Etiology analysis for term newborns with severe hyperbilirubinemia in eastern Guangdong of China

BACKGROUND Neonatal hyperbilirubinemia is one of the common diseases of newborns that typically presents with yellow staining of skin,resulting in sequelaes such as hearing loss,motor and intellectual development disorders,and even death.The pathogenic factors of neonatal hyperbilirubinemia are complex.Different cases of hyperbilirubinemia may have a single or mixed etiology.AIM To explore the etiological characteristics of severe hyperbilirubinemia in term newborns of eastern Guangdong of China.METHODS Term newborns with severe hyperbilirubinemia in one hospital from January 2012 to December 2021 were retrospectively analyzed.The etiology was determined according to the laboratory results and clinical manifestations.RESULTS Among 1602 term newborns with hyperbilirubinemia in eastern Guangdong of China,32.20%(580/1602)was severe hyperbilirubinemia.Among the causes of severe hyperbilirubinemia,neonatal hemolysis accounted for 15.17%,breast milk jaundice accounted for 12.09%,infection accounted for 10.17%,glucose-6-phosphate dehydrogenase(G6PD)deficiency accounted for 9.14%,and the coexistence of multiple etiologies accounted for 6.55%,unknown etiology accounted for 41.72%.ABO hemolysis and G6PD deficiency were the most common causes in the 20 cases with bilirubin encephalopathy.94 severe hyperbilirubinemia newborns were tested for uridine diphosphate glucuronosyl transferase 1A1(UGT1A1)*6 variant(rs4148323,c.211G>A,p.Arg71Gly),9 cases were 211 G to A homozygous variant,37 cases were 211 G to A heterozygous variant,and 48 cases were wild genotypes.CONCLUSION The main cause for severe hyperbilirubinemia and bilirubin encephalopathy in eastern Guangdong of China were the hemolytic disease of the newborns,G6PD deficiency and infection.UGT1A1 gene variant was also a high-risk factor for neonatal hyperbilirubinemia.Targeted prevention and treatment according to the etiology may reduce the occurrence of bilirubin encephalopathy and kernicterus.

Clinical features and genetic variations of severe neonatal hyperbilirubinemia:Five case reports

BACKGROUND Neonatal hyperbilirubinemia is a common problem faced by pediatricians.The role of genetic factors in neonatal jaundice has been gradually recognized.This study aims to identify genetic variants that influence the bilirubin level in five patients using next-generation sequencing(NGS).CASE SUMMARY Five neonates with severe hyperbilirubinemia were retrospectively studied.They exhibited bilirubin encephalopathy,hypothyroidism,ABO blood type incompatibility hemolysis,glucose-6-phosphate dehydrogenase(G6PD)deficiency and premature birth,respectively.A customized 22-gene panel was designed,and NGS was carried out for these neonates.Eight variations(G6PD c.G1388A,HBA2 c.C369G,ABCC2 c.C3825G,UGT1A1 c.G211A,SPTB c.A1729G,EPB41 c.G520A,c.1213-4T>G and c.A1474G)were identified in these five neonates.Genetic mutations of these genes are associated with G6PD deficiency,thalassemia,Dubin-Johnson syndrome,Gilbert syndrome,hereditary spherocytosis,and hereditary elliptocytosis.One of the neonates was found to have compound variants of the EPB41 splice site c.1213-4T>G and c.G520A(p.E174K),but no elliptocyte was seen on his blood smear of 4 years old.CONCLUSION Pathological factors of severe neonatal hyperbilirubinemia are complicated.Genetic variants may play an important role in an increased risk of neonatal hyperbilirubinemia,and severe jaundice in neonates may be related to a cumulative effect of genetic variants.

Prediction of active ingredients and potential mechanisms of Alisma decoction against atherosclerosis:A study based on UHPLC-Q-Orbitrap-HRMS and network pharmacology

Background:Atherosclerosis(AS)has been a potentially life-threatening disease worldwide.Alisma decoction(AD)is a famous Chinese formula in treating AS.However,the active components and potential mechanisms remain unknown.Methods:In this study,the active compositions of AD were analyzed by ultrahigh-performance liquid chromatography quadrupole-orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap-HRMS).The putative targets were predicted and interpreted by a series of bio-informative tools such as Venn,STRING,NetworkAnalyzer,ClusterMarker,and DAVID.Finally,the results were validated by molecular docking using AutoDock.Results:The results showed that alisol A,alisol B,23-o-Acetylalisol B,atractylenolideⅢand atractylenolideⅡwere the major compositions in AD.Thirty targets mainly distributed in three gene clusters were obtained after topological and cluster analysis.KEGG and GO analyses showed that genes in cluster 1 mainly participated in adipocytokine signaling pathway and played an important role in lipid metabolism,while genes in cluster 2 had regulatory actions via cAMP signaling pathway and may protect vascular function from AS,and genes in cluster 3 were closely related to inflammation.Furthermore,RXRA,AGT and CXCL8,the central gene of cluster 1,2 and 3,were verified to be strong binding with some major compositions in AD.Conclusion:The possible mechanisms of AD in the treatment of AS may be closely correlated with the regulation of lipid metabolism,vascular physiology and inflammation.Our study provided a new insight into the anti-AS effect of AD,but more pharmacological experiments should be performed for verification in the future.

simple and effective aerosol pathogen disinfection test for a flowing air disinfector

Aerosol transmission is an important disease transmission route and has been especially pertinent to hospital and biosafety laboratories during the SARS-CoV-2 pandemic.The thermal resistance of airborne SARS-CoV-2 is lower than that of Bacillus subtilis spores,which are often used to test the effectiveness of SARS-CoV-2 and other pathogen disinfection methods.Herein,we propose a new method to test the disinfection ability of a flowing air disinfector(a digital electromagnetic induction air heater)using B.subtilis spores.The study provides an alternative air disinfection test method.The new test system combined an aerosol generator and a respiratory filter designed in-house and could effectively recover spores on the filter membrane at the air outlet after passing through the flowing air disinfector.The total number of bacterial spores used in the test was within the range of 5×10^(5)–5×10^(6)colony-forming units(CFUs)specified in the technical standard for disinfection.The calculation was based on the calculation method in Air Disinfection Effect Appraisal Test in Technical Standard for Disinfection(2002 Edition).At an air speed of 3.5 m/s,we used a digital electromagnetic induction air heater to disinfect flowing air containing 4.100×10^(6)CFUs of B.subtilis spores and determined that the minimum disinfection temperature was 350℃for a killing rate of 99.99%.At 400℃,additional experiments using higher spore concentrations(4.700×10^(6)±1.871×10^(5)CFU)and a higher airspeed(4 m/s)showed that the killing rate remained>99.99%.B.subtilis spores,as a biological indicator for testing the efficiency of dry-heat sterilization,were killed by the high temperatures used in this system.The proposed method used to test the flowing air disinfector is simple,stable,and effective.This study provides a reference for the development of test systems that can assess the disinfection ability of flowing air disinfectors.