Genetic analyses in a cohort of 191 Chinese pulmonarv arterial hypertension patients

Objective Pulmonary arterial hypertension(PAH)is mainly characterized by pulmonary artery obstruction,which is diagnosed by a mean pulmonary artery pressure≥25 mm Hg at rest,and excluding other known causes of pulmonary hypertension.To identify genetic mutations and help make a precise diagnosis,we performed genetic testing in 191 probands with invasively confirmed PAH and tried to analyze the genotype-phenotype correlation.

CHDbase:A Comprehensive Knowledgebase for Congenital Heart Disease-related Genes and Clinical Manifestations

Congenital heart disease(CHD)is one of the most common causes of major birth defects,with a prevalence of 1%.Although an increasing number of studies have reported the etiology of CHD,the findings scattered throughout the literature are difficult to retrieve and utilize in research and clinical practice.We therefore developed CHDbase,an evidence-based knowledgebase of CHD-related genes and clinical manifestations manually curated from 1114 publications,linking 1124 susceptibility genes and 3591 variations to more than 300 CHD types and related syndromes.Metadata such as the information of each publication and the selected population and samples,the strategy of studies,and the major findings of studies were integrated with each item of the research record.We also integrated functional annotations through parsing50 databases/tools to facilitate the interpretation of these genes and variations in disease pathogenicity.We further prioritized the significance of these CHD-related genes with a gene interaction network approach and extracted a core CHD sub-network with 163 genes.The clear genetic landscape of CHD enables the phenotype classification based on the shared genetic origin.Overall,CHDbase provides a comprehensive and freely available resource to study CHD susceptibilities,supporting a wide range of users in the scientific and medical communities.CHDbase is accessible at http://chddb.fwgenetics.org.

Tuf m RNA rather than 16S r RNA is associated with culturable Staphylococcus aureus

AIM: To study the presence of various nucleic acids targets of Staphylococcus aureus(S. aureus) during bacterial growth and antibiotic induced killing in relation to viability.METHODS: S. aureus was cultured to log phase and spiked in Todd Hewitt(TH) broth and whole blood of healthy human volunteers. Viability of S. aureus after flucloxacillin treatment(0, 1, 3 and 6 d) was assessed by culture on bloodagar plates. DNA and RNA were isolated from 200 μL. c DNA synthesis was performed by using random primers. The presence of S. aureus DNA, r RNA, and m RNA were determined by real-time polymerase chain reaction of the 16 S r DNA and tuf gene(elongation factor Tu).RESULTS: S. aureus spiked in TH broth without antibiotics grew from day 0-6 and DNA(tuf and 16S), and 16 S r RNA remained detectable during this whole period. During flucloxacillin treatment S. aureus lost viability from day 3 onwards, while the 16 S r RNA-gene and its RNA transcripts remained detectable. DNA andr RNA can be detected in flucloxacillin treated S. aureus cultures that do not further contain culturable bacteria.However, tuf m RNA became undetectable from day 3onwards. Tuf m RNA can only be detected from samples with culturable bacteria. When spiking S. aureus in whole blood instead of broth no bacterial growth was seen, neither in the absence nor in the presence of flucloxacillin. Accordingly, no increase in DNA and RNA levels of both 16 S r DNA and the tuf gene were detected. CONCLUSION: Tuf m RNA expression is associated with culturable S. aureus and might be used to monitor antibiotic effects.

Making Elimination of Perinatal Hepatitis B Infection a Reality:The Chinese Contribution

Chronic hepatitis B virus(HBV)infection,referred to the presence of hepatitis B surface antigen(HBsAg)over 6 months,is a serious health issue because of its severe sequelae such as cirrhosis and hepatocellular carcinoma.Prevention of mother-to-child transmission(MTCT)of HBV is most important to control hepatitis B because a vast majority of HBV acquisition in infancy will become chronic carriers.

SIRT6 is an epigenetic repressor of thoracic aortic aneurysms via inhibiting inflammation and senescence

Thoracic aortic aneurysms(TAAs)develop asymptomatically and are characterized by dilatation of the aorta.This is considered a life-threating vascular disease due to the risk of aortic rupture and without effective treatments.The current understanding of the pathogenesis of TAA is still limited,especially for sporadic TAAs without known genetic mutation.Sirtuin 6(SIRT6)expression was significantly decreased in the tunica media of sporadic human TAA tissues.Genetic knockout of Sirt6 in mouse vascular smooth muscle cells accelerated TAA formation and rupture,reduced survival,and increased vascular inflammation and senescence after angiotensin II infusion.Transcriptome analysis identified interleukin(IL)-1βas a pivotal target of SIRT6,and increased IL-1βlevels correlated with vascular inflammation and senescence in human and mouse TAA samples.Chromatin immunoprecipitation revealed that SIRT6 bound to the Il1b promoter to repress expression partly by reducing the H3K9 and H3K56 acetylation.Genetic knockout of Il1b or pharmacological inhibition of IL-1βsignaling with the receptor antagonist anakinra rescued Sirt6 deficiency mediated aggravation of vascular inflammation,senescence,TAA formation and survival in mice.The findings reveal that SIRT6 protects against TAA by epigenetically inhibiting vascular inflammation and senescence,providing insight into potential epigenetic strategies for TAA treatment.

Breastmilk—Old but Not Obsolete:from the Safety of Breastfeeding During the Coronavirus Disease 2019 Pandemic to Broad Antiviral Drug Development

The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)poses a major threat to global health.The high mortality rate reported during the early stage of the COVID-19 pandemic resulted in panic among patients,including lactating mothers.1-3 The detection of SARS-CoV-2 RNA in breastmilk raised great concerns regarding the possibility of mother-tochild transmission(MTCT)of the virus.4 According to several reports on the presence of SARS-CoV-2 in breastmilk,some experts suggested that breastfeeding should be conducted with caution,while others recommended that,infants should be separated from their mother and breastfeeding should be discontinued.

Focus on lipoprotein(a):The time is now

1INTRODUCTION Low-density lipoprotein cholesterol(LDL-C)is the most important risk factor for atherosclerotic cardiovascular disease(ASCVD),but some individuals who meet the LDL-C treatment goal still have a residual risk of ASCVD[1].Numerous clinical studies and meta-analyses have shown that high lipoprotein(a)(Lp(a))concentration is a continuous,independent,and moderately significant risk factor for ASCVD,and that this association is not dependent on LDL-C or non-HDL-C levels or other risk factors[2].

Antibiotic resistance mechanisms of Myroides sp.

Bacteria of the genus Myroides （Myroides spp.） are rare opportunistic pathogens. Myroides sp. infections have been reported mainly in China. Myroides sp. is highly resistant to most available antibiotics, but the resistance mechanisms are not fully elucidated. Current strain identification methods based on biochemical traits are unable to identify strains accurately at the species level. While 16S ribosomal RNA （rRNA） gene sequencing can accurately achieve this, it fails to give information on the status and mechanisms of antibiotic resistance, because the 16S rRNA sequence contains no information on resistance genes, resistance islands or enzymes. We hypothesized that ob- taining the whole genome sequence of Myroides sp., using next generation sequencing methods, would help to clarify the mechanisms of pathogenesis and antibiotic resistance, and guide antibiotic selection to treat Myroides sp. infec- tions. As Myroides sp. can survive in hospitals and the environment, there is a risk of nosocomial infections and pandemics. For better management of Myroides sp. infections, it is imperative to apply next generation sequencing technologies to clarify the antibiotic resistance mechanisms in these bacteria.