1.Underlying target of bullatine A in treating rheumatoid arthritis based on LiP-SMap drug target proteomics
Hao-hong ZHANG ; Nan-ting ZOU ; Chun-fei ZHANG ; Qing-yan MO ; Ming-qian JU ; Xiao-hong LI ; Shuai LIU ; Mao-kui HUANG ; Hong-yun WANG ; Chun-ping WAN
Chinese Pharmacological Bulletin 2025;41(6):1072-1078
Aim To identify the underlying target of bullatine A(BA)against rheumatoid arthritis(RA)u-sing limited proteolysis-small molecule mapping(LiP-SMap)drug target proteomics and to provide a scientif-ic basis for clinical application of Aconiti brachypodi Radix in the treatment of RA.Methods LiP-SMap drug target proteomics was employed to perform bioin-formatics analysis for comparing and validating the dif-ferential protein expression after BA intervention.A collagen-induced arthritis(CIA)model was estab-lished in DBA/1 mice using bovine type Ⅱ collagen.The mice were then divided into the CIA model group,methotrexate-positive control group(MTX group),and BA groups(10 mg·kg-1 and 20 mg·kg-1)based on their clinical scores.After drug intervention,the thera-peutic efficacy against RA was assessed by joint index scores and foot thickness measurements.Histopatholog-ical changes in the arthritic joints of CIA mice were e-valuated using hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was employed to detect inflammatory cytokines interleukin-17(IL-17)and total IgG and IgG3 anti-collagen-spe-cific antibodies levels from the serum of CIA mice.Flow cytometry was used to detect the expression levels of intracellular Th17 cells(IL-17+CD4+T cells)and Th1 cells(IFN-γ+CD4+T cells).Fluorescent quanti-tative PCR was performed to detect the expression of genes related to differential proteins.Results The proteomic analysis identified Serpinb1a as a protein with strong binding affinity to BA,and KEGG enrich-ment analysis indicated IL-17 signaling pathway was a crucial pathway of BA in against RA.BA treatment significantly reduced clinical scores and foot thickness,improved local arthritis symptoms in CIA mice,and al-leviated inflammatory cell infiltration into arthritic joints(P<0.05).Differential protein validation re-sults showed that BA had strong affinity with Serpinb1a(-5.92 kJ·mol-1)and downregulated the expres-sion of Serpinb1a mRNA.Furthermore,the administra-tion of BA markedly reduced serum IL-17 A levels from CIA mice,inhibited the expression of intracellular IL-17 A and IFN-γ cytokines in splenic CD4+T cells(P<0.05),and significantly downregulated the transcrip-tional expression of IL-17F(P<0.05).Conclusion BA exhibits therapeutic effects on collagen-induced arthritis,and its mechanism of action may involve the regulation of Serpinb1a and the IL-17 signaling path-way.
2.Study on risk factors of colorectal adenomatous polyps and construction and validation of prediction model
Kui DONG ; Jie WU ; Jing YAN ; Haitao LIU ; Jun WANG ; Guan'en QIAO
The Journal of Practical Medicine 2025;41(6):838-845
Objective To identify risk factors for colorectal adenomatous polyps using logistic regression analysis,construct a prediction model based on these identified factors,and subsequently evaluate the performance of the model.Methods Encompassed 1,023 patients who underwent large intestine polyp resection at the First Hospital of Handan between January 2017 and January 2022.Among these patients,676 had adenomatous polyps(adenomatous polyp group)and 347 had non-adenomatous polyps(non-adenomatous polyp group).We collected data on basic information,medical history,colonoscopy results,and polyp pathology.By comparing the two groups,we identified significant differences in various indicators,which were selected as candidate factors for model construction.Patients were randomly divided into a training set and a validation set at an 8∶2 ratio.Using the training set data,we constructed a risk prediction model and developed a nomogram using R Studio software to visually present the model.Finally,we internally validated the model using the validation set.The model's discrimination ability was evaluated using the ROC curve,its accuracy was assessed via the calibration curve,and its clinical utility was evaluated through decision curve analysis(DCA).Results Significant differences were observed between the two groups in terms of age,drinking habits,family history of colorectal cancer,hyperlipid-emia,history of cholecystectomy,HP infection,and history of appendectomy(P<0.05).These variables were included in the model construction.A total of 818 participants were randomly assigned to the training set,while 205 were allocated to the validation set.Multivariate logistic regression analysis on the training set confirmed that age(OR=1.021,95%CI:1.006~1.036,P=0.006),alcohol consumption(OR=3.440,95%CI:2.251~5.257,P<0.001),first-degree relatives with colorectal cancer(OR=3.775,95%CI:1.881~7.577,P<0.001),hyperlipidemia(OR=3.428,95%CI:2.443~4.808,P<0.001),history of cholecystectomy(OR=3.916,95%CI:1.756~8.735,P<0.001),Helicobacter pylori(HP)infection(OR=3.292,95%CI:2.309~4.693,P<0.001),and history of appendectomy(OR=3.819,95%CI:2.002~7.286,P<0.001)were independent risk factors for adenomatous polyps.Consequently,a prediction model for large intestine adenomatous polyps was developed using the formula P=1/(1+e-Y),where Y=0.020×age+1.328×first-degree relatives with colorectal cancer+1.235×alcohol consumption+1.232×hyperlipidemia+1.365×cholecystectomy+1.192×HP infection+1.340×appendectomy-1.995.The model demonstrated good performance with AUC values of 0.763(95%CI:0.729~0.797)for the training set and 0.769(95%CI:0.644~0.787)for the validation set.The calibration curve indicated a good fit,and decision curve analysis showed that the model could achieve positive net benefit across a wide range of threshold probabilities,confirming its clinical utility.Conclusions Age,alcohol consumption,a family history of colorectal cancer in first-degree relatives,hyperlipidemia,cholecystectomy,HP infection,and appendectomy were identified as independent risk factors for adenomatous polyps.A prediction model incorporating these risk factors holds significant practical value for predicting the occurrence of colorectal adenomatous polyps.
3.Analysis of Cardiac Involvement in Patients With Fabry Disease in Anhui Region
Zhiquan LIU ; Qi WANG ; Kui MAO ; Xueping WEI ; Guohong WU ; Jia LIU ; Wei WEN ; Fei YU ; Hao SU ; Ji YAN ; Dongmei YANG ; Kangyu CHEN
Chinese Circulation Journal 2025;40(6):597-604
Objectives:To analyze the cardiac involvement of patients with Fabry disease(FD)in Anhui region.Methods:This retrospective analysis included 48 previously and currently diagnosed FD patients(25 males)in Anhui region,overall patient and gender specific cardiac involvement was analyzed.Results:The median age of FD patients is 28.0(19.0,46.0)years.The cardiac manifestations of patients with FD were most commonly characterized by palpitations/arrhythmias(13/42 cases)and exertional dyspnea(11/42 cases),electrocardiographic changes were most commonly characterized by T-wave inversion(22/42 cases),ST-segment depression(16/42 cases),and left ventricular hypervoltage(18/42 cases),cardiac structural and functional changes were most common in papillary muscle hypertrophy(29/36 cases),bilateral sign(22/37 cases)and left ventricular hypertrophy(21/46 cases),as well as reduced left ventricular global longitudinal strain(26/39 cases).Neuropathic pain(28/43 cases)was the most common extracardiac manifestation of FD patients.FD patients of different gender differed in age at diagnosis(P=0.018),alpha galactosidase A activity(P<0.001),globotriaosylsphingosine(lyso-GL3)levels(P<0.001),enzyme replacement therapy rate(P=0.043),dyshidrosis(P<0.01),and the incidence of angiokeratoma(P=0.004).Correlation analysis showed that genotype was not correlated with enzyme activity or Lyso-GL-3 levels,whereas the Sokolow-Lyon index was positively correlated with Lyso-GL-3 levels(ρ=0.423,P=0.008),and the Sokolow-Lyon indices(septal thickness:ρ=0.562,P<0.001;left ventricle posterior wall thickness:ρ=0.569,P<0.001)and QRS duration(septal thickness:ρ=0.543,P<0.001;left ventricle posterior wall thickness:ρ=0.557,P<0.001)were positively correlated with left ventricular wall thickness.Conclusions:Cardiac involvement in patients with FD in the Anhui region is characterised by palpitations or arrhythmias,accompanied by nonspecific electrocardiographic changes.Echocardiography frequently reveals papillary muscle hypertrophy.The manifestation of cardiac involvement in patients of different genders is similar.
4.Analysis of notifiable infectious diseases in Zhejiang Province in 2024
DING Zheyuan ; YANG Yan ; FU Tianying ; LU Qinbao ; WANG Xinyi ; WU Haocheng ; LIU Kui ; LIN Junfen ; WU Chen
Journal of Preventive Medicine 2025;37(5):433-438,442
Objective:
To investigate the epidemic situation of notifiable infectious diseases in Zhejiang Province in 2024, so as to summarize the epidemic characteristics.
Methods:
Data of notifiable infectious diseases cases in Zhejiang Province from January 1 to December 31, 2024 were collected from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. The epidemiological characteristics were analyzed according to the classification and transmission routes using the descriptive epidemiological method.
Results:
A total of 32 types of notifiable infectious diseases with 1 858 695 cases and 392 deaths were reported in Zhejiang Province in 2024, with a reported incidence of 2 804.73/105 and a reported mortality of 0.591 5/100 000. A total of 238 infectious disease public health emergencies were reported, of which 218 (91.60%) occurred in schools and kindergartens. There were 22 types of class A and B notifiable infectious diseases reported, with incidence of 470.62/100 000 and mortality of 0.591 5/100 000. Totally 10 types of class C notifiable infectious diseases, with a reported incidence of 2 334.11/105, and no deaths were reported. Classified by transmission route, respiratory infectious diseases had the highest reported incidence of 2 423.87/100 000, among which influenza exhibited the highest reported incidence of 2 024.22/100 000. The reported incidence of intestinal infectious diseases was 312.94/105, among which the incidence of other infectious diarrhea and hand-foot-mouth disease (HFMD) were high, with reported incidences of 169.52/100 000 and 136.18/100 000, respectively. Blood-borne and sexually transmitted infectious diseases accounted for the largest number of reported deaths, among which AIDS had the highest mortality of 0.424 0/100 000. Natural and insect-borne infectious diseases exhibited a low reported incidence of 1.37/105. The reported incidence of dengue fever was 0.40/100 000, and 95.08% of the cases were imported.
Conclusions
The reported incidence of respiratory and intestinal infectious diseases and the reported mortality of AIDS were high in Zhejiang Province in 2024. It is recommended to strengthen the prevention and control of infectious diseases such as influenza, other infectious diarrhea, and HMFD in schools and kindergartens.
5.Study on risk factors of colorectal adenomatous polyps and construction and validation of prediction model
Kui DONG ; Jie WU ; Jing YAN ; Haitao LIU ; Jun WANG ; Guan'en QIAO
The Journal of Practical Medicine 2025;41(6):838-845
Objective To identify risk factors for colorectal adenomatous polyps using logistic regression analysis,construct a prediction model based on these identified factors,and subsequently evaluate the performance of the model.Methods Encompassed 1,023 patients who underwent large intestine polyp resection at the First Hospital of Handan between January 2017 and January 2022.Among these patients,676 had adenomatous polyps(adenomatous polyp group)and 347 had non-adenomatous polyps(non-adenomatous polyp group).We collected data on basic information,medical history,colonoscopy results,and polyp pathology.By comparing the two groups,we identified significant differences in various indicators,which were selected as candidate factors for model construction.Patients were randomly divided into a training set and a validation set at an 8∶2 ratio.Using the training set data,we constructed a risk prediction model and developed a nomogram using R Studio software to visually present the model.Finally,we internally validated the model using the validation set.The model's discrimination ability was evaluated using the ROC curve,its accuracy was assessed via the calibration curve,and its clinical utility was evaluated through decision curve analysis(DCA).Results Significant differences were observed between the two groups in terms of age,drinking habits,family history of colorectal cancer,hyperlipid-emia,history of cholecystectomy,HP infection,and history of appendectomy(P<0.05).These variables were included in the model construction.A total of 818 participants were randomly assigned to the training set,while 205 were allocated to the validation set.Multivariate logistic regression analysis on the training set confirmed that age(OR=1.021,95%CI:1.006~1.036,P=0.006),alcohol consumption(OR=3.440,95%CI:2.251~5.257,P<0.001),first-degree relatives with colorectal cancer(OR=3.775,95%CI:1.881~7.577,P<0.001),hyperlipidemia(OR=3.428,95%CI:2.443~4.808,P<0.001),history of cholecystectomy(OR=3.916,95%CI:1.756~8.735,P<0.001),Helicobacter pylori(HP)infection(OR=3.292,95%CI:2.309~4.693,P<0.001),and history of appendectomy(OR=3.819,95%CI:2.002~7.286,P<0.001)were independent risk factors for adenomatous polyps.Consequently,a prediction model for large intestine adenomatous polyps was developed using the formula P=1/(1+e-Y),where Y=0.020×age+1.328×first-degree relatives with colorectal cancer+1.235×alcohol consumption+1.232×hyperlipidemia+1.365×cholecystectomy+1.192×HP infection+1.340×appendectomy-1.995.The model demonstrated good performance with AUC values of 0.763(95%CI:0.729~0.797)for the training set and 0.769(95%CI:0.644~0.787)for the validation set.The calibration curve indicated a good fit,and decision curve analysis showed that the model could achieve positive net benefit across a wide range of threshold probabilities,confirming its clinical utility.Conclusions Age,alcohol consumption,a family history of colorectal cancer in first-degree relatives,hyperlipidemia,cholecystectomy,HP infection,and appendectomy were identified as independent risk factors for adenomatous polyps.A prediction model incorporating these risk factors holds significant practical value for predicting the occurrence of colorectal adenomatous polyps.
6.Nailfold video capillaroscopy in the Raynaud′s phenomenon associated with connective tissue disease: a meta-analysis
Youqun ZHANG ; Yanwen LIU ; Cong LEI ; Kui ZHANG ; Yan ZHENG ; Ping ZHU
Chinese Journal of Rheumatology 2025;29(5):399-405
Objective:Nailfold video capillaroscopy (NVC) was used to evaluate the microvascular changes in patients with connective tissue diseases (CTD)-related Raynaud′s phenomenon and explore its potential application value in understanding the pathogenesis, diagnosis, and treatment of CTD.Methods:The literature on NVC of connective tissue disease related patients published by CNKI, China biomedical literature database, Weipu Database,Wanfang Database, PubMed, Embase, Web of Science and Cochrane were searched, and the publication cases of time was up until May 2024. Quality assessment of the included studies was performed using the National Institutes of Health observational cohort and cross-sectional study quality assessment tools. Begg′s test and Egger′s test were analyzed with random effects meta-analysis.Results:A total of 12 studies were included, including 495 cases of Raynaud′s phenomenon of Connective tissue diseases, and 716 no-Raynaud′s phenomenon of Connective tissue diseases. The abnormal rate of nail microcirculation in CTDs-RP group was higher than that in CTDs-nonRP group [ OR value(95% CI)=2.20 (1.55, 3.12), P<0.001], Subgroup analysis showed that the proportion of scleroderma pattern in the CTDs-RP group was higher than that in the control group [ OR value (95% CI)=10.88 (2.34, 50.52), P=0.002], Telangiectasia rate in the CTDs-RP group was higher than that in the control group [ OR value (95% CI)=5.12 (3.40, 7.70), P<0.001]. The SSc pattern was higher in patients with CTD-RP than in the control group [ OR (95% CI)=2.47 (1.60, 3.79), P<0.001], The rate of capillary malformation in the CTD-RP group was higher than that in the control group [ OR value (95% CI)=2.39 (1.36, 4.19), P=0.002], The capillary density was mild decreased in the CTD-RP group [SMD value (95% CI)=-0.27 (-0.66, 0.13), P=0.185]. Conclusion:The proportion of patients with nail-fold abnormality is higher in CTD-RP group was higher than in the CTD-noRP group, and the microcirculation injury is more severe in CTD-RP group.
7.Prescriptions and syndromes of Chaihu and Longgu Muli Decoction for treatment of tachyarrhythmia accompanied by anxiety state based on Delphi method.
Gang LIU ; Yan-Li LI ; Kui-Po YAN ; Hai-Feng YAN ; Lei ZHANG ; Ming-Yuan DU ; Yi-Zhuo LI ; Cui-Ling ZHU
China Journal of Chinese Materia Medica 2025;50(6):1680-1687
Chaihu and Longgu Muli Decoction has demonstrated significant efficacy in the treatment of tachyarrhythmia accompanied by anxiety and depression. However, there is a lack of standardized guidelines for its clinical application. In this study, the Chaihu and Longgu Muli Decoction was investigated through extensive research on ancient and modern literature, as well as a collection of clinical medical records. The basic information, medication details, and diagnostic information from medical records, personal experience literature, and clinical cases in the treatment of tachyarrhythmia accompanied by anxiety were extracted and analyzed to preliminarily identify the prescription characteristics and syndrome patterns. Subsequently, the Delphi method was employed to construct an item pool based on the data obtained in the first step. An expert questionnaire was prepared to collect scores and revision opinions from experts regarding these items. After statistical analysis and group discussions, a second round of questionnaires was formed by screening out certain items. This process was repeated until a final item set for the treatment of tachyarrhythmia accompanied by anxiety with Chaihu and Longgu Muli Decoction was determined. These findings provided guidance for clinical prescription practices. By extracting 71 syndromes and signs, as well as 33 tongue and pulse characteristics, the main syndrome features included palpitations, chest tightness, irritability, etc., which were basically consistent with the ancient syndromes. Through frequency analysis and group discussions, 71 items were screened out. After screening, modification, and primary and secondary division, 11 main diagnostic items and 10 secondary diagnostic items were determined. On this basis, the research team believes that Chaihu and Longgu Muli Decoction is mainly indicated for the following syndromes in the treatment of tachyarrhythmia accompanied by anxiety(palpitations, poor sleep, bitter taste, dry mouth, irritability/easily angered/anxiety/fearfulness/easily startled, red tongue with greasy yellow coating, rapid pulse, high work/life pressure, tachyarrhythmia on electrocardiogram/Holter monitor, and positive results on anxiety scale). Secondary syndromes include chest tightness, shortness of breath, feeling heavy and weak in the body, sweating, poor appetite, constipation, greasy white tongue coating, wiry pulse, slippery pulse, or knotted and intermittent pulse.
Drugs, Chinese Herbal/therapeutic use*
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Humans
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Delphi Technique
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Anxiety/complications*
;
Tachycardia/psychology*
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Female
;
Male
;
Middle Aged
;
Adult
;
Aged
8.Analysis of Cardiac Involvement in Patients With Fabry Disease in Anhui Region
Zhiquan LIU ; Qi WANG ; Kui MAO ; Xueping WEI ; Guohong WU ; Jia LIU ; Wei WEN ; Fei YU ; Hao SU ; Ji YAN ; Dongmei YANG ; Kangyu CHEN
Chinese Circulation Journal 2025;40(6):597-604
Objectives:To analyze the cardiac involvement of patients with Fabry disease(FD)in Anhui region.Methods:This retrospective analysis included 48 previously and currently diagnosed FD patients(25 males)in Anhui region,overall patient and gender specific cardiac involvement was analyzed.Results:The median age of FD patients is 28.0(19.0,46.0)years.The cardiac manifestations of patients with FD were most commonly characterized by palpitations/arrhythmias(13/42 cases)and exertional dyspnea(11/42 cases),electrocardiographic changes were most commonly characterized by T-wave inversion(22/42 cases),ST-segment depression(16/42 cases),and left ventricular hypervoltage(18/42 cases),cardiac structural and functional changes were most common in papillary muscle hypertrophy(29/36 cases),bilateral sign(22/37 cases)and left ventricular hypertrophy(21/46 cases),as well as reduced left ventricular global longitudinal strain(26/39 cases).Neuropathic pain(28/43 cases)was the most common extracardiac manifestation of FD patients.FD patients of different gender differed in age at diagnosis(P=0.018),alpha galactosidase A activity(P<0.001),globotriaosylsphingosine(lyso-GL3)levels(P<0.001),enzyme replacement therapy rate(P=0.043),dyshidrosis(P<0.01),and the incidence of angiokeratoma(P=0.004).Correlation analysis showed that genotype was not correlated with enzyme activity or Lyso-GL-3 levels,whereas the Sokolow-Lyon index was positively correlated with Lyso-GL-3 levels(ρ=0.423,P=0.008),and the Sokolow-Lyon indices(septal thickness:ρ=0.562,P<0.001;left ventricle posterior wall thickness:ρ=0.569,P<0.001)and QRS duration(septal thickness:ρ=0.543,P<0.001;left ventricle posterior wall thickness:ρ=0.557,P<0.001)were positively correlated with left ventricular wall thickness.Conclusions:Cardiac involvement in patients with FD in the Anhui region is characterised by palpitations or arrhythmias,accompanied by nonspecific electrocardiographic changes.Echocardiography frequently reveals papillary muscle hypertrophy.The manifestation of cardiac involvement in patients of different genders is similar.
9.Inhibition of KLK8 promotes pulmonary endothelial repair by restoring the VE-cadherin/Akt/FOXM1 pathway.
Ying ZHAO ; Hui JI ; Feng HAN ; Qing-Feng XU ; Hui ZHANG ; Di LIU ; Juan WEI ; Dan-Hong XU ; Lai JIANG ; Jian-Kui DU ; Ping-Bo XU ; Yu-Jian LIU ; Xiao-Yan ZHU
Journal of Pharmaceutical Analysis 2025;15(4):101153-101153
Image 1.
10.Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway.
Wen-Yan ZHOU ; Jian-Kui DU ; Hong-Hong LIU ; Lei DENG ; Kai MA ; Jian XIAO ; Sheng ZHANG ; Chang-Nan WANG
Journal of Integrative Medicine 2025;23(5):560-575
OBJECTIVE:
Baicalein has been reported to have wide therapeutic effects that act through its anti-inflammatory activity. This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy (SIC).
METHODS:
A thorough screening of a small library of natural products, comprising 100 diverse compounds, was conducted to identify the most effective drug against lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes. The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology.
RESULTS:
Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes. It exhibited a dose-dependent inhibitory effect on cell injury and inflammation. In the LPS-induced septic mouse model, baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits, inflammatory responses, and ferroptosis. Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit α (HIF1-α) is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury. By combining microRNA (miRNA) screening in LPS-treated myocardium with miRNA prediction targeting HIF1-α, we found that miR-299b-5p may serve as a regulator of HIF1-α. The reduction in miR-299b-5p levels in LPS-treated myocardium, compared to the control group, was reversed by baicalein treatment. The reverse transcription quantitative polymerase chain reaction, Western blotting, and dual-luciferase reporter gene analyses together identified HIF1-α as the target of miR-299b-5p in cardiomyocytes.
CONCLUSION
Baicalein mitigates SIC at the miRNA level, suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-α/ferroptosis pathway. Please cite this article as: Zhou WY, Du JK, Liu HH, Deng L, Ma K, Xiao J, Zhang S, Wang CN. Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway. J Integr Med. 2025; 23(5):560-575.
Flavanones/pharmacology*
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Animals
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MicroRNAs/genetics*
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Lipopolysaccharides
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Hypoxia-Inducible Factor 1, alpha Subunit/genetics*
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Ferroptosis/drug effects*
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Mice
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Myocytes, Cardiac/metabolism*
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Signal Transduction/drug effects*
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Rats
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Male
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Mice, Inbred C57BL
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Cardiomyopathies/etiology*
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Cell Line
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Sepsis/complications*


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