The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to...The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existi展开更多
Inflammatory bowel disease(IBD)is a chronic gastrointestinal inflammatory disease.With the emergence of biologics and other therapeutic methods,two biologics or one biologic combined with a novel small-molecule drug h...Inflammatory bowel disease(IBD)is a chronic gastrointestinal inflammatory disease.With the emergence of biologics and other therapeutic methods,two biologics or one biologic combined with a novel small-molecule drug has been proposed in recent years to treat IBD.Although treatment strategies for IBD are being optimized,their efficacy and risks still warrant further consideration.This editorial explores the current risks associated with dual-targeted treatment for IBD and the great potential that fecal microbiota transplantation(FMT)may have for use in combination therapy for IBD.We are focused on addressing refractory IBD or biologically resistant IBD based on currently available dual-targeted treatment by incorporating FMT as part of this dual-targeted treatment.In this new therapy regimen,FMT represents a promising combination therapy.展开更多
目的:探究榄香烯(ELE)增强卡巴他赛(CTX)抗胶质瘤疗效,制备一种共载ELE/CTX的双靶向阳离子脂质体(LIP)用于胶质瘤的治疗研究,并达到增加药效、减少不良反应的作用,经体外药效学试验揭露其优势及作用机制。方法:采用高速剪切法联合探头...目的:探究榄香烯(ELE)增强卡巴他赛(CTX)抗胶质瘤疗效,制备一种共载ELE/CTX的双靶向阳离子脂质体(LIP)用于胶质瘤的治疗研究,并达到增加药效、减少不良反应的作用,经体外药效学试验揭露其优势及作用机制。方法:采用高速剪切法联合探头超声法制备脂质体ELE/CTX@LIP,并采用纳米粒径电位仪对其粒径及电位进行表征,采用高效液相色谱法(HPLC)测定ELE/CTX包封率及载药量;采用细胞增殖与活性检测法(CCK-8)检测ELE/CTX体外细胞增殖抑制活性;通过JMP Pro 16软件,以包封率为指标优化脂质体(ELE/CTX@LIP)工艺参数;通过体外细胞增殖抑制活性和体外细胞摄取,筛选最佳阳离子材料种类、含量与配比,在此基础上制备双靶向阳离子脂质体并表征其形态、粒径稳定性等,验证其对RG2胶质瘤细胞的细胞周期和细胞凋亡的影响。结果:ELE/CTX抗胶质瘤活性结果显示ELE/CTX分别对C6、RG2细胞具有更强的细胞增殖抑制活性;体外细胞增殖抑制活性和体外细胞摄取结果显示阳离子材料用量为总含量的0.10%;T7、精氨酸-甘氨酸-天冬氨酸三肽序列(cRGD)与磷脂最佳配比为1∶1∶50。T7/cRGD-ELE/CTX@CLIP[1,2-二油酰氧基-3-二甲基氨基丙烷(DlinMC3-DMA)]、T7/cRGD-ELE/CTX@CLIP[二肉豆蔻酰甘油-聚乙二醇2000(DMG-PEG2000)]呈现多层次球状纳米结构,粒径分别为146.0 nm和111.3 nm,血清稳定性良好;体外细胞增殖抑制结果显示,与单靶向脂质体或双靶向非阳离子脂质体比较,T7/cRGD-ELE/CTX@CLIP在体外对胶质瘤细胞具有更高的细胞增殖抑制活性;T7/cRGD-ELE/CTX@CLIP影响胶质瘤细胞凋亡及周期,结果显示,ELE/CTX联用能通过脂质体载体能更加有效的激活细胞凋亡通道抑制胶质瘤细胞增殖,且使用T7/cRGD短肽及阳离子修饰后,增强了细胞凋亡诱导能力,ELE/CTX能有效将胶质瘤细胞周期阻滞于G2/M期,且经T7/cRGD靶向修饰后,效果增强。结论:ELE可以增强CTX抗胶�展开更多
Objective: The purpose of the study was to explore the application effects of the cloud platform-based comprehensive online management for breast cancer patients using dual-targeted therapy with macromolecular monoclo...Objective: The purpose of the study was to explore the application effects of the cloud platform-based comprehensive online management for breast cancer patients using dual-targeted therapy with macromolecular monoclonal antibodies. Methods: 120 breast cancer patients treated by dual-targeted therapy with macromolecular monoclonal antibodies were managed by a cloud platform from March to November 2019. Comprehensive online management included consultation about drugs and side effects and frequently asked questions in the dual-targeted therapy with macromolecular monoclonal antibodies. Results: In the consultation about drugs and side effects, there were five patients with fever, neutrophil, cough, and fatigue;24 with diarrhea;25 with nausea;11 with oral mucosal inflammation;10 with rashes and dry skin;8 with insomnia;and 1 with palpitation. Moreover, 110 patients with anxiety about the missed or delayed treatment were properly handled. Conclusion: The comprehensive online management of dual-targeted therapy with macromolecular monoclonal antibodies based on the cloud platform is helpful to satisfy the at-home breast cancer patients’ needs, ensure the continuity of dual-targeted therapy with macromolecular monoclonal antibodies for breast cancer patients, prevent misinformation, alleviate patients’ negative psychological emotions, and reduce patients’ economic losses. The online cloud platform integrated management model is crucial for managing patients with breast cancer treated by dual-targeted therapy.展开更多
Antioxidation and adjustable treatment strategies are critical for the effective treatment of Alzheimer’s disease(AD).Here,we design a dual-targeted Prussian blue nanoformulation(PTCN)that can cross the blood-brain b...Antioxidation and adjustable treatment strategies are critical for the effective treatment of Alzheimer’s disease(AD).Here,we design a dual-targeted Prussian blue nanoformulation(PTCN)that can cross the blood-brain barrier and target amyloid beta aggregates further exert antioxidant effects.An adjustable gradient dosing strategy with PTCN is used for the first time to design the preventive and therapeutic trials based on the severity of oxidative stress at different AD stages.The results show that PTCN could effectively ameliorate AD-related pathological processes,improve the cognitive decline,and rescue hippocampal atrophy of APP/PS1 mice in both preventive and therapeutic trials.Altogether,PTCN provided here is a successful combination of three traditional biomaterials with good biosafety,which has broad prospects for the early prevention,mild remission,and late treatment of AD,and is expected to be developed into personalized therapeutic drugs and healthcare products for clinical AD in the future.展开更多
Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic r...Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic regimens for this patient population.The present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients.Methods:Cell proliferation,vacuolization,apoptosis,cell cycle,and in-vivo tumor growth were evaluated.In addition,Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in B-ALL.Results:HZX-02-059 was found to inhibit cell proliferation,induce vacuolization,promote apoptosis,block the cell cycle,and reduce in-vivo tumor growth.Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these observations.Conclusion:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.展开更多
The performance of electric vehicles is affected by the shift quality of multi-gear transmission.The realization of dual-target tracking control requires the transmission control unit(TCU)to accurately measure and pro...The performance of electric vehicles is affected by the shift quality of multi-gear transmission.The realization of dual-target tracking control requires the transmission control unit(TCU)to accurately measure and process the input signals of the gear-shifting control system and precisely control the drive motor torque and the position of shift motors.An electric-vehicle-dedicated TCU was designed to meet the above design requirements.Its function modules included a single-chip control circuit,shift position signal sampling circuit,signal conditioning circuit of the rotational speed and angle,controller area network communication circuit,and shift motor drive circuit.A hardware-in-the-loop simulation test system showed that the TCU design scheme met measurement accuracy requirements and coordinated the actions of the shift actuator and motor control unit to achieve fast and smooth shifting before the road test.The power interruption time of the shifting process was within 350 ms.The reliability of the TCU design was further verified in a 150,000-km vehicle road test.展开更多
文摘The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existi
基金Supported by The Science and Technology Plan of Liaoning Province,China,No.2022JH2/101500063.
文摘Inflammatory bowel disease(IBD)is a chronic gastrointestinal inflammatory disease.With the emergence of biologics and other therapeutic methods,two biologics or one biologic combined with a novel small-molecule drug has been proposed in recent years to treat IBD.Although treatment strategies for IBD are being optimized,their efficacy and risks still warrant further consideration.This editorial explores the current risks associated with dual-targeted treatment for IBD and the great potential that fecal microbiota transplantation(FMT)may have for use in combination therapy for IBD.We are focused on addressing refractory IBD or biologically resistant IBD based on currently available dual-targeted treatment by incorporating FMT as part of this dual-targeted treatment.In this new therapy regimen,FMT represents a promising combination therapy.
文摘目的:探究榄香烯(ELE)增强卡巴他赛(CTX)抗胶质瘤疗效,制备一种共载ELE/CTX的双靶向阳离子脂质体(LIP)用于胶质瘤的治疗研究,并达到增加药效、减少不良反应的作用,经体外药效学试验揭露其优势及作用机制。方法:采用高速剪切法联合探头超声法制备脂质体ELE/CTX@LIP,并采用纳米粒径电位仪对其粒径及电位进行表征,采用高效液相色谱法(HPLC)测定ELE/CTX包封率及载药量;采用细胞增殖与活性检测法(CCK-8)检测ELE/CTX体外细胞增殖抑制活性;通过JMP Pro 16软件,以包封率为指标优化脂质体(ELE/CTX@LIP)工艺参数;通过体外细胞增殖抑制活性和体外细胞摄取,筛选最佳阳离子材料种类、含量与配比,在此基础上制备双靶向阳离子脂质体并表征其形态、粒径稳定性等,验证其对RG2胶质瘤细胞的细胞周期和细胞凋亡的影响。结果:ELE/CTX抗胶质瘤活性结果显示ELE/CTX分别对C6、RG2细胞具有更强的细胞增殖抑制活性;体外细胞增殖抑制活性和体外细胞摄取结果显示阳离子材料用量为总含量的0.10%;T7、精氨酸-甘氨酸-天冬氨酸三肽序列(cRGD)与磷脂最佳配比为1∶1∶50。T7/cRGD-ELE/CTX@CLIP[1,2-二油酰氧基-3-二甲基氨基丙烷(DlinMC3-DMA)]、T7/cRGD-ELE/CTX@CLIP[二肉豆蔻酰甘油-聚乙二醇2000(DMG-PEG2000)]呈现多层次球状纳米结构,粒径分别为146.0 nm和111.3 nm,血清稳定性良好;体外细胞增殖抑制结果显示,与单靶向脂质体或双靶向非阳离子脂质体比较,T7/cRGD-ELE/CTX@CLIP在体外对胶质瘤细胞具有更高的细胞增殖抑制活性;T7/cRGD-ELE/CTX@CLIP影响胶质瘤细胞凋亡及周期,结果显示,ELE/CTX联用能通过脂质体载体能更加有效的激活细胞凋亡通道抑制胶质瘤细胞增殖,且使用T7/cRGD短肽及阳离子修饰后,增强了细胞凋亡诱导能力,ELE/CTX能有效将胶质瘤细胞周期阻滞于G2/M期,且经T7/cRGD靶向修饰后,效果增强。结论:ELE可以增强CTX抗胶�
文摘Objective: The purpose of the study was to explore the application effects of the cloud platform-based comprehensive online management for breast cancer patients using dual-targeted therapy with macromolecular monoclonal antibodies. Methods: 120 breast cancer patients treated by dual-targeted therapy with macromolecular monoclonal antibodies were managed by a cloud platform from March to November 2019. Comprehensive online management included consultation about drugs and side effects and frequently asked questions in the dual-targeted therapy with macromolecular monoclonal antibodies. Results: In the consultation about drugs and side effects, there were five patients with fever, neutrophil, cough, and fatigue;24 with diarrhea;25 with nausea;11 with oral mucosal inflammation;10 with rashes and dry skin;8 with insomnia;and 1 with palpitation. Moreover, 110 patients with anxiety about the missed or delayed treatment were properly handled. Conclusion: The comprehensive online management of dual-targeted therapy with macromolecular monoclonal antibodies based on the cloud platform is helpful to satisfy the at-home breast cancer patients’ needs, ensure the continuity of dual-targeted therapy with macromolecular monoclonal antibodies for breast cancer patients, prevent misinformation, alleviate patients’ negative psychological emotions, and reduce patients’ economic losses. The online cloud platform integrated management model is crucial for managing patients with breast cancer treated by dual-targeted therapy.
基金supported by the National Natural Science Foundation of China(51873150,51573128).
文摘Antioxidation and adjustable treatment strategies are critical for the effective treatment of Alzheimer’s disease(AD).Here,we design a dual-targeted Prussian blue nanoformulation(PTCN)that can cross the blood-brain barrier and target amyloid beta aggregates further exert antioxidant effects.An adjustable gradient dosing strategy with PTCN is used for the first time to design the preventive and therapeutic trials based on the severity of oxidative stress at different AD stages.The results show that PTCN could effectively ameliorate AD-related pathological processes,improve the cognitive decline,and rescue hippocampal atrophy of APP/PS1 mice in both preventive and therapeutic trials.Altogether,PTCN provided here is a successful combination of three traditional biomaterials with good biosafety,which has broad prospects for the early prevention,mild remission,and late treatment of AD,and is expected to be developed into personalized therapeutic drugs and healthcare products for clinical AD in the future.
基金funded by the National Natural Science Foundation of China(No.81770126,No.81900160,No.81800163,No.22025702,and No.91853203)the Fujian Natural Science Foundation of China(No.2020J011246 and No.2021J011359)+2 种基金the Foundation of Health and Family Planning Commission of Fujian Province of China(No.2020GGB054)the Xiamen Municipal Bureau of Science and Technology(No.3502Z20209003)the Fundamental Research Funds for the Central Universities of China(No.20720190101).
文摘Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic regimens for this patient population.The present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients.Methods:Cell proliferation,vacuolization,apoptosis,cell cycle,and in-vivo tumor growth were evaluated.In addition,Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in B-ALL.Results:HZX-02-059 was found to inhibit cell proliferation,induce vacuolization,promote apoptosis,block the cell cycle,and reduce in-vivo tumor growth.Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these observations.Conclusion:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.
基金This work was supported by the National Natural Science Foundation of China(51775291)Provincial-College Cooperation Project(2019YFSY0008)Sichuan Science and Technology Project(Grant No.2019JDRC0002).
文摘The performance of electric vehicles is affected by the shift quality of multi-gear transmission.The realization of dual-target tracking control requires the transmission control unit(TCU)to accurately measure and process the input signals of the gear-shifting control system and precisely control the drive motor torque and the position of shift motors.An electric-vehicle-dedicated TCU was designed to meet the above design requirements.Its function modules included a single-chip control circuit,shift position signal sampling circuit,signal conditioning circuit of the rotational speed and angle,controller area network communication circuit,and shift motor drive circuit.A hardware-in-the-loop simulation test system showed that the TCU design scheme met measurement accuracy requirements and coordinated the actions of the shift actuator and motor control unit to achieve fast and smooth shifting before the road test.The power interruption time of the shifting process was within 350 ms.The reliability of the TCU design was further verified in a 150,000-km vehicle road test.
