ObjectiveTo analyze the processing mechanism underlying the enhanced effect of invigorating spleen and stopping diarrhea of soil-fried Atractylodis Macrocephalae Rhizoma（AMR） by analyzing the changes of microstructure， chemical composition and anti-ulcerative colitis（UC） activity before and after soil stir-frying. MethodsThe microstructure and elemental composition of AMR before and after soil stir-frying were analyzed by scanning electron microscopy-energy dispersive spectroscopy（SEM-EDS）， to investigate the differences in microstructure and the underlying causes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） coupled with UNIFI 1.9.2 natural product analysis platform were used to analyze and identify the chemical constituents in raw and soil-fried products， and multivariate statistical methods including principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to explore the differences and sources of chemical constituents between them. A dextran sulfate sodium（DSS）-induced UC mouse model was established. The method of disease activity index（DAI） was used to evaluate the severity of intestinal inflammation. Hematoxylin-eosin（HE） staining was used to observe the pathological changes of colon tissue， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of inflammatory factors， Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to analyze the expressions of key genes and proteins involved in the intestinal mucosal barrier. The 16S rRNA sequencing was used to evaluate the diversity of intestinal flora， headspace gas chromatography-mass spectrometry（HS-GC-MS） was used to explore the levels of short-chain fatty acids（SCFAs） in feces. Base on the above findings， this paper investigated the effects of raw and soil-fried AMR on the biological， chemical， mechanical and immune barriers of model animals， and the differences in pharmacological effects and underlying mechanisms from the perspective of regulating the intestinal mucosal barrier in UC mice. ResultsSEM observation revealed numerous hearth soil particles on the surface of soil-fried AMR， accompanied by bubble-like bulges. At the same time， there were many cracks and folds on the surface of the hearth soil. EDS analysis revealed that the contents of Si， Al， Mg and Ca in soil-fried AMR were significantly higher than those of raw products， and these elements constituted the primary components of hearth soil. UPLC-Q-TOF-MS combined with database comparison was used to identify the chemical constituents of raw and soil-fried AMR. In positive ion mode， a total of 132 components were identified， primarily comprising three categories of terpenoids， polyphenols and amino acids. In negative ion mode， a total of 40 components were identified， primarily polyphenolic and glycoside compounds. Among them， the contents of sesquiterpenes and polyphenolic acids were changed significantly before and after processing. Soil-fried AMR could reduce the DAI score of UC mice， alleviate the shortening of colon length， reduce the levels of pro-inflammatory factors such as interleukin（IL）-17， IL-18， γ-interferon（IFN-γ） and tumor necrosis factor（TNF）-α in serum， increase the levels of anti-inflammatory factors such as secretory immunoglobulin A（sIgA）， IL-10， IL-4 and transforming growth factor-β（TGF-β） in serum， increase the expressions of key genes and proteins of intestinal mucosal barrier such as tight junction protein-1（ZO-1）， Occludin， Claudin-1 and mucin 2（MUC2） in colonic mucosa， and improve the disorders of intestinal flora diversity and the levels of SCFAs（P<0.05， P<0.01）. The raw and stir-fried products of AMR also exhibited the aforementioned effects， but they were weaker than the soil-fried products. Additionally， the auxiliary material hearth soil also had a certain pharmacodynamic effect. ConclusionSoil-fried AMR can enhance the protective effect on intestinal mucosal barrier in UC mice. These changes or heating-induced alterations in the microscopic structure and chemical composition of AMR may be attributed to the dual effects of adsorption of hearth soil.

ObjectiveTo analyze the processing mechanism underlying the enhanced effect of invigorating spleen and stopping diarrhea of soil-fried Atractylodis Macrocephalae Rhizoma（AMR） by analyzing the changes of microstructure， chemical composition and anti-ulcerative colitis（UC） activity before and after soil stir-frying. MethodsThe microstructure and elemental composition of AMR before and after soil stir-frying were analyzed by scanning electron microscopy-energy dispersive spectroscopy（SEM-EDS）， to investigate the differences in microstructure and the underlying causes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） coupled with UNIFI 1.9.2 natural product analysis platform were used to analyze and identify the chemical constituents in raw and soil-fried products， and multivariate statistical methods including principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to explore the differences and sources of chemical constituents between them. A dextran sulfate sodium（DSS）-induced UC mouse model was established. The method of disease activity index（DAI） was used to evaluate the severity of intestinal inflammation. Hematoxylin-eosin（HE） staining was used to observe the pathological changes of colon tissue， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of inflammatory factors， Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to analyze the expressions of key genes and proteins involved in the intestinal mucosal barrier. The 16S rRNA sequencing was used to evaluate the diversity of intestinal flora， headspace gas chromatography-mass spectrometry（HS-GC-MS） was used to explore the levels of short-chain fatty acids（SCFAs） in feces. Base on the above findings， this paper investigated the effects of raw and soil-fried AMR on the biological， chemical， mechanical and immune barriers of model animals， and the differences in pharmacological effects and underlying mechanisms from the perspective of regulating the intestinal mucosal barrier in UC mice. ResultsSEM observation revealed numerous hearth soil particles on the surface of soil-fried AMR， accompanied by bubble-like bulges. At the same time， there were many cracks and folds on the surface of the hearth soil. EDS analysis revealed that the contents of Si， Al， Mg and Ca in soil-fried AMR were significantly higher than those of raw products， and these elements constituted the primary components of hearth soil. UPLC-Q-TOF-MS combined with database comparison was used to identify the chemical constituents of raw and soil-fried AMR. In positive ion mode， a total of 132 components were identified， primarily comprising three categories of terpenoids， polyphenols and amino acids. In negative ion mode， a total of 40 components were identified， primarily polyphenolic and glycoside compounds. Among them， the contents of sesquiterpenes and polyphenolic acids were changed significantly before and after processing. Soil-fried AMR could reduce the DAI score of UC mice， alleviate the shortening of colon length， reduce the levels of pro-inflammatory factors such as interleukin（IL）-17， IL-18， γ-interferon（IFN-γ） and tumor necrosis factor（TNF）-α in serum， increase the levels of anti-inflammatory factors such as secretory immunoglobulin A（sIgA）， IL-10， IL-4 and transforming growth factor-β（TGF-β） in serum， increase the expressions of key genes and proteins of intestinal mucosal barrier such as tight junction protein-1（ZO-1）， Occludin， Claudin-1 and mucin 2（MUC2） in colonic mucosa， and improve the disorders of intestinal flora diversity and the levels of SCFAs（P<0.05， P<0.01）. The raw and stir-fried products of AMR also exhibited the aforementioned effects， but they were weaker than the soil-fried products. Additionally， the auxiliary material hearth soil also had a certain pharmacodynamic effect. ConclusionSoil-fried AMR can enhance the protective effect on intestinal mucosal barrier in UC mice. These changes or heating-induced alterations in the microscopic structure and chemical composition of AMR may be attributed to the dual effects of adsorption of hearth soil.

Objective:To explore the effects of Rougan Huaxian Granules combined with nucleoside antiviral drugs on liver and kidney function, portal hemodynamics, vascular activity, antiviral indexes and aspartate transaminase-platelet ratio index in patients with hepatitis B decompensated cirrhosis.Methods:A case-control study was conducted on 150 patients with hepatitis B decompensated cirrhosis who were hospitalized in Tangshan Infectious Disease Institute and Affiliated Hospital of North China University of Science and Technology from June 2017 to December 2019 were enrolled. The patients were divided into control group and observation group by computer random random number method, with 75 cases in each group. The control group was given routine liver protection and antiviral treatment; the observation group was given Rougan Huaxian granules on the basis of the control group treatment. Observe the changes of liver and kidney function, portal vein system hemodynamics, vascular activity, antiviral index and aspartate transaminase-platelet ratio index in the two groups. Independent sample T test was used to compare the measurement data between the two groups, paired T test was used for comparison between the same groups before and after treatment, and χ2 test was used for counting data. Results:There were no significant differences in gender, age, course of cirrhosis, Child grade of liver function and baseline data of indexes before treatment between 2 groups (ALL P>0.05). After treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen, creatinine,diameter of portal vein (Dpv), diameter of splenic vein (Dsv), endothelin-1, nitric oxide, glucagon (GLA), APRI,were all lower than before treatment. Comparison between groups, observation group ALT (51.60±15.97) U/L, AST (62.65±26.28) U/L, urea nitrogen (10.25±1.65) mmol/L, creatinine (78.54±14.09) μmol/L, Dpv (10.20±1.10) mm, Dsv (8.08±0.68) mm, endothelin-1 (31.93±6.35) ng/L, nitric oxide (41.38±8.06) μg/L, GLA (69.54±12.14) mg/L, APRI (3.14±1.35), were significantly lower than those of control group ((97.49±30.87) U/L, (96.03±25.63) U/L, (17.49±2.55) mmol/L, (116.43±22.77) μmol/L, (13.42±1.26) mm, (10.44±0.83) mm, (44.34+11.88) ng/L, (63.47±15.50) μg/L, (107.11+25.29) mg/L, (5.91±1.93)), the differences were statistically significant ( t values were respectively 11.43, 7.87, 20.64, 12.26, 16.62, 18.99, 7.98, 10.96, 11.60, 10.23, all P<0.05). After treatment, albumin, portal vein velocity (Vpv), and velocity of splenic vein blood flow (Vsv) were all higher in the two groups than before treatment. However, there was no significant difference in Vsv of the control group before and after treatment ( t=0.51, P=0.613). Comparison between groups, albumin (39.42±7.35) g/L, Vpv ((25.72±4.06) cm/s), Vsv ((24.22±6.15) cm/s) in the observation group were significantly higher than those in the control group (34.66±7.95) g/L, (19.38±3.46) cm/s, (19.54±5.88) cm/s ( t values were 3.81, 10.28, 4.76, all P<0.05). After treatment, the total effective rate (96.00%(72/75) vs. 86.67%(65/75), χ2=4.13, P=0.042), HBV DNA negative conversion rate (76.00%(57/75) vs. 58.67%(44/75), χ2=5.12, P=0.024), HBeAg negative conversion rate (50.67%(38/75) vs. 30.67%(23/75), χ2=6.22, P=0.013) and serum HBeAg/HBeAb conversion (28.00%(21/75) vs. 13.33%(10/75), χ2=4.92, P=0.027) in observation group were higher than those in control group, and the differences were statistically significant ( P<0.05). HBsAg negative rate (8.00%(6/75) vs. 5.33%(4/75), χ2=0.43, P=0.513) was higher than that of control group, but the difference was not statistically significant ( P>0.05). Conclusion:Rougan Huaxian Granules combined with nucleoside antiviral drugs has significant effect on patients with decompensated liver cirrhosis of hepatitis B, improve liver and kidney function, liver fibrosis and hemodynamics of the portal vein system, increase vascular activity function, and reduce hepatitis B virus (HBV) DNA load, HBV replication, aspartate transaminase-platelet ratio index, APRI, Toll-like receptor (TLR-4) and transforming growth factor β1 (TGF-β1) levels and improves the body′s immune status.

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.

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:Using the 1: 1 nested case-control study and taking 6297 workers exposed to noise in a steel plant in Henan province as the cohort study population in July 2019, we screened those who have been exposed to noise for ≥3 years and whose binaural high frequency (3000, 4000, 6000 Hz) average hearing threshold is ≥40 dB (A) into the case group. The control group was selected according to the matching criteria of the same sex, same type of work, and the age difference was not more than 5 years old, and the working age difference was not more than 2 years. 276 subjects were selected into the case group and the control group respectively. The medium and high throughout single nucleotide polymorphism typing technology (SNPscanTM technology) was used to detect the polymorphism of three nucleotide sites of GSR gene, and conditional logistic regression was used to analyze the relationship between single nucleotide polymorphism (SNP) and NIHL, and the relationship between different polymorphic sites and the risk of NIHL after adjusting covariates. After stratification with different cumulative noise exposure (CNE) , Conditional logistic regression analysis was used to analysis the risk of NIHL at different loci.Results:The mean and standard deviation of age of the selected subjects was (40.28±8.00) , the mean and standard deviation of noise-exposed working years was (18.7±8.92) years. The range of noise exposure levels and comulative noise exposure were 80.05-93.35dB (A) and 86.83-107.92 dB (A) ·year, respectively. Compared with the control group, there were no statistically significant differences in age, noise-exposured working years, intensity of noise exposure, CNE, gender, drinking, hypertension prevalence and noise exposure level in the hearing loss group ( P>0.05) , while there were statistically difference in smoking, binaural high-frequency average hearing threshold and binaural speech frequency ( P<0.05) . After adjusting for smoking, drinking, hypertension and other factors, in the co-dominant model, compared with GGgenotype, the risk of NIHL was higher in rs1002149 GT genotype and rs2251780 GA genotype ( OR=1.558, 95% CI: 1.028-2.361; OR=1.550, 95% CI: 1.020-2.355, P<0.05) ; compared with TT/GT genotype, the rs1002149 TT genotype has a higher risk of developing NIHL ( OR=1.494, 95% CI: 1.002-2.228, P<0.05) , while rs3779647 genotype had no relationship with the risk of NIHL ( P>0.05) . In the equivalent sound level (L Aeq) of noise >85 dB (A) stratification, compared with GG genotype, carrying rs1002149 GT genotype and rs2251780 GT genotype has higher risk of nihl ( OR=1.801, 95% CI: 1.093-2.967; OR=1.720, 95% CI: 1.050-2.817, P<0.05) . Haplotype analysis of two sites, rs1002149 and rs2251780, was not found to be related to NIIHL susceptibility. Conclusion:The allele G of rs1695 and rs6591256 may be risk factors of NIHL.

Objective:To investigate the relationship between SNP and noise-induced hearing loss (NIHL) susceptibility in occupational noise exposure population in China.Methods:From 6297 for a certain steel works in contact with noise, contact length of 3 years or more and workplace noise exposure intensity of 80 dB (A) , ears or high frequency (3 000, 4 000, 6 000 Hz) average of hearing acuity 40 dB (HL) , or high frequency loss in both ears, on the basis of single whisper frequency (500, 1, 000, 2 000 Hz) average threshold of 26 dB (HL) or object as case group. A case-control study was designed with 1:1 matching. Subjects with the same gender, the same type of work, age ±5 years old, and working age ±2 years after noise exposure were selected as the control group. Subjects with any whisper frequency (500, 1, 000, 2, 000 Hz) whose hearing threshold in any frequency band was ≤25 dB (A) and whose average high-frequency hearing threshold in pure tone hearing test was <35 dB (A) were selected as the control group. Four sites of PON2 gene were genotyped by medium-and high-throughput SNP genotyping. Univariate logistic regression was used to analyze the relationship between single SNP polymorphism and NIHL.Results:A total of 286 case-control pairs were included. Smoking was statistically significant difference between cases and controls ( P<0.001) . Conclusion:No statistical difference has been found between single SNP polymorphism and NIHL. At the level of greater than 92 dB of high noise exposure, rs7785846 (CT+TT) genotype is a risk factor for occupational noise deafness, and its OR is 2.74 (95% CI: 1.09-6.89) compared with wild homozygous type (CC) . Conclusion. The rs7785846 (CT+TT) genotype carriers of PON2 gene are more susceptible to hearing impairment when exposed to high noise intensity.

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.