Background:Recent clinical trials have shown that inhibitors targeting programmed cell death protein 1(PD-1)or its ligand(programmed cell death-ligand 1[PD-L1])provide significant efficacy and clinical benefit in the ...Background:Recent clinical trials have shown that inhibitors targeting programmed cell death protein 1(PD-1)or its ligand(programmed cell death-ligand 1[PD-L1])provide significant efficacy and clinical benefit in the treatment of advanced ormetastatic urothelial carcinoma(UC).This systematic review and meta-analysis aimed to compare the effectiveness and safety of PD-1/PD-L1 inhibitors in combination with chemotherapy or PD-1/PD-L1 inhibitor monotherapy versus platinum-based chemotherapy as a first-line treatment for advanced UC.Materials and methods:From the beginning of the database construction to February 4,2024,a combination of medical subject headings and free-text words was searched using the Population Intervention Comparison Outcome Study design framework.The PubMed,Cochrane Library,Embase,and Web of Science electronic databases were searched.Meta-analyses of progressionfree survival,overall survival,objective response rate(ORR),complete remission rate,duration of remission,and grade≥3 adverse events were performed.Results:Four studieswere included in the meta-analysis.The PD-1/PD-L1 inhibitors plus chemotherapy therapy is associated with significantly better ORR compared with chemotherapy.Unfortunately,there were no significant differences between PD-1/PD-L1 inhibitor monotherapy and chemotherapy in terms of ORR,duration of remission,or overall survival.Conclusions:Our findings indicate that PD-1/PD-L1 inhibitors plus chemotherapy therapy provides more oncological advantages than standard chemotherapy and should be recommended as a first-line treatment for advanced or metastatic UC.Attention must also be paid to the adverse effects of the combination of PD-1/PD-L1 inhibitors and chemotherapy.展开更多
The two most critical factors in promoting the clinical translation of magnesium(Mg)are reducing its degradation rate and improving its osteogenesis.In this study,a Ca-deficient hydroxyapatite(CDHA)/MgF_(2)bilayer coa...The two most critical factors in promoting the clinical translation of magnesium(Mg)are reducing its degradation rate and improving its osteogenesis.In this study,a Ca-deficient hydroxyapatite(CDHA)/MgF_(2)bilayer coating was prepared on high-purity magnesium(HP Mg)rods by fluorination and hydrothermal treatment.Scanning electron microscope showed that the thickness of the bilayer coating was 3.78 lm and that the surface morphology was nanoscale.In an in vivo experiment on femoral condyle defects in rabbits,the serum magnesium ion levels of rabbits were always in the normal range after surgery,and the liver and kidney functions were not abnormal,which indicated that the CDHA/MgF_(2)bilayer coating has good biosafety.Micro-CT showed that the CDHA/MgF_(2)bilayer coating significantly reduced the degradation rate of the HP Mg rods and enhanced the promotion of bone formation.Hard tissue sections showed that the CDHA/MgF_(2)bilayer coating gave the bone tissue a tight contact interface with the HP Mg rod and improved the bone mass.Immunohistochemistry showed that the expression of vascular endothelial growth factor and BMP-2 was more obvious.These results confirm that the CDHA/MgF_(2)bilayer coating can improve the properties of HP Mg and provide a basis for the further transformation of HP Mg in the future.It also provides a new reference for the surface modification of magnesiummetal.展开更多
1 Introduction The lip reading involves converting the image sequence into the corresponding text sequence.Currently,lip reading has significant applications in many fields,such as assisted speech recognition,helping ...1 Introduction The lip reading involves converting the image sequence into the corresponding text sequence.Currently,lip reading has significant applications in many fields,such as assisted speech recognition,helping the speech impaired.Lip reading belongs to fine-grained video analysis and requires the local information and the overall spatial information of sequence.Most existing approaches capture local spatial information with CNN and temporal information with RNN generally.Considering these general methods,we propose a fine-grained method based on self-attention and self-distillation.The whole model mainly includes the CNN front-end,pixel-wise learning,temporal learning,and decoder.Specifically,we apply the CNN front-end to capture shallow spatial features inside the image sequence,and employ the Resformer module including self-attention to learn the global spatial correlation between pixels,namely,pixel-wise learning.展开更多
The vast majority of p53 missense mutants lose the wild-type (wt) function and/or exert ‘dominant-negative’ effects on their wt counterpart. Here, we identify a novel form of p53 mutation with an extended C-terminus...The vast majority of p53 missense mutants lose the wild-type (wt) function and/or exert ‘dominant-negative’ effects on their wt counterpart. Here, we identify a novel form of p53 mutation with an extended C-terminus (p53 long C-terminus, p53LC) in a variety of human cancers. Interestingly, the two representative mutants (named ‘p53-374*48’ and ‘p53-393*78’) as tested in this study show both loss-of-function and dominant-negative phenotypes in cell proliferation and colony formation assays. Mechanistically, p53LCs interact with and retain wt p53 in the cytoplasm and prevent it from binding to the promoters of target genes, consequently inhibiting its transcriptional activity. Also, p53LCs are very stable, though not acetylated in cells. Remarkably, the p53LCs can desensitize wt p53-containing cancer cells to p53-activating agents. Together, our results unveil a longer form of p53 mutant that possesses a dominant-negative effect on its wt counterpart, besides losing its wt activity.展开更多
Continuous advancements in medical technology and biomaterials have underscored the significant advantages of biodegradable implant materials for bone repair and remodelling over traditional inert metallic implants.No...Continuous advancements in medical technology and biomaterials have underscored the significant advantages of biodegradable implant materials for bone repair and remodelling over traditional inert metallic implants.Notably,biodegradable magnesium-based materials have gained much attention because of their optimal corrosion rates.Importantly,extensive clinical experience has resulted in the use of biodegradable magnesium-based orthopaedic implants.Both preclinical and clinical studies have consistently demonstrated that Mg has an excellent ability to promote bone tissue formation,a process that is closely associated with the release of Mg^(2+)and other degradation byproducts.Bone metabolism depends on a dynamic balance of bone formation and bone resorption.Mg^(2+)has been shown to increase osteoblast(OB)activity while suppressing osteoclast(OC)formation,thus playing a crucial role in bone remodelling and regeneration.In terms of osteolysis inhibition,Mg^(2+)plays a multifaceted role.First,Mg^(2+)inhibits OC formation by modulating the activity of mature OCs,their migratory behaviour and the activity of precursor cells.Second,Mg^(2+)influences OC production by regulating the expression of osteoprotegerin(OPG),receptor activator of nuclear factor kappa-Βligand(RANKL)and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB).Additionally,Mg^(2+)impacts bone resorption by altering the immune microenvironment and the levels of hormones and peptides within the body.Furthermore,the alkaline environment generated around the biodegradable magnesium implant and its degradation products(e.g.H2)also significantly inhibit OC formation.Recent research on magnesium-based implants has focused predominantly on their osteogenic properties,with few systematic reviews addressing the mechanisms through which biodegradable magnesium alloys suppress osteoclastic activity.This article summarizes the latest clinical research progress concerning biodegradable magnesium implant materials and their significant regulatory effects and discusses recent advances in the understanding of the regulatory mechanisms of action Mg-based biomaterials on OCs,with the aim of providing a more theoretical basis for the clinical application of biodegradable magnesium-based implants.展开更多
基金supported by the Guangxi Natural Science Foundation Program(no.2024GXNSFBA010036)the Scientific Research Foundation of Guangxi Health Commission(Z-B20220927)the Scientific Research Foundation of Guangxi Health Commission(Z-B20220930).
文摘Background:Recent clinical trials have shown that inhibitors targeting programmed cell death protein 1(PD-1)or its ligand(programmed cell death-ligand 1[PD-L1])provide significant efficacy and clinical benefit in the treatment of advanced ormetastatic urothelial carcinoma(UC).This systematic review and meta-analysis aimed to compare the effectiveness and safety of PD-1/PD-L1 inhibitors in combination with chemotherapy or PD-1/PD-L1 inhibitor monotherapy versus platinum-based chemotherapy as a first-line treatment for advanced UC.Materials and methods:From the beginning of the database construction to February 4,2024,a combination of medical subject headings and free-text words was searched using the Population Intervention Comparison Outcome Study design framework.The PubMed,Cochrane Library,Embase,and Web of Science electronic databases were searched.Meta-analyses of progressionfree survival,overall survival,objective response rate(ORR),complete remission rate,duration of remission,and grade≥3 adverse events were performed.Results:Four studieswere included in the meta-analysis.The PD-1/PD-L1 inhibitors plus chemotherapy therapy is associated with significantly better ORR compared with chemotherapy.Unfortunately,there were no significant differences between PD-1/PD-L1 inhibitor monotherapy and chemotherapy in terms of ORR,duration of remission,or overall survival.Conclusions:Our findings indicate that PD-1/PD-L1 inhibitors plus chemotherapy therapy provides more oncological advantages than standard chemotherapy and should be recommended as a first-line treatment for advanced or metastatic UC.Attention must also be paid to the adverse effects of the combination of PD-1/PD-L1 inhibitors and chemotherapy.
基金supported by Dalian Health Commission,medical key specialty of Dengfeng project[grant number(2021)243]National Orthopedics and Sports Rehabilitation Clinical Research Center Innovation Fund(2021-NCRC-CXJJ-ZH-28).
文摘The two most critical factors in promoting the clinical translation of magnesium(Mg)are reducing its degradation rate and improving its osteogenesis.In this study,a Ca-deficient hydroxyapatite(CDHA)/MgF_(2)bilayer coating was prepared on high-purity magnesium(HP Mg)rods by fluorination and hydrothermal treatment.Scanning electron microscope showed that the thickness of the bilayer coating was 3.78 lm and that the surface morphology was nanoscale.In an in vivo experiment on femoral condyle defects in rabbits,the serum magnesium ion levels of rabbits were always in the normal range after surgery,and the liver and kidney functions were not abnormal,which indicated that the CDHA/MgF_(2)bilayer coating has good biosafety.Micro-CT showed that the CDHA/MgF_(2)bilayer coating significantly reduced the degradation rate of the HP Mg rods and enhanced the promotion of bone formation.Hard tissue sections showed that the CDHA/MgF_(2)bilayer coating gave the bone tissue a tight contact interface with the HP Mg rod and improved the bone mass.Immunohistochemistry showed that the expression of vascular endothelial growth factor and BMP-2 was more obvious.These results confirm that the CDHA/MgF_(2)bilayer coating can improve the properties of HP Mg and provide a basis for the further transformation of HP Mg in the future.It also provides a new reference for the surface modification of magnesiummetal.
文摘1 Introduction The lip reading involves converting the image sequence into the corresponding text sequence.Currently,lip reading has significant applications in many fields,such as assisted speech recognition,helping the speech impaired.Lip reading belongs to fine-grained video analysis and requires the local information and the overall spatial information of sequence.Most existing approaches capture local spatial information with CNN and temporal information with RNN generally.Considering these general methods,we propose a fine-grained method based on self-attention and self-distillation.The whole model mainly includes the CNN front-end,pixel-wise learning,temporal learning,and decoder.Specifically,we apply the CNN front-end to capture shallow spatial features inside the image sequence,and employ the Resformer module including self-attention to learn the global spatial correlation between pixels,namely,pixel-wise learning.
文摘The vast majority of p53 missense mutants lose the wild-type (wt) function and/or exert ‘dominant-negative’ effects on their wt counterpart. Here, we identify a novel form of p53 mutation with an extended C-terminus (p53 long C-terminus, p53LC) in a variety of human cancers. Interestingly, the two representative mutants (named ‘p53-374*48’ and ‘p53-393*78’) as tested in this study show both loss-of-function and dominant-negative phenotypes in cell proliferation and colony formation assays. Mechanistically, p53LCs interact with and retain wt p53 in the cytoplasm and prevent it from binding to the promoters of target genes, consequently inhibiting its transcriptional activity. Also, p53LCs are very stable, though not acetylated in cells. Remarkably, the p53LCs can desensitize wt p53-containing cancer cells to p53-activating agents. Together, our results unveil a longer form of p53 mutant that possesses a dominant-negative effect on its wt counterpart, besides losing its wt activity.
基金supported by Dalian Key Medical Specialties"Peak Climbing"Program(No.2021[243])China Postdoctoral Science Foundation(No.2021M690494)+3 种基金Dongguan Science and Technology of Social Development Program(20211800904602)Youth Star of Science and Technology of Dalian(No.2022RQ001)Liaoning Provincial Science and Technology Plan Joint Plan(No.2024-MSLH-012)Dalian Life and Health Sector Guidance Program(No.2024ZDJH01PT141).
文摘Continuous advancements in medical technology and biomaterials have underscored the significant advantages of biodegradable implant materials for bone repair and remodelling over traditional inert metallic implants.Notably,biodegradable magnesium-based materials have gained much attention because of their optimal corrosion rates.Importantly,extensive clinical experience has resulted in the use of biodegradable magnesium-based orthopaedic implants.Both preclinical and clinical studies have consistently demonstrated that Mg has an excellent ability to promote bone tissue formation,a process that is closely associated with the release of Mg^(2+)and other degradation byproducts.Bone metabolism depends on a dynamic balance of bone formation and bone resorption.Mg^(2+)has been shown to increase osteoblast(OB)activity while suppressing osteoclast(OC)formation,thus playing a crucial role in bone remodelling and regeneration.In terms of osteolysis inhibition,Mg^(2+)plays a multifaceted role.First,Mg^(2+)inhibits OC formation by modulating the activity of mature OCs,their migratory behaviour and the activity of precursor cells.Second,Mg^(2+)influences OC production by regulating the expression of osteoprotegerin(OPG),receptor activator of nuclear factor kappa-Βligand(RANKL)and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB).Additionally,Mg^(2+)impacts bone resorption by altering the immune microenvironment and the levels of hormones and peptides within the body.Furthermore,the alkaline environment generated around the biodegradable magnesium implant and its degradation products(e.g.H2)also significantly inhibit OC formation.Recent research on magnesium-based implants has focused predominantly on their osteogenic properties,with few systematic reviews addressing the mechanisms through which biodegradable magnesium alloys suppress osteoclastic activity.This article summarizes the latest clinical research progress concerning biodegradable magnesium implant materials and their significant regulatory effects and discusses recent advances in the understanding of the regulatory mechanisms of action Mg-based biomaterials on OCs,with the aim of providing a more theoretical basis for the clinical application of biodegradable magnesium-based implants.
