1.Ferroptosis and osteoporosis
Cheng YANG ; Weimin LI ; Dongcheng RAN ; Jiamu XU ; Wangxiang WU ; Jiafu XU ; Jingjing CHEN ; Guangfu JIANG ; Chunqing WANG
Chinese Journal of Tissue Engineering Research 2025;29(3):554-562
BACKGROUND:It has also been confirmed that ferroptosis is closely related to a variety of musculoskeletal diseases,such as rheumatoid arthritis,osteosarcoma,and osteoporosis.The pathophysiological mechanisms of ferroptosis and osteoporosis need to be further studied and elucidated to broaden our understanding of iron metabolism and osteoporosis.It will provide research ideas for the future elucidation of new mechanisms of osteoporosis and the development of new technologies and drugs for the treatment of osteoporosis. OBJECTIVE:To provide an overview of the current status of research on ferroptosis in osteoporosis,to provide a new direction for future research on the specific molecular mechanisms of osteoporosis,and to provide more effective and better options for osteoporosis treatment strategies. METHODS:The first author used the computer to search the literature published from 2000 to 2024 in CNKI,WanFang,VIP,and PubMed databases with search terms"ferroptosis,iron metabolism,osteoporosis,osteoblast,osteoclast,bone metabolism,signal pathway,musculoskeletal,review"in Chinese and English.A total of 68 articles were finally included according to the selection criteria. RESULTS AND CONCLUSION:(1)Ferroptosis is a new type of cell death discovered in recent years,which is usually accompanied by a large amount of iron accumulation and lipid peroxidation during cell death,and its occurrence is iron-dependent.This is distinctly different from several types of cell death that are currently being hotly studied(e.g.,cellular pyroptosis,necrotic apoptosis,cuproptosis,and autophagy).(2)Intracellular iron homeostasis is manifested as a balance between iron uptake,export,utilization,and storage.The body's iron regulatory system includes systemic and intracellular regulation.The main factor of systemic regulation is hepcidin produced by hepatic secretion,and cellular regulation depends on the iron regulatory protein/iron response element system.Of course,intracellular iron homeostasis can be controlled by other factors,such as hypoxia,cytokines,and hormones.(3)Lipid peroxidation causes oxidative damage to biological membranes(plasma membrane and internal organelle membranes),lipoproteins,and other lipid-containing molecules.Polyunsaturated fatty acid-containing phospholipids are important targets of lipid peroxidation.Free polyunsaturated fatty acid is an important substrate for lipid oxidation and can bind to the phospholipid bilayer,leading to over-oxidation and thus triggering lipid apoptosis.(4)Several studies have shown that osteoblasts are overloaded with iron in different ways,resulting in the accumulation of unstable ferrous iron and the generation of reactive oxygen species and lipid peroxides,causing ferroptosis of osteoblasts and ultimately a decrease in bone formation,affecting bone homeostasis and the development of osteoporosis.(5)Osteoclasts are large multinucleated cells formed by the fusion of mononuclear macrophage cell lines or bone marrow mesenchymal stem cells induced by nuclear factor-κB ligand receptor activator,and they have the function of bone resorption.Iron ions can promote osteoclast differentiation and bone resorption through the production of intracellular lipid reactive oxygen species,while iron chelators can inhibit osteoclast formation in vitro and thus affect the occurrence and development of osteoporosis.
2.Construction of Risk Prediction Model for Poor Prognosis among Hemorrhagic Stroke Patients:A Cross-sectional Study
Xinsheng LIU ; Wangxiang JIANG
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2024;53(3):368-374
Objective To study the predictive factors for a poor prognosis of hemorrhagic stroke,build a prediction model,and improve the current evaluation system.Methods A cross-sectional survey was conducted from the perspective of pre-hospi-tal and intra-hospital integration.After single factor comparison,indicators with significant differences were sequentially includ-ed in univariant and multivariant Poisson regression analysis.The selected independent risk factors were constructed as predic-tive models.The prediction model was converted into a visual optimization rating scale in the form of a column chart to obtain the corresponding prediction probability for the corresponding rating.The ROC curve was used to test the effectiveness of opti-mizing scores and ICH-CT scores in predicting poor prognosis.Relevant data of patients in the validation group were extracted based on the two scoring information,and the final score of each validation group patient was obtained.The scoring and prog-nostic results were substituted into the ROC curve to evaluate the predictive ability of different prediction models,and the pre-diction models were converted into visual optimization scoring scales to quantify the probability of adverse prognosis outcomes.The ICH-CT model was used as a reference to explore the effectiveness of optimizing scoring in evaluating poor prognosis out-comes in patients with hemorrhagic stroke.Results After sample size calculation,273 patients were ultimately selected as the model group for this cross-sectional study:a total of 110 hemorrhagic stroke patients had poor prognosis,163 patients had a good prognosis,and the time span was from January 2021 to September 2021.Another 81 patients with acute hemorrhagic stroke between September 2021 and January 2022 were collected as the validation group:21 patients with poor prognosis and 60 patients with acceptable prognosis were included in the hemorrhagic stroke group.The demographic characteristics of the valida-tion group were compared,and significant statistical differences were observed in the proportion of men,age,and history of dia-betes(P<0.05),Comparison of other clinical data between groups showed significant statistical differences(P<0.05)in GCS score,visit time,amount of bleeding and hematoma,mixed sign,cerebral hernia,and intraventricular hemorrhage.The cut-off values for the optimization score and ICH-CT score were 186 and 128,respectively.The AUC and Youden indices of the optimi-zation score were both higher than those of the ICH-CT score.The evaluation efficiency of the optimization score for adverse prognosis was better than that of the ICH-CT score(Z=2.369,P<0.05).Conclusion A predictive model for poor prognosis in patients with hemorrhagic stroke was constructed in this study,and it was converted it into an optimized score that has strong feasibility in clinical practice.

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