OBJECTIVE To explore the mechanisms of the flavonoids from new "Zhe Eight Flavors" Quzhou Fructus Aurantii(PTFC) against hepatocellular carcinoma based on the prediction of network pharmacology and experimental verification. METHODS From TCMSP, TCMID, ETCM, BATMAN-TCM and SwissTargetPrediction databases, the potential target proteins of PTFC, including naringin, narirutin and neohesperidin were collected. Based on the GeneCards, CTD, Disgenet, and OMIM databases, a set of target proteins for hepatocellular carcinoma was constructed. Taking the intersection of potential target proteins of PTFC and target proteins of hepatocellular carcinoma, key target proteins were obtained and a protein-protein interaction network was established. Besides, GO function and KEGG pathway enrichment analysis on the core target proteins was performed and a Compounds-Targets-Pathways-Disease network was constructed. Through proliferation, cloning, wound healing, and migration experiments, the effects of PTFC on the viability of HepG2 liver cancer cells were analyzed. Using fluorescence probe staining the impacts of PTFC on the mitochondrial membrane potential and apoptosis of HepG2 were observed. Finally, the validation of the regulatory effect of PTFC on the key predicted target PRKCA were carried out through RT-qPCR. RESULTS Based on network pharmacology, a total of 217 potential target proteins for PTFC were screened, with 59 intersecting target proteins related to diseases, including ALB, ESR1, PRKCA, and others. GO functional and KEGG pathway enrichment analysis revealed that the PTFC target proteins were involved in 193 biological processes and 13 cancer-related signaling pathways. Experimental results demonstrated that PTFC could impact the proliferation, cloning, wound healing, and migration abilities of liver cancer cells, leading to a decrease in mitochondrial membrane potential and promoting cell apoptosis. The results of RT-qPCR confirmed a significant downregulation of PRKCA expression by PTFC, validating the predictions made by network pharmacology analysis. CONCLUSION This study has revealed the potential molecular mechanism of PTFC treating hepatocellular carcinoma via the PRKCA target, laying the foundation for clinical application of PTFC.

Objective:To analyze the influencing factors of platinum resistant recurrence in advanced epithelial ovarian cancer(AEOC),establish a nomogram model to predict platinum-resistant recurrence of AEOC,and inter-nally validate it.Methods:The clinicopathological data of 577 AEOC patients who achieved complete remission af-ter initial treatment in the Department of Gynecology,Yunnan Cancer Hospital from June 1,2013 to December 31,2021 were collected.According to whether the platinum free interval(PFI)was less than 6 months,the patients were divided into platinum-resistant recurrence group(130 cases)and non-platinum-resistant group(447 cases,including patients with platinum-sensitive recurrence and no recurrence after 6 months of follow-up).Multivariate Logistic regression analysis was used to screen for the independent risk factors affecting the recurrence of plati-num-resistant patients.Based on the independent risk factors,a nomogram prediction model was established,and Bootstrap method was used for internal verification.The area under the ROC curve(AUC),calibration curve and decision curve(DCA)were used to evaluate the performance of the model.Results:①There were statistically sig-nificant differences in age,bilateral ovarian invasion,FIGO staging,menopause,neoadjuvant chemotherapy(NACT),chemotherapy interval(TTC),platelet count(PLT),platelet count/lymphocyte count ratio(PLR),fibrino-gen/lymphocyte count ratio(FLR),prognostic nutritional index(PNI),albumin(ALB),CA125 level,ascites volume,residual lesions,perioperative chemotherapy frequency,and CA125 half-life between the two groups(P＜0.05).②Multivariate Logistic regression analysis showed that bilateral ovarian invasion,FIGO stage Ⅳ,TTC＞16 days,ini-tial ascites volume＞1000ml,perioperative chemotherapy frequency＞9 times,surgery with R2 resection,CA125 half-life＞52 days were independent risk factors for recurrence of platinum-resistant AEOC patients(OR＞1,P＜0.05).③The AUC of the nomogram model constructed based on the above 7 indicators was 0.791(95％Cl 0.747-0.835),and the calibration curve and ideal curve fitted well.DCA showed that the net benefit interval of the model was 0.037-0.800.Conclusions:The nomogram prediction model based on independent risk factors for the recurrence of platinum-resistance of AEOC patients has good discrimination,calibration and clinical appli-cability,which can better predict the recurrence risk of platinum-resistance in AEOC patients after the initial treat-ment.

Objective:To analyze the influencing factors of platinum resistant recurrence in advanced epithelial ovarian cancer(AEOC),establish a nomogram model to predict platinum-resistant recurrence of AEOC,and inter-nally validate it.Methods:The clinicopathological data of 577 AEOC patients who achieved complete remission af-ter initial treatment in the Department of Gynecology,Yunnan Cancer Hospital from June 1,2013 to December 31,2021 were collected.According to whether the platinum free interval(PFI)was less than 6 months,the patients were divided into platinum-resistant recurrence group(130 cases)and non-platinum-resistant group(447 cases,including patients with platinum-sensitive recurrence and no recurrence after 6 months of follow-up).Multivariate Logistic regression analysis was used to screen for the independent risk factors affecting the recurrence of plati-num-resistant patients.Based on the independent risk factors,a nomogram prediction model was established,and Bootstrap method was used for internal verification.The area under the ROC curve(AUC),calibration curve and decision curve(DCA)were used to evaluate the performance of the model.Results:①There were statistically sig-nificant differences in age,bilateral ovarian invasion,FIGO staging,menopause,neoadjuvant chemotherapy(NACT),chemotherapy interval(TTC),platelet count(PLT),platelet count/lymphocyte count ratio(PLR),fibrino-gen/lymphocyte count ratio(FLR),prognostic nutritional index(PNI),albumin(ALB),CA125 level,ascites volume,residual lesions,perioperative chemotherapy frequency,and CA125 half-life between the two groups(P＜0.05).②Multivariate Logistic regression analysis showed that bilateral ovarian invasion,FIGO stage Ⅳ,TTC＞16 days,ini-tial ascites volume＞1000ml,perioperative chemotherapy frequency＞9 times,surgery with R2 resection,CA125 half-life＞52 days were independent risk factors for recurrence of platinum-resistant AEOC patients(OR＞1,P＜0.05).③The AUC of the nomogram model constructed based on the above 7 indicators was 0.791(95％Cl 0.747-0.835),and the calibration curve and ideal curve fitted well.DCA showed that the net benefit interval of the model was 0.037-0.800.Conclusions:The nomogram prediction model based on independent risk factors for the recurrence of platinum-resistance of AEOC patients has good discrimination,calibration and clinical appli-cability,which can better predict the recurrence risk of platinum-resistance in AEOC patients after the initial treat-ment.

Objective:To analyze the influencing factors of platinum resistant recurrence in advanced epithelial ovarian cancer(AEOC),establish a nomogram model to predict platinum-resistant recurrence of AEOC,and inter-nally validate it.Methods:The clinicopathological data of 577 AEOC patients who achieved complete remission af-ter initial treatment in the Department of Gynecology,Yunnan Cancer Hospital from June 1,2013 to December 31,2021 were collected.According to whether the platinum free interval(PFI)was less than 6 months,the patients were divided into platinum-resistant recurrence group(130 cases)and non-platinum-resistant group(447 cases,including patients with platinum-sensitive recurrence and no recurrence after 6 months of follow-up).Multivariate Logistic regression analysis was used to screen for the independent risk factors affecting the recurrence of plati-num-resistant patients.Based on the independent risk factors,a nomogram prediction model was established,and Bootstrap method was used for internal verification.The area under the ROC curve(AUC),calibration curve and decision curve(DCA)were used to evaluate the performance of the model.Results:①There were statistically sig-nificant differences in age,bilateral ovarian invasion,FIGO staging,menopause,neoadjuvant chemotherapy(NACT),chemotherapy interval(TTC),platelet count(PLT),platelet count/lymphocyte count ratio(PLR),fibrino-gen/lymphocyte count ratio(FLR),prognostic nutritional index(PNI),albumin(ALB),CA125 level,ascites volume,residual lesions,perioperative chemotherapy frequency,and CA125 half-life between the two groups(P＜0.05).②Multivariate Logistic regression analysis showed that bilateral ovarian invasion,FIGO stage Ⅳ,TTC＞16 days,ini-tial ascites volume＞1000ml,perioperative chemotherapy frequency＞9 times,surgery with R2 resection,CA125 half-life＞52 days were independent risk factors for recurrence of platinum-resistant AEOC patients(OR＞1,P＜0.05).③The AUC of the nomogram model constructed based on the above 7 indicators was 0.791(95％Cl 0.747-0.835),and the calibration curve and ideal curve fitted well.DCA showed that the net benefit interval of the model was 0.037-0.800.Conclusions:The nomogram prediction model based on independent risk factors for the recurrence of platinum-resistance of AEOC patients has good discrimination,calibration and clinical appli-cability,which can better predict the recurrence risk of platinum-resistance in AEOC patients after the initial treat-ment.

Objective:To analyze the influencing factors of platinum resistant recurrence in advanced epithelial ovarian cancer(AEOC),establish a nomogram model to predict platinum-resistant recurrence of AEOC,and inter-nally validate it.Methods:The clinicopathological data of 577 AEOC patients who achieved complete remission af-ter initial treatment in the Department of Gynecology,Yunnan Cancer Hospital from June 1,2013 to December 31,2021 were collected.According to whether the platinum free interval(PFI)was less than 6 months,the patients were divided into platinum-resistant recurrence group(130 cases)and non-platinum-resistant group(447 cases,including patients with platinum-sensitive recurrence and no recurrence after 6 months of follow-up).Multivariate Logistic regression analysis was used to screen for the independent risk factors affecting the recurrence of plati-num-resistant patients.Based on the independent risk factors,a nomogram prediction model was established,and Bootstrap method was used for internal verification.The area under the ROC curve(AUC),calibration curve and decision curve(DCA)were used to evaluate the performance of the model.Results:①There were statistically sig-nificant differences in age,bilateral ovarian invasion,FIGO staging,menopause,neoadjuvant chemotherapy(NACT),chemotherapy interval(TTC),platelet count(PLT),platelet count/lymphocyte count ratio(PLR),fibrino-gen/lymphocyte count ratio(FLR),prognostic nutritional index(PNI),albumin(ALB),CA125 level,ascites volume,residual lesions,perioperative chemotherapy frequency,and CA125 half-life between the two groups(P＜0.05).②Multivariate Logistic regression analysis showed that bilateral ovarian invasion,FIGO stage Ⅳ,TTC＞16 days,ini-tial ascites volume＞1000ml,perioperative chemotherapy frequency＞9 times,surgery with R2 resection,CA125 half-life＞52 days were independent risk factors for recurrence of platinum-resistant AEOC patients(OR＞1,P＜0.05).③The AUC of the nomogram model constructed based on the above 7 indicators was 0.791(95％Cl 0.747-0.835),and the calibration curve and ideal curve fitted well.DCA showed that the net benefit interval of the model was 0.037-0.800.Conclusions:The nomogram prediction model based on independent risk factors for the recurrence of platinum-resistance of AEOC patients has good discrimination,calibration and clinical appli-cability,which can better predict the recurrence risk of platinum-resistance in AEOC patients after the initial treat-ment.

Objective:To analyze the influencing factors of platinum resistant recurrence in advanced epithelial ovarian cancer(AEOC),establish a nomogram model to predict platinum-resistant recurrence of AEOC,and inter-nally validate it.Methods:The clinicopathological data of 577 AEOC patients who achieved complete remission af-ter initial treatment in the Department of Gynecology,Yunnan Cancer Hospital from June 1,2013 to December 31,2021 were collected.According to whether the platinum free interval(PFI)was less than 6 months,the patients were divided into platinum-resistant recurrence group(130 cases)and non-platinum-resistant group(447 cases,including patients with platinum-sensitive recurrence and no recurrence after 6 months of follow-up).Multivariate Logistic regression analysis was used to screen for the independent risk factors affecting the recurrence of plati-num-resistant patients.Based on the independent risk factors,a nomogram prediction model was established,and Bootstrap method was used for internal verification.The area under the ROC curve(AUC),calibration curve and decision curve(DCA)were used to evaluate the performance of the model.Results:①There were statistically sig-nificant differences in age,bilateral ovarian invasion,FIGO staging,menopause,neoadjuvant chemotherapy(NACT),chemotherapy interval(TTC),platelet count(PLT),platelet count/lymphocyte count ratio(PLR),fibrino-gen/lymphocyte count ratio(FLR),prognostic nutritional index(PNI),albumin(ALB),CA125 level,ascites volume,residual lesions,perioperative chemotherapy frequency,and CA125 half-life between the two groups(P＜0.05).②Multivariate Logistic regression analysis showed that bilateral ovarian invasion,FIGO stage Ⅳ,TTC＞16 days,ini-tial ascites volume＞1000ml,perioperative chemotherapy frequency＞9 times,surgery with R2 resection,CA125 half-life＞52 days were independent risk factors for recurrence of platinum-resistant AEOC patients(OR＞1,P＜0.05).③The AUC of the nomogram model constructed based on the above 7 indicators was 0.791(95％Cl 0.747-0.835),and the calibration curve and ideal curve fitted well.DCA showed that the net benefit interval of the model was 0.037-0.800.Conclusions:The nomogram prediction model based on independent risk factors for the recurrence of platinum-resistance of AEOC patients has good discrimination,calibration and clinical appli-cability,which can better predict the recurrence risk of platinum-resistance in AEOC patients after the initial treat-ment.

Objective:To analyze the influencing factors of platinum resistant recurrence in advanced epithelial ovarian cancer(AEOC),establish a nomogram model to predict platinum-resistant recurrence of AEOC,and inter-nally validate it.Methods:The clinicopathological data of 577 AEOC patients who achieved complete remission af-ter initial treatment in the Department of Gynecology,Yunnan Cancer Hospital from June 1,2013 to December 31,2021 were collected.According to whether the platinum free interval(PFI)was less than 6 months,the patients were divided into platinum-resistant recurrence group(130 cases)and non-platinum-resistant group(447 cases,including patients with platinum-sensitive recurrence and no recurrence after 6 months of follow-up).Multivariate Logistic regression analysis was used to screen for the independent risk factors affecting the recurrence of plati-num-resistant patients.Based on the independent risk factors,a nomogram prediction model was established,and Bootstrap method was used for internal verification.The area under the ROC curve(AUC),calibration curve and decision curve(DCA)were used to evaluate the performance of the model.Results:①There were statistically sig-nificant differences in age,bilateral ovarian invasion,FIGO staging,menopause,neoadjuvant chemotherapy(NACT),chemotherapy interval(TTC),platelet count(PLT),platelet count/lymphocyte count ratio(PLR),fibrino-gen/lymphocyte count ratio(FLR),prognostic nutritional index(PNI),albumin(ALB),CA125 level,ascites volume,residual lesions,perioperative chemotherapy frequency,and CA125 half-life between the two groups(P＜0.05).②Multivariate Logistic regression analysis showed that bilateral ovarian invasion,FIGO stage Ⅳ,TTC＞16 days,ini-tial ascites volume＞1000ml,perioperative chemotherapy frequency＞9 times,surgery with R2 resection,CA125 half-life＞52 days were independent risk factors for recurrence of platinum-resistant AEOC patients(OR＞1,P＜0.05).③The AUC of the nomogram model constructed based on the above 7 indicators was 0.791(95％Cl 0.747-0.835),and the calibration curve and ideal curve fitted well.DCA showed that the net benefit interval of the model was 0.037-0.800.Conclusions:The nomogram prediction model based on independent risk factors for the recurrence of platinum-resistance of AEOC patients has good discrimination,calibration and clinical appli-cability,which can better predict the recurrence risk of platinum-resistance in AEOC patients after the initial treat-ment.

Objective:To analyze the influencing factors of platinum resistant recurrence in advanced epithelial ovarian cancer(AEOC),establish a nomogram model to predict platinum-resistant recurrence of AEOC,and inter-nally validate it.Methods:The clinicopathological data of 577 AEOC patients who achieved complete remission af-ter initial treatment in the Department of Gynecology,Yunnan Cancer Hospital from June 1,2013 to December 31,2021 were collected.According to whether the platinum free interval(PFI)was less than 6 months,the patients were divided into platinum-resistant recurrence group(130 cases)and non-platinum-resistant group(447 cases,including patients with platinum-sensitive recurrence and no recurrence after 6 months of follow-up).Multivariate Logistic regression analysis was used to screen for the independent risk factors affecting the recurrence of plati-num-resistant patients.Based on the independent risk factors,a nomogram prediction model was established,and Bootstrap method was used for internal verification.The area under the ROC curve(AUC),calibration curve and decision curve(DCA)were used to evaluate the performance of the model.Results:①There were statistically sig-nificant differences in age,bilateral ovarian invasion,FIGO staging,menopause,neoadjuvant chemotherapy(NACT),chemotherapy interval(TTC),platelet count(PLT),platelet count/lymphocyte count ratio(PLR),fibrino-gen/lymphocyte count ratio(FLR),prognostic nutritional index(PNI),albumin(ALB),CA125 level,ascites volume,residual lesions,perioperative chemotherapy frequency,and CA125 half-life between the two groups(P＜0.05).②Multivariate Logistic regression analysis showed that bilateral ovarian invasion,FIGO stage Ⅳ,TTC＞16 days,ini-tial ascites volume＞1000ml,perioperative chemotherapy frequency＞9 times,surgery with R2 resection,CA125 half-life＞52 days were independent risk factors for recurrence of platinum-resistant AEOC patients(OR＞1,P＜0.05).③The AUC of the nomogram model constructed based on the above 7 indicators was 0.791(95％Cl 0.747-0.835),and the calibration curve and ideal curve fitted well.DCA showed that the net benefit interval of the model was 0.037-0.800.Conclusions:The nomogram prediction model based on independent risk factors for the recurrence of platinum-resistance of AEOC patients has good discrimination,calibration and clinical appli-cability,which can better predict the recurrence risk of platinum-resistance in AEOC patients after the initial treat-ment.

Objective:To analyze the influencing factors of platinum resistant recurrence in advanced epithelial ovarian cancer(AEOC),establish a nomogram model to predict platinum-resistant recurrence of AEOC,and inter-nally validate it.Methods:The clinicopathological data of 577 AEOC patients who achieved complete remission af-ter initial treatment in the Department of Gynecology,Yunnan Cancer Hospital from June 1,2013 to December 31,2021 were collected.According to whether the platinum free interval(PFI)was less than 6 months,the patients were divided into platinum-resistant recurrence group(130 cases)and non-platinum-resistant group(447 cases,including patients with platinum-sensitive recurrence and no recurrence after 6 months of follow-up).Multivariate Logistic regression analysis was used to screen for the independent risk factors affecting the recurrence of plati-num-resistant patients.Based on the independent risk factors,a nomogram prediction model was established,and Bootstrap method was used for internal verification.The area under the ROC curve(AUC),calibration curve and decision curve(DCA)were used to evaluate the performance of the model.Results:①There were statistically sig-nificant differences in age,bilateral ovarian invasion,FIGO staging,menopause,neoadjuvant chemotherapy(NACT),chemotherapy interval(TTC),platelet count(PLT),platelet count/lymphocyte count ratio(PLR),fibrino-gen/lymphocyte count ratio(FLR),prognostic nutritional index(PNI),albumin(ALB),CA125 level,ascites volume,residual lesions,perioperative chemotherapy frequency,and CA125 half-life between the two groups(P＜0.05).②Multivariate Logistic regression analysis showed that bilateral ovarian invasion,FIGO stage Ⅳ,TTC＞16 days,ini-tial ascites volume＞1000ml,perioperative chemotherapy frequency＞9 times,surgery with R2 resection,CA125 half-life＞52 days were independent risk factors for recurrence of platinum-resistant AEOC patients(OR＞1,P＜0.05).③The AUC of the nomogram model constructed based on the above 7 indicators was 0.791(95％Cl 0.747-0.835),and the calibration curve and ideal curve fitted well.DCA showed that the net benefit interval of the model was 0.037-0.800.Conclusions:The nomogram prediction model based on independent risk factors for the recurrence of platinum-resistance of AEOC patients has good discrimination,calibration and clinical appli-cability,which can better predict the recurrence risk of platinum-resistance in AEOC patients after the initial treat-ment.

Background::The Global Leadership Initiative on Malnutrition (GLIM) criteria were published to build a global consensus on nutritional diagnosis. Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria. However, there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings. This study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition, as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic patients.Methods::This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1, 2018, and February 28, 2022, at Beijing You-An Hospital, Capital Medical University. Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography (CT) examination during hospitalization were included in the study. These patients were randomly divided into a modeling group (cohort 1, 667 patients) and a validation group (cohort 2, 335 patients). In cohort 1, optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index (L3-SMI) were determined using receiver operating characteristic analyses against in-hospital mortality in different gender groups. Next, patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. Additionally, the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1. Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes.Results::The optimal cut-off values of L3-SMI were 39.50 cm 2/m 2 for male patients and 33.06 cm 2/m 2 for female patients. Based on the cut-off values, 31.63% (68/215) of the male patients and 23.3% (28/120) of the female patients had CT-determined sarcopenia in cohort 2. The prevalence of GLIM-defined malnutrition in cirrhotic patients was 34.3% (115/335) and GLIM-defined malnutrition was an independent risk factor for in-hospital mortality in patients with liver cirrhosis ( Wald = 6.347, P = 0.012). Conclusions::This study provided reference values for skeletal muscle mass index and the prevalence of GLIM-defined malnutrition in hospitalized patients with liver cirrhosis. These reference values will contribute to applying the GLIM criteria in cirrhotic patients.