Phase 1 studies comparing safety, tolerability, pharmacokinetics and pharmacodynamics of HLX01(a rituximab biosimilar) to reference rituximab in Chinese patients with CD20-positive B-cell lymphoma

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.

Small-scale alpine topography at low latitudes and high altitudes:refuge areas of the genus Chrysanthemum and its allies

Cultivated chrysanthemum(Chrysanthemum morifolium Ramat.)is an economically important ornamental plant species grown worldwide.However,the origin of the genus Chrysanthemum remains unclear.This study was conducted in the Hengduan Mountains,Yunnan Province.We took advantage of a special geographic region where the southernmost species of Ajania and the highest altitude population of Chrysanthemum indicum coexist to investigate their evolutionary origins.Diversity analysis of 9 populations of 5 species that came from 3 genera was carried out based on morphological traits and SRAP markers.Furthermore,topographical and ecological analyses and surveys of the vegetation communities in the plots were carried out for correlation analysis,and past data were used to reconstruct the ancient topography and vegetation to estimate the migration path and divergence time.We found that Chrysanthemum and Ajania were closely related based on the smooth transition states among marginal female florets and their common pollination system.The genetic relationship between Phaeostigma and Chrysanthemum was relatively distant,and Ajania was between them.Low light intensity and relatively humid habitats may be driving the elongation and evolution of marginal female florets.We found that Chrysanthemum and related genera were largely restricted to stony topographies at an altitude of~3000 m.a.s.l.and in specialized alpine coniferous(Pinus)and broadleaved(Quercus)mixed forest marginal communities.These stony topographies have become ecological islands of refuge for these species in the current interglacial period.The Hengduan Mountains play a key role in the evolution,divergence,and survival of Chrysanthemum and its allies.

Anti-fatigue Effect of L-arginine Complex Preparation on Mice

Objective:To investigate the anti-fatigue effect of L-arginine complex preparation on mice.Methods:The experimental mice were divided into a blank group,low dose group,medium dose group and high dose group.L-arginine complex preparation mice were intragastrically administered for 30 days,and the mice were tested for exhaustive swimming time.At the same time,contents of plasma lactic acid,lactate dehydrogenase,urea nitrogen and hepatic glycogen were measured.Results:Compared with the blank control group,the weight-bearing swimming time and hypoxia-tolerant survival time of the low,middle and high dose groups was significantly increased(P<0.05).Whereas,the serum urea nitrogen levels and lactose content were significantly decreased(P<0.05).However,compared with the blank control group,the liver glycogen content of the middle and high dose groups was increased significantly(P<0.05),and there was no significant difference in the low dose group.Conclusion:The L-arginine complex preparation has an anti-fatigue function in mice.