2019年 · 第02卷第03期

Menopause is a biological event associated with the complete cessation of a woman’s reproductive ability. Early menopause is defined as entry into menopause between the ages of 40 and 45 years, and has a significant impact on the fertility of affected women. Early menopause is a complex and heterogeneous disorder that is influenced by multiple genetic and environmental factors, as well as the interactions between these factors. Genome-wide association study (GWAS) is a novel strategy that has recently come into use as a way to overcome the limitations of genome-wide linkage analyses and candidate gene association approaches to discover novel susceptibility loci for early menopause. GWAS has identified many new candidate genes or loci associated with early menopause. In this review, we provide an overview of the current understanding of the genetic factors associated with early menopause that have been identified by GWAS. We also discuss potential approaches that could be used in the future to identify new genes associated with early menopause.

The human leukocyte antigen (HLA) complex is involved in immunity, belongs to a highly polymorphic family of genes, and is found in a disease-associated region of the human genome. The HLA region of the genome has been associated with more than hundreds of diseases, including autoimmune diseases, cancer, and infectious diseases. Because of its extensive linkage disequilibrium, HLA represents one of the most attractive and valuable regions that have been discovered in numerous feasibility studies. However, despite its critical role, attempts to apply comprehensive and traditional strategies towards the characterization of the HLA locus have been limited. The recent development of genotyping arrays and sequencing technologies has resulted in the development of technologies that are capable of addressing the extreme polymorphism nature of HLA. In this review, we summarized the current approaches being used to capture, sequence, and analyze HLA genes and loci. In addition, we discussed the new methodologies being used for these applications, including HLA genotyping, population genetics, and disease-association studies.

Enlarged vestibular aqueduct (EVA) is a radiologic malformation of the inner ear most commonly seen in children with sensorineural hearing loss. Most cases of EVA with hearing loss are caused by biallelic mutations of SLC26A4. In this review, we discuss the potential mechanisms underlying the pathogenesis of hearing loss with EVA due to malfunction of SLC26A4, the detection rates of SLC26A4 mutations in EVA patients from different populations, and the role of other genetic factors (eg, mutations in FOXI1 and KCNJ10) as etiologic contributors to EVA. Elucidating the molecular etiology of EVA-associated hearing loss may facilitate genetic counseling and lead to potential therapeutic strategies.

A negative lymph node (NLN) count has been shown to have a significant impact on the prognosis of many types of cancer. However, its prognostic value for jejunoileal neuroendocrine tumors (NETs) remains unclear. In this study, we investigated the prognostic value of NLN count in patients with resected jejunoileal NETs diagnosed between 1988 and 2014. The data were retrieved from the Surveillance, Epidemiology and End Results database. The X-tile program was used to determine the cutoff value of the NLN count. Univariate and multivariate Cox proportional hazards models were used to assess the prognostic value of NLN count on survival. Harrell concordance index was used to compare the prognostic validity of NLN count with 2 current prognostic systems. The optimal cutoff point of the NLN count was 8. Kaplan-Meier analysis revealed a progressively worse overall survival (OS) with an NLN count ≤8 compared with an NLN count > 8 (P < 0.001). Univariate analysis showed that the NLN count, age, tumor site, tumor size and T classification were significant prognostic factors for the OS of jejunoileal NETs, while the number of positive lymph nodes had no significant impact on OS (P= 0.513). Multivariate analysis indicated that the NLN count was an independent prognostic factor for OS of jejunoileal NETs. A higher NLN count was associated with better OS (hazards ratio: 0.641; 95% confidence interval: 0.519-0.793; P < 0.001). Compared with 2 other prognostic systems, the NLN counts in this study had similar prognostic value in patients with jejunoileal NETs. Our findings suggest that the NLN count is an important independent prognostic factor for patients with jejunoileal NETs, and that it is a good adjunct for disease staging.

Inner ear hair cells are important for maintaining hearing. Irreversible damage to hair cells is an important cause of sensorineural deafness. Electromagnetic radiation, especially high-power microwave, is an important threat to human health in modern society and war. However, it is not clear whether high-power microwave has an effect on cochlea hair cells. This study aimed to assess the effects of high-power microwave on cochlear hair cells in guinea pigs, and investigate the potential protection of these cells against high-power microwave-induced damage by recombinant adenovirus A20. Based on experimental results, a 65 W/cm² irradiation density applied to guinea pigs in this study to establish a high-power microwave inner ear injury model. In addition, pAdEeay-1/A20 was injected via a round window into experimental guinea pig cochlea, whereas artificial perilymph was injected into the control group. Auditory function was assessed by testing the auditory brainstem response threshold, and damage to cochlear hair cells was investigated by cell counting and scanning electron microscopy observations of the basilar membrane. Inner ear injury was observed 6 hours after 65 W/cm² of irradiation and the auditory brainstem response threshold was significantly higher in the irradiation group (P < 0.05) compared with other groups. Propidium iodide staining and scanning electron microscopy results indicated that significant morphological changes occurred after radiation, especially to inner hair cells, which exhibited remarkable damage and the presence of several unknown spherical substances. Auditory brainstem response threshold was decreased in the pAdEeay-1/A20 group compared with the artificial perilymph group; moreover, damage to hair cells was milder in the pAdEeay-1/A20 group compared with the control group (P < 0.01). Thus, high-power microwave can cause damage to cochlear hair cells, as well as hearing loss with prolonged exposure and/or high dosage. In this regard, 65 W/cm² of irradiation for 6 hours is a reliable target dose for observation of damage. The zinc finger protein A20 can protect cochlear hair cells from high-power microwave-induced damage and prevent further hearing loss. This study was approved by the Laboratory Animal Welfare and Ethics Committee of the Third Military Medical University, China on April 18, 2017.

Flow has been widely studied in the field of positive psychology. However, little is known regarding its biological mechanism. This study aimed to ascertain flow-related gene loci. We investigated the association between flow and five single nucleotide polymorphisms associated with common mental disorders among a sample of 870 healthy 1^st year students of Jining Medical University, Shandong Province, China. This study was approved by the Ethics Committee of Jining Medical University (approval number: JNMC-2016-KY-001) on June 1, 2016. rs11191454 demonstrated significant statistical association with flow after adjusting for age and gender (P= 0.004). The allele carriers achieved higher scores in all 4 dimensions of flow: merging of action and awareness, challenge-skill balance, sense of control, and clear goals. This biological research article indicates that rs11191454 in the arsenite methyltransferase (AS3MT) gene might be associated with flow in a Chinese Han population, and that might result from altered arsenic metabolism.