Diabetes is a leading cause of mortality,morbidity and disability around the globe.In the past two decades,diabetes care has grown more complex as patients have received multi-component care.Recent studies have illumi...Diabetes is a leading cause of mortality,morbidity and disability around the globe.In the past two decades,diabetes care has grown more complex as patients have received multi-component care.Recent studies have illumined the complexity of drug therapy in patients with diabetes.A high level of drug utilization in diabetes patients has serious implications for quality of care,in terms of coordination of care,drug safety and access to care.Practitioners,researchers,payers and policy makers should be aware of these implications and incorporate the complexity of diabetes care into practice guidelines,benefit design and policy formulation to improve the quality of care.展开更多
A new type of implantable drug delivery devices （ DDD ） with complicated architectures were fubricated by three-dimensional printing technique, employing levofloxacin （LVFX） as a model drug. Processing parameters...A new type of implantable drug delivery devices （ DDD ） with complicated architectures were fubricated by three-dimensional printing technique, employing levofloxacin （LVFX） as a model drug. Processing parameters were optimized in riew of the layer thickness, spucing between printed lines, flow rate of liquid binder and the fast axis speed. The prepared DDD prototype consists of a double-layer structure, of which the upper region is a reservoir system and the lower region is a matrix one. The in vitro release test revealed that LVFX was released in a dual-puse pattern. This DDD may present a new strategy for the prophylaxis and treatment of diseases such as bone infection in the near future.展开更多
Metformin(Met)is a drug developed for the treatment of patients with typeⅡ diabetes.Recently,Met estimation in pharmaceutical formulations and human fluids has gained a growing interest.To extend requisite data that ...Metformin(Met)is a drug developed for the treatment of patients with typeⅡ diabetes.Recently,Met estimation in pharmaceutical formulations and human fluids has gained a growing interest.To extend requisite data that can be used to assessment of Met quantitatively based on charge-transfer(CT)complexation,the present study describes the synthesis and characterization of CT complexes that formed between drug Met and the organicπ-acceptors picric acid(PA),chloranilic acid(CLA),chloranil(CHL),7,7',8,8'-tetracyanoquinodimethane(TCNQ),and dichlorodicyanobenzoquinone(DDQ).The properties of the formed CT complexes were investigated by elemental,spectral(UV-visible,IR,and Raman spectroscopies),thermal(TG)and morphological(SEM)studies.IR results indicated that the complexation of Met with either PA or CLA acceptors occurs through proton transfer interaction,whereas its complexation with CHL,TCNQ,or DDQ acceptors occurs through n→π*interaction.展开更多
Three types of metal ions barium(Ⅱ),nickel(Ⅱ)and cerium(Ⅲ)complexity of ATN drug have been prepared and characterized using molar conductance method,FT-IR,electronic,and 1H-NMR analysis measurements.The chemical an...Three types of metal ions barium(Ⅱ),nickel(Ⅱ)and cerium(Ⅲ)complexity of ATN drug have been prepared and characterized using molar conductance method,FT-IR,electronic,and 1H-NMR analysis measurements.The chemical and physical results for all atenolol complexes are agreement with the speculated structures.For the divalent(Ba&Ni)and trivalent(Ce)metal atenolol a molar ratio 1∶2 was established.Qualitative chemical analysis showed that for the divalent metal complexes,the chloride ions are not involved in the complexes,suggesting that all of these complexes,[Ba(ATN)2]·2 H2O and[Ni(ATN)2(H2O)2]·4 H2O are neutral.However,for the cerium(Ⅲ)complex,[Ce(ATN)2(NO3)]·3 H2O,the nitrate group is existed inside the coordination sphere.ATN make astable metal complexity with barium(Ⅱ),nickel(Ⅱ)and cerium(Ⅲ)ions.Electronic absorption analysis of Atenolol give two fundamental peaks at 225 nm and 274 nm refers to variation in transition electrons of ligand,UV spectral analysis of the three complexity obtained give asymmetric broad band in the range 200~400 nm,the reults are convenient with the suggestion of metal-nitrogen and metal-oxygen bonds.The infrared analysis data proved that ATN act as bidentate ligand through the N atom of the-NH group and O atom of the deprotonated alcoholic OH group.Nickel(Ⅱ)and cerium(Ⅲ)complexity make six-coordinate geometry,whereas the barium(Ⅱ)complex exhibit four-coordinate geometry.Ni(Ⅱ)-ATN complex has an effective magnetic moment equal 3.12 B.M,that is assigned to octahedral structure.The 1H-NMR spectral results of Ba(Ⅱ)-ATN complexity give strong signal at^4.00 ppm due to protons of-CH2 that influenced by low degree due to complexity.These results confirm the position of chelation through the N atom of the-NH group and O atom of the deprotonated alcoholic OH group.展开更多
Objective:To study the characteristics and rules of medication regimen for patients with Liver insufficiency treated with Danshen Chuanxiongqin Injection.Methods:The inpatient information of Danshen Chuanxiongqin Inje...Objective:To study the characteristics and rules of medication regimen for patients with Liver insufficiency treated with Danshen Chuanxiongqin Injection.Methods:The inpatient information of Danshen Chuanxiongqin Injection with Liver insufficiency was extracted from the hospital information system(HIS)database of 12 Class A tertiary hospitals in China.Tabu search(TS)algorithm was used for obtaining sub-network and density matrix,matrix method or sociogram was used to show the relationship between different sub-networks,searching for core prescriptions of treatment options,associations and strong correlations between multiple drugs.Results:The treatment plan of integrated Chinese and Western medicine of Danshen Chuanxiongqin Injection on Liver insufficiency mainly includes of cerebrovascular disease in acute stress state:Danshen Chuanxiongqin Injection combined with alanyl glutamine;Treatment of acute ischemic cardiovascular and cerebrovascular diseases:Danshen Chuanxiongqin Injection combined with Levocarnitine+acetylsalicylic acid+inosine tablets+brain protein hydrolysate+glutathione+furosemide+Magnesium aspartate+metoprolol;Treatment of ischemic cardiomyopathy angina pectoris with traditional Chinese medicine:Danshen Chuanxiongqin Injection combined with Shexiang Baoxin Pills+Suxiao Jiuxin Pills+Fufang Danshen Drops;Treatment of ischemic cardiovascular disease complicated with Liver insufficiency with traditional Chinese medicine:Danshen Chuanxiongqin Injection combined with Dazhu Hongjingtian Capsule+Shuganning Injection.Conclusion:For Danshen Chuanxiongqin Injection in patients with Liver insufficiency,on the basis of conventional symptomatic treatment,attention should be paid to the liver function of the patients,integrated therapy can be more selective,can improve the efficacy in different degrees.Danshen Chuanxiongqin Injection combination scheme of Liver insufficiency in routine clinical diagnosis and treatment provides a more effective reference for clinical individualized treatment.展开更多
A rotundine-polyion complex(PIC)release system was prepared first by granulation of rotundine containing chitosan acetate solution and then by complexing with carboxymethyl glucomannan(CMGM)solution on the granular su...A rotundine-polyion complex(PIC)release system was prepared first by granulation of rotundine containing chitosan acetate solution and then by complexing with carboxymethyl glucomannan(CMGM)solution on the granular surface.The granules have an average diameter of 1.38-1.53 mm and the drug content reaches 62.89％.The external release tests showed T_(50) to be 45 rain and the total release time 4 h in an artificial gastric juice,while no more than 60％ of the drug was released in the same period of time in an ar- tificial intestinal fluid.The various factors affecting the external release were examined.展开更多
Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug r...Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug resistance is a pervasive obstacle to treating MM.Therefore,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies.To elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells.Differential gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion molecules.The upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion molecules.Furthermore,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules.Furthermore,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor immunity.Furthermore,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules.The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity.Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.展开更多
Heat shock proteins(Hsps)are a family of abundantly expressed ATP-dependent chaperone proteins.Hsp90 is an eminent member of Hsp family.Thus far,two primary functions have been described for Hsp90:first,as a regulator...Heat shock proteins(Hsps)are a family of abundantly expressed ATP-dependent chaperone proteins.Hsp90 is an eminent member of Hsp family.Thus far,two primary functions have been described for Hsp90:first,as a regulator of conformational change of some protein kinases and nuclear hormone receptors,and the other as an indispensable factor in cellular stress response.Hsp90 has an essential number of interaction proteins since it participates in almost every biological process and its importance is self-evident.Hsp90 has an inextricable relationship in the pathogenesis of cancer,especially in the proliferation and irradiation of cancer cells,thus being a notable cancer target.Since the discovery of geldanamycin,the first inhibitor of Hsp90,from the bacterial species Streptomyces hygroscopicus,even more attention has been focused toward Hsp90.Many structure-based inhibitors of Hsp90 have been designed to develop an innovative method to defeat cancer.However,already designed inhibitors have various deficiencies,such as hepatotoxicity,poor aqueous solubility,instability,and non-ideal oral bioavailability.Based on the aforementioned reasons and to achieve an optimal performance and fewer side effects,we designed a novel inhibitor of Hsp90,called FS5,and resolved the crystal structure of the Hsp90^N-FS5 complex(1.65 A°,PDB code 5XRB).Furthermore,we compared the complexes Hsp90^N,Hsp90^N-GDM,and Hsp90^N-ATP and suggest that the inhibitor FS5 may compete with ATP for binding to Hsp90,which can be regarded as a potential strategy for the development of novel cancer drugs in the future.展开更多
文摘Diabetes is a leading cause of mortality,morbidity and disability around the globe.In the past two decades,diabetes care has grown more complex as patients have received multi-component care.Recent studies have illumined the complexity of drug therapy in patients with diabetes.A high level of drug utilization in diabetes patients has serious implications for quality of care,in terms of coordination of care,drug safety and access to care.Practitioners,researchers,payers and policy makers should be aware of these implications and incorporate the complexity of diabetes care into practice guidelines,benefit design and policy formulation to improve the quality of care.
文摘A new type of implantable drug delivery devices （ DDD ） with complicated architectures were fubricated by three-dimensional printing technique, employing levofloxacin （LVFX） as a model drug. Processing parameters were optimized in riew of the layer thickness, spucing between printed lines, flow rate of liquid binder and the fast axis speed. The prepared DDD prototype consists of a double-layer structure, of which the upper region is a reservoir system and the lower region is a matrix one. The in vitro release test revealed that LVFX was released in a dual-puse pattern. This DDD may present a new strategy for the prophylaxis and treatment of diseases such as bone infection in the near future.
基金Study and Research,Taif University,Saudi Arabia under project Grants No.5545-438-1
文摘Metformin(Met)is a drug developed for the treatment of patients with typeⅡ diabetes.Recently,Met estimation in pharmaceutical formulations and human fluids has gained a growing interest.To extend requisite data that can be used to assessment of Met quantitatively based on charge-transfer(CT)complexation,the present study describes the synthesis and characterization of CT complexes that formed between drug Met and the organicπ-acceptors picric acid(PA),chloranilic acid(CLA),chloranil(CHL),7,7',8,8'-tetracyanoquinodimethane(TCNQ),and dichlorodicyanobenzoquinone(DDQ).The properties of the formed CT complexes were investigated by elemental,spectral(UV-visible,IR,and Raman spectroscopies),thermal(TG)and morphological(SEM)studies.IR results indicated that the complexation of Met with either PA or CLA acceptors occurs through proton transfer interaction,whereas its complexation with CHL,TCNQ,or DDQ acceptors occurs through n→π*interaction.
文摘Three types of metal ions barium(Ⅱ),nickel(Ⅱ)and cerium(Ⅲ)complexity of ATN drug have been prepared and characterized using molar conductance method,FT-IR,electronic,and 1H-NMR analysis measurements.The chemical and physical results for all atenolol complexes are agreement with the speculated structures.For the divalent(Ba&Ni)and trivalent(Ce)metal atenolol a molar ratio 1∶2 was established.Qualitative chemical analysis showed that for the divalent metal complexes,the chloride ions are not involved in the complexes,suggesting that all of these complexes,[Ba(ATN)2]·2 H2O and[Ni(ATN)2(H2O)2]·4 H2O are neutral.However,for the cerium(Ⅲ)complex,[Ce(ATN)2(NO3)]·3 H2O,the nitrate group is existed inside the coordination sphere.ATN make astable metal complexity with barium(Ⅱ),nickel(Ⅱ)and cerium(Ⅲ)ions.Electronic absorption analysis of Atenolol give two fundamental peaks at 225 nm and 274 nm refers to variation in transition electrons of ligand,UV spectral analysis of the three complexity obtained give asymmetric broad band in the range 200~400 nm,the reults are convenient with the suggestion of metal-nitrogen and metal-oxygen bonds.The infrared analysis data proved that ATN act as bidentate ligand through the N atom of the-NH group and O atom of the deprotonated alcoholic OH group.Nickel(Ⅱ)and cerium(Ⅲ)complexity make six-coordinate geometry,whereas the barium(Ⅱ)complex exhibit four-coordinate geometry.Ni(Ⅱ)-ATN complex has an effective magnetic moment equal 3.12 B.M,that is assigned to octahedral structure.The 1H-NMR spectral results of Ba(Ⅱ)-ATN complexity give strong signal at^4.00 ppm due to protons of-CH2 that influenced by low degree due to complexity.These results confirm the position of chelation through the N atom of the-NH group and O atom of the deprotonated alcoholic OH group.
基金Science and Technology Innovation Project of Chinese Academy of Traditional Chinese Medicine(Project No.CI2021A00702)National Key R&D Program"Evidence-based Evaluation of Ten Major Varieties of Chinese Medicines and Classical Formulas for the Treatment of Major Diseases and Demonstration of Their Effect Mechanisms after Marketing"(2018YFC1707400)。
文摘Objective:To study the characteristics and rules of medication regimen for patients with Liver insufficiency treated with Danshen Chuanxiongqin Injection.Methods:The inpatient information of Danshen Chuanxiongqin Injection with Liver insufficiency was extracted from the hospital information system(HIS)database of 12 Class A tertiary hospitals in China.Tabu search(TS)algorithm was used for obtaining sub-network and density matrix,matrix method or sociogram was used to show the relationship between different sub-networks,searching for core prescriptions of treatment options,associations and strong correlations between multiple drugs.Results:The treatment plan of integrated Chinese and Western medicine of Danshen Chuanxiongqin Injection on Liver insufficiency mainly includes of cerebrovascular disease in acute stress state:Danshen Chuanxiongqin Injection combined with alanyl glutamine;Treatment of acute ischemic cardiovascular and cerebrovascular diseases:Danshen Chuanxiongqin Injection combined with Levocarnitine+acetylsalicylic acid+inosine tablets+brain protein hydrolysate+glutathione+furosemide+Magnesium aspartate+metoprolol;Treatment of ischemic cardiomyopathy angina pectoris with traditional Chinese medicine:Danshen Chuanxiongqin Injection combined with Shexiang Baoxin Pills+Suxiao Jiuxin Pills+Fufang Danshen Drops;Treatment of ischemic cardiovascular disease complicated with Liver insufficiency with traditional Chinese medicine:Danshen Chuanxiongqin Injection combined with Dazhu Hongjingtian Capsule+Shuganning Injection.Conclusion:For Danshen Chuanxiongqin Injection in patients with Liver insufficiency,on the basis of conventional symptomatic treatment,attention should be paid to the liver function of the patients,integrated therapy can be more selective,can improve the efficacy in different degrees.Danshen Chuanxiongqin Injection combination scheme of Liver insufficiency in routine clinical diagnosis and treatment provides a more effective reference for clinical individualized treatment.
基金This project was supported by National Natural Science Foundation of China
文摘A rotundine-polyion complex(PIC)release system was prepared first by granulation of rotundine containing chitosan acetate solution and then by complexing with carboxymethyl glucomannan(CMGM)solution on the granular surface.The granules have an average diameter of 1.38-1.53 mm and the drug content reaches 62.89％.The external release tests showed T_(50) to be 45 rain and the total release time 4 h in an artificial gastric juice,while no more than 60％ of the drug was released in the same period of time in an ar- tificial intestinal fluid.The various factors affecting the external release were examined.
基金Research Projects-Joint Fund for Applied Basic Research of Kunming Medical University,Yunnan Provincial Department of Science and Technology(No.2018FE001(-113),No.202301AY070001-098)Open project of Yunnan Clinical Medical Center(Nos.2020LCZXKF-XY02,XY06,XY16+1 种基金2022LCZXKF-XY02)Yunnan Health Training Project of High Level Talents(No.D–2018018).
文摘Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug resistance is a pervasive obstacle to treating MM.Therefore,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies.To elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells.Differential gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion molecules.The upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion molecules.Furthermore,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules.Furthermore,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor immunity.Furthermore,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules.The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity.Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.
基金supported by the Open Project of Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases,Ministry of Education(No.XN201904)Gannan Medical University(No.QD201910)+1 种基金the National Natural Science Foundation of China(Nos.31770795 and 31971043)the Jiangxi Province Natural Science Foundation(No.20181ACB20014)
文摘Heat shock proteins(Hsps)are a family of abundantly expressed ATP-dependent chaperone proteins.Hsp90 is an eminent member of Hsp family.Thus far,two primary functions have been described for Hsp90:first,as a regulator of conformational change of some protein kinases and nuclear hormone receptors,and the other as an indispensable factor in cellular stress response.Hsp90 has an essential number of interaction proteins since it participates in almost every biological process and its importance is self-evident.Hsp90 has an inextricable relationship in the pathogenesis of cancer,especially in the proliferation and irradiation of cancer cells,thus being a notable cancer target.Since the discovery of geldanamycin,the first inhibitor of Hsp90,from the bacterial species Streptomyces hygroscopicus,even more attention has been focused toward Hsp90.Many structure-based inhibitors of Hsp90 have been designed to develop an innovative method to defeat cancer.However,already designed inhibitors have various deficiencies,such as hepatotoxicity,poor aqueous solubility,instability,and non-ideal oral bioavailability.Based on the aforementioned reasons and to achieve an optimal performance and fewer side effects,we designed a novel inhibitor of Hsp90,called FS5,and resolved the crystal structure of the Hsp90^N-FS5 complex(1.65 A°,PDB code 5XRB).Furthermore,we compared the complexes Hsp90^N,Hsp90^N-GDM,and Hsp90^N-ATP and suggest that the inhibitor FS5 may compete with ATP for binding to Hsp90,which can be regarded as a potential strategy for the development of novel cancer drugs in the future.
