Objective To evaluate the role of distortion product otoacoustic emissions (DPOAE) testing in evaluating early hearing loss among noise-exposed workers. Methods A total of 174 noise-exposed workers in a metal shipbuilding enterprise were selected as the research subjects by the convenience sampling method. Pure tone audiometry (PTA), DPOAE and the level of noise exposure were conducted on the workers. The rank correlation analysis was used to analyze the correlation between DPOAE amplitude and PTA threshold. The multilevel model was used to analyze the effects of gender, age, noise exposure intensity, cumulative noise exposure (CNE), hearing loss classification and PTA threshold on DPOAE results. Results At the frequencies of 0.50, 1.00, 2.00, 3.00, 4.00, 6.00 and 8.00 kHz, the DPOAE amplitude was negatively correlated with the PTA threshold (rank correlation coefficients were -0.12, -0.48, -0.47, -0.18, -0.23, -0.44, -0.19, respectively, all P<0.01). At the most frequencies, DPOAE amplitude was negatively correlated with age and CNE (all P<0.05). The results of multilevel model analysis showed that there were significant differences in DPOAE amplitudes at certain frequencies across gender, age, noise intensity, CNE, and hearing loss classification (all P<0.05). Significant differences in DPOAE responses were found among different CNE and hearing loss groups (all P<0.01). Conclusion DPOAE testing can objectively reflect the hearing status of noise-exposed workers and could be considered for inclusion in routine hearing monitoring to facilitate early detection of noise-induced hearing loss.

Postmenopausal osteoporosis (PMOP) is a chronic metabolic bone disease caused by a decrease in estrogen levels. With the acceleration of population aging process, the public health burden caused by it is becoming increasingly severe. The prevalence rate of osteoporosis in people over 65 years old in China is as high as 32%, which is especially prominent after menopause, which is about 5 times that of elderly men. About 40% of postmenopausal women are at risk of osteoporotic fractures, with a disability rate of up to 50% and a fatality rate of about 20%. The prevention and treatment of osteoporosis has become a major public health issue of global concern, and it is particularly urgent to develop reasonable and effective prevention and treatment programs and explore their scientific basis. Exercise is an important non-drug means for the prevention and treatment of PMOP, it can improve estrogen levels and the expression of bone formation transcription factors, and inhibit the levels of proinflammatory factors and bone resorption markers, macroscopically manifested by the improvement of bone microstructure and bone density. However, the effectiveness of exercise in improving bone mineral density (BMD) remains controversial. Some studies revealed significant changes of bone to mechanical stimulation, while others showed no significant effect of mechanical training, this heterogeneity in bone adapt to mechanical stimulation is particularly evident in postmenopausal women. Although the evidence that a wide range of exercise programs can improve osteoporosis, the optimal solution to address bone mineral loss remains unclear. The most effective exercise type, dosage and personalized adaptation are still being determined. This study will fully consider the differences in gender and hormone levels, searching and screening randomized controlled trials of PubMed, CNKI and other databases regarding exercise improving bone mineral density in women with PMOP. Strictly following the PRISMA guidelines to reviewed and compared the effects of different types of exercise modalities on BMD at different sites in women with PMOP by network Meta-analysis, to provide theoretical guidance to maintain or improve BMD in women with PMOP.

ObjectiveTo identify the active constituents of Kaixuan Jiedu core prescription （KXJD） and investigate its effective components and therapeutic targets in the treatment of common psoriasis. MethodsUltra-performance liquid chromatography-high resolution mass spectrometry （UPLC-Q-TOF MS） was used to identify and analyze the chemical components of KXJD and its blood-entering chemical components. The chemical components of the single decoction were further identified to clarify the source of the chemical components in KXJD. Then， all identified blood-entering compounds were screened for effective active ingredients through the Swiss ADME database. The active ingredient targets of KXJD were searched on the Swiss Target Prediction platform. The targets of common psoriasis were searched in OMIM， GEO， GeneCards， and DISGNET databases to obtain drug-disease intersection targets. The protein-protein interaction network of intersection targets was constructed using STRING， and then the core blood-entering component-intersection target network of KXJD was constructed. The core target proteins in the network were selected for molecular docking with the core components of KXJD. Small molecules and proteins were pretreated， and appropriate docking sites were selected. AutoDock Vina software was used for continuous local search and repeated iterations to find molecular docking conformations. PyMOL software and LigPlot+ software were used for analysis and visualization. Subsequently， the verification was carried out through animal experiments. SPF-grade male C57 mice were randomly divided into a blank group， a model group， a positive drug methotrexate group， and a KXJD group. In the model group， the methotrexate group， and the KXJD group， imiquimod was applied to the backs of the mice for modeling. The blank group and the model group were administered normal saline by gavage， while the methotrexate group and the KXJD group were respectively administered 1 mg·kg^-1 suspension and 30.42 g·kg^-1 decoction of traditional Chinese medicine by gavage. Five days after administration， the mice were sacrificed， and samples were collected. Hematoxylin-eosin （HE） staining was used to observe the skin tissue samples of mice， and the effect of KXJD on the pathological manifestations of psoriasis mice was analyzed. The expression areas of tumor necrosis factor-α （TNF-α）， cyclooxygenase 2 （PTGS2）， interleukin （IL）-1β， and IL-6 in the skin tissue of mice were detected by immunohistochemistry （IHC）. The mRNA expressions of TNF-α， IL-1β， IL-6， and PTGS2 in the skin tissue of mice were detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）. ResultsIn this study， 208 compounds in KXJD were identified by UPLC-Q-TOF MS， and 44 compounds were detected in serum， including 28 prototype components and 16 metabolites. 12 blood-entering active components were screened， and 1 153 active component targets and 1 076 psoriasis-related targets were identified. Eighty-five targets in the intersection set were drug-disease common targets. PPI network analysis showed that TNF-α， IL-1β， IL-6， PTGS2， and ALB were the key target proteins. The results of molecular docking showed that the binding ability of （+）-hexylphenylglycolic acid to key target proteins such as PTGS2 was stable， and PTGS2 showed high stability with a variety of core compounds. Compared with those in the blank group， the stratum corneum and epidermis in the model group mice were significantly thickened， and the pathological Baker score of the mice's skin in the model group was significantly higher than that of the blank group （P<0.01）. The expression areas of PTGS2， TNF-α， IL-1β， and IL-6 proteins in the skin tissue of the model group mice were significantly increased （P<0.01）， and the expression levels of PTGS2， TNF-α， IL-1β， and IL-6 mRNA in the skin tissue of the model group mice were significantly elevated （P<0.01）. Compared with the model group， the pathological Baker scores of the methotrexate group and the KXJD group were both decreased （P<0.01）， and the expression areas in the skin tissue of the methotrexate group and the KXJD group were significantly reduced （P<0.05， P<0.01）. The expression levels of PTGS2， TNF-α， IL-1β， and IL-6 mRNA in the skin tissue of the methotrexate group and the KXJD group were significantly decreased （P<0.01）. ConclusionKXJD can effectively improve the skin lesions of psoriasis model mice and reduce the expression of TNF-α， IL-1β， IL-6， and PTGS2 in the skin tissue of psoriasis model mice. PTGS2 has a stable binding ability with a variety of compounds in the decoction， which may be a key target for the treatment of psoriasis. The compound （+）-hexylphenylglycolic acid may play a key role.

ObjectiveTo use bioinformatics technology to screen the molecular patterns and diagnostic biomarkers of ferroptosis closely related to psoriasis， observe the therapeutic effect of Kaixuan Jiedu core prescription on psoriasis and explore its potential mechanism through animal experiments. MethodsPsoriasis microarray data from GEO were analyzed to identify differentially expressed genes （DEGs）. Intersection with a ferroptosis gene set yielded psoriasis ferroptosis-related genes （FRGs）， which underwent correlation， consensus clustering， enrichment， and immune infiltration analyses. Core diagnostic FRGs （Hub-FRGs） were identified using random forest （RF）， support vector machine （SVM）， LASSO regression， Nomogram， and ROC analyses. In vivo， imiquimod （5% cream） induced psoriasis in mice （except controls）. Drug treatment groups received respective doses， while control and model groups received saline via daily gavage for 7 days. Back skin changes were recorded and PASI scored. Hematoxylin-eosin （HE） staining assessed histopathology. The levels of ferrous ion （Fe²⁺）， malondialdehyde （MDA）， 4-hydroxynonenal （4-HNE） and free fatty acid （FFA） in skin tissue were detected. The level of reactive oxygen species （ROS） in skin tissue was detected by immunofluorescence. Immunohistochemistry was used to detect the expression of ChaC glutathione-specific γ-glutamyl transferase 1 （CHAC1）， arachidonic acid 12-lipoxygenase β （ALOX12B）， trimotif protein 21 （TRIM21）， proliferation marker （Ki67） and nuclear transcription factor-κB （NF-κB） protein. ResultsAnalysis of GSE30999 identified 2 100 DEGs and 24 FRGs. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment revealed 1 000 biological functions and 75 pathways. After cluster analysis， combined with three machine learning algorithms， Nomogram and ROC curve analysis， the core Hub-FRGs （CHAC1， ALOX12 B， TRIM21） were obtained. Immunoinfiltration showed inactive memory CD4⁺T cells and activated dendritic cells abundance significantly correlated with Hub-FRGs. In vivo， model group vs. control showed significantly increased PASI/Baker scores （P<0.05）， epidermal hyperkeratosis， inflammatory infiltration， and elevated levels of Fe²⁺， MDA， 4-HNE， FFA， ROS， CHAC1， ALOX12B， TRIM21， Ki67， and NF-κB （P<0.05）. Drug groups vs. model group exhibited significantly reduced scores （P<0.05）， alleviated skin lesions， and decreased levels of Fe²⁺， MDA， 4-HNE， FFA， ROS， Hub-FRGs， Ki67， and NF-κB （P<0.05）. ConclusionKaixuan Jiedu core prescription can significantly improve the skin pathological injury of psoriasis mice， showing good therapeutic and repair effects， and its mechanism may be related to regulating the expression of ferroptosis genes CHAC1， ALOX12B and TRIM21， which are closely related to the pathogenesis of psoriasis.

ObjectiveTo identify the active constituents of Kaixuan Jiedu core prescription （KXJD） and investigate its effective components and therapeutic targets in the treatment of common psoriasis. MethodsUltra-performance liquid chromatography-high resolution mass spectrometry （UPLC-Q-TOF MS） was used to identify and analyze the chemical components of KXJD and its blood-entering chemical components. The chemical components of the single decoction were further identified to clarify the source of the chemical components in KXJD. Then， all identified blood-entering compounds were screened for effective active ingredients through the Swiss ADME database. The active ingredient targets of KXJD were searched on the Swiss Target Prediction platform. The targets of common psoriasis were searched in OMIM， GEO， GeneCards， and DISGNET databases to obtain drug-disease intersection targets. The protein-protein interaction network of intersection targets was constructed using STRING， and then the core blood-entering component-intersection target network of KXJD was constructed. The core target proteins in the network were selected for molecular docking with the core components of KXJD. Small molecules and proteins were pretreated， and appropriate docking sites were selected. AutoDock Vina software was used for continuous local search and repeated iterations to find molecular docking conformations. PyMOL software and LigPlot+ software were used for analysis and visualization. Subsequently， the verification was carried out through animal experiments. SPF-grade male C57 mice were randomly divided into a blank group， a model group， a positive drug methotrexate group， and a KXJD group. In the model group， the methotrexate group， and the KXJD group， imiquimod was applied to the backs of the mice for modeling. The blank group and the model group were administered normal saline by gavage， while the methotrexate group and the KXJD group were respectively administered 1 mg·kg^-1 suspension and 30.42 g·kg^-1 decoction of traditional Chinese medicine by gavage. Five days after administration， the mice were sacrificed， and samples were collected. Hematoxylin-eosin （HE） staining was used to observe the skin tissue samples of mice， and the effect of KXJD on the pathological manifestations of psoriasis mice was analyzed. The expression areas of tumor necrosis factor-α （TNF-α）， cyclooxygenase 2 （PTGS2）， interleukin （IL）-1β， and IL-6 in the skin tissue of mice were detected by immunohistochemistry （IHC）. The mRNA expressions of TNF-α， IL-1β， IL-6， and PTGS2 in the skin tissue of mice were detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）. ResultsIn this study， 208 compounds in KXJD were identified by UPLC-Q-TOF MS， and 44 compounds were detected in serum， including 28 prototype components and 16 metabolites. 12 blood-entering active components were screened， and 1 153 active component targets and 1 076 psoriasis-related targets were identified. Eighty-five targets in the intersection set were drug-disease common targets. PPI network analysis showed that TNF-α， IL-1β， IL-6， PTGS2， and ALB were the key target proteins. The results of molecular docking showed that the binding ability of （+）-hexylphenylglycolic acid to key target proteins such as PTGS2 was stable， and PTGS2 showed high stability with a variety of core compounds. Compared with those in the blank group， the stratum corneum and epidermis in the model group mice were significantly thickened， and the pathological Baker score of the mice's skin in the model group was significantly higher than that of the blank group （P<0.01）. The expression areas of PTGS2， TNF-α， IL-1β， and IL-6 proteins in the skin tissue of the model group mice were significantly increased （P<0.01）， and the expression levels of PTGS2， TNF-α， IL-1β， and IL-6 mRNA in the skin tissue of the model group mice were significantly elevated （P<0.01）. Compared with the model group， the pathological Baker scores of the methotrexate group and the KXJD group were both decreased （P<0.01）， and the expression areas in the skin tissue of the methotrexate group and the KXJD group were significantly reduced （P<0.05， P<0.01）. The expression levels of PTGS2， TNF-α， IL-1β， and IL-6 mRNA in the skin tissue of the methotrexate group and the KXJD group were significantly decreased （P<0.01）. ConclusionKXJD can effectively improve the skin lesions of psoriasis model mice and reduce the expression of TNF-α， IL-1β， IL-6， and PTGS2 in the skin tissue of psoriasis model mice. PTGS2 has a stable binding ability with a variety of compounds in the decoction， which may be a key target for the treatment of psoriasis. The compound （+）-hexylphenylglycolic acid may play a key role.

ObjectiveTo use bioinformatics technology to screen the molecular patterns and diagnostic biomarkers of ferroptosis closely related to psoriasis， observe the therapeutic effect of Kaixuan Jiedu core prescription on psoriasis and explore its potential mechanism through animal experiments. MethodsPsoriasis microarray data from GEO were analyzed to identify differentially expressed genes （DEGs）. Intersection with a ferroptosis gene set yielded psoriasis ferroptosis-related genes （FRGs）， which underwent correlation， consensus clustering， enrichment， and immune infiltration analyses. Core diagnostic FRGs （Hub-FRGs） were identified using random forest （RF）， support vector machine （SVM）， LASSO regression， Nomogram， and ROC analyses. In vivo， imiquimod （5% cream） induced psoriasis in mice （except controls）. Drug treatment groups received respective doses， while control and model groups received saline via daily gavage for 7 days. Back skin changes were recorded and PASI scored. Hematoxylin-eosin （HE） staining assessed histopathology. The levels of ferrous ion （Fe²⁺）， malondialdehyde （MDA）， 4-hydroxynonenal （4-HNE） and free fatty acid （FFA） in skin tissue were detected. The level of reactive oxygen species （ROS） in skin tissue was detected by immunofluorescence. Immunohistochemistry was used to detect the expression of ChaC glutathione-specific γ-glutamyl transferase 1 （CHAC1）， arachidonic acid 12-lipoxygenase β （ALOX12B）， trimotif protein 21 （TRIM21）， proliferation marker （Ki67） and nuclear transcription factor-κB （NF-κB） protein. ResultsAnalysis of GSE30999 identified 2 100 DEGs and 24 FRGs. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment revealed 1 000 biological functions and 75 pathways. After cluster analysis， combined with three machine learning algorithms， Nomogram and ROC curve analysis， the core Hub-FRGs （CHAC1， ALOX12 B， TRIM21） were obtained. Immunoinfiltration showed inactive memory CD4⁺T cells and activated dendritic cells abundance significantly correlated with Hub-FRGs. In vivo， model group vs. control showed significantly increased PASI/Baker scores （P<0.05）， epidermal hyperkeratosis， inflammatory infiltration， and elevated levels of Fe²⁺， MDA， 4-HNE， FFA， ROS， CHAC1， ALOX12B， TRIM21， Ki67， and NF-κB （P<0.05）. Drug groups vs. model group exhibited significantly reduced scores （P<0.05）， alleviated skin lesions， and decreased levels of Fe²⁺， MDA， 4-HNE， FFA， ROS， Hub-FRGs， Ki67， and NF-κB （P<0.05）. ConclusionKaixuan Jiedu core prescription can significantly improve the skin pathological injury of psoriasis mice， showing good therapeutic and repair effects， and its mechanism may be related to regulating the expression of ferroptosis genes CHAC1， ALOX12B and TRIM21， which are closely related to the pathogenesis of psoriasis.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

Objective To explore the effect of rifampicin on the pharmacokinetics of linezolid in mice and provide pharmacokinetic evidence for the formulation of safe drugs for clinical use of pulmonary tuberculosis.Methods Fifty male KM mice were randomly divided into 2 groups:Control group,rifampicin group;the control group was given 15 mg·kg-1 linezolid;the rifampicin group was given 100 mg·mL-1 rifampicin,continuous administration for 7 days,followed by gavage,administration of 15 mg·kg-1 linezolid;blood and lung tissue were collected from mouse at different time points after administration.High performance liquid mass spectrometry(LC-MS/MS)was used to determine plasma concentration of linezolid and compared the pharmacokinetics between groups.Pharmacokinetic parameters were calculated using DAS 2.0 software.Results Main pharmacokinetic parameters of plasma linezolid in control group,rifampicin group were as follows:AUC0_t were(23.88±1.16)and(19.06±2.56)pg·mL-1·h,respectively;t1/2 were((1.15±0.11)and(1.11±0.10)h,respectively;Cmax were(9.93±0.46)and(7.74±1.17)μg·mL-1,respectively.The main pharmacokinetic parameters of the lungs in the control group and the rifampicin group were as follows:AUC0_t were(18.76±4.29)and(14.90±1.52)μg·mL-1·h,respectively;t1/2 were(1.94±0.50)and(1.44±0.07)h,respectively;Cmax were(8.28±2.67)and(6.82±1.57)μg·mL-1,respectively.AUC0_t and Cmax in plasma and AUC0_t in lung tissue of control group were significantly different from those of rifampicin group(all P＜0.05).Conclusion After the combination of rifampicin,linezolid plasma and lung tissue exposure decreased significantly,and attention should be paid to monitoring linezolid trough concentration when the two drugs were combined to avoid treatment failure caused by low effective concentration.

Nowadays,with the continuous deepening and development of vocational education teaching reform,medical higher vocational education always takes moral education as the fundamental task.As an independent type of education,vocational education should always deepen the integration of industry and education and the integration of science and education.Through the teaching research of"problem chain+course ideological and political case",this study innovates the coordinated education team of drug nursing curriculum,the collaborative education method and the collaborative education evaluation,and improves the teaching effect.