Background Kurtosis reflecting noise's temporal structure is an effective metric for evaluating noise-induced hearing loss (NIHL), and its threshold is still unclear. Objective To explore the energy range of kurtosis and the threshold of NIHL induced by kurtosis in this energy rangeMethods Using cross-sectional design, 4631 noise-exposed workers in manufacturing industry were selected. The hearing loss and noise exposure data of each worker were collected. Logistic regression model was used to establish the dose-response relationship between noise exposure and hearing loss and estimate the range of energy effects. Restricted cubic spline model was utilized to analyze the dose-response relationship curves of kurtosis to noise-induced hearing loss (NIHI) and high-frequency noise-induced hearing loss (HFNIHL) under different 8 h equivalent sound levels (L_{EX,8 h}), as well as to estimate the kurtosis effect threshold. Results The logistic regression model analysis showed that the prevalence of NIHI and HFNIHL increased significantly with increase of L_{EX,8 h} for steady noise; when L_{EX,8 h} of non-steady noise was 80-100 dB(A), the risk of hearing loss increased with an increase in kurtosis (P<0.05). The restricted cubic spline model showed that when L_{EX,8 h} of non-steady noise was 0-80 dB(A) or >100 dB(A), there was no significant relationship between kurtosis and NIHI or HFNIHL. When L_{EX,8 h} was 80-100 dB(A), there was a significant nonlinear dose-response relationship between kurtosis and NIHL or HFNIHL (P <0.001), and kurtosis > 28.08 exerted effect in elevating NIHI or HFNIHL. Conclusion The effect threshold of kurtosis on NIHL is 28.08 when non-steady noise levels are in the range of 80-100 dB(A). The effect threshold of kurtosis needs further verification.

Background Temporal kurtosis (without frequency weighting, i.e., Z-weighted kurtosis) can evaluate noise-induced hearing loss (NIHL). However, few studies have considered the function of frequency weighting (A- or C-weighted) kurtosis on NIHL. Objective To study the significance of A- and C-weighted kurtosis adjustment for equivalent sound level (L'_{EX,8 h}) in evaluating occupational hearing loss. Methods A cross-sectional survey was used to select 973 noise-exposed workers in seven industries as the subjects. The noise exposure of all workers was assessed by distributions of A-, C-, and Z-weighted kurtosis (e.g., K_A, K_C, and K_Z) and respective adjusted equivalent sound level (e.g., L'_{EX,8 h}-K_A, L'_{EX,8 h}-K_C, and L'_{EX,8 h}-K_Z). The significance of A- and C-weighted kurtosis in evaluating NIHL was evaluated by correlations between three types of L'_{EX,8 h} and NIHL, and improvement of noise-induced permanent threshold shift (NIPTS) underestimation predicted by the ISO prediction model (Acoustics—Estimation of noise-induced hearing loss, ISO 1999-2013). Results The median K_A, K_C, and K_Z were 68.33, 28.22, and 19.82, respectively. The binary logistic regression showed that L_{EX, 8 h}-K_A, L_{EX, 8 h}-K_C, and L'_{EX, 8 h}-K_Z were risk factors for NIHL (OR>1, P<0.001). The receiver operating characteristic (ROC) curve showed that when the outcome variable was noise-induced hearing impairment (NIHI), the areas under the curves corresponding to L'_{EX,8 h}-K_A, L'_{EX,8 h}-K_C, and L'_{EX,8 h}-K_Z were 0.625, 0.628, and 0.625, respectively. When the outcome variable was high-frequency noise-induced hearing loss (HFNIHL), the areas under the curves corresponding to L'_{EX,8 h}-K_A, L'_{EX, 8 h}-K_C, and L'_{EX,8 h}-K_Z were 0.624, 0.623, and 0.622, respectively (P<0.05). The order of underestimation improvement values predicted by L'_{EX,8 h} for NIPTS₁₂₃₄ was: L'_{EX,8 h}-K_A (4.68 dB HL)>L'_{EX,8 h}-K_C (4.38 dB HL)>L'_{EX,8 h}-K_Z (4.28 dB HL) (P<0.001). The order of underestimation improvement values predicted by L'_{EX,8 h}-K for NIPTS₃₄₆ was: L'_{EX,8 h}-K_A (7.20 dB HL)>L'_{EX,8 h}-K_C (6.83 dB HL)>L'_{EX,8 h}-K_Z (6.71 dB HL) (P<0.001). Conclusion The adjustment of A- and C-weighted kurtosis to equivalent sound level L_{EX,8 h} can effectively improve the accuracy of the ISO 1999 prediction model in NIPTS prediction, and compared with the C-weighted, the A-weighted kurtosis can improve the result of the ISO 1999 prediction model in terms of underestimating NIPTS.

background Current assessment of noise-induced hearing loss relies on the hearing threshold statistical distribution table of ISO 7029-2017 standard (ISO 7029), which is based on foreign population data and lacks a hearing threshold distribution table derived from pure-tone audiometry data of the Chinese population, hindering accurate evaluation of hearing loss in this group. Objective To establish a statistical distribution table of hearing threshold level (HTL) for otologically normal Chinese adults and to provide a scientific basis for revising the diagnostic criteria of occupational noise-induced deafness in China. Methods A total of 1271 otologically normal Chinese adults aged 18-60 years were divided into four groups with 10-year age intervals. Based on the pure tone audiometry data and power function operation formula, the relevant parameters of the median and percentile calculation formula of ISO 7029 were adjusted. Based on the adjusted parameters, a statistical distribution table of HTL of normal Chinese adults in otology was preliminarily constructed according to the calculation formula of ISO 7029. A nonparametric rank sum test was used to compare the difference between the adjusted median deviation value and the ISO 7029 calculation. Results Except for a few frequencies (2000, 3000, and 8000 Hz), the value of parameter α adjusted for the auditory threshold deviation of the Chinese population (α_CHN-md) increased with the increase of frequency, while the value of parameter β adjusted for the auditory threshold deviation of the Chinese population (β_CHN-md) decreased with the increase of frequency. The preliminary distribution table of otologically normal Chinese adults' median hearing threshold deviation (ΔH_CHN-md) showed that the hearing threshold deviation increased with age and frequency. At 8000 Hz, the increase in ΔH_CHN-md with age was the greatest for both men and women, from 0 dB to 23 dB and 21 dB respectively. The minimal threshold elevation was noted at 500, 1000, and 2000 Hz, which increased from 0 dB to 2 dB. In otologically normal Chinese adults, the maximum increase of ΔH_CHN-md with frequency was observed at age of 50 years, which increased from 2 dB at 500 Hz to 23 dB at 8000 Hz in men and from 2 dB at 500 Hz to 21 dB at 8000 Hz in women. The comparison results with the ISO 7029 calculation showed that the trend was consistent. The median hearing threshold deviation value of the adjusted Chinese population was lower than that of the ISO 7029 calculation (ΔH_md). However, they had no significant statistical difference (P>0.05). For otologically normal normal Chinese men and women, the maximum difference of ΔH_md between the 50-year-old group and the ISO calculation at 8000 Hz was 7 dB and 9 dB, respectively. Conclusion This preliminary analysis of hearing threshold deviations in otologically normal Chinese adults suggests that current standards may potentially underestimate hearing loss at frequencies below 8000 Hz while possibly overestimating it at 8000 Hz. These findings require further validation through expanded sample sizes to more accurately assess the characteristics of hearing thresholds in the Chinese population and their discrepancies with existing standards.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective The objective of this study is to examine the expression level of the S100A7A protein in both gastric cancer tissues and cells,as well as to evaluate its impact on the malignant phenotype of gastric cancer(GC)cells.Methods Immunohistochemical assay was used to detect the expression characteristics of S100A7A in 21 gastric cancer tissues and their corresponding paracancerous tissues,as well as to investigate its correlation with gastric cancer clinicopathological factors.Gastric cancer cells were genetically modified to overex-press S100A7A through plasmid transfection.Subsequently,the impact of S100A7A on the proliferation,migra-tion,and invasion capacities of gastric cancer cells was assessed using cell proliferation assays(EdU assay and plate cloning assay)as well as cell migration and invasion assays(Transwell assay and scratch assay).Results The expression of S100A7A protein was higher in GC tissues than in paracancerous tissues;Overexpression of S100A7A may increase gastric cancer cell proliferation,migration,and invasion.Conclusion S100A7A is a possible oncogene in GC and is predicted to serve as a new diagnostic and therapeutic target for the disease.

ObjectiveTo systematically review the efficacy and safety of exosomes derived from bone marrow mesenchymal stem cells (BMSC) on animal models of spinal cord injury. MethodsAnimal studies about BMSC-derived exosomes for spinal cord injury were retrieved from databases of PubMed, Cochrane Library, Web of Science, CNKI and Wangfang Data, from establishment to October, 2021. Two researchers independently screened and extracted the data, and evaluated the risk of bias. The studies were qualitatively analyzed. ResultsA total of 21 studies were included, involving 1 342 animals. Male or female Sprague-Dawley rats were selected for 18 studies, and the body mass of the rats was (200±50) g in 19 studies. The injury nodes focused on T_9-11 spinal cord, with various methods. The types, medication time, frequency, concentration and dose of the exosomes were heterogeneous. ConclusionsThe BMSC-derived exosomes can improve the motor function after spinal cord injury, reduce the damage of spinal cord, resist apoptosis and inflammation, reduce the permeability of blood-spinal cord barrier, and promote the growth of axons and blood vessels. More high-quality studies are needed for further verification.

Objective To compare the difference in the effects on liver function between transjugular intrahepatic portosystemic shunt (TIPS) alone and the combination of TIPS and left gastric vein embolization (LGVE) in patients with liver cirrhosis.Methods This research was a retrospective study.From September 2014 to September 2015,31 patients with liver cirrhosis underwent TIPS (TIPS group) and 29 patients with liver cirrhosis underwent TIPS combined with LGVE (TIPS+LGVE group) were enrolled.The data of the liver function of patients before and after operation were collected and the Child-Pugh score and model for end-stage liver disease (MELD) were also calculated.Student's t test and chi-squared test were performed for statistical analysis.Results The preoperative portal vein pressures of TIPS group and TIPS+LGVE group were (28.48±2.77) mmHg (1 mmHg=0.133 kPa) and (28.38± 2.92) mmHg,respectively.And after operation,the portal vein pressures decreased to (17.81 ± 1.47) mmHg and (17.97 ± 2.04) mmHg,respectively,and the differences were both statistically significant (t=18.908 and 11.648,both P＜0.01).At 12 months after operation,Child-Pugh score of TIPS+ LGVE group was 5.69 ± 1.19,which was significantly lower than that before operation (7.03±1.76),and the difference was statistically significant (t=3.398,P=0.001),which was also lower than that of TIPS group at the same time point (6.52 ± 1.54),and the difference was statistically significant (t =2.303,P=0.025).At 12 months after operation,the component ratio of patients with Child-Pugh grade A of TIPS±LGVE group was 89.7％ (26/29),which was higher than that before operation (44.8％,13/29),and the difference was statistically significant (x2=13.228,P＜0.01).The component ratio of patients with Child-Pugh grade B was 6.9 ％ (2/29),which was lower than that before operation (41.4 ％,12/29),and the difference was statistically significant (x2 =9.416,P＜ 0.01).Conclusions TIPS significantly reduces portal vein pressure in patients with liver cirrhosis and it does not deteriorate liver function of patients in the long term.The combination of TIPS and LGVE is better than TIPS alone in improving liver function in patients with liver cirrhosis,especially in improvig long-term liver function in patients of Child-Pugh A and B grade.

Objective:To detect and verifica the gene profile difference of microRNA-146a (miR-146a) and its role in the pro-liferation of vascular smooth muscle cells (VSMCs) by gene chip technology. Methods: Artificially synthesized miR-146a mimics(50 nmol/L) ,miR-146 inhibitor ( 50 nmol/L ) , scramble ( 50 nmol/L ) and PBS were transfected into cultured primary rat VSMCs in vitro. After transfection,Real time PCR was used to measure the levels of miR-146a and the cell counting kit 8(CCK8) was employed to investigate the proliferation of VSMCs. The VSMCs interfered by miR-146a inhibitor or miR-146a control were examined by gene chips and the profile of gene were analyzed by bioinformatics technology to detect the different genes and signal transduction pathway. The changes in mRNAs and proteins were accessed separately by Real time PCR and Western blot. Results: Compared with sham and control VSMCs,miR-146a expression level was significantly decreased in treatment with miR-146a inhibitor(P<0. 01),as well as optical density(OD) was also shown remarkably down regulated simultaneously(P<0. 05). The investigation of gene profile revealed that the p53 signal pathway was up-regulated in VSMCs interfered by miR-146a. The mRNA and protein expression levels of p53, caspase3 and PTEN in p53 signal transduction pathway didn′t show significant differences(P>0. 05),however,the mRNA and protein expression levels of cyclin D1 significantly increased in treatment with miR-146a mimics VSMCs group and decreased in miR-146a inhibitor VSMCs group ( compared with sham VSMCs group, both P<0. 05 ) . Conclusion: Our data indicated that miR-146a may promote the proliferation of rat VSMCs by up-regulating cyclin D1 expression.

Objective To investigate the effect of triptolide on asthmatic airway remodeling and signal transducer and activator of transcription 6 (STAT6), acid neutrophil chemokines (eotaxin) impact. Methods The total of 30 mice with ovalbumin (OVA) model of asthma were randomly divided into three groups, control group, asthma group and triptolide group. After 24 hours of the last shot, lung tissue was stained Bronchial inflammatory cell infiltration was determined by using semi-quantitative method and calculate the proportion of goblet cells in airway epithelial cells. Hydroxyproline was determined by McMillan airway mucus score. The mRNA level and protein level of STAT6 and eotaxin in airway epithelium were determined by RT-PCR and immunohistochemistry. Results Compared with asthma group, peribronchial inflammatory cells infiltration of triptolide group were reduced, which mucus index is (1.31 ± 0.23) and hydroxyproline is (284 ± 13) μmg/100 mg. it had a significant in asthma group (P < 0.05). Besides, the protein level and mRNA level of STAT6 and eotaxin were significantly decreased (P < 0.05). Moreover, it was a positive correlation between STAT6 and eotaxin level in airway epithelial (r = 0.668, P < 0.05). Conclusion Triptolide can inhibit airway remodeling and might through the down regulation of STAT6 and eotaxin expression.