Ferroptosis is a regulated form of cell death, with its core mechanism being intracellular iron overload-induced lipid peroxidation, leading to cellular dysfunction and mitochondrial structural abnormalities. Ferroptosis is closely related to various diseases including neurodegenerative disorders, tumors, and ischemia-reperfusion organ damage, and has become a potential therapeutic target. Iron is essential for life but can also cause cell death. Despite continuous progress in iron-related biomedical research, many questions remain unanswered. Advances in high-throughput technologies, genomics and proteomics are expected to reveal the cellular iron regulatory mechanism and open up new therapeutic approaches for ferroptosis-related diseases. This article reviews the research progress on iron in terms of its biology, metabolism, regulation, and related diseases, aiming to provide clues and references for developing new ferroptosis-targeted therapeutic strategies and facilitating more in-depth molecular studies from multiple perspectives.
Humans ; Ferroptosis/physiology* ; Iron/metabolism* ; Animals ; Neoplasms/metabolism* ; Neurodegenerative Diseases/metabolism*

BACKGROUND:In recent years,brain-computer interface technology has shown significant promise for rehabilitating limb dysfunction in stroke patients.With ongoing research deepening and its broader clinical application,combining brain-computer interface with other rehabilitation therapies to improve limb function has become a focal point of study.OBJECTIVE:To analyze and summarize the efficacy of brain-computer interface combined with various therapies in treating limb dysfunction in stroke patients and to explore the clinical value of these combined strategies.METHODS:The search terms used for the literature review in Chinese databases were"brain-computer interface,BCI,stroke,"while the terms"brain-computer interface,BCI,brain-computer interaction,brain-machine interface,BMI,stroke"were used for English databases.Literature searches were conducted in CNKI,WanFang,VIP,PubMed,Embase,and Web of Science,from the time of database construction to September 2024.Finally,a total of 3 054 articles were retrieved,and 75 articles were included after screening for summarization.RESULTS AND CONCLUSION:Currently,brain-computer interfaces,used alone or in combination with other treatments such as Chinese medical treatment,conventional rehabilitation therapy,or physical factor therapy,are achieving better outcomes in treating limb dysfunction in stroke patients.However,the efficacy of brain-computer interfaces combined with transcranial direct current stimulation for treating upper and lower limb dysfunctions is still debated.Researchers are increasingly recognizing the feasibility of these combined therapies.Yet,challenges such as limited exploration of therapeutic mechanisms,absence of standardized protocols,and small sample sizes hinder their broad application.Future research should therefore focus on understanding the mechanisms by which brain-computer interfaces can enhance effects when combined with other therapies and on standardizing criteria for clinical trials to enable widespread clinical adoption.

BACKGROUND:At present,a large number of studies have shown that mesenchymal stem cells can be combined with different strategies to more effectively improve liver fibrosis and inhibit its progression to end-stage liver disease.OBJECTIVE:To explore the mechanism of mesenchymal stem cells combined with different strategies to improve liver fibrosis compared with mesenchymal stem cells alone.METHODS:The first author used computers to search CNKI,WanFang,VIP,PubMed,Web of Science,and Nature databases involving mesenchymal stem cells combined with different strategies to improve liver fibrosis.The search terms were"mesenchymal stem cells,liver fibrosis,combination therapy,liver stellate cells"in Chinese,and"mesenchymal stem/stromal cells,liver/hepatic fibrosis/cirrhosis,combination therapy,hepatic stellate cells/HSCs"in English.By quickly browsing the title and abstract of the article,excluding the articles that are not closely related to the topic,104 articles were finally selected for review analysis.RESULTS AND CONCLUSION:Mesenchymal stem cells improve liver fibrosis by differentiating into hepato-like cells,inhibiting hepatic stellate cell activation,immune regulation,and other mechanisms.However,the low rate of liver colonization,low survival rate,and short action time of mesenchymal stem cells after transplantation limit their clinical application.Mesenchymal stem cells can improve liver fibrosis through a combination of drugs,gene modification,cytokines and other strategies,and the efficacy is better than that of mesenchymal stem cells alone.Moreover,the combination of mesenchymal stem cells and different strategies can effectively improve liver fibrosis by promoting mesenchymal stem cell homing,inhibiting hepatic stellate cell activation,regulating the microenvironment,and regulating signaling pathways.Mesenchymal stem cells can also show better liver-derived differentiation,homing and survival functions in reducing liver fibrosis through pretreatment,miRNA regulation and combination with other cells.The combination of mesenchymal stem cells and different strategies cannot avoid the potential risks of mesenchymal stem cells alone in the treatment of liver fibrosis,and the safety of these strategies(drugs,gene modifications,cytokines,etc.)is also worth considering.In addition,the number and route of mesenchymal stem cell transplantation need to be further studied.

Objective:To investigate the prevalence and severity of symptom burden among long-term survivors of oropharyngeal cancer after radiotherapy, to identify core symptom clusters, and to explore their correlation with quality of life.Methods:A previous retrospective study was conducted by the Cancer Hospital, Chinese Academy of Medical Sciences on patients with oropharyngeal cancer who underwent radiotherapy between January 2010 and December 2020. Patients who were still alive as of December 2023 were further followed and analyzed. From December 2023 to August 2024, symptom burden and quality of life were assessed using the Chinese version of the MD Anderson Symptom Inventory–Head and Neck Module (MDASI-HN) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Exploratory factor analysis (principal component analysis with Promax rotation) were used to identify symptom clusters. Spearman correlation analysis was performed to explore the relationship between total symptom cluster scores and standardized domain scores of quality of life. Multivariate linear regression analysis was further employed to determine the relationship between identified symptom clusters and overall quality of life.Results:A total of 273 patients were included, with a median follow-up duration of 6.2 years (range: 3.5-14.5 years) and a median age of 61 years (range: 27-88 years) at follow-up. The top 5 incidence rates of symptom reported by patients were mucus problems in the mouth or throat (147 cases, 53.8%), dental or gum issues (143 cases, 52.4%), xerostomia (140 cases, 51.3%), difficulty swallowing or chewing (95 cases, 34.8%), and taste disturbance (79 cases, 28.9%). Among them, xerostomia was the most serious symptom. The most frequently reported interference was impact on work (including household chores) (55 cases, 20.1%). Exploratory factor analysis identified 3 symptom clusters: fatigue-nausea cluster, eating-voice cluster, and xerostomia-sleep cluster, all of which were significantly correlated with lower overall quality of life of patients (all P<0.001). Conclusion:Long-term survivors of oropharyngeal cancer after radiotherapy experience substantial symptom burden. The fatigue-nausea, eating-voice, and xerostomia-sleep clusters are the core symptom clusters impacting quality of life.

BACKGROUND:In recent years,brain-computer interface technology has shown significant promise for rehabilitating limb dysfunction in stroke patients.With ongoing research deepening and its broader clinical application,combining brain-computer interface with other rehabilitation therapies to improve limb function has become a focal point of study.OBJECTIVE:To analyze and summarize the efficacy of brain-computer interface combined with various therapies in treating limb dysfunction in stroke patients and to explore the clinical value of these combined strategies.METHODS:The search terms used for the literature review in Chinese databases were"brain-computer interface,BCI,stroke,"while the terms"brain-computer interface,BCI,brain-computer interaction,brain-machine interface,BMI,stroke"were used for English databases.Literature searches were conducted in CNKI,WanFang,VIP,PubMed,Embase,and Web of Science,from the time of database construction to September 2024.Finally,a total of 3 054 articles were retrieved,and 75 articles were included after screening for summarization.RESULTS AND CONCLUSION:Currently,brain-computer interfaces,used alone or in combination with other treatments such as Chinese medical treatment,conventional rehabilitation therapy,or physical factor therapy,are achieving better outcomes in treating limb dysfunction in stroke patients.However,the efficacy of brain-computer interfaces combined with transcranial direct current stimulation for treating upper and lower limb dysfunctions is still debated.Researchers are increasingly recognizing the feasibility of these combined therapies.Yet,challenges such as limited exploration of therapeutic mechanisms,absence of standardized protocols,and small sample sizes hinder their broad application.Future research should therefore focus on understanding the mechanisms by which brain-computer interfaces can enhance effects when combined with other therapies and on standardizing criteria for clinical trials to enable widespread clinical adoption.

BACKGROUND:At present,a large number of studies have shown that mesenchymal stem cells can be combined with different strategies to more effectively improve liver fibrosis and inhibit its progression to end-stage liver disease.OBJECTIVE:To explore the mechanism of mesenchymal stem cells combined with different strategies to improve liver fibrosis compared with mesenchymal stem cells alone.METHODS:The first author used computers to search CNKI,WanFang,VIP,PubMed,Web of Science,and Nature databases involving mesenchymal stem cells combined with different strategies to improve liver fibrosis.The search terms were"mesenchymal stem cells,liver fibrosis,combination therapy,liver stellate cells"in Chinese,and"mesenchymal stem/stromal cells,liver/hepatic fibrosis/cirrhosis,combination therapy,hepatic stellate cells/HSCs"in English.By quickly browsing the title and abstract of the article,excluding the articles that are not closely related to the topic,104 articles were finally selected for review analysis.RESULTS AND CONCLUSION:Mesenchymal stem cells improve liver fibrosis by differentiating into hepato-like cells,inhibiting hepatic stellate cell activation,immune regulation,and other mechanisms.However,the low rate of liver colonization,low survival rate,and short action time of mesenchymal stem cells after transplantation limit their clinical application.Mesenchymal stem cells can improve liver fibrosis through a combination of drugs,gene modification,cytokines and other strategies,and the efficacy is better than that of mesenchymal stem cells alone.Moreover,the combination of mesenchymal stem cells and different strategies can effectively improve liver fibrosis by promoting mesenchymal stem cell homing,inhibiting hepatic stellate cell activation,regulating the microenvironment,and regulating signaling pathways.Mesenchymal stem cells can also show better liver-derived differentiation,homing and survival functions in reducing liver fibrosis through pretreatment,miRNA regulation and combination with other cells.The combination of mesenchymal stem cells and different strategies cannot avoid the potential risks of mesenchymal stem cells alone in the treatment of liver fibrosis,and the safety of these strategies(drugs,gene modifications,cytokines,etc.)is also worth considering.In addition,the number and route of mesenchymal stem cell transplantation need to be further studied.

Objective:To investigate the prevalence and severity of symptom burden among long-term survivors of oropharyngeal cancer after radiotherapy, to identify core symptom clusters, and to explore their correlation with quality of life.Methods:A previous retrospective study was conducted by the Cancer Hospital, Chinese Academy of Medical Sciences on patients with oropharyngeal cancer who underwent radiotherapy between January 2010 and December 2020. Patients who were still alive as of December 2023 were further followed and analyzed. From December 2023 to August 2024, symptom burden and quality of life were assessed using the Chinese version of the MD Anderson Symptom Inventory–Head and Neck Module (MDASI-HN) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Exploratory factor analysis (principal component analysis with Promax rotation) were used to identify symptom clusters. Spearman correlation analysis was performed to explore the relationship between total symptom cluster scores and standardized domain scores of quality of life. Multivariate linear regression analysis was further employed to determine the relationship between identified symptom clusters and overall quality of life.Results:A total of 273 patients were included, with a median follow-up duration of 6.2 years (range: 3.5-14.5 years) and a median age of 61 years (range: 27-88 years) at follow-up. The top 5 incidence rates of symptom reported by patients were mucus problems in the mouth or throat (147 cases, 53.8%), dental or gum issues (143 cases, 52.4%), xerostomia (140 cases, 51.3%), difficulty swallowing or chewing (95 cases, 34.8%), and taste disturbance (79 cases, 28.9%). Among them, xerostomia was the most serious symptom. The most frequently reported interference was impact on work (including household chores) (55 cases, 20.1%). Exploratory factor analysis identified 3 symptom clusters: fatigue-nausea cluster, eating-voice cluster, and xerostomia-sleep cluster, all of which were significantly correlated with lower overall quality of life of patients (all P<0.001). Conclusion:Long-term survivors of oropharyngeal cancer after radiotherapy experience substantial symptom burden. The fatigue-nausea, eating-voice, and xerostomia-sleep clusters are the core symptom clusters impacting quality of life.

Objective:To prospectively observe the changes of tumor-related symptoms in patients with nasopharyngeal carcinoma following the administration of nimotuzumab one week before radiotherapy.Methods:Non-metastatic nasopharyngeal carcinoma patients with positive epidermal growth factor receptor (EGFR) expression and symptoms caused by the primary lesion or metastatic cervical lymph nodes admitted to Cancer Hospital of Chinese Academy of Medical Sciences were prospectively recruited. Investigators recorded tumor-related symptoms in recruited patients one day before the first administration of nimotuzumab (D0) and conducted follow-up visits from day 2 to day 7 after the first administration (D2-D7) to document symptom changes. All recruited patients were asked to assess tumor-related symptoms on D0 and D7 by visual analogue scale (VAS) scores. VAS scores were analyzed by paired t-test. Results:From June 2020 to April 2023, a total of 21 patients met the inclusion criteria. The median age was 49 years (range: 27-69 years), with a male-to-female ratio of 1.3:1. Among the patients, 17 patients (81%) received concurrent nimotuzumab for 8 cycles, 7 cycles for 3 cases (14%), and 6 cycles for 1 case (5%), respectively. All patients completed symptom assessments as required. The overall response rate of symptoms after the first administration of nimotuzumab was 62%, with response rates of 4/6、5/8、4/10、4/10、4/11、3/11 for tinnitus, headache, aural fullness, secondary pain caused by neck mass, nasal bleeding, and nasal obstruction, respectively. The VAS scores for overall symptoms were significantly decreased after the administration of nimotuzumab one week before radiotherapy ( P<0.001), with the most significant decrease in VAS scores for tinnitus, aural fullness, and headache. Conclusion:The administration of nimotuzumab one week before radiotherapy significantly alleviates tumor-related symptoms in patients with nasopharyngeal carcinoma, particularly in alleviating tinnitus, aural fullness, and headache.

BACKGROUND:It was found that the ligands and receptors of Notch are both cell membrane surface proteins,which are important proteins to mediate intercellular communication,and the Notch signaling pathway plays a crucial regulatory role in the proliferation and differentiation of mesenchymal stem cells. OBJECTIVE:To review the regulatory mechanism of the Notch signaling pathway on the proliferation and differentiation of mesenchymal stem cells,summarize and clarify the research advance in how the Notch signaling pathway regulates the proliferation and differentiation of mesenchymal stem cells,and provide theoretical support for the future use of stem cells to treat various related diseases. METHODS:By using the computer,the first author searched the relevant studies involving Notch signaling pathway regulation of mesenchymal stem cell proliferation and differentiation on CNKI,Wanfang,VIP,PubMed,Web of Science,and Nature databases with Chinese search terms"mesenchymal stem cells,Notch,Notch signaling pathway,proliferation,differentiation"and the English search terms"mesenchymal stem cells,MSC,Notch,Notch signaling pathway,proliferation,differentiation".Part of the literature was searched in combination with the literature tracing method.Finally,87 articles were included in the review analysis. RESULTS AND CONCLUSION:(1)Notch signaling pathway is a conserved signaling pathway in multicellular organisms,which plays an important role in regulating cell differentiation,proliferation,apoptosis,and the cell cycle by mediating communication between neighboring cells through receptor-ligand binding.(2)Mesenchymal stem cells are a class of adult stem cells with self-proliferative and multi-directional differentiation potential,which can be regulated by external signaling pathways to affect their proliferation and differentiation.Notch signaling pathway,as one of them,when Notch ligands are activated,the Notch proteins will undergo two protein hydrolysis cleavages to release Notch intracellular structural domain NICD,which then enters the nucleus and thus promotes the transcription of target genes to regulate the proliferation and differentiation of mesenchymal stem cells from different sources,such as bone marrow,adipose,and umbilical cord.However,the specific mechanisms that regulate the proliferation and differentiation of mesenchymal stem cells from different tissue sources of the same species are different.(3)The Notch signaling pathway can regulate the differentiation of mesenchymal stem cells into different target cells,but due to different target cells,the expression levels of receptors or ligands in the Notch signaling pathway vary.(4)Clinical targeting of the Notch signaling pathway to promote mesenchymal stem cells for the treatment of various refractory diseases,such as aplastic anemia,severe joint injuries,ischemic strokes,and myocardial infarctions,has a promising application.(5)By exploring the Notch signaling pathway via regulating the expression levels of its receptors and ligands in bone marrow mesenchymal stem cells from rat,mouse,and human,it can be found that the Notch signaling pathway expression levels in the proliferation and differentiation of mesenchymal stem cells from different species origins are also different.(6)The role of mesenchymal stem cells in tissue engineering has been gradually highlighted due to their advantages of safety,low immune rejection,and wide therapeutic prospects.The Notch signaling pathway regulates the proliferation and differentiation of mesenchymal stem cells with a wide range of influencing factors,and subsequent studies should further optimize the influencing factor variables and explore the standardized studies of regulating the proliferation and differentiation of mesenchymal stem cells.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.