1.Risk factors for venous thromboembolism after pancreatic surgery
Ze YU ; Yan LUO ; Hua CHEN ; Gang WANG ; Rui KONG ; Hongtao TAN ; Yongwei WANG ; Bei SUN
Chinese Journal of General Surgery 2025;40(3):195-200
Objective:To discuss the risk factors for postoperative venous thromboembolism (VTE) in patients undergoing pancreatic surgery.Methods:The clinical data of 488 patients who underwent pancreatectomy at the First Affiliated Hospital of Harbin Medical University from Jan 2016 to Sep 2024 was retrospectively analyzed.Results:One hundred and sixteen patients (23.8%) developed VTE after pancreatic surgery. Logistic analysis showed that advanced age, abdominal surgery history, high preoperative white blood cell count, high platelet lymphocyte ratio (PLR), distal pancreatectomy with splenectomy, open surgery, conversion to open surgery, and long surgery duration were risk factors.Nomogram prediction model based on the above risk factors was constructed and the area under the ROC curve was subsequently measured to be 0.781 (95% CI: 0.731-0.830). Conclusion:The prevention and control of VTE should be strengthened for patients undergoing pancreatic surgery with advanced age, abdominal surgery history, high preoperative white blood cell count, high PLR, distal pancreatectomy with splenectomy, open surgery, conversion to open surgery, and long surgery duration.
2.Analysis of clinical features and risk factors for severe acute pancreatitis complicated with biliary system diseases
Qiyuan LI ; Yan LUO ; Hua CHEN ; Rui KONG ; Yongwei WANG ; Guanqun LI ; Yiqin SONG ; Xin ZHENG ; Jiajun LI ; Jiawen WU ; Dongxue JU ; Bei SUN
Chinese Journal of Surgery 2025;63(8):712-719
Objective:To explore the clinical characteristics of biliary system diseases complicated by severe acute pancreatitis(SAP) and the risk factors.Methods:This is a retrospective cohort study. A retrospective analysis was conducted on the clinical data of 159 SAP patients admitted to the Department of Pancreatic and Biliary Surgery,the First Affiliated Hospital of Harbin Medical University from January 2019 to October 2024. There were 105 male cases, 54 female cases;aged (42.3±10.8)years (range:20 to 71 years). Grouping was performed according to the presence or absence of concurrent acute acalculous cholecystitis (AAC) and biliary stricture. There were 58 cases in the AAC group,including 40 males and 18 females;aged (43.8±10.6) years (range:28 to 71 years);101 cases in the non-AAC group,including 64 males and 37 females;aged (41.5±10.8) years (range:20 to 64 years);there were statistically significant differences between the two groups in terms of admission total bilirubin,Balthazar-CTSI score,fasting time,and the proportions of concurrent shock and sepsis (all P<0.05);the time from onset of SAP to diagnosis of AAC( M (IQR)) was 10.5 (13.3) days (range: 3 to 34 days). There were 15 cases in the biliary stricture group,including 13 males and 2 females;age (46.5±10.0) years (range:33 to 63 years);141 cases in the non-biliary stricture group,including 89 males and 52 females;age (41.9±10.8) years (range: 20 to 71 years); there were statistically significant differences between the two groups in the proportions of infected pancreatic necrosis,pancreatic head necrosis,and lower extremity venous thrombosis (all P<0.05);the time from the onset of SAP to the diagnosis of biliary stenosis in patients with biliary stenosis was 2.0 (3.0) months (range: 1 to 19 months). Univariate analysis was performed using independent sample t-test, Mann-Whitney U test, χ 2 test,or Fisher′s exact probability method,and variables with P<0.05 in univariate analysis were included in multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic and predictive value of the multivariate logistic regression model for AAC and biliary stricture. Results:There were statistically significant differences in fasting time,Balthazar-CTSI score,admission total bilirubin,and the proportions of concurrent shock and sepsis between the AAC group and non-AAC group ( P<0.05). Multivariate logistic analysis showed that admission total bilirubin ( OR=1.033,95% CI: 1.010 to 1.058, P=0.004),Balthazar-CTSI score ( OR=1.276,95% CI: 1.036 to 1.572, P=0.022),fasting time ( OR=1.127,95% CI: 1.044 to 1.216, P=0.002), and sepsis ( OR=4.033, 95% CI: 1.419 to 11.462, P=0.009) were independent risk factors for AAC complicated by SAP. The area under the curve (AUC) of the ROC curve was 0.820 (95% CI: 0.752 to 0.888). There were statistically significant differences in the proportions of infected pancreatic necrosis,pancreatic head necrosis,and lower extremity venous thrombosis between the biliary stricture group and non-biliary stricture group ( P<0.05). Multivariate logistic analysis showed that infected pancreatic necrosis ( OR=7.376,95% CI:1.566 to 37.750, P=0.012) and pancreatic head necrosis ( OR=3.898,95% CI:1.180 to 12.877, P=0.026) were independent risk factors for biliary stricture complicated by SAP. The AUC of the ROC curve was 0.806 (95% CI:0.715 to 0.898). Conclusions:AAC typically occurs in the early stage of SAP,and biliary stricture usually occurs in the late stage of SAP. Admission total bilirubin,Balthazar-CTSI score,fasting duration,and concurrent sepsis are independent risk factors for AAC complicating SAP. Infected pancreatic necrosis and pancreatic head necrosis are independent risk factors for biliary stricture complicating SAP.
3.Protein kinase D inhibitor CRT0066101 suppresses tumor growth by inhibiting the PI3K/AKT signaling pathway to promote apoptosis and autophagy in hepatocellular carcinoma cells
Hao-hua DENG ; Bao-yuan TANG ; Bei XIE ; Lin-jing LI
Chinese Pharmacological Bulletin 2025;41(12):2297-2305
Aim To investigate the inhibitory effect of the protein kinase D(PKD)-specific inhibitor CRT0066101 on hepatocellular carcinoma(HCC)and its underlying molecular mechanisms,providing new theoretical insights and therapeutic strategies for targe-ted HCC treatment.Methods HCC cell lines were treated with varying concentrations of CRT0066101.The inhibitory effects on cell proliferation were assessed using the CCK-8 assay,colony formation assay,and EdU staining.The impact on cell migration and inva-sion was evaluated through wound-healing assays and Transwell migration and invasion assays.was employed toThe effects of CRT0066101 on the phosphorylation levels of PKD and key proteins in the downstream PI3K/AKT signaling pathway were analyzed using Western blot.Additionally,the drug's regulatory effects on apoptosis and autophagy in HCC cells were examined using Western blot,flow cytometry,and the mRFP-GFP-LC3 dual-fluorescence reporter system.Results CRT0066101 significantly inhibited the pro-liferation,migration and invasion of HCC cells.West-ern blotting results demonstrated that CRT0066101 dose-dependently suppressed the phosphorylation of PKD family proteins and downregulated the activation of the PI3K/AKT signaling pathway.Furthermore,CRT0066101 treatment upregulated the expression of the pro-apoptotic protein Bax while downregulating the anti-apoptotic protein Bcl-2.It also markedly increased the expression levels of autophagy marker proteins Bec-lin-1 and LC3B-Ⅱ,suggesting that the drug simulta-neously induced apoptosis and autophagy in HCC cells.Conclusions CRT0066101 specifically inhibits PKD activity,blocks the PI3K/AKT signaling path-way,suppresses HCC cell proliferation and metastasis,and induces apoptosis and autophagy.These findings indicate that CRT0066101 is a promising small-mole-cule inhibitor for targeted HCC therapy with potential clinical applications.
4.Risk factors for venous thromboembolism after pancreatic surgery
Ze YU ; Yan LUO ; Hua CHEN ; Gang WANG ; Rui KONG ; Hongtao TAN ; Yongwei WANG ; Bei SUN
Chinese Journal of General Surgery 2025;40(3):195-200
Objective:To discuss the risk factors for postoperative venous thromboembolism (VTE) in patients undergoing pancreatic surgery.Methods:The clinical data of 488 patients who underwent pancreatectomy at the First Affiliated Hospital of Harbin Medical University from Jan 2016 to Sep 2024 was retrospectively analyzed.Results:One hundred and sixteen patients (23.8%) developed VTE after pancreatic surgery. Logistic analysis showed that advanced age, abdominal surgery history, high preoperative white blood cell count, high platelet lymphocyte ratio (PLR), distal pancreatectomy with splenectomy, open surgery, conversion to open surgery, and long surgery duration were risk factors.Nomogram prediction model based on the above risk factors was constructed and the area under the ROC curve was subsequently measured to be 0.781 (95% CI: 0.731-0.830). Conclusion:The prevention and control of VTE should be strengthened for patients undergoing pancreatic surgery with advanced age, abdominal surgery history, high preoperative white blood cell count, high PLR, distal pancreatectomy with splenectomy, open surgery, conversion to open surgery, and long surgery duration.
5.Effects of different CO2 pneumoperitoneum pressures on overweight or obese patients with laparoscopic panhysterectomy in Trendelenburg position
Hao WANG ; Ke GU ; Li-hua RAO ; Bei HU ; Wei-wei JI ; Zhen TIAN ; Ti-jun DAI
Journal of Regional Anatomy and Operative Surgery 2025;34(2):150-153
Objective To explore the effects of different CO2 pneumoperitoneum pressures during surgery on overweight or obese patients with laparoscopic panhysterectomy in Trendelenburg position.Methods A total of 88 overweight or obese patients who underwent laparoscopic panhysterectomy were selected and randomly divided into the low-pressure group and the high-pressure group according to random number table method,with 44 patients in each group.All patients used CO2 as the pneumoperitoneum medium during surgery,with 10 mmHg of CO2 pneumoperitoneum pressure in the low-pressure group and 15 mmHg of CO2 pneumoperitoneum pressure in the high-pressure group.The operation-related indexes,respiratory indicators,nasopharyngeal temperature and adverse reactions of patients were compared between the two groups.Results There was no significant difference in the surgical time,blood loss,intraoperative infusion volume,incidence of organ injury,and laparotomy rate between the two groups(P>0.05).The recovery time of anesthesia of patients in the low-pressure group was shorter than that in the high-pressure group(P<0.05).At 30 minutes after the establishment of pneumoperitoneum,the peak airway pressure(Ppeak)and plateau pressure(Pplat)of patients in the high-pressure group were significantly higher than those in the low-pressure group(P<0.05),while the dynamic lung compliance(Cdyn)of patients in the high-pressure group was significantly lower than that in the low-pressure group(P<0.05).At 60 minutes after the establishment of pneumoperitoneum and the end of pneumoperitoneum,the nasopharyngeal temperature of patients in the high-pressure group were significantly lower than those in the low-pressure group(P<0.05).The incidences of intraoperative hypothermia and shivering in the high-pressure group were significantly higher than those in the low-pressure group(P<0.05).Conclusion Compared with 15 mmHg of CO2 pneumoperitoneum pressure,10 mmHg of CO2 pneumoperitoneum pressure on overweight or obese patients with laparoscopic panhysterectomy in Trendelenburg position does not increase surgical difficulty,and the patients has lower airway pressure,better lung compliance,fewer adverse reactions,and faster recovery,which can also avoid intraoperative hypothermia.
6.Optimized timing analysis for elective surgery after stent placement in malignant obstructive colorectal cancer
Zong-bei LI ; Hong-chao AN ; Hua-zhi LI
Chinese Journal of Current Advances in General Surgery 2025;28(9):707-714
Objective:To explore the influence of different time intervals after stent implantation on the efficacy and prognosis of elective surgery in patients with malignant obstructive colorectal cancer(MOCRC).Methods:A total of 182 MOCRC patients were enrolled,including 92 who underwent emergency surgery(ES group)and 90 who received elective surgery after stent placement(SEMS group).The SEMS group was further divided into three subgroups based on the interval between stent placement and surgery:<11 d(n=27),11-17 d(n=39),and>17 d(n=24).Kaplan-Meier analysis was used to compare overall survival(OS)and disease-free survival(DFS),and Cox proportional hazards re-gression was employed to identify prognostic factors.Prognostic models based on surgical timing were constructed,and receiver operating characteristic(ROC)curves were drawn with area under the curve(AUC)calculated to assess model discrimination.A total of 182 patients with MOCRC were included.Among them,92 underwent emergency sur-gery(ES group),and 90 underwent elective surgery after stent implantation(SEMS group).The SEMS group was di-vided into the<11 d group(n=27),the 11-17 d group(n=39),and the>17 d group(n=24)according to the operation interval.Overall survival(OS)and disease-free survival(DFS)were compared using the Kaplan-Meier method,and prognostic factors were analyzed by Cox regression.Result:Compared with the ES group,the SEMS group had a higher rate of laparoscopic surgery and significantly less intraoperative blood loss(P<0.05),with no significant differ-ences in postoperative complication rate,stoma formation rate(P>0.05).Among SEMS patients,the 11~17 d group had the shortest hospital stay and the lowest complication rate(7.69%).Multivariate Cox analysis showed that surgery performed 11-17 d group significantly reduced the risk of death compared to emergency surgery(HR=0.650,P=0.034),while surgery 11 d group significantly increased the risk(HR=2.051,P=0.042).Independent predictors of OS in-cluded age(HR=1.060,P<0.001),preoperative CEA level(HR=1.323,P=0.002),tumor size(HR=1.421,P=0.028),tumor differentiation(HR=1.123,P=0.005),and venous invasion(HR=2.792,P<0.001).For DFS,age,tumor size,venous inva-sion,and perineural invasion were identified as independent risk factors(P<0.05),while surgical timing showed no sig-nificant association(P>0.05).Kaplan-Meier analysis revealed no significant difference in OS among different groups in stage Ⅰ-Ⅱ patients,whereas in stage Ⅲ patients,the 11-17 d group had better OS,and the>17 d group had signifi-cantly worse DFS than other groups(P=0.017).ROC curve analysis showed that the AUCs for OS prediction were 0.636(<11 d),0.601(11-17 d),and 0.750(>17 d);and for DFS prediction were 0.655,0.567,and 0.874,respectively,indicating that surgical timing has moderate discriminative value for survival outcomes.Conclusion:Elective surgery performed 11 to 17 d after stent placement can reduce mortality and improve postoperative recovery,although it has no significant impact on recurrence risk.Venous and peripheral nerve invasion are major factors affecting disease-free survival(DFS);therefore,clinical management should focus on identifying high-risk patients and optimizing individual-ized treatment strategies.
7.Optimized timing analysis for elective surgery after stent placement in malignant obstructive colorectal cancer
Zong-bei LI ; Hong-chao AN ; Hua-zhi LI
Chinese Journal of Current Advances in General Surgery 2025;28(9):707-714
Objective:To explore the influence of different time intervals after stent implantation on the efficacy and prognosis of elective surgery in patients with malignant obstructive colorectal cancer(MOCRC).Methods:A total of 182 MOCRC patients were enrolled,including 92 who underwent emergency surgery(ES group)and 90 who received elective surgery after stent placement(SEMS group).The SEMS group was further divided into three subgroups based on the interval between stent placement and surgery:<11 d(n=27),11-17 d(n=39),and>17 d(n=24).Kaplan-Meier analysis was used to compare overall survival(OS)and disease-free survival(DFS),and Cox proportional hazards re-gression was employed to identify prognostic factors.Prognostic models based on surgical timing were constructed,and receiver operating characteristic(ROC)curves were drawn with area under the curve(AUC)calculated to assess model discrimination.A total of 182 patients with MOCRC were included.Among them,92 underwent emergency sur-gery(ES group),and 90 underwent elective surgery after stent implantation(SEMS group).The SEMS group was di-vided into the<11 d group(n=27),the 11-17 d group(n=39),and the>17 d group(n=24)according to the operation interval.Overall survival(OS)and disease-free survival(DFS)were compared using the Kaplan-Meier method,and prognostic factors were analyzed by Cox regression.Result:Compared with the ES group,the SEMS group had a higher rate of laparoscopic surgery and significantly less intraoperative blood loss(P<0.05),with no significant differ-ences in postoperative complication rate,stoma formation rate(P>0.05).Among SEMS patients,the 11~17 d group had the shortest hospital stay and the lowest complication rate(7.69%).Multivariate Cox analysis showed that surgery performed 11-17 d group significantly reduced the risk of death compared to emergency surgery(HR=0.650,P=0.034),while surgery 11 d group significantly increased the risk(HR=2.051,P=0.042).Independent predictors of OS in-cluded age(HR=1.060,P<0.001),preoperative CEA level(HR=1.323,P=0.002),tumor size(HR=1.421,P=0.028),tumor differentiation(HR=1.123,P=0.005),and venous invasion(HR=2.792,P<0.001).For DFS,age,tumor size,venous inva-sion,and perineural invasion were identified as independent risk factors(P<0.05),while surgical timing showed no sig-nificant association(P>0.05).Kaplan-Meier analysis revealed no significant difference in OS among different groups in stage Ⅰ-Ⅱ patients,whereas in stage Ⅲ patients,the 11-17 d group had better OS,and the>17 d group had signifi-cantly worse DFS than other groups(P=0.017).ROC curve analysis showed that the AUCs for OS prediction were 0.636(<11 d),0.601(11-17 d),and 0.750(>17 d);and for DFS prediction were 0.655,0.567,and 0.874,respectively,indicating that surgical timing has moderate discriminative value for survival outcomes.Conclusion:Elective surgery performed 11 to 17 d after stent placement can reduce mortality and improve postoperative recovery,although it has no significant impact on recurrence risk.Venous and peripheral nerve invasion are major factors affecting disease-free survival(DFS);therefore,clinical management should focus on identifying high-risk patients and optimizing individual-ized treatment strategies.
8.Effects of different CO2 pneumoperitoneum pressures on overweight or obese patients with laparoscopic panhysterectomy in Trendelenburg position
Hao WANG ; Ke GU ; Li-hua RAO ; Bei HU ; Wei-wei JI ; Zhen TIAN ; Ti-jun DAI
Journal of Regional Anatomy and Operative Surgery 2025;34(2):150-153
Objective To explore the effects of different CO2 pneumoperitoneum pressures during surgery on overweight or obese patients with laparoscopic panhysterectomy in Trendelenburg position.Methods A total of 88 overweight or obese patients who underwent laparoscopic panhysterectomy were selected and randomly divided into the low-pressure group and the high-pressure group according to random number table method,with 44 patients in each group.All patients used CO2 as the pneumoperitoneum medium during surgery,with 10 mmHg of CO2 pneumoperitoneum pressure in the low-pressure group and 15 mmHg of CO2 pneumoperitoneum pressure in the high-pressure group.The operation-related indexes,respiratory indicators,nasopharyngeal temperature and adverse reactions of patients were compared between the two groups.Results There was no significant difference in the surgical time,blood loss,intraoperative infusion volume,incidence of organ injury,and laparotomy rate between the two groups(P>0.05).The recovery time of anesthesia of patients in the low-pressure group was shorter than that in the high-pressure group(P<0.05).At 30 minutes after the establishment of pneumoperitoneum,the peak airway pressure(Ppeak)and plateau pressure(Pplat)of patients in the high-pressure group were significantly higher than those in the low-pressure group(P<0.05),while the dynamic lung compliance(Cdyn)of patients in the high-pressure group was significantly lower than that in the low-pressure group(P<0.05).At 60 minutes after the establishment of pneumoperitoneum and the end of pneumoperitoneum,the nasopharyngeal temperature of patients in the high-pressure group were significantly lower than those in the low-pressure group(P<0.05).The incidences of intraoperative hypothermia and shivering in the high-pressure group were significantly higher than those in the low-pressure group(P<0.05).Conclusion Compared with 15 mmHg of CO2 pneumoperitoneum pressure,10 mmHg of CO2 pneumoperitoneum pressure on overweight or obese patients with laparoscopic panhysterectomy in Trendelenburg position does not increase surgical difficulty,and the patients has lower airway pressure,better lung compliance,fewer adverse reactions,and faster recovery,which can also avoid intraoperative hypothermia.
9.Analysis of clinical features and risk factors for severe acute pancreatitis complicated with biliary system diseases
Qiyuan LI ; Yan LUO ; Hua CHEN ; Rui KONG ; Yongwei WANG ; Guanqun LI ; Yiqin SONG ; Xin ZHENG ; Jiajun LI ; Jiawen WU ; Dongxue JU ; Bei SUN
Chinese Journal of Surgery 2025;63(8):712-719
Objective:To explore the clinical characteristics of biliary system diseases complicated by severe acute pancreatitis(SAP) and the risk factors.Methods:This is a retrospective cohort study. A retrospective analysis was conducted on the clinical data of 159 SAP patients admitted to the Department of Pancreatic and Biliary Surgery,the First Affiliated Hospital of Harbin Medical University from January 2019 to October 2024. There were 105 male cases, 54 female cases;aged (42.3±10.8)years (range:20 to 71 years). Grouping was performed according to the presence or absence of concurrent acute acalculous cholecystitis (AAC) and biliary stricture. There were 58 cases in the AAC group,including 40 males and 18 females;aged (43.8±10.6) years (range:28 to 71 years);101 cases in the non-AAC group,including 64 males and 37 females;aged (41.5±10.8) years (range:20 to 64 years);there were statistically significant differences between the two groups in terms of admission total bilirubin,Balthazar-CTSI score,fasting time,and the proportions of concurrent shock and sepsis (all P<0.05);the time from onset of SAP to diagnosis of AAC( M (IQR)) was 10.5 (13.3) days (range: 3 to 34 days). There were 15 cases in the biliary stricture group,including 13 males and 2 females;age (46.5±10.0) years (range:33 to 63 years);141 cases in the non-biliary stricture group,including 89 males and 52 females;age (41.9±10.8) years (range: 20 to 71 years); there were statistically significant differences between the two groups in the proportions of infected pancreatic necrosis,pancreatic head necrosis,and lower extremity venous thrombosis (all P<0.05);the time from the onset of SAP to the diagnosis of biliary stenosis in patients with biliary stenosis was 2.0 (3.0) months (range: 1 to 19 months). Univariate analysis was performed using independent sample t-test, Mann-Whitney U test, χ 2 test,or Fisher′s exact probability method,and variables with P<0.05 in univariate analysis were included in multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic and predictive value of the multivariate logistic regression model for AAC and biliary stricture. Results:There were statistically significant differences in fasting time,Balthazar-CTSI score,admission total bilirubin,and the proportions of concurrent shock and sepsis between the AAC group and non-AAC group ( P<0.05). Multivariate logistic analysis showed that admission total bilirubin ( OR=1.033,95% CI: 1.010 to 1.058, P=0.004),Balthazar-CTSI score ( OR=1.276,95% CI: 1.036 to 1.572, P=0.022),fasting time ( OR=1.127,95% CI: 1.044 to 1.216, P=0.002), and sepsis ( OR=4.033, 95% CI: 1.419 to 11.462, P=0.009) were independent risk factors for AAC complicated by SAP. The area under the curve (AUC) of the ROC curve was 0.820 (95% CI: 0.752 to 0.888). There were statistically significant differences in the proportions of infected pancreatic necrosis,pancreatic head necrosis,and lower extremity venous thrombosis between the biliary stricture group and non-biliary stricture group ( P<0.05). Multivariate logistic analysis showed that infected pancreatic necrosis ( OR=7.376,95% CI:1.566 to 37.750, P=0.012) and pancreatic head necrosis ( OR=3.898,95% CI:1.180 to 12.877, P=0.026) were independent risk factors for biliary stricture complicated by SAP. The AUC of the ROC curve was 0.806 (95% CI:0.715 to 0.898). Conclusions:AAC typically occurs in the early stage of SAP,and biliary stricture usually occurs in the late stage of SAP. Admission total bilirubin,Balthazar-CTSI score,fasting duration,and concurrent sepsis are independent risk factors for AAC complicating SAP. Infected pancreatic necrosis and pancreatic head necrosis are independent risk factors for biliary stricture complicating SAP.
10.Protein kinase D inhibitor CRT0066101 suppresses tumor growth by inhibiting the PI3K/AKT signaling pathway to promote apoptosis and autophagy in hepatocellular carcinoma cells
Hao-hua DENG ; Bao-yuan TANG ; Bei XIE ; Lin-jing LI
Chinese Pharmacological Bulletin 2025;41(12):2297-2305
Aim To investigate the inhibitory effect of the protein kinase D(PKD)-specific inhibitor CRT0066101 on hepatocellular carcinoma(HCC)and its underlying molecular mechanisms,providing new theoretical insights and therapeutic strategies for targe-ted HCC treatment.Methods HCC cell lines were treated with varying concentrations of CRT0066101.The inhibitory effects on cell proliferation were assessed using the CCK-8 assay,colony formation assay,and EdU staining.The impact on cell migration and inva-sion was evaluated through wound-healing assays and Transwell migration and invasion assays.was employed toThe effects of CRT0066101 on the phosphorylation levels of PKD and key proteins in the downstream PI3K/AKT signaling pathway were analyzed using Western blot.Additionally,the drug's regulatory effects on apoptosis and autophagy in HCC cells were examined using Western blot,flow cytometry,and the mRFP-GFP-LC3 dual-fluorescence reporter system.Results CRT0066101 significantly inhibited the pro-liferation,migration and invasion of HCC cells.West-ern blotting results demonstrated that CRT0066101 dose-dependently suppressed the phosphorylation of PKD family proteins and downregulated the activation of the PI3K/AKT signaling pathway.Furthermore,CRT0066101 treatment upregulated the expression of the pro-apoptotic protein Bax while downregulating the anti-apoptotic protein Bcl-2.It also markedly increased the expression levels of autophagy marker proteins Bec-lin-1 and LC3B-Ⅱ,suggesting that the drug simulta-neously induced apoptosis and autophagy in HCC cells.Conclusions CRT0066101 specifically inhibits PKD activity,blocks the PI3K/AKT signaling path-way,suppresses HCC cell proliferation and metastasis,and induces apoptosis and autophagy.These findings indicate that CRT0066101 is a promising small-mole-cule inhibitor for targeted HCC therapy with potential clinical applications.

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