Background:N-Alkylamides(NAAs),derived from Anacyclus pyrethrum(L.)DC,have potential anti-tumor effects.To explore the molecular mechanism and chemo-preventive capacity of NAAs,we synthesized an NAA(H-10)and evaluated...Background:N-Alkylamides(NAAs),derived from Anacyclus pyrethrum(L.)DC,have potential anti-tumor effects.To explore the molecular mechanism and chemo-preventive capacity of NAAs,we synthesized an NAA(H-10)and evaluated whether it could inhibit the proliferation of B16,HepG2,HeLa,and HCT116 cancer cells in 2D culture.Methods:To evaluate the antiproliferative activity of H-10 in 2D and 3D culture of BD,HepG2,HeLa,and HCT116 cells,multicellular tumor spheroids were constructed to more accurately reflect the cell tumor environment.To visualize nuclear changes related to apoptosis,Hoechst 33258 staining and propidium iodide-Annexin V double staining were performed.Results:Compound H-10 strongly inhibited the growth of all tested cell lines.Hoechst 33258 staining and propidium iodide-Annexin V double staining revealed that H-10 did not cause morphological alterations in the nuclei and moderately induced late apoptosis only when treated at 180 mM.The strongest inhibitory effect was observed in HCT116 cells.Flow cytometry analysis indicated that treatment of HCT116 cells with compound H-10 resulted in robust cell growth arrest in G2 phase in 2D and 3D cell culture;in 3D-cultured HCT116 cells,growth arrest occurred in G1 phase.Treatment with compound H-10 also significantly suppressed angiogenesis of chick chorioallantoic membrane in vivo.Conclusion:Treatment with compound H-10 strongly affected clonogenic survival(in the long-term)and migration of HCT116 cells.Therefore,H-10,a compound of NAAs may be useful for treating cancer because of its anti-neoplastic effect and easy synthesis.展开更多
Background:Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia.We compared the effects of acarbose and sitagliptin add ...Background:Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia.We compared the effects of acarbose and sitagliptin add on to metformin on time in range(TIR)and glycemic variability(GV)in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring(CGM).Methods:This study was a randomized,open-label,active-controlled,parallel-group trial conducted at 15 centers in China from January 2020 to August 2022.We recruited patients with type 2 diabetes aged 18–65 years with body mass index(BMI)within 19–40 kg/m 2 and hemoglobin A1c(HbA1c)between 6.5%and 9.0%.Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days.After the first 14-day treatment period,patients wore CGM and entered another 14-day treatment period.The primary outcome was the level of TIR after treatment between groups.We also performed time series decomposition,dimensionality reduction,and clustering using the CGM data.Results:A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin.There was no statistically significant difference in TIR between the two groups.Time below range(TBR)and coefficient of variation(CV)levels in acarbose users were significantly lower than those in sitagliptin users.Median(25th percentile,75th percentile)of TBR below target level<3.9 mmol/L(TBR 3.9):Acarbose:0.45%(0,2.13%)vs.Sitagliptin:0.78%(0,3.12%),P=0.042;Median(25th percentile,75th percentile)of TBR below target level<3.0 mmol/L(TBR 3.0):Acarbose:0(0,0.22%)vs.Sitagliptin:0(0,0.63%),P=0.033;CV:Acarbose:22.44±5.08%vs.Sitagliptin:23.96±5.19%,P<0.001.By using time series analysis and clustering,we distinguished three groups of patients with representative metabolism characteristics,especially in GV(group with small wave,moderate wave and big wave).No significant difference was found in the complexity of glucose time series index(CGI)between acarbose users and sitagliptin users.By using time series analysis and clustering,we distinguished three groups of patients with representative metabolism characteristics,especially in GV.Conclusions:Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia.Time series analysis of CGM data may predict GV and the risk of hypoglycemia.Trial Registration:Chinese Clinical Trial Registry:ChiCTR2000039424.展开更多
Objectives:To establish Nomogram to predict the overall survival(OS)rate of pancreatic cancer patients with lung metastasis by utilizing the database of the Surveillance,Epidemiology,and End Results(SEER)Program.Metho...Objectives:To establish Nomogram to predict the overall survival(OS)rate of pancreatic cancer patients with lung metastasis by utilizing the database of the Surveillance,Epidemiology,and End Results(SEER)Program.Methods:We obtained the data of 363 pancreatic cancer patients with lung metastasis who were diagnosed between 2010 and 2016 from the SEER database.These patients were randomly divided into training(n=255)and validation(n=108)cohorts.The Cox proportional hazards regression model was performed to evaluate the prognostic effects of multiple clinicopathologic factors on OS.Significant prognostic factors were combined to build Nomogram.The predictive performance of Nomogram was evaluated via internal(training cohort data)and external validation(validation cohort data)by calculating index of concordance(C-index)and plotting area under curve(AUC)and calibration curves.All data from SEER database have been fully de-identified and may be used without further independent ethics committee approval.Results:In the training cohort,the results of Cox proportional hazards regression model showed that,tumor location,surgery,chemotherapy and other organ of metastasis were significantly associated with the survival prognosis(P<.05).These factors were used to establish Nomogram.The Nomogram showed good accuracy in predicting OS rate,with C-index of 0.727[95%CI was(0.689,0.764)]in internal validation and C-index of 0.738[95%CI was(0.679,0.796)]in external validation.All calibration curves showed excellent consistency between prediction by Nomogram and actual observation.Conclusion:Novel Nomogram for pancreatic cancer patients with lung metastasis was established to predict OS in our study.It has good prognostic significance.And it could provide the clinicians with more accurate and practical predictive tools which can quickly and accurately assess the patients’survival prognosis individually,and make clinical suggestion for doctors in the follow-up treatment of patients.展开更多
基金This study was supported by The Natural Science Foundation of the Xinjiang Uygur Autonomous Region(201318101-5).
文摘Background:N-Alkylamides(NAAs),derived from Anacyclus pyrethrum(L.)DC,have potential anti-tumor effects.To explore the molecular mechanism and chemo-preventive capacity of NAAs,we synthesized an NAA(H-10)and evaluated whether it could inhibit the proliferation of B16,HepG2,HeLa,and HCT116 cancer cells in 2D culture.Methods:To evaluate the antiproliferative activity of H-10 in 2D and 3D culture of BD,HepG2,HeLa,and HCT116 cells,multicellular tumor spheroids were constructed to more accurately reflect the cell tumor environment.To visualize nuclear changes related to apoptosis,Hoechst 33258 staining and propidium iodide-Annexin V double staining were performed.Results:Compound H-10 strongly inhibited the growth of all tested cell lines.Hoechst 33258 staining and propidium iodide-Annexin V double staining revealed that H-10 did not cause morphological alterations in the nuclei and moderately induced late apoptosis only when treated at 180 mM.The strongest inhibitory effect was observed in HCT116 cells.Flow cytometry analysis indicated that treatment of HCT116 cells with compound H-10 resulted in robust cell growth arrest in G2 phase in 2D and 3D cell culture;in 3D-cultured HCT116 cells,growth arrest occurred in G1 phase.Treatment with compound H-10 also significantly suppressed angiogenesis of chick chorioallantoic membrane in vivo.Conclusion:Treatment with compound H-10 strongly affected clonogenic survival(in the long-term)and migration of HCT116 cells.Therefore,H-10,a compound of NAAs may be useful for treating cancer because of its anti-neoplastic effect and easy synthesis.
文摘Background:Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia.We compared the effects of acarbose and sitagliptin add on to metformin on time in range(TIR)and glycemic variability(GV)in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring(CGM).Methods:This study was a randomized,open-label,active-controlled,parallel-group trial conducted at 15 centers in China from January 2020 to August 2022.We recruited patients with type 2 diabetes aged 18–65 years with body mass index(BMI)within 19–40 kg/m 2 and hemoglobin A1c(HbA1c)between 6.5%and 9.0%.Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days.After the first 14-day treatment period,patients wore CGM and entered another 14-day treatment period.The primary outcome was the level of TIR after treatment between groups.We also performed time series decomposition,dimensionality reduction,and clustering using the CGM data.Results:A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin.There was no statistically significant difference in TIR between the two groups.Time below range(TBR)and coefficient of variation(CV)levels in acarbose users were significantly lower than those in sitagliptin users.Median(25th percentile,75th percentile)of TBR below target level<3.9 mmol/L(TBR 3.9):Acarbose:0.45%(0,2.13%)vs.Sitagliptin:0.78%(0,3.12%),P=0.042;Median(25th percentile,75th percentile)of TBR below target level<3.0 mmol/L(TBR 3.0):Acarbose:0(0,0.22%)vs.Sitagliptin:0(0,0.63%),P=0.033;CV:Acarbose:22.44±5.08%vs.Sitagliptin:23.96±5.19%,P<0.001.By using time series analysis and clustering,we distinguished three groups of patients with representative metabolism characteristics,especially in GV(group with small wave,moderate wave and big wave).No significant difference was found in the complexity of glucose time series index(CGI)between acarbose users and sitagliptin users.By using time series analysis and clustering,we distinguished three groups of patients with representative metabolism characteristics,especially in GV.Conclusions:Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia.Time series analysis of CGM data may predict GV and the risk of hypoglycemia.Trial Registration:Chinese Clinical Trial Registry:ChiCTR2000039424.
基金financially supported by the National Natural Science Foundation of China(NSFC 81872008 to ZW and NSFC 8207102675 to ZW)the Science and Technology Innovation as a Whole Plan Projects of Shaanxi Province,China(No.2016KJZDSF01-05-01).
文摘Objectives:To establish Nomogram to predict the overall survival(OS)rate of pancreatic cancer patients with lung metastasis by utilizing the database of the Surveillance,Epidemiology,and End Results(SEER)Program.Methods:We obtained the data of 363 pancreatic cancer patients with lung metastasis who were diagnosed between 2010 and 2016 from the SEER database.These patients were randomly divided into training(n=255)and validation(n=108)cohorts.The Cox proportional hazards regression model was performed to evaluate the prognostic effects of multiple clinicopathologic factors on OS.Significant prognostic factors were combined to build Nomogram.The predictive performance of Nomogram was evaluated via internal(training cohort data)and external validation(validation cohort data)by calculating index of concordance(C-index)and plotting area under curve(AUC)and calibration curves.All data from SEER database have been fully de-identified and may be used without further independent ethics committee approval.Results:In the training cohort,the results of Cox proportional hazards regression model showed that,tumor location,surgery,chemotherapy and other organ of metastasis were significantly associated with the survival prognosis(P<.05).These factors were used to establish Nomogram.The Nomogram showed good accuracy in predicting OS rate,with C-index of 0.727[95%CI was(0.689,0.764)]in internal validation and C-index of 0.738[95%CI was(0.679,0.796)]in external validation.All calibration curves showed excellent consistency between prediction by Nomogram and actual observation.Conclusion:Novel Nomogram for pancreatic cancer patients with lung metastasis was established to predict OS in our study.It has good prognostic significance.And it could provide the clinicians with more accurate and practical predictive tools which can quickly and accurately assess the patients’survival prognosis individually,and make clinical suggestion for doctors in the follow-up treatment of patients.
