Objective: To identify phytochemical constituents present in the extract of flowers of Xanthoceras sorbifolia and evaluate their anti-oxidant and anti-hyperglycemic capacities.Methods: The AlCl3colorimetric method and...Objective: To identify phytochemical constituents present in the extract of flowers of Xanthoceras sorbifolia and evaluate their anti-oxidant and anti-hyperglycemic capacities.Methods: The AlCl3colorimetric method and Prussian Blue assay were used to determine the contents of total flavonoids and total phenolic acids in extraction layers, and the bioactive layers was screened through anti-oxidative activity in vitro. The Waters ACQUITY UPLC system and a Waters ACQUITY UPLC BEH C18column(2.0 mm × 150 mm, 5 μm) were used to identify the ingredients. And anti-oxidative ingredients were screened by off-line UPLC-QTOF-MS/MS-free radical scavenging. The ameliorative role of it was further evaluated in a high-fat, streptozotocin-induced type 2 diabetic rat model and the study was carried out on NADPH oxidase(PDB ID: 2CDU) by molecular docking.Results: Combined with the results of activity screening in vitro, the anti-oxidative part was identified as the ethyl acetate layer. A total of 24 chemical constituents were identified by liquid chromatographymass spectrometry in the ethyl acetate layer and 13 main anti-oxidative active constituents were preliminarily screened out through off-line UPLC-QTOF-MS/MS-free radical scavenging. In vivo experiments showed that flowers of X. sorbifolia could significantly reduce the blood glucose level of diabetic mice and alleviate liver cell damage. Based on the results of docking analysis related to the identified phytocompounds and oxidase which involved in type 2 diabetes, quercetin 3-O-rutinoside, kaempferol-3-O-rhamnoside, isorhamnetin-3-O-glucoside, and isoquercitrin showed a better inhibitory profile.Conclusion: The ethyl acetate layer was rich in flavonoids and phenolic acids and had significant anti-oxidant activity, which could prevent hyperglycemia. This observed activity profile suggested X. sorbifolia flowers as a promising new source of tea to develop alternative natural anti-diabetic products with a high safety margin.展开更多
Since the outbreak of the pandemic coronavirus disease 2019(COVID-19),various articles on different fields of the disease published in medical and related journals increased in a way of explosion.A recent literature s...Since the outbreak of the pandemic coronavirus disease 2019(COVID-19),various articles on different fields of the disease published in medical and related journals increased in a way of explosion.A recent literature search at PubMed using the term“COVID-19”only displayed more than 314000 articles.展开更多
In adults, the presence of the BRAF^(V600E) mutation in papillary thyroid cancer(PTC) has been demonstrated to be strongly associated with aggressive cancer-cell characteristics and poor patient prognosis. In contrast...In adults, the presence of the BRAF^(V600E) mutation in papillary thyroid cancer(PTC) has been demonstrated to be strongly associated with aggressive cancer-cell characteristics and poor patient prognosis. In contrast, the frequency of this mutation in pediatric PTC has undergone limited study, and the few available estimates range from 0 to 63%. Furthermore, the role of the BRAF^(V600E) mutation in pediatric PTC is controversial; thus, the present study aimed to investigate the prevalence and role of the BRAF^(V600E) mutation in48 pediatric patients with PTC, aged 3–13 years. Of these patients, 41 were diagnosed with classic PTC, five were found to have a follicular variant of PTC, and two to exhibit a diffuse sclerosing PTC variant. The BRAF^(V600E) mutation was identified to be present in 35.4% of the 48 analyzed patients, and in 41.5% of the patients diagnosed with classical PTC. Furthermore, the presence of the BRAF^(V600E) mutation was found to be associated with a patient age at diagnosis of less than ten years(P=0.011), the performance of a thyroidectomy(P=0.03), exhibited tumor multifocality(P=0.02) and/or extra-thyroidal invasion(P=0.003), and both a low MACIS(Metastases, Age, Completeness of resection, Invasion, Size)(P=0.036) and AMES(Age, Metastasis, Extent of tumor,Size)(P=0.001)score. Together, these data suggest that the presence of the BRAF^(V600E) mutation may be negatively correlated with partial aggressive clinicopathological features of pediatric PTC.展开更多
Introduction Futang Research Center of Pediatric Development(FRCPD),the first nonprofit social service organization engaging in pediatric research in China,was founded in May 2013.Until August 2021,FRCPD has 40 tertia...Introduction Futang Research Center of Pediatric Development(FRCPD),the first nonprofit social service organization engaging in pediatric research in China,was founded in May 2013.Until August 2021,FRCPD has 40 tertiary children’s hospitals,accounting for about 65.6%of all national public children’s hospitals,which was reported to be 61 in China Health Statistical Yearbook(2020).The hospitals are distributed in 30 provinces,autonomous regions,and municipalities(except for Tibet autonomous region),and most of them are in the capital of the province,forming a broad frontline representing the best quality of health care for the diagnosis and treatment of children’s disease in China.Based on the idea of sharing,FRCPD realized the exchange of experts,medical resources,research findings,educational events,preventive strategies,and management experiences among members.In the long run,FRCPD aims to continuously promote the quality of healthcare and medical service capability for children in China.展开更多
The aims of the present study were to reveal the prevalence of the TERT C228 T mutation in pediatric papillary thyroid carcinoma(PPTC) and to further investigate the role of the TERT C228 T mutation in PPTC. We also t...The aims of the present study were to reveal the prevalence of the TERT C228 T mutation in pediatric papillary thyroid carcinoma(PPTC) and to further investigate the role of the TERT C228 T mutation in PPTC. We also tested another TERT mutation, TERT C250 T, although this was not detected in PPTC patients. In this study, 48 patients with PPTC(41 with classic PPTC) were enrolled. DNA was extracted from PPTC tissues and TERT C228 T mutation analysis was performed. Chi-squared analysis,Fisher’s exact test, and a t-test were applied to test the significance of differences. The TERT C228 T mutation presented in 13(27.1%) of the 48 PPTC patients and 10(24.4%) of the 41 classical PPTC patients. There were significant differences between PPTC patients with the TERT C228 T mutation and those without in terms of modified radical neck dissection, multifocality,capsular invasion, extrathyroidal invasion, and American Joint Committee on Cancer(AJCC) tumor stage(P<0.05). In classical PPTC, there were additional significant differences in other clinic-pathological features, such as AJCC nodal stage(P=0.009)and American Thyroid Association(ATA) PPTC stage(P=0.021) between patients with and without the TERT C228 T mutation.These findings indicate that the TERT C228 T mutation is significantly correlated with certain aggressive clinic-pathological features of PPTC.展开更多
High-throughput next generation sequencing (NGS) is a shotgun approach applied in a parallel fashion by which the genome is fragmented and sequenced through small pieces and then analyzed either by aligning to a known...High-throughput next generation sequencing (NGS) is a shotgun approach applied in a parallel fashion by which the genome is fragmented and sequenced through small pieces and then analyzed either by aligning to a known reference genome or by de novo assembly without reference genome.This technology has led researchers to conduct an explosion of sequencing related projects in multidisciplinary fields of science.However,due to the limitations of sequencing-based chemistry,length of sequencing reads and the complexity of genes,it is difficult to determine the sequences of some portions of the human genome,leaving gaps in genomic data that frustrate further analysis.Particularly,some complex genes are difficult to be accurately sequenced or mapped because they contain high GC-content and/or low complexity regions,and complicated pseudogenes,such as the genes encoding xenobiotic metabolizing enzymes and transporters (XMETs).The genetic variants in XMET genes are critical to predicate interindividual variability in drug efficacy,drug safety and susceptibility to environmental toxicity.We summarized and discussed challenges,wet-lab methods,and bioinformatics algorithms in sequencing "complex" XMET genes,which may provide insightful information in the application of NGS technology for implementation in toxicogenomics and pharmacogenomics.展开更多
Obstructive sleep apnea(OSA)is a common sleep-disordered breathing disease that often leads to many comorbidities(e.g.,cognitive dysfunction),which adversely affect the quality of life for patients with OSA.Thus far,t...Obstructive sleep apnea(OSA)is a common sleep-disordered breathing disease that often leads to many comorbidities(e.g.,cognitive dysfunction),which adversely affect the quality of life for patients with OSA.Thus far,the underlying mechanisms of this dysfunction remain unclear.Many studies have focused on OSA-related characteristics,including intermittent hypoxemia and sleep fragmentation.There is increasing emphasis on neuroimaging studies to explore underlying relationships between neuropathological changes and cognitive dysfunction.This article reviews recent research progress concerning cognitive dysfunction associated with OSA to reveal potential mechanisms that contribute to this dysfunction.展开更多
Antiviral therapy with antiviral agents is a very important component of treatment for the 2019 novel coronavirus disease(COVID-19)caused by the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).It is import...Antiviral therapy with antiviral agents is a very important component of treatment for the 2019 novel coronavirus disease(COVID-19)caused by the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).It is important to clarify how to evaluate efficacy and safety of antiviral agents in treatment of COVID-19 during the pandemic of this disease.We need to answer the following questions:do we still need to use rigorously designed randomized controlled clinical trials(RCTs)?Or,will it be enough if we use loosened criteria,observational studies or even retrospective case series and case reports?The answer is"No,we still need to use the strictly designed preferably blinded multicenter RCTs to evaluate the antiviral agents."In this article,we reviewed almost all the RCT reports on monotherapies and combined therapies with antiviral agents for COVID-19,and found that among the reports on monotherapies,only remdesivir,and among combined antiviral agents,only the combined regimen with interferon-β1b,lopinavir-ritonavir and ribavirin were effective and safe based on evidences from RCTs.The results of five RCTs for chloroquine or hydroxychloroquine consistently showed that they were ineffective and unsafe in the treatment of COVID-19,especially at larger doses.Many aspects in the design of the clinical trials may be related to success or failure of a trial and the relevant factors need to be analyzed,discussed and emphasized from the specific requirements and considerations of antiviral therapies.We hope such discussions be of certain use in designing clinical trials for pediatric antiviral therapies.展开更多
INTRODUCTION Pediatric foreign body aspiration can be a life-threatening emergency requiring immediate intervention.The standard intervention for the vast majority of airway foreign bodies is rigid bronchoscopy,1 whic...INTRODUCTION Pediatric foreign body aspiration can be a life-threatening emergency requiring immediate intervention.The standard intervention for the vast majority of airway foreign bodies is rigid bronchoscopy,1 which was first performed by Gustav Killian in 1897.However,for some large or irregular airway foreign bodies,endoscopic removal remains challenging,even in the most experienced hands.In such cases,open surgery may be preferred to protect the airway and facilitate foreign body removal.We present a unique case of a 9-cm sharp metallic chain lodged in the lower trachea and right main bronchus of a 16-month-old girl,which was removed using combined low tracheotomy and rigid bronchoscopy.This case highlights the treatment options for large and irregular airway foreign bodies in rare locations.展开更多
The morphologies of alveolar rhabdomyosarcoma(ARMS) are various. Some cases entirely lack an alveolar pattern and instead display a histological pattern that overlaps with embryonal rhabdomyosarcoma(ERMS). The method ...The morphologies of alveolar rhabdomyosarcoma(ARMS) are various. Some cases entirely lack an alveolar pattern and instead display a histological pattern that overlaps with embryonal rhabdomyosarcoma(ERMS). The method of pathological diagnosis of ARMS and ERMS has been updated in the 4th edition of the World Health Organization's guidelines for classification of skeletal muscle tumors. Under the new guidelines, there is still no molecular test to distinguish between these two subtypes of rhabdomyosarcoma(RMS). In the present study, we applied fluorescent in situ hybridization(FISH) and found that the Forkhead box O1(FOXO1) gene broke apart, amplified, and displayed an aneuploid signal that was related to the RMS pathological subtype.Aside from the fact that FOXO1 break-apart and its amplification were correlated with atypical ARMS, aneuploidies were usually found in atypical ERMS. In conclusion, our results detail a potential biomarker to improve the accuracy of pathological diagnosis by discriminating between atypical ARMS and atypical ERMS.展开更多
Neuroblastoma(NB)is one of the most common malignant tumors in children,with variable clinical behaviors and a 15%death rate of all malignancies in childhood.However,genetic susceptibility to sporadic NB in Han Chines...Neuroblastoma(NB)is one of the most common malignant tumors in children,with variable clinical behaviors and a 15%death rate of all malignancies in childhood.However,genetic susceptibility to sporadic NB in Han Chinese patients is largely unknown.To identify genetic risk factors for NB,we performed an association study on 357 NB patients and 738 control subjects among Han Chinese children.We focused on DEAD box 1(DDX1),a putative RNA helicase,which is involved in NB carcinogenesis.The potential association of DDX1 polymorphisms with NB has not been discovered.Our results demonstrate that rs72780850(NM_004939.2:c.-1555 T>C)located in the DDX1 promoter region is significantly associated with higher expression of DDX1 transcript and increased NB risk(odds ratio=1.64,95%confidence interval=1.03%–2.60%,P=0.004),especially in aggressive NB compared with ganglioneuroma and ganglioneuroblastoma in a dominant model(TC+CC vs.TT).Furthermore,the MYC-associated protein X(MAX)transcription factor showed stronger binding affinity to the DDX1 rs72780850 CC allele compared with the TT allele,explaining the molecular mechanism of the increased NB risk caused by the rs72780850 polymorphism.Our results highlight the involvement of regulatory genetic variants of DDX1 in NB.展开更多
Importance:First branchial cleft anomalies(FBCAs)are rare congenital malformations,accounting for<8%of all branchial cleft anomalies.However,little is currently known about the cause of FBCAs at the molecular level...Importance:First branchial cleft anomalies(FBCAs)are rare congenital malformations,accounting for<8%of all branchial cleft anomalies.However,little is currently known about the cause of FBCAs at the molecular level.Objective:To identify genomic alterations related to the genetic etiology of FBCAs in Chinese children.Methods:We performed whole-exome sequencing of samples from 10 pediatric patients with FBCAs.Data analysis was carried out using the Burrow-Wheeler Alignment software package,and the dbSNP database for comparisons.Rare variants were further validated by Sanger sequencing.Insertion/deletions(indels)were examined using the Genome Analysis Toolkit.Results:We identified 14 non-synonymous mutations in seven potential FBCA-susceptibility genes(TRAPPC12,NRP2,NPNT,SH3RF2,RHPN1,TENM4,and ARMCX4).We also detected 133 shared small indels in 125 genes.Gene Ontology analysis indicated that most of the identified genes played critical roles in development and differentiation pathways involved in regulating organ development.Interpretation:We characterized the mutational landscape in pathways involved in development and differentiation in Chinese children with FBCA.The results identified potential pathogenic genes and mutations related to FBCA,and provide molecular-level support for the branchial theory of FBCA pathogenesis.展开更多
Introduction:Cardiac neoplasms are particularly rare in children,and the majority of these tumors are benign.Approximately 10%of cardiac neoplasms are malignant,including soft tissue sarcomas and lymphomas.Cardiac tum...Introduction:Cardiac neoplasms are particularly rare in children,and the majority of these tumors are benign.Approximately 10%of cardiac neoplasms are malignant,including soft tissue sarcomas and lymphomas.Cardiac tumors could also be metastases.Primitive EWSR1-negative round or spindle cell undifferentiated sarcoma harboring CIC gene translocation is a highly aggressive malignancy mainly occurring in soft tissues.However,it has not yet been described in the heart.Case presentation:We report a sarcoma that arose from the right ventricle in a 1-year-old girl.Histologically,it was composed of closely arranged small round or oval undifferentiated cells with fibrovascular separation,hyaline degeneration,and geographical necrosis.Immunohistochemically,the neoplastic cells exhibited focal membrane positivity for CD99 and diffuse positivity for WT1 and ETV4.Fluorescent in situ hybridization analysis showed EWSR1-negative but CIC-positive split signals.The breakpoint was also confirmed by whole genome sequencing.Conclusion:Based on morphological,immunohistochemical and molecular findings,this cardiac mass was diagnosed as CIC-rearranged sarcoma.展开更多
Importance Rhabdomyosarcoma(RMS)is the most common soft tissue sarcoma in children.More than 90%of cases are classified as embryonic RMS(ERMS)or alveolar RMS(ARMS).ERMS has a worse prognosis than ARMS.Early differenti...Importance Rhabdomyosarcoma(RMS)is the most common soft tissue sarcoma in children.More than 90%of cases are classified as embryonic RMS(ERMS)or alveolar RMS(ARMS).ERMS has a worse prognosis than ARMS.Early differential diagnosis is of paramount importance for optimization of treatment.Objective To identify genes that are differentially expressed between ARMS and ERMS,which can be used for accurate rhabdomyosarcoma classification.Methods Three Gene Expression Omnibus datasets composed of ARMS and ERMS samples were screened and 35 differentially expressed genes(DEGs)were identified.Receiver operating characteristic curve analysis and area under the curve analysis was performed for these 35 DEGs and seven candidate genes with the best differential expression scores between ARMS and ERMS were determined.The expression of these seven candidate genes was validated by immunohistochemical analysis of pre-chemotherapy ARMS and ERMS specimens.Results The levels of DCX and CRABP2 were confirmed to be remarkably different between paraffin-embedded ARMS and ERMS tissues,while EGFR abundance was only marginally different between these two RMS subtypes.Interpretation DCX and CRABP2 are potential biomarkers for distinguishing ARMS from ERMS in pre-chemotherapy pediatric patients.展开更多
Next-generation sequencing (NGS) is being used in clinical testing.Government authorities in both China and the United States are overseeing the clinical application of NGS instruments and reagents.In addition,the US ...Next-generation sequencing (NGS) is being used in clinical testing.Government authorities in both China and the United States are overseeing the clinical application of NGS instruments and reagents.In addition,the US Association for Molecular Pathology and the College of American Pathologists have jointly released a guidance to standardize the analysis and interpretation of NGS data involved in clinical testing.At present,the analysis strategies and pipelines for NGS data related to the clinical detection of pediatric disease are similar to those used for adult diseases.However,for rare pediatric diseases without linkage to known genetic variants,it is currently difficult to detect the relevant pathogenic genes using NGS technology.Additionally,it is challenging to identify novel pathogenic genes of familial pediatric tumors.Therefore,characterization of the pathogenic genes associated with above diseases is important for the diagnosis and treatment of rare diseases in children.This article introduces the general pipelines for NGS data analyses of diseases and elucidates data analysis strategies for the pathogenic genes of rare pediatric diseases and familial pediatric tumors.展开更多
基金the Fourth National Investigation of Chinese materia medica resources in Liaoning Province (LN2018017, LN2019019)Career Development Support Plan for Young and Middle-aged Teachers in Shenyang Pharmaceutical University (No. ZQN2021014)Key Laboratory of Marine Biogenetic Resources, Ministry of Natural Resources (No. HY202105)
文摘Objective: To identify phytochemical constituents present in the extract of flowers of Xanthoceras sorbifolia and evaluate their anti-oxidant and anti-hyperglycemic capacities.Methods: The AlCl3colorimetric method and Prussian Blue assay were used to determine the contents of total flavonoids and total phenolic acids in extraction layers, and the bioactive layers was screened through anti-oxidative activity in vitro. The Waters ACQUITY UPLC system and a Waters ACQUITY UPLC BEH C18column(2.0 mm × 150 mm, 5 μm) were used to identify the ingredients. And anti-oxidative ingredients were screened by off-line UPLC-QTOF-MS/MS-free radical scavenging. The ameliorative role of it was further evaluated in a high-fat, streptozotocin-induced type 2 diabetic rat model and the study was carried out on NADPH oxidase(PDB ID: 2CDU) by molecular docking.Results: Combined with the results of activity screening in vitro, the anti-oxidative part was identified as the ethyl acetate layer. A total of 24 chemical constituents were identified by liquid chromatographymass spectrometry in the ethyl acetate layer and 13 main anti-oxidative active constituents were preliminarily screened out through off-line UPLC-QTOF-MS/MS-free radical scavenging. In vivo experiments showed that flowers of X. sorbifolia could significantly reduce the blood glucose level of diabetic mice and alleviate liver cell damage. Based on the results of docking analysis related to the identified phytocompounds and oxidase which involved in type 2 diabetes, quercetin 3-O-rutinoside, kaempferol-3-O-rhamnoside, isorhamnetin-3-O-glucoside, and isoquercitrin showed a better inhibitory profile.Conclusion: The ethyl acetate layer was rich in flavonoids and phenolic acids and had significant anti-oxidant activity, which could prevent hyperglycemia. This observed activity profile suggested X. sorbifolia flowers as a promising new source of tea to develop alternative natural anti-diabetic products with a high safety margin.
文摘Since the outbreak of the pandemic coronavirus disease 2019(COVID-19),various articles on different fields of the disease published in medical and related journals increased in a way of explosion.A recent literature search at PubMed using the term“COVID-19”only displayed more than 314000 articles.
基金supported in part by Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201508)Beijing Municipal Science and Technology Project (D131100005313014)Beijing Health System Top Level Health Technical Personnel Training Plan (20153079)
文摘In adults, the presence of the BRAF^(V600E) mutation in papillary thyroid cancer(PTC) has been demonstrated to be strongly associated with aggressive cancer-cell characteristics and poor patient prognosis. In contrast, the frequency of this mutation in pediatric PTC has undergone limited study, and the few available estimates range from 0 to 63%. Furthermore, the role of the BRAF^(V600E) mutation in pediatric PTC is controversial; thus, the present study aimed to investigate the prevalence and role of the BRAF^(V600E) mutation in48 pediatric patients with PTC, aged 3–13 years. Of these patients, 41 were diagnosed with classic PTC, five were found to have a follicular variant of PTC, and two to exhibit a diffuse sclerosing PTC variant. The BRAF^(V600E) mutation was identified to be present in 35.4% of the 48 analyzed patients, and in 41.5% of the patients diagnosed with classical PTC. Furthermore, the presence of the BRAF^(V600E) mutation was found to be associated with a patient age at diagnosis of less than ten years(P=0.011), the performance of a thyroidectomy(P=0.03), exhibited tumor multifocality(P=0.02) and/or extra-thyroidal invasion(P=0.003), and both a low MACIS(Metastases, Age, Completeness of resection, Invasion, Size)(P=0.036) and AMES(Age, Metastasis, Extent of tumor,Size)(P=0.001)score. Together, these data suggest that the presence of the BRAF^(V600E) mutation may be negatively correlated with partial aggressive clinicopathological features of pediatric PTC.
文摘Introduction Futang Research Center of Pediatric Development(FRCPD),the first nonprofit social service organization engaging in pediatric research in China,was founded in May 2013.Until August 2021,FRCPD has 40 tertiary children’s hospitals,accounting for about 65.6%of all national public children’s hospitals,which was reported to be 61 in China Health Statistical Yearbook(2020).The hospitals are distributed in 30 provinces,autonomous regions,and municipalities(except for Tibet autonomous region),and most of them are in the capital of the province,forming a broad frontline representing the best quality of health care for the diagnosis and treatment of children’s disease in China.Based on the idea of sharing,FRCPD realized the exchange of experts,medical resources,research findings,educational events,preventive strategies,and management experiences among members.In the long run,FRCPD aims to continuously promote the quality of healthcare and medical service capability for children in China.
基金supported in part by Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201508)Beijing Municipal Science and Technology Project (D131100005313014)+1 种基金Beijing Health System Top Level Health Technical Personnel Training Plan (20153079)Key subjects of medical science research in Hebei Province (20170395)
文摘The aims of the present study were to reveal the prevalence of the TERT C228 T mutation in pediatric papillary thyroid carcinoma(PPTC) and to further investigate the role of the TERT C228 T mutation in PPTC. We also tested another TERT mutation, TERT C250 T, although this was not detected in PPTC patients. In this study, 48 patients with PPTC(41 with classic PPTC) were enrolled. DNA was extracted from PPTC tissues and TERT C228 T mutation analysis was performed. Chi-squared analysis,Fisher’s exact test, and a t-test were applied to test the significance of differences. The TERT C228 T mutation presented in 13(27.1%) of the 48 PPTC patients and 10(24.4%) of the 41 classical PPTC patients. There were significant differences between PPTC patients with the TERT C228 T mutation and those without in terms of modified radical neck dissection, multifocality,capsular invasion, extrathyroidal invasion, and American Joint Committee on Cancer(AJCC) tumor stage(P<0.05). In classical PPTC, there were additional significant differences in other clinic-pathological features, such as AJCC nodal stage(P=0.009)and American Thyroid Association(ATA) PPTC stage(P=0.021) between patients with and without the TERT C228 T mutation.These findings indicate that the TERT C228 T mutation is significantly correlated with certain aggressive clinic-pathological features of PPTC.
基金supported by the FDA Project(E0765001)the National Key Research and Development Program of China(2016YFC0902100 to Geng Chen)
文摘High-throughput next generation sequencing (NGS) is a shotgun approach applied in a parallel fashion by which the genome is fragmented and sequenced through small pieces and then analyzed either by aligning to a known reference genome or by de novo assembly without reference genome.This technology has led researchers to conduct an explosion of sequencing related projects in multidisciplinary fields of science.However,due to the limitations of sequencing-based chemistry,length of sequencing reads and the complexity of genes,it is difficult to determine the sequences of some portions of the human genome,leaving gaps in genomic data that frustrate further analysis.Particularly,some complex genes are difficult to be accurately sequenced or mapped because they contain high GC-content and/or low complexity regions,and complicated pseudogenes,such as the genes encoding xenobiotic metabolizing enzymes and transporters (XMETs).The genetic variants in XMET genes are critical to predicate interindividual variability in drug efficacy,drug safety and susceptibility to environmental toxicity.We summarized and discussed challenges,wet-lab methods,and bioinformatics algorithms in sequencing "complex" XMET genes,which may provide insightful information in the application of NGS technology for implementation in toxicogenomics and pharmacogenomics.
基金Capital Funds for Health Improvement and Research(2018-1-2091)National Natural Science Foundation of China(81970900)+1 种基金Natural Science Foundation of Beijing Municipality(7194262)Pediatric Medical Coordinated Development Center of Beijing Municipal Administration(XTZD20180101)。
文摘Obstructive sleep apnea(OSA)is a common sleep-disordered breathing disease that often leads to many comorbidities(e.g.,cognitive dysfunction),which adversely affect the quality of life for patients with OSA.Thus far,the underlying mechanisms of this dysfunction remain unclear.Many studies have focused on OSA-related characteristics,including intermittent hypoxemia and sleep fragmentation.There is increasing emphasis on neuroimaging studies to explore underlying relationships between neuropathological changes and cognitive dysfunction.This article reviews recent research progress concerning cognitive dysfunction associated with OSA to reveal potential mechanisms that contribute to this dysfunction.
文摘Antiviral therapy with antiviral agents is a very important component of treatment for the 2019 novel coronavirus disease(COVID-19)caused by the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).It is important to clarify how to evaluate efficacy and safety of antiviral agents in treatment of COVID-19 during the pandemic of this disease.We need to answer the following questions:do we still need to use rigorously designed randomized controlled clinical trials(RCTs)?Or,will it be enough if we use loosened criteria,observational studies or even retrospective case series and case reports?The answer is"No,we still need to use the strictly designed preferably blinded multicenter RCTs to evaluate the antiviral agents."In this article,we reviewed almost all the RCT reports on monotherapies and combined therapies with antiviral agents for COVID-19,and found that among the reports on monotherapies,only remdesivir,and among combined antiviral agents,only the combined regimen with interferon-β1b,lopinavir-ritonavir and ribavirin were effective and safe based on evidences from RCTs.The results of five RCTs for chloroquine or hydroxychloroquine consistently showed that they were ineffective and unsafe in the treatment of COVID-19,especially at larger doses.Many aspects in the design of the clinical trials may be related to success or failure of a trial and the relevant factors need to be analyzed,discussed and emphasized from the specific requirements and considerations of antiviral therapies.We hope such discussions be of certain use in designing clinical trials for pediatric antiviral therapies.
文摘INTRODUCTION Pediatric foreign body aspiration can be a life-threatening emergency requiring immediate intervention.The standard intervention for the vast majority of airway foreign bodies is rigid bronchoscopy,1 which was first performed by Gustav Killian in 1897.However,for some large or irregular airway foreign bodies,endoscopic removal remains challenging,even in the most experienced hands.In such cases,open surgery may be preferred to protect the airway and facilitate foreign body removal.We present a unique case of a 9-cm sharp metallic chain lodged in the lower trachea and right main bronchus of a 16-month-old girl,which was removed using combined low tracheotomy and rigid bronchoscopy.This case highlights the treatment options for large and irregular airway foreign bodies in rare locations.
基金supported in part by Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201508)Beijing Health System Top Level Health Technical Personnel Training Plan (20153079)the Beijing Talents Fund (2015000021469G210)
文摘The morphologies of alveolar rhabdomyosarcoma(ARMS) are various. Some cases entirely lack an alveolar pattern and instead display a histological pattern that overlaps with embryonal rhabdomyosarcoma(ERMS). The method of pathological diagnosis of ARMS and ERMS has been updated in the 4th edition of the World Health Organization's guidelines for classification of skeletal muscle tumors. Under the new guidelines, there is still no molecular test to distinguish between these two subtypes of rhabdomyosarcoma(RMS). In the present study, we applied fluorescent in situ hybridization(FISH) and found that the Forkhead box O1(FOXO1) gene broke apart, amplified, and displayed an aneuploid signal that was related to the RMS pathological subtype.Aside from the fact that FOXO1 break-apart and its amplification were correlated with atypical ARMS, aneuploidies were usually found in atypical ERMS. In conclusion, our results detail a potential biomarker to improve the accuracy of pathological diagnosis by discriminating between atypical ARMS and atypical ERMS.
基金supported by the National Natural Science Foundation of China(81472369 and 81502144)Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education(KZ201810025034)+2 种基金Clinical Application Research Funds of Capital Beijing(Z171100001017051)Beihang University&Capital Medical University Advanced Innovation Center for Big Data-Based Precision Medicine Plan(BHME-201804 and BHME201904)The Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority(XTCX201806)。
文摘Neuroblastoma(NB)is one of the most common malignant tumors in children,with variable clinical behaviors and a 15%death rate of all malignancies in childhood.However,genetic susceptibility to sporadic NB in Han Chinese patients is largely unknown.To identify genetic risk factors for NB,we performed an association study on 357 NB patients and 738 control subjects among Han Chinese children.We focused on DEAD box 1(DDX1),a putative RNA helicase,which is involved in NB carcinogenesis.The potential association of DDX1 polymorphisms with NB has not been discovered.Our results demonstrate that rs72780850(NM_004939.2:c.-1555 T>C)located in the DDX1 promoter region is significantly associated with higher expression of DDX1 transcript and increased NB risk(odds ratio=1.64,95%confidence interval=1.03%–2.60%,P=0.004),especially in aggressive NB compared with ganglioneuroma and ganglioneuroblastoma in a dominant model(TC+CC vs.TT).Furthermore,the MYC-associated protein X(MAX)transcription factor showed stronger binding affinity to the DDX1 rs72780850 CC allele compared with the TT allele,explaining the molecular mechanism of the increased NB risk caused by the rs72780850 polymorphism.Our results highlight the involvement of regulatory genetic variants of DDX1 in NB.
基金Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education(KZ201810025034)Fund of Beijing Excellent Talent Training(2017000021469G252)+1 种基金Special Fund of The Pediatric Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals(XTCX201806)Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University & Capital Medical University, Beijing(BHME- 201804)
文摘Importance:First branchial cleft anomalies(FBCAs)are rare congenital malformations,accounting for<8%of all branchial cleft anomalies.However,little is currently known about the cause of FBCAs at the molecular level.Objective:To identify genomic alterations related to the genetic etiology of FBCAs in Chinese children.Methods:We performed whole-exome sequencing of samples from 10 pediatric patients with FBCAs.Data analysis was carried out using the Burrow-Wheeler Alignment software package,and the dbSNP database for comparisons.Rare variants were further validated by Sanger sequencing.Insertion/deletions(indels)were examined using the Genome Analysis Toolkit.Results:We identified 14 non-synonymous mutations in seven potential FBCA-susceptibility genes(TRAPPC12,NRP2,NPNT,SH3RF2,RHPN1,TENM4,and ARMCX4).We also detected 133 shared small indels in 125 genes.Gene Ontology analysis indicated that most of the identified genes played critical roles in development and differentiation pathways involved in regulating organ development.Interpretation:We characterized the mutational landscape in pathways involved in development and differentiation in Chinese children with FBCA.The results identified potential pathogenic genes and mutations related to FBCA,and provide molecular-level support for the branchial theory of FBCA pathogenesis.
基金Special Fund of The Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority[XTCX201806]Beijing Hospitals Authority Clinical medicine Development of Special Funding Support[XMLX202121]Beijing Advanced Innovation Center for Big Data-Based Precision Medicine,Beihang University&Capital Medical University,Beijing[BHME-201904].
文摘Introduction:Cardiac neoplasms are particularly rare in children,and the majority of these tumors are benign.Approximately 10%of cardiac neoplasms are malignant,including soft tissue sarcomas and lymphomas.Cardiac tumors could also be metastases.Primitive EWSR1-negative round or spindle cell undifferentiated sarcoma harboring CIC gene translocation is a highly aggressive malignancy mainly occurring in soft tissues.However,it has not yet been described in the heart.Case presentation:We report a sarcoma that arose from the right ventricle in a 1-year-old girl.Histologically,it was composed of closely arranged small round or oval undifferentiated cells with fibrovascular separation,hyaline degeneration,and geographical necrosis.Immunohistochemically,the neoplastic cells exhibited focal membrane positivity for CD99 and diffuse positivity for WT1 and ETV4.Fluorescent in situ hybridization analysis showed EWSR1-negative but CIC-positive split signals.The breakpoint was also confirmed by whole genome sequencing.Conclusion:Based on morphological,immunohistochemical and molecular findings,this cardiac mass was diagnosed as CIC-rearranged sarcoma.
基金Beijing Hospitals Authority’Ascent Plan(20191201)Beijing Municipal Science and Technology Commission Fund(Z201100005520077)National Natural Science Foundation of China(81702787).
文摘Importance Rhabdomyosarcoma(RMS)is the most common soft tissue sarcoma in children.More than 90%of cases are classified as embryonic RMS(ERMS)or alveolar RMS(ARMS).ERMS has a worse prognosis than ARMS.Early differential diagnosis is of paramount importance for optimization of treatment.Objective To identify genes that are differentially expressed between ARMS and ERMS,which can be used for accurate rhabdomyosarcoma classification.Methods Three Gene Expression Omnibus datasets composed of ARMS and ERMS samples were screened and 35 differentially expressed genes(DEGs)were identified.Receiver operating characteristic curve analysis and area under the curve analysis was performed for these 35 DEGs and seven candidate genes with the best differential expression scores between ARMS and ERMS were determined.The expression of these seven candidate genes was validated by immunohistochemical analysis of pre-chemotherapy ARMS and ERMS specimens.Results The levels of DCX and CRABP2 were confirmed to be remarkably different between paraffin-embedded ARMS and ERMS tissues,while EGFR abundance was only marginally different between these two RMS subtypes.Interpretation DCX and CRABP2 are potential biomarkers for distinguishing ARMS from ERMS in pre-chemotherapy pediatric patients.
基金National Natural Science Foundation of China(81502144,81472369,31671377)%National Key Research and Development Program of China(2015AA020108)%Beijing Health System Top Level Health Technical Personnel Training Plan(20153079)
文摘Next-generation sequencing (NGS) is being used in clinical testing.Government authorities in both China and the United States are overseeing the clinical application of NGS instruments and reagents.In addition,the US Association for Molecular Pathology and the College of American Pathologists have jointly released a guidance to standardize the analysis and interpretation of NGS data involved in clinical testing.At present,the analysis strategies and pipelines for NGS data related to the clinical detection of pediatric disease are similar to those used for adult diseases.However,for rare pediatric diseases without linkage to known genetic variants,it is currently difficult to detect the relevant pathogenic genes using NGS technology.Additionally,it is challenging to identify novel pathogenic genes of familial pediatric tumors.Therefore,characterization of the pathogenic genes associated with above diseases is important for the diagnosis and treatment of rare diseases in children.This article introduces the general pipelines for NGS data analyses of diseases and elucidates data analysis strategies for the pathogenic genes of rare pediatric diseases and familial pediatric tumors.
