Ankylosing spondylitis(AS), a common type of spondyloarthropathy, is a chronic inflammatory autoimmune disease that mainly affects spine joints, causing severe, chronic pain;additionally, in more advanced cases, it ca...Ankylosing spondylitis(AS), a common type of spondyloarthropathy, is a chronic inflammatory autoimmune disease that mainly affects spine joints, causing severe, chronic pain;additionally, in more advanced cases, it can cause spine fusion. Significant progress in its pathophysiology and treatment has been achieved in the last decade. Immune cells and innate cytokines have been suggested to be crucial in the pathogenesis of AS, especially human leukocyte antigen(HLA)?B27 and the interleukin?23/17 axis.However, the pathogenesis of AS remains unclear. The current study reviewed the etiology and pathogenesis of AS, including genome-wide association studies and cytokine pathways. This study also summarized the current pharmaceutical and surgical treatment with a discussion of future potential therapies.展开更多
1.Research and development(R&D)and the challenges of raw materials for medical additive manufacturing Raw materials for medical additive manufacturing have a wide range of commonalities that are also seen in many ...1.Research and development(R&D)and the challenges of raw materials for medical additive manufacturing Raw materials for medical additive manufacturing have a wide range of commonalities that are also seen in many other fields,making them an important basis in the field of three-dimensional(3D)printing.Problems and challenges related to material types,powder properties,formability,viscoelasticity,and so forth also share common features.For example,many metal materials are used in the field of aviation,while metals,polymers,and inorganic materials are used in the field of biomedicine.The most widely used materials in biomedicine are biocompatible.Various homogeneous and non-homogeneous composites are also available for 3D printing,and impose an additional challenge in additive manufacturing;the use of heterogeneous composites in 3D printing is particularly challenging.展开更多
Filamin B(FLNB)is a large dimeric actin-binding protein which crosslinks actin cytoskeleton filaments into a dynamic structure.Up to present,pathogenic mutations in FLNB are solely found to cause skeleta deformities,i...Filamin B(FLNB)is a large dimeric actin-binding protein which crosslinks actin cytoskeleton filaments into a dynamic structure.Up to present,pathogenic mutations in FLNB are solely found to cause skeleta deformities,indicating the important role of FLNB in skeletal development.FLNB-related disorders are classifiedasspondylocarpotarsalsynostosis(SCT),Larsensyndrome(LS),atelosteogenesis(AO)boomerang dysplasia(BD),and isolated congenital talipes equinovarus,presenting with scoliosis,shortlimbed dwarfism,clubfoot,joint dislocation and other unique skeletal abnormalities.Several mecha?nisms of FLNB mutations causing skeletal malformations have been proposed,including delay of ossification in long bone growth plate,reduction of bone mineral density(BMD),dysregulation of muscle differentiation,ossification of intervertebral disc(IVD),disturbance of proliferation,differentiation and apoptosis in chondrocytes,impairment of angiogenesis,and hypomotility of osteoblast,chondrocyte and fibroblast.Interventions on FLNB-related diseases require prenatal surveillance by sonography,gene testing in high-risk carriers,andproper orthosis or orthopedic surgeries to correct malformations including scoliosis,cervical spine instability,large joint dislocation,and clubfoot.Gene and cell therapies for FLNB-related diseases are also promising but require further studies.展开更多
Short stature is among the most common endocrinological disease phenotypes of childhood and may occur as an isolated finding or in conjunction with other clinical manifestations.Although the diagnostic utility of clin...Short stature is among the most common endocrinological disease phenotypes of childhood and may occur as an isolated finding or in conjunction with other clinical manifestations.Although the diagnostic utility of clinical genetic testing in short stature has been implicated,the genetic architecture and the utility of genomic studies such as exome sequencing(ES)in a sizable cohort of patients with short stature have not been investigated systematically.In this study,we recruited 561 individuals with short stature from two centers in China during a 4-year period.We performed ES for all patients and available parents.All patients were retrospectively divided into two groups:an isolated short stature group(group I,n=257)and an apparently syndromic short stature group(group II,n=304).Causal variants were identified in 135 of 561(24.1%)patients.In group I,29 of 257(11.3%)of the patients were solved by variants in 24 genes.In group II,106 of 304(34.9%)patients were solved by variants in 57 genes.Genes involved in fundamental cellularprocess played an important role in the genetic architecture of syndromic short stature.Distinct genetic architectures and pathophysiological processes underlie isolated and syndromic short stature.展开更多
Dear Editor,Congenital scoliosis(CS)is a spinal malformation charac-terized by failure of vertebral formation or segmentation,or a mix of these deformities,resulting in longitudinal and rotational imbalance,and affect...Dear Editor,Congenital scoliosis(CS)is a spinal malformation charac-terized by failure of vertebral formation or segmentation,or a mix of these deformities,resulting in longitudinal and rotational imbalance,and affects 0.05-0.1%of new-borns(Wu et al.2015).It is generally understood that the development of CS has an underlying genetic basis.Specifically,genes related to somite regulation or osteo-genesis during embryonic development are believed to be responsible for the vertebral malformations observed in CS patients(Pourquie 2011).展开更多
Developments in genetics and genomics are progressing at an unprecedented speed.Twenty years ago,the human genome project provided the first glimpses into the human genome sequence and launched a new era of human gene...Developments in genetics and genomics are progressing at an unprecedented speed.Twenty years ago,the human genome project provided the first glimpses into the human genome sequence and launched a new era of human genetics.The emerging of next-generation sequencing(NGS)in 2005 then made possible comprehensive genetic testing such as exome sequencing and genome sequencing.Meanwhile,great efforts have been put into the optimization of bioinformatic pipelines to make increasingly speedy and accurate variant analyses based on NGS data.These advances in sequencing technologies and analytical methods have revolutionized the diagnostic odyssey of suspected hereditary diseases.More recently,the genotype-phenotype relationship and polygenic risk scores(PRSs)generated from genome-wide association studies have expanded our horizon from rare genetic mutations to a genomic landscape implicated by the combined effect of both rare variants and polymorphisms.At the same time,clinicians and genetic counselors are facing huge challenges conferred by overwhelming genomic knowledge and long sheets of testing reports for comprehensive genomic sequencing.The path toward the“next-generation”clinical genetics and genomics may underlie semiautomatic pipelines assisted by artificial intelligence techniques.展开更多
基金supported by the Beijing Natural Science Foundation youth project (7184325)the China Postdoctoral Foundation NO.62 general program
文摘Ankylosing spondylitis(AS), a common type of spondyloarthropathy, is a chronic inflammatory autoimmune disease that mainly affects spine joints, causing severe, chronic pain;additionally, in more advanced cases, it can cause spine fusion. Significant progress in its pathophysiology and treatment has been achieved in the last decade. Immune cells and innate cytokines have been suggested to be crucial in the pathogenesis of AS, especially human leukocyte antigen(HLA)?B27 and the interleukin?23/17 axis.However, the pathogenesis of AS remains unclear. The current study reviewed the etiology and pathogenesis of AS, including genome-wide association studies and cytokine pathways. This study also summarized the current pharmaceutical and surgical treatment with a discussion of future potential therapies.
文摘1.Research and development(R&D)and the challenges of raw materials for medical additive manufacturing Raw materials for medical additive manufacturing have a wide range of commonalities that are also seen in many other fields,making them an important basis in the field of three-dimensional(3D)printing.Problems and challenges related to material types,powder properties,formability,viscoelasticity,and so forth also share common features.For example,many metal materials are used in the field of aviation,while metals,polymers,and inorganic materials are used in the field of biomedicine.The most widely used materials in biomedicine are biocompatible.Various homogeneous and non-homogeneous composites are also available for 3D printing,and impose an additional challenge in additive manufacturing;the use of heterogeneous composites in 3D printing is particularly challenging.
基金supported by the National Natural Science Foundation of China(Nos.81501852,81472046 and 81472045)the Beijing Natural Science Foundation(No.7172175)+6 种基金the Beijing nova program(No.2161100004916123)the Beijing nova program interdisciplinary collaborative project(No.xxjc201717)the 2016 Milstein Medical Asian American Partnership Foundation Fellowship Award in Translational Medicine,the Central Level Public Interest Program for Scientific Research Institute(No.2016ZX310177)the PUMC Youth Fund&the Fundamental Research Funds for the Central Universities(No.3332016006)the CAMS Initiative for Innovative Medicine(No.2016-12M-3-003)the Distinguished Youth foundation of Peking Union Medical College Hospital(No.JQ201506)the National Key Research and Development Program of China(No.2016YFC0901501)
文摘Filamin B(FLNB)is a large dimeric actin-binding protein which crosslinks actin cytoskeleton filaments into a dynamic structure.Up to present,pathogenic mutations in FLNB are solely found to cause skeleta deformities,indicating the important role of FLNB in skeletal development.FLNB-related disorders are classifiedasspondylocarpotarsalsynostosis(SCT),Larsensyndrome(LS),atelosteogenesis(AO)boomerang dysplasia(BD),and isolated congenital talipes equinovarus,presenting with scoliosis,shortlimbed dwarfism,clubfoot,joint dislocation and other unique skeletal abnormalities.Several mecha?nisms of FLNB mutations causing skeletal malformations have been proposed,including delay of ossification in long bone growth plate,reduction of bone mineral density(BMD),dysregulation of muscle differentiation,ossification of intervertebral disc(IVD),disturbance of proliferation,differentiation and apoptosis in chondrocytes,impairment of angiogenesis,and hypomotility of osteoblast,chondrocyte and fibroblast.Interventions on FLNB-related diseases require prenatal surveillance by sonography,gene testing in high-risk carriers,andproper orthosis or orthopedic surgeries to correct malformations including scoliosis,cervical spine instability,large joint dislocation,and clubfoot.Gene and cell therapies for FLNB-related diseases are also promising but require further studies.
基金funded in part by the Beijing Natural Science Foundation(JQ20032 to N.W.and to 7191007 to Z.W.)National Natural Science Foundation of China(81822030 and 82072391 to N.W.,81772299and 81930068 to Z.W.,81772301 and 81972132 to G.Q.,81672123and 81972037 to J.Z.)+7 种基金Capital's Funds for Health Improvement and Research(2020-4-40114 to N.W.)Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research ProgramNational Key Research and Development Program of China(2018YFC0910500 to N.W.and Z.W.,2016YFC0901501 to S.Z.)the PUMC Youth Fund and the Fundamental Research Funds for the Central Universities(3332019052 to Y.M.)the CAMS Initiative Fund for Medical Sciences(2016-I2M-3-003 to G.Q.and N.W.,2016-I2M-2-006 and 2017-I2M-2-001 to Z.W.)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019PT320025 to N.W.)sponsored by GeneScience Pharmaceuticals Co.,Ltd.(Changchun,China)funded by the United States National Institutes of Health(UM1HG006542 and K08 HG008986)。
文摘Short stature is among the most common endocrinological disease phenotypes of childhood and may occur as an isolated finding or in conjunction with other clinical manifestations.Although the diagnostic utility of clinical genetic testing in short stature has been implicated,the genetic architecture and the utility of genomic studies such as exome sequencing(ES)in a sizable cohort of patients with short stature have not been investigated systematically.In this study,we recruited 561 individuals with short stature from two centers in China during a 4-year period.We performed ES for all patients and available parents.All patients were retrospectively divided into two groups:an isolated short stature group(group I,n=257)and an apparently syndromic short stature group(group II,n=304).Causal variants were identified in 135 of 561(24.1%)patients.In group I,29 of 257(11.3%)of the patients were solved by variants in 24 genes.In group II,106 of 304(34.9%)patients were solved by variants in 57 genes.Genes involved in fundamental cellularprocess played an important role in the genetic architecture of syndromic short stature.Distinct genetic architectures and pathophysiological processes underlie isolated and syndromic short stature.
基金This research was funded in part by Beijing Natural Science Foundation(JQ20032 to N.W.,7191007 to ZW)the National Natural Science Foundation of China(81822030 and 82072391 to NW,81930068 and 81772299 to ZW,81972132 to GQ,81672123 and 81972037 to TJZ,81871746 to YW)the China Postdoctoral Science Foundation(No.2020TQ0052 to ZL).
文摘Dear Editor,Congenital scoliosis(CS)is a spinal malformation charac-terized by failure of vertebral formation or segmentation,or a mix of these deformities,resulting in longitudinal and rotational imbalance,and affects 0.05-0.1%of new-borns(Wu et al.2015).It is generally understood that the development of CS has an underlying genetic basis.Specifically,genes related to somite regulation or osteo-genesis during embryonic development are believed to be responsible for the vertebral malformations observed in CS patients(Pourquie 2011).
基金supported by the National Natural Science Founda-tion of China(Grant Nos.81822030 and 82072391 to N.W.,81930068 and 81772299 to Z.W.,81772301 and 81972132 to G.Q.,81672123 and 81972037 to J.Z.)Beijing Natural Science Foundation(Grant Nos.JQ20032 to N.W.,and 7191007 to Z.W.)+1 种基金Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program,Non-profit Central Research Institute Fund of Chinese Academy of Med-ical Sciences(Grant No.2019PT320025)the National Undergradu-ates Innovation and Training Program of Peking Union Medical College(Grant Nos.202010023022 to S.Z.).
文摘Developments in genetics and genomics are progressing at an unprecedented speed.Twenty years ago,the human genome project provided the first glimpses into the human genome sequence and launched a new era of human genetics.The emerging of next-generation sequencing(NGS)in 2005 then made possible comprehensive genetic testing such as exome sequencing and genome sequencing.Meanwhile,great efforts have been put into the optimization of bioinformatic pipelines to make increasingly speedy and accurate variant analyses based on NGS data.These advances in sequencing technologies and analytical methods have revolutionized the diagnostic odyssey of suspected hereditary diseases.More recently,the genotype-phenotype relationship and polygenic risk scores(PRSs)generated from genome-wide association studies have expanded our horizon from rare genetic mutations to a genomic landscape implicated by the combined effect of both rare variants and polymorphisms.At the same time,clinicians and genetic counselors are facing huge challenges conferred by overwhelming genomic knowledge and long sheets of testing reports for comprehensive genomic sequencing.The path toward the“next-generation”clinical genetics and genomics may underlie semiautomatic pipelines assisted by artificial intelligence techniques.
