[Research on early warning model of the hearing loss of workers exposed to noise].

Objective: To explore the change of hearing threshold of workers exposed to noise, establish an individual-based hearing loss early warning model, accurately and differentiated the health of workers exposed to noise. Methods: In September 2019, all physical examination data of 561 workers exposed to noise from an enterprise were collected since their employment. Three indicators of average hearing threshold of the better ear, namely, at high frequency, 4000 Hz and speech frequency, were constructed. The generalized estimating equation (GEE) was used to adjust gender and age and establish the warning model of each indicator. Finally, sensitive indicators and warning models were screened according to AUC and Yoden index. Results: Among the 561 workers exposed to noise, 26 (4.6%) workers had hearing loss. The sensitivity indicators were the average hearing threshold at speech frequency ≥20 dB, high frequency ≥30 dB and 4000 Hz ≥25 dB. The AUC of each index was 0.602, 0.794 and 0.804, and the Youden indexes were 0.204, 0.588 and 0.608, respectively. In GEE of hearing loss warning models, high-frequency hearing threshold ≥20 dB and 4000 Hz hearing threshold ≥25 dB were the optimal models, with AUC of 0.862. Conclusion: Combined with the changes of individual hearing threshold over the years, can accurately assess the risk of individual hearing loss of workers exposed to noise.

[Discussion on the application of ventilatory threshold in classification of physical workload in plateau].

Objective: To explore the application of the first ventilatory threshold (VT1) and the second ventilatory threshold (VT2) in the classification of physical workload for plateau workers, to provide reference for formulating the classification in plateau. Methods: In August 2018, 88 male workers from substations at different altitudes (500 m, 2000 m, 3000 m and 4000 m) of a company were selected as study subjects by cluster sampling. They were divided into plain group and plateau groups.The intensities of workload were simulated by power bicycle, and physiologic parameters, including VO(2), heart rate (HR) and energy metabolic rate per body surface area (E/BSA) , were recorded in test system when reaching VT1, VT2 and peak oxygen uptake (VO(2)Peak) . The ratios of VT1, VT2 and VO(2)Peak to the quiet and work potential at different altitudes were compared. Results: In a quiet state, compared with the plain group, the HR and E/BSA of the workers in the 2000 m and 3000 m groups increased, and the differences were statistically significant (P<0.05) . At VT2, compared with the plain group, the HR of the workers in the 4000 m group decreased, the difference was statistically significant (P<0.05) . VO(2) and E/BSA of workers in each plateau group were lower than those in the plain group at VO(2)Peak, and the differences were statistically significant (P<0.05) . At VT2 and VO(2)Peak, the ratios of VO(2), HR, and E/BSA relative to the quiet state of the workers in each plateau group were lower than those of the plain group, and the differences were statistically significant (P<0.05) . In the quiet state and VT1, compared with the plain group, the remaining percentages of VO(2) and E/BSA of workers in each plateau group decreased, and the differences were statistically significant (P<0.05) . Taking VT1, VT2 and VO(2)Peak as cut-off points and VO(2), HR and E/BSA as indicators, the physical workload in plateau could be divided into four levels, namely medium, heavy, extremely heavy and extreme physical workload. Conclusion: It is practicable to use ventilatory threshold to classification of physical workload. VT1 and VT2 can be applied to the classification in plateau to supplement and optimize current national standard of physical workload.

A novel HER2 gene body enhancer contributes to HER2 expression.

The transcriptional regulation of the human epidermal growth factor receptor-2 (HER2) contributes to an enhanced HER2 expression in HER2-positive breast cancers with HER2 gene amplification and HER2-low or HER2-negative breast cancers following radiotherapy or endocrine therapy, and this drives tumorigenesis and the resistance to therapy. Epigenetic mechanisms are critical for transcription regulation, however, such mechanisms in the transcription regulation of HER2 are limited to the involvement of tri-methylated histone 3 lysine 4 (H3K4me3) and acetylated histone 3 lysine 9 (H3K9ac) at the HER2 promoter region. Here, we report the identification of a novel enhancer in the HER2 3' gene body, which we have termed HER2 gene body enhancer (HGE). The HGE starts from the 3' end of intron 19 and extends into intron 22, possesses enhancer histone modification marks in specific cells and enhances the transcriptional activity of the HER2 promoters. We also found that TFAP2C, a known regulator of HER2, binds to HGE and is required for its enhancer function and that DNA methylation in the HGE region inhibits the histone modifications characterizing enhancer and is inversely correlated with HER2 expression in breast cancer samples. The identification of this novel enhancer sheds a light on the roles of epigenetic mechanisms in HER2 transcription, in both HER2-positive breast cancer samples and individuals with HER2-low or HER2-negative breast cancers undergoing radiotherapy or endocrine therapy.

Risk factors for respiratory failure with tetraplegia after acute traumatic cervical spinal cord injury.

OBJECTIVE: To analyze risk factors for respiratory failure with tetraplegia after acute traumatic cervical spinal cord injury (CSCI). PATIENTS AND METHODS: Total 180 tetraplegia cases after acute traumatic CSCI treated in Shanghai Changzheng Hospital from 2001 to 2011 were reviewed retrospectively and the frequency of respiratory failure in these patients were analyzed against the factors including age, gender, cause of injury, level/severity of injury, high-dose methylprednisolone (MP) therapy, and surgery intervention, using Chi-square test to look into the correlations of the prevalence of respiratory failure to those factors. RESULTS: Of the 180 tetraplegia with acute traumatic CSCI, 29 patients (16.11%) developed respiratory failure. The factors, including age, level and severity of injury, high-dose MP therapy, and surgery intervention, were found to significantly correlate with the appearance of respiratory failure in tetraplegia after acute traumatic CSCI (p < 0.05), while no significant correlation was found between the other factors: gender and cause of injury and the frequency of respiratory failure. CONCLUSIONS: Age, level/severity of injury, high-dose MP therapy, and surgery intervention are the four major relevant factors of respiratory failure in patients with acute traumatic CSCI. The appropriate and timing treatments involving high-dose MP therapy and surgical decompression and reconstruction can substantially increase the rates of clinical improvements and reduce the frequency of respiratory failure.

Occurrence of Grapevine Leafroll-Associated Viruses in China.

To characterize the prevalence of viruses associated with grapevine leafroll disease in China, 249 grapevine (Vitis spp.) samples (86 popular cultivars and a rootstock) from 19 provinces and regions were collected and tested for Grapevine leafroll-associated virus 1 (GLRaV-1), GLRaV-2, GLRaV-3, GLRaV-4, and GLRaV-4 strain 5 by SYBR Green real-time reverse-transcription polymerase chain reaction (RT-PCR), and RT-PCR and sequencing. GLRaV-3 was found in 100% of the samples while GLRaV-1, GLRaV-2, and GLRaV-4 were detected in 24.9% (62/249), 15.3% (38/249), and 0.80% (2/249) of the samples, respectively. Single infections with GLRaV-3 were found in 66.3% (165/249) of the samples, and the remaining samples were mixed infections of GLRaV-3 with one or two other GLRaVs, those with GLRaV-1 being the most common (18.5%, 46/249). The genetic variability of Chinese GLRaV-3 isolates was characterized based on the coat protein (CP) gene. In total, 153 full-length CP gene sequences (94 sequences newly generated) of Chinese GLRaV-3 isolates from different grapevine-growing regions showed 89.3 to 100.0% and 92.7 to 100.0% identity at the nucleotide and amino acid levels, respectively. The average nucleotide diversity for the population of Chinese GLRaV-3 isolates was estimated at 0.037 (standard error = 0.0032). GLRaV-3 isolates from China segregated into five distinct phylogenetic groups and two novel recombination events were found in the viral population. This is the first and most extensive report of the prevalent species of GLRaV in China, which also provides an assessment of genetic variability of GLRaV-3 Chinese isolates.

Abrogation of DNA vector-based RNAi during apoptosis in mammalian cells due to caspase-mediated cleavage and inactivation of Dicer-1.

RNA interference (RNAi) is used as a reverse-genetic tool to examine functions of a gene in different cellular processes including apoptosis. As key cellular proteins are inactivated during apoptosis, and as RNAi requires cooperation of many cellular proteins, we examined whether DNA vector-based RNAi would continue to function during apoptosis. The short hairpin RNA transcribed from the DNA vector is processed by Dicer-1 to form small interfering RNA that is incorporated in the RNA-induced silencing complex (RISC) to guide a sequence-specific silencing of the target mRNA. We report here that DNA vector-based RNAi of three different genes, namely poly(ADP-ribose) polymerase-1, p14(ARF) and lamin A/C are abrogated during apoptosis. The failure of DNA vector-based RNAi was not at the level of Ago-2 or RISC-mediated step of RNAi but due to catalytic inactivation of Dicer-1 on specific cleavage at the STTD(1476) and CGVD(1538) sites within its RNase IIIa domain. Using multiple approaches, caspase-3 was identified as the major caspase responsible for the cleavage and inactivation of Dicer-1. As Dicer-1 is also the common endonuclease required for formation of microRNA (miRNA) in mammalian cells, we observed decreased levels of mature forms of miR-16, miR-21 and let-7a. Our results suggest a role for apoptotic cleavage and inactivation of Dicer-1 in controlling apoptotic events through altered availability of miRNA.