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Objective: To characterize the serum bile acid profiles of healthy children in Zhejiang Province. Methods: A cross-sectional study was conducted on 245 healthy children who underwent imaging and laboratory biochemical tests during routine physical examinations at the Children's Hospital of Zhejiang University School of Medicine from January 2020 to July 2022. Overnight fasting venous blood samples were collected, and the concentrations of 18 individual bile acids in the serum were accurately quantitated using tandem mass spectrometry. The concentration difference of bile acid were compared between different genders and to explore the correlation between age and bile acid levels. Used the Mann-Whitney U test for intergroup comparison and Spearman test to correlation analysis. Results: A total of 245 health children with a age of 10 (8, 12) years including 125 boys and 120 girls. There were no significant differences in levels of total bile acids, primary and secondary bile acids, free and conjugated bile acids between the two gender groups (all P>0.05). The serum concentrations of ursodeoxycholic acid and glycoursodeoxycholic acid in girls were significantly higher than those in boys (199.0 (66.9, 276.5) vs. 154.7 (49.3, 205.0) nmol/L, 274.0 (64.8, 308.0) vs. 181.0 (43.8, 209.3) nmol/L, Z=2.06, 2.71, both P<0.05). The serum taurolithocholic acid in both boys and girls were positively correlated with age (r=0.31, 0.32, both P<0.05). The serum chenodeoxycholic acid and glycochenodeoxycholic acid in the boys group were positively correlated with age (r=0.20, 0.23, both P<0.05), whereas the serum tauroursodeoxycholic acid in the girls group was negatively correlated with age (r=-0.27, P<0.05), and the serum cholic acid was positively correlated with age (r=0.34, P<0.05). Conclusions: The total bile acid levels are relatively stable in healthy children in Zhejiang province. However, individual bile acids showed gender differences and were correlated with age.
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Humans , Child , Female , Male , Cross-Sectional Studies , Bile Acids and Salts , Hospitals, Pediatric , LaboratoriesABSTRACT
Objective:To analyze the application of robot-assisted thoracoscopic surgery in the treatment of pulmonary sequestration in children.Methods:The clinical data of 20 children with pulmonary sequestration admitted to the Children's Hospital Zhejiang University School of Medicine from May to November 2020 were analyzed retrospectively. There were 13 males and 7 females, ages ranged from 6 months to 5 years old, with median age of 10 months. Body weight ranged from 7.5 to 18.0 kg, with mean weight of(9.95±2.46)kg. Abnormal blood supply vessels in pulmonary sequestration were found by chest enhanced CT and were further confirmed during surgery. All the other 19 cases were found to have pulmonary lesions by prenatal ultrasound except 1 case due to repeated infection. The lesions were located in left lung in 15 cases and right lung in 5 cases.Results:1 case was converted to thoracotomy due to failure of intraoperative single lung ventilation and inability of artificial pneumothorax to collapse the lung lobe, and other 19 cases were successfully completed by robot-assisted thoracoscopic surgery. The operation time ranged from 40 to 270 min, mean(88.25±55.68) min. All 10 patients with extralobar sequestration underwent simple pneumonectomy, including 2 patients with intra-diaphragmatic pulmonary sequestration. In 10 cases of intralobar sequestration, 2 cases underwent wedge resection, 2 cases underwent segmental resection, and 6 cases underwent lobectomy. No operative death occurred. The postoperative hospital time ranged from 3 to 10 days, mean(5.00±1.89) days. All patients recovered well and no complications such as pleural effusion and atelectasis were observed during 1-6 months follow-up.Conclusion:The robotic surgical system is safe and effective for the treatment of pulmonary sequestration in children.
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Objective:To explore the correlation between preoperative echocardiography indicators and surgical prognosis of children with ventricular septal defect (VSD) and conduct verification based on significant indicators and indicator ratios.Methods:A total of 1 357 children with VSD who were admitted to the Children′s Hospital, Zhejiang University School of Medicine from June 2016 to June 2021 were selected. Various measurements including the size of the VSD, left ventricular ejection fraction (LVEF), left atrial (LA) diameter, the aortic (AO) flow rate, the tricuspid regurgitation velocity and pressure gradient were extracted from preoperative echocardiography reports. This paper explored the correlation between echocardiography reports indicators, indicator ratios and postoperative auxiliary ventilation time, respectively. The patients were divided into two groups according to whether there were complications, and the differences of echocardiography reports indicators between the two groups were compared. A linear regression model was established to predict the postoperative auxiliary ventilation time using these indicators, and the least absolute shrinkage and selection operator (LASSO) regression model was used for variable selection.Results:The VSD size and AO flow velocity were weakly correlated with the postoperative auxiliary ventilation time ( r=0.32, 0.25; all P<0.01). There was no significant correlation between VSD flow velocity and postoperative auxiliary ventilation time. The AO flow velocity/VSD flow velocity and LVEF/VSD flow velocity were strongly correlated with the postoperative auxiliary ventilation time ( r=0.67, 0.51; all P<0.01). In the significance test, there were no significant differences in tricuspid regurgitation flow velocity, tricuspid regurgitation pressure gradient, LA diameter, and LVEF between the complication group and the non-complication group(all P>0.01). However, the ratio of LVEF/tricuspid regurgitation velocity in the complication group was significantly lower than that in the non-complication group, and the ratio of tricuspid regurgitation pressure gradient/LA diameter was significantly higher than that in the non-complication group (all P<0.01). The postoperative auxiliary ventilation time of VSD patients was predicted on an independent test set, with an R2 of 0.51. Conclusions:Echocardiography report indicator ratios of AO flow velocity/VSD flow velocity and LVEF/VSD flow velocity have strong correlations with postoperative auxiliary ventilation time in children with VSD, and the ratios of LVEF/tricuspid regurgitation velocity and tricuspid regurgitation pressure gradient/LA diameter are significantly different between groups with and without postoperative complications. The ratios of indicators can significantly improve this correlation and difference, which can be used to predict the prognosis of VSD operation.
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Objective:To investigate the correlation between protein C -1641A/-1654C haplotype and coagulation disorder in Chinese Han septic patients.Methods:The genotypes of protein C gene -1641A>G (rs1799809) and -1654C>T (RS1799808) in septic patients were detected by direct sequencing, and their haplotypes were analyzed and divided into two groups according to the haplotype, -1641A/-1654C (AC) carriers and non-AC haplotype carriers. At the same time, unpaired t test or Mann-Whitney U test was used to compare the differences in coagulation/fibrinolytic parameters, including partial activated thrombin time, prothrombin time, internationally standardized ratio of prothrombin time, thrombin time, fibrinogen and D-dimer levels, as well as APC levels between the two groups. Results:A total of 174 septic patients were included in this study, including 60 AC haplotype carriers and 114 non-AC haplotype carriers. Compared with non-AC haplotype carriers, AC haplotype carriers had significantly lower platelet counts, significantly longer partial activated thrombin time, and significantly decreased activated protein C levels. Other coagulation/fibrinolytic parameters including prothrombin time, internationally standardized ratio of prothrombin time, thrombin time, fibrinogen and D-dimer were not significantly different between the two groups.Conclusions:In this study, the protein C-1641A/-1654C haplotype was found to lead to decreased circulating activated protein C levels decreased platelet counts, and prolonged partial activated thrombin time in septic patients. These results suggest that the protein C-1641A/-1654C haplotype may directly affect the APC level and consequently influence the coagulation disorder of sepsis.
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Objective@#To investigate the genotypes and prognosis of infants with definitive diagnosis of inherited metabolic diseases during neonatal screening in Zhejiang Province from 2009 to 2021, so as to provide insights into the management of birth defects.@*Methods@#The medical records of infants with definitive diagnosis of inherited metabolic diseases by tandem mass spectrometry during neonatal screening in Zhejiang Province from 2009 to 2021 were collected from the database created by Zhejiang Provincial Center for Neonatal Disease Screening. The prevalence, genotypes and prognosis of inherited metabolic diseases were analyzed. @*Results@#A total of 1 038 infants were definitively diagnosed with inherited metabolic diseases in Zhejiang Province from 2009 to 2021, with an overall incidence rate of 1/4 535. There were 400 infants with amino acid metabolic disorders (AAD), 342 infants with fatty acid oxidation metabolic disorders and 296 infants with organic acid metabolic disorders (OAD), with incidence of 1/11 767, 1/13 763 and 1\15 902, respectively. There were 32 types of diseases, including 13 types of AAD, 8 types of FAOD and 11 types of OAD identified, and phenylketonuria and tetrahydrobiopterin deficiency (PKU/BH4D), primary carnitine deficiency (PCD) and methylmalonic academia (MMA) were detected as the most common forms of AAD, FAOD and OAD, with incidence of 1/20 827, 1/24 262 and 1\49 030, respectively. A total of 789 infants received genetic testing (76.01%), and genetic testing was performed among 70.00% of infants with AAD, 83.04% of infants with FAOD and 76.01% of infants with OAD. The c.728G >A (p.R243Q) variant was the most common mutation in infants with PKU (29.17%), c.1400C>G (p.S467C) variant was the most common mutation in infants with PCD (33.46%), c.609G>A (p.W203X) variant was the most common mutation in infants with combined MMA (40.00%), and c.1663G>A (p.A555T) variant was the most common mutation in infants with MMA (17.86%). Among the 997 infants (96.05%) with successful follow-up, 973 infants (93.74%) had normal intelligence and physical developments, and 41 infants died (3.95%), including 9 deaths due to AAD, 15 deaths due to FAOD and 17 deaths due to OAD. @*Conclusions @#The incidence of PKU, PCD and MMA was high among infants with inherited metabolic diseases in Zhejiang Province from 2009 to 2021, with c.728G>A (p.R243Q), c.1400C>G (p.S467C) and c.609G>A (p.W203X) variants as common gene mutations, respectively. Most infants with inherited metabolic diseases had a favorable prognosis; however, the mortality of OAD was relatively high.
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The electronic stethoscope combined with artificial intelligence (AI) technology has realized the digital acquisition of heart sounds and intelligent identification of congenital heart disease, which provides objective basis for heart sound auscultation and improves the accuracy of congenital heart disease diagnosis. At the present stage, the AI based cardiac auscultation technique mainly focuses on the research of AI algorithms, and the researchers have designed and summarized a variety of effective algorithms based on the characteristics of cardiac audio data, among which the mel-frequency cepstral coefficients (MFCC) is the most effective one, and widely used in the cardiac auscultation. However, the current cardiac sound analysis techniques are based on specific data sets, and have not been validated in clinic, so the performance of algorithms need to be further verified. The lack of heart sound data, especially the high-quality, standardized, publicly available heart sound database with disease labeling, further restricts the development of heart sound diagnostic analysis and its application in screening. Therefore, expert consensus is necessary in establishing an authoritative heart sound database and standardizing the heart sound auscultation screening process for congenital heart disease. This paper provides an overview of the research and application status of auscultation algorithm and hardware equipment based on AI in auscultation screening of congenital heart disease, and puts forward the problems to be solved in clinical application of AI auscultation screening technology.
Subject(s)
Humans , Algorithms , Artificial Intelligence , Heart Auscultation/trends , Heart Defects, Congenital/diagnosis , Mass Screening/methodsABSTRACT
Laboratory testing plays an important role in the diagnosis and treatment of patients with Novel Coronavirus pneumonia. However, the lack of understanding of the virus in the early stage led to great difficulties in biosafety protection for clinical laboratories. Based on the latest researches and findings about the virus, this paper provides some personal opinions on the biosafety prevention in clinical laboratorians under epidemic condition for the reference of laboratory workers.
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December 2019 witnessed the outbreak of COVID-19 in Wuhan, Hubei province of China, which has soon spread nationwide and across national borders, posting a menacing pandemic threat. Children are themselves highly susceptible infectious diseases in normal times not to mention an epidemic period. Coupled with the high incidence of seasonal influenza, it is imperative to strengthen epidemiological screening of children, along with effective isolation, treatment, prevention and control measures. In view of specifics of the hospital, the authors proposed to further improve the medical emergency procedure, strictly enforcing screening and isolation regulations, and standardizing medical procedure. They also proposed scientific layout and use of the infection wards. These measures are designed to control the epidemic and protect the safety of medical staff.
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The pneumonia caused by the novel coronavirus (2019-nCoV), which began in December 2019, has become the most serious public health problem, threatening people's health and life. This threat is posing a severe challenge on the diagnosis and treatment of 2019-nCoV infection, the prevention and control of hospital cross infection of medical staff. It is suggested that in addition to strengthening the organization and leadership of the abovementioned work, establishing and improving the prevention and control mechanism deserve greater attention. Furthermore, special attention should be given to the safety of the medical staff, strengthening their infection monitoring and outbreak management. Medical staff in different work areas and positions should be placed under careful protection, cleaning and disinfection measures. The protection during specimen collection, transportation and medical waste management should also be prioritized. This paper also put forward management suggestions for the outpatient department, isolation ward and other key departments. These measures are proposed to provide a guidance for the prevention and control of 2019-nCoV nosocomial infection in the pediatric outpatient and ward.
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Objective@#Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province.@*Methods@#A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data.@*Results@#The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05).@*Conclusions@#The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.
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The pathogenesis of very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is highly heterogeneous and still unclear. Additional novel variants have been recently detected in the population. The molecular and cellular effects of these previously unreported variants are still poorly understood and require further characterization. To address this problem, we have evaluated the various functions and biochemical consequences of six novel missense variants that lead to mild VLCAD deficiency. Marked deficiencies in fatty acid oxidation (FAO) and other mitochondrial defects were observed in cells carrying one of these six variants (c.541C>T, c.863T>G, c.895A>G, c.1238T>C, c.1276G>A, and c.1505T>A), including reductions in mitochondrial respiratory-chain function and adenosine triphosphate (ATP) production, and increased levels of mitochondrial reactive oxygen species (ROS). Intriguingly, higher apoptosis levels were found in cells carrying the mutant VLCAD under glucose-limited stress. Moreover, the stability of the mutant homodimer was disturbed, and major conformational changes in each mutant VLCAD structure were predicted by molecular dynamics (MD) simulation. The data presented here may provide valuable information for improving management of diagnosis and treatment of VLCAD deficiency and for a better understanding of the general molecular bases of disease variability.
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The coronavirus disease 2019 (COVID-19) has caused a global pandemic. All people including children are generally susceptible to COVID-19, but the condition is relatively mild for children. The diagnosis of COVID-19 is largely based on the epidemiological evidence and clinical manifestations, and confirmed by positive detection of virus nucleic acid in respiratory samples. The main symptoms of COVID-19 in children are fever and cough; the total number of white blood cell count is usually normal or decreased; the chest imaging is characterized by interstitial pneumonia, which is similar to other respiratory virus infections and infections. Early identification, early isolation, early diagnosis and early treatment are important for clinical management. The treatment of mild or moderate type of child COVID-19 is mainly symptomatic. For severe and critical ill cases, the oxygen therapy, antiviral drugs, antibacterial drugs, glucocorticoids, mechanical ventilation or even extracorporeal membrane oxygenation (ECMO) may be adopted, and the treatment plan should be adjusted timely through multi-disciplinary cooperation.
Subject(s)
Child , Humans , Betacoronavirus , Coronavirus Infections , Diagnosis , Pathology , Therapeutics , Pandemics , Pneumonia, Viral , Diagnosis , Diagnostic Imaging , Pathology , TherapeuticsABSTRACT
Coronavirus disease 2019 (COVID-19) is a grade B infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In pace with the spreading of the disease, biosafety risk of the biological specimen preservation in biobanks has been significantly increased and biosafety protection during biological specimen preservation become increasingly important. According to the related national rules and the corresponding guidelines of Chinese Medical Association, this paper introduced the etiology about SARS-CoV-2, epidemiology about COVID-19, and the biosafety protection principles of individuals and biological specimen storage places in the process of personal protection, protection of collection, transport, handling, preservation, detection, post-detection disposal and emergencies of biological specimen. Emphasized to carry out a strict biosafety-risk assessment on biological specimen basing on virus load information, infectivity, and sample type (possible contact transmission, aerosol transmission, and fecal oral transmission).
Subject(s)
Humans , Betacoronavirus , Containment of Biohazards , Reference Standards , Coronavirus Infections , Epidemiology , Pandemics , Pneumonia, Viral , Epidemiology , Prevalence , Risk Assessment , Specimen Handling , Reference StandardsABSTRACT
December 2019 witnessed the outbreak of COVID-19 in Wuhan, Hubei province of China, which soon spread nationwide and across national borders to pose a menacing pandemic threat. Children are themselves highly susceptible to infectious diseases in normal times not to mention an epidemic. Coupled with the high incidence of seasonal influenza, it is imperative to strengthen epidemiological screening of children, along with effective isolation, treatment, prevention and control measures. In view of the specifics of the hospital, the authors proposed to further improve the medical emergency procedure, for strictly enforcing screening and isolation regulations, and standardizing medical procedure. They also proposed scientific layout and use of the infection wards. All these measures are designed to control the epidemic and protect the safety of children, families and medical staff.
ABSTRACT
The epidemic of COVID-19 has become the topmost public health threat worldwide. The authors suggested that in addition to strengthening the organization and leadership of the abovementioned work, greater attention be paid to establishing and improving the prevention and control mechanism.Furthermore, special efforts should be given to the safety of the medical workers, by strengthening their infection monitoring and outbreak management. Medical workers in different work areas and positions should be placed under careful protection with due cleaning and disinfection measures. The protection during specimen collection, transportation and medical waste management should also be prioritized. Such special issues in the management of pediatric patients, as allocation of nurses, the screening and management of caregivers, the problem of breastfeeding, and the disinfection of children′s toys and diapers were discussed. This paper also put forward management suggestions for the outpatient department, isolation ward and other key departments, which aim to guide the prevention and control of COVID-19 nosocomial infection in the pediatric outpatient and ward.
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Laboratory testing plays an important role in the diagnosis and treatment of patients with novel coronavirus pneumonia. However, the lack of understanding of the virus in the early stage led to great difficulties in biosafety protection for clinical laboratories. Based on the latest researches and findings about the virus, this paper provides some personal opinions on the biosafety prevention in clinical laboratorians under epidemic condition for the reference of laboratory workers.
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Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.
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Objective To investigate the prevalence of hypertension and its risk factors among residents with age between 35 and 75 years old in Chongqing and provide evidence for the prevention and control of hypertension. Methods During 2016-2018, 101036 eligible subjects aged 35-75 years from 8 sites of China Patient-centered Evaluative Assessment of Cardiac Events in Chongqing were interviewed and examined. The data were analyzed by SPSS 20.0. The difference of the prevalence of hypertension of different population were compared chi-square test. Risk factors of hypertension was identified by step backward multivariate Logistic regression model. Results The crude prevalence and age standardization prevalence of hypertension was 40.80% and 33.91% respectively. The results of multivariate logistic regression indicated that the risk factors of hypertension were residence, ethnicity, age, medical insurance ,drinking, present smoking , indoor passive smoking , overweight , obesity , central obesity , diabetes and dyslipidemia ,while the protective factors of hypertension of those were education level and income. Conclusion The prevalence of hypertension was high among residents with age between 35 and 75 years old in Chongqing ; Residence, ethnicity, age, medical insurance, education level, income, drinking, present smoking , indoor passive smoking , overweight , obesity , central obesity , diabetes and dyslipidemia are the related factors of hypertension.
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N-methyladenosine (mA), catalyzed by the methyltransferase complex consisting of Mettl3 and Mettl14, is the most abundant RNA modification in mRNAs and participates in diverse biological processes. However, the roles and precise mechanisms of mA modification in regulating neuronal development and adult neurogenesis remain unclear. Here, we examined the function of Mettl3, the key component of the complex, in neuronal development and adult neurogenesis of mice. We found that the depletion of Mettl3 significantly reduced mA levels in adult neural stem cells (aNSCs) and inhibited the proliferation of aNSCs. Mettl3 depletion not only inhibited neuronal development and skewed the differentiation of aNSCs more toward glial lineage, but also affected the morphological maturation of newborn neurons in the adult brain. mA immunoprecipitation combined with deep sequencing (MeRIP-seq) revealed that mA was predominantly enriched in transcripts related to neurogenesis and neuronal development. Mechanistically, mA was present on the transcripts of histone methyltransferase Ezh2, and its reduction upon Mettl3 knockdown decreased both Ezh2 protein expression and consequent H3K27me3 levels. The defects of neurogenesis and neuronal development induced by Mettl3 depletion could be rescued by Ezh2 overexpression. Collectively, our results uncover a crosstalk between RNA and histone modifications and indicate that Mettl3-mediated mA modification plays an important role in regulating neurogenesis and neuronal development through modulating Ezh2.
Subject(s)
Animals , Adenosine , Metabolism , Adult Stem Cells , Cell Biology , Metabolism , Brain , Metabolism , Cell Differentiation , Genetics , Cell Proliferation , Enhancer of Zeste Homolog 2 Protein , Metabolism , Gene Expression Regulation , Methyltransferases , Metabolism , Mice, Inbred C57BL , Neural Stem Cells , Cell Biology , Metabolism , Neurogenesis , Genetics , Neurons , Cell Biology , Metabolism , RNA, Messenger , Genetics , MetabolismABSTRACT
OBJECTIVE@#To explore the clinical features and variations of ACADVL gene in 9 neonates with very long chain acyl-coenzyme A dehydrogenase deficiency (VLCADD).@*METHODS@#VLCADD was suspected based on the results of neonatal screening by tandem mass spectrometry (MS-MS), with tetradecenoylcarnitine ± tetradecenoylcarnitine/octanoylcarnitine (C14: 1 ± C14: 1/C8) as the mark indexes. Infants with positive outcome were confirmed by sequencing of the ACADVL gene.@*RESULTS@#Among 9 VLCADD cases, one case lost during follow-up, the observed phenotypes comprised 2 with severe early-onset form, 1 with hepatic form and 5 with late-onset form. Optimal outcome was acquired for all patients except the 2 early-onset cases. In total 16 ACADVL variations were detected among the 9 infants, which included 8 novel variations (c.96-105del GCCCGGCCCT, c.541C>T, c.863T>G, c.878+1G>C, c.895A>G, c.1238T>C, c.1276G>A, and c.1505T>A) and 11 missense variations. There were 9 genotypic combinations, including 1 homozygote and 8 compound heterozygotes. Except for two patients carrying null variations, all had a good outcome.@*CONCLUSION@#VLCADD is relatively rare in southern China, for which late-onset form is common. Carriers of null variations of the ACADVL gene may have relatively poorer clinical outcome. Above results will provide valuable information for the diagnosis and management of VLCADD.