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.

BACKGROUND:Whether activating transcription factor 7 interacting protein(Atf7ip)is involved in the regulation in osteogenic differentiation is still controversial,and studying its impact on osteogenic differentiation and its specific mechanisms is of great significance. OBJECTIVE:To investigate the effect of Atf7ip on bone morphogenetic protein 2 promoting osteogenic differentiation of mouse embryonic osteoblast precursor cells(MC3T3-E1). METHODS:MC3T3-E1 cells cultured in vitro were divided into three groups:normal group,interference group(NC-siRNA group,Atf7ip-siRNA group),and high expression group(CMV-VC group and CMV-Atf7ip group),and were transfected for 24 hours,and then treated with 200 ng/mL bone morphogenetic protein 2 for 0,12,24,and 48 hours,respectively.qRT-PCR was used to detect the mRNA expression levels of Atf7ip,alkaline phosphatase,osteocalcin,type I collagen α1 in the cells of each group.Western blot assay was used to detect the protein expression of osteogenic differentiation markers Sp7 and Runx2,and the expression of Atf7ip binding molecule SETDB1,histone H3 and H3K9me3.Alkaline phosphatase activity was detected by alkaline phosphatase staining. RESULTS AND CONCLUSION:(1)With the increase of bone morphogenetic protein 2 treatment time,the protein and mRNA expression of Atf7ip decreased,while the protein expression of Sp7,Runx2 and the mRNA expression of osteocalcin and alkaline phosphatase increased significantly(P<0.05).There was no significant change in the protein expression of Atf7ip binding molecule SETDB1.(2)Compared with the NC-siRNA group,the protein expression of Sp7,Runx2 and the mRNA expression of osteocalcin and type I collagen α1 were significantly up-regulated(P<0.05),and alkaline phosphatase activity was significantly enhanced;and H3K9 methylation significantly decreased in the Atf7ip-siRNA group(P<0.05).(3)Compared with the CMV-VC group,the protein expression of Sp7 and Runx,as well as mRNA expression of osteocalcin,alkaline phosphatase,and type I collagen α1 was significantly downregulated(P<0.05),and the alkaline phosphatase activity was significantly reduced in the CMV-Atf7ip group,while the H3K9 methylation protein in the CMV-Atf7ip group was significantly upregulated compared to the control group(P<0.05).(4)In conclusion,Atf7ip expression was decreased during bone morphogenetic protein 2-induced osteogenic differentiation of MC3T3-E1,and osteogenic differentiation was significantly increased after knockdown of Atf7ip.Overexpression of Atf7ip significantly weakened osteogenic differentiation,indicating that Atf7ip is a negative regulatory factor of bone morphogenetic protein 2 promoting osteogenic differentiation of MC3T3-E1 cells.

Objective To explore the causal relationship between ischemic stroke and different types of epilepsy so as to provide genetic evidence for the risk of epilepsy after ischemic stroke.Methods Based on the summary data of genome-wide association study,Mendelian randomization (MR ) analysis was performed with MR-Egger regression,weighted median and inverse-variance weighting.Sensitivity analysis was conducted by using MR-Egger regression test,MR-PRESSO test and leave-one-out method.Results Two-sample MR analysis showed that there was a causal relationship between ischemic stroke and the risk of epilepsy (OR=1.10,P=0.036)and generalized epilepsy (OR=1.25,P=0.001 ),but no such relationship was observed with the risk of focal epilepsy (OR=1.06,P=0.360).In addition,diastolic blood pressure (OR=1.12,P=0.002)and BMI (OR=1.08,P=0.015)also had a causal relationship with the risk of epilepsy. After adjusting confounding factors,multivariate MR analysis revealed that only ischemic stroke (OR=1.18,P=3.770×10-6)and epilepsy risk had a causal relationship.Conclusion There is a causal relationship between ischemic stroke and the risk of generalized epilepsy,which can be used to stratify the risk of post-stroke epilepsy.

Transjugular intrahepatic portosystemic shunt （TIPS） has been recommended as a treatment method for cirrhotic portal hypertension in domestic and foreign guidelines， but there is still uncertainty in its therapeutic efficacy. More and more studies have shown that TIPS combined with collateral vessel embolization （TIPS+E） has certain advantages in the treatment of gastroesophageal variceal bleeding in liver cirrhosis. This article reviews the major studies on TIPS+E in China and globally， summarizes related recommendations in guidelines and the current status of clinical application， and proposes the issues that need to be solved， such as indication， hemodynamic criteria， and selection of materials for embolization， and large－sample multicenter randomized controlled trials are needed for further clarification.

Objective:To observe the maximum tongue pressure and study the oropharyngeal activity during swallowing of patients with nasopharyngeal carcinoma (NPC) after radiotherapy so as to correlate the maximum tongue pressure with swallowing function.Methods:The mean maximum tongue pressure of nineteen NPC patients with dysphagia was measured at the anterior (TA), middle (TM) and posterior (TP) positions, followed by video fluoroscopy. Oral transit time (OTT), upper esophageal sphincter(UES)opening time (UOT) and UES opening range (UOR) were correlated with the mean maximum tongue pressures.Results:The maximum pressure at the TM and TP positions was significantly negatively correlated with OTT, but there was no significant correlation with the anterior readings. The maximum pressures at all three tongue positions were, however, positively correlated with UOT and UOR.Conclusion:The maximum pressure at the TA, TM and TP positions is strongly correlated with the swallowing function of NPC patients.

Objective: To identify the pathophysiological characteristics of cortical stroke survivors′ swallowing. Methods: Sixty cortical stroke survivors with dysphagia and cognitive impairment were enrolled into the observation group, while another 16 with dysphagia but without cognitive impairment formed the unimpaired control group and 16 healthy counterparts were selected for a normal control group. Each subject was recorded videofluoroscopically while swallowing 5ml of a liquid of medium consistency. The occurrence of refusing to eat, mouth opening difficulty, incomplete oral closure, residue in the oral cavity, residue in the pharyngeal cavity, leakage and aspiration were observed. Each subject′s swallowing time and kinematic parameters were analyzed from the fluoroscopic videos. Results: The incidence of refusing to eat (37.5%) and/or incomplete mouth closure (68.75%) were significantly higher in the observation group than in the other two groups. The incidence of difficulty in opening the mouth (37.5%), residue in the oral cavity (81.25%), residue in the pharyngeal cavity (56.25%), leakage (56.25%) and aspiration (50%) of the observation group were significantly higher in the observation group than among the normal controls, but were not significantly different from those incidences among the group without cognitive impairment. The average oral transit time and soft palate elevation time of the observation group were significantly longer than those of the other two groups. The observation group′s average hyoid movement time was significantly longer than that of the normal control group, but not significantly different from that of the group without cognitive impairment. There were no significant differences among the groups in average upper esophageal sphincter opening time, larynx closure time or the kinematic parameters. Conclusions Stroke survivors with dysphagia and cognitive impairment present dysphagia characteristic of oral phase swallowing difficulties.

Objective:To explore the clinical utility of tongue pressure resistance feedback training in the treatment of post-stroke dysphagia.Methods:Twenty stroke survivors with dysphagia were randomly divided into an experimental group and a control group. Both groups were given conventional swallowing rehabilitation training, while the experimental group was additionally provided with tongue pressure resistance feedback training. Before and after the treatment, MBSImp analysis and the Rosenbek penetration aspiration scale were used to quantify the control of the tongue, food delivery, oral residue, laryngeal elevation, hyoid bone movement, epiglottis turnover, larynx closure, vestibular larynx closure, pharyngal peristalsis and contraction, opening of the upper esophageal sphincter UES, contraction of the base of the tongue, pharyngeal residue and aspiration.Results:No significant differences were observed between the two groups before the intervention. Afterward the average pharyngeal period and aspiration score of the experimental group had decreased significantly compared with the control group′s values.Conclusions:Tongue pressure resistance feedback training is effective in improving pharyngeal swallowing and reducing the risk of aspiration after swallowing.

Objective:To observe the immediate effect of neuromuscular electrical stimulation (NMES) on the initiation of swallowing among stroke survivors with dysphagia.Methods:Forty-two patients with delayed swallowing initiation were asked to eat 3 boluses of a thin liquid before and during NMES stimulation. The process was recorded and analyzed using a digital data acquisition and analysis system, including the initiation of the pharyngeal swallow (IPS), oral transit time (OTT), larynx closure duration (LCD), and pharynx transit time (PTT). They were also evaluated using the Rosenbek penetration-aspiration scale (PAS).Results:During NMES, significant improvement was observed in the average IPS, PAS and OTT results compared to before the intervention. There was, however, no significant difference in the average LCD or PTT. No obvious adverse reactions were observed during the stimulation.Conclusion:NMES has an immediate effect on improving IPS, PAS and OTT, and can be used as a new compensatory early treatment for stroke survivors with dysphagia.

Objective:To develop a lung cancer risk prediction model for female non-smokers.Methods:Based on the Kailuan prospective dynamic cohort (2006.05-2015.12), a nested case-control study was conducted. Participants diagnosed with primary pathologically confirmed lung cancer during follow-up were identified as the case group, and others were identified as the control group. A total of 24 701 subjects were included in the study, including 86 lung cancer cases and 24 615 control population, respectively. Questionnaires, physical examinations, and laboratory tests were conducted to collect relevant information. Multivariable-adjusted logistic regressions were conducted to develop a lung cancer risk prediction model. Area Under the Curve (AUC) and Hosmer-Lemeshow tests were used to evaluate discrimination and calibration, respectively. Ten-fold cross-validation was used for internal validation.Results:Two sets of models were developed: the simple model (including age and monthly income) and the metabolic index model [including age, monthly income, fasting blood glucose (FBG), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C)].The AUC (95%CI) [0.745 (0.719-0.771)] of the metabolic index model was higher than that of the simple prediction model [0.688 (0.660-0.716)] ( P=0.004). Both the simple model ( PHL=0.287) and the metabolic index model ( PHL=0.134) were well-calibrated. The results of ten-fold cross-validation indicated sufficient stability, with an average AUC of 0.699 and a standard error (SD) of 0.010. Conclusion:By incorporating metabolic markers, accurate and reliable lung cancer risk prediction model for female non smokers could be developed.

Objective:To develop a lung cancer risk prediction model for female non-smokers.Methods:Based on the Kailuan prospective dynamic cohort (2006.05-2015.12), a nested case-control study was conducted. Participants diagnosed with primary pathologically confirmed lung cancer during follow-up were identified as the case group, and others were identified as the control group. A total of 24 701 subjects were included in the study, including 86 lung cancer cases and 24 615 control population, respectively. Questionnaires, physical examinations, and laboratory tests were conducted to collect relevant information. Multivariable-adjusted logistic regressions were conducted to develop a lung cancer risk prediction model. Area Under the Curve (AUC) and Hosmer-Lemeshow tests were used to evaluate discrimination and calibration, respectively. Ten-fold cross-validation was used for internal validation.Results:Two sets of models were developed: the simple model (including age and monthly income) and the metabolic index model [including age, monthly income, fasting blood glucose (FBG), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C)].The AUC (95%CI) [0.745 (0.719-0.771)] of the metabolic index model was higher than that of the simple prediction model [0.688 (0.660-0.716)] ( P=0.004). Both the simple model ( PHL=0.287) and the metabolic index model ( PHL=0.134) were well-calibrated. The results of ten-fold cross-validation indicated sufficient stability, with an average AUC of 0.699 and a standard error (SD) of 0.010. Conclusion:By incorporating metabolic markers, accurate and reliable lung cancer risk prediction model for female non smokers could be developed.