The aim of this study was to investigate the clinical heterogeneity of Parkinson's disease(PD) among a cohort of Chinese patients in early stages.Clinical data on demographics,motor variables,motor phenotypes,dise...The aim of this study was to investigate the clinical heterogeneity of Parkinson's disease(PD) among a cohort of Chinese patients in early stages.Clinical data on demographics,motor variables,motor phenotypes,disease progression,global cognitive function,depression,apathy,sleep quality,constipation,fatigue,and L-dopa complications were collected from 138 Chinese PD subjects in early stages(Hoehn and Yahr stages 1-3).The PD subject subtypes were classified using k-means cluster analysis according to the clinical data from five-to three-cluster consecutively.Kappa statistical analysis was performed to evaluate the consistency among different subtype solutions.The cluster analysis indicated four main subtypes:the non-tremor dominant subtype(NTD,n=28,20.3%),rapid disease progression subtype(RDP,n=7,5.1%),young-onset subtype(YO,n=50,36.2%),and tremor dominant subtype(TD,n=53,38.4%).Overall,78.3%(108/138) of subjects were always classified between the same three groups(52 always in TD,7 in RDP,and 49 in NTD),and 98.6%(136/138) between five-and four-cluster solutions.However,subjects classified as NTD in the four-cluster analysis were dispersed into different subtypes in the three-cluster analysis,with low concordance between four-and three-cluster solutions(kappa value= 0.139,P=0.001).This study defines clinical heterogeneity of PD patients in early stages using a data-driven approach.The subtypes generated by the four-cluster solution appear to exhibit ideal internal cohesion and external isolation.展开更多
There have been multiple NOD2/CARD15 genotype- phenotype analyses undertaken in patients with Crohn’s disease since the gene’s discovery in 2001. This review focuses on the major published series based upon their si...There have been multiple NOD2/CARD15 genotype- phenotype analyses undertaken in patients with Crohn’s disease since the gene’s discovery in 2001. This review focuses on the major published series based upon their size and on the presence of specific clinical and genetic information provided in the published material from 2001 to 2005. Twelve studies provided raw data to carry out comparisons of disease location while ten studies included analysis of NOD2/CARD15 genotypes. NOD2/CARD15 variant frequency in ileal disease did not differ significantly among studies, whereas a comparison of disease location demonstrated highly significant differences among studies. Meta-analysis confirmed significant associations between NOD2/CARD15 variants and both ileal and ileocolonic disease locations, and with both stricturing and penetrating forms of disease behavior. This review underlines the significant phenotypic differences that exist among populations, including similar ethnic groups, and has demonstrated the need for further studies of patients with long-term “inflammatory” Crohn’s disease.展开更多
脆性X综合征(fragile X syndrome,FXS)是FMR1基因CGG异常重复扩增导致的疾病。本文报告1对经基因检测诊断为FXS的兄弟,2例患者分别为15岁和14岁,均存在语言障碍、智力障碍、注意力缺陷障碍、孤独症谱系障碍和FXS特征性面容等临床表现,...脆性X综合征(fragile X syndrome,FXS)是FMR1基因CGG异常重复扩增导致的疾病。本文报告1对经基因检测诊断为FXS的兄弟,2例患者分别为15岁和14岁,均存在语言障碍、智力障碍、注意力缺陷障碍、孤独症谱系障碍和FXS特征性面容等临床表现,其中先证者伴有罕见的晚发性癫痫发作,经左乙拉西坦治疗效果良好,而其弟弟经反复随访未见脑电图异常。该对病例提示FXS临床表型具有多样性和异质性。展开更多
Examining age-specific heterogeneity of susceptibility to cardiovascular disease is also essential in individuals without prediabetes to determine its relative size and direction compared to those with prediabetes.Of ...Examining age-specific heterogeneity of susceptibility to cardiovascular disease is also essential in individuals without prediabetes to determine its relative size and direction compared to those with prediabetes.Of particular interest,age-specific heterogeneity in genetic susceptibility may exhibit opposite directions depending on the presence or absence of prediabetes.展开更多
The incidence of autoimmune liver diseases(ALDs)and research on their pathogenesis are increasing annually.However,except for autoimmune hepatitis,which responds well to immunosuppression,primary biliary cholangitis a...The incidence of autoimmune liver diseases(ALDs)and research on their pathogenesis are increasing annually.However,except for autoimmune hepatitis,which responds well to immunosuppression,primary biliary cholangitis and primary sclerosing cholangitis are insensitive to immunosuppressive therapy.Besides the known effects of the environment,genetics,and immunity on ALDs,the heterogeneity of target cells provides new insights into their pathogenesis.This review started by exploring the heterogeneity in the development,structures,and functions of hepatocytes and epithelial cells of the small and large bile ducts.For example,cytokeratin(CK)8 and CK18 are primarily expressed in hepatocytes,while CK7 and CK19 are primarily expressed in intrahepatic cholangiocytes.Additionally,emerging technologies of single-cell RNA sequencing and spatial transcriptomic are being applied to study ALDs.This review offered a new perspective on understanding the pathogenic mechanisms and potential treatment strategies for ALDs.展开更多
Chronic obstructive pulmonary disease(COPD)is a heterogeneous disease with a complex pathogenesis,which causes the lack of precise and personalized prevention,control,and treatment approaches in clinical practice.Trad...Chronic obstructive pulmonary disease(COPD)is a heterogeneous disease with a complex pathogenesis,which causes the lack of precise and personalized prevention,control,and treatment approaches in clinical practice.Traditional Chinese medicine(TCM)with multiple components acting on multiple targets plays a role in the prevention and treatment of COPD.After evaluating the treatment of cough,dyspnea,and lung distension based on syndrome differentiation in TCM,we summarized the commonly used TCMpreparations for treating COPD.These preparations are mainly composed of medicines for clearing interior heat and releasing exterior,tonifying,activating blood and resolving stasis,resolving phlegm,relieving cough and breathlessness,and regulating Qi movement.Because all of them contain a variety of active ingredients such as flavonoids,terpenoids,and phenols,we analyzed the mechanisms of the classic prescriptions alone or in combination with othermedicines or therapeuticmethods.These mechanisms involve counteracting inflammation,oxidative stress,and fibrosis,inhibiting apoptosis,alleviating airway remodeling,and enhancing immunity.Meantime,we summarized the existing problems in the treatment of COPD by TCM.This review provides a scientific basis for the research and treatment of COPD in the future.展开更多
Idiopathic pulmonary fibrosis(IPF)is characterized by accumulation of myofibroblasts(MYFs)and extracellular matrix components,which leads to severe distortion and scarring of the gas exchange units of the lung,the alv...Idiopathic pulmonary fibrosis(IPF)is characterized by accumulation of myofibroblasts(MYFs)and extracellular matrix components,which leads to severe distortion and scarring of the gas exchange units of the lung,the alveoli,and ultimately respiratory failure.Fibrosis-associated MYFs are therefore widely regarded as the culprits that compromise the architectural makeup of the lung in fibrotic disease.During the past decade,the cellular source of MYFs has been intensely investigated.The rationale for such studies is that identifying the origin of these cells might help identify novel therapeutic targets and candidates to treat IPF patients.Recent advances in basic and translational research employing lineage tracing and multi-omics approaches have helped address the identity of MYF precursors,highlight the underlying heterogeneity,and to a less extent investigate MYF fate during fibrosis resolution.In this review,we discuss the current understanding of such important aspects of MYF biology as well as recent developments in the treatment of IPF.展开更多
基金Project (No. 2006AA02A408) supported by the National High-Tech R & D Program (863) of China
文摘The aim of this study was to investigate the clinical heterogeneity of Parkinson's disease(PD) among a cohort of Chinese patients in early stages.Clinical data on demographics,motor variables,motor phenotypes,disease progression,global cognitive function,depression,apathy,sleep quality,constipation,fatigue,and L-dopa complications were collected from 138 Chinese PD subjects in early stages(Hoehn and Yahr stages 1-3).The PD subject subtypes were classified using k-means cluster analysis according to the clinical data from five-to three-cluster consecutively.Kappa statistical analysis was performed to evaluate the consistency among different subtype solutions.The cluster analysis indicated four main subtypes:the non-tremor dominant subtype(NTD,n=28,20.3%),rapid disease progression subtype(RDP,n=7,5.1%),young-onset subtype(YO,n=50,36.2%),and tremor dominant subtype(TD,n=53,38.4%).Overall,78.3%(108/138) of subjects were always classified between the same three groups(52 always in TD,7 in RDP,and 49 in NTD),and 98.6%(136/138) between five-and four-cluster solutions.However,subjects classified as NTD in the four-cluster analysis were dispersed into different subtypes in the three-cluster analysis,with low concordance between four-and three-cluster solutions(kappa value= 0.139,P=0.001).This study defines clinical heterogeneity of PD patients in early stages using a data-driven approach.The subtypes generated by the four-cluster solution appear to exhibit ideal internal cohesion and external isolation.
文摘There have been multiple NOD2/CARD15 genotype- phenotype analyses undertaken in patients with Crohn’s disease since the gene’s discovery in 2001. This review focuses on the major published series based upon their size and on the presence of specific clinical and genetic information provided in the published material from 2001 to 2005. Twelve studies provided raw data to carry out comparisons of disease location while ten studies included analysis of NOD2/CARD15 genotypes. NOD2/CARD15 variant frequency in ileal disease did not differ significantly among studies, whereas a comparison of disease location demonstrated highly significant differences among studies. Meta-analysis confirmed significant associations between NOD2/CARD15 variants and both ileal and ileocolonic disease locations, and with both stricturing and penetrating forms of disease behavior. This review underlines the significant phenotypic differences that exist among populations, including similar ethnic groups, and has demonstrated the need for further studies of patients with long-term “inflammatory” Crohn’s disease.
文摘脆性X综合征(fragile X syndrome,FXS)是FMR1基因CGG异常重复扩增导致的疾病。本文报告1对经基因检测诊断为FXS的兄弟,2例患者分别为15岁和14岁,均存在语言障碍、智力障碍、注意力缺陷障碍、孤独症谱系障碍和FXS特征性面容等临床表现,其中先证者伴有罕见的晚发性癫痫发作,经左乙拉西坦治疗效果良好,而其弟弟经反复随访未见脑电图异常。该对病例提示FXS临床表型具有多样性和异质性。
基金Supported by National Research Foundation of Korea,No.2018R1A2B6004867.
文摘Examining age-specific heterogeneity of susceptibility to cardiovascular disease is also essential in individuals without prediabetes to determine its relative size and direction compared to those with prediabetes.Of particular interest,age-specific heterogeneity in genetic susceptibility may exhibit opposite directions depending on the presence or absence of prediabetes.
文摘The incidence of autoimmune liver diseases(ALDs)and research on their pathogenesis are increasing annually.However,except for autoimmune hepatitis,which responds well to immunosuppression,primary biliary cholangitis and primary sclerosing cholangitis are insensitive to immunosuppressive therapy.Besides the known effects of the environment,genetics,and immunity on ALDs,the heterogeneity of target cells provides new insights into their pathogenesis.This review started by exploring the heterogeneity in the development,structures,and functions of hepatocytes and epithelial cells of the small and large bile ducts.For example,cytokeratin(CK)8 and CK18 are primarily expressed in hepatocytes,while CK7 and CK19 are primarily expressed in intrahepatic cholangiocytes.Additionally,emerging technologies of single-cell RNA sequencing and spatial transcriptomic are being applied to study ALDs.This review offered a new perspective on understanding the pathogenic mechanisms and potential treatment strategies for ALDs.
基金supported by National Natural Science Foundation of China(no.82104502)Scientific and technological innovation project of China Academy of Chinese Medical Sciences(no.CI2021B015,CI2021A04615)the Central Public-interest Scientific Institution Basal Research Fund(no.ZZ13-YQ-060,ZXKT21020,ZXKT23006).
文摘Chronic obstructive pulmonary disease(COPD)is a heterogeneous disease with a complex pathogenesis,which causes the lack of precise and personalized prevention,control,and treatment approaches in clinical practice.Traditional Chinese medicine(TCM)with multiple components acting on multiple targets plays a role in the prevention and treatment of COPD.After evaluating the treatment of cough,dyspnea,and lung distension based on syndrome differentiation in TCM,we summarized the commonly used TCMpreparations for treating COPD.These preparations are mainly composed of medicines for clearing interior heat and releasing exterior,tonifying,activating blood and resolving stasis,resolving phlegm,relieving cough and breathlessness,and regulating Qi movement.Because all of them contain a variety of active ingredients such as flavonoids,terpenoids,and phenols,we analyzed the mechanisms of the classic prescriptions alone or in combination with othermedicines or therapeuticmethods.These mechanisms involve counteracting inflammation,oxidative stress,and fibrosis,inhibiting apoptosis,alleviating airway remodeling,and enhancing immunity.Meantime,we summarized the existing problems in the treatment of COPD by TCM.This review provides a scientific basis for the research and treatment of COPD in the future.
基金B was supported by grants from the German Research Foundation(DFGNos.BE 4443/1-1,BE 4443/4-1,BE4443/6-1,KFO309284237345 P7 and CRC1213268555672 projects A02 and A04)+3 种基金German Center for Lung Research(DZL),and Excellence Cluster CardioPulmonary Institute(CPINo.EXC2026390649896)XC acknowledges the support of the Natural Science Foundation of Zhejiang Grant(No.LQ24H210001)EEA was supported by the DFG(Nos.EL 931/5-1,EL 931/4-1,KFO309284237345 P7 and SFB CRC1213268555672 project A04),Institute for Lung Health(ILH),CPI,and DZL.
文摘Idiopathic pulmonary fibrosis(IPF)is characterized by accumulation of myofibroblasts(MYFs)and extracellular matrix components,which leads to severe distortion and scarring of the gas exchange units of the lung,the alveoli,and ultimately respiratory failure.Fibrosis-associated MYFs are therefore widely regarded as the culprits that compromise the architectural makeup of the lung in fibrotic disease.During the past decade,the cellular source of MYFs has been intensely investigated.The rationale for such studies is that identifying the origin of these cells might help identify novel therapeutic targets and candidates to treat IPF patients.Recent advances in basic and translational research employing lineage tracing and multi-omics approaches have helped address the identity of MYF precursors,highlight the underlying heterogeneity,and to a less extent investigate MYF fate during fibrosis resolution.In this review,we discuss the current understanding of such important aspects of MYF biology as well as recent developments in the treatment of IPF.
