Objective:CDK4/6 inhibitors(CDK4/6is)in combination with endocrine therapy have secured a central role in the treatment of hormone receptor(HR)-positive advanced breast cancer(ABC)and have transformed the therapeutic ...Objective:CDK4/6 inhibitors(CDK4/6is)in combination with endocrine therapy have secured a central role in the treatment of hormone receptor(HR)-positive advanced breast cancer(ABC)and have transformed the therapeutic landscape.Cross-line CDK4/6i therapy in which another CDK4/6i is continued after progression on a prior CDK4/6i may still offer advantageous therapeutic effects.Cross-line CDK4/6i therapy is an area of active investigation in the ongoing pursuit to improve outcomes for patients with HR+/human epidermal growth factor receptor 2(HER2)–ABC.Methods:This retrospective study enrolled 82 patients with HR+/HER2–ABC who were treated with cross-line CDK4/6is(abemaciclib,palbociclib,ribociclib,and dalpiciclib)after progression with another CDK4/6i.The primary endpoint was progression-free survival(PFS)according to version 1.1 of the Response Evaluation Criteria in Solid Tumors.Secondary endpoints included toxicity,objective response rate,disease control rate,and overall survival.Adverse events(AEs)were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events,as promulgated by the U.S.Department of Health and Human Services.Results:Eighty-two HR+/HER2–ABC patients who received cross-line CDK4/6i therapy from January 2022 to February 2024 were enrolled.The median age of the patients was 60 years.The median PFS of all patients was 7.6 months(95%CI,5.9-9.2).Cox regression analysis identified lung metastasis and a switch to endocrine therapy following prior CDK4/6i therapy as independent predictive factors for PFS.Notably,patients who previously received abemaciclib and switched to palbociclib upon disease progression had a median PFS of 10.7 months.The strategy of transitioning to chemotherapy after progression on a prior CDK4/6i,then to a subsequent CDK4/6i merits further investigation.Hematologic toxicity was the most common grade≥3 AEs.No instances of fatal safety events were observed.Conclusions:Cross-line CDK4/6i therapy is associated with significant clinical benefits and manageable safety profiles in patients with HR+/HER2–ABC,which underscores cross-line CDK4/6i therapy potential as an effective treatment strategy.展开更多
Objective:This study aimed to investigate the effects of TH/CTS/β-CD microspheres by oral administration on ovalbumin allergic asthma of a rat model.Methods:Spray drying method was applied for preparing the TH/CTS/β...Objective:This study aimed to investigate the effects of TH/CTS/β-CD microspheres by oral administration on ovalbumin allergic asthma of a rat model.Methods:Spray drying method was applied for preparing the TH/CTS/β-CD microspheres,which were used in treatment of asthmatic rats.At a predetermined time,the levels of eosinophil(Eos),protein,lactate dehydrogenase(LDH),aspartate transaminase(AST),glutamic pyruvic transaminase(GPT),and creatinine(Cr)were ascertained by automatic hematology and biochemical analyzers.Lung tissue histology was performed by hematoxylin-eosin staining.Results:No significant differences were found about the contents of Eos in the blood,and the contents of Eos,protein and LDH in the bronchoalveolar lavage fluid between the microsphere-treated and dexamethasone-treated groups,but the levels were lower in both treated groups than in the model group.In the microsphere-treated group,the levels of Cr,AST,and GPT in the serum of rats showed no significant differences compared with the normal group.Based on lung histopathological findings,the microspheres attenuated inflammatory cell infiltration and mucus hypersecretion compared with the model group.Conclusion:This study demonstrated that TH/CTS/β-CD microspheres exerted an anti-inflammatory effect and could serve as a novel promising drug delivery system for asthma treatment.展开更多
Hepatitis B virus(HBV)represents the commonest etiologic agent of acute-on-chronic liver failure(ACLF)in most Asian countries.Nucleos(t)ide analogs(NAs)are effective in the treatment of chronic HBV infections,but may ...Hepatitis B virus(HBV)represents the commonest etiologic agent of acute-on-chronic liver failure(ACLF)in most Asian countries.Nucleos(t)ide analogs(NAs)are effective in the treatment of chronic HBV infections,but may also exacerbate the disease and stimulate its development into HBV-associated ACLF if not used appropriately.The current study aimed to assess the prevalence and severity of HBV-associated ACLF as a result from irregular medication of NAs(IMNA).A total of 1134 individuals with HBV-associated ACLF in nine hospitals in Heilongjiang Province were enrolled in this study between 2005 and 2015.Among these,777 chronic hepatitis B(CHB)and 357 HBV-associated liver cirrhosis cases were classified based on various predisposing factors,including IMNA,HBV reactivation(HBVR),infections,treatment drugs,alcohol use and others(hepatitis C virus,hepatitis E virus,gastrointestinal bleeding and unknown reasons).The percentage and improvement rate were examined.Among individuals with HBV-associated ACLF and CHB,IMNA was found in 9.01%,HBVR in 46.20%,infections in 9.52%,treatment drugs in 14.67%,alcohol in 11.71%,and others in 24.58%as predisposing factors.Improvement rates in cases with IMNA,HBVR,infections,treatment drugs,alcohol and others were 41.43%,58.50%,58.11%,56.14%,53.85%,and 65.97%,respectively.Multivariable analysis showed that IMNA,others,infections,hepatic encephalopathy and hepatorenal syndrome were associated with prognosis.Only IMNA independently predicted HBV-associated ACLF prognosis.Overall,our study demonstrated that the percentage of IMNAinduced HBV-associated ACLF was 12.61%,and worse disease conditions resulted from IMNA compared with other factors.Thus,the suitability of treatment with NAs should be thoroughly evaluated.展开更多
Developing chemotherapy drugs with high efficacy and few side effects has been a bottleneck problem that requires an efficient solution.The active cancer treatment ingredient disulfiram(DSF),inspired by the copper(II)...Developing chemotherapy drugs with high efficacy and few side effects has been a bottleneck problem that requires an efficient solution.The active cancer treatment ingredient disulfiram(DSF),inspired by the copper(II)diethyldithiocarbamate complex(CuET),can be used in a one-pot synthesis method to construct a CuET delivery nanosystem(CuET-ZIFCu@HA).Due to the high biocompatibility,targeting of CD44 overexpressed cancer cells,and acid response of zeolitic imidazolate framework(ZIF)materials of hyaluronic acid(HA),we realized that CuET-ZIFCu@HA could become an effective and highly selective cancer treatment.Both in vivo and in vitro experiments have demonstrated that CuET-ZIFCu@HA has robust anti-tumor properties without evident side effects.This research provided a promising strategy for DSF nanosystems that involves simple preparation and high efficacy,both of which are key to reusing DSF in cancer treatment.展开更多
基金supported by grants from the CAMS Innovation Fund for Medical Sciences[CIFMS](Grant Nos.2021-I2M-1-014 and 2022-I2M-2-002).
文摘Objective:CDK4/6 inhibitors(CDK4/6is)in combination with endocrine therapy have secured a central role in the treatment of hormone receptor(HR)-positive advanced breast cancer(ABC)and have transformed the therapeutic landscape.Cross-line CDK4/6i therapy in which another CDK4/6i is continued after progression on a prior CDK4/6i may still offer advantageous therapeutic effects.Cross-line CDK4/6i therapy is an area of active investigation in the ongoing pursuit to improve outcomes for patients with HR+/human epidermal growth factor receptor 2(HER2)–ABC.Methods:This retrospective study enrolled 82 patients with HR+/HER2–ABC who were treated with cross-line CDK4/6is(abemaciclib,palbociclib,ribociclib,and dalpiciclib)after progression with another CDK4/6i.The primary endpoint was progression-free survival(PFS)according to version 1.1 of the Response Evaluation Criteria in Solid Tumors.Secondary endpoints included toxicity,objective response rate,disease control rate,and overall survival.Adverse events(AEs)were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events,as promulgated by the U.S.Department of Health and Human Services.Results:Eighty-two HR+/HER2–ABC patients who received cross-line CDK4/6i therapy from January 2022 to February 2024 were enrolled.The median age of the patients was 60 years.The median PFS of all patients was 7.6 months(95%CI,5.9-9.2).Cox regression analysis identified lung metastasis and a switch to endocrine therapy following prior CDK4/6i therapy as independent predictive factors for PFS.Notably,patients who previously received abemaciclib and switched to palbociclib upon disease progression had a median PFS of 10.7 months.The strategy of transitioning to chemotherapy after progression on a prior CDK4/6i,then to a subsequent CDK4/6i merits further investigation.Hematologic toxicity was the most common grade≥3 AEs.No instances of fatal safety events were observed.Conclusions:Cross-line CDK4/6i therapy is associated with significant clinical benefits and manageable safety profiles in patients with HR+/HER2–ABC,which underscores cross-line CDK4/6i therapy potential as an effective treatment strategy.
基金the foundation for visiting scholar abroad in Weifang Medical University,National Natural Science Foundation of China(No.81973671,81774125)Weifang Science and Technology Development Plan Project(2018YX060).
文摘Objective:This study aimed to investigate the effects of TH/CTS/β-CD microspheres by oral administration on ovalbumin allergic asthma of a rat model.Methods:Spray drying method was applied for preparing the TH/CTS/β-CD microspheres,which were used in treatment of asthmatic rats.At a predetermined time,the levels of eosinophil(Eos),protein,lactate dehydrogenase(LDH),aspartate transaminase(AST),glutamic pyruvic transaminase(GPT),and creatinine(Cr)were ascertained by automatic hematology and biochemical analyzers.Lung tissue histology was performed by hematoxylin-eosin staining.Results:No significant differences were found about the contents of Eos in the blood,and the contents of Eos,protein and LDH in the bronchoalveolar lavage fluid between the microsphere-treated and dexamethasone-treated groups,but the levels were lower in both treated groups than in the model group.In the microsphere-treated group,the levels of Cr,AST,and GPT in the serum of rats showed no significant differences compared with the normal group.Based on lung histopathological findings,the microspheres attenuated inflammatory cell infiltration and mucus hypersecretion compared with the model group.Conclusion:This study demonstrated that TH/CTS/β-CD microspheres exerted an anti-inflammatory effect and could serve as a novel promising drug delivery system for asthma treatment.
基金This work was supported by the National Science and Technology Major Project(2017ZX10202203-007-007,2017ZX10202203-008-007).
文摘Hepatitis B virus(HBV)represents the commonest etiologic agent of acute-on-chronic liver failure(ACLF)in most Asian countries.Nucleos(t)ide analogs(NAs)are effective in the treatment of chronic HBV infections,but may also exacerbate the disease and stimulate its development into HBV-associated ACLF if not used appropriately.The current study aimed to assess the prevalence and severity of HBV-associated ACLF as a result from irregular medication of NAs(IMNA).A total of 1134 individuals with HBV-associated ACLF in nine hospitals in Heilongjiang Province were enrolled in this study between 2005 and 2015.Among these,777 chronic hepatitis B(CHB)and 357 HBV-associated liver cirrhosis cases were classified based on various predisposing factors,including IMNA,HBV reactivation(HBVR),infections,treatment drugs,alcohol use and others(hepatitis C virus,hepatitis E virus,gastrointestinal bleeding and unknown reasons).The percentage and improvement rate were examined.Among individuals with HBV-associated ACLF and CHB,IMNA was found in 9.01%,HBVR in 46.20%,infections in 9.52%,treatment drugs in 14.67%,alcohol in 11.71%,and others in 24.58%as predisposing factors.Improvement rates in cases with IMNA,HBVR,infections,treatment drugs,alcohol and others were 41.43%,58.50%,58.11%,56.14%,53.85%,and 65.97%,respectively.Multivariable analysis showed that IMNA,others,infections,hepatic encephalopathy and hepatorenal syndrome were associated with prognosis.Only IMNA independently predicted HBV-associated ACLF prognosis.Overall,our study demonstrated that the percentage of IMNAinduced HBV-associated ACLF was 12.61%,and worse disease conditions resulted from IMNA compared with other factors.Thus,the suitability of treatment with NAs should be thoroughly evaluated.
基金the National Natural Science Foundation of China(Grant Nos.81774125 and 81973671)the Natural Science Foundation of Shandong Province(Grant No.ZR2019BB071)+1 种基金the Major Innovation and Technology Engineering Project of Shandong Province(Grant No.2019JZZY011106)the Science and Technology Innovation Fund for College Students of Weifang Medical University,and the Weifang Medical University-Sponsored Visiting Schola Research.
文摘Developing chemotherapy drugs with high efficacy and few side effects has been a bottleneck problem that requires an efficient solution.The active cancer treatment ingredient disulfiram(DSF),inspired by the copper(II)diethyldithiocarbamate complex(CuET),can be used in a one-pot synthesis method to construct a CuET delivery nanosystem(CuET-ZIFCu@HA).Due to the high biocompatibility,targeting of CD44 overexpressed cancer cells,and acid response of zeolitic imidazolate framework(ZIF)materials of hyaluronic acid(HA),we realized that CuET-ZIFCu@HA could become an effective and highly selective cancer treatment.Both in vivo and in vitro experiments have demonstrated that CuET-ZIFCu@HA has robust anti-tumor properties without evident side effects.This research provided a promising strategy for DSF nanosystems that involves simple preparation and high efficacy,both of which are key to reusing DSF in cancer treatment.
