CD4^(+)T-helper 1 cell(Th1)function is closely regulated by an intrinsic developmental program in which activation/induction and proinflammatory interferon(IFN)-γ secretion are followed by a deactivation/contraction ...CD4^(+)T-helper 1 cell(Th1)function is closely regulated by an intrinsic developmental program in which activation/induction and proinflammatory interferon(IFN)-γ secretion are followed by a deactivation/contraction period characterized by a switch into cosecretion of immunoregulatory interleukin(IL)-10.展开更多
Fetal skeletal dysplasia(FSD)encompasses diverse clinical features and complicates prenatal diagnosis and perinatal care.In this retrospective study,we integrate prenatal deep phenotyping with exome or genome sequenci...Fetal skeletal dysplasia(FSD)encompasses diverse clinical features and complicates prenatal diagnosis and perinatal care.In this retrospective study,we integrate prenatal deep phenotyping with exome or genome sequencing(ES/GS)to elucidate comprehensive genotype and phenotype landscapes,diagnostic outcomes,genotype-phenotype correlations,and postnatal follow-up findings and to refine genetic counseling and clinical decision-making.The study includes a cohort of 152 fetuses with FSD in China.All fetuses undergo prenatal deep phenotyping followed by ES/GS analysis.Prenatal deep phenotyping enables classification into isolated and non-isolated FSD groups and identifies previously unrecognized prenatal features associated with KBG syndrome and Segawa syndrome.Among skeletal anomalies,limb bone anomalies are the most common(72.4%).Genetic testing yields positive diagnoses in 88 fetuses(57.9%).Notably,fetuses with cranial and limb bone abnormalities demonstrate a higher diagnostic yield.Comparative analysis of prenatal and postnatal genotypes and phenotypes in individuals harboring pathogenic variants in four hotspot genes provides a deeper understanding of skeletal dysplasia phenotypes.Genetic findings from this cohort directly inform reproductive decisions in 16 subsequent pregnancies.Our findings significantly enhance genotype-phenotype correlations and contribute to improved prenatal counseling,informed clinical decision-making,and optimized perinatal care,and advance precision medicine strategies for FSD-affected families.展开更多
Despite recent advances in technology,clinical phenotyping of Parkinson’s disease(PD)has remained relatively limited as current assessments are mainly based on empirical observation and subjective categorical judgmen...Despite recent advances in technology,clinical phenotyping of Parkinson’s disease(PD)has remained relatively limited as current assessments are mainly based on empirical observation and subjective categorical judgment at the clinic.A lack of comprehensive,objective,and quantifiable clinical phenotyping data has hindered our capacity to diagnose,assess patients’conditions,discover pathogenesis,identify preclinical stages and clinical subtypes,and evaluate new therapies.Therefore,deep clinical phenotyping of PD patients is a necessary step towards understanding PD pathology and improving clinical care.In this review,we present a growing community consensus and perspective on how to clinically phenotype this disease,that is,to phenotype the entire course of disease progression by integrating capacity,performance,and perception approaches with state-of-the-art technology.We also explore the most studied aspects of PD deep clinical phenotypes,namely,bradykinesia,tremor,dyskinesia and motor fluctuation,gait impairment,speech impairment,and non-motor phenotypes.展开更多
The TRacing Etiology of Non-communicable Diseases(TREND)cohort is a prospective longitudinal cohort and biobank that is mainly based in Ma’anshan,Anhui Province,China.The primary aim of the study is to decipher compr...The TRacing Etiology of Non-communicable Diseases(TREND)cohort is a prospective longitudinal cohort and biobank that is mainly based in Ma’anshan,Anhui Province,China.The primary aim of the study is to decipher comprehensive molecular characterization and deep phenotyping for a broad spectrum of chronic non-communicable diseases(NCDs),which focuses on providing mechanistic insights with diagnostic,prognostic and therapeutic implications.The recruitment was initiated in 2023 and is expected to complete in 2025 with 20,000 participants originated from urban and rural area.In the first phase,3360 participants were recruited.Follow-up visits are scheduled annually and intervally for a total of 30 years.The cohort includes individuals aged over 18 years.Two participants with first-degree linkage were recruited from a household.The age distribution of recruited participants was stratified into four categories:18-45,45-55,55-65,and≥65 years,aligning with the population proportions of Ma’anshan.Meanwhile,the gender distribution was controlled by pairing men and women from the same household.Data collected at baseline includes socio-economic information,medical history,lifestyle and nutritional habits,anthropometrics,blood oxygen,electrocardiogram(ECG),heart sound,as well as blood,urine and feces tests results.Molecular profiling includes genome,proteome,metabolome,microbiome and extracellular vesicles-omics.Blood,urine and fecal samples are collected and stored at−80°C in a storage facility for future research.展开更多
文摘CD4^(+)T-helper 1 cell(Th1)function is closely regulated by an intrinsic developmental program in which activation/induction and proinflammatory interferon(IFN)-γ secretion are followed by a deactivation/contraction period characterized by a switch into cosecretion of immunoregulatory interleukin(IL)-10.
基金the National Key Research and Development Program of China(2022YFC2703100 to S.Z.,2024YFC2707100 for Q.Q.,2022YFC2703901 to Z.W.,2022YFC2703102 to N.W.)National Natural Science Foundation of China(82172525 to G.Q.,82172382 to J.Z.)+2 种基金CAMS Innovation Fund for Medical Sciences(CIFMS,2021-I2M-1-051 to J.Z.and N.W.,2021-I2M-1-052 and 2022-I2M-2-001 to Z.W.,2023-I2M-C&T-A-003 to J.Z.)National High Level Hospital Clinical Research Funding(2022-PUMCH-D-004 to J.Z.and N.W.,2022-PUMCH-C-033 to N.W.,2022-PUMCH-D-002 to Z.W.)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019PT320025 to N.W.).
文摘Fetal skeletal dysplasia(FSD)encompasses diverse clinical features and complicates prenatal diagnosis and perinatal care.In this retrospective study,we integrate prenatal deep phenotyping with exome or genome sequencing(ES/GS)to elucidate comprehensive genotype and phenotype landscapes,diagnostic outcomes,genotype-phenotype correlations,and postnatal follow-up findings and to refine genetic counseling and clinical decision-making.The study includes a cohort of 152 fetuses with FSD in China.All fetuses undergo prenatal deep phenotyping followed by ES/GS analysis.Prenatal deep phenotyping enables classification into isolated and non-isolated FSD groups and identifies previously unrecognized prenatal features associated with KBG syndrome and Segawa syndrome.Among skeletal anomalies,limb bone anomalies are the most common(72.4%).Genetic testing yields positive diagnoses in 88 fetuses(57.9%).Notably,fetuses with cranial and limb bone abnormalities demonstrate a higher diagnostic yield.Comparative analysis of prenatal and postnatal genotypes and phenotypes in individuals harboring pathogenic variants in four hotspot genes provides a deeper understanding of skeletal dysplasia phenotypes.Genetic findings from this cohort directly inform reproductive decisions in 16 subsequent pregnancies.Our findings significantly enhance genotype-phenotype correlations and contribute to improved prenatal counseling,informed clinical decision-making,and optimized perinatal care,and advance precision medicine strategies for FSD-affected families.
基金JW received research funding from Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01,and 21S31902200)ZJ Lab,Shanghai Center for Brain Science and Brain-Inspired Technology,and the National Nature Science Foundation of China(grant numbers:82171421,91949118 and 81771372).
文摘Despite recent advances in technology,clinical phenotyping of Parkinson’s disease(PD)has remained relatively limited as current assessments are mainly based on empirical observation and subjective categorical judgment at the clinic.A lack of comprehensive,objective,and quantifiable clinical phenotyping data has hindered our capacity to diagnose,assess patients’conditions,discover pathogenesis,identify preclinical stages and clinical subtypes,and evaluate new therapies.Therefore,deep clinical phenotyping of PD patients is a necessary step towards understanding PD pathology and improving clinical care.In this review,we present a growing community consensus and perspective on how to clinically phenotype this disease,that is,to phenotype the entire course of disease progression by integrating capacity,performance,and perception approaches with state-of-the-art technology.We also explore the most studied aspects of PD deep clinical phenotypes,namely,bradykinesia,tremor,dyskinesia and motor fluctuation,gait impairment,speech impairment,and non-motor phenotypes.
基金supported by:Municipal Designated Funds of Ma'anshan for Chronic Non-communicable Diseases Prevention,National Natural Science Foundation of China(NSFC,32394052,82204033,32270077 and Excellent Young Scientists Fund Program Overseas-2022)Jiangsu Shuangchuang Project(Medical Innovation Team,Medical Expert and JSSCBS20221815)+6 种基金Designated Funds for Provincial Demonstration Areas for Comprehensive Prevention and Control of Chronic Non-communicable Diseases,Desiginated Funds for Basic Healthcare and Health Promotion,the Natural Sci-ence Foundation of Jiangsu grant(BK2022020826,BK20220709)Fundamental Research Funds for the Central Universities of China(2242022R10062/3225002202A1)Medical Foundation of Southeast University(4060692202/021)Zhishan Young Scholar Award at the Southeast University(2242023R40031)The Scientific Research Pro-ject for Health Commission of Anhui Province(AHWJ2023A20172,AHWJ2023BAa20055)Nanjing Medical University(CMCM202204,303073572NC21&YNRCZN0301)Development of Jiangsu Higher Education Institutions Priority Academic Program(PAPD).
文摘The TRacing Etiology of Non-communicable Diseases(TREND)cohort is a prospective longitudinal cohort and biobank that is mainly based in Ma’anshan,Anhui Province,China.The primary aim of the study is to decipher comprehensive molecular characterization and deep phenotyping for a broad spectrum of chronic non-communicable diseases(NCDs),which focuses on providing mechanistic insights with diagnostic,prognostic and therapeutic implications.The recruitment was initiated in 2023 and is expected to complete in 2025 with 20,000 participants originated from urban and rural area.In the first phase,3360 participants were recruited.Follow-up visits are scheduled annually and intervally for a total of 30 years.The cohort includes individuals aged over 18 years.Two participants with first-degree linkage were recruited from a household.The age distribution of recruited participants was stratified into four categories:18-45,45-55,55-65,and≥65 years,aligning with the population proportions of Ma’anshan.Meanwhile,the gender distribution was controlled by pairing men and women from the same household.Data collected at baseline includes socio-economic information,medical history,lifestyle and nutritional habits,anthropometrics,blood oxygen,electrocardiogram(ECG),heart sound,as well as blood,urine and feces tests results.Molecular profiling includes genome,proteome,metabolome,microbiome and extracellular vesicles-omics.Blood,urine and fecal samples are collected and stored at−80°C in a storage facility for future research.
