Objective:To establish a method for the determination of 2-amino-5-chloro-N, 3-dimethylbenzamide in blood by ultra-performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS) .Methods:In October 2022, 200 μl of blood samples were taken and 800 μl of acetonitrile was added. The samples were centrifuged at 3500 r/min (with a centrifugation radius of 6.6 cm) for 15 minutes. The supernatant was detected in the positive ion target tandem mass spectrometry (Target MS 2) mode and quantified by the external standard method. Methodological validation was also carried out for the established method. Results:The working curve of 2-amino-5-chloro-N, 3-dimethylbenzamide showed good linearity in the concentration range of 2.07-165.44 μg/L, with a correlation coefficient ( r) of 0.9994. The intra-day and inter-day relative standard deviations ( RSD) for the detection of 2-amino-5-chloro-N, 3-dimethylbenzamide were 2.6%-3.0% and 3.1%-3.5%, respectively. Analytical accuracy of 2-amino-5-chloro-N, 3-dimethylbenzamide quantification ranged from 101.0 % to 108.4 %, and the limit of detection and limit of quantification were 0.11 μg/L and 0.36 μg/L, respectively. The blood samples were able to be stored at -20 ℃ for at least 7 days. Conclusion:The UPLC-Q-Orbitrap HRMS determination method is sensitive, efficient and accurate, and can be used for the determination of 2-amino-5-chloro-N, 3-dimethylbenzamide in blood.

Objective:To establish a method for the determination of 2-amino-5-chloro-N, 3-dimethylbenzamide in blood by ultra-performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS) .Methods:In October 2022, 200 μl of blood samples were taken and 800 μl of acetonitrile was added. The samples were centrifuged at 3500 r/min (with a centrifugation radius of 6.6 cm) for 15 minutes. The supernatant was detected in the positive ion target tandem mass spectrometry (Target MS 2) mode and quantified by the external standard method. Methodological validation was also carried out for the established method. Results:The working curve of 2-amino-5-chloro-N, 3-dimethylbenzamide showed good linearity in the concentration range of 2.07-165.44 μg/L, with a correlation coefficient ( r) of 0.9994. The intra-day and inter-day relative standard deviations ( RSD) for the detection of 2-amino-5-chloro-N, 3-dimethylbenzamide were 2.6%-3.0% and 3.1%-3.5%, respectively. Analytical accuracy of 2-amino-5-chloro-N, 3-dimethylbenzamide quantification ranged from 101.0 % to 108.4 %, and the limit of detection and limit of quantification were 0.11 μg/L and 0.36 μg/L, respectively. The blood samples were able to be stored at -20 ℃ for at least 7 days. Conclusion:The UPLC-Q-Orbitrap HRMS determination method is sensitive, efficient and accurate, and can be used for the determination of 2-amino-5-chloro-N, 3-dimethylbenzamide in blood.

Objective: To investigate the status of occupational health examination institutions in Zhejiang Province, so as to provide suggestions for quality control of occupational health examination institutions. Methods: The 312 occupational health examination institutions in Zhejiang Province that have completed filing before September 30, 2023 were selected. The comprehensive capability, service quality, technical capability, and information reporting status were surveyed and evaluated through on-site inspection and skill assessment. Results: There were 161 public hospitals (51.60%), 147 private organizations (47.12%), and 4 centers for disease control and prevention (CDCs)/ occupational disease prevention and control institutes (1.28%). The pass rates of comprehensive capability, service quality, technical capability and information reporting were 90.02%, 69.89%, 84.07% and 86.78%, respectively. Among the indicators of comprehensive capability, the compliance rate for staffing was the highest at 95.06%, while the qualification rate of quality control in occupational health examinations was the lowest at 84.83%. Among the indicators of service quality, the compliance rate of the physical examination report format was the highest at 95.83%, while the accuracy rate of the audiometry examination was the lowest at 76.60%. In terms of technical capabilities, the qualification rates for blood lead testing, pneumoconiosis reading, and audiogram diagnostic ability were 87.92%, 89.42% and 75.34%, respectively. In terms of information reporting, the qualification rates for reporting completeness, reporting timeliness, suspected occupational disease reporting timeliness, and reporting accuracy were 89.10%, 81.09%, 96.47% and 80.45%, respectively. Among the three types of institutions, private institutions had the lowest average qualification rates for comprehensive capability, service quality, and technical capability, which were 89.83%, 69.06% and 80.00%, respectively. Conclusions Public hospitals and private organizations were the main types of occupational health examination institutions in Zhejiang Province. However, there were deficiencies in quality control, audiogram examination and diagnosis, and the accuracy of information reporting among occupational health examination institutions.

Background Noise is the most common occupational hazard in the automobile manufacturing industry with the most workers exposed. Automobile manufacturing industry is a high-risk industry for noise-induced hearing loss. Objective To understand the epidemiological characteristics of noise-induced hearing loss among workers in automobile manufacturing industry and explore related influencing factors. Methods A questionnaire survey, individual noise recording, and pure tone audiometry were conducted among workers (n=656) exposed to noise from five automobile manufacturing enterprises. The data on age, sex, exposure duration, noise intensity, kurtosis, and hearing loss were obtained. The positive rates of high-frequency noise-induced hearing loss (HFNIHL) and speech-frequency noise-induced hearing loss (SFNIHL) were calculated, and each factor was compared between workers with and without HFNIHL. Chi-square test and analysis of trend were conducted among different groups of age, sex, exposure duration, A-weighted equivalent continuous sound pressure level normalized to a nominal 8-hour working day (L_Aeq,8h), and kurtosis. Logistic regression analysis was conducted to analyze the factors influencing the positive rates of HFNIHL and SFNIHL. Results The exposure rates of non-Gaussian noise was 73.6%. The positive rates of HFNIHL and SFNIHL were 32.6% (214 workers) and 6.7% (44 workers), respectively. The HFNIHL workers showed older age, higher proportion of male, longer exposure duration, higher noise intensity (L_{Aeq,8 h}), and increased kurtosis than those without HFNIHL (P<0.05). The positive rates of HFNIHL increased with the increase of age, exposure duration, L_{Aeq,8 h}, and kurtosis (\begin{document}$ {\chi ^2} $\end{document}_trend-age=49.25, P<0.001; \begin{document}$ {\chi ^2} $\end{document}_{trend-duration}=22.19, P<0.001; \begin{document}$ {\chi ^2} $\end{document}_trend-LAeq=6.91, P=0.009; \begin{document}$ {\chi ^2} $\end{document}_{trend-kurtosis}=8.56, P=0.003). The results of logistic regression showed that age (OR=2.13, 95%CI: 1.67-2.71, P<0.001), sex (OR=2.29, 95%CI: 1.44-3.62, P<0.001), exposure duration (OR=1.43, 95%CI: 1.11-1.85, P=0.006), L_Aeq,8h (OR=1.37, 95%CI: 1.08~1.76, P=0.011), and kurtosis (OR=1.37, 95%CI: 1.14-1.63, P=0.001) were factors associated with the risk of HFNIHL, while only age was associated with the risk of SFNIHL (OR=2.15, 95%CI: 1.33-3.33, P=0.001). Conclusion Workers exposed to noise in automobile manufacturing industry are at a high risk of hearing loss. Age, sex, exposure duration, L_{Aeq,8 h}, and kurtosis are key influencing factors of hearing loss.

The existing measuring methods of noise exposure on the basis of equal energy hypothesis are applicable to Gaussian noise while not fully applicable to non-Gaussian noise. Studies have shown that temporal structure (kurtosis) combined with noise energy has the potential to quantify non-Gaussian noise exposure effectively. However, there is no unified measuring method adopting this joint metric. In this paper, the measuring method of non-Gaussian noise exposure based on kurtosis adjustment was introduced, detailing measurement indicators, adjustment schemes, applicable objects, instrument requirements, and measurement steps. Adjusting the exposure duration of cumulative noise exposure (CNE) by kurtosis or adjusting the equivalent continuous A-weighted sound pressure level (L_Aeq) by an adjustment coefficient based on animal or population studies can more accurately quantify workers' exposure to non-Gaussian noise and improve the underestimation of hearing loss caused by non-Gaussian noise. A large number of population studies are warranted in the future to verify the effectiveness of these two adjustment schemes.

Background Occupational noise-induced hearing loss (NIHL) is one of the most prevalent occupational diseases in the world. With the development of industry, noise sources in the workplace have become increasingly complex. Objective To apply kurtosis-adjusted cumulative noise exposure (CNE) to assess the occupational hearing loss among furniture manufacturing workers, and to provide a basis for revising noise measurement methods and occupational exposure limits in China. Methods A cross-sectional survey was conducted to select 694 manufacturing workers, including 542 furniture manufacturing workers exposed to non-Gaussian noise, and 152 textile manufacturing workers and paper manufacturing workers exposed to Gaussian noise. The job titles involving non-Gaussian noise were gunning and nailing, and woodworking, while those involving Gaussian noise were weaving, spinning, and pulping. High frequency noise-induced hearing loss (HFNIHL) and noise exposure data were collected for each study subject. Noise energy metrics included eight-hour equivalent continuous A-weighted sound pressure level (L_{Aeq,8 h}) and CNE. Kurtosis was a noise temporal structure metric. Kurtosis-adjusted CNE was a combined indicator of noise energy and temporal structure. Results The age of the study subjects was (35.64±10.35) years, the exposure duration was (6.71±6.44) years, and the proportion of males was 75.50%. The L_{Aeq,8 h} was (89.43±6.01) dB(A). About 81.42% of the study subjects were exposed to noise levels above 85 dB(A), the CNE was (95.85±7.32) dB(A)·year, with a kurtosis of 99.34 ± 139.19, and the prevalence rate of HFNIHL was 35.59%. The mean kurtosis of the non-Gaussian noise group was higher than that of the Gaussian noise group (125.33±147.17 vs. 5.86±1.94, t=−21.04, P<0.05). The results of binary logistic regression analysis showed that kurtosis was an influential factor of workers' HFNIHL after correcting for age, exposure duration, and L_{Aeq,8 h} (OR=1.49, P<0.05). The results of multiple linear regression analysis showed that the effects of age, exposure duration, L_{Aeq,8 h}, and kurtosis on noise-induced permanent threshold shift at frequencies of 3, 4, and 6 kHz of the poor hearing ear were statistically significant (all P<0.05). The results of chi-square trend analysis showed that when CNE ≥ 90 dB(A)·year, the HFNIHL prevalence rate elevated with increasing kurtosis (P<0.05). The mean HFNIHL prevalence rate was higher in the non-Gaussian noise group than in the Gaussian noise group (31.7% vs. 22.0%, P<0.05). After applying kurtosis-adjusted CNE, the linear equation between CNE and HFNIHL prevalence rate for the non-Gaussian noise group almost overlapped with that for the Gaussian noise group, and the mean difference in HFNIHL prevalence rate between the two groups decreased from 9.7% to 1.4% (P<0.05). Conclusion Noise kurtosis is an effective metric for NIHL evaluation. Kurtosis-adjusted CNE can effectively evaluate occupational hearing loss due to non-Gaussian noise exposure in furniture manufacturing workers, and is expected to be a new indicator of non-Gaussian noise measurement and assessment.

Background Non-Gaussian noise has become the dominant noise type in industry. However, the epidemiological characteristics of non-Gaussian noise exposure and associated noise-induced hearing loss (NIHL) are still unclear. Objective To summarize the epidemiological characteristics of NIHL associated with non-Gaussian noise in manufacturing industry in China and provide a basis for the early prevention and control of occupational hearing loss. Methods Chinese and English literature on hearing loss associated with non-Gaussian noise in China were retrieved. The overall prevalence was calculated based on the prevalence data provided by each included study. A meta-analysis of studies with Gaussian noise as a control group was also performed and the overall weighted odds ratio (OR) was calculated to compare the effects of non-Gaussian noise and Gaussian noise on hearing loss. Publication bias was evaluated by funnel plot and Egger regression, and a sensitivity analysis was performed by eliminating references in turn. Results A total of 37 cross-sectional studies involving 25 055 Chinese manufacturing workers exposed to non-Gaussian noise were included, 92.5% of whom were male. These workers aged (32.7±9.6) years were exposed to non-Gaussian noise at (87.0±4.2) dB(A) for (6.8±4.9) years. The mean cumulative noise exposure (CNE) was (95.9±8.0) dB(A)·year. The prevalence rate of high-frequency NIHL (HFNIHL) and speech-frequency NIHL (SFNIHL) were 29.0% and 14.2%, respectively. The results of the meta-analysis treating 19 cross-sectional studies with Gaussian noise as a control group showed that there were no significant differences in age, exposure duration, and equivalent continuous A-weighted sound pressure level (L_Aeq), and CNE between the non-Gaussian noise group and the Gaussian noise group. The overall weighted OR of HFNIHL was 1.87 (95%CI: 1.46−2.41), which was statistically significant. The funnel plot showed good symmetry and the result of Egger regression was t=−0.11, P=0.910 (>0.05), suggesting a low risk of publication bias in this meta-analysis. The sensitivity analysis showed no significant changes of results after eliminating references in turn, indicating that the results were robust. Conclusion Chinese manufacturing workers, mainly young adult males, are exposed to non-Gaussian noise at high levels for a long time and have a high prevalence of NIHL. Compared to workers exposed to Gaussian noise, those exposed to non-Gaussian noise suffer from more serious hearing loss.

OBJECTIVE: To explore the molecular basis for a rare case with Para-Bombay AB blood type. METHODS: Serological method was used to determine the blood type of the proband. Exons 6 and 7 of the ABO gene and the coding regions of FUT1 and FUT2 genes were analyzed by direct sequencing. RESULTS: Serological results showed that the proband was a Para-Bombay AB subtype. His genotype was determined as ABO*A1.02/B.01. The proband was also found to harbor c.551-552delAG and c.881-882delTT of the FUT1 gene. For his four children, there were three type B and one type A, though the expression of the H type was normal. CONCLUSION The double deletions in the coding region of the FUT1 gene probably underlay the Para-Bombay blood type in the proband. Carrier of single-strand deletions may have a normal ABO phenotype.
ABO Blood-Group System/genetics* ; Alleles ; Fucosyltransferases/genetics* ; Genotype ; Humans ; Male ; Phenotype ; Sequence Analysis

Objective To evaluate the effect of compound glycyrrhizin on the prevention and cure of cytarabine syndromes. Methods A total of 130 patients with hematological malignancies treated by moderate or high dose of cytarabine in the 303th Hospital of PLA from July 2010 to July 2016 were included. Patients were randomly divided into the control group and the experiment group by using random number table method, and each group had 65 patients. In the control group, patients were treated with cytarabine alone. In the experiment group, patients were treated with cytarabine plus compound glycyrrhizin. Skin rash and fever in patients of the two groups were also recorded. Results of blood routine tests, liver and kidney function tests were monitored during the treatment. Results Sixty-one patients in the experiment group and 63 patients in the control group were enrolled finally. In experiment group and control group, the differences in the incidence of cytarabine syndromes [8.2 % (5/61) vs. 41.3 % (26/63), χ2＝ 18.1, P < 0.001], skin rash [1.6 % (1/61) vs. 12.7 % (8/63), χ2＝16.3, P <0.001], and fever [6.6 % (4/61) vs. 36.5 % (23/63), χ2＝5.63, P <0.017] were statistically significant. There was no significant difference of the incidence of liver injury and minimum blood cell count between the two groups (P＞ 0.05). Conclusion Compound glycyrrhizin can effectively reduce the incidence of cytarabine syndromes, but the larger size and multiple center studies are needed to further verify the effect.

Objective To explore the role of σ1 receptor (σ1R) in the clinical prognosis of cervical cancer,and provide a theoretical basis for σ1R targeted molecular therapy through observing the inhibition of synthetic σ1R-specific ligand compounds on the growth of cervical cancer cells. Methods (1) Immunohistochemical or immunocytochemistry staining were respectively used to detect the expression and localization of σ1R protein.(2)The Cancer Genome Atlas (TCGA) data set was used to validate our results. (3)Two series of 4 novel σ1R ligand compounds were synthesized by altering the N-terminal substituents on the piperidine ring of the prezamicol analogue, named as 14a, 14e, 15c and 15f. Methyl thiazolyl-tetrazolium (MTT) assay was detect the anti-proliferative effect of the four compounds on HeLa and SiHa cells. Compound 14a with potent inhibitory activity and the highest specificity of σ1R was selected for further experiments. Scratch test was observed the migration effect of compound 14a on HeLa and SiHa cells. Flow cytometry was determined cell cycles and apoptosis. Results (1) Immunostaining of σ1R protein was located in the cytoplasm and nucleus of cervical epithelium. The expression of cervical squamous cell carcinoma (SCC) was significantly higher than those of high-grade squamous intraepithelial lesion (HSIL) or normal cervical tissues. There was no significant difference in the expression of σ1R between HSIL and normal cervical tissues. σ1R expression in cervical adenocarcinoma (AC) was higher than that in SCC (P=0.020). The nuclear expression rate of σ1R in AC (10/18) was higher than that of SCC (27.1%, 19/70; P=0.024). The median overall survival (MOS) of σ1R-positive SCC patients was lower than that of σ1R-negative patients [(45.8±3.1) vs (51.7±2.9) months, P=0.045]. MOS of the patients with σ1R nuclear positive SCC was lower than that of non-nuclear staining [(38.9±3.8) vs (48.7±2.1) months, P=0.022]. MOS of the patients with σ1R nuclear positive AC was lower than that of non-nuclear staining [(35.0± 6.3) vs (44.2±4.2) months, P=0.034]. (2) Analysis of TCGA data showed that σ1R expression of in SCC was correlated with age (P=0.005). σ1R expression in AC was significantly associated with advanced stage, lymphnode metastasis and vascular invasion (all P<0.05). MOS of AC patients with σ1R overexpression was significantly lower than that of the patients with low expression (P=0.034). There was no significant difference in the MOS of different expression of σ1R mRNA in SCC patients(P=0.930). (3) MTT assay showed that these four compounds could suppressed the growth of HeLa and SiHa cells in time- and dose-dependent manner. The growth inhibition rates of HeLa and SiHa cells at 48 hours treated by combination of different concentrations of nedaplatin (NDP) with compound 14a (6 μmol/L) were significantly higher than those treated by NDP alone. Compound 14a (30 μmol/L) significantly inhibited the migration (both P<0.01) and induced the apoptosis of HeLa or SiHa cells (both P<0.01). Conclusions σ1R is over-expressed in cervical cancer and HSIL. σ1R nuclear expression is an important marker of AC. σ1R over-expression, especially σ1R nuclear expression is associated with the poor prognosis of cervical cancer. Our study is mostly consistent with cervical cancer data of TCGA. These results suggest that the novel synthetic prezamicol analogues 14a for σ1R could inhibit the growth of cervical cancer cells and cell migration through inducing apoptosis and arresting cell cycle in G0/G1 period, enhance NDP-induced cytotoxicity.