Role of epigenetic abnormalities and intervention in obstructive sleep apnea target organs

Obstructive sleep apnea(OSA)is a common condition that has considerable impacts on human health.Epigenetics has become a rapidly developing and exciting area in biology,and it is defined as heritable alterations in gene expression and has regulatory effects on disease progression.However,the published literature that is integrating both of them is not sufficient.The purpose of this article is to explore the relationship between OSA and epigenetics and to offer better diagnostic methods and treatment options.Epigenetic modifications mainly manifest as post-translational modifications in DNA and histone proteins and regulation of non-coding RNAs.Chronic intermittent hypoxia-mediated epigenetic alterations are involved in the progression of OSA and diverse multiorgan injuries,including cardiovascular disease,metabolic disorders,pulmonary hypertension,neural dysfunction,and even tumors.This article provides deeper insights into the disease mechanism of OSA and potential applications of targeted diagnosis,treatment,and prognosis in OSA complications.

Haploinsufficiency of KCNAB3 causes sudden cardiac death through delayed inactivation of Kv1.5 channel upon depolarization and induced myocardial apoptosis

Sudden cardiac death(SCD)is the leading cause of death from out-of-hospital cardiovascular disease worldwide,with an annual incidence of 1.4 per 100,000 in females and 6.8 per 100,000 in males.1 Most cases of SCD in older patients(>45 years)are caused by atherosclerotic coronary artery disease.SCD in younger patients(<45 years)is caused by inherited cardiovascular diseases.

Early chronic obstructive pulmonary disease:A new perspective

Chronic obstructive pulmonary disease(COPD)is a respiratory disease with a high incidence,mortality,and disability rate.Because there are few symptoms in the early stages of COPD,diagnosis and treatment are seriously insufficient.It is necessary to find effective clues for early COPD diagnosis and provide appropriate interventions.Several studies suggest that small airway disease is the earliest stage of COPD because it is correlated with subsequent development of airflow obstruction.However,there are currently no globally accepted criteria for defining early COPD.This study mainly introduced risk factors,definition,diagnosis,and treatment of early COPD from a new perspective.

Association between PTCH1 gene polymorphisms and chronic obstructive pulmonary disease susceptibility in a Chinese Han population:a case-control study

Background:Chronic obstructive pulmonary disease(COPD)is a leading cause of morbidity and mortality worldwide.Genome-wide association studies in non-Asian population revealed a link between COPD and mutations in the PTCH1 gene encoding Patched1,a receptor in the Hedgehog signaling pathway important for lung morphogenesis and pulmonary function.The aim of this study was to investigate the association between PTCH1 polymorphisms and the COPD risk in the Chinese Han population.Methods:We performed a case-control study including 296 patients with COPD and 300 healthy individuals.Single-nucleotide polymorphisms in the PTCH1 gene were identified and genotyped based on the linkage disequilibrium analysis in all participants.Odds ratios(ORs)and 95%confidence intervals(95%CIs)were estimated using logistic regression analysis after adjustment for age,gender,and smoking.Results:In total,28 single-nucleotide polymorphisms were identified in patients with COPD.Among them,"A"allele of rs28491365(OR:1.388,95%CI:1.055-1.827,P=0.018),and"G"alleles of rs10512248(OR:1.299,95%CI:1.021-1.653,P=0.033)and rs28705285(OR:1.359,95%CI:1.024-1.803,P=0.033;respectively)were significantly associated with an increased COPD risk.Genetic model analysis revealed that the"T/T"genotype of rs34695652 was associated with a decreased COPD risk under the recessive model(OR:0.490,95%CI:0.270-0.880,P=0.010),whereas rs28504650/rs10512248 haplotype CG was significantly associated with an increased COPD risk after adjustment for age,gender,and smoking status(OR:6.364,95%CI:1.220-33.292,P=0.028).Conclusions:The study provides a new insight into the role of PTCH1 polymorphisms in the susceptibility to COPD in the Chinese Han population.

Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice

Primary ciliary dyskinesia(PCD)is a congenital,motile ciliopathy with pleiotropic symptoms.Although nearly 50 causative genes have been identified,they only account for approximately 70%of definitive PCD cases.Dynein axonemal heavy chain 10(DNAH10)encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella.Based on the common axoneme structure of motile cilia and sperm flagella,DNAH10 variants are likely to cause PCD.Using exome sequencing,we identified a novel DNAH10 homozygous variant(c.589C>T,p.R197W)in a patient with PCD from a consanguineous family.The patient manifested sinusitis,bronchiectasis,situs inversus,and asthenoteratozoospermia.Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia,and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella.Subsequently,animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD,including chronic respiratory infection,male infertility,and hydrocephalus.To the best of our knowledge,this study is the first to report DNAH10 deficiency related to PCD in human and mouse models,which suggests that DNAH10 recessive mutation is causative of PCD.

Mutant CARD10 in a family with progressive immunodeficiency and autoimmunity

Autoimmunity and immunodeficiency were previously considered to be mutually exclusive conditions.However,an increased understanding of the complex immune regulatory systems and signaling mechanisms,coupled with the application of genetic analysis,has demonstrated the complex relationships between the two kinds of diseases.1 In recent years,several mild forms of primary immunodeficiencies have been discovered,presenting with opportunistic infections overlapping autoimmunity and/or allergy late in life.

Secondary Amenorrhea in a Patient with Common Variable Immunodeficiency

Common variable immunodeficiency （CV1D） is a heterogeneous immunodeficiency syndrome characterized by defective antibody formation. Approximately 70-80% of patients are diagnosed based on a previous history of recurrent sinus and lung and gastrointestinal infections. The diagnosis is based on the exclusion of other known causes of humoral defects,