2020 were enrolled and treated with sofosbuvir/velpatasvir alone or in combination with ribavirin for 12 weeks, and they were followed up for 12 weeks after drug withdrawal. The patients were evaluated in terms of sustained virologic response at 12 weeks after treatment (SVR12) and adverse reactions. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; the Agresti-Coull method was used to evaluate the 95% confidence interval (CI) of SVR12; univariate and multivariate non-conditional logistic regression analyses were used to investigate the influencing factors for SVR. ResultsThe 299 patients with genotype 3B HCV/HIV infection had a mean age of 43.92±6.84 years, among whom the male patients accounted for 77.3% (231/299), the patients with liver cirrhosis accounted for 36.5% (109/299), the patients with a history of antiviral therapy accounted for 13.4% (40/299), and the patients receiving sofosbuvir/velpatasvir combined with ribavirin accounted for 27.8% (83/299). The overall SVR was 87.0% (260/299) for all patients, and there was no significant difference in SVR12 between the patients receiving sofosbuvir/velpatasvir alone and those receiving sofosbuvir/velpatasvir combined with ribavirin (87.5% vs 85.5%, χ2=0.203, P=0.653). There was a significant difference in SVR12 between the patients without liver cirrhosis and those with liver cirrhosis (90.0% vs 81.7%, χ2=4.256, P=0.039), and the patients receiving antiviral therapy for the first time had a significantly higher SVR12 than the treatment-experienced patients (93.4% vs 45.0%, χ2=71.670, P<0.001). The univariate and multivariate logistic regression analyses showed that platelet count (odds ratio [OR]=0.957, 95%CI: 0.931 — 0.984, P=0.002), liver stiffness measurement (OR=1.446, 95%CI: 1.147 — 1.822, P=0.002), and experience in treatment (OR=13.807, 95%CI: 2.970 — 64.174, P=0.001) were independent influencing factors for SVR in patients with genotype 3B HCV/HIV infection. There were 41 cases of serious adverse events, all of which occurred within 2 weeks after antiviral therapy, and 28 cases were resolved without drug withdrawal or active treatment, while 13 cases were not resolved after active treatment and were resolved after the antiviral drugs were stopped for 2 — 5 days, with no similar reactions observed when the drugs were used again after remission. ConclusionSofosbuvir/velpatasvir alone or in combination with ribavirin has relatively good efficacy and safety in patients with genotype 3B HCV/HIV infection.
10.MACC1 knockdown enhances RSL3-induced ferroptosis in human colorectal cancer cells by inhibiting GPX4 expression
Shuo SUN ; Xin HUANG ; Guodong LI ; Chunyun ZHANG ; Zemei LU ; Weiwei ZHANG ; Zeyan LI ; Qingzhu YANG
Journal of Southern Medical University 2024;44(1):173-178
Objective To investigate the effect of MACC1 on RSL3-induced ferroptosis in colorectal cancer cells and explore its molecular mechanism.Methods MACC1 expression was detected in SW620,HCT116,LOVO and RKO cells using Western blotting.The effects of different concentrations of RSL3(an inducer of ferroptosis)or Fer-1(an inhibitor of ferroptosis)alone,or 10 μmol/L RLS3 combined with 10 μmol/L Fer-1,on viability of SW620 cells were examined using MTT assay.The survival of SW620 cells with mRNA interference of MACC1 was analyzed following treatment with RSL3,and RT-qPCR and Western blotting were performed to detect the changes in MACC1 expressions after RSL3 treatment at different concentrations and the changes in GPX4 expression after MACC1 knockdown.Flow cytometry and laser confocal microscopy were used to analyze the changes in ROS-induced lipid peroxidation in SW620 cells after MACC1 knockdown.Results SW620 cells had the highest MACC1 expression among the 4 colorectal cancer cell lines.Treatment with RSL3 significantly inhibited the viability of SW620 cells in a dose-dependent manner,while Fer-1 did not significantly affect the survival of SW620 cells.RSL3 alone reduced SW620 cell survival by 50%(P<0.01),and the combined treatment with RSL3 and Fer-1 caused no significant changes in cell survival(P>0.05).Treatment with RSL3 concentration-dependently suppressed MACC1 expressions at both the mRNA and protein levels in SW620 cells(P<0.01).MACC1 knockdown obviously enhanced the cytotoxic effect of RSL3,inhibited the expression of GPX4,and increased ROS-induced lipid peroxidation in SW620 cells(P<0.05).Conclusion MACC1 knockdown enhances RSL3-induced ferroptosis in cultured colorectal cancer cells by inhibiting the expression of GPX4.


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