Magnesium-based biodegradable metals (BMs) as bone implants have better mechanical properties than biodegradable polymers, yet their strength is roughly less than 350 MPa. In this work, binary Zn alloys with alloying elements Mg, Ca, Sr, Li, Mn, Fe, Cu, and Ag respectively, are screened systemically by in vitro and in vivo studies. Li exhibits the most effective strengthening role in Zn, followed by Mg. Alloying leads to accelerated degradation, but adequate mechanical integrity can be expected for Zn alloys when considering bone fracture healing. Adding elements Mg, Ca, Sr and Li into Zn can improve the cytocompatibility, osteogenesis, and osseointegration. Further optimization of the ternary Zn-Li alloy system results in Zn-0.8Li-0.4Mg alloy with the ultimate tensile strength 646.69 ± 12.79 MPa and Zn-0.8Li-0.8Mn alloy with elongation 103.27 ± 20%. In summary, biocompatible Znbased BMs with strength close to pure Ti are promising candidates in orthopedics for loadbearing applications.

No abstract

AcbstractBackgroundInhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has been intensively studied to lower low-density lipoprotein cholesterol (LDL-C) levels. The purpose of this meta-analysis was to evaluate the safety and efficacy of anti-PCSK9 antibodies in randomized, controlled trials (RCTs).MethodsPubMed, EMBASE, CENTRAL databases, and recent conferences were searched. Safety outcomes were rates of common adverse events. Efficacy outcomes included percentages of LDL-C lowering and other lipid changes compared with placebo and ezetimibe, respectively.ResultsTwenty-five RCTs encompassing 12,200 patients were included. The rates of common adverse events were firstly reported in our study by pooling together all evidence in RCTs, showing largely no significant difference between anti-PCSK9 antibodies and placebo (or ezetimibe), except that alirocumab was associated with reduced rates of death (relative risk (RR): 0.43, 95 % confidence interval (CI): 0.19 to 0.96, P = 0.04) and an increased rate of injection-site reactions (RR: 1.48, 95 % CI: 1.05 to 2.09, P = 0.02); evolocumab reduced the rate of abnormal liver function (RR: 0.43, 95 % CI: 0.20 to 0.93, P = 0.03), both compared with placebo. No significant difference in safety outcomes was detected between monthly 420 mg and biweekly 140 mg evolocumab treatments. Monthly 420 mg evolocumab treatment significantly reduced LDL-C by −54.6 % (95 % CI: −58.7 to −50.5 %) and by absolute −78.9 mg/dl (95 % CI: −88.9 to −68.9 mg/dl) versus placebo, and by −36.3 % (95 % CI: −38.8 to −33.9 %) versus ezetimibe, and increased high-density lipoprotein cholesterol (HDL-C) by 7.6 % (95 % CI: 5.7 to 9.5 %) versus placebo and 6.4 % (95 % CI: 4.3 to 8.4 %) versus ezetimibe. An equal or even greater change was observed following biweekly 140 mg administration. Significant and favorable changes were also detected in other lipids following evolocumab treatment. Biweekly 50 to 150 mg alirocumab lowered LDL-C by −52.6 % (95 % CI: −58.2 to −47.0 %) versus placebo, by −29.9 % (95 % CI: −32.9 to −26.9 %) versus ezetimibe, and increased HDL-C by 8.0 % (95 % CI: 4.2 to 11.7 %) versus placebo.ConclusionsEvolocumab and alirocumab were safe and well-tolerated from our most-powered analyses. Both antibodies substantially reduced the LDL-C level by over 50 %, increased the HDL-C level, and resulted in favorable changes in other lipids.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0358-8) contains supplementary material, which is available to authorized users.