HMG-CoA reductase (HMGCR) protein is usually upregulated after statin (HMGCR inhibitor) treatment, which inevitably diminishes its therapeutic efficacy, provoking the need for higher doses associated with adverse effects. The proteolysis targeting chimera (PROTAC) technology has recently emerged as a powerful approach for inducing protein degradation. Nonetheless, due to their bifunctional nature, developing orally bioavailable PROTACs remains a great challenge. Herein, we identified a powerful HMGCR-targeted PROTAC (

Objective:To evaluate the nutritional status of elderly inpatients with heart failure, and to analyze risk factors for malnutrition.Methods:A total of 221 patients with heart failure in our hospital from January 2018 to March 2019 were enrolled in the study.The demographic characteristics and medical record data were collected.All patients received Nutritional Risk Screening 2002(NRS-2002)and a questionnaire survey relating to heart failure.We investigated the effects of risk factors on the detection rate of malnutrition by using Mann-Whitney U test or Chi-square test, and the independent risk factors for malnutrition were analyzed by multivariate Logistic regression analysis.Results:The detection rate of nutritional risk was 45.2% in 221 patients.The detection rate of nutritional risk increased along with lower degree of education and worse cardiac function( P<0.05). The detection rate of nutritional risk was higher in patients with peripheral vascular disease and osteoporosis than in patients without them( P<0.05), and in patients with the increased numbers of complication and drugs( P<0.05). Patients with nutritional risk had a higher degree of frailty and a worse quality of activities of daily living( P<0.05). Multivariate Logistic regression analysis indicated that great age, ejection fraction, B-type natriuretic peptide(BNP), NYHA classification, numbers of drugs and diseases, frailty, low quality of life were independent risk factors for nutritional risk, and Digoxin was the independent protective factor for nutritional risk( P<0.05). Conclusions:The great age, severity of heart failure, numbers of drugs and diseases, frailty, low quality of daily life may be the independent risk factors for nutritional risk in elderly patients with heart failure, and oral Digoxin may be the independent protective factor for nutritional risk.

Objective:To evaluate the associations of depression and anxiety statues with serum inflammatory biomarkers in elderly patients with chronic heart failure.Methods:From January 2018 to January 2020, 225 elderly patients with chronic heart failure were enrolled from our hospital. Zung Self-Rating Depression Scale (SDS) and Zung Self-Rating Anxiety Scale (SAS) were performed in all patients to determine if the patients were with depression and anxiety statues and evaluate the degrees of depression and anxiety. The differences in demographic and clinical data, geriatric comprehensive assessment indicators, and serum inflammatory markers were compared among patients in the control group (without depression and anxiety), depression group, anxiety group, and depression and anxiety group (with both depression and anxiety). Spearman correlation test was used to analyze the correlation between the levels of serum inflammatory markers and the degrees of depression and anxiety in patients with depression and anxiety. Binary Logistic regression analysis was used to determine the independent influencing factors for depression and anxiety.Results:(1) As compared with those in the control group, patients in the depression group, anxiety group, and depression and anxiety group had significantly increased scores of Chinese version of Tilburg Frailty Indicator, statistically decreased Mini Mental State Examination (MMSE) scores, significantly increased Minnesota Living with Heart Failure Questionnaire (MLWHFQ) scores, increased proportions of patients with 2-4 kinds of diseases and those taking 2-4 kinds of drugs, and decreased Basic Activity of Daily Living (BADL) scores ( P<0.05); as compared with those in the depression group and the anxiety group, the changes of the above indicators in the depression and anxiety group were more obvious with significant differences ( P<0.05). As compared with those in the control group, patients in the depression group, anxiety group, and depression and anxiety group had significantly increased serum interleukin (IL)-6 and C-reactive protein (CRP) levels, patients in the anxiety group and depression and anxiety group had statistically elevated serum homocysteine (Hcy) level, and patients in the depression group and depression and anxiety group had significantly increased serum tumor necrosis factor α (TNF-α) level ( P<0.05); the serum levels of CRP, Hcy and TNF-α in patients from the depression and anxiety group were significantly higher than those in depression group ( P<0.05); the levels of IL-6, CRP, Hcy and TNF-α in the depression and anxiety group were significantly higher than those in the anxiety group ( P<0.05). As compared with that in the control group, the proportion of patients with nutritional risk in the depression and anxiety group was statistically higher ( P<0.05). (2) The serum levels of IL-6, CRP and TNF-α in depression patients were positively correlated with the depression degrees ( P<0.05); the serum levels of IL-6, CRP and Hcy in anxiety patients were positively correlated with the anxiety degrees ( P<0.05). (3) Results of binary Logistic regression analysis showed that IL-6 was an independent risk factor for depression in elderly patients with chronic heart failure ( OR=1.093, 95%CI: 1.049-1.139, P=0.000); Hcy was an independent risk factor for anxiety in elderly patients with chronic heart failure ( OR=1.114, 95%CI: 1.030-1.205, P=0.007); CRP, TNF-α, IL-6 and Hcy were independent risk factors for depression and anxiety in elderly patients with chronic heart failure ( P<0.05). Conclusion:The depression and anxiety degrees and expressions of inflammatory markers in elderly patients with chronic heart failure have synergistic effects.

Objective:To explore the relationship among CDH23 gene variation and the risk of noise-induced hearing loss (NIHL) .Methods:The nested case-control study was performed and this study followed a cohort of 6297 noise-exposed workers in a steel factory of Henan province in China from January 1, 2006 to December 31, 2015. In July 2019, subjects whose average hearing threshold were more than 40 dB in high frequency were defined as the case group, and subjects whose average hearing threshold were less than 35 dB in high frequency and less than 25 dB in speech frequency were defined as the control group. A nested case-control study which included 572 subjects was carried out, in which subjects consisted of 286 cases and 286 controls. 18 single nucleotide polymorphisms (SNPs) in CDH23 were selected and genotyped, then we analyzed the association among SNPs in CDH23, haplotypes in CDH23 and NIHL risk. Logistic regression was performed to analyze the main effects of SNPs and the interactions between CNE and SNPs adjusting cumulative noise exposure (CNE) , smoking, drinking, physical exercise and hypertension. Moreover, the association between haplotypes in CDH23 and NIHL risk were also analyzed. We ananlyzed the relationship amongst different SNP groups and NIHL risk using the generalized multifactor dimensionality reduction (GMDR) method.Results:The results suggested that significant associations were observed for rs3802711, rs3752751, rs3752752, rs11592462, rs10762480, rs3747867 for NIHL overall and/or various CNE strata by adjusting CNE, smoking, drinking, physical exercise and blood pressure. For rs3802711, workers exposure to noise carrying the AA/GA genotype of rs3802711 increased risk of NIHL than those carrying GG genotype ( OR=3.121; 95% CI:1.054-9.239, P=0.035) in overall; In the stratified analysis of CNE (>97 dB (A) ·year at rs3802711 locus, workers exposure to noise carrying GA genotype ( OR=2.056; 95% CI:1.226~3.448, P=0.006) and GA+AA/GA genotype ( OR=2.221; 95% CI:1.340~3.681, P=0.002) increased NIHL risk. For rs11592462, workers exposure to noise carrying the GG genotype of rs11592462 increased risk of NIHL than those carrying CC genotype in overall ( OR=3.951; 95% CI:1.104-14.137, P=0.04) ; workers exposure to noise carrying the GG genotype of rs11592462 increased risk of NIHL than those carrying CG+CC genotype in overall ( OR=4.06; 95% CI:1.145-14.391, P=0.03) . After adjusting CNE, smoking, drinking, physical exercise and blood pressure, the haplotypes of CDH23 rs1227049, rs10999947, rs3752752, rs3752751, rs10762480, rs3802711, rs11592462, rs10466026, rs4747194, rs4747195 were not associated with the risk of NIHL. GMDR analysis showed no association between SNP combination and NIHL risk after adjusting CNE, smoking, drinking, physical exercise and blood pressure. Conclusion:Gene polymorphisms in CDH23 might associate significantly with the risk of NIHL.

Objective:The purpose of this study was to explore the association between gene in the potassium recycling pathway 4 (KCNQ4) polymorphisms and the susceptibility to noise-induced hearing loss (NIHL) , and analysis the effect of cumulative noise exposure (CNE) and noise exposure duration on this association.Methods:A nested case-control study with 1∶1 matched was used based on the cohort of noise exposure in a steel factory. A total of 286 cases were selected as the group of hearing loss and 286 controls were chosen according to the matching standards of same gender, same type of work, age difference ≤ 5 years, noise exposure duration ≤ 2 years. The single nucleotide polymorphisms (SNPs) of rs4660468, rs4660470, rs34287852 in KCNQ4 were genotyped by SNPscan TM method. The codominant, dominant and recessive models were established to study KCNQ4 polymorphisms and the susceptibility to NIHL by single-factor conditional logistic regression analysis. The COX regression analysis was used to analyze the risk of developing NIHL in individuals with different genotypes along with the extending of noise exposure duration or CNE. Results:In the case of CNE≤96 dB (A) ·year, the risk of developing NIHL in individuals with TA genotype of rs4660470 was 2.197 times than individuals with TT genotypes (95% CI: 1.032~4.677) , and those with TA+AA and TT genotypes (HR=2.467, 95% CI: 1.025~5.934) With the increase of noise exposure duration, in rs4660470, individuals with TA genotype had a higher risk of suffering NIHL than those with TT genotype (HR=1.461, 95% CI: 1.061~2.011) , individuals with TA and/or AA genotype had a earlier risk of suffering NIHL than those with TT genotype. Conclusion:The mutant allele A of rs4660470 in KCNQ4 may be a risk factor for developing NIHL, CNE≤100 dB (A) ·year or the increase of noise exposure duration may further increase the risk of NIHL.

Multicolor imaging (MCI) based on confocal scanning laser ophthalmoscopy can gather more diagnostic information than traditional fundus photographs through utilizing three wavelengths of laser to scan posterior retina, which gain different layer reflected signal since the depth of penetration into retina is different for each wavelength. Currently, it provides important information and reference value for diagnose of different layer diseases on retina or choroid combining MCI with OCT, FAF, FFA and so on. However, there are still misunderstandings in the diagnosis of retinal diseases with MCI. Careful observation of retinal details in MCI, CFP and other imaging methods is more conducive to the correct diagnosis of fundus ophthalmopathy.

Objective:To identify association between genetic polymorphism in the Glutathione peroxidase 1 gene (GPX1) and noise-induced hearing loss (NIHL) .Methods:A nested case control study was conducted based on a cohort of noise-exposed subjects. 392 cases were selected from the steel factory in Henan Province, 392 matched control subjects for each case were designated on the basis of the matched criterion including same gender, age (±5years) and duration of exposure to noise (±2years) . Two single nucleotide polymorphisms (SNPs) of GPX1 were genotyped by SNPscanTM multiplex SNP genotyping kit. Hardy-Weinberg equilibrium (HWE) tests were performed using Pearson's χ 2 for each SNP among control group, effects of genotypes of GPX1 on NIHL were analyzed by logistic regression. Results:All two SNPs were in HWE. After adjustment for covariates including smoking status, rs1987628 polymorphism was statistically significantly associated with the NIHL risk under codominant and Dominant inheritance models; In the subjects carrying rs1987628 GA genotype had a higher NIHL risk than those carrying the GG genotype, the adjusted OR value was 1.803 (95% CI 1.215-2.676, P=0.003) . And meanwhile, rs1987628 GA+AA genotype had a higher NIHL risk than those carrying the GG genotype, the adjusted OR value was 1.762 (95% CI 1.197-2.593, P=0.004) . Conclusion:It was suggested that genetic polymorphism in the GPX1 gene might be the genetic susceptible factor for NIHL.

Objective:To investigate the association between the single nucleotide polymorphisms (SNPS) at rs1695 and rs6591256 in glutathione S-transferase P1 (GSTP1) gene and susceptibility to noise-induced hearing loss in Chinese Han workers exposed to noise.Methods:A 1: 2 matched nested case-control study was performed, which based on the cohort of 6297 workers exposed to noise in an iron and steel plant in Henan, China, who were followed up from January 1, 2006 to December 31, 2015. According to the criteria of binaural average high-frequency hearing threshold ≥40 dB, a total of 292 workers were enrolled as hearing loss group; after the adjustment for sex, type of work, age (difference≤5 years) , and working years of noise exposure (difference≤2 years) , according to the criteria of binaural average high-frequency hearing threshold <35 dB, and the speech frequency hearing threshold of any ear at any frequency band ≤25 dB, a total of 584 workers were enrolled as control group. The single nucleotide polymorphisms (SNPs) of rs1695 and rs6591256 in GSTP1 were genotyped by high throughput SNP genotyping assay. Hardy-Weinberg equilibrium of control group was checked. The association between the SNPs at the two loci and susceptibility to NIHL was analyzed.Results:The L Aeq, 8 h range of workers exposed to noise was 80.2-98.8 dB (A) . The risk of NIHL in individuals with allele G of rs1695 was 1.291 times of those with allele A (95% CI: 1.042-1.598, P<0.05) . The risk of NIHL in individuals with allele G of rs6591256 was 1.390 times of those with allele A (95% CI: 1.119-1.728, P<0.05) . The risk of NIHL in individuals with AG and GG genotypes of rs6591256 was 1.437 times of those with AA genotype (95% CI: 1.057-1.952, P<0.05) . With the increase of noise exposure duration, individuals with AG and GG genotypes of rs6591256 had a higher risk of NIHL than those with AA genotype (HR=1.273, 95% CI: 1.002-1.616, P<0.05) . Conclusion:The allele G of rs1695 and rs6591256 may be risk factors of NIHL.

Objective:To explore the relationship among CDH23 gene variation and the risk of noise-induced hearing loss (NIHL) .Methods:The nested case-control study was performed and this study followed a cohort of 6297 noise-exposed workers in a steel factory of Henan province in China from January 1, 2006 to December 31, 2015. In July 2019, subjects whose average hearing threshold were more than 40 dB in high frequency were defined as the case group, and subjects whose average hearing threshold were less than 35 dB in high frequency and less than 25 dB in speech frequency were defined as the control group. A nested case-control study which included 572 subjects was carried out, in which subjects consisted of 286 cases and 286 controls. 18 single nucleotide polymorphisms (SNPs) in CDH23 were selected and genotyped, then we analyzed the association among SNPs in CDH23, haplotypes in CDH23 and NIHL risk. Logistic regression was performed to analyze the main effects of SNPs and the interactions between CNE and SNPs adjusting cumulative noise exposure (CNE) , smoking, drinking, physical exercise and hypertension. Moreover, the association between haplotypes in CDH23 and NIHL risk were also analyzed. We ananlyzed the relationship amongst different SNP groups and NIHL risk using the generalized multifactor dimensionality reduction (GMDR) method.Results:The results suggested that significant associations were observed for rs3802711, rs3752751, rs3752752, rs11592462, rs10762480, rs3747867 for NIHL overall and/or various CNE strata by adjusting CNE, smoking, drinking, physical exercise and blood pressure. For rs3802711, workers exposure to noise carrying the AA/GA genotype of rs3802711 increased risk of NIHL than those carrying GG genotype ( OR=3.121; 95% CI:1.054-9.239, P=0.035) in overall; In the stratified analysis of CNE (>97 dB (A) ·year at rs3802711 locus, workers exposure to noise carrying GA genotype ( OR=2.056; 95% CI:1.226~3.448, P=0.006) and GA+AA/GA genotype ( OR=2.221; 95% CI:1.340~3.681, P=0.002) increased NIHL risk. For rs11592462, workers exposure to noise carrying the GG genotype of rs11592462 increased risk of NIHL than those carrying CC genotype in overall ( OR=3.951; 95% CI:1.104-14.137, P=0.04) ; workers exposure to noise carrying the GG genotype of rs11592462 increased risk of NIHL than those carrying CG+CC genotype in overall ( OR=4.06; 95% CI:1.145-14.391, P=0.03) . After adjusting CNE, smoking, drinking, physical exercise and blood pressure, the haplotypes of CDH23 rs1227049, rs10999947, rs3752752, rs3752751, rs10762480, rs3802711, rs11592462, rs10466026, rs4747194, rs4747195 were not associated with the risk of NIHL. GMDR analysis showed no association between SNP combination and NIHL risk after adjusting CNE, smoking, drinking, physical exercise and blood pressure. Conclusion:Gene polymorphisms in CDH23 might associate significantly with the risk of NIHL.

Objective:The purpose of this study was to explore the association between gene in the potassium recycling pathway 4 (KCNQ4) polymorphisms and the susceptibility to noise-induced hearing loss (NIHL) , and analysis the effect of cumulative noise exposure (CNE) and noise exposure duration on this association.Methods:A nested case-control study with 1∶1 matched was used based on the cohort of noise exposure in a steel factory. A total of 286 cases were selected as the group of hearing loss and 286 controls were chosen according to the matching standards of same gender, same type of work, age difference ≤ 5 years, noise exposure duration ≤ 2 years. The single nucleotide polymorphisms (SNPs) of rs4660468, rs4660470, rs34287852 in KCNQ4 were genotyped by SNPscan TM method. The codominant, dominant and recessive models were established to study KCNQ4 polymorphisms and the susceptibility to NIHL by single-factor conditional logistic regression analysis. The COX regression analysis was used to analyze the risk of developing NIHL in individuals with different genotypes along with the extending of noise exposure duration or CNE. Results:In the case of CNE≤96 dB (A) ·year, the risk of developing NIHL in individuals with TA genotype of rs4660470 was 2.197 times than individuals with TT genotypes (95% CI: 1.032~4.677) , and those with TA+AA and TT genotypes (HR=2.467, 95% CI: 1.025~5.934) With the increase of noise exposure duration, in rs4660470, individuals with TA genotype had a higher risk of suffering NIHL than those with TT genotype (HR=1.461, 95% CI: 1.061~2.011) , individuals with TA and/or AA genotype had a earlier risk of suffering NIHL than those with TT genotype. Conclusion:The mutant allele A of rs4660470 in KCNQ4 may be a risk factor for developing NIHL, CNE≤100 dB (A) ·year or the increase of noise exposure duration may further increase the risk of NIHL.