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Objective To evaluate the role of autophagy in cognitive decline caused by sevoflurane anesthesia and the relationship with neurogenesis in aged mice.Methods Forty-five healthy SPF male mice,aged 20-22 months,weighing 25-35 g,were divided into 3 groups (n=15 each) using a random number table method:control group (group C),sevoflurane anesthesia group (group S) and autophagy agonist rapamycin group (group R).Rapamycin 0.2 mg/kg was intraperitoneally injected every day for 7 days in group R,while the equal volume of solvent dimethyl sulfoxide was given instead in S and C groups.In group S and group R,3％ sevoflurane was inhaled for 2 h once a day for 3 consecutive days starting from 5th day of administration,while the mixture of air and oxygen was inhaled instead in group C.Five mice in each group were randomly selected after the last anaesthesia and sacrificed,and the hippocampus was removed for determination of the expression of microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ) and Beclin-1 by Western blot.The other mice were sacrificed after Morris water maze test was performed,and hippocampi were isolated for determination of doublecortin (DCX) positive cells in the dentate gyrus by immunohistochemistry.Results Compared with group C,the escape latency was significantly prolonged,the percentage of time spent in the target quadrant was decreased,the expression of LC3 Ⅱ and Beclin-1 was down-regulated,LC3 Ⅱ/LC3 Ⅰ ratio was decreased,and DCX positive cell counts were reduced in S and R groups (P＜0.05).Compared with group S,the escape latency was significantly shortened,the percentage of time spent in the target quadrant was increased,the expression of LC3 Ⅱ and Beclin-1 was up-regulated,LC3Ⅱ/LC3 Ⅰ ratio was increased,and DCX positive cell counts were increased in group R (P＜0.05).Conclusion Autophagy is involved in the process of cognitive decline caused by sevoflurane anesthesia,which is related to inhibiting neurogenesis in the hippocampus of aged mice.
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Objective To evaluate the effects of sevoflurane on hippocampal neurogenesis in den-tate gyrus (DG) of mice of different ages. Methods Ninety-six SPF healthy male C57BL∕6 mice, aged 2 weeks, 6 weeks, 9 months and 20 months (24 mice for each age, 12 mice for each group), were divided into 2 groups (n＝48 each) using a random number table method: control group (group C) and sevoflurane group (group S). Group S inhaled 3. 0% sevoflurane for 2 h once a day for 3 consecutive days, while group C inhaled the mixture of air and O2. Six mice of each age were selected, and 5′-bromo-2′-deoxyuridine (BrdU) 50 mg∕kg was intraperitoneally injected immediately before and after inhalation once a day for 3 consecutive days in two groups. Mice were sacrificed at 24 h after the last inhalation (T1), brains were re-moved and hippocampi isolated for determination of the number of nestin and doublecortin ( DCX) positive cells in DG by immunohistochemistry. Mice were sacrificed at 4 weeks after the last inhalation ( T2), brains were removed and hippocampi isolated for determination of the number of neuronal nuclei antigen (NeuN)∕BrdU and glial fibrillary acid protein ( GFAP )∕BrdU positive cells by immunofluorescence. Re-sults Compared with group C, the number of nestin and DCX positive cells was significantly reduced at T1, and the number of NeuN∕BrdU and GFAP∕BrdU positive cells was reduced at T2in mice of 2 weeks and 20 months old (P＜0. 05), and no significant change was found in the indices mentioned above in mice of 6 weeks and 9 months old in group S ( P＞0. 05). Conclusion Three percent sevoflurane can inhibit hipp-ocampal neurogenesis in DG of immature and old mice and exerts no influence on hippocampal neurogenesis in DG of juvenile and adult mice.
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Objective@#To explore the relationship between mitochondrial 12 S rRNA gene variation, tRNA gene variation and cytochrome oxidase Ⅱ gene point mutations and the risk of noise-induced hearing loss (NIHL).@*Methods@#A nested case-control study was performed that followed a cohort of 7 445 noise-exposed workers in a steel factory in Henan province, China, from January 1, 2006 to December 31, 2015. Subjects whose average hearing threshold was more than 40 dB(A) in high frequency were defined as the case group, and subjects whose average hearing threshold was less than 35 dB(A) in high frequency and less than 25 dB (A) in speech frequency were defined as the control group. Subjects was recruited into the case group (n=286) and the control group (n=286) according to gender, age, job category and time of exposure to noise, and a 1∶1 case-control study was carried out. We genotyped eight single nucleotide polymorphisms in the mitochondrial 12 S rRNA gene, the mitochondrial tRNA gene and the mitochondrial cytochrome oxidase Ⅱ gene using SNPscan high-throughput genotyping technology from the recruited subjects. The relationship between polymorphic sites and NIHL, adjusted for covariates, was analyzed using conditional logistic regression analysis, as were the subgroup data.@*Results@#The average age of the recruited subjects was (40.3±8.1) years and the length of service exposure to noise was (18.6±8.9) years. The range of noise exposed levels and cumulative noise exposure (CNE) was 80.1- 93.4 dB (A) and 86.8- 107.9 dB (A) · year, respectively. For workers exposed to noise at a CNE level<98 dB (A) · year, smokers showed an increased risk of NIHL of 1.88 (1.16-3.05) compared with non-smokers; for workers exposed to noise at a CNE level ≥98 dB(A) · year, smokers showed an increased risk of NIHL of 2.53 (1.49- 4.30) compared with non-smokers. For workers exposed to noise at a CNE level<98 dB (A) · year, the results of univariate analysis and multifactor analysis, adjusted by smoking and CNE, suggested that the risk of NIHL in workers exposed to noise carrying the GG genotype (G827A) was lower than that of NIHL workers exposed to noise carrying the AA genotype (G827A) [OR (95% CI) were 0.18 (0.04- 0.82) and 0.19 (0.04- 0.88), respectively].@*Conclusion@#Smoking increased the risk of NIHL in the present study. For workers subjected to a CNE<98 dB(A)·year, the mitochondrial genetic variant G827A was found to be significantly associated with the risk of NIHL.
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Objective@#To identify the association between genetic polymorphisms in the eye absent homolog 4 (EYA4) gene and noise-induced hearing loss (NIHL).@*Method@#A nested case control study was conducted based on a cohort of noise-exposed subjects. In total, 292 cases were selected from a steel factory from 6 297 subjects during Jan 1, 2006 to Dec 12, 2015,who had an average hearing threshold of more than 40 dB(A); 584 matched control subjects for each case were designated on the basis of matched criteria including same gender, age (±5 years) and duration of exposure to noise (±2 years). What's more, the control group had an average hearing threshold of less than 35 dB(A) in high frequency and less than 25 dB(A) in speech frequency. Four single nucleotide polymorphisms (SNPs) of the EYA4 gene were genotyped using a SNPscanTM multiplex SNP genotyping kit. Hardy-Weinberg equilibrium tests were performed using a χ2 test for goodness-of-fit for each SNP among the control group, and the effects of genotypes of the EYA4 gene on NIHL were analyzed by logistic regression. The haplotypes were established and their frequencies in the two groups were assessed using Haploview 4.2 and Phase 2.1 software, and interactive effects between haplotypes and cumulative noise exposure were analyzed.@*Results@#The average age of the subjects was (40.1±8.4) years and the average number of noise-exposed working years was 20.3 (8.4, 27.3) years. The range of noise exposure levels and the cumulative noise exposure were 80.2- 98.8 dB (A) and 86.6- 111.2 dB(A) · year, respectively. After adjustment for covariates including height, blood pressure, drinking status and smoking status, in the noise intensity>85 dB (A) group, subjects carrying the rs3813346 TT genotype had a higher NIHL risk than those carrying the GG genotype, and the adjusted OR (95% CI) value was 2.12 (1.21- 3.69). In the cumulative noise exposure>98 dB (A) · year group, compared with haplotype TGC, haplotype CGT showed a protective effect in the development of NIHL, with an adjusted OR (95% CI) value of 0.60 (0.37-0.97), however, the significance of intercation between EY4 gene of noise was lost after Bonferroni correction.@*Conclusion@#Genetic polymorphism in the EYA4 gene may be a genetic susceptibility factor for NIHL.
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Objective@#The aim of this study was to investigate whether genetic variability in the protocadherin 15 (PCDH15) gene may correspond with increased susceptibility to noise-induced hearing loss (NIHL) in a Chinese population.@*Methods@#A nested case-control study was performed that followed a cohort of 7 445 noise-exposed workers in a steel factory of Henan province in China from January 1, 2006 to December 31, 2015. In this study, 394 cases who had an average hearing threshold of more than 40 dB (A) in high frequency were defined as the case group, and 721 controls who had an average hearing threshold of less than 35 dB (A) in high frequency and less than 25 dB (A) in speech frequency were defined as the control group. A questionnaire was completed by participants and a physical test was also conducted. SNP genotyping was performed using the SNPscanTM Kit. Multivariate unconditional logistic regression additive models were used to analyze the genotypes in different groups, and the association with NIHL. Unconditional logistic regression models were used to assess the associations between the genotypes and NIHL.@*Results@#The average age of study participants was (40.5±8.3) years and the median number of noise-exposed working years M (P25, P75) was 21.1 (9.1, 27.3). The range of noise exposed levels and the levels of cumulative noise exposure (CNE) were 80.1- 98.8 dB(A) and 86.6- 111.2 dB(A), respectively. Only the distribution of the genotypes (TT/CC/CT) of rs11004085 in the PCDH15 gene showed a significant difference between the case and control groups (P=0.049). In the case group, the distribution was 370 (93.9%), 24 (6.1%) and 0; in the control group, the distribution was 694 (96.3%), 23 (3.2%) and 1 (0.1% ). After smoking, drinking, hypertension, height and CNE adjustment, compared with the TT genotype individuals with the CC/CT genotype had a 1.90-fold increased risk of NIHL (95% CI: 1.06- 3.40). After stratified these data by the noise exposure level or CNE when the noise exposure level was>85 dB (A), compared with cases with the AA genotype of rs10825113, individuals with the GA/GG genotype had a 2.63-fold increased risk of NIHL (95% CI: 1.12- 6.14). When the CNE was ≤ 98 dB(A), compared with cases with the TT genotype of rs11004085, individuals with the CC/CT genotype had a 2.96-fold increased risk of NIHL (95% CI: 1.33- 6.56). However, these differences were not significant after Bonferroni correction had been applied.@*Conclusions@#The results confirmed that genetic variation within the PCDH15 gene may affect the susceptibility to NIHL.
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Objective:To investigate association between genetic polymorphism in the grainyhead-like 2 gene (GRHL2)and noise-induced hearing loss (NIHL)in the Chinese population.Methods:A matched case-control association study was employed,In which,3 790 workers exposed to continuous and steady-state occupational noise in a steel factory participated.The questionnaires were adopted to col-lect individual features and audiometry tests performed.In the sstudy,286 subjects were diagnosed as ca-ses,Which were each designated on the basis of the matched criterion,and 286 paired samples were se-lected finally.Noise intensity was measured according to the standards given in ‘Measurement of Noise in the Workplace’(Occupational Health Standard of the People’s Republic of China,GBZ /T1 89.8 -2007).Cumulative noise exposure (CNE)was calculated,according to monitoring data on A-weighed sound pressure level and employment time.Genomic DNA was obtained from peripheral blood samples using 2 mL DNA extraction Kit following the manufacturer’s protocol.Five single nucleotide polymor-phisms (SNPs)of GRHL2 were genotyped by multiplex SNP genotyping kit.The continuous variables and categorical variables were analyzed by t-test and chi-square test respectively.Multivariate Logistic re-gression was used to test the association between genetic frequency and disease status,with adjustments for the possible confounding variables.The haplotypes were established and their frequencies in the two groups were assessed by haploview and phase softwares.Results:All the five SNPs (rs373571 3, rs3824090,rs373571 4,rs373571 5 and rs61 1 41 9)were in Hardy-Weinberg equilibrium (HWE)(P >0.05).The subjects carrying rs373571 5 GG genotype had a higher NIHL risk than those carrying the GA genotype under the co-dominant model (OR =0.644,95% CI:0.442 -0.939,P =0.022)after ad-justment for height,blood pressure,drinking status and smoking status.After being stratified by CNE,in the CNE ≥ 98 dB (A)group,rs373571 5 polymorphism was associated with the NIHL under the co-dominant model (OR =0.509,95% CI:0.281 -0.923,P =0.026)after adjustment for height,blood pressure,drinking status and smoking status as well.However,no statistical significant difference was found in variant genotypes of the other SNPs between the case and control subjects.Four-locus (rs373571 3,rs3824090,rs373571 4 and rs373571 5)haplotypes were constructed,and no risk or protec-tive haplotypes was identified.Conclusion:It is suggested that GRHL2 polymorphisms may be associated with development of NIHL.