Objective To investigate the predictive factors for the occurrence of HBsAg clearance in patients with HBeAg-negative chronic hepatitis B(CHB)receiving peginterferon alfa-2b(PEG-IFN-α-2b)treatment,analyze the effects of various indicators on the HBsAg clearance rate under different characteristics,and construct and evaluate a combined predictive model.Methods We included 125 patients with HBeAg-negative CHB at Kunming Third People's Hospital from May 2021 to May 2023.After treatment with PEG-IFN-α-2b combined with nucleoside analogues for a course of 48 weeks,they were divided into HBsAg clearance group and HBsAg non-clearance group.Their general information and serological,biochemical,and virological indicators at different time points during treatment were recorded.Continuous data in normal distribution were compared using the t test.Continuous data in non-normal distribution were compared using the Mann-Whitney U test,and comparisons across different time points were performed using the multiple paired-sample Friedman test.Categorical data were compared using the χ2 test.A Logistic regression analysis was used to select variables to establish a combined multi-parameter predictive model.Receiver operating characteristic(ROC)curves were generated to evaluate the diagnostic value of individual indicators and the combined predictive model for HBsAg clearance.Results Before treatment,there were significant differences in baseline HBsAg level(Z=-3.997,P<0.05)and treatment history(χ2=8.221,P<0.05)between the two groups.During treatment,gradually decreasing trends were observed in white blood cell count(χ2=104.944),neutrophil count(χ2=132.036),platelet count(χ2=162.881),and thyroid-stimulating hormone level(TSH,χ2=83.304,all P<0.05),while alanine aminotransferase(ALT,χ2=157.618)and alpha fetoprotein(χ2=159.472)showed gradually increasing trends(both P<0.05).At 48 weeks of treatment,treatment history(odds ratio[OR]=0.232,95%confidence interval[CI]:0.071-0.753),baseline HBsAg level(OR=13.423,95%CI:3.276-54.997),the extent of decrease in HBsAg from baseline after 12 weeks of treatment(OR=0.143,95%CI:0.040-0.515),the maximum ALT level during treatment(OR=0.986,95%CI:0.980-0.993),and the minimum TSH level during treatment(OR=3.281,95%CI:1.413-7.619)were independent factors affecting HBsAg clearance(all P<0.05).A combined predictive model for HBsAg clearance was built:Y=-1.603-1.462×treatment history+2.597×baseline HBsAg value-1.944×the extent of HBsAg reduction from baseline after 12 weeks of treatment-0.014×the maximum ALT value during treatment+1.188×the minimum TSH value during treatment.The diagnostic value of the individual indicators for HBsAg clearance from high to low was as following:the maximum ALT value during treatment(AUC=0.824),baseline HBsAg value(AUC=0.727),the minimum TSH value during treatment(AUC=0.707),the extent of HBsAg reduction from baseline after 12 weeks of treatment(AUC=0.641),and treatment history(AUC=0.636).The combined model showed better predictive performance than the individual indicators,with the AUC being 0.921(all P<0.05).Conclusion The combined model,constructed with baseline HBsAg value,the extent of HBsAg reduction from baseline after 12 weeks of treatment,the maximum ALT value during treatment,and the minimum TSH value during treatment,has high predictive value for the occurrence of HBsAg clearance in patients with HBeAg-negative CHB after 48 weeks of treatment with PEG-IFN-α-2b,which can provide a reference for identifying suitable patients for treatment and predicting clinical outcome.

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.

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.

Objective To analyze the influencing factors of chronic liver failure in patients with primary hepatic carcinoma(PHC)before intervention,and to establish and evaluate a nomogram risk prediction model.Methods A retrospective analysis was conducted by collecting general data and clinical test data within 24 hours of admission for PHC patients.Univariate analysis and Lasso regression were used for variable selection,followed by multivariate logistic regression analysis to identify independent influencing factors for CLF before PHC intervention,leading to the establishment of a nomogram risk prediction model.The model was evaluated using the Hosmer-Lemeshow test,receiver operating characteristic(ROC)curve,calibration curve,clinical decision curve,and clinical impact curve.Result A total of 353 cases of PHC patients were collected,including 153 cases in the liver failure group and 200 cases in the non-liver failure group,with a prevalence rate of 43.3％.Variables selected by Lasso regression included gastrointestinal bleeding,prothrombin time(PT),albumin(ALB),total bilirubin(TBIL),and gamma glutamyl transferase(GGT).Multivariate logistic regression analysis showed that gastrointestinal bleeding(OR=13.549,95％CI:2.899～63.322,P=0.001),PT(OR=1.599,95％CI:1.282～1.995,P＜0.001),TBIL(OR=1.016,95％CI:1.006～1.025,P=0.002),and GGT(OR=1.002,95％CI:1.000～1.003,P=0.028)were independent risk factors for chronic liver failure prior to PHC intervention,leading to the establishment of a nomogram risk prediction model.The Hosmer Lemeshow test showed that the model had a good fit(x2=6.152,P＞0.05);the area under ROC was 0.902(0.869-0.934),with a sensitivity of 80.4％and a specificity of 87.5％.The calibration curve indicated that the model predicts chronic liver failure prior to PHC intervention with good consistency.Clinical decision curve analysis and clinical impact curve analysis showed that the model has good clinical utility within a certain threshold range.Conclusion Gastrointestinal bleeding,PT ≥16.05s,TBIL≥37.80 mmol/L,and GGT≥ 99.00 U/L are independent risk factors for the occurrence of chronic liver failure before PHC intervention.The established nomogram risk prediction model has certain clinical application value in predicting the risk of chronic liver failure before PHC intervention.

Objective To compare the efficacy of Tenofovir Alafenamide(TMF)and Tenofovir Disoproxil Fumarate(TDF)in terms of liver function restoration,virus clearance,immune regulation,anti liver fibrosis,lipid metabolism,bone and renal safety,and adverse reactions.Methods A retrospective analysis was conducted on 110 patients with chronic hepatitis B(CHB)admitted to Kunming Third People's Hospital from January 2022 to December 2022.Patients were divided into the TMF treatment group(n=55)and the TDF treatment group(n=55)based on their treatment regimen.We compared the levels of transaminase levels,antiviral efficacy,T cell subsets,renal function electrolytes,lipid metabolism,four liver fibrosis-related indicators,and changes in liver stiffness grading before and after treatment in two groups of patients.The incidence of adverse reactions post-treatment was also compared.Results After 48 weeks of treatment,the levels of TBIL,ALT,AST,GGT,and GLOB in both groups of patients were significantly lower than pre-treatment levels(P<0.05).The decrease in AST levels in the TMF group was lower than that in the TDF group(P<0.05).After 48 weeks of treatment,the HBV-DNA seroconversion rate in the TMF group(90.90%)was higher than that in the TDF group(83.64%).The serological HBsAg clearance rate in the TMF group(7.3%)was lower than that in the TDF group(9.1%),while the HBeAg clearance rate in the TMF group(38.2%)was significantly higher than that in the TDF group(18.2%),with statistical significance(P<0.05).After 48 weeks of treatment,levels of CD3+,CD4+,and CD8+in both groups were significantly elevated compared to pre-treatment levels(P<0.05);notably,the TMF group had higher post-treatment levels of CD3+,CD4+,and CD8+than the TDF group.After 48 weeks,the average values of HA,IV-C,and LN among the TMF group for liver fibrosis indicators were significantly lower than those in the TDF group(P<0.05).The proportions of F0 and F2 in both groups significantly increased post-treatment,while the proportions of F3 and F4 significantly decreased(P to be supplemented);furthermore,the proportions of F0 and F2 in the TMF group were significantly higher than those in the TDF group,and the proportions of F3 and F4 in the TMF group were significantly lower than those in the TDF group(P<0.05).After 48 weeks,HDL-C levels in the TMF group increased compared to pre-treatment(P<0.05).There were no significant differences in TG,TC,HDL-C,or LDL-C levels in the TDF group compared to pre-treatment(P>0.05).After 48 weeks of treatment,there was no difference in the levels of BUN、Cr、P+,and Ca+in the TMF group compared to pre-treatment(P>0.05);however,BUN and Cr levels in the TDF group were significantly higher than pre-treatment levels,while P+and Ca+levels were significantly lower(P<0.05).The incidence of elevated uric acid and bone pain was significantly higher in the TMF group compared to the TDF group(P<0.05);the incidence of diarrhea and abdominal pain was slightly higher in the TMF group compared to the TDF group(P>0.05).Conclusion Compared to TDF,TMF demonstrates a higher rate of liver function recovery,a greater virological response,enhanced anti fibrotic efficacy,and improved drug safety,making it worthy of clinical application in the future.

Objective To 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).Methods A 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.Results There 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).Conclusion EZ-ALBI score and the presence or absence of peritoneal effusion can be used as predictors of the survival of HCV-HCC patients.

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.

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.

AIM:To investigate the effects of nebulized sodium tanshinone ⅡA sulfonate(STS)in a mouse model of pulmonary hypertension associated with chronic obstructive pulmonary disease(COPD-PH).METHODS:A to-tal of 32 healthy SPF-grade male C57BL/6 mice were randomly divided into 4 groups:control(CTL,n=8)group,COPD-PH(CS+LPS,n=8)group,STS-treated COPD-PH(CS+LPS+STS,n=8)group,and STS(n=8)group.The COPD-PH model was established through whole-body exposure to cigarette smoke(CS)combined with lipopolysaccharide(LPS)in-halation.Mice were subjected to cigarette smoke exposure in a chamber(9 cigarettes/h,2 h/session,2 sessions/d,6 d/week)for 60 d,except on days of LPS inhalation.On days 1 and 14,COPD-PH model mice received LPS(7.5 μg/mouse in 50 μL saline)via intranasal inhalation,while the CTL and STS groups received an equivalent volume of saline.STS was administered via nebulized inhalation(5 mg/kg,30 min per session,twice daily)immediately before CS exposure.At the end of the modeling period,lung function and right heart pressure were assessed.Bronchoalveolar lavage fluid(BALF)was collected for inflammatory cell counting.Levels of interleukin-6(IL-6)in BALF supernatants and plasma were measured using ELISA.Pathological changes in the airway and lung tissues were evaluated.RESULTS:(1)Com-pared to CTL mice,those exposed to CS and LPS exhibited lesions characteristic of COPD-PH,including emphysema,lung inflammation,decreased lung function,and increased right ventricular systolic pressure(RVSP)and right ventricu-lar hypertrophy index(RVHI)(P<0.05);(2)COPD-PH mice showed significantly elevated IL-6 levels in both BALF and plasma(P<0.05);(3)STS treatment alleviated emphysema and lung inflammation,improved lung function,prevent-ed increases in RVSP and the RV/(LV+S)ratio,and reduced IL-6 levels in both BALF and plasma(P<0.05).CON-CLUSION:The results indicate that nebulized inhalation of STS significantly slows the progression of COPD-PH,likely due to its ability to inhibit lung inflammation and reduce IL-6 expression in the lungs.

AIM:This study aims to investigate the molecular mechanism by which tubeimoside I(TBMS1)inhibits Snail expression in pancreatic cancer cells(PANC-1).METHODS:Human pancreatic cancer PANC-1 cells were cultured in vitro.The inhibitory effect of TBMS1 on PANC-1 cells was assessed using the MTT assay,and the data were analyzed based on the IC50 value of TBMS1.The impact of TBMS1 on the clonal formation ability of PANC-1 cells was evaluated through colony formation assays.The Transwell assay was employed to assess the effect of TBMS1 on the migrato-ry capability of PANC-1 cells.Apoptosis and cell cycle alterations in PANC-1 cells were analyzed using acridine orange staining and flow cytometry.The expression of Snail protein in pancreatic cancer and its relationship with survival of the patients were analyzed using the GEPIA database and Kaplan-Meier Plotter data.Immunofluorescence staining was con-ducted to investigate the effect of TBMS1 on Snail expression,while Western blot was used to evaluate the expression of poly(ADP-ribose)polymerase(PARP),E-cadherin and Snail in the cells.The ubiquitination of Snail protein was mea-sured using immunoprecipitation techniques.RESULTS:As the concentration of TBMS1 increased,the survival rate and number of clones formed by PANC-1 cells progressively decreased,leading to apoptosis,cleavage of PARP,and cell cycle arrest in the G1 phase.There was also a reduction in the proportion of cells in the S phase and a decrease in cell migration ability.The expression of Snail protein,a critical factor in cell migration,was inhibited,while E-cadherin protein levels were increased.Treatment with the proteasome inhibitor MG132 was able to reverse the suppression of Snail protein ex-pression caused by TBMS1.Immunoprecipitation results indicated that TBMS1 enhances the ubiquitination and subse-quent degradation of Snail protein.CONCLUSION:TBMS1 effectively inhibits the malignant progression of pancreatic cancer cells by promoting the ubiquitination and degradation of Snail protein in PANC-1 cells.