Safety and tolerability of a single dose T0001 in Chinese healthy adult volunteers: a first-in-human ascending dose study

T0001 is the first mutant of etanercept with a higher affinity to tumor necrosis factor α (TNF-α) than etanercept. In order to investigate the safety and tolerability of T0001, a study was carried out in healthy Chinese subjects. A first-in-human, dose escalation study was conducted in healthy Chinese subjects. Fifty-six subjects were divided into six dose cohorts (10 mg, 20 mg, 35 mg, 50 mg, 65 mg and 75 mg) to receive a single subcutaneous injection of T0001. Safety and tolerability assessment were based on the records of vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms and adverse events (AEs). All subjects were in good compliance and none withdraw due to AEs. No serious AEs occurred. A total of twenty-three AEs in sixteen subjects were recorded, and eighteen of these AEs were believed to be related to T0001. The most frequently reported AEs were injection site reactions and white blood cell count increase. All these AEs were of mild to moderate intensity and most of them recovered spontaneously within 14 days. In this study, no dose-limiting toxicity was observed, and the maximum tolerated dose was identified as 75 mg. T0001 was considered safe and generally well tolerated at doses up to 75 mg in healthy Chinese volunteers

Experimental study on the survival of venous flap with different pedicle styles / 中华整形外科杂志

<p><b>OBJECTIVE</b>To study a new method of venous flap that is improved on its persistence and quality.</p><p><b>METHODS</b>New Zealand white rabbits were subdivided randomly into 4 groups. All rabbits were operated by harvesting a flap from the latero-abdominal wall and then sutured it in the original position. Group A: the superficial epigastric vein in the pedicle was left open (only one inflow vein remained). Group B: the pedicle vein of the proximal and distant end were left open (keeping an inflow vein and a principal out). Group C: the pedicle vein and a tributary vein were left open (keeping an inflow vein and a tributary outflow vein). Group D: the pedicle vein and two tributary veins were left open (keeping an inflow vein and two tributary outflow veins). Survival rate, MDA of the tissue, histology and ultra-microstructure were examined.</p><p><b>RESULTS</b>Survival rate of A, B, C, D were improved in order. Statistic difference is significant (P < 0.05) between group and group other than C and D. The content of MDA was heightened with statistically significant differences (A > B > C > D) among the four groups 8 hours postoperatively, but fell back to the normal level in group D and C and kept a high level in group A and B at 72 hour postoperatively. Histology and ultra-microstructure exam showed that degeneration of collagen fiber and karyopyknosis of cell is more obvious in Group A and Group B than Group C and Group D.</p><p><b>CONCLUSIONS</b>The higher survival rate of venous flap is possible by designing the more reasonable venous flap outputs pedicles which can alleviate the high tension dropsy and maintain the valid equilibrium of pour with flow in the venous flap.</p>