BACKGROUND Colorectal cancer is a common digestive malignancy,and chemotherapy remains a cornerstone of treatment.Myelosuppression,a frequent hematologic toxicity,poses significant clinical challenges.However,no inter...BACKGROUND Colorectal cancer is a common digestive malignancy,and chemotherapy remains a cornerstone of treatment.Myelosuppression,a frequent hematologic toxicity,poses significant clinical challenges.However,no interpretable machine learning-based nomogram exists to predict chemotherapy-induced myelosuppression in colorectal cancer patients.This study aimed to develop and validate an inter-pretable clinic-machine learning nomogram integrating clinical predictors with multiple algorithms via a feature mapping algorithm.The model provides accurate risk estimation and clinical interpretability,supporting individualized prevention strategies and optimizing decision-making in patients receiving first-line chemotherapy.AIM To develop and validate an interpretable clinic-machine learning nomogram predicting chemotherapy-induced myelosuppression in colorectal cancer.METHODS This retrospective study enrolled 855 colorectal cancer patients receiving first-line chemotherapy.Data were split into training(n=612),validation(n=153),and testing(n=90)cohorts.Ten predictors were identified through least absolute shrinkage and selection operator,decision tree,random forest,and expert con-sensus.Ten machine learning algorithms were applied,with performance assessed by area under the receiver operating characteristic curve(AUC),area under the precision-recall curve(AUPRC),calibration,and decision curves.The optimal model was integrated into a clinic-machine learning nomogram via the feature mapping algorithm,which was internally validated for predictive accuracy and clinical utility.(AUPRC),calibration,and decision curves.The optimal model was integrated into a clinic-machine learning nomogram via the feature mapping algorithm,which was internally validated for predictive accuracy and clinical utility.RESULTS A total of 855 colorectal cancer patients were enrolled,with 765 cases(April 2020 to December 2023)used for model training and validation,and 90 cases(January 2024 to July 2024)for internal testing.Baseline clinical features did not differ significantly between training and validation cohorts(P>0.05).Ten predictors were identified through integrated feature selection and expert consensus,including age,body surface area,body mass index,tumor position,albumin,carcinoembryonic antigen,carbohydrate antigen(CA)19-9,CA125,chemotherapy regimen,and chemotherapy cycles.Among ten machine learning algorithms,extreme gradient boosting achieved the best validation performance(AUC=0.97,AUPRC=0.92,sensitivity=0.79,specificity=0.92,accuracy=0.88).Logistic regression confirmed extra trees and random forest as independent predictors,which were incorporated into a clinic-machine learning nomogram.The clinic-machine learning nomogram demonstrated superior discrimination(AUC=0.96,AUPRC=0.93,accuracy=0.90,specificity=0.95),good calibration,and greater net clinical benefit across a wide probability range(10%-90%).Internal testing further confirmed its robustness and generalizability(AUC=0.95).CONCLUSION The clinic-machine learning nomogram accurately predicts chemotherapy-induced myelosuppression in colorectal cancer,providing interpretability and clinical utility to support individualized risk assessment and treatment decision-making.展开更多
To investigate the mechanism by which ZrO_(2)modification affects the electrochemical performance of the NaNi_(1/3)Fe_(1/3)Mn_(1/3)O_(2)(NFM)cathode material for sodium-ion batteries,ZrO_(2)-coated NFM(ZrO_(2)@NFM)was...To investigate the mechanism by which ZrO_(2)modification affects the electrochemical performance of the NaNi_(1/3)Fe_(1/3)Mn_(1/3)O_(2)(NFM)cathode material for sodium-ion batteries,ZrO_(2)-coated NFM(ZrO_(2)@NFM)was prepared via high-temperature calcination.XRD refinement results revealed that ZrO_(2)modification increased the Na-layer spacing in the NFM material.XPS analysis results demonstrated that ZrO_(2)modification adjusted the Mn^(3+)/Mn^(4+)ratio in NFM by reducing the Mn^(3+)content.Electrochemical test results revealed that,compared to NFM,ZrO_(2)@NFM exhibited superior rate capability and cycling stability.It also exhibited significantly enhanced Na^(+)diffusion coefficients and reduced interfacial charge transfer resistance.The ZrO_(2)coating increased Na-layer spacing,reduced electrochemical polarization,and inhibited side reactions.In summary,the synergistic effect of component regulation and surface engineering through ZrO_(2)coating improved Na^(+)diffusion kinetics and enhanced cycling stability.展开更多
Natural products are the important sources in cardiovascular drug development.In this study,twenty-nine buthutin derivatives were designed,synthesized,and evaluated for their NHE-1 inhibition and protective effects on...Natural products are the important sources in cardiovascular drug development.In this study,twenty-nine buthutin derivatives were designed,synthesized,and evaluated for their NHE-1 inhibition and protective effects on cardiomyo-cyte injury.The structure of the newly synthesized compounds had been confirmed by 1H-NMR,13C-NMR,and HR-ESI-MS spectra.Among all target compounds at 1μM,compounds 9d,9f,9k,9m,and 9n,with a protection ratio exceeding 30%,exerted stronger protective effects on H9c2 cardiomyocyte than positive control dexrazoxane and buthutin A.Meanwhile,compounds 9k,9m,and 9o showed the significant NHE-1 inhibitory activities on H9c2 cardiomyocyte,all with a dpHi/min value less than 0.23.What is more,compounds 9k,9m,9o and buthutin A all exhibited the specificity on NHE-1 inhibition.Molecular modelling studies suggested the ability of compounds 9m and 9o to establish interactions with three hydrogen bonds to Asp267 and Glu346 of NHE-1,but also the ability with much lower CDOCKER energies than positive control cariporide and buthutin A.The structure-activity relationship(SAR)studies suggested that the presences of amide group,four-carbon linker,and para hydroxyl benzene ring were advantageous pharmacophores for above two pharmacological actions.This research would open new avenues for developing amide-guanidine-based cardioprotective agents.展开更多
Background: Cimetidine, an antagonist of histamine type II receptors, has shown protective effects against γ-rays or neutrons. However, there have been no reports on the effects of cimetidine against neutrons combine...Background: Cimetidine, an antagonist of histamine type II receptors, has shown protective effects against γ-rays or neutrons. However, there have been no reports on the effects of cimetidine against neutrons combined with γ-rays. This study was carried out to evaluate the protective effects of cimetidine on rats exposed to long-term, low-dose-rate neutron and γ-ray combined irradiation(n-γ LDR).Methods: Fifty male Sprague-Dawley(SD) rats were randomly divided into 5 groups: the normal control group, radiation model group, 20mg/(kg·d) cimetidine group, 80mg/(kg·d) cimetidine group and 160mg/(kg·d) cimetidine group(10 rats per group). Except for the normal control group, 40 rats were simultaneously exposed to fission neutrons(^(252)Cf, 0.085 m Gy/h) for 22 h every day and γ-rays(^(60)Co, 0.097Gy/h) for 1.03 h once every three days, and the cimetidine groups were administered intragastrically with cimetidine at doses of 20, 80 and 160mg/kg each day. Peripheral blood WBC of the rats was counted the day following exposure to γ-rays. The rats were anesthetized and sacrificed on the day following exposure to ^(252)Cf for 28 days. The spleen, thymus, testicle, liver and intestinal tract indexes were evaluated. The DNA content of bone marrow cells and concanavalin A(Con A)-induced lymphocyte proliferation were measured. The frequency of micronuclei in polychromatic erythrocytes(f MNPCEs), superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione peroxidase(GSH-Px) in the serum and liver tissues were detected.Results: The peripheral blood WBC in the cimetidine groups was increased significantly on the 8th day and the 26 th day compared with those in the radiation model group. The spleen, thymus and testicle indexes of the cimetidine groups were higher than those of the radiation model group. The DNA content of bone marrow cells and lymphocyte proliferation in the cimetidine groups were increased significantly, and fMNPCE was reduced 1.41-1.77 fold in cimetidine treated groups. The activities of SOD and GSH-Px in the cimetidine groups were increased significantly, and the content of MDA in the cimetidine groups was decreased significantly.Conclusions: The results suggested that cimetidine alleviated damage induced by long-term, low-dose-rate neutron and γ combined irradiation via antioxidation and immunomodulation. Cimetidine might be useful as a potent radioprotector for radiotherapy patients as well as for occupational exposure workers.展开更多
Aim: Diabetes mellitus is a metabolic disorder leading to hyperglycemia and exhibiting altered fat and protein metabolism. Diabetes altered cellular microenvironment caused myriad untoward effects. Periodontitis is ch...Aim: Diabetes mellitus is a metabolic disorder leading to hyperglycemia and exhibiting altered fat and protein metabolism. Diabetes altered cellular microenvironment caused myriad untoward effects. Periodontitis is chronic inflammatory disease. Diabetes and periodontitis had higher prevalence in populations. The objective studied the relationship between diabetes and periodontitis associated with cell apoptosis and the influence of diabetes enhanced inflammation on apoptosis and periodontitis. Methods: This paper studied and analyzed the papers which published in the worldwide associated with the influence of diabetes enhanced inflammation on cell apoptosis and periodontitis, and reviewed the probably mechanism associated with apoptosis. Results: Diabetes induced hyperglycemia enhanced inflammation related to cell apoptosis. Periodontitis had a higher morbidity on diabetes patients. Periodontal intervention may be benefit to controlling the diabetes. The bidirectional efficiency happened between diabetes and periodontitis. Anti-apoptotic and anti-inflammation option can improve the therapeutic effects on diabetes and periodontitis. The finding included following several aspects. 1) Advanced glycation end products enhanced inflammatory response;2) Hyperglycemia induced cell apoptosis;3) inflammatory cytokines caused cell apoptosis;4) Mutuality between cell apoptosis and periodontitis;5) Diabetes induce periodontitis and bone loss;6) Periodontitis induced insulin resistance. 7) TNFα induce prostaglandins elicited cell apoptosis;8) periodontal therapies had effects on diabetes. Conclusion: Diabetes can enhance inflamemation leading to apoptosis and periodontitis. Effective periodontal therapy and control glucose may produce better effects on diabetes or periodontitis. Further research required to investigate the bidirectional mechanism between diabetes and periodontitis.展开更多
CO2reservoirs are widely distributed within the Yingcheng Formation in the Songliao Basin, but the extreme horizontal heterogeneity of CO2content causes difficulties in the exploration and exploitation of methane. For...CO2reservoirs are widely distributed within the Yingcheng Formation in the Songliao Basin, but the extreme horizontal heterogeneity of CO2content causes difficulties in the exploration and exploitation of methane. Former studies have fully covered the lithology, structure, and distribution of the reservoirs high in CO2content, but few are reported about migration and accumulation of CO2. Using the East Changde Gas Field as an example, we studied the accumulation mechanisms of CO2 gas. Two original types of accumulation model are proposed in this study. The fault-controlled accumulation model refers to gas accumulation in the reservoir body that is cut by a basement fault(the West Xu Fault), allowing the hydrocarbon gas generated in the lower formation to migrate into the reservoir body through the fault, which results in a relatively lower CO2content. The volcanic conduit-controlled accumulation model refers to a reservoir body that is not cut by the basement fault, which prevents the hydrocarbon gas from being mixed in and leads to higher CO2contents. This conclusion provides useful theories for prediction of CO2distribution in similar basins and reservoirs.展开更多
基金Supported by the Beijing Municipal Natural Science Foundation,No.7252262High Level Chinese Medical Hospital Promotion Project,No.HLCMHPP2023085+2 种基金National Natural Science Foundation of China,No.82174463National Administration of Traditional Chinese Medicine,No.ZYYCXTD-C-C202205China Academy of Chinese Medical Sciences,No.CI2021A01804 and No.2022S469.
文摘BACKGROUND Colorectal cancer is a common digestive malignancy,and chemotherapy remains a cornerstone of treatment.Myelosuppression,a frequent hematologic toxicity,poses significant clinical challenges.However,no interpretable machine learning-based nomogram exists to predict chemotherapy-induced myelosuppression in colorectal cancer patients.This study aimed to develop and validate an inter-pretable clinic-machine learning nomogram integrating clinical predictors with multiple algorithms via a feature mapping algorithm.The model provides accurate risk estimation and clinical interpretability,supporting individualized prevention strategies and optimizing decision-making in patients receiving first-line chemotherapy.AIM To develop and validate an interpretable clinic-machine learning nomogram predicting chemotherapy-induced myelosuppression in colorectal cancer.METHODS This retrospective study enrolled 855 colorectal cancer patients receiving first-line chemotherapy.Data were split into training(n=612),validation(n=153),and testing(n=90)cohorts.Ten predictors were identified through least absolute shrinkage and selection operator,decision tree,random forest,and expert con-sensus.Ten machine learning algorithms were applied,with performance assessed by area under the receiver operating characteristic curve(AUC),area under the precision-recall curve(AUPRC),calibration,and decision curves.The optimal model was integrated into a clinic-machine learning nomogram via the feature mapping algorithm,which was internally validated for predictive accuracy and clinical utility.(AUPRC),calibration,and decision curves.The optimal model was integrated into a clinic-machine learning nomogram via the feature mapping algorithm,which was internally validated for predictive accuracy and clinical utility.RESULTS A total of 855 colorectal cancer patients were enrolled,with 765 cases(April 2020 to December 2023)used for model training and validation,and 90 cases(January 2024 to July 2024)for internal testing.Baseline clinical features did not differ significantly between training and validation cohorts(P>0.05).Ten predictors were identified through integrated feature selection and expert consensus,including age,body surface area,body mass index,tumor position,albumin,carcinoembryonic antigen,carbohydrate antigen(CA)19-9,CA125,chemotherapy regimen,and chemotherapy cycles.Among ten machine learning algorithms,extreme gradient boosting achieved the best validation performance(AUC=0.97,AUPRC=0.92,sensitivity=0.79,specificity=0.92,accuracy=0.88).Logistic regression confirmed extra trees and random forest as independent predictors,which were incorporated into a clinic-machine learning nomogram.The clinic-machine learning nomogram demonstrated superior discrimination(AUC=0.96,AUPRC=0.93,accuracy=0.90,specificity=0.95),good calibration,and greater net clinical benefit across a wide probability range(10%-90%).Internal testing further confirmed its robustness and generalizability(AUC=0.95).CONCLUSION The clinic-machine learning nomogram accurately predicts chemotherapy-induced myelosuppression in colorectal cancer,providing interpretability and clinical utility to support individualized risk assessment and treatment decision-making.
基金supported by the Central South University Innovation-Driven Research Programme,China(No.2023CXQD053)the National Natural Science Foundation of China(No.52274310)financial support from the Government of Chongzuo,Guangxi Zhuang Autonomous Region,China(No.FA20210713).
文摘To investigate the mechanism by which ZrO_(2)modification affects the electrochemical performance of the NaNi_(1/3)Fe_(1/3)Mn_(1/3)O_(2)(NFM)cathode material for sodium-ion batteries,ZrO_(2)-coated NFM(ZrO_(2)@NFM)was prepared via high-temperature calcination.XRD refinement results revealed that ZrO_(2)modification increased the Na-layer spacing in the NFM material.XPS analysis results demonstrated that ZrO_(2)modification adjusted the Mn^(3+)/Mn^(4+)ratio in NFM by reducing the Mn^(3+)content.Electrochemical test results revealed that,compared to NFM,ZrO_(2)@NFM exhibited superior rate capability and cycling stability.It also exhibited significantly enhanced Na^(+)diffusion coefficients and reduced interfacial charge transfer resistance.The ZrO_(2)coating increased Na-layer spacing,reduced electrochemical polarization,and inhibited side reactions.In summary,the synergistic effect of component regulation and surface engineering through ZrO_(2)coating improved Na^(+)diffusion kinetics and enhanced cycling stability.
基金supported by the National Natural Science Foundation of China(NSFC)Youth Project(No.82204397).
文摘Natural products are the important sources in cardiovascular drug development.In this study,twenty-nine buthutin derivatives were designed,synthesized,and evaluated for their NHE-1 inhibition and protective effects on cardiomyo-cyte injury.The structure of the newly synthesized compounds had been confirmed by 1H-NMR,13C-NMR,and HR-ESI-MS spectra.Among all target compounds at 1μM,compounds 9d,9f,9k,9m,and 9n,with a protection ratio exceeding 30%,exerted stronger protective effects on H9c2 cardiomyocyte than positive control dexrazoxane and buthutin A.Meanwhile,compounds 9k,9m,and 9o showed the significant NHE-1 inhibitory activities on H9c2 cardiomyocyte,all with a dpHi/min value less than 0.23.What is more,compounds 9k,9m,9o and buthutin A all exhibited the specificity on NHE-1 inhibition.Molecular modelling studies suggested the ability of compounds 9m and 9o to establish interactions with three hydrogen bonds to Asp267 and Glu346 of NHE-1,but also the ability with much lower CDOCKER energies than positive control cariporide and buthutin A.The structure-activity relationship(SAR)studies suggested that the presences of amide group,four-carbon linker,and para hydroxyl benzene ring were advantageous pharmacophores for above two pharmacological actions.This research would open new avenues for developing amide-guanidine-based cardioprotective agents.
基金supported by the Research Fund of National Science and Technology Major Project of China(No.2014ZX09J14103-07B)
文摘Background: Cimetidine, an antagonist of histamine type II receptors, has shown protective effects against γ-rays or neutrons. However, there have been no reports on the effects of cimetidine against neutrons combined with γ-rays. This study was carried out to evaluate the protective effects of cimetidine on rats exposed to long-term, low-dose-rate neutron and γ-ray combined irradiation(n-γ LDR).Methods: Fifty male Sprague-Dawley(SD) rats were randomly divided into 5 groups: the normal control group, radiation model group, 20mg/(kg·d) cimetidine group, 80mg/(kg·d) cimetidine group and 160mg/(kg·d) cimetidine group(10 rats per group). Except for the normal control group, 40 rats were simultaneously exposed to fission neutrons(^(252)Cf, 0.085 m Gy/h) for 22 h every day and γ-rays(^(60)Co, 0.097Gy/h) for 1.03 h once every three days, and the cimetidine groups were administered intragastrically with cimetidine at doses of 20, 80 and 160mg/kg each day. Peripheral blood WBC of the rats was counted the day following exposure to γ-rays. The rats were anesthetized and sacrificed on the day following exposure to ^(252)Cf for 28 days. The spleen, thymus, testicle, liver and intestinal tract indexes were evaluated. The DNA content of bone marrow cells and concanavalin A(Con A)-induced lymphocyte proliferation were measured. The frequency of micronuclei in polychromatic erythrocytes(f MNPCEs), superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione peroxidase(GSH-Px) in the serum and liver tissues were detected.Results: The peripheral blood WBC in the cimetidine groups was increased significantly on the 8th day and the 26 th day compared with those in the radiation model group. The spleen, thymus and testicle indexes of the cimetidine groups were higher than those of the radiation model group. The DNA content of bone marrow cells and lymphocyte proliferation in the cimetidine groups were increased significantly, and fMNPCE was reduced 1.41-1.77 fold in cimetidine treated groups. The activities of SOD and GSH-Px in the cimetidine groups were increased significantly, and the content of MDA in the cimetidine groups was decreased significantly.Conclusions: The results suggested that cimetidine alleviated damage induced by long-term, low-dose-rate neutron and γ combined irradiation via antioxidation and immunomodulation. Cimetidine might be useful as a potent radioprotector for radiotherapy patients as well as for occupational exposure workers.
文摘Aim: Diabetes mellitus is a metabolic disorder leading to hyperglycemia and exhibiting altered fat and protein metabolism. Diabetes altered cellular microenvironment caused myriad untoward effects. Periodontitis is chronic inflammatory disease. Diabetes and periodontitis had higher prevalence in populations. The objective studied the relationship between diabetes and periodontitis associated with cell apoptosis and the influence of diabetes enhanced inflammation on apoptosis and periodontitis. Methods: This paper studied and analyzed the papers which published in the worldwide associated with the influence of diabetes enhanced inflammation on cell apoptosis and periodontitis, and reviewed the probably mechanism associated with apoptosis. Results: Diabetes induced hyperglycemia enhanced inflammation related to cell apoptosis. Periodontitis had a higher morbidity on diabetes patients. Periodontal intervention may be benefit to controlling the diabetes. The bidirectional efficiency happened between diabetes and periodontitis. Anti-apoptotic and anti-inflammation option can improve the therapeutic effects on diabetes and periodontitis. The finding included following several aspects. 1) Advanced glycation end products enhanced inflammatory response;2) Hyperglycemia induced cell apoptosis;3) inflammatory cytokines caused cell apoptosis;4) Mutuality between cell apoptosis and periodontitis;5) Diabetes induce periodontitis and bone loss;6) Periodontitis induced insulin resistance. 7) TNFα induce prostaglandins elicited cell apoptosis;8) periodontal therapies had effects on diabetes. Conclusion: Diabetes can enhance inflamemation leading to apoptosis and periodontitis. Effective periodontal therapy and control glucose may produce better effects on diabetes or periodontitis. Further research required to investigate the bidirectional mechanism between diabetes and periodontitis.
基金founded by the S&T development project ‘‘Key Factors Controlling Accumulation in Old Petroleum System (No. 2016A-0206)’’ by the China National Petroleum Corporation
文摘CO2reservoirs are widely distributed within the Yingcheng Formation in the Songliao Basin, but the extreme horizontal heterogeneity of CO2content causes difficulties in the exploration and exploitation of methane. Former studies have fully covered the lithology, structure, and distribution of the reservoirs high in CO2content, but few are reported about migration and accumulation of CO2. Using the East Changde Gas Field as an example, we studied the accumulation mechanisms of CO2 gas. Two original types of accumulation model are proposed in this study. The fault-controlled accumulation model refers to gas accumulation in the reservoir body that is cut by a basement fault(the West Xu Fault), allowing the hydrocarbon gas generated in the lower formation to migrate into the reservoir body through the fault, which results in a relatively lower CO2content. The volcanic conduit-controlled accumulation model refers to a reservoir body that is not cut by the basement fault, which prevents the hydrocarbon gas from being mixed in and leads to higher CO2contents. This conclusion provides useful theories for prediction of CO2distribution in similar basins and reservoirs.
