1.The mechanism of Laggerae Herba in improving chronic heart failure by inhibiting ferroptosis through the Nrf2/SLC7A11/GPX4 signaling pathway
Jinling XIAO ; Kai HUANG ; Xiaoqi WEI ; Xinyi FAN ; Wangjing CHAI ; Jing HAN ; Kuo GAO ; Xue YU ; Fanghe LI ; Shuzhen GUO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):343-353
Objective:
To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice.
Methods:
Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue.
Results:
Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group.
Conclusion
Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.
2.Influence of occupational hazard factors on incidence of hypertension in calcium carbide plant: Historical cohort study
Meng LIU ; Wei ZHANG ; Qi ZHUANG ; Xingyu PENG ; Jinling LIU ; Tiantian CHEN ; Hongmei GU ; Shu GUO
Journal of Environmental and Occupational Medicine 2025;42(5):565-570
Background The high work intensity and possible subsequently increased susceptibility to occupational hazards of calcium carbide plants may lead to hypertension in workers, but there are few studies on the relationship between occupational hazard exposure and hypertension in workers involving the production process of calcium carbide. Objective To explore the influence of occupational hazards on the incidence of hypertension in calcium carbide plants. Methods Using historical cohort design, the employees of a calcium carbide factory in the western part of Inner Mongolia Autonomous Region were selected as research subjects. According to the pre-determined inclusion and exclusion criteria, the study population comprised an exposure group of 377 employees (including furnace workers, inspection workers, and maintenance workers) exposed to dust, noise & carbon monoxide, and a control group of 388 employees (including central control workers, electricians, and administrative personnel) without above-mentioned exposure. The total sample size was 765 participants. The follow-up period was from April 2011 to October 2022, and the study endpoint was defined as the conclusion of the follow-up period or diagnosed hypertension in annual occupational health examination. Information on general demographic characteristics, living habits, and work status was collected from all study subjects. Cox proportional hazards regression model was used to analyze the association between occupational hazard exposure and the risk of hypertension among the calcium carbide plant employees. Results The average age, mean systolic and diastolic blood pressure, proportion of males, smoking rate, and alcohol consumption rate in the exposure group were higher than those in the control group (P<0.05). Compared to baseline, both systolic and diastolic blood pressure levels increased in the exposure group and the control group at the end of the follow-up (P<0.05). At the end of the follow-up, the average differences between systolic/ diastolic blood pressure and baseline values in the exposure group were higher than those in the control group (P<0.05). During the follow-up period, a total of 223 cases of hypertension occurred, with a total follow-up of
3.Establishment and evaluation of an animal model of heart failure with preserved ejection fraction integrating disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis
Xiaoqi WEI ; Xinyi FAN ; Feng JIANG ; Wangjing CHAI ; Jinling XIAO ; Fanghe LI ; Kuo GAO ; Xue YU ; Wei WANG ; Shuzhen GUO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):501-515
Objective:
This study aimed to construct an animal model of heart failure with preserved ejection fraction (HFpEF) that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis and to evaluate it comprehensively.
Methods:
The HFpEF mouse model was constructed using a combination of Nω-nitro-L-arginine methyl ester (L-NAME) and a high-fat diet. According to the random number table method, SPF-grade male C57BL/6J mice were randomly assigned to the control, L-NAME, high-fat diet, and model groups, 10 in each group. Comprehensive observations and data collection on macroscopic signs (e.g., fur condition, mental state, stool and urine, oral and nasal condition, paw and body condition, etc.) and cardiac function were performed after 10 and 16 weeks of model induction. Additionally, the syndrome evolution was elucidated based on diagnostic criteria for clinical syndromes of heart failure. Furthermore, pathological and molecular biological examinations of myocardial tissue were performed to assess the stability and reliability of the model.
Results:
Mice in the model group showed typical characteristics of syndrome of qi deficiency and blood stasis, as well as syndrome of internal heat accumulation, including lethargy, slow response, dull paw color and oral/nasal color, exercise intolerance, abnormal platelet activation, dry feces, and dark yellow urine. The time window for these syndromes was between 10 and 16 weeks post-modeling. Cardiac function assessments revealed severe diastolic dysfunction, concentric myocardial hypertrophy, and myocardial fibrosis in the model group. Pathological examinations showed a significantly increased collagen deposition in the myocardial interstitium, enlarged cross-sectional area of cardiomyocytes, and sparse coronary microvasculature in the model group. Molecular biological analyses indicated marked activation of the inducible nitric oxide synthase/nuclear factor kappa-light-chain-enhancer of activated B cells/NOD-like receptor family pyrin domain containing 3 inflammatory pathway and significantly elevated inflammation levels in the myocardial tissue of the model group. Although mice in the L-NAME and high-fat diet groups also showed certain manifestations of qi deficiency syndrome, the substantial cardiac damage was relatively limited compared to the control group.
Conclusion
This study has constructed an animal model of HFpEF that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis. The macroscopic and microscopic characteristics of this model are consistent with the manifestations of syndrome of qi deficiency and blood stasis, toxin syndrome, and syndrome of internal heat accumulation. Moreover, it can stably simulate the HFpEF state and reflect phenotypic changes in human disease. This model provides a suitable experimental platform to explore the pathogenesis of HFpEF, evaluate the effectiveness of traditional Chinese medicine (TCM) treatment regimens, and promote in-depth research on TCM syndromes of heart failure.
4.Relationship between serum perlecan,neurociliin-1 levels and disease condition,perinatal outcome of gestational hypertension patients in late pregnancy
Jinling ZHANG ; Lihong GUO ; Xiaojie WANG
International Journal of Laboratory Medicine 2024;45(4):495-499
Objective To explore the relationship between the levels of serum perlecan and neurociliin-1(NRP-1)and disease condition,perinatal outcome of gestational hypertension patients in late pregnancy.Meth-ods A total of 103 gestational hypertension patients in late pregnancy admitted to the hospital from January 2021 to January 2023 were selected as the subjects of this study.According to the severity of the disease,they were divided into simple hypertension group(n=46),mild eclampsia group(n=35)and severe eclampsia group(n=22).The perinatal outcomes of the patients were recorded and divided into good outcome group(n=72)and poor outcome group(n=31).Serum perlecan and NRP-1 levels were detected by enzyme-related immunosorbent assay,and the predictive value of serum perlecan and NRP-1 on perinatal outcomes in gesta-tional hypertension patients in late pregnancy was investigated by receiver operating characteristic(ROC)curve analysis.Multivariate Logistic regression analysis was used to investigate the influencing factors of peri-natal outcomes in gestational hypertension patients in late pregnancy.Results The serum levels of perlecan and NRP-1 in mild eclampsia group and severe eclampsia group were lower than those in simple hypertension group,and the difference was statistically significant(P<0.05);Serum levels of perlecan and NRP-1 in severe eclampsia group were lower than those in mild eclampsia group,and the difference was statistically significant(P<0.05).The serum levels of perlecan and NRP-1 in the good outcome group were higher than those in the bad outcome group,and the difference was statistically significant(P<0.05).The clinical efficacy of serum perlecan and NRP-1 combined in predicting perinatal outcomes of gestational hypertension patients in late pregnancy was better than that of single index.The proportion of age≥35 years old,pre-pregnancy body mass index(BMI)≥24 kg/m2,history of abortion,systolic blood pressure,diastolic blood pressure and 24 h urinary protein in the adverse outcome group were higher than those in the good outcome group,and the differences were statistically significant(P<0.05).Multivariate Logistic regression analysis showed that pre-pregnancy BMI≥24 kg/m2,history of abortion,high systolic blood pressure,perlecan≤8.63 nmol/L and RNP-1≤4.37 ng/mL were independent risk factors for adverse perinatal outcomes in gestational hypertension patients in late pregnancy(P<0.05).Conclusion The decrease of serum perlecan and NRP-1 levels is associated with the aggravation of the disease and adverse perinatal outcomes in gestational hypertension patients in late preg-nancy,and the two indicators can be used as biological markers to predict the perinatal outcomes of patients.
5.Analysis of Cognition Status and Influencing Factors of Medical Research Ethics Review Standards among Physicians in Tertiary Hospitals
Jinling GUO ; Beibei LIU ; Shanshan YIN ; Hua FENG ; Shuying LIANG
Chinese Hospital Management 2024;44(10):62-66
Objective To understand the cognition status of medical scientific research ethics review norms among physicians in tertiary hospitals and the factors influencing their awareness.Methods A survey was conducted using a questionnaire.A total of 2 067 questionnaires were distributed to physicians in tertiary hospitals in Henan Province,with an effective response rate of 81.95%.Results(1)Physicians'awareness rate of Regulations on Ethical Review of Biomedical Research Involving Human Subjects reached 69.01%,while that of Opinions on Strengthening Ethical Governance in Science and Technology was only 34.30%.A total of 310 respondents were aware of all six medical research ethics-related regulations.(2)1 153 respondents were familiar with all four basic principles of medical ethics.(3)78.98%of physicians had received training in medical research ethics knowledge.Learning through medical school and special lectures made it easier for physicians to understand medical research ethics knowledge(P<0.05).(4)The results of binary logistic regression analysis showed that educational level,membership in an ethics committee,and receipt of ethics training significantly influenced physicians'understanding of medical research ethics knowledge(P<0.05).Conclusion Physicians have low awareness of newly issued medical research ethics review norms,targeted training is needed to enhance physicians'research ethics literacy.
6.Analysis of Cognition Status and Influencing Factors of Medical Research Ethics Review Standards among Physicians in Tertiary Hospitals
Jinling GUO ; Beibei LIU ; Shanshan YIN ; Hua FENG ; Shuying LIANG
Chinese Hospital Management 2024;44(10):62-66
Objective To understand the cognition status of medical scientific research ethics review norms among physicians in tertiary hospitals and the factors influencing their awareness.Methods A survey was conducted using a questionnaire.A total of 2 067 questionnaires were distributed to physicians in tertiary hospitals in Henan Province,with an effective response rate of 81.95%.Results(1)Physicians'awareness rate of Regulations on Ethical Review of Biomedical Research Involving Human Subjects reached 69.01%,while that of Opinions on Strengthening Ethical Governance in Science and Technology was only 34.30%.A total of 310 respondents were aware of all six medical research ethics-related regulations.(2)1 153 respondents were familiar with all four basic principles of medical ethics.(3)78.98%of physicians had received training in medical research ethics knowledge.Learning through medical school and special lectures made it easier for physicians to understand medical research ethics knowledge(P<0.05).(4)The results of binary logistic regression analysis showed that educational level,membership in an ethics committee,and receipt of ethics training significantly influenced physicians'understanding of medical research ethics knowledge(P<0.05).Conclusion Physicians have low awareness of newly issued medical research ethics review norms,targeted training is needed to enhance physicians'research ethics literacy.
7.Analysis of Cognition Status and Influencing Factors of Medical Research Ethics Review Standards among Physicians in Tertiary Hospitals
Jinling GUO ; Beibei LIU ; Shanshan YIN ; Hua FENG ; Shuying LIANG
Chinese Hospital Management 2024;44(10):62-66
Objective To understand the cognition status of medical scientific research ethics review norms among physicians in tertiary hospitals and the factors influencing their awareness.Methods A survey was conducted using a questionnaire.A total of 2 067 questionnaires were distributed to physicians in tertiary hospitals in Henan Province,with an effective response rate of 81.95%.Results(1)Physicians'awareness rate of Regulations on Ethical Review of Biomedical Research Involving Human Subjects reached 69.01%,while that of Opinions on Strengthening Ethical Governance in Science and Technology was only 34.30%.A total of 310 respondents were aware of all six medical research ethics-related regulations.(2)1 153 respondents were familiar with all four basic principles of medical ethics.(3)78.98%of physicians had received training in medical research ethics knowledge.Learning through medical school and special lectures made it easier for physicians to understand medical research ethics knowledge(P<0.05).(4)The results of binary logistic regression analysis showed that educational level,membership in an ethics committee,and receipt of ethics training significantly influenced physicians'understanding of medical research ethics knowledge(P<0.05).Conclusion Physicians have low awareness of newly issued medical research ethics review norms,targeted training is needed to enhance physicians'research ethics literacy.
8.Analysis of Cognition Status and Influencing Factors of Medical Research Ethics Review Standards among Physicians in Tertiary Hospitals
Jinling GUO ; Beibei LIU ; Shanshan YIN ; Hua FENG ; Shuying LIANG
Chinese Hospital Management 2024;44(10):62-66
Objective To understand the cognition status of medical scientific research ethics review norms among physicians in tertiary hospitals and the factors influencing their awareness.Methods A survey was conducted using a questionnaire.A total of 2 067 questionnaires were distributed to physicians in tertiary hospitals in Henan Province,with an effective response rate of 81.95%.Results(1)Physicians'awareness rate of Regulations on Ethical Review of Biomedical Research Involving Human Subjects reached 69.01%,while that of Opinions on Strengthening Ethical Governance in Science and Technology was only 34.30%.A total of 310 respondents were aware of all six medical research ethics-related regulations.(2)1 153 respondents were familiar with all four basic principles of medical ethics.(3)78.98%of physicians had received training in medical research ethics knowledge.Learning through medical school and special lectures made it easier for physicians to understand medical research ethics knowledge(P<0.05).(4)The results of binary logistic regression analysis showed that educational level,membership in an ethics committee,and receipt of ethics training significantly influenced physicians'understanding of medical research ethics knowledge(P<0.05).Conclusion Physicians have low awareness of newly issued medical research ethics review norms,targeted training is needed to enhance physicians'research ethics literacy.
9.Analysis of Cognition Status and Influencing Factors of Medical Research Ethics Review Standards among Physicians in Tertiary Hospitals
Jinling GUO ; Beibei LIU ; Shanshan YIN ; Hua FENG ; Shuying LIANG
Chinese Hospital Management 2024;44(10):62-66
Objective To understand the cognition status of medical scientific research ethics review norms among physicians in tertiary hospitals and the factors influencing their awareness.Methods A survey was conducted using a questionnaire.A total of 2 067 questionnaires were distributed to physicians in tertiary hospitals in Henan Province,with an effective response rate of 81.95%.Results(1)Physicians'awareness rate of Regulations on Ethical Review of Biomedical Research Involving Human Subjects reached 69.01%,while that of Opinions on Strengthening Ethical Governance in Science and Technology was only 34.30%.A total of 310 respondents were aware of all six medical research ethics-related regulations.(2)1 153 respondents were familiar with all four basic principles of medical ethics.(3)78.98%of physicians had received training in medical research ethics knowledge.Learning through medical school and special lectures made it easier for physicians to understand medical research ethics knowledge(P<0.05).(4)The results of binary logistic regression analysis showed that educational level,membership in an ethics committee,and receipt of ethics training significantly influenced physicians'understanding of medical research ethics knowledge(P<0.05).Conclusion Physicians have low awareness of newly issued medical research ethics review norms,targeted training is needed to enhance physicians'research ethics literacy.
10.Analysis of Cognition Status and Influencing Factors of Medical Research Ethics Review Standards among Physicians in Tertiary Hospitals
Jinling GUO ; Beibei LIU ; Shanshan YIN ; Hua FENG ; Shuying LIANG
Chinese Hospital Management 2024;44(10):62-66
Objective To understand the cognition status of medical scientific research ethics review norms among physicians in tertiary hospitals and the factors influencing their awareness.Methods A survey was conducted using a questionnaire.A total of 2 067 questionnaires were distributed to physicians in tertiary hospitals in Henan Province,with an effective response rate of 81.95%.Results(1)Physicians'awareness rate of Regulations on Ethical Review of Biomedical Research Involving Human Subjects reached 69.01%,while that of Opinions on Strengthening Ethical Governance in Science and Technology was only 34.30%.A total of 310 respondents were aware of all six medical research ethics-related regulations.(2)1 153 respondents were familiar with all four basic principles of medical ethics.(3)78.98%of physicians had received training in medical research ethics knowledge.Learning through medical school and special lectures made it easier for physicians to understand medical research ethics knowledge(P<0.05).(4)The results of binary logistic regression analysis showed that educational level,membership in an ethics committee,and receipt of ethics training significantly influenced physicians'understanding of medical research ethics knowledge(P<0.05).Conclusion Physicians have low awareness of newly issued medical research ethics review norms,targeted training is needed to enhance physicians'research ethics literacy.


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