1.Effect of Qianyang Yuyin Granules on Mesenchymal Transdifferentiation of Renal Tubular Epithelial Cells Induced by TGF-β1
Xue KONG ; Guoshun HUANG ; Xueling HAN ; Jinbo ZHANG ; Jing DAI ; Mengnan SHANG ; Chong ZOU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):56-63
ObjectiveBy observing the effect of Qianyang Yuyin granules on the phenotype of renal tubule epithelial cells, the intervention of Qianyang Yuyin granule on renal interstitial fibrosis was investigated. MethodThe renal tubular epithelial cells (HK-2) were treated with different concentrations of transforming growth factor (TGF)-β1 (5, 10, 15, 20, 25 μg·L-1) for 24 hours, and cell morphology and growth state were observed with an inverted phase contrast microscope. The 20 μg·L-1 was selected as the most appropriate concentration of TGF-β1 according to Western blot results for subsequent experiments. HK-2 cells were divided into six groups: blank group, TGF-β1 group (concentration of 20 μg·L-1), low, medium, and high dose Qianyang Yuyin granule groups (concentration of 0.5, 1, 2 g·L-1), and valsartan group (1 × 10-5 mol·L-1). The cell activity was measured by cell proliferation and cell counting kit-8 (CCK-8). The cell migration ability was detected by scratch test. The Transwell method was used to detect the invasiveness of cells. Western blot was used to detect levels of fibronectin (FN), E-cadherin, α-smooth muscle activator (α-SMA), Vimentin, collagen type Ⅰ(Col Ⅰ), collagen type Ⅳ(Col Ⅳ), and other related proteins. ResultTGF-β1 stimulating epithelial-mesenchymal transition (EMT) in renal tubular epithelial cells was time- and concentration-dependent. Compared with the blank group, higher concentration in the TGF-β1 group indicates longer intervention time and more obvious long spindle change of cells, and the migration and invasion ability of the cells was significantly enhanced. The protein expression level of FN, α-SMA, Vimentin, Col Ⅰ, and Col Ⅳ increased significantly (P<0.05, P<0.01), while the expression level of E-cadherin protein decreased (P<0.05). Compared with the TGF-β1 group, Qianyang Yuyin granule groups could maintain normal cell morphology, and the migration and invasion ability of the cells was inhibited. The protein expression level of FN, α-SMA, Vimentin, Col Ⅰ, and Col Ⅳ decreased (P<0.05, P<0.01), and the expression of E-cadherin protein was significantly restored (P<0.05). ConclusionQianyang Yuyin granule can reverse TGF-β1-induced interstitial transformation of renal tubular epithelial cells by reducing the phenotypic expression of mesenchymal cells and increasing the phenotypic expression of epithelial cells.
2.Treatment progress of cirrhotic portal hypertension
Guoshun ZHANG ; Chao LIU ; Suying WANG ; Meiyu JIANG ; Dongxue MEI ; Xuehui YANG ; Yingying XIN ; Zheng SHI
Clinical Medicine of China 2024;40(3):223-227
Cirrhotic portal hypertension (CPH) is a manifestation of decompensated liver cirrhosis, with ascites, portal collateral circulation formation, hypersplenism and splenomegaly as the typical clinical symptoms. In recent years, the incidence of CPH has been increasing year by year, and the treatment of CPH has gradually become a hot issue in medical research. In order to further explore the diagnosis and treatment scheme of CPH. We briefly describe the pathophysiological mechanism and diagnosis of CPH, and the current situation of CPH treatment and the new progress of internal and external treatment were reviewed.
3.Therapeutic effect of probiotics combined with ornithine aspartate on patients with liver cirrhosis complicated with hepatic encephalopathy
Dongxue MEI ; Guoshun ZHANG ; Suying WANG
Clinical Medicine of China 2023;39(5):326-331
Objective:To explore the safety and therapeutic effect of probiotics combined with ornithine aspartate on patients with liver cirrhosis complicated by hepatic encephalopathy.Methods:72 patients with hepatic encephalopathy hospitalized in the Affiliated Hospital of North China University of Technology from January 2017 to December 2021 were randomly. According to the principle of comparability between groups in terms of gender and age, the group was divided into an observation group (36 cases) and a control group (36 cases) using a random number table method. The control group was treated with ornithine aspartate, while the case group was treated with probiotics combined with ornithine aspartate. The curative effect of the two groups of patients and the changes of serum inflammatory factors, intestinal flora and intestinal mucosal barrier function were observed.Results:The total effective rate of the case group was higher than that of the control group [97.22%(35/36) vs 83.33%(30/36)], The difference between groups is statistically significant (χ 2=2.53, P=0.112). After treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), blood ammonia, interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor (TNF) in the two groups-α (TNF-α)、C-reactive protein (CRP), enterobacter, enterococcus content, endotoxin, D-lactic acid, diamine oxidase, and digital connection test (NCT) time were lower than before treatment [(-130.89±31.67) U/L vs (-98.64±43.41) U/L,(-137.81±31.92) U/L vs (-79.58±45.42) U/L, (-57.13±21.07) μmol/L vs (-45.92±18.11) μmol/L,(-164.06±19.30) μmol/L vs (-148.98±12.97) μmol/L, (-5.35±2.30) ng/L vs (2.18±2.77) ng/L,(-5.51±2.07) μmol/L vs (-3.72±1.50) ng/L, (-12.60±3.65) ng/L比(-7.97±5.86) ng/L, (-45.95±20.34) mg/L vs (-21.14±19.09) mg/L, (-2.70±1.53) vs (-1.31±2.47), (-2.50±1.26) vs (-1.39±1.97),(-0.32±0.09) EU/ml vs (-0.19±0.09) EU/ml, (-47.58±18.52) nmol/L vs (-32.31±22.21) nmol/L,(-3.44±1.06) U/ml vs (-1.86±1.30) U/ml, (-31.75±10.09) s vs (-14.58±10.10) s] and the scores of bifidobacterium, lactobacillus, and digital sign test (DST) were higher than before treatment [(2.77±1.76) vs (1.13±2.06), (3.23±1.61) vs (1.06±2.31), (32.58±5.72) vs (16.33±6.16)]. After treatment, ALT, AST, TBIL, blood ammonia, IL-6, IL-8, TNF in the case group-α, CRP, Enterobacter, Enterococcus content, endotoxin, D-lactic acid, diamine oxidase, NCT time were lower than those in the control group, and bifidobacterium, lactobacillus, DST scores were higher than those in the control group, with statistically significant differences(t-values of 3.60, 6.29, 2.42, 3.89, 5.28, 4.21, 4.03, 5.34, 2.87, 2.86, 6.11, 3.17, 5.63, 7.21, 3.61, 4.64 and 11.59. P-values of 0.001, <0.001, 0.018, <0.001, <0.001, <0.001, <0.001, <0.001, 0.005, 0.006, <0.001, 0.002, <0.001, <0.001, 0.001, <0.001, and <0.001). Conclusions:Micro-ecological preparation combined with ornithine aspartate has a significant therapeutic effect on patients with hepatic encephalopathy, which can significantly improve liver function and cognitive function of patients, reduce blood ammonia level, inhibit inflammatory reaction, improve intestinal flora and intestinal mucosal barrier function, with good safety, and is worthy of clinical promotion.
4.Clinical observation of Rougan Huaxian granule combined with nucleoside antiviral drugs in treatment of patients with decompensated cirrhosis of hepatitis B
Hua SHANG ; Guoshun ZHANG ; Guikai WU ; Diyang WU ; Liuqing WANG ; Hongshan WEI
Clinical Medicine of China 2022;38(1):53-61
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.
5.Effects of ursolic acid on oxidative stress and inflammatory factors in a rat model of AR after PM2.5 exposure
Na SUN ; Ruxin ZHANG ; Hong WANG ; Yu HUANG ; Zhijin HAN ; Jing BAO ; Yusen DUAN ; Weiyang DONG ; Congrui DENG ; Guoshun ZHUANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2022;57(7):860-867
Objective:To investigate the effects of ursolic acid (UA) on oxidative stress and inflammatory factors in a rat model of AR after PM2.5 exposure.Methods:Sixty healthy female SD rats were randomly divided into five groups: normal control group (NC group), PM2.5 unexposed AR group (AR group), PM2.5 exposed AR group (ARE group), UA intervention AR group (AR+UA group), and UA intervention PM2.5 exposed AR group (ARE+UA group), with 12 rats in each group. AR model was performed by a basal sensitization with intraperitoneal injection of ovalbumin (OVA) and followed by nasal instillation. PM2.5 exposure was carried out by inhalation exposure system at a concentration of 200 μg/m 3 for 3 h/d for 30 days. UA intervention group was given UA intragastric administration at 20 mg/(kg·d). AR symptoms including sneezing, nasal scratching and nasal secretion of rats in each group were observed. The activities of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in nasal mucosa were tested. The pathological changes of nasal mucosa were observed by HE staining. The levels of OVA-sIgE, IL-6 and IL-17 in serum were measured by enzyme-linked immunosorbent assay (ELISA). Protein microarray was used to measure the expression of multiple inflammation cell factors in nasal mucosa. Statistical analysis was performed with SPSS 20.0. Results:After UA intervention, the frequency of nasal sneezing, scratching and nasal secretion in ARE+UA group were lower than those of ARE group ( P<0.05). Pathological examination of nasal mucosa showed that ARE+UA group had less inflammatory granulocyte infiltration and less pathological damage to the epithelial layer than ARE group. The activities of SOD in nasal mucosa of ARE+UA group were higher than those of ARE group ((50.10±3.09) U/mg vs (20.13±1.30) U/mg, F value was 597.54, P<0.01). The contents of MDA in nasal mucosa of ARE+UA group were lower than those of ARE group ((57.78±12.36) nmol/g vs (124.12±9.40) nmol/g, F value was 115.51, P<0.01). The expression levels of OVA-sIgE, IL-6 and IL-17 proteins were lower in the ARE+UA group than those in ARE group ((11.61±0.27) ng/ml vs (20.30±0.67) ng/ml, (47.59±15.49) pg/ml vs (98.83±10.98) pg/ml, (623.30±8.75) pg/ml vs (913.32±9.06) pg/ml, F value was 283.42, 80.45, 683.73, respectively, all P<0.01). After UA intervention, protein microarray analysis showed that the expression of IL-4, IL-6, IL-13, chemokine CXCL7, IL-1α, IL-1β, MMP-8 and MCP-1 in ARE+UA group was decreased compared with ARE group while IFN-γ and IL-10 increased (all P<0.01). Conclusion:UA can reduce the aggravated AR symptoms and pathological damage of nasal mucosa, inhibit oxidative stress and release of inflammatory factors after PM2.5 exposure, and thus plays a protective role in the pathological damage of AR induced by PM2.5 exposure.
6.Determination of 8 Glycosides and 4 Aglycones in Directionally Processed Astragalus membranaceus under Different Temperatures by UPLC-MS
Pengpeng LIU ; Fan ZHANG ; Ji SHI ; Guoshun SHAN ; Tianzhu JIA
China Pharmacy 2020;31(3):287-293
OBJECTIVE:To establish a method for the determination of 8 glycosides(astragaloside Ⅰ,Ⅱ,Ⅲ,Ⅳ and calycosin glucopyranoside ,2′-hydroxy-3′,4′-dimethoxy-isoflavan-glucoside and 9,10-dimethoxy-pterocarpan-glucoside) and 4 aglycones(calycosin,formononetin,7,2′-dihydroxy-3′,4′-dimethoxy-isoflavan and 3-hydroxy-9,10-dimethoxy-pterocarpan) in Astragalus membranaceus ,and to investigate the effects of different processing temperatures on the contents of above 12 components. METHODS :The contents of 12 components in A. membranaceus and samples processed under different temperatures(120,140,160,180,200 ℃)were determined by UPLC-MS/MS. The determination was performed on ACQUITY UPLC HSS T 3 column with mobile phase consisted of 0.1 mol/L formic acid water solution -0.1 mol/L formic acid acetonitrile solution (gradient elution )at the flow rate of 0.5 mL/min. The column temperature was 30 ℃. The detection wavel ength was 260 nm,and sample size was 2 μL. Electrospray ion source(ESI)was used under positive ion mode (ESI+). The mass scanning range was mass ratio (m/z)of 50-1 500,with capillary voltage of 2 000 V and ion source temperature of 100 ℃. The desolvation temperature was 400 ℃;flow rate of atomizing gas (N2) was 40 L/h,and that of desolvation was 800 L/h;collision energy (CE)was 20-30 V;data acquisition rate was 0.5 s/scan. RESULTS:The linear range of astragaloside Ⅰ,astragaloside Ⅱ,astragaloside Ⅲ,astragaloside Ⅳ,calycosin-glucopyranoside, calycosin,ononin,formononetin,2′-hydroxy-3′,4′-dimethoxy-isoflavan-glucoside,7,2′-dihydroxy-3′,4′-dimethoxy-isoflavan,9, 10-dimethoxy-pterocarpan-glucoside and 3-hydroxy-9,10-dimethoxy-pterocarpan were 0.001 16-0.232 0,0.000 276-0.055 2, 0.000 22-0.044 0,0.000 225-0.045 0,0.000 734-0.587 0,0.001 17-0.234 0,0.000 742- 0.148 0,0.001 30-0.260,0.003 98-0.795 0, 0.000 476-0.476 0,0.001 89-0.378 0,0.000 336-0.336 0 μg(all R2≥0.999 2),respectively. The limits of detection were 6.2×10-6, 4.8×10-6,3.8×10-6,3.4×10-6,5.8×10-6,4.8×10-6,4.2×10-6,3.2×10-6,5.8×10-6,2.6×10-6,4.2×10-6,6.4×10-6 μg,respectively. The limits of quantitation were 12.6×10-6,16.2×10-6,14.4×10-6,14.8×10-6,18.8×10-6,16.4×10-6,15.4×10-6,10.8×10-6,20.2×10-6, 12.4×10-6,14.6×10-6,23.4×10-6 μg,respectively. RSDs of precision ,stability(24 h)and repetition tests were all lower than 3.0%(n=6). The average recoveries were 99.1%,100.2%,98.7%,101.9%,98.6%,102.1%,99.2%,100.3%,98.7%, 99.2%,99.3% and 100.8%,with the RSDs of 1.9%,2.2%,2.4%,1.8%,2.1%,1.7%,2.3%,1.9%,2.4%,1.8%,2.2% and 1.9%(n=6),respectively. The results showed that the contents of astragaloside Ⅰ,Ⅱ and Ⅲ decreased gradually with the increase of processing temperature ;the content of astragaloside Ⅳ increased gradually with the increase of temperature. The content of flavonoid glycosides ,such as calycosin glucopyranoside ,ononin,2′-hydroxy-3′,4′-dimethoxy-isoflavan-glucoside and 9, 10-dimethoxy-pterocarpan-glucoside decreased with the increase of temperature ;the corresponding aglycone components as flavonoid glycosides ,formononetin,3-hydroxy-9,10-dimethoxy- pterocarpan increased firstly and then decreased with the increase ; the content of 7,2′-dihydroxy-3′,4′- dimethoxy-isoflavan decreased with the increase of temperature. CONCLUSIONS :Established UPLC-MS/MS method can be used for determination of 12 components in A. membranaceus . After processed under different temperature,the contents of glycosides decreased in general ,while the contents of aglycones increased in general.
7.Relationship research among CDH23 gene and the risk of noise-induced hearing loss
Jie JIAO ; Guizhen GU ; Guoshun CHEN ; Huanling ZHANG ; Hui WU ; Yanhong LI ; Wenhui ZHOU ; Shanfa YU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2020;38(2):84-90
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.
8.Prediction of KCNQ4gene polymorphism varies with CNE or noise exposure duration on the Risk of NIHL-Cox model analysis based on cohort study
Wenhui ZHOU ; Guizhen GU ; Hui WU ; Yanhong LI ; Guoshun CHEN ; Huanling ZHANG ; Shanfa YU ; Yuxin ZHENG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2020;38(2):111-116
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.
9.Association between GSTP1 gene polymorphisms and susceptibility to noise-induced hearing loss
Lulu YUAN ; Guoshun CHEN ; Jie JIAO ; Wenhui ZHOU ; Hui WU ; Guizhen GU ; Huanling ZHANG ; Yuxin ZHENG ; Shanfa YU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2020;38(2):101-107
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.
10.Association between PON2 gene polymorphisms and susceptibility to noise-induced hearing loss
Shanshan WU ; Jinning YU ; Jie JIAO ; Guoshun CHEN ; Changyun ZHANG ; Shanfa YU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2020;38(2):128-132
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.

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