A machine learning screening model for identifying the risk of high-frequency hearing impairment in a general population.

BACKGROUND: Hearing impairment (HI) has become a major public health issue in China. Currently, due to the limitations of primary health care, the gold standard for HI diagnosis (pure-tone hearing test) is not suitable for large-scale use in community settings. Therefore, the purpose of this study was to develop a cost-effective HI screening model for the general population using machine learning (ML) methods and data gathered from community-based scenarios, aiming to help improve the hearing-related health outcomes of community residents. METHODS: This study recruited 3371 community residents from 7 health centres in Zhejiang, China. Sixty-eight indicators derived from questionnaire surveys and routine haematological tests were delivered and used for modelling. Seven commonly used ML models (the naive Bayes (NB), K-nearest neighbours (KNN), support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGBoost), boosting, and least absolute shrinkage and selection operator (LASSO regression)) were adopted and compared to develop the final high-frequency hearing impairment (HFHI) screening model for community residents. The model was constructed with a nomogram to obtain the risk score of the probability of individuals suffering from HFHI. According to the risk score, the population was divided into three risk stratifications (low, medium and high) and the risk factor characteristics of each dimension under different risk stratifications were identified. RESULTS: Among all the algorithms used, the LASSO-based model achieved the best performance on the validation set by attaining an area under the curve (AUC) of 0.868 (95% confidence interval (CI): 0.847-0.889) and reaching precision, specificity and F-score values all greater than 80%. Five demographic indicators, 7 disease-related features, 5 behavioural factors, 2 environmental exposures, 2 hearing cognitive factors, and 13 blood test indicators were identified in the final screening model. A total of 91.42% (1235/1129) of the subjects in the high-risk group were confirmed to have HI by audiometry, which was 3.99 times greater than that in the low-risk group (22.91%, 301/1314). The high-risk population was mainly characterized as older, low-income and low-educated males, especially those with multiple chronic conditions, noise exposure, poor lifestyle, abnormal blood indices (e.g., red cell distribution width (RDW) and platelet distribution width (PDW)) and liver function indicators (e.g., triglyceride (TG), indirect bilirubin (IBIL), aspartate aminotransferase (AST) and low-density lipoprotein (LDL)). An HFHI nomogram was further generated to improve the operability of the screening model for community applications. CONCLUSIONS: The HFHI risk screening model developed based on ML algorithms can more accurately identify residents with HFHI by categorizing them into the high-risk groups, which can further help to identify modifiable and immutable risk factors for residents at high risk of HI and promote their personalized HI prevention or intervention.

Association Between ABCA1 Gene Polymorphisms and the Risk of Hypertension in the Chinese Han Population.

Background: Hypertension is rising as a major public health burden around the world. This study explored the association between single-nucleotide polymorphisms (SNPs) in the adenosine triphosphate (ATP)-Binding Cassette Subfamily A1 (ABCA1) gene and hypertension among Chinese Han adults. Method: A total of 2,296 Han Chinese in southeast China were recruited for this study. We collected medical reports, lifestyle details, and blood samples from individuals. The polymerase chain reaction-ligase detection reaction (PCR-LDR) method was used to detect the genotypes of these SNPs in the ABCA1 gene. Results: After adjusting some covariates, the additive and recessive models of the rs2472510 and rs2515614 were significantly associated with hypertension. The haplotypes TCTA (rs2297406-rs2472433-rs2472510-rs2515614) were associated with high SBP, and the haplotypes CCTA, TCTA, and TTTA were associated with high diastolic blood pressure (DBP). Conclusion: The results of the relationship between the polymorphisms of rs2297406, rs2472433, rs2472510, and rs2515614 in ABCA1 and hypertension in southeastern China would provide a theoretical basis for genetic screening and disease prevention.

Design and Preliminary Realization of a Screening and Early Warning Health Management System for Populations at High Risk for Depression.

Depression has a high incidence in the world. Based on the concept of preventive treatment of disease of traditional Chinese medicine, timely screening and early warning of depression in populations at high risk for this condition can avoid, to a certain extent, the dysfunctions caused by depression. This work studied a method to collect information on depression, generate a database of depression features, design algorithms for screening populations at high risk for depression and creating an early warning model, develop an early warning short-message service (SMS) platform, and implement a scheme of depression screening and an early warning health management system. The implementation scheme included mobile application (app), cloud form, screening and early warning model, cloud platform, and computer software. Multiple modules jointly realized the screening, early warning, and management of the health functions of individuals at high risk for depression. At the same time, function modules such as mobile app and cloud form for collecting depression health information, early warning SMS platform, and health management software were designed, and the functions of the modules were preliminarily developed. Finally, the black-box test and white-box test were used to assess the system's functions and ensure the reliability of the system. Through the integration of mobile app and computer software, this study preliminarily realized the screening and early warning health management of a population at high risk for depression.

Construction and Evaluation of a High-Frequency Hearing Loss Screening Tool for Community Residents.

Early screening and detection of individuals at high risk of high-frequency hearing loss and identification of risk factors are critical to reduce the prevalence at community level. However, unlike those for individuals facing occupational auditory hazards, a limited number of hearing loss screening models have been developed for community residents. Therefore, this study used lasso regression with 10-fold cross-validation for feature selection and model construction on 38 questionnaire-based variables of 4010 subjects and applied the model to training and testing cohorts to obtain a risk score. The model achieved an area under the curve (AUC) of 0.844 in the model validation stage and individuals' risk scores were subsequently stratified into low-, medium-, and high-risk categories. A total of 92.79% (1094/1179) of subjects in the high-risk category were confirmed to have hearing loss by audiometry test, which was 3.7 times higher than that in the low-risk group (25.18%, 457/1815). Half of the key indicators were related to modifiable contexts, and they were identified as significantly associated with the incident hearing loss. These results demonstrated that the developed model would be feasible to identify residents at high risk of hearing loss via regular community-level health examinations and detecting individualized risk factors, and eventually provide precision interventions.

Relationship between cigarette smoking and hearing loss in China: A cross-sectional study in Zhejiang province.

INTRODUCTION: Hearing loss and cigarette smoking are major challenges that affect public health in China. Revealing the effect of smoking on hearing loss in the Chinese general population is critical for hearing health protection. We investigated the relationship between smoking status and hearing loss in China, especially in stratified sex and age groups. METHODS: A cross-sectional study was conducted on 4685 individuals aged 20- 80 years in Zhejiang province from 2016 to 2018, with audiometric testing for hearing loss and a structured questionnaire for collecting smoking status and covariates. Logistic regression was used to estimate the association between smoking and hearing loss. RESULTS: Cigarette smoking was not significantly associated with hearing loss in females and young males. In middle-aged males, after adjusting for covariates, current smokers and past smokers had a significantly higher prevalence of speech-frequency loss (OR=1.65; 95% CI: 1.17-2.33 and OR=1.88; 95% CI: 1.11-3.17; respectively) and high-frequency hearing loss (OR=2.01; 95% CI: 1.43-2.84 and OR=2.64; 95% CI: 1.50-4.66; respectively). In older males, only past smokers had a significantly higher prevalence of speech-frequency hearing loss than never smokers (OR=2.58; 95% CI: 1.38-4.85). Regarding middle-aged and older current smokers, a dose-dependent relationship between smoking intensity and hearing loss was found. Passive smoking was not significantly associated with an increased hearing loss risk in all the three male groups. CONCLUSIONS: The relationship between cigarette smoking and hearing loss varied according to gender and age. Therefore, the interventions for smoking need to be tailored according to age in males.

Status and Influential Factors of Intelligent Healthcare in Nursing Homes in China.

With the support of the Chinese government, nursing homes have increasingly adopted Internet and intelligent information technology to provide daily healthcare services to residents. However, no research has reported the status of intelligent healthcare in nursing homes. From September 2017 to May 2018, we conducted a survey of 197 nursing homes and collected information on their general characteristics, the intelligent healthcare services provided, the effectiveness of the application products used, and the attitudes of the staff and residents toward intelligent healthcare. Overall, 79.69% of the surveyed nursing homes have provided intelligent healthcare services, including medical care services (eg, chronic disease management and intelligent nursing) and daily life services (eg, fall monitoring and wireless positioning). Portable health monitoring devices and data management and service platforms are the most used healthcare products. The attitudes of staff probably affected the development of intelligent healthcare. Financial investment and the attitudes of staff and residents are factors that influence the effectiveness of the application of intelligent healthcare products in nursing homes. With the support of national policies, nursing homes have implemented primary intelligent healthcare. Stakeholders play pivotal roles in the provision of intelligent healthcare services.

Environmental exposure to organochlorine pesticides and its association with the risk of hearing loss in the Chinese adult population: A case-control study.

Hearing loss is a common chronic sensory deficit that has become a major public health concern worldwide. Hearing loss is well documented to be induced by noise and ototoxic drugs, and the association of hearing loss with environmental pollutants has received increasing attention. Organochlorine pesticides (OCPs) are an important group of environmental pollutants that exist ubiquitously in the human body and continue to represent a significant environmental health concern. Our case-control study was performed to explore the association between serum levels of OCPs and the risk of hearing loss in China, including 87 case-control pairs. Serum concentrations of 15 OCPs were measured. Pearson's correlation analysis and principal component analysis of frequently detected (>80%) OCPs showed a different distribution pattern, indicating possible exposure sources/scenarios for the case-control adult population. A higher α-hexachlorocyclohexane (α-HCH) level was a risk factor for an increased prevalence of hearing loss. The risk of hearing loss was increased by approximately 5.25-fold in the highest tertile compared with the lowest tertile. Furthermore, a significant association of the α-HCH level with an increased hearing threshold was observed at mid/high frequencies. This study provided the first evidence indicating that exposure to α-HCH might be a potential risk factor for hearing loss.

Health Education Intervention on Hearing Health Risk Behaviors in College Students.

Young people, like college students, are at risk of hearing loss from prolonged and excessive exposure to loud sounds. However, behavioral interventional studies on them are inadequate. This study explored the application of a health belief model to the health education intervention on college students for improving hearing health knowledge, health belief, and hearing behaviors. From November 2017 to September 2018, a cluster randomized controlled trial was conducted, enrolling 830 college students, with 419 in the intervention group and 411 in the control group. The intervention group received a 3-month hearing health education, while the control group received no intervention. The information of hearing health knowledge, health belief, and hearing behaviors were collected using hearing health questionnaires before the intervention, after the intervention, and 3 months after the intervention cessation. The intervention significantly improved hearing health knowledge, health belief, perceived severity, and self-efficacy in female students, and effectively reduced the frequency of using headphones per day, duration of using headphones each time, and proportion of using headphones at high volume in female students, and reduced the behaviors of sleeping with headphones listening in females and males. Therefore, this study confirms the effectiveness of health belief model-based intervention for changing hearing loss-related risk behaviors.

Increased atherogenic index in the general hearing loss population.

PURPOSE: The purpose of this study was to evaluate the association of hearing loss with atherogenic index (AI) in the general population. METHODS: A multistage study using cluster random sampling method was conducted in the Zhejiang province from 2016 to 2018. Pure-tone air-conduction hearing thresholds were measured at frequencies of 0.125-8 kHz for each subject. After obtaining their consent, all participants were asked to provide their own plasma lipid data. RESULTS: A total of 3,414 eligible participants were included, 1,765 (51.7%) were men and 1,649 (48.3%) were women and 1,113 (32.6%) had hearing loss. Ridge regression showed increased AI in subjects with hearing loss. The subgroup with the highest quartile of AI, presenting the highest risk of hearing loss as compared to the lowest quartile, comprised young and middle-aged women. Further analysis revealed that the AI in people with different categories of hearing loss was higher than that in the normal population, except for those with (extremely) severe hearing loss. Moreover, the young and middle-aged women exhibited the most significant correlations between AI and hearing loss. CONCLUSION: AI was positively associated with hearing loss in the general population, especially the young and middle-aged women.

Correction: Association between polymorphisms of heat-shock protein 70 genes and noise-induced hearing loss: A meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0188539.].

Environmental exposure to lead and cadmium and hearing loss in Chinese adults: A case-control study.

Hearing loss is the second most common nonfatal problem affecting the Chinese population. Historical studies have suggested an association between exposure to heavy metals, such as cadmium and lead, and hearing loss. Few studies have investigated this relationship in the general population in China. We conducted a case-control study with 1008 pairs of participants from a cross-sectional epidemiological survey conducted in Zhejiang Province. A self-designed questionnaire was adopted to collect information on demographics, chronic diseases, lifestyles and environmental noise. Pure-tone averages of hearing thresholds at frequencies of 0.5, 1, 2, and 4 kHz were computed. Blood lead and cadmium levels were analyzed with an atomic absorption spectrometer. After adjusting for all other potential confounding factors, compared with the lowest blood cadmium quartile (0.00-0.53 µg/L), blood cadmium quartile 2 (0.54-0.92 µg/L), quartile 3 (0.93-1.62 µg/L) and quartile 4 (1.63-57.81 µg/L) exhibited significantly elevated risks for hearing loss, with odds ratios of 1.932 (95% CI: 1.356-2.751), 2.036 (95% CI: 1.423-2.914) and 1.495 (95% CI: 1.048-2.133), respectively (P-trend<0.001). However, an association of lead with hearing loss was not found. Young age (less than 60 years), male sex and current smoking were associated with increased blood cadmium concentration. Additionally, a positive association between blood cadmium and lead concentrations was found. Therefore, we conclude that exposure to environmental cadmium may be a risk factor for hearing loss among the general population in China.

Association between Leucocyte Telomere Length and Risk of Hearing Loss in the General Population: A Case-Control Study in Zhejiang Province, China.

Limited studies have assessed the relation between telomere length and risk of hearing loss; moreover, they have reported equivocal associations. In the first case-control study, the subjects were chosen from the general population of Zhejiang province in order to assess the association between leucocyte telomere length and risk of hearing loss from 2016 to 2018. A total of 817 cases (55.93 ± 8.99 years) and 817 age-, sex- and residential city-matched controls (55.91 ± 9.03 years) were included for analysis. In the multivariable models, individuals in the top quartile of relative telomere length (RTL) had an odds ratio (OR) for hearing loss of 0.53 (95% confidence intervals [CI], 0.38-0.74) compared to those in the bottom quartile, and specifically, the OR was 0.45 (95% CI, 0.28-0.73) in females. In females, the risk of hearing loss decreased by 46% as RTL doubling increased; the standard deviation of RTL was associated with a 29% decrease in hearing loss risk. Additional analysis showed significant difference between participants in the female mild hearing loss group and corresponding controls. These results suggest that telomere length is associated with hearing loss in the general population, particularly in females with mild hearing loss. Telomere length might be a potential predictive biomarker of hearing loss at early stage.

Associations of noise kurtosis, genetic variations in NOX3 and lifestyle factors with noise-induced hearing loss.

BACKGROUND: Noise-induced hearing loss (NIHL) is a complex disease caused by environmental and genetic risk factors. This study was to explore the association of noise kurtosis, triphosphopyridine nucleotide oxidase 3 (NOX3) and lifestyles with NIHL. METHODS: This case-control study included 307 patients with NIHL and 307 matched control individuals from Zhejiang province of China. General characteristics, noise exposure data, the exfoliated cells of the oral mucosa, and lifestyle details of individuals were collected. The kompetitive allele specific polymerase chain reaction (KASP) method was used to analyze the genotypes of three single nucleotide polymorphisms (SNPs) of NOX3. RESULTS: People who exposed to complex noise had a higher risk of NIHL than those exposed to steady noise (adjusted: OR = 1.806, P = 0.002). The GT genotype of additive model and TT + GT genotype of dominant model in NOX3 rs12195525 decreased the risk of NIHL (adjusted: OR = 0.618, P = 0.043; OR = 0.622, P = 0.036). Smoking and exposure to high video volume increased the risk of NIHL (adjusted: OR = 1.486, P = 0.038; OR = 1.611, P = 0.014). Oppositely, regular physical exercise decreased the risk of NIHL (adjusted: OR = 0.598, P = 0.004). A positive interaction was found between complex noise and lifestyles including high video volume exposure and no physical exercise in the additive models (RERI = 1.088, P < 0.001; RERI = 1.054, P = 0.024). A positive interaction was also found between NOX3 rs12195525 GG genotype and lifestyles including smoking and high video volume exposure in the additive models (RERI = 1.042, P = 0.005; RERI = 0.774, P = 0.044). CONCLUSIONS: Noise temporal structure, NOX3 rs12195525 polymorphism, and the three lifestyles of smoking, video volume, and physical exercise were related to the NIHL. There were the interactions between noise temporal structure and the lifestyle of video volume or physical exercise, as well as between NOX3 and the lifestyle of smoking or video volume. These results provide a theoretical basis for the prevention and genetic testing of NIHL.

Higher serum magnesium concentration is associated with lower hearing thresholds and risk of hearing loss among a Chinese population.

BACKGROUND AND OBJECTIVES: Hearing loss is a sensory impairment caused by genetic and environmental factors. Previous epidemiological studies of magnesium intake and hearing loss have yielded conflicting results. METHODS AND STUDY DESIGN: We investigated the association between serum magnesium concentrations and hearing loss in a population from the Zhejiang region of China. A cross-sectional study of 3,267 participants aged 18 years and older from five hospitals was conducted from October 2016 to May 2018. An audiometric examination was conducted, and hearing thresholds were computed as pure-tone averages (PTAs) at speech (0.5, 1, 2, and 4 kHz) and high frequencies (3, 4, and 6 kHz). Magnesium concentrations were measured using an inductively coupled plasma mass spectrometer. RESULTS: A linear regression analysis revealed a negative association between magnesium levels and hearing losses from lower to high PTAs. After the adjustment of potential confounders, participants in the highest magnesium quartile had a lower PTA (quartile 4: -1.89%; 95% confidence interval (CI: -3.07 to -0.701); p=0.022) and high PTA (quartile 4: -3.05%; 95% CI: -4.64 to -1.46; p=0.005) than those in the lowest quartile. A logistic regression analysis showed a dose-dependent reduction in the odds of high frequency hearing loss across magnesium quartiles. In model 3, after adjusting for all potential confounders, participants with the highest magnesium quartiles had a 54.0% (OR: 0.460; 95% CI: 0.339-0.587) reduction in the odds of high-frequency hearing loss. CONCLUSIONS: Higher whole blood levels of magnesium in this population were associated with lower hearing thresholds and risk of hearing loss.

Relationship between alcohol use, blood pressure and hypertension: an association study and a Mendelian randomisation study.

BACKGROUND: Past studies have found a strong relationship between alcohol drinking and human health. METHODS: In this study, we first tested the association of rs671 with alcohol use in 2349 participants in southeast China. We then evaluated the causal impact between alcohol use and cardiovascular traits through a Mendelian randomisation (MR) analysis. RESULTS: We found strong evidence for the association of rs671 in the ALDH2 gene with alcohol drinking (p=6.08×10-47; ORadj G=4.50, 95% CI 3.67 to 5.52). We found that female G carriers of rs671 had a higher proportion of non-drinkers than male G carriers (88.01% vs 38.70%). In non-drinkers, the female G allele frequency was higher than the male G allele frequency (71.1% vs 55.2%). MR analysis suggested that alcohol use had a causal effect on blood pressure (increasing 9.46 mm Hg for systolic blood pressure (p=9.67×10-4) and 7.50 mm Hg for diastolic blood pressure (p=9.62×10-5)), and on hypertension in men (p=0.011; OR =1.19, 95% CI 1.04 to 1.36) and in pooled samples (p=0.013; OR =1.20, 95% CI 1.04 to 1.39), but not in women. We did not observe a causal effect of alcohol use on body mass index and lipid levels; further studies are needed to clarify the non-causal relationship. CONCLUSIONS: Compared to never-drinkers, current and previous alcohol use had a causal effect on blood pressure and hypertension in pooled samples and in men. These results reflect Chinese culture which does not encourage women to drink.

Hearing threshold levels and hearing loss among people in Zhejiang, China: a population-based cross-sectional study.

Hearing loss (≥26 dB threshold in the better ear), as a common chronic condition in humans, is increasingly gaining attention. Relevant research in China is relatively scarce, so we conduct a population-based study to investigate the prevalence of hearing loss among age groups, genders and ears in Zhejiang province, China, from September 2016 to June 2018. STUDY DESIGN: Population-based cross-sectional study PARTICIPANTS: A total of 3754 participants aged 18-98 years and living in Zhejiang province, China. OUTCOME MEASURES: Pure-tone audiometric thresholds were measured at frequencies of 0.125-8 kHz for each subject. All participants were asked to complete a structured questionnaire, in the presence of a healthcare official. RESULTS: The prevalence of speech-frequency and high-frequency hearing loss was 27.9% and 42.9%, respectively, in Zhejiang. There were significant differences in auditory thresholds at most frequencies among the age groups, genders (male vs female: 31.6%vs24.1% at speech frequency; 48.9% vs 36.8% at high frequency) and ears. In addition to the common factors affecting both types of hearing loss, a significant correlation was found between personal income and speech-frequency hearing loss (OR=0.69, 95% CI 0.52 to 0.92), and between hyperlipidaemia and high-frequency hearing loss (OR=1.45, 95% CI 1.02 to 2.07). CONCLUSION: The prevalence of hearing loss was high among people living in Zhejiang, particularly males, and in the left ear. Moreover, hearing thresholds increased with age. Several lifestyle and environment factors, which can be influenced by awareness and education, were significantly associated with hearing loss.

Carotenoid metabolic (BCO1) polymorphisms and personal behaviors modify the risk of coronary atherosclerosis: a nested case-control study in Han Chinese with dyslipidaemia (2013-2016).

BACKGROUND AND OBJECTIVES: ß-Carotene-15,15'-oxygenase (BCO1) is a key enzyme involved in carotenoid metabolism and has been linked with the development of coronary atherosclerosis. This study investigated the association between BCO1 polymorphisms and the risk of coronary atherosclerosis in dyslipidemia participants, and analyzed the influence of personal behaviors on coronary atherosclerosis. METHODS AND STUDY DESIGN: A nested case-control study was conducted from 2013 to 2016 in which 1359 dyslipidemia participants were recruited. Personal lifestyle parameters, mainly physical activities and diet, were obtained by questionnaires and the genotypes of rs11641677, rs11646692, rs12934922, rs6564851 and rs7501331 in BCO1 were analyzed by ligase detection reaction. In 2016, 166 participants were diagnosed with coronary atherosclerosis and 498 age-and gendermatched controls were recruited. The association between BCO1 polymorphisms and risk of coronary atherosclerosis were analyzed with logistic regression, and the effect of gene-behaviors interaction on the risk of coronary atherosclerosis were determined with crossover analysis. RESULTS: After adjustment for potential confounders, logistic regression analysis showed that fried food intake (OR=1.637, 95% CI: 1.127~2.378; p=0.010), dessert intake (OR=1.733, 95% CI: 1.158~2.595; p=0.008), and physical activity (OR=0.511, 95% CI: 0.309~0.846; p=0.009) were risk factors for coronary atherosclerosis. Rs12934922 and rs11646692 reflected high susceptibility to coronary atherosclerosis. Crossover analysis indicated that rs12934922 and rs11646692 interacted with physical activity (Inter-OR=8.82; Inter-OR=3.69), fried food intake (Inter-OR=2.95; Inter-OR=2.36) and dessert intake (Inter-OR=3.95; Inter-OR=2.39) to influence the risk of coronary atherosclerosis. CONCLUSIONS: In dyslipidemia patients, rs12934922 and rs11646692 may influence the development of coronary atherosclerosis. A combination of BCO1 polymorphisms and several behavioral factors may affect the development of coronary atherosclerosis.

Associations of Genetic Variations in ABCA1 and Lifestyle Factors with Coronary Artery Disease in a Southern Chinese Population with Dyslipidemia: A Nested Case-Control Study.

Coronary artery disease has become a major health concern over the past several decades. We aimed to explore the association of single nucleotide polymorphisms (SNPs) in the ATP-binding cassette subfamily A member 1 (ABCA1) and lifestyle factors with coronary artery disease (CAD) in dyslipidemia. This nested case-control study included 173 patients with CAD and 500 matched control individuals (1:3, case: control) from a district in southern China. We collected medical reports, lifestyle details, and blood samples of individuals with dyslipidemia and used the polymerase chain reaction-ligase detection reaction method to genotype the SNPs. The CC genotype of the additive and recessive models of rs4149339, together with regular intake of fried foods or dessert, increased the risk of CAD (adjusted odd ratio (OR) = 1.91, p = 0.030; adjusted OR = 1.97, p = 0.017; adjusted OR = 1.80, p = 0.002; adjusted OR = 1.98, p = 0.001). The AT + AA genotype of the dominant model of rs4743763 and moderate/heavy physical activity reduced the risk of CAD (adjusted OR = 0.66, p = 0.030; adjusted OR = 0.44, p = 0.001). The CT + CC genotype of the dominant model of rs2472386 reduced the risk of CAD only in males (adjusted OR = 0.36, p = 0.001). The interaction between rs4149339 and rs4743763 of ABCA1 and haplotype CTT (comprising rs4149339, rs4743763, and rs2472386) appeared to increase the risk of CAD (relative excess risk due to interaction (RERI) = 3.19, p = 0.045; OR = 1.49, p = 0.019). Polymorphisms of rs4149339, rs4743763 and rs2472386 in ABCA1 and three lifestyle factors (physical activity, fried food intake, and dessert intake) were associated with CAD in people with dyslipidemia in southern China. These results provide the theoretical basis for gene screening and the prevention of chronic cardiovascular diseases.

Latency-associated nuclear antigen inhibits lytic replication of Kaposi's sarcoma-associated herpesvirus by regulating let-7a/RBPJ signaling.

Latency-associated nuclear antigen (LANA) is the key factor in the establishment and maintenance of latency of Kaposi's sarcoma-associated herpesvirus (KSHV). A cellular protein, recombination signal binding protein for immunoglobulin kappa J region (RBPJ), is essential for the lytic reactivation of KSHV. However, whether RBPJ expression is regulated by KSHV is not clear. Here, we show that LANA upregulates let-7a and its primary transcripts in parallel with its reduction of RBPJ expression. An increase in notch intracellular domain (NICD) and the downregulation of NF-κB and LIN28B contribute to the upregulation of let-7a by LANA. Let-7a represses RBPJ expression by directly binding the 3' untranslated region of RBPJ. Let-7a overexpression or RBPJ knockdown led to a dose- and time-dependent inhibition of lytic reactivation of KSHV. Collectively, these findings support a model wherein LANA inhibits the lytic replication of KSHV by regulating let-7a/RBPJ signaling.