Iron is an essential trace element in the human body, crucial in maintaining normal physiological functions. Recent studies have identified iron ions as a significant factor in initiating the ferroptosis process, a novel mode of programmed cell death characterized by iron overload and lipid peroxide accumulation. The iron metabolism pathway is one of the primary mechanisms regulating ferroptosis, as it maintains iron homeostasis within the cell. Numerous studies have demonstrated that abnormalities in iron metabolism can trigger the Fenton reaction, exacerbating oxidative stress, and leading to cell membrane rupture, cellular dysfunction, and damage to tissue structures. Therefore, regulation of iron metabolism represents a key strategy for ameliorating ferroptosis and offers new insights for treating diseases associated with iron metabolism imbalances. This review first summarizes the mechanisms that regulate iron metabolic pathways in ferroptosis and discusses the connections between the pathogenesis of various diseases and iron metabolism. Next, we introduce natural and synthetic small molecule compounds, hormones, proteins, and new nanomaterials that can affect iron metabolism. Finally, we provide an overview of the challenges faced by iron regulators in clinical translation and a summary and outlook on iron metabolism in ferroptosis, aiming to pave the way for future exploration and optimization of iron metabolism regulation strategies.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective:To systematically analyze the incidence and influencing factors of frailty in elderly patients with hematologic malignancies.Methods:Research on frailty in elderly patients with hematologic malignancies was retrieved from Chinese and English databases such as China National Knowledge Infrastructure, Wanfang Data, PubMed, and Web of Science. The search period was from database establishment to August 23, 2024. Two researchers screened the included studies, conducted quality assessment, and extracted data. Meta-analysis was conducted using Stata 18 and RevMan 5.4.Results:A total of seven studies were included, encompassing 19 076 elderly hematologic malignancy patients, with a frailty incidence of 59% [95% CI (0.48, 0.69) ]. Meta-analysis revealed that age [ MD=4.31, 95% CI (3.67, 4.96) ], gender [ OR=0.88, 95% CI (0.83, 0.93) ], alcohol consumption [ OR=1.67, 95% CI (1.15, 2.44) ], self-care ability [ MD=-1.79, 95% CI (-3.17, -0.41) ], anemia [ OR=6.67, 95% CI (2.94, 15.14) ], infection [ OR=1.81, 95% CI (1.16, 2.84) ], and neuropathy [ OR=2.52, 95% CI (1.38, 4.61) ] were the influencing factors of frailty in elderly patients with hematologic malignancies. Conclusions:The incidence of frailty is high in elderly patients with hematologic malignancies. Elderly patients with hematologic malignancies who are older, female, consume alcohol, have low self-care ability, anemia, infections, and neuropathy are prone to frailty. Healthcare providers can conduct early screening and intervention for high-risk populations of frailty based on risk factors to improve the quality of life for elderly hematologic malignancy patients.

Objective:To investigate the role of cognitive appraisal and benefit-finding in the association be-tween fear of progression and quality of life among patients with chronic heart failure.Methods:A total of 362 chronic heart failure(CHF)patients from two tertiary hospitals were assessed with the Fear of Progression Ques-tionnaire-Short Form(FoP-Q-SF),Cognitive Appraisal of Health Scale(CAHS),Benefit-Finding Scale(BFS),and Minnesota Living with Heart Failure Questionnaire(MLHFQ).Results:The MLHFQ total scores were positively correlated with the scores of FoP-Q-SF and CAHS(r=0.57,0.44,Ps＜0.01),and negatively correlated with the BFS scores(r=0.47,P＜0.01).Structural equation modeling revealed that cognitive appraisal and benefit-finding sequentially mediated the relationship between fear of progression and quality of life,accounting for 27.43％of the total indirect effect.Conclusion:The psychological adaptation of chronic heart failure patients follows a negative chain path of"fear→maladaptive cognition→ meaning deprivation".while the synergistic intervention of cognitive reappraisal and benefit-finding could disrupt this cascade.Interventions combining cognitive reappraisal and benefit-finding may interrupt this process and improve quality of life.

OBJECTIVE: To construct a prediction model for the clinical effect of eye acupuncture combined with rehabilitation therapy on ischemic stroke based on interpretable machine learning. METHODS: From January 1st, 2020 to October 1st, 2024, the clinical data of 470 patients with ischemic stroke were collected in the the Second Department of Encephalopathy Rehabilitation of the Affiliated Hospital of Liaoning University of TCM. The modified Barthel index (MBI) score before and after treatment was used to divide the patients into an effect group (291 cases) and a non-effect group (179 cases). Random forest and recursive feature elimination with cross-validation were combined to screen the predictors of the therapeutic effect of patients. Seven representative machine learning models with different principles were established according to the screening results. The predictive effect of the best model was evaluated by receiver operating characteristics (ROC), calibration, and clinical decision-making (DCA) curves. Finally, the Shapley additive explanation (SHAP) framework was used to interpret the prediction results of the best model. RESULT: ①All the machine learning models presented the area under curve (AUC) to be above 85%. Of these models, the random forest model showed the best prediction ability, with AUC of 0.96 and the precision of 0.87. ②The prediction probability of calibration curve and the actual probability showed a good prediction consistency. ③The net benefit rate of DCA curve in the range of 0.1 to 1.0 was higher than the risk threshold, indicating a good effect of model. ④SHAP explained the characteristic values of variables that affected the prediction effect of the model, meaning, more days of treatment, lower MBI score before treatment, lower level of fibrinogen, shorter days of onset and younger age. These values demonstrated the better effect of eye acupuncture rehabilitation therapy. CONCLUSION The rehabilitation effect prediction model constructed in this study presents a good performance, which is conductive to assisting doctors in formulating targeted personalized rehabilitation programs, and identifying the benefit groups of eye acupuncture combined with rehabilitation therapy and finding the advantageous groups with clinical effect. It provides more ideas for the treatment of ischemic stroke with eye acupuncture combined with rehabilitation therapy.
Humans ; Acupuncture Therapy ; Machine Learning ; Male ; Female ; Middle Aged ; Ischemic Stroke/rehabilitation* ; Aged ; Stroke Rehabilitation ; Adult ; Eye

Objective:To investigate the role of cognitive appraisal and benefit-finding in the association be-tween fear of progression and quality of life among patients with chronic heart failure.Methods:A total of 362 chronic heart failure(CHF)patients from two tertiary hospitals were assessed with the Fear of Progression Ques-tionnaire-Short Form(FoP-Q-SF),Cognitive Appraisal of Health Scale(CAHS),Benefit-Finding Scale(BFS),and Minnesota Living with Heart Failure Questionnaire(MLHFQ).Results:The MLHFQ total scores were positively correlated with the scores of FoP-Q-SF and CAHS(r=0.57,0.44,Ps＜0.01),and negatively correlated with the BFS scores(r=0.47,P＜0.01).Structural equation modeling revealed that cognitive appraisal and benefit-finding sequentially mediated the relationship between fear of progression and quality of life,accounting for 27.43％of the total indirect effect.Conclusion:The psychological adaptation of chronic heart failure patients follows a negative chain path of"fear→maladaptive cognition→ meaning deprivation".while the synergistic intervention of cognitive reappraisal and benefit-finding could disrupt this cascade.Interventions combining cognitive reappraisal and benefit-finding may interrupt this process and improve quality of life.

Objective:To systematically analyze the incidence and influencing factors of frailty in elderly patients with hematologic malignancies.Methods:Research on frailty in elderly patients with hematologic malignancies was retrieved from Chinese and English databases such as China National Knowledge Infrastructure, Wanfang Data, PubMed, and Web of Science. The search period was from database establishment to August 23, 2024. Two researchers screened the included studies, conducted quality assessment, and extracted data. Meta-analysis was conducted using Stata 18 and RevMan 5.4.Results:A total of seven studies were included, encompassing 19 076 elderly hematologic malignancy patients, with a frailty incidence of 59% [95% CI (0.48, 0.69) ]. Meta-analysis revealed that age [ MD=4.31, 95% CI (3.67, 4.96) ], gender [ OR=0.88, 95% CI (0.83, 0.93) ], alcohol consumption [ OR=1.67, 95% CI (1.15, 2.44) ], self-care ability [ MD=-1.79, 95% CI (-3.17, -0.41) ], anemia [ OR=6.67, 95% CI (2.94, 15.14) ], infection [ OR=1.81, 95% CI (1.16, 2.84) ], and neuropathy [ OR=2.52, 95% CI (1.38, 4.61) ] were the influencing factors of frailty in elderly patients with hematologic malignancies. Conclusions:The incidence of frailty is high in elderly patients with hematologic malignancies. Elderly patients with hematologic malignancies who are older, female, consume alcohol, have low self-care ability, anemia, infections, and neuropathy are prone to frailty. Healthcare providers can conduct early screening and intervention for high-risk populations of frailty based on risk factors to improve the quality of life for elderly hematologic malignancy patients.

Objective:To evaluate the impact of roxadustat on thyroid function and to identify the associated factors in patients undergoing maintenance peritoneal dialysis (PD).Methods:This study was a single-center retrospective study. PD patients who received roxadustat or recombinant human erythropoietin (rHuEPO) treatment at Nanjing Drum Tower Hospital between January 2020 and June 2024 were included. The general and clinical information as well as laboratory indexes were collected. Serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were compared before and after treatment initiation. Hemoglobin (Hb) responses were also observed between the two groups. Logistic regression analysis was performed to explore the factors associated with thyroid function changes.Results:A total of 120 patients were enrolled, with an age of (55.17±16.42) years, including 66 males (55.0%). There were 81 patients received roxadustat (roxadustat group) and 39 patiens received rHuEPO (rHuEPO group). Compared to the rHuEPO group, the roxadustat group had a higher proportion of patients with diabetes ( χ 2= 4.172, P=0.041), a shorter PD vintage ( Z=-3.406, P=0.002), a lower serum level of total cholesterol ( Z=-2.082, P=0.037) and a lower level of fasting blood glucose ( Z=-2.589, P=0.010). Following treatment with roxadustat, the levels of FT4 ( Z=-5.349, P<0.01) and TSH ( Z=-3.720, P<0.01) decreased significantly. In contrast, no significant changes in FT4 or TSH levels were observed in the rHuEPO group (both P>0.05). For both roxadustat and rHuEPO groups, there were no significant changes in FT3 levels after treatment (both P>0.05). Multivariate analysis identified that higher baseline TSH (TSH≥2.27 μIU/ml, OR=1.581, 95% CI 1.196-2.089, P=0.001) and roxadustat exposure ( OR=3.432, 95% CI 1.410-8.355, P=0.007) as independent associated factors of subsequent TSH decline, and identified that higher baseline FT4 (FT4≥14.9 pmol/L, OR=1.390, 95% CI 1.162-1.662, P=0.001) and roxadustat exposure ( OR=5.798, 95% CI 2.225-15.113, P=0.001) as independent associated factors of subsequent FT4 decline. The degrees of hemoglobin changes after roxadustat or rHuEPO treatment did not differ significantly between roxadustat group and rHuEPO group ( t=-1.062, P=0.290). Of the 31 patients who underwent a second thyroid function test during roxadustat treatment, 24 continued with the original regimen, while 7 discontinued roxadustat. Among 24 patients who maintained roxadustat treatment, TSH ( Z=-0.400, P=0.689) and FT4 ( t=0.143, P=0.888) remained stable between the second and third tests. All 7 patients who discontinued roxadustat treatment showed TSH rebound and the changes of TSH levels were more significant than that in continuers ( Z=-2.505, P=0.012). FT4 recovery occurred in only 3 of them, with no significant difference in FT4 change between discontinuers and continuers ( Z=-0.685, P=0.493). Conclusions:Roxadustat commonly suppresses TSH and FT4, but not FT3, in PD patients. Baseline levels of TSH and FT4 are key associated factors of the inhibitory effect of roxadustat on thyroid function. This suppression does not intensify with prolonged exposure and is reversible after discontinuation, with TSH levels normalizing more quickly than FT4. Roxadustat-induced thyroid suppression does not compromise its efficacy in treating renal anemia.

Objective:To investigate the dynamic cerebral oxygen metabolism characteristics in drug-naive patients with primary insomnia (PI), and analyze the association between the cerebral oxygen metabolism and insomnia symptoms.Methods:A total of 31 drug-naive patients with PI and 36 healthy controls were recruited from July 2024 to February 2025. Insomnia symptoms were assessed by the Pittsburgh sleep quality index (PSQI). Functional near infrared spectroscopy (fNIRS) technique was employed to collect 180 s resting-state oxygenated hemoglobin concentration changes from dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex, temporal lobe (TL), parietal lobe (PL) and occipital lobe. Sliding time window analysis and K-means clustering algorithm were applied to cluster the oxygenation data into K temporal categories. Statistical analysis, including t-test, Wilcoxon rank-sum test, chi-square test, Pearson/Spearman correlation analysis, and multiple linear regression were performed using SPSS 26.0 software. Results:Clustering analysis revealed 4 characteristic temporal categories (K=4) during the 180 s resting-state. Compared to healthy controls, drug-naive PI patients exhibited higher oxygenation levels in bilateral TLs during the second temporal category(left TL(18.19±6.18)mmol/dL, (16.82±4.47)mmol/dL; right TL(18.20±8.97)mmol/dL, (16.17±5.64)mmol/dL), but lower levels during the third temporal category(left TL(16.54± 5.09)mmol/dL, (17.98±5.34)mmol/dL; right TL(15.82±7.29)mmol/dL, (17.84±5.94)mmol/dL), and exhibited lower oxygenation level in right PL during the second category((16.16±6.56)mmol/dL, (17.60±5.84)mmol/dL) (all P<0.05). Oxygenation levels in the right DLPFC during the first temporal category ( β=0.44, t=2.52, P=0.018), in the left DLPFC during the second temporal category( β=-0.47, t=-2.82, P=0.009), and in the right PL during the second temporal category( β=-0.46, t=-2.78, P=0.010) were influencing factors for the PSQI score. Conclusions:The bilateral TLs and right PL in drug-naive PI patients exhibit phase-specific abnormalities in oxygen metabolism, potentially attributable to the insomnia-induced dysregulation of endogenous neural oscillations. The oxygen concentration changes in bilateral DLPFCs and right TL are associated with insomnia symptoms.

Objective:To investigate the dynamic cerebral oxygen metabolism characteristics in drug-naive patients with primary insomnia (PI), and analyze the association between the cerebral oxygen metabolism and insomnia symptoms.Methods:A total of 31 drug-naive patients with PI and 36 healthy controls were recruited from July 2024 to February 2025. Insomnia symptoms were assessed by the Pittsburgh sleep quality index (PSQI). Functional near infrared spectroscopy (fNIRS) technique was employed to collect 180 s resting-state oxygenated hemoglobin concentration changes from dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex, temporal lobe (TL), parietal lobe (PL) and occipital lobe. Sliding time window analysis and K-means clustering algorithm were applied to cluster the oxygenation data into K temporal categories. Statistical analysis, including t-test, Wilcoxon rank-sum test, chi-square test, Pearson/Spearman correlation analysis, and multiple linear regression were performed using SPSS 26.0 software. Results:Clustering analysis revealed 4 characteristic temporal categories (K=4) during the 180 s resting-state. Compared to healthy controls, drug-naive PI patients exhibited higher oxygenation levels in bilateral TLs during the second temporal category(left TL(18.19±6.18)mmol/dL, (16.82±4.47)mmol/dL; right TL(18.20±8.97)mmol/dL, (16.17±5.64)mmol/dL), but lower levels during the third temporal category(left TL(16.54± 5.09)mmol/dL, (17.98±5.34)mmol/dL; right TL(15.82±7.29)mmol/dL, (17.84±5.94)mmol/dL), and exhibited lower oxygenation level in right PL during the second category((16.16±6.56)mmol/dL, (17.60±5.84)mmol/dL) (all P<0.05). Oxygenation levels in the right DLPFC during the first temporal category ( β=0.44, t=2.52, P=0.018), in the left DLPFC during the second temporal category( β=-0.47, t=-2.82, P=0.009), and in the right PL during the second temporal category( β=-0.46, t=-2.78, P=0.010) were influencing factors for the PSQI score. Conclusions:The bilateral TLs and right PL in drug-naive PI patients exhibit phase-specific abnormalities in oxygen metabolism, potentially attributable to the insomnia-induced dysregulation of endogenous neural oscillations. The oxygen concentration changes in bilateral DLPFCs and right TL are associated with insomnia symptoms.