BACKGROUND Medial dished(MD)liner designs for cruciate-retaining(CR)total knee arthroplasty(TKA)are a relatively novel development.MD tibial inserts have a more constraining medial side,which allows for more similar k...BACKGROUND Medial dished(MD)liner designs for cruciate-retaining(CR)total knee arthroplasty(TKA)are a relatively novel development.MD tibial inserts have a more constraining medial side,which allows for more similar kinematics and function to a native knee.AIM To evaluate the clinical results and patient-reported outcomes after CR TKA procedures utilizing a kinematically designed medial dish system.METHODS A multicenter,retrospective cohort review of 139 primary elective TKAs utilizing a kinematically designed CR Knee System(JOURNEY™II CR MD;Smith and Nephew,Memphis,TN,United States)at three different institutions with a minimum of two years of follow-up.Demographic information,clinical outcomes,and patient-reported outcome measures were collected and analyzed.RESULTS With up to 3.7 years from surgery,overall implant survivorship was 98.6%.There were significant postoperative increases in the average Knee Injury and Osteoarthritis Outcome Score for Joint Replacement scores(17.4 at 6 months,26.1 points at two years or more,P<0.001).CONCLUSION The combination of high implant survivorship and substantial improvements in patient-reported outcome measures suggests that the medial dish tibial insert represents a safe and effective option within TKA.Additional investigation is necessary to evaluate the long-term survivorship of this design.展开更多
Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genoty...Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.展开更多
基因调控网络是基于微阵列基因表达数据,对基因之间表达关系依赖程度的一种仿真或重建。从基因表达数据挖掘基因之间存在的一定程度因果关系,对重构基因调控网络具有十分重要的意义。提出一种基于频繁原子序列关联熵的基因关联分析算法...基因调控网络是基于微阵列基因表达数据,对基因之间表达关系依赖程度的一种仿真或重建。从基因表达数据挖掘基因之间存在的一定程度因果关系,对重构基因调控网络具有十分重要的意义。提出一种基于频繁原子序列关联熵的基因关联分析算法,通过基因关联熵有效识别基因之间的因果关系,并采用启发式搜索策略构建基因关联贝叶斯调控网络(gene association based Bayesian regulatory,GABR)。与基因贝叶斯网络描述基因表达水平值之间依赖关系不同,GABR是一种基因序列贝叶斯网络,基因关联分析对象是生物组织样本的基因表达值排序并置换为基因列下标所形成的序列。算法的优势在于基因变量取值原子序列,该基因为原子序列的结果,基因关联熵以及条件概率分布的计算更符合基因表达数据分析的生物本质特征。ALARM网络模拟数据的实验结果表明,基因关联分析算法性能明显优于同类算法。在酵母菌微阵列基因数据GDS2267和小鼠胚胎基因GSE76118等GEO数据集进行实验,测试结果表明GABR方法重构的基因调控网络具有较高的有效性和鲁棒性。展开更多
Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration...Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.展开更多
BACKGROUND Childhood obesity is a significant public health concern,particularly amongst children with chronic kidney disease requiring kidney transplant(KT).Obesity,defined as a body mass index(BMI)of 30 kg/m^(2) or ...BACKGROUND Childhood obesity is a significant public health concern,particularly amongst children with chronic kidney disease requiring kidney transplant(KT).Obesity,defined as a body mass index(BMI)of 30 kg/m^(2) or greater,is prevalent in this population and is associated with disease progression.While BMI in-fluences adult KT eligibility,its impact on pediatric transplant outcomes remains unclear.This study investigates the effect of BMI on graft survival and patient outcomes,addressing gaps in the literature and examining disparities across BMI classifications.AIM To assess the impact of BMI classifications on graft and patient survival following KT.METHODS A retrospective cohort study analyzed 23081 pediatric transplant recipients from the Standard Transplant Analysis and Research database(1987-2022).Patients were grouped into six BMI categories:Underweight,healthy weight,overweight,and Class 1,2,and 3 obesity.Data were analyzed using one-way way analysis of variance,Kruskal-Wallis tests,Chi-squared tests,Kaplan-Meier survival analysis with log-rank tests,and Cox proportional hazard regressions.Statistical significance was set at P<0.05.RESULTS Class 3 obese recipients had lower 1-year graft survival(88.7%)compared to healthy-weight recipients(93.1%,P=0.012).Underweight recipients had lower 10-year patient survival(81.3%,P<0.05)than healthy-weight recipients.Class 2 and 3 obese recipients had the lowest 5-year graft survival(67.8%and 68.3%,P=0.013)and Class 2 obesity had the lowest 10-year graft survival(40.7%).Cox regression identified increases in BMI category as an independent predictor of graft failure[hazard ratio(HR)=1.091,P<0.001]and mortality(HR=1.079,P=0.008).Obese patients experienced longer cold ischemia times(11.6 and 13.1 hours vs 10.2 hours,P<0.001).Class 3 obesity had the highest proportion of Black recipients(26.2%vs 17.9%,P<0.001).CONCLUSION Severe obesity and underweight status are associated with poorer long-term outcomes in pediatric KT recipients,emphasizing the need for nuanced transplant eligibility criteria addressing obesity-related risks and socioeconomic disparities.展开更多
Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural regeneration.Both intrinsic and extrinsic factors ...Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural regeneration.Both intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following injury.At the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to regenerate.Recent works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of regeneration.The role of glia in neuron regeneration has long been studied.展开更多
Large language models(LLMs),such as ChatGPT developed by OpenAI,represent a significant advancement in artificial intelligence(AI),designed to understand,generate,and interpret human language by analyzing extensive te...Large language models(LLMs),such as ChatGPT developed by OpenAI,represent a significant advancement in artificial intelligence(AI),designed to understand,generate,and interpret human language by analyzing extensive text data.Their potential integration into clinical settings offers a promising avenue that could transform clinical diagnosis and decision-making processes in the future(Thirunavukarasu et al.,2023).This article aims to provide an in-depth analysis of LLMs’current and potential impact on clinical practices.Their ability to generate differential diagnosis lists underscores their potential as invaluable tools in medical practice and education(Hirosawa et al.,2023;Koga et al.,2023).展开更多
癌症是人类健康的第一杀手。随着测序技术的快速发展,积累了海量的癌症基因表达数据,利用计算方法进行致病基因预测成为癌症研究领域新的热点。然而,目前致病基因预测大多基于基因相互作用网络等,很少考虑网络局部连接与基因差异表达间...癌症是人类健康的第一杀手。随着测序技术的快速发展,积累了海量的癌症基因表达数据,利用计算方法进行致病基因预测成为癌症研究领域新的热点。然而,目前致病基因预测大多基于基因相互作用网络等,很少考虑网络局部连接与基因差异表达间的潜在联系。针对上述问题,首先利用患病前后的基因表达差异数据,通过互信息计算基因间的相关性并构建邻接网络,然后设计特征向量模型用于癌症致病基因预测。向量特征包括候选基因及其近邻的差异表达信息。从TCGA,OMIM和GEO等公共数据库获取癌症相关的致病与非致病基因以及患病前后基因差异表达数据进行实验,利用邻接网络中基因及其近邻的差异表达信息进行癌症致病基因预测(Differential Information of Gene and Nearest Neighbor for Cancer Pathogenic Gene Prediction,DICPG)。实验结果表明,DICPG癌症基因分类模型的生物学意义明显,分类精度和AUC等性能指标优于同类方法。展开更多
文摘BACKGROUND Medial dished(MD)liner designs for cruciate-retaining(CR)total knee arthroplasty(TKA)are a relatively novel development.MD tibial inserts have a more constraining medial side,which allows for more similar kinematics and function to a native knee.AIM To evaluate the clinical results and patient-reported outcomes after CR TKA procedures utilizing a kinematically designed medial dish system.METHODS A multicenter,retrospective cohort review of 139 primary elective TKAs utilizing a kinematically designed CR Knee System(JOURNEY™II CR MD;Smith and Nephew,Memphis,TN,United States)at three different institutions with a minimum of two years of follow-up.Demographic information,clinical outcomes,and patient-reported outcome measures were collected and analyzed.RESULTS With up to 3.7 years from surgery,overall implant survivorship was 98.6%.There were significant postoperative increases in the average Knee Injury and Osteoarthritis Outcome Score for Joint Replacement scores(17.4 at 6 months,26.1 points at two years or more,P<0.001).CONCLUSION The combination of high implant survivorship and substantial improvements in patient-reported outcome measures suggests that the medial dish tibial insert represents a safe and effective option within TKA.Additional investigation is necessary to evaluate the long-term survivorship of this design.
基金supported by the National Natural Science Foundation of China(Grant No.82220108002 to F.C.and Grant No.82273737 to R.Z.)the U.S.National Institutes of Health(Grant Nos.CA209414,HL060710,and ES000002 to D.C.C.,Grant Nos.CA209414 and CA249096 to Y.L.)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)supported by the Qing Lan Project of the Higher Education Institutions of Jiangsu Province and the Outstanding Young Level Academic Leadership Training Program of Nanjing Medical University.
文摘Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.
基金supported by the National Natural Science Foundation of China(No.82160051,32100908)the Jiangxi Provincial Natural Science Foundation(No.20232BAB206018)+2 种基金the Science and Technology Research Project in the Education Department of Jiangxi Province,China(No.GJJ2200904)the Ph.D.Start-up Research Fund in Jiangxi University of Chinese Medicine(No.2020BSZR009)the Discipline of Chinese and Western Integrative Medicine in Jiangxi University of Chinese Medicine(No.zxyylxk20220103)。
文摘基因调控网络是基于微阵列基因表达数据,对基因之间表达关系依赖程度的一种仿真或重建。从基因表达数据挖掘基因之间存在的一定程度因果关系,对重构基因调控网络具有十分重要的意义。提出一种基于频繁原子序列关联熵的基因关联分析算法,通过基因关联熵有效识别基因之间的因果关系,并采用启发式搜索策略构建基因关联贝叶斯调控网络(gene association based Bayesian regulatory,GABR)。与基因贝叶斯网络描述基因表达水平值之间依赖关系不同,GABR是一种基因序列贝叶斯网络,基因关联分析对象是生物组织样本的基因表达值排序并置换为基因列下标所形成的序列。算法的优势在于基因变量取值原子序列,该基因为原子序列的结果,基因关联熵以及条件概率分布的计算更符合基因表达数据分析的生物本质特征。ALARM网络模拟数据的实验结果表明,基因关联分析算法性能明显优于同类算法。在酵母菌微阵列基因数据GDS2267和小鼠胚胎基因GSE76118等GEO数据集进行实验,测试结果表明GABR方法重构的基因调控网络具有较高的有效性和鲁棒性。
基金supported in part by NIH R01 NS100531,R01 NS103481NIH R21NS130241(to LD)+3 种基金Merit Review Award I01 BX002356,I01 BX003705 from the U.S.Department of Veterans AffairsIndiana Spinal Cord and Brain Injury Research Foundation(No.19919)Mari Hulman George Endowment Funds(to XMX)Indiana Spinal Cord&Brain Injury Research Fund from ISDH(to NKL and LD)。
文摘Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.
文摘BACKGROUND Childhood obesity is a significant public health concern,particularly amongst children with chronic kidney disease requiring kidney transplant(KT).Obesity,defined as a body mass index(BMI)of 30 kg/m^(2) or greater,is prevalent in this population and is associated with disease progression.While BMI in-fluences adult KT eligibility,its impact on pediatric transplant outcomes remains unclear.This study investigates the effect of BMI on graft survival and patient outcomes,addressing gaps in the literature and examining disparities across BMI classifications.AIM To assess the impact of BMI classifications on graft and patient survival following KT.METHODS A retrospective cohort study analyzed 23081 pediatric transplant recipients from the Standard Transplant Analysis and Research database(1987-2022).Patients were grouped into six BMI categories:Underweight,healthy weight,overweight,and Class 1,2,and 3 obesity.Data were analyzed using one-way way analysis of variance,Kruskal-Wallis tests,Chi-squared tests,Kaplan-Meier survival analysis with log-rank tests,and Cox proportional hazard regressions.Statistical significance was set at P<0.05.RESULTS Class 3 obese recipients had lower 1-year graft survival(88.7%)compared to healthy-weight recipients(93.1%,P=0.012).Underweight recipients had lower 10-year patient survival(81.3%,P<0.05)than healthy-weight recipients.Class 2 and 3 obese recipients had the lowest 5-year graft survival(67.8%and 68.3%,P=0.013)and Class 2 obesity had the lowest 10-year graft survival(40.7%).Cox regression identified increases in BMI category as an independent predictor of graft failure[hazard ratio(HR)=1.091,P<0.001]and mortality(HR=1.079,P=0.008).Obese patients experienced longer cold ischemia times(11.6 and 13.1 hours vs 10.2 hours,P<0.001).Class 3 obesity had the highest proportion of Black recipients(26.2%vs 17.9%,P<0.001).CONCLUSION Severe obesity and underweight status are associated with poorer long-term outcomes in pediatric KT recipients,emphasizing the need for nuanced transplant eligibility criteria addressing obesity-related risks and socioeconomic disparities.
文摘Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural regeneration.Both intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following injury.At the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to regenerate.Recent works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of regeneration.The role of glia in neuron regeneration has long been studied.
文摘Large language models(LLMs),such as ChatGPT developed by OpenAI,represent a significant advancement in artificial intelligence(AI),designed to understand,generate,and interpret human language by analyzing extensive text data.Their potential integration into clinical settings offers a promising avenue that could transform clinical diagnosis and decision-making processes in the future(Thirunavukarasu et al.,2023).This article aims to provide an in-depth analysis of LLMs’current and potential impact on clinical practices.Their ability to generate differential diagnosis lists underscores their potential as invaluable tools in medical practice and education(Hirosawa et al.,2023;Koga et al.,2023).
文摘癌症是人类健康的第一杀手。随着测序技术的快速发展,积累了海量的癌症基因表达数据,利用计算方法进行致病基因预测成为癌症研究领域新的热点。然而,目前致病基因预测大多基于基因相互作用网络等,很少考虑网络局部连接与基因差异表达间的潜在联系。针对上述问题,首先利用患病前后的基因表达差异数据,通过互信息计算基因间的相关性并构建邻接网络,然后设计特征向量模型用于癌症致病基因预测。向量特征包括候选基因及其近邻的差异表达信息。从TCGA,OMIM和GEO等公共数据库获取癌症相关的致病与非致病基因以及患病前后基因差异表达数据进行实验,利用邻接网络中基因及其近邻的差异表达信息进行癌症致病基因预测(Differential Information of Gene and Nearest Neighbor for Cancer Pathogenic Gene Prediction,DICPG)。实验结果表明,DICPG癌症基因分类模型的生物学意义明显,分类精度和AUC等性能指标优于同类方法。
