Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

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 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 evaluate the effect of imatinib on growth impairment in children with chronic myeloid leukemia (CML-CP) in the chronic phase.Methods:From July 2018 to July 2019, questionnaires were distributed to CML children aged <18 years at the time of diagnosis who were receiving imatinib for at least 3 months or to their parents in China. The height-for-age standard deviation score (HtSDS) and the difference of standard deviation integral (△HtSDS) were used to explore the change in height with imatinib therapy.Results:The data of 238 respondents were included; 138 (58.0% ) respondents were men. The median age at the first diagnosis of CML was 11.0 years (range, 1.4-17.9 years) , and 93 (39.0% ) respondents were at the prepuberty stage. At the time of completing the questionnaires, the median age was 15.0 years (range, 2.0-34.0 years) . The median duration of imatinib therapy was 28 months (range, 3-213 months) . Among all the respondents, the mean HtSDS when completing the questionnaires (-0.063±1.361) was significantly lower than that at the time of starting imatinib treatment (0.391±1.244) ( P<0.001) . Total 71.0% respondents showed growth impairment that was more common in those starting imatinib therapy at prepubertal age than in those starting at pubertal age. Multivariate analysis showed that younger at the start of imatinib therapy ( P<0.001) and longer duration of imatinib therapy ( P<0.001) were significantly associated with severe growth impairment on imatinib therapy. Conclusions:Imatinib induced growth impairment in children with CML-CP. Younger the age of initiation and longer the duration of imatinib therapy, more obvious the effect of imatinib on growth impairment.

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 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 analyze the incidence rate of occupational noise-induced hearing loss in noise-exposed workers in an iron and steel plant from 2006 to 2015. Methods: Using a cohort study method, workers exposed to occupational noise from Jan 1, 2006 to Dec 12, 2015 were followed up and the pure tone hearing test was conducted. In total, 6 297 subjects completed two or more physical checks and the pure tone hearing test and were included in the analysis. The noise exposure level at the workplace and the equivalent continuous A-weighted sound pressure level for workers was monitored and the cumulative noise exposure dose was evaluated. The subjects were divided into low, middle and high exposure groups according to the noise exposure level, and the equivalent continuous A-weighted sound pressure level for 8 hours for each group was 80.6-85.0, 85.1-90.0 and 90.1-103.4 dB (A), respectively. While the RR and 95% CI were derived from unconditional logistic regression models. In logistic regression analysis, confounding factors such as age, gender, smoking habit, drinking habit, high temperature exposure and chemical hazards exposure level were controlled. Results: During the follow-up period, 392 cases of occupational noise-induced hearing loss were diagnosed among the 6 297 subjects, with an incidence rate of 6.23%; 318 cases of high-frequency hearing loss were diagnosed, with an incidence rate of 5.05%; and 74 cases of occupational noise-induced deafness were diagnosed, with an incidence rate of 1.18% . The incidence rates of hearing loss among the high, medium and low exposure groups were 9.22% (158/1 737), 6.49% (204/3 142) and 2.08% (30/1 442), respectively; the rates of high-frequency hearing loss were 7.41% (127/1 737), 5.25% (165/3 142) and 1.80% (26/1 442), respectively; and the rates of occupational noise-induced deafness were 1.81% (31/1 737), 1.24% (39/3 142) and 0.28% (4/1 442), respectively. For the groups corresponding to cumulative noise exposure doses of ≤84.99, 85.00- 87.99, 88.00- 90.99, 91.00- 93.99, 94.00- 96.99, 97.00- 100.99, 101.00- 102.99 and ≥103.00 dB (A) · year, the incidence rates of hearing loss were 0 (0/185), 1.22% (2/164), 2.52% (17/674), 3.83% (35/913), 5.80% (106/1 827), 6.02% (67/1 113), 9.20% (95/1 003) and 18.04% (70/388), respectively. Compared with the low exposure group, the RR of hearing loss, high-frequency hearing loss and occupational noise-induced deafness for the high exposure group were 4.78 (95% CI: 3.22- 7.11), 4.36 (95% CI: 2.84- 6.69) and 6.63 (95% CI: 2.33- 18.82), respectively; and for the medium exposure group were 3.27 (95% CI: 2.22-4.82), 3.02 (95% CI: 1.99-4.59) and 4.52 (95% CI: 1.61-12.67), respectively. Conclusion The incidence rate of hearing loss for workers exposed to noise in an iron and steel plant was related to the cumulative noise exposure dose, gender, age, educational level, smoking habits, drinking habits and exposure to high temperature.

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 SNPscan^TM 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.