1.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.
2.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.
3.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.
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.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
8.Dosimetric and radiobiological differences in three radiotherapy techniques of whole breast irradiation with simultaneous integrated boost
Jiming YANG ; Hang CHENG ; Rui HU ; Xuhao DAI ; Yong WU ; Pengrong LOU ; Jianliang ZHOU ; Jianxin GUO ; Jiangping REN
Chinese Journal of Radiological Medicine and Protection 2024;44(9):764-770
Objective:To identify the dosimetric and radiobiological differences of three radiotherapy techniques of whole breast irradiation with simultaneous integrated boost (WBI-SIB) following breast-conserving surgery for early breast cancer (EBC).Methods:The data of 20 patients with early left-sided breast cancer who received radiotherapy following breast-conserving surgery were retrospectively analyzed. Three radiotherapy techniques, namely hybrid intensity-modulated radiotherapy (HIMRT), intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT), were redesigned with the same prescription dose and target conditions. Then, doses to target volume (TV) and organs at risk (OAR), along with the normal tissue complication probability (NTCP) and secondary cancer risk (SCR) for specific organs, were compared.Results:Compared to HIMRT and IMRT, VMAT led to significant decreases in various dosimetric indices of the affected lung and heart and increases in the Dmean doses to the healthy lung and healthy breast and V5 Gy doses to the healthy breast, with the differences being significantly different ( P < 0.05). The average NTCP values of cardiac death, radiation pneumonitis, and pulmonary fibrosis induced by VMAT were 0.41%, 1.62%, and 23.59%, respectively, significantly lower than those caused by other two techniques ( P < 0.05). No statistical differences were found in 10 dosimetric indices of OAR between IMRT and HIMRT, while the NTCP analysis suggested that the risks of cardiac death ( t = 2.70, P < 0.05) and pulmonary fibrosis ( t =4.11, P < 0.05) induced by IMRT were slightly lower than those caused by HIMRT. In addition, the excess absolute risk (EAR) to the healthy lung posed by VMAT was 1.65 and 1.83 times those induced by HIMRT and IMRT, respectively ( z = -3.92, t = -6.43, P < 0.05). In contrast, the EAR to the healthy breast induced by VMAT was 2.79 and 2.65 times those posed by HIMRT and IMRT, respectively ( z = -3.21, -3.70, P < 0.05). Conclusions:Among three intensive-modulated radiotherapy techniques of WBI-SIB for EBC, VMAT provides the optimal protection for the heart and affected lung but leads to the highest SCR to the healthy lung and breast. When VMAT is employed for young EBC patients or those with normal cardiopulmonary function, special attention should be paid to reducing low-dose irradiations to the healthy breast and thereby minimizing SCR. In contrast, VMAT might be more favorable for patients with pronounced cardiopulmonary risks or aged patients.
9.Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients
Jinlin HOU ; Edward GANE ; Rozalina BALABANSKA ; Wenhong ZHANG ; Jiming ZHANG ; Tien Huey LIM ; Qing XIE ; Chau-Ting YEH ; Sheng-Shun YANG ; Xieer LIANG ; Piyawat KOMOLMIT ; Apinya LEERAPUN ; Zenghui XUE ; Ethan CHEN ; Yuchen ZHANG ; Qiaoqiao XIE ; Ting-Tsung CHANG ; Tsung-Hui HU ; Seng Gee LIM ; Wan-Long CHUANG ; Barbara LEGGETT ; Qingyan BO ; Xue ZHOU ; Miriam TRIYATNI ; Wen ZHANG ; Man-Fung YUEN
Clinical and Molecular Hepatology 2024;30(2):191-205
Background/Aims:
Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients.
Methods:
This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks.
Results:
68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported.
Conclusions
48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.
10.Effects of flurochloridone on apoptosis and Nrf2/HO-1 and NFκB signaling pathways in mouse testis and TM4 cells
Shuqi ZHAO ; Yanna WANG ; Zhijing NI ; Fang TIAN ; Rui LI ; Jiming ZHANG ; Xiuli CHANG ; Zhijun ZHOU
Journal of Environmental and Occupational Medicine 2023;40(6):673-680
Background Flurochloridone (FLC) is toxic to male reproduction and can induce apoptosis of testicular tissue and supporting cells under oxidative stress. Of particular concern is whether nuclear factor-erythrocyte 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway and nuclear factor kappa B (NFκB) signaling pathway participate this process. Objective To observe apoptosis of testicular tissue and sertoli TM4 cells and alterations of Nrf2/HO-1 and NFκB signaling pathways in mice treated with FLC in vivo/in vitro. Methods (1) Animal experiment. Testis samples were harvested from male C57BL/6 mice after 28-day FLC (0, 3, 15, 75, and 375 mg·kg−1 per day) exposure via oral route. Malondialdehyde (MDA) and superoxide dismutase (SOD) in homogenate of testicular tissue were measured by colorimetry. Apoptosis of testicular tissue was evaluated by TUNEL staining. Expression and distribution of Nrf2 and NFκB were detected by immunohistochemistry. Protein expression levels of Nrf2, HO-1, NAD(P)H: quinone oxidoreductase 1 (NQO1), NFκB, inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ), and phosphorylated recombinant inhibitory subunit of nuclear factor kappa-B alpha (P-IκBα) in testicular tissue homogenate were determined by Western blotting. (2) Cell experiment. TM4 cell lines were treated with 40, 80, 120, 160, and 200 μmol·L−1 FLC for 6 h, and cell viability was detected by CCK-8. After 6 h exposure to 40, 80, and 160 μmol·L−1 FLC, the apoptosis rate was detected by flow cytometry, and the protein expression levels of Nrf2, HO-1, NQO1, NFκB, IKKβ, and IκBα were detected by Western blotting. Results (1) Animal experiment. Apoptosis occurred in the interstitial and basal parts of spermatogenic tubules in male C57BL/6 mice after 28 days of oral FLC exposure. Compared with the control group, the MDA level in testicular tissue of the 375 mg·kg−1 FLC-treated group was significantly increased (P<0.05), and the SOD activity was significantly decreased (P<0.05). After 375 mg·kg−1 FLC exposure, apoptosis occurred in the interstitial and basal parts of spermatogenic tubules. The results of immunohistochemistry showed the expression of Nrf2 and NFκB in the interstitium and basal part of spermatogenic tubules of the treated groups. Compared with the control group, the protein levels of Nrf2, NQO1, P-IκBα, NFκB, and IKKβ in the 15, 75, and 375 mg·kg-1 groups were significantly increased (P<0.001), and the HO-1 protein level was significantly increased in the 375 mg·kg−1 group (P<0.001). (2) Cell experiment. Compared with the control group, the TM4 cell viabilities in the 40, 80, 120, 160, and 200 μmol·L−1 FLC-treated groups significantly decreased (P<0.01). The apoptosis rates were significantly increased (P<0.05), and the apoptosis rates increased from 5.7% in the control group to 7.4%, 9.4%, and 11.7% in the 40, 80, and 160 μmol·L−1, respectively. The Nrf2 protein level in the 40 μmol·L−1 group was significantly increased (P<0.01), while the levels significantly decreased in the 80 and 160 μmol·L−1 groups (P<0.01). The HO-1 protein levels in the 40, 80, and 160 μmol·L−1 groups were significantly increased (P<0.01). The level of NQO1 protein in the 40 μmol·L−1 group was significantly increased (P<0.01). The NFκB protein levels were significantly increased in the 80 and 160 μmol·L−1 groups (P<0.001). The IκBα protein levels were significantly decreased in all treated groups (P<0.001). The IKKβ protein had no significant change. Conclusion FLC induces testicular tissue apoptosis, and the process affects Nrf2/HO-1 signaling pathway and NFκB signaling pathway. The in vitro study confirms that FLC could induce apoptosis of TM4 cells and activate Nrf2/HO-1 and NFκB signaling pathways.


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