Objective: This study aimed to compare the pharmacokinetic, pharmacodynamic and safety profiles of HLX01(a rituximab biosimilar) and reference rituximab sourced from China(Mab Thera?;rituximab-CN).Methods: Here we rep...Objective: This study aimed to compare the pharmacokinetic, pharmacodynamic and safety profiles of HLX01(a rituximab biosimilar) and reference rituximab sourced from China(Mab Thera?;rituximab-CN).Methods: Here we report the results of two phase 1 studies. In the phase 1 a, open-label, dose-escalation study(NCT03218072, CTR20140400), eligible patients received 250, 375 and 500 mg/m^(2) HLX01 sequentially at 7-day intervals, after confirming no dose-limiting toxicity(DLT). In the phase 1 b, double-blind study(NCT02584920,CTR20140764), eligible patients were given a single dose of 375 mg/m^(2) HLX01 or rituximab-CN. The primary endpoints included safety and tolerability parameters for the phase 1 a and the area under the plasma concentrationtime curve from time zero to day 91(AUC0-91 d) for the phase 1 b study. Equivalence was concluded if 90%confidence interval(90% CI) for the geometric least squares mean ratio(GLSMR) fell in the pre-specified equivalence criteria(80%-125%).Results: Between June 20, 2014 and January 5, 2015, 12 patients were enrolled in the phase 1 a study. The pharmacokinetics of HLX01 showed dose proportionality and accumulation to steady state. HLX01 was well tolerated, with no serious adverse events(AEs), discontinuations or DLTs. Between November 8, 2014 and August13, 2015, 87 eligible patients were enrolled in the phase 1 b study, including 43 who received HLX01 and 44 who were treated with rituximab-CN. The equivalence endpoint was met with GLSMR for AUC0-91 d being 89.6%(90% CI: 80.4%-99.8%). AEs, anti-drug antibodies, and CD19+ and CD20+ B lymphocyte counts were similar between the HLX01 and rituximab-CN treatment groups.Conclusions: Treatment with HLX01 was safe and well tolerated in Chinese patients with B-cell lymphoma.HLX01 and rituximab-CN have similar pharmacokinetic, pharmacodynamic and safety profiles.展开更多
Endogenous metabolites play key functions in many important physiological and biochemical processes.The comprehensive in situ detection and direct imaging of metabolites in bio-tissues by matrix-assisted laser desorpt...Endogenous metabolites play key functions in many important physiological and biochemical processes.The comprehensive in situ detection and direct imaging of metabolites in bio-tissues by matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI)is very important for understanding complex and diverse biological processes and has become an essential aspect of spatial omics.In this work,4-aminoazobenzene(AAB)was successfully screened and optimized as a new negative ion(-)MALDI matrix to enhance the in situ detection and imaging of metabolites in tissues using MALDIMSI.Obviously,AAB exhibited superior properties in terms of ultraviolet absorption,background ion interference,matrix morphology,and metabolite ionization efficiency.AAB was used for in situ detection and imaging of metabolites in rat brain and germinating Chinese yew seed tissue sections,where 264and 339 metabolite ion signals were successfully detected and imaged using(-)MALDI-MS,respectively.In addition,high-resolution imaging of mouse eyeball section using MALDI-tims TOF MSI with spatial resolution of up to 10μm was successfully carried out,showing that AAB is an efficient(-)MALDI matrix for capturing high-resolution images of metabolites in biological tissue sections.展开更多
BACKGROUND： Bone marrow-derived mesenchymal stem cells （BMSCs） are a potentially useful source for cell replacement therapy following spinal cord injury. However, the homing characteristics of BMSCs in vivo remain ...BACKGROUND： Bone marrow-derived mesenchymal stem cells （BMSCs） are a potentially useful source for cell replacement therapy following spinal cord injury. However, the homing characteristics of BMSCs in vivo remain unclear. Low-dose radiation has been shown to promote homing of BMSCs to exposed sites. OBJECTIVE： To investigate the effects of low-dose local radiation to non-injured areas on the ability of human BMSCs to home to the injured mouse spinal cord, as well as recovery of spinal cord injury. DESIGN, TIME AND SE＇I-FING： A randomized, controlled, animal experiment was performed at the Central Laboratory, Second Affiliated Hospital of Soochow University between October 2007 and October 2008. MATERIALS： BMSCs were isolated from four adult, human donors. METHODS： Fifty adult, female, Balb/c mice were subjected to adjusted weight-drop impact resulting in complete paraplegia. Three days later, mice were randomly assigned to a radiation ＋ transplantation group （n = 23） and a transplantation group （n = 20）. In total, 2 x 106 carboxyfluorescein diacetate succinimidyl ester-labeled BMSCs were injected into each mouse via the caudal vein. Mice in the radiation ＋ transplantation group received 2.5 Gy local X-ray irradiation 2 hours before BMSCs injection. MAIN OUTCOME MEASURES： The homing of BMSCs to injured cord and irradiated skin after transplantation was observed by fluorescence microscope; the structure recovery of injured cord was assessed by magnetic resonance imaging. RESULTS： Compared with the transplantation group, at 24 hours after transplantation, the number of BMSCs was significantly increased in the injured area and the exposed site （P 〈 0.05）, and inflammation and edema were significantly alleviated in the injured cord in the radiation ＋ transplantation group. CONCLUSION： Local low-dose radiation has the potential to promote homing of BMSCs and recovery of spinal cord injury, although the radiated region was not injured area.展开更多
Low-molecular-weight(LMW)compounds are ubiquitous in living organisms and play essential roles in biological processes.The direct analysis of LMW compounds in biological tissues by matrix-assisted laser desorption/ion...Low-molecular-weight(LMW)compounds are ubiquitous in living organisms and play essential roles in biological processes.The direct analysis of LMW compounds in biological tissues by matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI)could provide a more comprehensive understanding of their essential functions.Here,we evaluated 4-nitrocatechol(4-NC)as a novel positive-ion matrix for enhancing in situ detection and imaging of LMW compounds from the rat liver,brain,and germinating Chinese-yew seed by MALDI-MS.Our results showed that the 4-NC possessed remarkable features,including strong ultraviolet absorption,uniform matrix crystal,excellent chemical stability,and fewer matrix-related background peaks.The use of 4-NC led to the successful detection of 232,218,and193 LMW compounds from the three abovementioned tissue sections,respectively.Also,the use of 4-NC improved the imaging quality of LMW compounds in tissue sections through MALDI-MSI and has the potential as a matrix for MALDI tissue imaging of LMW compounds.展开更多
基金funded by Shanghai Henlius Biotech, Inc., Science and Technology Commission of Shanghai Municipality (No. 14431908500)China National Major Project for New Drug Innovation (No. 2012ZX09303012)。
文摘Objective: This study aimed to compare the pharmacokinetic, pharmacodynamic and safety profiles of HLX01(a rituximab biosimilar) and reference rituximab sourced from China(Mab Thera?;rituximab-CN).Methods: Here we report the results of two phase 1 studies. In the phase 1 a, open-label, dose-escalation study(NCT03218072, CTR20140400), eligible patients received 250, 375 and 500 mg/m^(2) HLX01 sequentially at 7-day intervals, after confirming no dose-limiting toxicity(DLT). In the phase 1 b, double-blind study(NCT02584920,CTR20140764), eligible patients were given a single dose of 375 mg/m^(2) HLX01 or rituximab-CN. The primary endpoints included safety and tolerability parameters for the phase 1 a and the area under the plasma concentrationtime curve from time zero to day 91(AUC0-91 d) for the phase 1 b study. Equivalence was concluded if 90%confidence interval(90% CI) for the geometric least squares mean ratio(GLSMR) fell in the pre-specified equivalence criteria(80%-125%).Results: Between June 20, 2014 and January 5, 2015, 12 patients were enrolled in the phase 1 a study. The pharmacokinetics of HLX01 showed dose proportionality and accumulation to steady state. HLX01 was well tolerated, with no serious adverse events(AEs), discontinuations or DLTs. Between November 8, 2014 and August13, 2015, 87 eligible patients were enrolled in the phase 1 b study, including 43 who received HLX01 and 44 who were treated with rituximab-CN. The equivalence endpoint was met with GLSMR for AUC0-91 d being 89.6%(90% CI: 80.4%-99.8%). AEs, anti-drug antibodies, and CD19+ and CD20+ B lymphocyte counts were similar between the HLX01 and rituximab-CN treatment groups.Conclusions: Treatment with HLX01 was safe and well tolerated in Chinese patients with B-cell lymphoma.HLX01 and rituximab-CN have similar pharmacokinetic, pharmacodynamic and safety profiles.
基金supported by the National Natural Science Foundation of China(Nos.31770384 and 21605164)the Youth Academic Team Project of MUC(No.10301-02200301)+1 种基金the Huayi Technology Innovation Center for Research Resources(No.HTIC P01RR2017001A)the Key Laboratory Construction Funds of State Ethnic Affairs Commission of China(No.10301-02200303)。
文摘Endogenous metabolites play key functions in many important physiological and biochemical processes.The comprehensive in situ detection and direct imaging of metabolites in bio-tissues by matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI)is very important for understanding complex and diverse biological processes and has become an essential aspect of spatial omics.In this work,4-aminoazobenzene(AAB)was successfully screened and optimized as a new negative ion(-)MALDI matrix to enhance the in situ detection and imaging of metabolites in tissues using MALDIMSI.Obviously,AAB exhibited superior properties in terms of ultraviolet absorption,background ion interference,matrix morphology,and metabolite ionization efficiency.AAB was used for in situ detection and imaging of metabolites in rat brain and germinating Chinese yew seed tissue sections,where 264and 339 metabolite ion signals were successfully detected and imaged using(-)MALDI-MS,respectively.In addition,high-resolution imaging of mouse eyeball section using MALDI-tims TOF MSI with spatial resolution of up to 10μm was successfully carried out,showing that AAB is an efficient(-)MALDI matrix for capturing high-resolution images of metabolites in biological tissue sections.
基金a Project for Nuclear Military Personal Health Assessment and Radiation Damage Treat-ment, No. 616010305
文摘BACKGROUND： Bone marrow-derived mesenchymal stem cells （BMSCs） are a potentially useful source for cell replacement therapy following spinal cord injury. However, the homing characteristics of BMSCs in vivo remain unclear. Low-dose radiation has been shown to promote homing of BMSCs to exposed sites. OBJECTIVE： To investigate the effects of low-dose local radiation to non-injured areas on the ability of human BMSCs to home to the injured mouse spinal cord, as well as recovery of spinal cord injury. DESIGN, TIME AND SE＇I-FING： A randomized, controlled, animal experiment was performed at the Central Laboratory, Second Affiliated Hospital of Soochow University between October 2007 and October 2008. MATERIALS： BMSCs were isolated from four adult, human donors. METHODS： Fifty adult, female, Balb/c mice were subjected to adjusted weight-drop impact resulting in complete paraplegia. Three days later, mice were randomly assigned to a radiation ＋ transplantation group （n = 23） and a transplantation group （n = 20）. In total, 2 x 106 carboxyfluorescein diacetate succinimidyl ester-labeled BMSCs were injected into each mouse via the caudal vein. Mice in the radiation ＋ transplantation group received 2.5 Gy local X-ray irradiation 2 hours before BMSCs injection. MAIN OUTCOME MEASURES： The homing of BMSCs to injured cord and irradiated skin after transplantation was observed by fluorescence microscope; the structure recovery of injured cord was assessed by magnetic resonance imaging. RESULTS： Compared with the transplantation group, at 24 hours after transplantation, the number of BMSCs was significantly increased in the injured area and the exposed site （P 〈 0.05）, and inflammation and edema were significantly alleviated in the injured cord in the radiation ＋ transplantation group. CONCLUSION： Local low-dose radiation has the potential to promote homing of BMSCs and recovery of spinal cord injury, although the radiated region was not injured area.
基金supported by the National Natural Science Foundation of China(Nos.31770384 and 21605164)the Youth Academic Team Project of MUC(No.10301-02200301)+1 种基金the Huayi Technology Innovation Center for Research Resources(No.HTIC P01RR2017001A)the Key Laboratory Construction Funds of State Ethnic Affairs Commission of China(No.10301-02200303)。
文摘Low-molecular-weight(LMW)compounds are ubiquitous in living organisms and play essential roles in biological processes.The direct analysis of LMW compounds in biological tissues by matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI)could provide a more comprehensive understanding of their essential functions.Here,we evaluated 4-nitrocatechol(4-NC)as a novel positive-ion matrix for enhancing in situ detection and imaging of LMW compounds from the rat liver,brain,and germinating Chinese-yew seed by MALDI-MS.Our results showed that the 4-NC possessed remarkable features,including strong ultraviolet absorption,uniform matrix crystal,excellent chemical stability,and fewer matrix-related background peaks.The use of 4-NC led to the successful detection of 232,218,and193 LMW compounds from the three abovementioned tissue sections,respectively.Also,the use of 4-NC improved the imaging quality of LMW compounds in tissue sections through MALDI-MSI and has the potential as a matrix for MALDI tissue imaging of LMW compounds.
