1.Assignment of chemical exposure parameter in occupational health risk assessment models: Key consideration
Jiayun DING ; Meixia LIU ; Jiming ZHANG ; Yan YIN ; Zhijun ZHOU
Journal of Environmental and Occupational Medicine 2025;42(4):497-502
The core idea of occupational health risk assessment models is to systematically evaluate occupational health risks according to target hazard characteristics and relevant exposure levels of workers. Occupational exposure assessment is based on concentration, frequency, exposure time, and other indicators that indicate actual exposure of workers to occupational hazards, which is a critical component of health risk assessment. However, the accuracy and comparability of assessment results are affected by differences in parameter assignment for exposure assessment across different studies, as well as insufficient emphasis on multiple occupational hazard exposure. This review aimed to explore the assignment and standardization of exposure assessment parameters for occupational health risk assessment modeling, and systematically sorted out the meaning, assignment methods, and sources of exposure assessment related parameters in commonly used occupational health risk assessment models, with the goal of providing researchers with standardized assessment tools to enhance the scientific rigor and practicality of occupational health risk assessments. Considering the individual differences and temporal fluctuations in occupational exposure, it is recommended that researchers should adopt appropriate sampling strategies, reasonably select sample subjects and time based on the division of similar exposure group (SEG), and conduct statistical inference on the obtained data to derive representative exposure parameters. For combined exposure to chemicals with similar toxic effects, the health risk assessment methods are relatively mature. However, the assessment of combined exposure to hazards with different properties and health effects still lacks scientific authority and needs further research and discussion.
2.Application of bilateral hip magnetic resonance imaging to predict risk of osteonecrosis of femoral head
Jiming JIN ; Yangquan HAO ; Rushun ZHAO ; Yuting ZHANG ; Yonghong JIANG ; Peng XU ; Chao LU
Chinese Journal of Tissue Engineering Research 2025;29(9):1890-1896
BACKGROUND:Magnetic resonance imaging is the gold standard for the diagnosis of osteonecrosis of femoral head,and previous methods of predicting osteonecrosis of femoral head collapse based on magnetic resonance images mostly require the combined assessment of coronal and sagittal images.However,osteonecrosis of femoral head tends to occur bilaterally,most hospitals perform bilateral hip magnetic resonance imaging scans during clinical examinations,but the bilateral hip scans can only view coronal and cross-sectional images,and it is difficult to obtain sagittal images,which affects the assessment of the risk of collapse.Therefore,it is of clinical value to establish a method to assess the risk of early osteonecrosis of femoral head collapse by applying the images that can be obtained after bilateral hip magnetic resonance scanning. OBJECTIVE:To establish a method of applying coronal and cross-sectional images of bilateral hip magnetic resonance imaging to assess the risk of osteonecrosis of femoral head collapse. METHODS:The medical records of 111 patients(181 hips)with early-stage osteonecrosis of femoral head diagnosed at the outpatient clinic of Honghui Hospital Affiliated to Xi'an Jiaotong University from October 2017 to October 2019 were retrospectively analyzed.They were categorized into collapsed and non-collapsed groups according to the femoral head collapse at the final follow-up,with 69 hips in the collapsed group and 112 hips in the non-collapsed group.The angle of necrotic range on the images of median coronal plane,transverse plane or one level above and below it was measured on the magnetic resonance imaging system.The sum of the two angles of necrotic angle on the coronal and transverse planes was used as the combined necrotic angle.The average of the three combined necrotic angles of each hip was taken to get the average combined necrotic angle of each hip.Finally,the correlation between the three combined necrotic angles and the average combined necrotic angle with the collapse of osteonecrosis of femoral head was analyzed,and the specificity and sensitivity of the four combined necrotic angles in predicting collapse were evaluated by using receiver operating characteristic curves. RESULTS AND CONCLUSION:(1)Totally 69 hips(38.1%)had femoral head collapse at the last follow-up and were included in the collapsed group;112 hips(61.9%)did not have progression of collapse and were included in the non-collapsed group.(2)The difference between the collapsed group and the non-collapsed group in terms of Association Research Circulation Osseous(ARCO)stage was significant(P<0.001).The difference in age,body mass index,follow-up time,gender distribution,side of onset,and causative factors was not significant(P>0.05).(3)The results of independent samples t-test suggested that all four combined necrotic angles were significantly correlated with collapse(P<0.000 1);and the differences in combined necrotic angles between the collapsed group and the non-collapsed group of ARCO stage I and the two groups of ARCO stage II were all significant(P<0.000 1).(4)In the analysis of the receiver operating characteristic,the area under the curve of the average combined necrotic angle was greater than that of the combined necrotic angle on the lower level of the median,the middle level,and the upper level of the median.(5)The average combined necrotic angle had a higher accuracy in the prediction of collapse than the lower level of the median,the middle level,and the upper level of the combined necrotic angle.(6)It is concluded that the accuracy of the average combined necrotic angle in predicting the risk of osteonecrosis of femoral head collapse is higher,and the clinical practicability is stronger,so we can consider using this method to predict the risk of osteonecrosis of femoral head collapse.
3.Integration strategy for chronic disease screening indicators in occupational medical examinations
Tianyang SHEN ; Jiming ZHANG ; Tengxiao SHAN ; Zhijun ZHOU
China Occupational Medicine 2025;52(3):336-340
As the prevalence of chronic diseases increases among occupational populations in China, the focus of occupational health management has shifted from ″occupational disease prevention and control″ to ″occupational disease and chronic disease prevention and control″. At present, occupational medical examinations (OME) are mainly focused on occupational disease prevention and control, and generally lack of chronic disease indicators such as blood lipids and blood glucose, limiting the role of OME in life-cycle health management of workers. To address this gap, it is necessary to incorporate chronic disease screening indicators into OME. Integrating OME and chronic disease screening faces bottlenecks, including concerns about increased operating costs in small- and medium-sized enterprises, and the risk of employment discrimination caused by the leakage of employee health privacy. A tiered strategy is recommended. Incorporating low-cost indicators such as blood lipids, waist circumference into routine examinations, and customizing advanced screening for elder or high-risk position workers. The prioritization of screening indicators can be determined by expert consultation and employer-employee discussions. Meanwhile, the results of chronic disease screening indicators should not be included in occupational health surveillance records to protect workers′ privacy. In summary, expanding OME to cover more chronic disease indicators provides valuable economic and social benefits. In the long run, common chronic disease screening indicators should be included in the regular medical examination indicators of OME, thereby reducing the burden of chronic diseases on occupational populations and promoting the health management of occupational populations.
4.Establishment of high-throughput liquid chromatography tandem mass spectrometry method for determination of 53 per- and polyfluoroalkyl substances in serum
Zheng WANG ; Boya ZHANG ; Jiming ZHANG ; Chao FENG ; Yuanjie LIN ; Chunhua WU ; Dasheng LU ; Zhijun ZHOU
Journal of Environmental and Occupational Medicine 2024;41(4):375-383
Background Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants that possess potential toxicity to the human body. The production and utilization of diverse emerging PFAS have resulted in widespread human exposure. Therefore, it is imperative to establish a quantitative methodology encompassing a wide range of PFAS for a comprehensive assessment of human exposure to these compounds. Objective To establish a high-throughput quantitative method for the simultaneous determination of 53 PFAS in human serum based on ultra-high-performance liquid chromatography-Q Exactive high resolution mass spectrometry (UPLC-Q Exactive HRMS). Methods The extraction recoveries of hydrophilic-lipophilic balance (HLB) column, weak anionexchange (WAX) column, and 96-well WAX μElution plate were compared to select the SPE column with the highest recovery. The retention time and peak shape of the target compounds were compared between ACQUITY UPLC BEH C18 column and Accucore aQ column, and the more cost-effective column was chosen. The effects of adding different levels of ammonium formate (0, 2, 5 and 10 mmol·L−1) in mobile phase on peak shape and target response were compared to determine the optimal buffer salt concentration. The optimal spray voltage was obtained by comparing −2 kV and −4 kV. The proposed method was validated from the aspects of selectivity, standard curve, limits of detection, precision, accuracy, and matrix effect. The method was applied to 142 umbilical serum samples. Results The best recovery rate (64%-118%) was achieved by using 96-well WAX μElution plate. The optimal separation and peak shape were obtained by utilizing Accucore aQ column with H2O-methanol (containing 5 mmol·L−1 ammonium formate) as the mobile phase. Less in-source collision and better target response were observed when the spray voltage was set to −2 kV. All target analytes had a good linearity, with R2 > 0.99. The limits of detection ranged from 0.01 to 0.50 μg·L−1, and the recovery ranged from 69% to 127% with the precision less than 26%. A total of 31 PFAS were detected in the 142 actual samples, among which 14 PFAS had a detection frequency over 50%. Perfluorooctanoic acid showed the highest median concentration of 4.16 μg·L−1, followed by 6:2 chlorinated polyfluorinated ether sulfonate and perfluorooctane sulfonates (3.50 μg·L−1 and 1.59 μg·L−1, respectively). Conclusion In this study, we establish a UPLC-Q Excative HRMS method for simutanious determination of 53 PFAS concentrations in serum. This method has the advantages of wide coverage of PFAS, good selectivity, and easy operation, and is suitable for biological detection with a large sample size.
5.Kidney function among male workers of a lithium-ion battery-related enterprise in Shanghai
Qinyu ZHANG ; Zhiping DUAN ; Qiang HOU ; Jiming ZHANG ; Zhijun ZHOU
Journal of Environmental and Occupational Medicine 2024;41(4):390-396
Background Under the guidance of achieving carbon peaking and carbon neutrality goals, the demand for lithium-ion batteries has increased significantly. However, during the production, use, and maintenance of lithium-ion batteries, workers are inevitably exposed to various occupational hazards, and some chemicals are nephrotoxic. Objective To evaluate the kidney function and potential determinants among male workers in a lithium-ion battery-related enterprise in Shanghai. Methods The data of occupational health examination carried out by an occupational disease prevention and control institution for workers in a lithium-ion battery-related enterprise in Shanghai were collected. The workers participating pre-employment occupational health examination were treated as a control group, and the other group was recruited from those participating periodic health examination. Serum creatinine, urea nitrogen, uric acid, and renal ultrasound were used to assess the kidney function of workers. Kidney function was classified according to the reference range of kidney function indicators in Diagnostics (9th Edition, national planning textbook for high education in medicine). Binary logistic regression and generalized linear regression were used to identify potential determinants of abnormal values in kidney function indicators in workers. Results There were 6184 workers in the control group (pre-employment) with a mean age of (27.40±4.50) years. There were 3526 workers on the job with a mean age of (29.40±4.99) years and the median time of service was 2.00 (1.00, 3.42) years. The prevalence rates of high serum creatinine, high urea nitrogen, and high uric acid, and abnormal kidney ultrasound among the control group were 0.66%, 2.47%, 30.32%, and 10.12%, respectively; the indicators in the on-the-job workers were 0.96%, 3.35%, 38.25%, and 12.68%, respectively, significantly higher than those in the control group (P<0.05). After adjusting for worker age, length of service, smoking status, drinking status, hypertension, and hyperglycemia, the binary logistic regression models showed that regular smokers had a higher risk of high urea nitrogen than nonsmokers (OR=1.411, 95%CI: 1.011, 1.969). The risk of high uric acid was lower in older workers (OR=0.966, 95%CI: 0.953, 0.979), and higher in workers with more years of service (≤1 year, OR=1.295, 95%CI: 1.093, 1.534; >1-3 years, OR=1.747, 95%CI: 1.494, 2.042; >3 years, OR=1.866, 95%CI: 1.511, 2.304), hypertension (OR=1.400, 95%CI: 1.055, 1.859), and hyperglycemia (OR=1.565, 95%CI: 1.221, 2.006). Workers who were older (OR=1.038, 95%CI: 1.022, 1.054) and had longer working years (>1-3 years, OR=1.518, 95%CI: 1.201, 1.920), occasional smoking habits (OR=1.239, 95%CI: 1.039, 1.478), regular drinking habits (OR=1.875, 95%CI: 1.139, 3.087), and hypertension (OR=1.465, 95%CI: 1.075, 1.998) were at a higher risk of renal ultrasound abnormalities. The generalized linear models showed that length of service (>1-3 years, β=1.120, 95%CI: 0.360, 1.880; >3 years, β=1.451, 95%CI: 0.543, 2.358), smoking status (occasional, β=0.818, 95%CI: 0.156, 1.479; regular, β=0.841, 95%CI: 0.066, 1.616), and hypertension (β=2.742, 95%CI: 1.390, 4.094) were the influencing factors of serum creatinine concentration in the workers. Age (β=0.014, 95%CI: 0.009, 0.019) and length of service (>1-3 years, β=0.079, 95%CI: 0.012, 0.146) were the influencing factors of urea nitrogen. Age (β=−1.759, 95%CI: −2.288, −1.231), length of service (≤1 year, β=10.676, 95%CI: 4.035, 17.316; >1-3 years, β=26.117, 95%CI: 19.962, 32.272; >3 years, β=34.558, 95%CI: 26.116, 43.001), hypertension (β=23.162, 95%CI: 11.617, 34.707), and hyperglycemia (β=15.017, 95%CI: 4.853, 25.180) were the influencing factors of uric acid. Conclusion The prevalence of abnormal kidney function of workers in selected lithium-ion battery-related enterprise is varied by age, length of service, smoking status, drinking status, hypertension, and hyperglycemia. There may be a trend that the longer the time working in a lithium-ion battery-related enterprise, the worse the workers' kidney function. Therefore, the enterprise should pay attention to the possible reasons for their changes and take targeted interventions.
6.Effectss of persistent obesity on lung function in school age children
Chinese Journal of School Health 2024;45(4):549-553
Objective:
To analyze the impact of persistent obesity on their lung function, so as to offer insights for implementing intervention measures to increase lung function in obese school age children.
Methods:
A total of 335 children from the Sheyang Mini Birth Cohort established in 2009 in Yancheng City, Jiangsu Province, who participated in the follow up at the ages of 7 years (2016) and 10 years (2019), were selected as the study participants. Physical measurements including height, weight, and lung function were recorded. According to the World Health Organization standard, that is, gender and age specific to correct the body mass index to calculate the body mass index Z score, was used to evaluate the obesity status of children at the age of 7 and 10. Children were divided into four groups, including sustained non obesity group, restored obesity group, newly classified obesity group, and persistent obesity group. Meanwhile, the lung function prediction equations recommended by the Global Lung Function Initiative were used to standardize the lung function indexes of children. Pulmonary function differences among these groups were examined, and the relationship between childhood obesity and pulmonary function was longitudinally analyzed using generalized estimating equations.
Results:
The prevalence of obesity were 9.0% and 16.1% at the age of 7 and 10 years, respectively. The proportion of both newly classified and persistent obesity group were 8.1%, respectively. The forced expiratory volume in one second (FEV 1) and forced vital capacity (FVC) were (1 269.90±202.70) and (1 415.70±230.00) mL, respectively, at the age of 7 years. FEV 1 and FVC at the age of 10 years were (1 440.80±403.20) and (1 555.60±517.60) mL, respectively. Cross sectional analysis at age 7 showed that forced expiratory flow at 75% vital capacity (FEF 75 ) ( β=-0.52, 95%CI =-0.96--0.07) and maximal mid expiratary flow (MMEF) ( β=-0.45, 95%CI =-0.89--0.00) were significantly lower in obese children compared to their non obese peers ( P < 0.05). Longitudinal analysis indicated that obese children had lower levels of lung pulmonary function, with a statistically significant difference in FEV 1 ( β=-0.44, 95%CI=-0.85--0.02, P <0.05). There was no significant difference among the various obesity groups ( P >0.05), while gender stratified results revealed significant reductions in FEV 1/FVC in newly classified obese girls at age 10 years ( β=-1.76, 95%CI =-3.13--0.38) and in MMEF in persistently obese girls at age 10 years ( β=-1.44, 95%CI = -2.79- -0.09) ( P <0.05).
Conclusion
Obesity may contribute to reduced lung function levels in school aged children, with newly classified and persistent obesity having more pronounced effects on lung function in girls.
7.The experience on the construction of the cluster prevention and control system for COVID-19 infection in designated hospitals during the period of "Category B infectious disease treated as Category A"
Wanjie YANG ; Xianduo LIU ; Ximo WANG ; Weiguo XU ; Lei ZHANG ; Qiang FU ; Jiming YANG ; Jing QIAN ; Fuyu ZHANG ; Li TIAN ; Wenlong ZHANG ; Yu ZHANG ; Zheng CHEN ; Shifeng SHAO ; Xiang WANG ; Li GENG ; Yi REN ; Ying WANG ; Lixia SHI ; Zhen WAN ; Yi XIE ; Yuanyuan LIU ; Weili YU ; Jing HAN ; Li LIU ; Huan ZHU ; Zijiang YU ; Hongyang LIU ; Shimei WANG
Chinese Critical Care Medicine 2024;36(2):195-201
The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.
8.Health status of photovoltaic module production workers in Shanghai
Zhiping DUAN ; Qinyu ZHANG ; Xuetao ZHANG ; Qiang HOU ; Yulai TIAN ; Jiming ZHANG ; Zhijun ZHOU
Journal of Environmental and Occupational Medicine 2024;41(2):153-159
Background Photovoltaic (PV) cells can convert solar energy into electricity and alleviate the dilemma of energy supply shortage. Shanghai's PV module industry is booming, but there are few reports on the health status of the workers and there is an urgent need for health risk assessment. Objective To evaluate the health status of PV module production workers and the association between work and health status, in order to provide a direction for the health management of the workers. Methods Among the PV module production workers who completed prescriptive occupational health examination by a designated medical institution in 2021, 2453 workers with more than one year of working age were selected as the exposure group and 538 newly hired workers as the control group. On the basis of the Technical specifications for occupational health surveillance (GBZ 188−2014), the health examination included physical examination and laboratory examination and information such as sociodemographics, living habits, and disease history. We compared the indicators of pure-tone hearing test, blood routine examination, electrocardiogram (ECG), liver function, and kidney function between the two groups. The blood routine results included erythrocyte-related indicators, leukocyte-related indicators, and platelet-related indicators, and the results of liver function included hepatocyte injury indicators, hepatic secretory function indicators, and hepatic synthesis function indicators. The workers were divided into four groups by quartiles of working age. Trend chi-square test was used to analyze differences in health status between the four working age groups. Multiple logistic regression models were used to evaluate the association between working age and health indicators. Results Among the exposure group workers, 2035 (83.0%) were male and 418 (17.0%) were female. The median (P25, P75) age was 34.0 (30.0, 39.0) years and the median (P25, P75) working age was 6.0 (3.0, 10.0) years. The abnormality rate of blood routine was 61.7%. Among them, the abnormality rates of platelet-related indicators and liver secretory function indicators were 39.8% and 48.1% respectively. The risks of abnormal hepatocyte injury-related indicators, fatty liver, and platelet-related indicator abnormalities among the exposure group were 1.471 (95%CI: 1.060, 2.054), 1.691 (95%CI: 1.208, 2.385), and 7.576 (95%CI: 4.967, 11.994) times higher than those in the control group respectively. The single-factor analysis demonstrated a positively linear trend between working age and hypertension prevalence, electrical audiometry abnormality rate, or liver secretory function indicator abnormality rate. Corrected for gender, age, smoking status, hypertension, etc., the results of logistic analysis showed that quartile working age was positively related to abnormal liver secretion function and abnormal platelet-related indicators respectively (OR=1.047, P=0.005; OR=1.037, P=0.014), and inversely associated with the abnormal rate of renal function (OR=0.953, P=0.044). Conclusion Negative associations between health status and working age are identified in PV module production workers. The target PV module production employees are in younger age, and with the increase of working age, the abnormalities of liver function and platelets may increase. Therefore, the enterprises should extend occupational health work from workplace to workers.
9.Levels and influencing factors of perfluorinated and polyfluoroalkyl substances in umbilical cord serum from Sheyang Mini Birth Cohort Study, Jiangsu Province
Ruonan TAN ; Zheng WANG ; Jiming ZHANG ; Yiming DAI ; Jianqiu GUO ; Xiaojuan QI ; Dasheng LU ; Xiuli CHANG ; Chunhua WU ; Zhijun ZHOU
Journal of Environmental and Occupational Medicine 2024;41(8):841-848
Background Perfluorinated and polyfluoroalkyl substances (PFAS), a large group of emerging pollutants, are ubiquitous in the ecological environment. Their multiple organ toxic effects on human body are reported. Understanding the exposure level of PFAS in cord serum and associated influencing factors can provide scientific evidence for studying maternal and newborn health effects and risk regulation. Objective To explore the exposure levels of PFAS in cord serum and potential impact factors. Methods This study was based on the maternal and infant database and the cord serum sample bank of the Sheyang Mini Birth Cohort Study (SMBCS) established in 2009. A self-designed questionnaire was used to collect information on sociodemographic characteristics, living environment, and lifestyle of mothers during pregnancy. A total of
10.MIF inhibitor ISO-1 alleviates sepsis-induced acute kidney injury by suppressing oxidative stress, inflammation, and apoptosis
Fukang Yin ; Xiaoxia Zhang ; Xiaojun Yang ; Jiming Li
Acta Universitatis Medicinalis Anhui 2024;59(12):2079-2086
Objective:
To investigate the effects and underlying mechanisms of the macrophage migration inhibitory factor(MIF) inhibitor(S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester(ISO-1) on sepsis-induced acute kidney injury(AKI).
Methods:
Human renal tubular epithelial HK-2 cells were divided into Con group(without any treatment), ISO-1 group(10 μg/ml ISO-1 treatment for 24 h) and LPS group(10 μg/ml LPS treatment for 24 h), LPS+ISO-1 group(10 μg/ml LPS treatment for 24 h followed by 10 μg/ml ISO-1 treatment for 24 h). ELISA was used to measure the levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6) in the cell supernatants. Reactive oxygen species(ROS) levels were assessed using the 6-carboxyl-2 ′,7′-dichlorodihydrofluorescein diacetate fluorescent indicator(DCFH-DA) method. Apoptosis levels were detected by TUNEL staining, and Western blot was employed to analyze the expression of proteins of Kelch like ECH associated protein 1(Keap1), NFE2 like bZIP transcription factor 2(Nrf2), heme oxygenase-1(HO-1), as well as apoptosis-related proteins Bcl-2, Bax, and cleaved Caspase-3(c-Caspase-3). A sepsis mouse model was established using the cecal ligation and puncture(CLP) method, and the mice were divided into four groups: sham-operated(Sham), ISO-1 control(ISO-1), CLP, and ISO-1 treatment(CLP+ISO-1). After the experiment, mouse kidney tissues were collected for HE staining to observe pathological changes. Blood urea nitrogen(BUN), serum creatinine(Scr), myeloperoxidase(MPO) levels in kidney tissues, glutathione(GSH) and superoxide dismutase(SOD) activities were measured. Western blot was also used to detect the expression of MIF and proteins in the Nrf2/Keap1 signaling pathway and apoptosis-related proteins in kidney tissues.
Results:
Compared to the Con group, the LPS and LPS+ISO-1 groups showed significantly increased levels of TNF-α, IL-1β, IL-6, TUNEL-positive rates, ROS levels, and protein expressions of Keap1, Bax, and c-Caspase-3 in HK-2 cells(P<0.05), while the expressions of Nrf2, HO-1, and Bcl-2 significantly decreased(P<0.05). The ISO-1 group showed no significant changes(P>0.05). Compared to the LPS group, the LPS+ISO-1 group exhibited significantly decreased levels of TNF-α, IL-1β, IL-6, TUNEL-positive rates, ROS levels, and protein expressions of Keap1, Bax, and c-Caspase-3, while the expressions of Nrf2, HO-1, and Bcl-2 significantly increased(P<0.05). In the mouse experiments, compared to the Sham group, the CLP and CLP+ISO-1 groups showed severe kidney tissue damage, increased levels of serum BUN, Scr, and kidney MIF, Keap1, Bax, and c-Caspase-3 protein expressions(P<0.05), while GSH, SOD activities, and protein expressions of Nrf2, HO-1, and Bcl-2 significantly decreased(P<0.05). The ISO-1 group showed no significant changes(P>0.05). Compared to the CLP group, the CLP+ISO-1 group showed significant improvements in the aforementioned indicators(P<0.05).
Conclusion
The specific MIF inhibitor ISO-1 can ameliorate sepsis-induced AKI by inhibiting oxidative stress, inflammatory response, and apoptosis bothin vitroandin vivo. The mechanism may be through Nrf2/Keap1 signaling pathway.


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