1.Mechanism of Yangxin Dingji Capsules in Preventing Ventricular Arrhythmia Based on TAK1/MKK3/p38 MAPK Pathway
Mian LI ; Zheng ZHANG ; Xinyue LI ; Xue TIAN ; Wenlu ZHENG ; Jinwei WU ; Gang LIU ; Wenjie LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):86-95
ObjectiveTo explore the protective effect and mechanism of Yangxin Dingji capsules on isoproterenol (ISO)-induced ventricular arrhythmia in SD rat cardiomyocytes based on the transforming growth factor-β activated kinase 1 (TAK1)-mitogen-activated protein kinase kinase 3 (MKK3)-p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. MethodFifty male SPF-grade SD rats were randomly divided into a normal group, a model group, a propranolol group, a low-dose Chinese medicine group, and a high-dose Chinese medicine group. The ventricular arrhythmia model was constructed using the ISO "6+1" method. The propranolol group received propranolol at 0.015 g·kg-1·d-1. The Chinese medicine groups received Yangxin Dingji capsules at doses of 0.5、 2 g·kg-1·d-1, respectively. The normal and model groups were given an equal volume of 0.9% NaCl solution. Electrocardiogram (ECG) changes in SD rats were recorded using the BL-420F biological function experimental system. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in the heart. Serum levels of cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1) were measured using enzyme-linked immunosorbent assay (ELISA). The mRNA expression of IL-1β and TNF-α was assessed using real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Reactive oxygen species (ROS) expression was detected using immunofluorescence. Protein expression levels of TAK1, phosphorylated TAK1 (p-TAK1), MKK3, phosphorylated MKK3 (p-MKK3), p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK), nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), IL-1β, and TNF-α were measured using Western blot or immunohistochemistry. ResultCompared with normal group, the model group showed significant ventricular arrhythmia in ECG, with an increased arrhythmia score (P<0.01). Pathological damage to myocardial tissue was evident, and serum levels of cTnI, CK-MB, IL-1β, TNF-α, and TGF-β1 were elevated (P<0.01). The mRNA and protein expression of IL-1β and TNF-α in myocardial tissue was also increased (P<0.01). ROS level and protein expression of p-TAK1, p-MKK3, p-p38 MAPK, and p-NF-κB were elevated in myocardial tissue (P<0.01). In the propranolol and Chinese medicine groups, the incidence of sustained ventricular tachycardia (SVT) and arrhythmia scores were significantly reduced compared to model group (P<0.05, P<0.01). Pathological damage to cardiomyocytes was alleviated, and levels of myocardial injury markers and inflammatory factors in serum and myocardial tissue were decreased. The ROS level in myocardial tissue was also reduced (P<0.01), with a noticeable reduction in related molecules in the p38 MAPK pathway (P<0.05, P<0.01). ConclusionThe expression of p38 MAPK pathway molecules was up-regulated in myocardial tissue of ISO-induced ventricular arrhythmia rats. Yangxin Dingji capsules may inhibit cardiac inflammation damage by regulating the expression of related molecules in the p38 MAPK pathway, thereby exerting a protective effect on myocardial cells, with TAK1 being a potential target.
2.Interaction of occupational and non-occupational noise exposure leads to high frequency hearing loss
Luxi BAI ; Ying XIAO ; Danping DUAN ; Jinwei ZHANG ; Huidong SONG ; Zhi WANG
China Occupational Medicine 2024;51(2):163-167
ObjectiveTo explore the impact of the interaction between occupational and non-occupational noise exposure on the risk of high-frequency hearing loss (HFHL) in noise-exposed workers. Methods A total of 602 male workers with normal hearing, engaged in an automobile manufacturing company between 2016 and 2018, were selected as the study subjects using the retrospective cohort study method. Pure-tone audiometry and questionnaire surveys were conducted on the workers. The Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression model were used to analyze the interaction between occupational and non-occupational noise exposure and the risk of HFHL in these workers. Results The prevalence of HFHL of the workers was 34.1% in 2020, without any cases of speech frequency hearing loss. Kaplan-Meier survival analysis result showed that the risk of HFHL increased in workers with excessive national occupational noise exposure intensity, self-reported noisy living environments, and both excessive national occupational noise exposure intensity and self-reported noisy living environments (all P<0.01). The results of the Cox proportional hazards model showed that the combined effect of excessive national occupational noise exposure intensity and self-reported noisy living environments [relative risk (RR)=2.40, P<0.01] was higher than the individual effects of excessive national occupational noise exposure intensity (RR=2.09, P<0.01) and self-reported noisy living environments (RR=2.39, P<0.01). There was an antagonistic effect between excessive national occupational noise exposure intensity and self-reported noisy living environments (interaction index <1.00). Conclusion Both occupational and non-occupational noise exposure can increase the risk of HFHL in noise-exposed workers, and there is an interaction between them.
3.Research progress on cognitive dysfunction induced by occupational noise and combined exposure to heavy metals
Caixia LI ; Kangyong WU ; Yixian REN ; Bin LIN ; Jinwei ZHANG ; Zhi WANG ; Jiabin LIANG
China Occupational Medicine 2024;51(2):172-176
Exposure to occupational noise and heavy metals are common occupational hazards in workplaces. Occupational noise exposure not only leads to noise-induced hearing loss but also cognitive dysfunction. Exposure to common heavy metals such as lead, manganese, and cadmium during work is closely related to cognitive dysfunction in workers. Combined exposure to noise and heavy metals is common in workplaces. However, current research on the combined effects of exposure to occupational noise with lead or manganese on workers' cognitive function is not comprehensive or systematic. The method for cognitive dysfunction identification varies, leading to a lack of comparability. And the causality between occupational exposure and cognitive dysfunction in workers has not been clarified. Therefore, studying the cognitive dysfunction due to combined exposure to noise and common heavy metals is of great significance for workers' occupational health. In the future, it is necessary to unify the method for cognitive dysfunction identification and conduct systematic and comprehensive research on the effects, mechanisms, and combined effects of exposure to occupational noise with lead, manganese, cadmium, and other heavy metals on workers' cognitive dysfunction, to ensure the occupational health rights and interests of workers.
4.GLUT1-targeted Nano-delivery System for Active Ingredients of Traditional Chinese Medicine:A Review
Hua ZHU ; Huimin LUO ; Si LIN ; Bingbing WANG ; Jinwei LI ; Liba XU ; Miao ZHANG ; Fengfeng XIE ; Long CHEN ; Meilin LI ; Lu LU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):270-280
Tumor cells use glycolysis to provide material and energy under hypoxic conditions to meet the energy requirements for rapid growth and proliferation, namely the Warburg effect. Even under aerobic conditions, tumor cells mainly rely on glycolysis to provide energy. Therefore, glucose transporter protein 1(GLUT1), which is involved in the process of glucose metabolism, plays an important role in tumorigenesis, development and drug resistance, and is considered to be one of the important targets in the treatment of malignant tumors. In recent years, research on tumor glucose metabolism has gradually become a hot spot. It has been shown that various factors are involved in the regulation of tumor energy metabolism, among which the role of GLUT1 is the most critical. In this paper, the authors reviewed the latest research progress of GLUT1-targeted traditional Chinese medicine(TCM) active ingredient nano-delivery system in tumor therapy, aiming to reveal the feasibility and effectiveness of this system in the delivery of chemotherapeutic drugs. The GLUT1-targeted TCM active ingredient nano-delivery system can overcome the bottleneck of the traditional targeting strategy as well as the high-permeability long retention(EPR) effect. In summary, the authors believe that the GLUT1-targeted TCM active ingredient nano-delivery system provides a new strategy for targeted treatment of tumors and has a broad application prospect in tumor prevention and treatment.
5.Global trends in the incidence and prevalence of pneumoconiosis in 204 countries/territories from 1990 to 2019
Shihao TANG ; Jiaxin CUI ; Yuquan CHEN ; Qiuyuan MAI ; Jinwei ZHANG ; Zhi WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(2):123-128
Objective:To analyze the changing trend of incidence and prevalence of pneumoconiosis globally, and provide scientific basis for the formulation of health policy.Methods:In June 2022, through the Global Health Data exchange (GHDx) query tool (http: //ghdx.healthdata.org/gbd-results-tool) , the pneumoconiosis incidence and prevalence data was downloaded and organized. Estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trends of pneumoconiosis from 1990 to 2019. EAPC was estimated by linear regression model based on ASR.Results:The overall ASR of the incidence and prevalence of pneumoconiosis decreased from 1990 to 2019, and their EAPCs were-0.85% (95% CI: -1.11%--0.60%) and -0.78% (95% CI: -1.08%--0.49%) . Over the past 30 years, the incidence and prevalence of pneumoconiosis in all SDI areas showed decreasing trends, especially in high SDI areas, their EAPCs were -1.46% (95% CI: -1.76%--1.15%) and -1.99% (95% CI: -2.44%--1.53%) . 110 countries/areas showed increasing trends in age standardized incidence rate (ASIR) , with Iran and Georgia showing the most pronounced upward trend, their EAPCs were 5.32% (95% CI: 4.43%-6.22%) and 4.39% (95% CI: 3.81%-4.97%) . 125 countries/areas showed anincreasing trends in prevalence ASR, with Iran had the fastest rise in prevalence (EAPC=6.40%, 95% CI: 5.33%-7.49%) . Conclusion:Although decreasing trends in the burden of pneumoconiosis are observed globally from 1990 to 2019, but the burden of pneumoconiosis in low-and middle-income countries or regions are still heavy. We need more effective strategies to prevent and reduce the burden of pneumoconiosis.
6.Role of CTGF and PI3K/Akt signaling pathway in paraquat-induced mesenchymal changes in alveolar epithelial cells
Yiwei SU ; Guangzhen LI ; Wenxin FANG ; Jinwei ZHANG ; Yimin LIU ; Zhi WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(6):401-407
Objective:To investigate the role of connective tissue growth factor (CTGF) and PI3K/Akt signaling pathways in paraquat (PQ) -induced alterations in alveolar epithelial cell mesenchymalization (EMT) .Methods:In February 2023, RLE-6TN cells were divided into 2 groups, which were set as uncontaminated group and contaminated group (200 μmol/L PQ), and cellular EMT alteration, CTGF and PI3K/Akt signaling pathway related molecules expression were detected by cell scratch assay, qRT-PCR and western-blot assay. Using shRNA interference technology to specifically inhibit the expression of CTGF, RLE-6TN cells were divided into four groups: control group, PQ group (200 μmol/L PQ), interference group (transfected with a plasmid with shRNA-CTGF+200 μmol/L PQ), and null-loaded group (transfected with a plasmid with scramble- CTGF+200 μmol/L PQ), qRT-PCR and western blot were used to examine the alteration of the cellular EMT and the expression of molecules related to the activity of PI3K/Akt pathway. The PI3K/Akt signaling pathway was blocked by the PI3K inhibitor LY294002, and the expression of EMT-related molecules in cells of the control group, PQ group (200 μmol/L PQ), and inhibitor group (200 μmol/L PQ+20 μmol/L LY294002) was examined by qRT-PCR and western blot.The t-test was used to compare the differences between the two groups, while the analysis of variance (ANOVA) was applied to compare the differences among multiple groups. For further pairwise comparisons, the Bonferroni method was adopted.Results:The results of cell scratch test showed that compared with the uncontaminated group, RLE-6TN cells in the contaminated group had faster migration rate, lower mRNA and protein expression levels of E-Cadherin, and higher mRNA and protein expression levels of α-SMA, CTGF, PI3K and Akt, with statistical significance ( P<0.05). After specific inhibition of CTGF expression, the mRNA and protein expression of CTGF, PI3K, Akt, and α-SMA in the cells of the interference group were significantly lower than that of the PQ group and the null-loaded group ( P<0.05/6), whereas that of E-Cadherin was higher than that of the PQ group and the null-loaded group ( P<0.05/6). Specifically blocking the PI3K/Akt signaling pathway, the mRNA and protein expression of PI3K, Akt and α-SMA in the cells of the inhibitor group was decreased compared with that of the PQ group ( P<0.05/3), while the expression of E-Cadherin was elevated compared with that of the PQ group ( P<0.05/3) . Conclusion:CTGF may promote PQ-induced alveolar epithelial cell EMT through activation of the PI3K/Akt signaling pathway. Inhibition of CTGF expression or blockade of PI3K/Akt signaling pathway activity can alleviate the extent of PQ-induced alveolar epithelial cell EMT.
7.Analysis of disease burden and trends of noise-induced hearing loss in China from 1990 to 2019
Lin CHEN ; Yang LIAO ; Zibo CEN ; Jinwei ZHANG ; Minghui XIAO ; Zhi WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(10):730-734
Objective:To analyze the disease burden of Noise-Induced Hearing Loss (NIHL) in China from 1990 to 2019, forecast the disease burden of NIHL from 2020 to 2030, and provide data support for the prevention and control of NIHL.Methods:In July 2022, the disease burden data of NIHL in different age groups and genders in China during 1990-2019 were selected from the GBD database. The Jointpoint regression model was established to analyze the trend of the disease burden of NIHL in China. An age-period-cohort model was constructed to analyze the changing trend of NIHL in terms of age, period, and cohort, and a Bayesian age-period-cohort model was developed to predict the disease burden of NIHL in China from 2020 to 2030.Results:From 1990 to 2019, the disability adjusted life year (DALY) of China's NIHL increased from 1361600 to 2327700 years. The coarse rate of DALY increased from 115.03/100000 to 163.65/100000 (AAPC=1.23, P<0.001), and the normalization rate of DALY decreased from 127.67/100000 to 119.83/100000 (AAPC=-0.21, P<0.001). It is predicted that from 2020 to 2030, the DALYs of China's NIHL will increase from 2412900 in 2020 to 2655000 in 2030, and the DALY normalization rate will decrease from 241.29/100000 in 2020 to 125.71/100000 in 2030. Conclusion:The burden of noise-induced hearing loss (NIHL) in China is significant and should not be overlooked. To reduce this burden, we need to focus on strengthening source management, process control, personal protection, and comprehensive prevention and treatment through various methods.
8.Analysis on Application and Funding Situation of General,Young Scholar and Regional Scholar Programs from NSFC in Field of Integrated Traditional Chinese and Western Medicine in 2023
Yuan XU ; Zipeng GONG ; Juan LI ; Jinwei ZHANG ; Xuewei LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):172-178
By combing the application and funding situation of general, young scholar and regional scholar programs from National Natural Science Foundation of China(NSFC) in field of integrated traditional Chinese and western medicine in 2023, this paper summarizes the distribution of supporting units, application and funding hotspots, and the problems of application and funding projects in this discipline, in order to provide a reference for applicants and supporting organizations to understand the hotspot dynamics and reporting requirements of the discipline. In 2023, the discipline of integrated traditional Chinese and western medicine received a total of 2 793 applications, and there were 1 254 applications for general programs, 1 278 applications for young scholar programs, and 261 applications for regional scholar programs. The amounts of project funding obtained by the three were 145, 164 and 35, respectively, and the funding rates were 11.56%, 12.83% and 13.41% in that order. From the situation of obtaining funding, the age distribution of the project leaders who obtained funding for the general, young scholar and regional scholar programs were mainly distributed in the age of 40-46, 30-34, 38-44 years, respectively. Within the supported programs, the Chinese medicine affiliations accounted for 55.52%. With respect to research subjects, the proportion of one single Chinese herbs, or monomers, or extracts accounted for 29.4%, but the proportion of Chinese herb pairs or prescriptions accounted for 47.1%. Research hotspots included ferroptosis, bile acid metabolism, macrophages, mitochondria, microglia, exosomes, intestinal flora, microecology and so on. The current research mainly focused on the common key problems of the advantageous diseases of Chinese and western integrative medicine, but still need to be improved in the basic theories of Chinese and western medicine and multidisciplinary cross-disciplinary research.
9.Global trends in the incidence and prevalence of pneumoconiosis in 204 countries/territories from 1990 to 2019
Shihao TANG ; Jiaxin CUI ; Yuquan CHEN ; Qiuyuan MAI ; Jinwei ZHANG ; Zhi WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(2):123-128
Objective:To analyze the changing trend of incidence and prevalence of pneumoconiosis globally, and provide scientific basis for the formulation of health policy.Methods:In June 2022, through the Global Health Data exchange (GHDx) query tool (http: //ghdx.healthdata.org/gbd-results-tool) , the pneumoconiosis incidence and prevalence data was downloaded and organized. Estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trends of pneumoconiosis from 1990 to 2019. EAPC was estimated by linear regression model based on ASR.Results:The overall ASR of the incidence and prevalence of pneumoconiosis decreased from 1990 to 2019, and their EAPCs were-0.85% (95% CI: -1.11%--0.60%) and -0.78% (95% CI: -1.08%--0.49%) . Over the past 30 years, the incidence and prevalence of pneumoconiosis in all SDI areas showed decreasing trends, especially in high SDI areas, their EAPCs were -1.46% (95% CI: -1.76%--1.15%) and -1.99% (95% CI: -2.44%--1.53%) . 110 countries/areas showed increasing trends in age standardized incidence rate (ASIR) , with Iran and Georgia showing the most pronounced upward trend, their EAPCs were 5.32% (95% CI: 4.43%-6.22%) and 4.39% (95% CI: 3.81%-4.97%) . 125 countries/areas showed anincreasing trends in prevalence ASR, with Iran had the fastest rise in prevalence (EAPC=6.40%, 95% CI: 5.33%-7.49%) . Conclusion:Although decreasing trends in the burden of pneumoconiosis are observed globally from 1990 to 2019, but the burden of pneumoconiosis in low-and middle-income countries or regions are still heavy. We need more effective strategies to prevent and reduce the burden of pneumoconiosis.
10.Role of CTGF and PI3K/Akt signaling pathway in paraquat-induced mesenchymal changes in alveolar epithelial cells
Yiwei SU ; Guangzhen LI ; Wenxin FANG ; Jinwei ZHANG ; Yimin LIU ; Zhi WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(6):401-407
Objective:To investigate the role of connective tissue growth factor (CTGF) and PI3K/Akt signaling pathways in paraquat (PQ) -induced alterations in alveolar epithelial cell mesenchymalization (EMT) .Methods:In February 2023, RLE-6TN cells were divided into 2 groups, which were set as uncontaminated group and contaminated group (200 μmol/L PQ), and cellular EMT alteration, CTGF and PI3K/Akt signaling pathway related molecules expression were detected by cell scratch assay, qRT-PCR and western-blot assay. Using shRNA interference technology to specifically inhibit the expression of CTGF, RLE-6TN cells were divided into four groups: control group, PQ group (200 μmol/L PQ), interference group (transfected with a plasmid with shRNA-CTGF+200 μmol/L PQ), and null-loaded group (transfected with a plasmid with scramble- CTGF+200 μmol/L PQ), qRT-PCR and western blot were used to examine the alteration of the cellular EMT and the expression of molecules related to the activity of PI3K/Akt pathway. The PI3K/Akt signaling pathway was blocked by the PI3K inhibitor LY294002, and the expression of EMT-related molecules in cells of the control group, PQ group (200 μmol/L PQ), and inhibitor group (200 μmol/L PQ+20 μmol/L LY294002) was examined by qRT-PCR and western blot.The t-test was used to compare the differences between the two groups, while the analysis of variance (ANOVA) was applied to compare the differences among multiple groups. For further pairwise comparisons, the Bonferroni method was adopted.Results:The results of cell scratch test showed that compared with the uncontaminated group, RLE-6TN cells in the contaminated group had faster migration rate, lower mRNA and protein expression levels of E-Cadherin, and higher mRNA and protein expression levels of α-SMA, CTGF, PI3K and Akt, with statistical significance ( P<0.05). After specific inhibition of CTGF expression, the mRNA and protein expression of CTGF, PI3K, Akt, and α-SMA in the cells of the interference group were significantly lower than that of the PQ group and the null-loaded group ( P<0.05/6), whereas that of E-Cadherin was higher than that of the PQ group and the null-loaded group ( P<0.05/6). Specifically blocking the PI3K/Akt signaling pathway, the mRNA and protein expression of PI3K, Akt and α-SMA in the cells of the inhibitor group was decreased compared with that of the PQ group ( P<0.05/3), while the expression of E-Cadherin was elevated compared with that of the PQ group ( P<0.05/3) . Conclusion:CTGF may promote PQ-induced alveolar epithelial cell EMT through activation of the PI3K/Akt signaling pathway. Inhibition of CTGF expression or blockade of PI3K/Akt signaling pathway activity can alleviate the extent of PQ-induced alveolar epithelial cell EMT.

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