Objective:To investigate the effect of copper chlorophyllin sodium salt(CHL)on the sensitivity of human pancreatic cancer cells in response to gemcitabine(GEM)therapy and on the therapeutic effect on pancreatic cancer cells that have developed GEM resistance.Methods:MIA GR(a pancreatic cancer cell line resistant to GEM)was induced by a low-dose continuous incremental method,and the half inhibitory concentration(IC50)of MIA WT and MIA GR to GEM treatment was detected by the CCK-8 method,and the resistance index was calculated;the difference in IC50 of CHL on the two types of cells was detected by the CCK-8 method after treating MIA WT and MIA GR cells with different concentrations of CHL,CCK-8 method was used to detect the difference in IC50 of CHL on the two types of cells;on the basis of IC50,MIA WT and MIA GR cells were intervened with CHL and(or)GEM with different multiplicity of IC50,respectively,and the growth inhibition curves of MIA WT and MIA GR cells were detected by the CCK-8 method under the intervention of CHL combined with GEM;After the intervention of MIA WT and MIA GR cells with CHL and(or)GEM at IC50,respectively,the effects on the proliferation of the two different cells were detected using the clone formation assay;the effects on cytotoxicity/activity were observed under fluorescence microscopy;and the effects on apoptosis were detected using flow cytometry.Finally,western blotting was used to detect the effects of CHL and(or)GEM interventions on the drug resistance-associated molecules P-glycoprotein(P-gp)and ribonucleotide reductase regulatory subunit M2(RRM2)in MIA GR cells,the and sensitivity-related molecule deoxycytidine kinase(DCK)on protein expression levels.Results:MIA GR cells were verified to be well drug resistant,with resistance indices of 549.1 and 667.9 after 48 h and 96 h after GEM intervention compared to homologous wild-type MIA WT cells,respectively;CHL intervention inhibited the proliferation of MIA GR cells more significantly compared to that of MIA WT cells;and CHL in combination with GEM exerted a more significant growth inhibitory effect compared to GEM alone in both MIA WT cells(P<0.001)and MIA GR cells(P<0.01).CHL significantly inhibited the tumor proliferation of MIA GR cells,and the inhibitory effect was more pronounced in both cells when combined with GEM(P<0.000 1);furthermore,compared to GEM alone,the intervention with CHL could cause more pronounced cytotoxicity(P<0.000 1)in both MIA WT and MIA GR cells.caused more pronounced cytotoxicity(P<0.000 1)and induced a higher percentage of apoptosis than GEM alone.The results of the western blotting assay showed that CHL intervention caused a decrease in the expression levels of P-gp and RRM2 proteins,as well as an increase in the protein expression level of DCK in MIA GR cells.Conclusion:CHL increases the sensitivity of pancreatic cancer cells to GEM and also induces a decrease in the resistance of drug-resistant pancreatic cancer cells to GEM.

Objective To construct and validate an effective prognostic nomogram for the patients with incidental gallbladder cancer(IGBC).Methods The clinical data of 161 patients with IGBC requiring radical surgery admitted to the First Affiliated Hospital of Xi'an Jiaotong University from May 2011 to October 2022 was analyzed retrospectively.COX proportional risk regression model was used to screen for influencing factors on overall survival(OS)of IGBC.Nomogram was constructed based on independent influencing factors that affected the prognosis of IGBC patients.The concordance index(C-index)and calibration curve were used to validate the performance of the model.Receiver operating characteristic(ROC)curve analysis and decision curve analysis(DCA)were used to validate the predictive accuracy and net benefit of the plotted column chart.Results Univariate COX regression analysis suggested that age,T stage,N stage,M stage,preoperative carcinoembryonic antigen(CEA),preoperative carbohydrate antigenl9-9(CA19-9),preoperative red blood cell volume distribution on width coefficient of variation(RDW-CV),treatment method,and recurrence and metastasis were risk factors which affected the long-term survival of IGBC patients after radical surgery.Multivariate COX regression analysis suggested that T stage,N stage,preoperative CA19-9,preoperative RDW-CV,preoperative AST,treatment methods,and recurrence and metastasis were independent risk factors which affected the prognosis of IGBC patients.The C-index of the constructed prognostic model was 0.872.The calibration plot demonstrated good performance of the Nomogram.ROC curve analysis showed an area under the curve of 0.869,confirming a high sensitivity and specificity.A high net benefit was proven by DCA.Conclusions The constructed Nomogram.can accurately and intuitively predict the survival probability of IGBC patients after radical surgery.

Pancreatic cancer has a very poor prognosis.Early diagnosis and treatment are especially critical for improving its prognosis.Nanotechnology has been widely used in the diagnosis and treatment of pancreatic cancer.Relying on the unique physicochemical properties of nanoparticles and their rich surface modifications,effective enrichment of tumor sites can be achieved.Magnetic iron oxide nanoparticles(MIONPs)is one of the commonly used nanomaterials in the diagnosis and treatment of pancreatic cancer,and has good biocompatibility.Through special surface modification,it can be used in targeted diagnosis and treatment of pancreatic cancer.MIONPs can be used as a contrast agent for MRI,and by modifying the surface,they also can be used in targeted imaging of pancreatic cancer.And they can also be modified as a drug delivery system to achieve targeted delivery of drugs and improve therapeutic effects.However,the application of MIONPs in pancreatic cancer diagnosis and treatment still faces some challenges,such as nanotoxicity and cost issues.With the development of technology,MIONPs are expected to play an important role in the personalized diagnosis and treatment of pancreatic cancer.

Objective:To investigate the effect of copper chlorophyllin sodium salt(CHL)on the sensitivity of human pancreatic cancer cells in response to gemcitabine(GEM)therapy and on the therapeutic effect on pancreatic cancer cells that have developed GEM resistance.Methods:MIA GR(a pancreatic cancer cell line resistant to GEM)was induced by a low-dose continuous incremental method,and the half inhibitory concentration(IC50)of MIA WT and MIA GR to GEM treatment was detected by the CCK-8 method,and the resistance index was calculated;the difference in IC50 of CHL on the two types of cells was detected by the CCK-8 method after treating MIA WT and MIA GR cells with different concentrations of CHL,CCK-8 method was used to detect the difference in IC50 of CHL on the two types of cells;on the basis of IC50,MIA WT and MIA GR cells were intervened with CHL and(or)GEM with different multiplicity of IC50,respectively,and the growth inhibition curves of MIA WT and MIA GR cells were detected by the CCK-8 method under the intervention of CHL combined with GEM;After the intervention of MIA WT and MIA GR cells with CHL and(or)GEM at IC50,respectively,the effects on the proliferation of the two different cells were detected using the clone formation assay;the effects on cytotoxicity/activity were observed under fluorescence microscopy;and the effects on apoptosis were detected using flow cytometry.Finally,western blotting was used to detect the effects of CHL and(or)GEM interventions on the drug resistance-associated molecules P-glycoprotein(P-gp)and ribonucleotide reductase regulatory subunit M2(RRM2)in MIA GR cells,the and sensitivity-related molecule deoxycytidine kinase(DCK)on protein expression levels.Results:MIA GR cells were verified to be well drug resistant,with resistance indices of 549.1 and 667.9 after 48 h and 96 h after GEM intervention compared to homologous wild-type MIA WT cells,respectively;CHL intervention inhibited the proliferation of MIA GR cells more significantly compared to that of MIA WT cells;and CHL in combination with GEM exerted a more significant growth inhibitory effect compared to GEM alone in both MIA WT cells(P<0.001)and MIA GR cells(P<0.01).CHL significantly inhibited the tumor proliferation of MIA GR cells,and the inhibitory effect was more pronounced in both cells when combined with GEM(P<0.000 1);furthermore,compared to GEM alone,the intervention with CHL could cause more pronounced cytotoxicity(P<0.000 1)in both MIA WT and MIA GR cells.caused more pronounced cytotoxicity(P<0.000 1)and induced a higher percentage of apoptosis than GEM alone.The results of the western blotting assay showed that CHL intervention caused a decrease in the expression levels of P-gp and RRM2 proteins,as well as an increase in the protein expression level of DCK in MIA GR cells.Conclusion:CHL increases the sensitivity of pancreatic cancer cells to GEM and also induces a decrease in the resistance of drug-resistant pancreatic cancer cells to GEM.

Objective:To investigate the drug resistance factors in postoperative gemci-tabine chemotherapy after radical resection of pancreatic cancer.Methods:The retrospective case-control study was constructed. The clinicopathological data of 255 patients with pancreatic cancer who were firstly admitted to the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi ′an Jiaotong University from January 2018 to June 2021 were collected. There were 140 males and 115 females, aged (59±10)years. All patients underwent radical resection of pancreatic cancer and received postoperative gemcitabine-based adjuvant chemotherapy. Observation indicators: (1) follow-up; (2) postoperative chemotherapy; (3) drug resistance and changing of regimen; (4) factors influencing postoperative chemotherapy resistance. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and compari-son between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the Pearson chi-square test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model with forward method. Kaplan-Meier method was used to draw survival curve, and Log-Rank test was used for survival analysis. Results:(1) Follow-up. All 255 patients were followed up for 18.6(16.7,21.4)months. The median survival time of 255 patients was 18.2[95% confidence interval ( CI) as 15.8-20.6]months. (2) Postoperative chemotherapy. Of the 255 patients, there were 5 cases receiving postoperative chemotherapy as gemcitabine monotherapy, 167 cases receiving postoperative chemotherapy as the AG combination (gemcitabine plus albumin-bound paclitaxel), 74 cases receiving postoperative chemotherapy as the GS combination (gemcitabine plus S-1) and 9 cases receiving postoperative chemotherapy as the GP combination (gemcitabine plus platinum). (3) Drug resistance and changing of regimen. Of the 255 patients, 81 cases completed the course of postoperative chemotherapy and evaluation. Of the 81 patients, there were 18 cases with no recurrence or metastasis of tumor, 10 cases with tumor local recurrence, 40 cases with tumor lymph node metastasis or distant metas-tasis, 3 cases with tumor local recurrence combined with distant metastasis, 10 cases with elevation of CA19-9. Of the 81 patients, 18 cases responded to chemotherapy, 63 cases underwent resistant to chemotherapy, including 11 cases with primary resistance and 52 cases with acquired resistance. The 63 patients with chemotherapy resistance underwent changing of regimen. (4) Factors influencing postoperative chemotherapy resistance. Results of multivariate analysis showed that chemotherapy cycle<6 is an independent risk factor for postoperative chemotherapy resistance in patients ( hazard ratio=17.18, 95% CI as 2.07-142.28, P<0.05). Conclusion:Adjuvant chemotherapy cycle <6 is an independent risk factor for postoperative chemotherapy resistance for gemcitabine based chemo-therapy in pancreatic cancer patients receiving radical resection.