Objective:To compare the efficacy and safety of LY01011,a recombinant anti-RANKL fully human monoclonal antibody injection,versus denosumab in the treatment of bone metastases from solid tumors.Methods:A randomized,double-blind,positive drug parallel-controlled,multicenter clinical trial was conducted.A total of 850 subjects were randomly assigned(1:1)to either the experimental group(424 subjects)or the control group(426 subjects).The experimental group received 13 doses of LY01011,while the control group received 3 doses of denosumab followed by 10 doses of LY01011.Results:The primary efficacy endpoint was the natural logarithmic change from baseline in urinary N-terminal telopeptide of type I collagen corrected by urinary creatinine(uNTX/uCr)at week 13.The change was-1.740(0.042 0)in the experimental group and-1.745(0.042 1)in the control group.The least-squares mean difference between groups was 0.005(90%CI:-0.088 to 0.097),indicating no statistically significant difference(P>0.05).Safety profiles,including treatment-emergent adverse events,laboratory tests,vital signs,physical examinations,and electrocardiograms,were comparable between groups(P>0.05).Conclusions:LY01011 demonstrated biosimilarity to denosumab,with favorable safety profile,tolerability,and potential for clinical application.

Objective:To compare the efficacy and safety of LY01011,a recombinant anti-RANKL fully human monoclonal antibody injection,versus denosumab in the treatment of bone metastases from solid tumors.Methods:A randomized,double-blind,positive drug parallel-controlled,multicenter clinical trial was conducted.A total of 850 subjects were randomly assigned(1:1)to either the experimental group(424 subjects)or the control group(426 subjects).The experimental group received 13 doses of LY01011,while the control group received 3 doses of denosumab followed by 10 doses of LY01011.Results:The primary efficacy endpoint was the natural logarithmic change from baseline in urinary N-terminal telopeptide of type I collagen corrected by urinary creatinine(uNTX/uCr)at week 13.The change was-1.740(0.042 0)in the experimental group and-1.745(0.042 1)in the control group.The least-squares mean difference between groups was 0.005(90%CI:-0.088 to 0.097),indicating no statistically significant difference(P>0.05).Safety profiles,including treatment-emergent adverse events,laboratory tests,vital signs,physical examinations,and electrocardiograms,were comparable between groups(P>0.05).Conclusions:LY01011 demonstrated biosimilarity to denosumab,with favorable safety profile,tolerability,and potential for clinical application.

Objective:To study the effect of Long non-coding RNA(LncRNA)small nucleolar RNA host gene 12(SNHG12)regulating miR-138-5p/hypoxia inducible factor-1(HIF-1α)axis on improving the damage of hypoxia/reoxygenation(H/R)human vas-cular endothelial cells.Methods:Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and randomly divided into control group,H/R model group,H/R+LncRNA SNHG12 overexpression group,H/R+miR-138-5p mimics group,H/R+co-transfec-tion group and H/R+co-transfection negative control group,each transfection group was transfected separately,and except for control group,the remaining groups were given hypoxia for 5 hours and then reoxygenated for 1 hour to induce the cell models,and then the cell viability of each group was detected by CCK-8 experiment;the cell apoptosis in each group was detected by flow cytometry experi-ment,and the apoptosis rate of each group was compared;the levels of reactive oxygen species(ROS),lactate dehydrogenase(LDH)and inflammatory factors IL-6,IL-17 and IL-18 in each group were measured by the kit;the expressions of miR-138-5p and HIF-1α mRNA in cells of each group were measured by real-time quantitative PCR(qRT-PCR)experiment;the expressions of apoptotic pro-teins caspase-9,Bcl-2-associated X protein(Bax)and HIF-1α in each group were evaluated by Western blot.Results:Compared with control group,the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular HIF-1α mRNA and protein levels,cellular caspase-9,Bax and HIF-1α protein levels were increased in H/R model group(P<0.05),the cell viability and miR-138-5p level were decreased(P<0.05).Compared with H/R model group and H/R+co-transfection group,the cell viability,cell HIF-1αmRNA and protein levels were increased in H/R+LncRNA SNHG12 overexpression group(P<0.05),the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular caspase-9 and Bax protein levels,and miR-138-5p level were decreased(P<0.05);the cell viability,cellular HIF-1α mRNA and protein levels were decreased in H/R+miR-138-5p mimics group(P<0.05),the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular caspase-9 and Bax protein levels were increased(P<0.05).Com-pared with H/R model group,there was no significant difference in cell index levels between the H/R+co-transfection negative control group and the H/R+co-transfection group(P>0.05).Conclusion:LncRNA SNHG12 can upregulate HIF-1α expression by downregulat-ing miR-138-5p expression,inhibit H/R-induced inflammation and oxidative stress in HUVECs,and reduce cell damage and apoptosis.