Current materials comprising suture anchors used to reconstruct ligament-bone junctions still have limitation in biocompatibility,degradability or mechanical properties.Magnesium alloys are potential bone implant mate...Current materials comprising suture anchors used to reconstruct ligament-bone junctions still have limitation in biocompatibility,degradability or mechanical properties.Magnesium alloys are potential bone implant materials,and Mg^(2+) has been shown to promote ligament-bone healing.Here,we used Mg-2 wt.%Zn-0.5 wt.%Y-1 wt.%Nd-0.5 wt.%Zr(ZE21C)alloy and Ti6Al4V(TC4)alloy to prepare suture anchors to reconstruct the patellar ligament-tibia in SD rats.We studied the degradation behavior of the ZE21C suture anchor via in vitro and in vivo experiments and assessed its reparative effect on the ligament-bone junction.In vitro,the ZE21C suture anchor degraded gradually,and calcium and phosphorus products accumulated on its surface during degradation.In vivo,the ZE21C suture anchor could maintain its mechanical integrity within 12 weeks of implantation in rats.The tail of the ZE21C suture anchor in high stress concentration degraded rapidly during the early implantation stage(0-4weeks),while bone healing accelerated the degradation of the anchor head in the late implantation stage(4-12weeks).Radiological,histological,and biomechanical assays indicated that the ZE21C suture anchor promoted bone healing above the suture anchor and fibrocartilaginous interface regeneration in the ligament-bone junction,leading to better biomechanical strength than the TC4 group.Hence,this study provides a basis for further research on the clinical application of degradable magnesium alloy suture anchors.展开更多
Accumulating evidence supports the association of somatic mutations with tumor occurrence and development.We aimed to identify somatic mutations with important implications in hepatocellular carcinoma(HCC)and explore ...Accumulating evidence supports the association of somatic mutations with tumor occurrence and development.We aimed to identify somatic mutations with important implications in hepatocellular carcinoma(HCC)and explore their possible mechanisms.The gene mutation profiles of HCC patients were assessed,and the tumor mutation burden was calculated.Gene mutations closely associated with tumor mutation burden and patient overall survival were identified.In vivo and in vitro experiments were performed to verify the effects of putative genes on proliferation,invasion,drug resistance,and other malignant biological behaviors of tumor cells.Fourteen genes with a high mutation frequency were identified.The mutation status of 12 of these genes was closely related to the mutation burden.Among these 12 genes,LRP1B mutation was closely associated with patient prognosis.Nine genes were associated with immune cell infiltration.The results of in vivo and in vitro experiments showed that the knockdown of LRP1B promotes tumor cell proliferation and migration and enhances the resistance of tumor cells to liposomal doxorubicin.LRP1B could directly bind to NCSTN and affect its protein expression level,thereby regulating the PI3K/AKT pathway.Our mutational analysis revealed complex and orchestrated liposomal alterations linked to doxorubicin resistance that may also render cancers less susceptible to immunotherapy and also provides new treatment alternatives.展开更多
基金supported by Scientific and Technological Project in Henan Province(212102310236,202102210015)National Natural Science Foundation of China(51701184,51671175)+1 种基金the Key Projects of the Joint Fund of the National Natural Science Foundation of China(U1804251)the Postgraduate Independent Innovation Project of Zhengzhou University(20211203).
文摘Current materials comprising suture anchors used to reconstruct ligament-bone junctions still have limitation in biocompatibility,degradability or mechanical properties.Magnesium alloys are potential bone implant materials,and Mg^(2+) has been shown to promote ligament-bone healing.Here,we used Mg-2 wt.%Zn-0.5 wt.%Y-1 wt.%Nd-0.5 wt.%Zr(ZE21C)alloy and Ti6Al4V(TC4)alloy to prepare suture anchors to reconstruct the patellar ligament-tibia in SD rats.We studied the degradation behavior of the ZE21C suture anchor via in vitro and in vivo experiments and assessed its reparative effect on the ligament-bone junction.In vitro,the ZE21C suture anchor degraded gradually,and calcium and phosphorus products accumulated on its surface during degradation.In vivo,the ZE21C suture anchor could maintain its mechanical integrity within 12 weeks of implantation in rats.The tail of the ZE21C suture anchor in high stress concentration degraded rapidly during the early implantation stage(0-4weeks),while bone healing accelerated the degradation of the anchor head in the late implantation stage(4-12weeks).Radiological,histological,and biomechanical assays indicated that the ZE21C suture anchor promoted bone healing above the suture anchor and fibrocartilaginous interface regeneration in the ligament-bone junction,leading to better biomechanical strength than the TC4 group.Hence,this study provides a basis for further research on the clinical application of degradable magnesium alloy suture anchors.
基金funded by the National Natural Science Foundation of China(No.81871653)the Natural Science Foundationof Chongqing,China(No.cstc2020jcyjmsxmx0159)+3 种基金Chongqing Science and Health Joint Medical High-end Talent Project(China)(No.2022GDRC012)Science and Technology Research Program of Chongqing Municipal Education Commission(China)(No.KJZDK202100402 and KJQN201900449)CQMU Program for Youth Innovation in Future Medicine(China)(No.W0073)Second Hospital of Shandong University Cultivation Funding(China)(No.2022YP45).
文摘Accumulating evidence supports the association of somatic mutations with tumor occurrence and development.We aimed to identify somatic mutations with important implications in hepatocellular carcinoma(HCC)and explore their possible mechanisms.The gene mutation profiles of HCC patients were assessed,and the tumor mutation burden was calculated.Gene mutations closely associated with tumor mutation burden and patient overall survival were identified.In vivo and in vitro experiments were performed to verify the effects of putative genes on proliferation,invasion,drug resistance,and other malignant biological behaviors of tumor cells.Fourteen genes with a high mutation frequency were identified.The mutation status of 12 of these genes was closely related to the mutation burden.Among these 12 genes,LRP1B mutation was closely associated with patient prognosis.Nine genes were associated with immune cell infiltration.The results of in vivo and in vitro experiments showed that the knockdown of LRP1B promotes tumor cell proliferation and migration and enhances the resistance of tumor cells to liposomal doxorubicin.LRP1B could directly bind to NCSTN and affect its protein expression level,thereby regulating the PI3K/AKT pathway.Our mutational analysis revealed complex and orchestrated liposomal alterations linked to doxorubicin resistance that may also render cancers less susceptible to immunotherapy and also provides new treatment alternatives.