【Background】The application of beneficial-microbial seed soaking prior to sowing represents a novel technology that has not been employed in Lanzhou lily cultivation.We conducted an experiment to explore the impact ...【Background】The application of beneficial-microbial seed soaking prior to sowing represents a novel technology that has not been employed in Lanzhou lily cultivation.We conducted an experiment to explore the impact of this soaking method on the fungal and bacterial community structures using next-generation sequencing technology(NGS).【Methods】Lily bulbs were soaked in a seed treating agent containing beneficial microbes(SP treatment)for 4 hours.Subsequently,they were planted in soil in July and sampled in September to assess plant growth,rhizosphere soil physicochemical properties,and microorganism community structures.In addition,we employed the software PICRUSt and FUNGuild to predict bacterial pathways and fungal functions.【Results】Under SP treatment,there were significant alterations in fungi and bacteria community structures,accompanied by improved soil nutrient status.Notably,the relative abundance of dominant microorganism groups,such as the fungi Basidiomycota,Pseudeurotium,Cladophialophora,Microascus,and Dactylonectria,as well as the bacteria Proteobacteria,Chloroflexi,Ochrobactrium,Lysobacter,and RB41,underwent notable changes.Microorganism function prediction results indicated a reduction in pathotrophic fungi(including plant pathogens)and an increase in endophytic and saprotrophic fungi under SP treatment.Among the top 20 metabolism pathways,80%were upregulated in SP treatment compared to the CK.【Conclusions】Seed soaking with beneficial microbial strain promotes the growth of Lanzhou lily bulbs.The beneficial microorganisms play a crucial role in regulating soil microbial structures,enhancing the accumulation of endophytic fungi,reducing the abundance of pathogens,and improving soil functions.Furthermore,specific microbial groups are found to be involved in maintaining soil health.展开更多
Purpose:Derivative chromosomes,resulting from complex structural rearrangements,pose significant challenges in prenatal diagnosis due to their unpredictable inheritance patterns and potential phenotypic consequences.T...Purpose:Derivative chromosomes,resulting from complex structural rearrangements,pose significant challenges in prenatal diagnosis due to their unpredictable inheritance patterns and potential phenotypic consequences.This study evaluates the efficacy of multiple genetic technologies-including karyotyping,fluorescence in situ hybridization(FISH),chromosomal microarray analysis(CMA),and next-generation sequencing(NGS)-in detecting and characterizing derivative chromosomes in prenatal samples.methodology:We analyzed 150 cases of suspected chromosomal abnormalities,comparing detection rates,resolution,and clinical utility across these methods.Results:Our findings demonstrate that integrated multi-technology approaches significantly improve diagnostic accuracy,with NGS-based structural variation analysis achieving the highest detection sensitivity(99.2%)for cryptic rearrangements.Conclusions:Additionally,long-read sequencing(PacBio/Oxford Nanopore)enabled precise breakpoint mapping in 92%of cases,facilitating more accurate genetic counseling.Clinically,this approach enhances risk assessment for fetal anomalies,guides pregnancy management,and improves parental counseling for recurrence risks.展开更多
Background:Precision medicine is an emerging approach for treating pediatric cancer due to its ability to target tumor-specific genetic drivers rather than provide broad and aggressive treatments.The study aimed to ou...Background:Precision medicine is an emerging approach for treating pediatric cancer due to its ability to target tumor-specific genetic drivers rather than provide broad and aggressive treatments.The study aimed to outline the establishment and impact of a Precision Medicine Clinic(PMC)in the setting of pediatric oncology,with the objective of offering targeted treatment options within the institution and creating a scalable model for adoption by other healthcare systems to achieve a wider impact.Methods:Recognizing this need for an individualized approach to treating patients,Cook Children’s Medical Center(CCMC)established a multidisciplinary molecular tumor board in 2019,followed by the launch of an official PMC in 2021.Before this,there was no dedicated place to discuss and evaluate genetic sequencing results.Results:In 2022 and 2023,the PMC discussed 69 patients with a wide variety of oncologic diagnoses.Through the clinic’s efforts,133 genetic variants across 101 genes have been identified,spanning oncogenic pathways related to cell cycling,DNA processing,and cell signaling.Of the sequenced patients,four have received targeted therapy according to recommendations from the PMC.Conclusion:While the PMC continues to evaluate patients and their long-term outcomes,the continually growing PMC at CCMC represents the beginning of the advancement of treating pediatric oncology patients through the interpretation of genetic sequencing results,making actionable targeted treatment recommendations,and continuing to follow the patient’s course of care over time.This additionally provides a framework for starting a PMC that can be adapted for specific clinical needs and implemented broadly.展开更多
Non-small cell lung cancer(NSCLC)accounts for the majority of lung cancer cases and remains the leading cause of cancer-related mortality worldwide.Firstly,this review explores the limitations of conventional therapie...Non-small cell lung cancer(NSCLC)accounts for the majority of lung cancer cases and remains the leading cause of cancer-related mortality worldwide.Firstly,this review explores the limitations of conventional therapies,chemotherapy,radiotherapy,and surgery,focusing on the development of drug resistance and significant toxicity that often hinder their efficacy.Thereafter,advancements in targeted therapies,such as immune checkpoint inhibitors(ICIs)and tyrosine kinase inhibitors(TKIs),are discussed,highlighting their impact on improving outcomes for patients with specific genetic mutations,including c-ros oncogene 1 receptor tyrosine kinase(ROS1),anaplastic lymphoma kinase(ALK),and epidermal growth factor receptor(EGFR).Additionally,the emergence of novel immunotherapies and phytochemicals is examined,emphasizing their potential to overcome therapeutic resistance,particularly in advanced-stage diseases.The review also delves into the role of next-generation sequencing(NGS)in enabling personalized treatment approaches and explores the clinical potential of innovative agents,such as bispecific T-cell engagers(BiTEs)and antibody-drug conjugates(ADCs).Finally,we address the socioeconomic barriers that limit the accessibility of these therapies in low-resource settings and propose future research directions aimed at improving the long-term efficacy and accessibility of these treatments.展开更多
Objectives:Intravesical Bacillus Calmette-Guérin(BCG)therapy is a gold standard for patients with high-risk non-muscle invasive bladder cancer(NMIBC).Although a long-lasting therapeutic response is observed in mo...Objectives:Intravesical Bacillus Calmette-Guérin(BCG)therapy is a gold standard for patients with high-risk non-muscle invasive bladder cancer(NMIBC).Although a long-lasting therapeutic response is observed in most patients,BCG failure occurs in 30%–50%of patients and a progression to muscle-invasive disease is found in 10%–15%.Therefore,predicting high-risk patients who might not benefit from BCG treatment is critical.The purpose of this study was to identify,whether the presence of specific oncogenic mutations might be indicative of BCG treatment response.Methods:Nineteen high-grade NMIBC patients who received intravesical BCG were retrospectively enrolled and divided into“responders”and“non-responders”groups.Tissue samples from transurethral resection of bladder cancer were performed before starting therapy and were examined using a multigene sequencing panel.Results:Mutations in TP53,FGFR3,PIK3CA,KRAS,CTNNB1,ALK and DDR2 genes were detected.TP53 and FGFR3 were found to be the most frequently mutated genes in our cohort(31.6%and 26.3%,respectively),followed by PIK3CA(15.8%).In the BCG-responsive patient group,90%of samples were found to have mutated genes,with almost 50%of them showing mutations in tyrosine kinase receptors and CTNNB1 genes.On the other hand,in the BCG-unresponsive group,we found mutations in 44.4%of samples,mainly in TP53 gene.Conclusions:Our findings suggest that a Next-Generation Sequencing(NGS)multigene panel is useful in predicting BCG response in patients with NMIBC.展开更多
The migration of nitroglycerin(NG) has always been the critical issue that harmfully impacts the structural integrity and operational reliability of the solid rocket motor, which is mainly composed by Nitrate Ester Pl...The migration of nitroglycerin(NG) has always been the critical issue that harmfully impacts the structural integrity and operational reliability of the solid rocket motor, which is mainly composed by Nitrate Ester Plasticized Polyether(NEPE) propellant/Hydroxyl-terminated Polybutadiene(HTPB) liner/Ethylene Propylene Diene Monomer(EPDM) insulation bonding system. This paper proposes an innovative surface modification method attempting to modify the EPDM insulation layer coated with reduced graphene oxide(RGO), which exhibits ability to weaken the NG absorption by EPDM insulation layer,blocking the pathway of NG migration into EPDM insulation materials. The microstructure of RGO-coated layer was analyzed and the formation mechanism was investigated. The RGO-coated layer is well bonded to the HTPB liner, and its anti-migration performance to NG at different temperatures has been evaluated. Comparing with blank samples under the same storage conditions, the RGO-coated layers can reduce the diffusion coefficient of NG by up to 87.3% and increase the diffusion activation energy of NG by14.8 kJ,mol^(-1). This research provides a new strategy to effectively inhibit NG migration in NEPE propellant/HTPB liner/EPDM insulation bonding system.展开更多
Neuron glia antigen-2(NG2)glia,also known as oligodendrocyte precursor cells(OPCs),are essential for maintaining the normal function and structure of the central nervous system(CNS)due to their supportive role[1].Unde...Neuron glia antigen-2(NG2)glia,also known as oligodendrocyte precursor cells(OPCs),are essential for maintaining the normal function and structure of the central nervous system(CNS)due to their supportive role[1].Under physiological conditions,NG2 glia are involved in myelination by differentiating into oligodendrocytes,which are responsible for forming the myelin sheath around axons[2].In addition,the NG2 glia can directly influence the activity of neuronal circuits by receiving synaptic input from neurons and generating action potentials[3].Under pathological conditions,such as in response to injury or disease,the NG2 glia proliferate and differentiate to replace damaged oligodendrocytes,contributing to the repair and regeneration of myelin[4].展开更多
BACKGROUND Kidney transplantation is an effective renal replacement therapy for improving survival and quality of life in chronic kidney disease patients.Kidney transplant recipients need lifelong immunosuppression to...BACKGROUND Kidney transplantation is an effective renal replacement therapy for improving survival and quality of life in chronic kidney disease patients.Kidney transplant recipients need lifelong immunosuppression to prevent rejection and allograft dysfunction.Tacrolimus,a calcineurin inhibitor,is metabolized differently based on cytochrome P4503A(CYP3A)5 genetic variations and this impacts the graft outcome.AIM To examine the clinical outcomes in kidney transplant recipients affected by the variable metabolism of tacrolimus due to the CYP3A5 genetic variation,emphasizing personalized immunosuppression strategies to optimize efficacy,minimize toxicity,and enhance long-term graft survival.METHODS A retrospective study was conducted at a tertiary care center in Central India on 95 kidney transplant recipients.Patient demographics,medical history,CYP3A5 polymorphism,post-transplant investigations,graft biopsy results,preexisting comorbidities,history of post–kidney transplant infections,and new onset diabetes after transplantation(NODAT)was collected.Tacrolimus was initiated at 0.1 mg/kg/day for CYP3A5 expressors and 0.05 mg/kg/day for non-expressors,with dose adjustments to maintain target C0 levels of 7-10 ng/mL for first 6 months and 5-7 ng/mL from 6 months to 12 months posttransplant.Patients were followed regularly for one year for glomerular filtration rate(GFR),creatinine,and the tacrolimus trough concentration(ng/mL)/daily tacrolimus dose(mg/kg/day)ratio(C/D).A P value≤0.05 was considered statistically significant.RESULTS Kidney transplant recipients were classified as expressors(CYP3A51 carriers,n=35)and non-expressors(CYP3A5*3*3,n=60).Both groups were comparable for age,sex,and donor characteristics.Tacrolimus dose was comparable post-transplant except at 6 months and 12 months,where expressors required higher doses.Kidney function(creatinine and estimated GFR),NODAT,hypomagnesemia,and infections showed no significant differences between the two groups over 12 months of follow-up.Biopsy-proven acute rejection(BPAR)was found to be more in expressors(22.9%vs 13.3%,P=0.2340)though it was not found to be statistically significant.Nonexpressors had a significantly higher tacrolimus levels and C/D ratio at multiple follow-ups.CONCLUSION CYP3A5 expressors require higher tacrolimus doses to maintain therapeutic levels as compared to non-expressors.BPAR was higher in expressors but the difference was not significant.Graft function,infection rate,and NODAT were comparable irrespective of CYP3A5 expression status,emphasizing the importance of pretransplant CYP3A5 genotyping and therapeutic drug monitoring to guide tacrolimus dosing for individualized immunosuppressive management.展开更多
在全球气候变化和高强度人类活动的共同影响下,许多流域天然水循环过程受到破坏。径流序列呈现明显的非平稳特性,给水资源规划、管理、预测和调控带来一定的挑战。揭示径流序列的非平稳特性可以有效应对全球气候变化下的复杂水问题,对...在全球气候变化和高强度人类活动的共同影响下,许多流域天然水循环过程受到破坏。径流序列呈现明显的非平稳特性,给水资源规划、管理、预测和调控带来一定的挑战。揭示径流序列的非平稳特性可以有效应对全球气候变化下的复杂水问题,对降低水文分析难度和提高径流预测精度具有十分重要的意义。研究以汾河上游兰村站为研究对象,分析该站1958-2016年年径流和月径流序列是否平稳。首先从随机水文学角度,采用Mann-Kendall检验法和小波分析法识别径流序列的趋势、突变和周期特征。在此基础上,从统计水文学角度引入Ng-Perron单位根检验方法。通过Mann-Kendall趋势检验和散点图法选择合适的检验方程,对径流序列进行广义最小二乘法(Generalized Least Squares,GLS)退势,并利用修正的信息准则(Modified information criterion,MIC)计算最优时间滞后阶数,判别径流序列是否具有非平稳性。结果显示,径流序列存在趋势、突变和周期成分,为非平稳径流序列。同时Ng-Perron单位根检验表明,该站年、月径流序列在1%显著性水平上具有非平稳特性。相较传统单位根检验方法,Ng-Perron单位根检验采用更为稳健的修正检验统计量,显著调整小样本情况下水平扭曲的现象,具有更好检验水平和功效,因而可以得到更合理的检验结果。研究成果为径流序列非平稳性检验理论的进一步改进及径流预测模型发展与应用提供参考。展开更多
文摘【Background】The application of beneficial-microbial seed soaking prior to sowing represents a novel technology that has not been employed in Lanzhou lily cultivation.We conducted an experiment to explore the impact of this soaking method on the fungal and bacterial community structures using next-generation sequencing technology(NGS).【Methods】Lily bulbs were soaked in a seed treating agent containing beneficial microbes(SP treatment)for 4 hours.Subsequently,they were planted in soil in July and sampled in September to assess plant growth,rhizosphere soil physicochemical properties,and microorganism community structures.In addition,we employed the software PICRUSt and FUNGuild to predict bacterial pathways and fungal functions.【Results】Under SP treatment,there were significant alterations in fungi and bacteria community structures,accompanied by improved soil nutrient status.Notably,the relative abundance of dominant microorganism groups,such as the fungi Basidiomycota,Pseudeurotium,Cladophialophora,Microascus,and Dactylonectria,as well as the bacteria Proteobacteria,Chloroflexi,Ochrobactrium,Lysobacter,and RB41,underwent notable changes.Microorganism function prediction results indicated a reduction in pathotrophic fungi(including plant pathogens)and an increase in endophytic and saprotrophic fungi under SP treatment.Among the top 20 metabolism pathways,80%were upregulated in SP treatment compared to the CK.【Conclusions】Seed soaking with beneficial microbial strain promotes the growth of Lanzhou lily bulbs.The beneficial microorganisms play a crucial role in regulating soil microbial structures,enhancing the accumulation of endophytic fungi,reducing the abundance of pathogens,and improving soil functions.Furthermore,specific microbial groups are found to be involved in maintaining soil health.
文摘Purpose:Derivative chromosomes,resulting from complex structural rearrangements,pose significant challenges in prenatal diagnosis due to their unpredictable inheritance patterns and potential phenotypic consequences.This study evaluates the efficacy of multiple genetic technologies-including karyotyping,fluorescence in situ hybridization(FISH),chromosomal microarray analysis(CMA),and next-generation sequencing(NGS)-in detecting and characterizing derivative chromosomes in prenatal samples.methodology:We analyzed 150 cases of suspected chromosomal abnormalities,comparing detection rates,resolution,and clinical utility across these methods.Results:Our findings demonstrate that integrated multi-technology approaches significantly improve diagnostic accuracy,with NGS-based structural variation analysis achieving the highest detection sensitivity(99.2%)for cryptic rearrangements.Conclusions:Additionally,long-read sequencing(PacBio/Oxford Nanopore)enabled precise breakpoint mapping in 92%of cases,facilitating more accurate genetic counseling.Clinically,this approach enhances risk assessment for fetal anomalies,guides pregnancy management,and improves parental counseling for recurrence risks.
文摘Background:Precision medicine is an emerging approach for treating pediatric cancer due to its ability to target tumor-specific genetic drivers rather than provide broad and aggressive treatments.The study aimed to outline the establishment and impact of a Precision Medicine Clinic(PMC)in the setting of pediatric oncology,with the objective of offering targeted treatment options within the institution and creating a scalable model for adoption by other healthcare systems to achieve a wider impact.Methods:Recognizing this need for an individualized approach to treating patients,Cook Children’s Medical Center(CCMC)established a multidisciplinary molecular tumor board in 2019,followed by the launch of an official PMC in 2021.Before this,there was no dedicated place to discuss and evaluate genetic sequencing results.Results:In 2022 and 2023,the PMC discussed 69 patients with a wide variety of oncologic diagnoses.Through the clinic’s efforts,133 genetic variants across 101 genes have been identified,spanning oncogenic pathways related to cell cycling,DNA processing,and cell signaling.Of the sequenced patients,four have received targeted therapy according to recommendations from the PMC.Conclusion:While the PMC continues to evaluate patients and their long-term outcomes,the continually growing PMC at CCMC represents the beginning of the advancement of treating pediatric oncology patients through the interpretation of genetic sequencing results,making actionable targeted treatment recommendations,and continuing to follow the patient’s course of care over time.This additionally provides a framework for starting a PMC that can be adapted for specific clinical needs and implemented broadly.
文摘Non-small cell lung cancer(NSCLC)accounts for the majority of lung cancer cases and remains the leading cause of cancer-related mortality worldwide.Firstly,this review explores the limitations of conventional therapies,chemotherapy,radiotherapy,and surgery,focusing on the development of drug resistance and significant toxicity that often hinder their efficacy.Thereafter,advancements in targeted therapies,such as immune checkpoint inhibitors(ICIs)and tyrosine kinase inhibitors(TKIs),are discussed,highlighting their impact on improving outcomes for patients with specific genetic mutations,including c-ros oncogene 1 receptor tyrosine kinase(ROS1),anaplastic lymphoma kinase(ALK),and epidermal growth factor receptor(EGFR).Additionally,the emergence of novel immunotherapies and phytochemicals is examined,emphasizing their potential to overcome therapeutic resistance,particularly in advanced-stage diseases.The review also delves into the role of next-generation sequencing(NGS)in enabling personalized treatment approaches and explores the clinical potential of innovative agents,such as bispecific T-cell engagers(BiTEs)and antibody-drug conjugates(ADCs).Finally,we address the socioeconomic barriers that limit the accessibility of these therapies in low-resource settings and propose future research directions aimed at improving the long-term efficacy and accessibility of these treatments.
文摘Objectives:Intravesical Bacillus Calmette-Guérin(BCG)therapy is a gold standard for patients with high-risk non-muscle invasive bladder cancer(NMIBC).Although a long-lasting therapeutic response is observed in most patients,BCG failure occurs in 30%–50%of patients and a progression to muscle-invasive disease is found in 10%–15%.Therefore,predicting high-risk patients who might not benefit from BCG treatment is critical.The purpose of this study was to identify,whether the presence of specific oncogenic mutations might be indicative of BCG treatment response.Methods:Nineteen high-grade NMIBC patients who received intravesical BCG were retrospectively enrolled and divided into“responders”and“non-responders”groups.Tissue samples from transurethral resection of bladder cancer were performed before starting therapy and were examined using a multigene sequencing panel.Results:Mutations in TP53,FGFR3,PIK3CA,KRAS,CTNNB1,ALK and DDR2 genes were detected.TP53 and FGFR3 were found to be the most frequently mutated genes in our cohort(31.6%and 26.3%,respectively),followed by PIK3CA(15.8%).In the BCG-responsive patient group,90%of samples were found to have mutated genes,with almost 50%of them showing mutations in tyrosine kinase receptors and CTNNB1 genes.On the other hand,in the BCG-unresponsive group,we found mutations in 44.4%of samples,mainly in TP53 gene.Conclusions:Our findings suggest that a Next-Generation Sequencing(NGS)multigene panel is useful in predicting BCG response in patients with NMIBC.
基金National Natural Science Foundation of China(Grant No.22175059)to provide fund for conducting experiments.
文摘The migration of nitroglycerin(NG) has always been the critical issue that harmfully impacts the structural integrity and operational reliability of the solid rocket motor, which is mainly composed by Nitrate Ester Plasticized Polyether(NEPE) propellant/Hydroxyl-terminated Polybutadiene(HTPB) liner/Ethylene Propylene Diene Monomer(EPDM) insulation bonding system. This paper proposes an innovative surface modification method attempting to modify the EPDM insulation layer coated with reduced graphene oxide(RGO), which exhibits ability to weaken the NG absorption by EPDM insulation layer,blocking the pathway of NG migration into EPDM insulation materials. The microstructure of RGO-coated layer was analyzed and the formation mechanism was investigated. The RGO-coated layer is well bonded to the HTPB liner, and its anti-migration performance to NG at different temperatures has been evaluated. Comparing with blank samples under the same storage conditions, the RGO-coated layers can reduce the diffusion coefficient of NG by up to 87.3% and increase the diffusion activation energy of NG by14.8 kJ,mol^(-1). This research provides a new strategy to effectively inhibit NG migration in NEPE propellant/HTPB liner/EPDM insulation bonding system.
基金supported by the National Natural Science Foundation of China(32300959)a Guangzhou Scientific Research Grant(SL2024A04J00578)the SCNU Young Faculty Development Program(22KJ04).
文摘Neuron glia antigen-2(NG2)glia,also known as oligodendrocyte precursor cells(OPCs),are essential for maintaining the normal function and structure of the central nervous system(CNS)due to their supportive role[1].Under physiological conditions,NG2 glia are involved in myelination by differentiating into oligodendrocytes,which are responsible for forming the myelin sheath around axons[2].In addition,the NG2 glia can directly influence the activity of neuronal circuits by receiving synaptic input from neurons and generating action potentials[3].Under pathological conditions,such as in response to injury or disease,the NG2 glia proliferate and differentiate to replace damaged oligodendrocytes,contributing to the repair and regeneration of myelin[4].
文摘BACKGROUND Kidney transplantation is an effective renal replacement therapy for improving survival and quality of life in chronic kidney disease patients.Kidney transplant recipients need lifelong immunosuppression to prevent rejection and allograft dysfunction.Tacrolimus,a calcineurin inhibitor,is metabolized differently based on cytochrome P4503A(CYP3A)5 genetic variations and this impacts the graft outcome.AIM To examine the clinical outcomes in kidney transplant recipients affected by the variable metabolism of tacrolimus due to the CYP3A5 genetic variation,emphasizing personalized immunosuppression strategies to optimize efficacy,minimize toxicity,and enhance long-term graft survival.METHODS A retrospective study was conducted at a tertiary care center in Central India on 95 kidney transplant recipients.Patient demographics,medical history,CYP3A5 polymorphism,post-transplant investigations,graft biopsy results,preexisting comorbidities,history of post–kidney transplant infections,and new onset diabetes after transplantation(NODAT)was collected.Tacrolimus was initiated at 0.1 mg/kg/day for CYP3A5 expressors and 0.05 mg/kg/day for non-expressors,with dose adjustments to maintain target C0 levels of 7-10 ng/mL for first 6 months and 5-7 ng/mL from 6 months to 12 months posttransplant.Patients were followed regularly for one year for glomerular filtration rate(GFR),creatinine,and the tacrolimus trough concentration(ng/mL)/daily tacrolimus dose(mg/kg/day)ratio(C/D).A P value≤0.05 was considered statistically significant.RESULTS Kidney transplant recipients were classified as expressors(CYP3A51 carriers,n=35)and non-expressors(CYP3A5*3*3,n=60).Both groups were comparable for age,sex,and donor characteristics.Tacrolimus dose was comparable post-transplant except at 6 months and 12 months,where expressors required higher doses.Kidney function(creatinine and estimated GFR),NODAT,hypomagnesemia,and infections showed no significant differences between the two groups over 12 months of follow-up.Biopsy-proven acute rejection(BPAR)was found to be more in expressors(22.9%vs 13.3%,P=0.2340)though it was not found to be statistically significant.Nonexpressors had a significantly higher tacrolimus levels and C/D ratio at multiple follow-ups.CONCLUSION CYP3A5 expressors require higher tacrolimus doses to maintain therapeutic levels as compared to non-expressors.BPAR was higher in expressors but the difference was not significant.Graft function,infection rate,and NODAT were comparable irrespective of CYP3A5 expression status,emphasizing the importance of pretransplant CYP3A5 genotyping and therapeutic drug monitoring to guide tacrolimus dosing for individualized immunosuppressive management.
文摘在全球气候变化和高强度人类活动的共同影响下,许多流域天然水循环过程受到破坏。径流序列呈现明显的非平稳特性,给水资源规划、管理、预测和调控带来一定的挑战。揭示径流序列的非平稳特性可以有效应对全球气候变化下的复杂水问题,对降低水文分析难度和提高径流预测精度具有十分重要的意义。研究以汾河上游兰村站为研究对象,分析该站1958-2016年年径流和月径流序列是否平稳。首先从随机水文学角度,采用Mann-Kendall检验法和小波分析法识别径流序列的趋势、突变和周期特征。在此基础上,从统计水文学角度引入Ng-Perron单位根检验方法。通过Mann-Kendall趋势检验和散点图法选择合适的检验方程,对径流序列进行广义最小二乘法(Generalized Least Squares,GLS)退势,并利用修正的信息准则(Modified information criterion,MIC)计算最优时间滞后阶数,判别径流序列是否具有非平稳性。结果显示,径流序列存在趋势、突变和周期成分,为非平稳径流序列。同时Ng-Perron单位根检验表明,该站年、月径流序列在1%显著性水平上具有非平稳特性。相较传统单位根检验方法,Ng-Perron单位根检验采用更为稳健的修正检验统计量,显著调整小样本情况下水平扭曲的现象,具有更好检验水平和功效,因而可以得到更合理的检验结果。研究成果为径流序列非平稳性检验理论的进一步改进及径流预测模型发展与应用提供参考。