Microvesicles （MVs） are the heterogeneous mixtures of vesicles. MVs released by leukemia cells constitute an important part of the leukemia microenvironment. MVs might act as important reser- voirs of microRNAs （mi...Microvesicles （MVs） are the heterogeneous mixtures of vesicles. MVs released by leukemia cells constitute an important part of the leukemia microenvironment. MVs might act as important reser- voirs of microRNAs （miRNAs）. It is worth evaluating whether MVs possess some unique miRNA con- tents that are valuable in understanding the pathogenesis. In this study, we investigated the miRNA ex- pression patterns of Nalm-6-derived MVs, Jurkat-derived MVs and normal cell-derived MVs using miRNA microarrays. The potential target genes regulated by differentially expressed miRNAs were also predicted and analyzed. Results demonstrated that 182 miRNAs and 166 miRNAs were differentially expressed in Nalm-6-MVs and Jurkat-MVs, respectively. Many oncogenes, tumor suppressors and sig- nal pathway genes were targeted by these aberrantly expressed miRNAs, which might contribute to the development of B-ALL or T-ALL. Our findings expanded the potential diagnostic markers of ALL and provided useful information for ALL pathogenesis.展开更多
Background Newborn screening(NBS)is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn disease...Background Newborn screening(NBS)is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases.The develop-ment of next-generation sequencing(NGS)technology provides new opportunities to expand current newborn screening methodologies.Methods We designed a a newborn genetic screening(NBGS)panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS.With this panel,a large-scale,multicenter,prospective multidisease analysis was conducted on dried blood spot(DBS)profiles from 21,442 neonates nationwide.Results We presented the positive detection rate and carrier frequency of diseases and related variants in different regions;and 168(0.78%)positive cases were detected.Glucose-6-Phosphate Dehydrogenase deficiency(G6PDD)and phenylketonuria(PKU)had higher prevalence rates,which were significantly different in different regions.The positive detection of G6PD variants was quite common in south China,whereas PAH variants were most commonly identified in north China.In addi-tion,NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants,which were normal in conventional NBS,but were confirmed later as abnormal in repeated biochemical testing after recall.Eighty percent of high-frequency gene carriers and 60%of high-frequency variant carriers had obvious regional differences.On the premise that there was no significant difference in birth weight and gestational age,the biochemical indicators of SLC22A5 c.1400C>G and ACADSB c.1165A>G carriers were significantly different from those of non-carriers.Conclusions We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS methods.Our data also showed that the prevalence of diseases has significant regional charac-teristics,which provides a theoretical basis for screening diseases in different regions.展开更多
Background:Moxibustion is a traditional Chinese medicine therapy to cure diseases by fumigating meridians or affected parts via burning of moxa floss.Moxa smoke(MS)is one of the key factors in moxibustion.In this stud...Background:Moxibustion is a traditional Chinese medicine therapy to cure diseases by fumigating meridians or affected parts via burning of moxa floss.Moxa smoke(MS)is one of the key factors in moxibustion.In this study,we adopted digital gene expression profiling,a next-generation gene sequencing technology,to investigate the effect of MS,inhalable particulate matter(PM10),on human lung adenocarcinoma A549 cells.Methods:The effects of MS PM10 on A549 cells,over different treatment durations were investigated in different groups:the 4-h group(4-h MS group and 4-h control group)and the 20-h group(20-h MS group and 20-h control group).Samples collected from the four groups were stored at80C for subsequent digital gene expression analysis.The differentially expressed genes(DEGs),identified after PM10 treatment,were screened,and their expression patterns analyzed by cluster analysis,Gene Ontology term enrichment,and Kyoto Encyclopedia of Genes and Genomes pathway analysis.Results:Compared with two control groups,1109 DEGs were identified after 4 h of MS intervention and 3565 DEGs were found after 20 h of MS intervention,respectively.Compared with that after 4-h intervention,2149 DEGs were identified after 20-h intervention.Cluster analysis demonstrated that PM10 can significantly inhibit cell cycle process with the prolongation of intervention time.Significant pathway enrichment analysis showed that MS PM10 can inhibit A549 cell cycle process at all phases.When MS PM10 exposure time prolongs,the inhibitory effect on cell cycle process becomes more obvious.Conclusion:MS PM10 has many biological activities,and may cause differential expression of genes involved in various biological processes.Nevertheless,further research on MS is warranted for better understanding of the mechanistic details.展开更多
Background To optimize and apply an approach suitable for large-scale neonatal thalassemia genetic screening in China,thalassemia genotypes were determined by polymerase chain reaction-reverse dot blot using DNA extra...Background To optimize and apply an approach suitable for large-scale neonatal thalassemia genetic screening in China,thalassemia genotypes were determined by polymerase chain reaction-reverse dot blot using DNA extracted from dried blood spots(DBS)obtained from newborn screening programs.Methods Firstly,the most suitable commercial DNA extraction kit for DBS was screened.Then,the appropriate amount of DBS required for the automated high-throughput DNA extraction system was evaluated.Finally,the thalassemia prevalence and genotype spectrum in Shenzhen were investigated in 2028 newborns using the optimized screening procedure.Results The Magentec extraction kit was best suited for the automated DBS DNA extraction system using eight 3-mm DBS discs.The neonatal thalassemia prevalence in Shenzhen was 9.12%;6.31%α-thalassemia,2.37%β-thalassemia,and 0.44%α-/β-thalassemia.Conclusions Genetic screening based on DBS can precisely identify the thalassemia genotypes.Bothα-andβ-thalassemia are widely distributed in Shenzhen newborns.Newborn genetic screening is important for establishing a comprehensive thalassemia prevention program and for public education.展开更多
To the editor:Spinal muscular atrophy(SMA)is a severe autosomal recessive neuromuscular disorder with an incidence of approximately one in 10000 live births.Patients exhibit progressive muscle weakness and atrophy,wit...To the editor:Spinal muscular atrophy(SMA)is a severe autosomal recessive neuromuscular disorder with an incidence of approximately one in 10000 live births.Patients exhibit progressive muscle weakness and atrophy,with the most severe type 1 cases often leading to mortality before the age of 2 years.The advent of disease-modifying therapies(DMTs)has altered the natural history of SMA,and multiple real-world cohort studies have revealed the benefit of early access to disease-modifying therapies,1,2 thus necessitating new management strategies for evolving patient needs.Two DMTs,nusinersen(SPINRAZA)and risdiplam(EVRYSDI)have been approved for use in China.Specifically,the oral dispersible formulation of risdiplam is indicated for the treatment of SMA patients aged 16 days and older in China,while it has been approved by the Food and Drug Administration for use in patients of all ages in the United States since 2022.On the other hand,local pilot studies on SMA newborn screening(NBS)are also being conducted in China.展开更多
基金supported by the National Natural Science Foundation of China(No.81170462)
文摘Microvesicles （MVs） are the heterogeneous mixtures of vesicles. MVs released by leukemia cells constitute an important part of the leukemia microenvironment. MVs might act as important reser- voirs of microRNAs （miRNAs）. It is worth evaluating whether MVs possess some unique miRNA con- tents that are valuable in understanding the pathogenesis. In this study, we investigated the miRNA ex- pression patterns of Nalm-6-derived MVs, Jurkat-derived MVs and normal cell-derived MVs using miRNA microarrays. The potential target genes regulated by differentially expressed miRNAs were also predicted and analyzed. Results demonstrated that 182 miRNAs and 166 miRNAs were differentially expressed in Nalm-6-MVs and Jurkat-MVs, respectively. Many oncogenes, tumor suppressors and sig- nal pathway genes were targeted by these aberrantly expressed miRNAs, which might contribute to the development of B-ALL or T-ALL. Our findings expanded the potential diagnostic markers of ALL and provided useful information for ALL pathogenesis.
基金the Foundation of National Key R&D Program of China of Research on Application Demonstration and Evaluation of Comprehensive Prevention And Control Technology of Birth Defects(Grant No.2018YFC1002700)Zhejiang R&D Research Project Research on New Technologies for Birth Health,Birth Safety and Perinatal Disease Diagnosis and Treatment(Grant No.2021C03099).
文摘Background Newborn screening(NBS)is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases.The develop-ment of next-generation sequencing(NGS)technology provides new opportunities to expand current newborn screening methodologies.Methods We designed a a newborn genetic screening(NBGS)panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS.With this panel,a large-scale,multicenter,prospective multidisease analysis was conducted on dried blood spot(DBS)profiles from 21,442 neonates nationwide.Results We presented the positive detection rate and carrier frequency of diseases and related variants in different regions;and 168(0.78%)positive cases were detected.Glucose-6-Phosphate Dehydrogenase deficiency(G6PDD)and phenylketonuria(PKU)had higher prevalence rates,which were significantly different in different regions.The positive detection of G6PD variants was quite common in south China,whereas PAH variants were most commonly identified in north China.In addi-tion,NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants,which were normal in conventional NBS,but were confirmed later as abnormal in repeated biochemical testing after recall.Eighty percent of high-frequency gene carriers and 60%of high-frequency variant carriers had obvious regional differences.On the premise that there was no significant difference in birth weight and gestational age,the biochemical indicators of SLC22A5 c.1400C>G and ACADSB c.1165A>G carriers were significantly different from those of non-carriers.Conclusions We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS methods.Our data also showed that the prevalence of diseases has significant regional charac-teristics,which provides a theoretical basis for screening diseases in different regions.
基金This work was supported by the National Natural Science Foundation of China(81574068).
文摘Background:Moxibustion is a traditional Chinese medicine therapy to cure diseases by fumigating meridians or affected parts via burning of moxa floss.Moxa smoke(MS)is one of the key factors in moxibustion.In this study,we adopted digital gene expression profiling,a next-generation gene sequencing technology,to investigate the effect of MS,inhalable particulate matter(PM10),on human lung adenocarcinoma A549 cells.Methods:The effects of MS PM10 on A549 cells,over different treatment durations were investigated in different groups:the 4-h group(4-h MS group and 4-h control group)and the 20-h group(20-h MS group and 20-h control group).Samples collected from the four groups were stored at80C for subsequent digital gene expression analysis.The differentially expressed genes(DEGs),identified after PM10 treatment,were screened,and their expression patterns analyzed by cluster analysis,Gene Ontology term enrichment,and Kyoto Encyclopedia of Genes and Genomes pathway analysis.Results:Compared with two control groups,1109 DEGs were identified after 4 h of MS intervention and 3565 DEGs were found after 20 h of MS intervention,respectively.Compared with that after 4-h intervention,2149 DEGs were identified after 20-h intervention.Cluster analysis demonstrated that PM10 can significantly inhibit cell cycle process with the prolongation of intervention time.Significant pathway enrichment analysis showed that MS PM10 can inhibit A549 cell cycle process at all phases.When MS PM10 exposure time prolongs,the inhibitory effect on cell cycle process becomes more obvious.Conclusion:MS PM10 has many biological activities,and may cause differential expression of genes involved in various biological processes.Nevertheless,further research on MS is warranted for better understanding of the mechanistic details.
文摘Background To optimize and apply an approach suitable for large-scale neonatal thalassemia genetic screening in China,thalassemia genotypes were determined by polymerase chain reaction-reverse dot blot using DNA extracted from dried blood spots(DBS)obtained from newborn screening programs.Methods Firstly,the most suitable commercial DNA extraction kit for DBS was screened.Then,the appropriate amount of DBS required for the automated high-throughput DNA extraction system was evaluated.Finally,the thalassemia prevalence and genotype spectrum in Shenzhen were investigated in 2028 newborns using the optimized screening procedure.Results The Magentec extraction kit was best suited for the automated DBS DNA extraction system using eight 3-mm DBS discs.The neonatal thalassemia prevalence in Shenzhen was 9.12%;6.31%α-thalassemia,2.37%β-thalassemia,and 0.44%α-/β-thalassemia.Conclusions Genetic screening based on DBS can precisely identify the thalassemia genotypes.Bothα-andβ-thalassemia are widely distributed in Shenzhen newborns.Newborn genetic screening is important for establishing a comprehensive thalassemia prevention program and for public education.
基金supported by the Cyrus Tang Foundation through the project“Early Identification and Intensive Management of Severe Neurogenetic Diseases Affecting Children’s Physical and Mental Health”
文摘To the editor:Spinal muscular atrophy(SMA)is a severe autosomal recessive neuromuscular disorder with an incidence of approximately one in 10000 live births.Patients exhibit progressive muscle weakness and atrophy,with the most severe type 1 cases often leading to mortality before the age of 2 years.The advent of disease-modifying therapies(DMTs)has altered the natural history of SMA,and multiple real-world cohort studies have revealed the benefit of early access to disease-modifying therapies,1,2 thus necessitating new management strategies for evolving patient needs.Two DMTs,nusinersen(SPINRAZA)and risdiplam(EVRYSDI)have been approved for use in China.Specifically,the oral dispersible formulation of risdiplam is indicated for the treatment of SMA patients aged 16 days and older in China,while it has been approved by the Food and Drug Administration for use in patients of all ages in the United States since 2022.On the other hand,local pilot studies on SMA newborn screening(NBS)are also being conducted in China.
