Objective To retrospectively analyze multicenter data from domestic sources, aiming to explore the link between intrahepatic cholangiocarcinoma (ICC) tumor size and prognosis, establishing a classification system based on tumor size. Methods Between December 2011 and September 2018, 280 ICC patients from 13 hospitals were included. The tumor size prognosis cutoff was identified by the minimum P-value method, and the classification's overall survival related effectiveness was assessed by Kaplan-Meier analysis. Results All 280 patients were divided into the group of tumor maximum diameter ≤4 cm and >4 cm. Tumor size was confirmed as an independent prognosis factor by multivariate COX regression analysis (HR=2.110, 95% CI: 1.358-3.280). Conclusions The tumor size dichotomy classification system based on the Chinese patient group can expediently predict ICC prognosis and offers an important basis for selecting post-operative individualized adjuvant therapy and follow up plans.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Objective:To examine a survival prognostic model applicable for patients with intrahepatic cholangiocarcinoma (ICC) based on Bayesian network.Methods:The clinical and pathological data of ICC patients who underwent curative intent resection in ten Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected.A total of 516 patients were included in the study. There were 266 males and 250 females.The median age( M( Q R)) was 58(14) years.One hundred and sixteen cases (22.5%) with intrahepatic bile duct stones,and 143 cases (27.7%) with chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis.The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.One-year survival prediction models based on tree augmented naive Bayesian (TAN) and na?ve Bayesian algorithm were established by Bayesialab software according to different variables,a nomogram model was also developed based on the independent predictors.The receiver operating characteristic curve and the area under curve (AUC) were used to evaluate the prediction effect of the models. Results:The overall median survival time was 25.0 months,and the 1-,3-and 5-year cumulative survival rates was 76.6%,37.9%,and 21.0%,respectively.Univariate analysis showed that gender,preoperative jaundice,pathological differentiation,vascular invasion,microvascular invasion,liver capsule invasion,T staging,N staging,margin,intrahepatic bile duct stones,carcinoembryonic antigen,and CA19-9 affected the prognosis(χ 2=5.858-54.974, all P<0.05).The Cox multivariate model showed that gender,pathological differentiation,liver capsule invasion, T stage,N stage,intrahepatic bile duct stones,and CA19-9 were the independent predictive factors(all P<0.05). The AUC of the TAN model based on all 19 clinicopathological factors was 74.5%,and the AUC of the TAN model based on the 12 prognostic factors derived from univariate analysis was 74.0%,the AUC of the na?ve Bayesian model based on 7 independent prognostic risk factors was 79.5%,the AUC and C-index of the nomogram survival prediction model based on 7 independent prognostic risk factors were 78.8% and 0.73,respectively. Conclusion:The Bayesian network model may provide a relatively accurate prognostic prediction for ICC patients after curative intent resection and performed superior to the nomogram model.

Objective:To examine a survival prognostic model applicable for patients with intrahepatic cholangiocarcinoma (ICC) based on Bayesian network.Methods:The clinical and pathological data of ICC patients who underwent curative intent resection in ten Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected.A total of 516 patients were included in the study. There were 266 males and 250 females.The median age( M( Q R)) was 58(14) years.One hundred and sixteen cases (22.5%) with intrahepatic bile duct stones,and 143 cases (27.7%) with chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis.The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.One-year survival prediction models based on tree augmented naive Bayesian (TAN) and na?ve Bayesian algorithm were established by Bayesialab software according to different variables,a nomogram model was also developed based on the independent predictors.The receiver operating characteristic curve and the area under curve (AUC) were used to evaluate the prediction effect of the models. Results:The overall median survival time was 25.0 months,and the 1-,3-and 5-year cumulative survival rates was 76.6%,37.9%,and 21.0%,respectively.Univariate analysis showed that gender,preoperative jaundice,pathological differentiation,vascular invasion,microvascular invasion,liver capsule invasion,T staging,N staging,margin,intrahepatic bile duct stones,carcinoembryonic antigen,and CA19-9 affected the prognosis(χ 2=5.858-54.974, all P<0.05).The Cox multivariate model showed that gender,pathological differentiation,liver capsule invasion, T stage,N stage,intrahepatic bile duct stones,and CA19-9 were the independent predictive factors(all P<0.05). The AUC of the TAN model based on all 19 clinicopathological factors was 74.5%,and the AUC of the TAN model based on the 12 prognostic factors derived from univariate analysis was 74.0%,the AUC of the na?ve Bayesian model based on 7 independent prognostic risk factors was 79.5%,the AUC and C-index of the nomogram survival prediction model based on 7 independent prognostic risk factors were 78.8% and 0.73,respectively. Conclusion:The Bayesian network model may provide a relatively accurate prognostic prediction for ICC patients after curative intent resection and performed superior to the nomogram model.

Objective:To examine the value of number of metastatic lymph nodes(NMLN), lymph node ratio(LNR) and log odds of metastatic lymph nodes(LODDS) in assessing the prognosis of patients with intrahepatic cholangiocarcinoma(ICC).Methods:The clinical and pathological data of 440 ICC patients who underwent curative-intent resection in 10 of Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected, and the deadline of follow-up was April 30th, 2019. Among them, 205 were males and 235 were females, with age of (57.0±9.9) years (range:23-83 years).Eighty-five cases (19.3%) had intrahepatic bile duct stones, and 98 cases (22.3%) had chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis. The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.Results:A total of 440 patients underwent curative-intent resection and lymphadenectomy.R0 resection were achieved in 424 cases (96.4%) and R1 resection were in 16 cases (3.6%). The results of postoperative pathological examination showed that high, moderate and poor differentiation was 4.2%(18/426), 60.6%(258/426) and 35.2%(150/426), respectively.Adenocarcinoma was seen in 90.2%(397/440) and non-adenocarcinoma was seen in 9.8%(43/440), respectively. T stage: 2 cases (0.5%) with Tis, 83 cases(18.9%) with T1a, 97 cases(22.0%) with T1b, 95 cases(21.6%) with T2, 122 cases (27.7%) with T3 and 41 cases(9.3%) with T4.The overall median survival time was 24.0 months, and the 1-,3-, and 5-year survival rate was 74.3%, 37.7% and 18.3%, respectively. Lymphatic metastasis occurred in 175 patients(39.8%), the median total number of TNLE( M( Q R)) was 6(5), the median number of NMLN was 0(1), the median number of LNR was 0 (0.33) and the median number of LODDS was -0.70(-0.92). Rerults of univariate analysis showed that combined stones, pathological differentiation, vascular invasion, LODDS, margin and T staging affected the prognosis (all P<0.05). Rerults of multivariate analysis showed that pathological differentiation, LODDS, margin, and T staging were independent risk factors affecting the prognosis of ICC patients (all P<0.05). Conclusion:LODDS could be used as an optimal prognostic lymph node staging index for ICC, and it is also an independent risk factor for survival after curative intent resection.

Objective:To examine the value of number of metastatic lymph nodes(NMLN), lymph node ratio(LNR) and log odds of metastatic lymph nodes(LODDS) in assessing the prognosis of patients with intrahepatic cholangiocarcinoma(ICC).Methods:The clinical and pathological data of 440 ICC patients who underwent curative-intent resection in 10 of Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected, and the deadline of follow-up was April 30th, 2019. Among them, 205 were males and 235 were females, with age of (57.0±9.9) years (range:23-83 years).Eighty-five cases (19.3%) had intrahepatic bile duct stones, and 98 cases (22.3%) had chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis. The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.Results:A total of 440 patients underwent curative-intent resection and lymphadenectomy.R0 resection were achieved in 424 cases (96.4%) and R1 resection were in 16 cases (3.6%). The results of postoperative pathological examination showed that high, moderate and poor differentiation was 4.2%(18/426), 60.6%(258/426) and 35.2%(150/426), respectively.Adenocarcinoma was seen in 90.2%(397/440) and non-adenocarcinoma was seen in 9.8%(43/440), respectively. T stage: 2 cases (0.5%) with Tis, 83 cases(18.9%) with T1a, 97 cases(22.0%) with T1b, 95 cases(21.6%) with T2, 122 cases (27.7%) with T3 and 41 cases(9.3%) with T4.The overall median survival time was 24.0 months, and the 1-,3-, and 5-year survival rate was 74.3%, 37.7% and 18.3%, respectively. Lymphatic metastasis occurred in 175 patients(39.8%), the median total number of TNLE( M( Q R)) was 6(5), the median number of NMLN was 0(1), the median number of LNR was 0 (0.33) and the median number of LODDS was -0.70(-0.92). Rerults of univariate analysis showed that combined stones, pathological differentiation, vascular invasion, LODDS, margin and T staging affected the prognosis (all P<0.05). Rerults of multivariate analysis showed that pathological differentiation, LODDS, margin, and T staging were independent risk factors affecting the prognosis of ICC patients (all P<0.05). Conclusion:LODDS could be used as an optimal prognostic lymph node staging index for ICC, and it is also an independent risk factor for survival after curative intent resection.

ABSTRACT:Objective To study the effects of propofol on the metastasis of tumor cells related PI3K/Akt signaling pathway.Methods The breast cancer model was established by transplanting human derived breast cancer cell lines into immunodeficient mice with naked gene.The mice,inoculated successfully,were randomly divided into 4 groups:control group (C group,n =6),propofol group (P group,n =6),propofol+PI3K inhibitor (BYL71 9)group (P+B group,n =6),and PI3K inhibitor group (BYL71 9)(B group,n =6).The expressions of PI3K,p-Akt and Akt were examined by Western blot at week 4 after administration;the gene levels of PI3KR1, Akt1 and Akt2 were detected by RT-PCR at week 4 after administration;the number of metastatic lung nodules from both lungs was also observed at week 4 after administration.Results Compared with those in C group,the expressions of PI3K and p-Akt were significantly higher in P group (P <0.05),the level of PI3KR1 mRNA but not Akt1 and Akt2 mRNA was significantly increased(P < 0.05 ),and metastatic lung nodules significantly decreased (P <0.05).In B group,the expressions of PI3K and p-Akt were significantly decreased (P <0.05 ),the levels of PI3KR1,Akt1 and Akt2 mRNA were not significantly increased (P >0.05),but metastatic lung nodules significantly increased (P < 0.05 ).Compared with those in B group,in P+ B group the expressions of PI3K and p-Akt were markedly higher (P <0.05),the level of PI3KR1 mRNA but not Akt1 and Akt2 mRNA was significantly increased (P <0.05),and metastatic lung nodules significantly decreased (P <0.05).Conclusion Propofol can inhibit the metastasis of tumor cells through the upregulated and activated PI3K/Akt signaling pathway.

Objective To develop a real-time fluorescent quantitative PCR method for the detection of toxic gene copy number of microcystin algae,so as to realize warning detection of microcystin algae.Methods With the primers based on microcystin synthetase gene mcy A,racy D and partial Microcystis-specific 16S rDNA,the target gene was inserted into pMD (R) 18-T Vector for the preparation of plasmid standards to establish the standard curve of real-time fluorescent quantitative PCR method and through the standard curve to calculate the toxin-producing gene copy number of the unknown sample.Results The exponential curve of the initial template was linear with the Ct value and the related coefficient r2 was all higher than 0.995 and had good reproducibility.The established method could yield the same result as the recommended international standard method.Conclusions With good accuracy,sensitivity,specificity and practicability,this method could be used for predictive detection of water-borne toxin-produced microcystin algae.

Objective To develop a real-time fluorescent quantitative PCR method for the detection of toxic gene copy number of microcystin algae,so as to realize warning detection of microcystin algae.Methods With the primers based on microcystin synthetase gene mcy A,racy D and partial Microcystis-specific 16S rDNA,the target gene was inserted into pMD (R) 18-T Vector for the preparation of plasmid standards to establish the standard curve of real-time fluorescent quantitative PCR method and through the standard curve to calculate the toxin-producing gene copy number of the unknown sample.Results The exponential curve of the initial template was linear with the Ct value and the related coefficient r2 was all higher than 0.995 and had good reproducibility.The established method could yield the same result as the recommended international standard method.Conclusions With good accuracy,sensitivity,specificity and practicability,this method could be used for predictive detection of water-borne toxin-produced microcystin algae.