Objective:Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro.This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with ...Objective:Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro.This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with hormone receptor positive(HR+)/human epidermal growth factor receptor-2-negative(HER2−)recurrent or metastatic breast cancer.Methods:Patients were intramuscularly administered fulvestrant 500 mg(day 1 per cycle for 28 days)and oral vinorelbine(60 mg/m2 on days 1,8,and 15 of each cycle).The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival,objective response rate,disease control rate,duration of response,and safety.Results:A total of 38 patients with HR+/HER2−advanced breast cancer included in the study were followed up for a median time of 25.1 months.The overall median PFS was 9.86 months[95%confidence interval(CI)7.2-23.13],and the median PFS of the first-line and the second-line treatment population was 20.73 months(95%CI 9.82 to NR)and 4.27 months(95%CI 3.68 to NR),respectively.Most adverse events reported were of grade 1/2,and none were of grade 4/5.Conclusions:This is the first exploratory study of a fulvestrant and oral vinorelbine regimen in the treatment of HR+/HER2−recurrent and metastatic breast cancer.The combination chemo-endocrine therapy was efficacious,safe,and promising for patients with HR+/HER2−advanced breast cancer.展开更多
Number and quantities of reference standards (RS) needed for the quality control of drugs are increasing, bringing great pressure to the calibration and using company. This manuscript summarized the four generations f...Number and quantities of reference standards (RS) needed for the quality control of drugs are increasing, bringing great pressure to the calibration and using company. This manuscript summarized the four generations for the development of RS including physical RS, paper atlas, substitute RS and electronic databases. The advantages and disadvantages of each generation were summarized. The concept of digital RS (DRS) was proposed based on this, and summed up the definition, advantages, and technical architecture of DRS. The 10 characteristics of five aspects of the DRS were discussed including digital, multi-dimension, big data, cloud computing, internet, internet of things, sharing, multi-terminal, intelligence, and compliance certification. Then, the necessity of its formation and application in the medicine holistic quality control of internet plus era was discussed in this manuscript.展开更多
Acute respiratory distress syndrome(ARDS)is one of the most fatal diseases worldwide.Pulmonary fibrosis occurs early in ARDS,and its severity plays a crucial role in ARDS mortality rate.Some studies suggested that fib...Acute respiratory distress syndrome(ARDS)is one of the most fatal diseases worldwide.Pulmonary fibrosis occurs early in ARDS,and its severity plays a crucial role in ARDS mortality rate.Some studies suggested that fibroproliferation is an essential mechanism in ARDS.Mitofusion2(Mfn2)overexpression plays a role in inhibiting cell proliferation.However,the role and potential mechanism of Mfn2 on the proliferation of fibroblasts is still unknown.In this study,we aimed at exploring the effect of Mfn2 on the human embryonic lung fibroblasts(HELF)and discussed its related mechanism.The HELF were treated with the Mfn2 overexpressing lentivirus(adv-Mfn2).The cell cycle was detected by flow cytometry.MTT,PCR and Western blotting were used to investigate the effect of Mfn2 on the proliferation of the HELF,collagen expression,the RAS-RAF-1-ERK1/2 pathway and the expression of cycle-related proteins(p21,p27,Rb,Raf-1,p-Raf-1,Erk1/2 and p-Erk1/2).The co-immunoprecipitation assay was used to explore the interaction between Mfn2 and Ras.The results showed that the overexpression of Mfn2 inhibited the proliferation of the HELF and induced the cell cycle arrest at the G0/G1 phase.Meanwhile,Mfn2 also inhibited the expression of collagen I,p-Erk and p-Raf-1.In addition,an interaction between Mfn2 and Ras existed in the HELF.This study suggests that the overexpression of Mfn2 can decrease the proliferation of HELF in ARDS,which was associated with the inhibition of the RAS-RAF-1-ERK1/2 pathway.The results may offer a potential therapeutic intervention for patients with ARDS.展开更多
Objective This study was conducted to examine the absorption and translocation of conjugated bile acids(BAs)in Calculus bovis and its substitutes to detect differences in these materials.Methods A Caco-2 monolayer cel...Objective This study was conducted to examine the absorption and translocation of conjugated bile acids(BAs)in Calculus bovis and its substitutes to detect differences in these materials.Methods A Caco-2 monolayer cell model was used to compare the apparent permeability coefficient(Papp)value and efflux ratio(ER)of BAs in natural cow-bezoar(NCB),artificial cow-bezoar(ACB),and in vitro cultured cow-bezoar(Ivt-CCB).Papp and ER values were determined by liquid chromatography-mass spectrometry.Samples were separated on an analytical column.Results The distribution of BAs in NCB was significantly different from that in ACB and Ivt-CCB.The percentages of conjugated BAs were significantly higher in NCB than in the two substitutes.The distribution differences of conjugated and unconjugated BAs can be used to distinguish costly NCB from relatively inexpensive substitutes.Conclusion The transport characteristics of BAs in Ivt-CCB were more consistent with NCB than with ACB,even when the proportions of BAs in Ivt-CCB were closer to those of ACB.展开更多
The conductive polymer composites(CPCs) with highly efficient electromagnetic interference(EMI)shielding effectiveness(SE) are always accompanied with excessive reflectivity, which would cause serious secondary EMI po...The conductive polymer composites(CPCs) with highly efficient electromagnetic interference(EMI)shielding effectiveness(SE) are always accompanied with excessive reflectivity, which would cause serious secondary EMI pollution. In this regard, the significant reduction of EMI reflection of CPCs to alleviate secondary pollution is deemed to be very important. Herein, a promising cyanate ester(CE) based composite was successfully fabricated by compounding carbonized spent coffee grounds(C-SCG) and graphene nanosheets(GNSs) via a facile solution blending followed by a hot-pressing method. Benefiting from the porous structure of C-SCG and the layered structure of GNSs, a three-dimensional(3 D)multi-interface conductive network in the CE was easily constructed. The EMI SE of the resultant 9 wt%C-SCG/CE composite(C9) is 15.38 d B and dramatically enhanced to 31.09 d B with the presence of 3 wt% GNSs. The remarkable enhancement is mainly attributed to the formation of the efficient conductive pathways as well as the well-dispersion of the incorporated fillers. Meanwhile, the absorption-dominated shielding mechanism in the prepared composites gets benefit from the synergistic effect of porous C-SCG and lamellar GNSs, which effectively captures and attenuates electromagnetic waves. These encouraging findings extend the practical applications of porous biocarbon materials in EMI shielding field.展开更多
Background：Hypocretin （HCRT） signaling plays an important role in the pathogenesis of narcolepsy and can be significantly influenced by Chinese herbal therapy.Our previous study showed that xingshentongqiao decocti...Background：Hypocretin （HCRT） signaling plays an important role in the pathogenesis of narcolepsy and can be significantly influenced by Chinese herbal therapy.Our previous study showed that xingshentongqiao decoction （XSTQ） is clinically effective for the treatment of narcolepsy.To determine whether XSTQ improves narcolepsy by modulating HCRT signaling,we investigated its effects on SH-SY5Y cell proliferation,apoptosis,and HCRT receptor 1/2 （orexin receptor 1 [OXl R] and orexin receptor 2 [OX2R]） expression.The signaling pathways involved in these processes were also assessed.Methods：The effects of XSTQ on proliferation and apoptosis in SH-SY5Y cells were assessed using cell counting kit-8 and annexin V-fluorescein isothiocyanate assays.OX1R and OX2R expression was assessed by quantitative real-time polymerase chain reaction analysis.Western blotting for mitogen-activated protein kinase （MAPK） pathway activation was performed to further assess the signaling mechanism of XSTQ.Results：XSTQ reduced the proliferation and induced apoptosis of SH-SY5Y cells.This effect was accompanied by the upregulation of OX 1R and OX2R expression and the reduced phosphorylation of extracellular signal-regulated kinase （Erk） 1/2,p38 MAPK and c-Jun N-terminal kinase （JNK）.Conclusions：XSTQ inhibits proliferation and induces apoptosis in SH-SY5Y cells.XSTQ also promotes OX1R and OX2R expression.These effects are associated with the repression of the Erkl/2,p38 MAPK,and JNK signaling pathways.These results define a molecular mechanism for XSTQ in regulating HCRT and MAPK activation,which may explain its ability to treat narcolepsy.展开更多
基金supported by grants from the National Key R&D Program of China(Grant No.2018YFC0115204)the National Natural Science Foundation of China(Grant No.81672634)+3 种基金the Chinese Society of Clinical Oncology Foundation(Grant No.Y-2019AZMS-0377)the Beijing Medical Award Foundation(Grant No.YXJL-2020-0941-0763)Beijing Hope Run Special Fund of Cancer Foundation of China(Grant No.LC2019B16)Beijing Xisike Clinical Oncology Research Foundation(Grant No.Y-pirrefabre202101-0008).
文摘Objective:Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro.This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with hormone receptor positive(HR+)/human epidermal growth factor receptor-2-negative(HER2−)recurrent or metastatic breast cancer.Methods:Patients were intramuscularly administered fulvestrant 500 mg(day 1 per cycle for 28 days)and oral vinorelbine(60 mg/m2 on days 1,8,and 15 of each cycle).The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival,objective response rate,disease control rate,duration of response,and safety.Results:A total of 38 patients with HR+/HER2−advanced breast cancer included in the study were followed up for a median time of 25.1 months.The overall median PFS was 9.86 months[95%confidence interval(CI)7.2-23.13],and the median PFS of the first-line and the second-line treatment population was 20.73 months(95%CI 9.82 to NR)and 4.27 months(95%CI 3.68 to NR),respectively.Most adverse events reported were of grade 1/2,and none were of grade 4/5.Conclusions:This is the first exploratory study of a fulvestrant and oral vinorelbine regimen in the treatment of HR+/HER2−recurrent and metastatic breast cancer.The combination chemo-endocrine therapy was efficacious,safe,and promising for patients with HR+/HER2−advanced breast cancer.
文摘Number and quantities of reference standards (RS) needed for the quality control of drugs are increasing, bringing great pressure to the calibration and using company. This manuscript summarized the four generations for the development of RS including physical RS, paper atlas, substitute RS and electronic databases. The advantages and disadvantages of each generation were summarized. The concept of digital RS (DRS) was proposed based on this, and summed up the definition, advantages, and technical architecture of DRS. The 10 characteristics of five aspects of the DRS were discussed including digital, multi-dimension, big data, cloud computing, internet, internet of things, sharing, multi-terminal, intelligence, and compliance certification. Then, the necessity of its formation and application in the medicine holistic quality control of internet plus era was discussed in this manuscript.
基金This project was supported by Wuhan Medical Science Foundation of China(No.WX17B07,No.WX19A09,and No.WJ2019H324).
文摘Acute respiratory distress syndrome(ARDS)is one of the most fatal diseases worldwide.Pulmonary fibrosis occurs early in ARDS,and its severity plays a crucial role in ARDS mortality rate.Some studies suggested that fibroproliferation is an essential mechanism in ARDS.Mitofusion2(Mfn2)overexpression plays a role in inhibiting cell proliferation.However,the role and potential mechanism of Mfn2 on the proliferation of fibroblasts is still unknown.In this study,we aimed at exploring the effect of Mfn2 on the human embryonic lung fibroblasts(HELF)and discussed its related mechanism.The HELF were treated with the Mfn2 overexpressing lentivirus(adv-Mfn2).The cell cycle was detected by flow cytometry.MTT,PCR and Western blotting were used to investigate the effect of Mfn2 on the proliferation of the HELF,collagen expression,the RAS-RAF-1-ERK1/2 pathway and the expression of cycle-related proteins(p21,p27,Rb,Raf-1,p-Raf-1,Erk1/2 and p-Erk1/2).The co-immunoprecipitation assay was used to explore the interaction between Mfn2 and Ras.The results showed that the overexpression of Mfn2 inhibited the proliferation of the HELF and induced the cell cycle arrest at the G0/G1 phase.Meanwhile,Mfn2 also inhibited the expression of collagen I,p-Erk and p-Raf-1.In addition,an interaction between Mfn2 and Ras existed in the HELF.This study suggests that the overexpression of Mfn2 can decrease the proliferation of HELF in ARDS,which was associated with the inhibition of the RAS-RAF-1-ERK1/2 pathway.The results may offer a potential therapeutic intervention for patients with ARDS.
基金support from the Youth Development Research Foundation of NIFDC(2014A1)National Science and Technology Major Project(2017ZX09101002-002-008)the National Natural Science Foundation of China(No.81403171 and No.81603517)
文摘Objective This study was conducted to examine the absorption and translocation of conjugated bile acids(BAs)in Calculus bovis and its substitutes to detect differences in these materials.Methods A Caco-2 monolayer cell model was used to compare the apparent permeability coefficient(Papp)value and efflux ratio(ER)of BAs in natural cow-bezoar(NCB),artificial cow-bezoar(ACB),and in vitro cultured cow-bezoar(Ivt-CCB).Papp and ER values were determined by liquid chromatography-mass spectrometry.Samples were separated on an analytical column.Results The distribution of BAs in NCB was significantly different from that in ACB and Ivt-CCB.The percentages of conjugated BAs were significantly higher in NCB than in the two substitutes.The distribution differences of conjugated and unconjugated BAs can be used to distinguish costly NCB from relatively inexpensive substitutes.Conclusion The transport characteristics of BAs in Ivt-CCB were more consistent with NCB than with ACB,even when the proportions of BAs in Ivt-CCB were closer to those of ACB.
基金financial support from the National Natural Science Foundation of China (No. 51773167)the Natural Science Foundation of Shaanxi Province (No. 2019CGXNG-033)+2 种基金the Science and Technology Plan Project of Xi’an (Nos. 2019217814GXRC014CG015-GXYD14.7, and 2019217814GXRC014CG015-GXYD14.8)the China Postdoctoral Science Foundation (No. 2019M650268)the Opening Project of State Key Laboratory of Polymer Materials Engineering (Sichuan University) (No. sklpme2020-4-16)。
文摘The conductive polymer composites(CPCs) with highly efficient electromagnetic interference(EMI)shielding effectiveness(SE) are always accompanied with excessive reflectivity, which would cause serious secondary EMI pollution. In this regard, the significant reduction of EMI reflection of CPCs to alleviate secondary pollution is deemed to be very important. Herein, a promising cyanate ester(CE) based composite was successfully fabricated by compounding carbonized spent coffee grounds(C-SCG) and graphene nanosheets(GNSs) via a facile solution blending followed by a hot-pressing method. Benefiting from the porous structure of C-SCG and the layered structure of GNSs, a three-dimensional(3 D)multi-interface conductive network in the CE was easily constructed. The EMI SE of the resultant 9 wt%C-SCG/CE composite(C9) is 15.38 d B and dramatically enhanced to 31.09 d B with the presence of 3 wt% GNSs. The remarkable enhancement is mainly attributed to the formation of the efficient conductive pathways as well as the well-dispersion of the incorporated fillers. Meanwhile, the absorption-dominated shielding mechanism in the prepared composites gets benefit from the synergistic effect of porous C-SCG and lamellar GNSs, which effectively captures and attenuates electromagnetic waves. These encouraging findings extend the practical applications of porous biocarbon materials in EMI shielding field.
文摘Background：Hypocretin （HCRT） signaling plays an important role in the pathogenesis of narcolepsy and can be significantly influenced by Chinese herbal therapy.Our previous study showed that xingshentongqiao decoction （XSTQ） is clinically effective for the treatment of narcolepsy.To determine whether XSTQ improves narcolepsy by modulating HCRT signaling,we investigated its effects on SH-SY5Y cell proliferation,apoptosis,and HCRT receptor 1/2 （orexin receptor 1 [OXl R] and orexin receptor 2 [OX2R]） expression.The signaling pathways involved in these processes were also assessed.Methods：The effects of XSTQ on proliferation and apoptosis in SH-SY5Y cells were assessed using cell counting kit-8 and annexin V-fluorescein isothiocyanate assays.OX1R and OX2R expression was assessed by quantitative real-time polymerase chain reaction analysis.Western blotting for mitogen-activated protein kinase （MAPK） pathway activation was performed to further assess the signaling mechanism of XSTQ.Results：XSTQ reduced the proliferation and induced apoptosis of SH-SY5Y cells.This effect was accompanied by the upregulation of OX 1R and OX2R expression and the reduced phosphorylation of extracellular signal-regulated kinase （Erk） 1/2,p38 MAPK and c-Jun N-terminal kinase （JNK）.Conclusions：XSTQ inhibits proliferation and induces apoptosis in SH-SY5Y cells.XSTQ also promotes OX1R and OX2R expression.These effects are associated with the repression of the Erkl/2,p38 MAPK,and JNK signaling pathways.These results define a molecular mechanism for XSTQ in regulating HCRT and MAPK activation,which may explain its ability to treat narcolepsy.
