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.

ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal （HPG） axis by modified Erxian decoction in rats with perimenopausal syndrome （PMS） and to further analyze the expression of proteins related to the silent information regulator 1 （SIRT1）/hypothalamic kisspeptin （Kisspeptin）/gonadotropin-releasing hormone （GnRH） signaling pathway in the arcuate nucleus region （ARC） of the hypothalamus， so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method， with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling， including a sham operation group， a model group， an estradiol valerate group （0.09 mg∙kg^-1∙d^-1）， high-， medium-， and low-dose modified Erxian decoction groups （7.614， 3.807，1.903 5 g∙kg^-1∙d^-1）， with 8 rats in each group. The estradiol valerate group and the high-， medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days， and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and gonadotropin-releasing hormone （GnRH）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to determine the expression levels of SIRT1， Kisspeptin， kisspeptin receptor （GPR54）， and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor （GnRH-R） in pituitary. ResultsCompared with the sham operation group， rats in the model group had a significantly increased body weight （P0.01）， reduced wet weight and index of uterus （P0.01）， endometrial thinning or atrophy， glandular atrophy， and a decreasing number of glands. Additionally， serum levels of E₂ and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased （P0.01）. Serum levels of FSH， LH， and GnRH， the expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus， and GnRH-R in pituitary significantly increased （P0.01）. Compared with the model group， the estradiol valerate group and the high-， medium-dose modified Erxian decoction groups had significantly reduced body weight， serum levels of FSH， LH， and GnRH， and expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary （P0.05， P0.01） and significantly increased wet weight and index of uterus， serum level of E₂， and expression of SIRT1 in the ARC region of the hypothalamus （P0.05， P0.01）. In addition， they showed thickened endometrium， increased number of endometrial glands， and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets， and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus， the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway， the regulation of the expression of GnRH-R in the pituitary， the restoration of secretion balance of gonadotropins， and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.

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.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

The term yin excess originated in the Huang Di Nei Jing, which refers to the phenomenon of "heavy yin" when wind pathogens invades the human body and defensive qi enters the yin part of the human body. Later doctors have played a role in yin excess. Theoretically, yin and yang are out of balance in the human body, and yin is too much and yang is not enough, which is the process of physiological transformation to pathology; from the diagnosis point of view, patients with yin deficiency have less pulse and more blood; from the clinical manifestations, patients with yin excess appear cold from the back, hands and feet cold reverse; from the point of view of treatment, bitter cold products can cause yin excess. Modern research specifies yin as phlegm, dampness, stasis and other pathological products, and emphasize the relation between yin excess and yang deficiency. Yin excess includes pathological factors such as phlegm stasis cold, external cold straight in the liver wood, set in the hypochasm, resulting in mass; or overthinking and cold drink injury spleen, phlegm turbidiousness, long and hard phlegm forming lumps, thus resulting yin excess; or it may deplete the yang energy of the heart, leading to neglect of the warming function and stagnation of blood stasis; or if the kidney yang is deficient and the body lacks warmth, and there is no true yang in the ridge, then the wood will sink and congest blood stasis; the above etiology and pathogenesis lead to the occupation of yin pathogens, resulting in liver cancer. The treatment methods include liver cold turbidizing, warming liver and dispelling cold, with Wuzhuyu Decoction; spleen-deficiency phlegm production, the treatment should be warm the middle and resolving the phlegm, with Linggui Zhugan Decoction and Zhenwu Decoction; Yang deficiency and stasis, the treatment should warm kidney to remove blood stasis, with Poyu Decoction.

Objective To explore the clinical efficacy of sacubitril/valsartan combined with crea-tine phosphate sodium in heart failure patients with reduced ejection fraction(HFrEF).Methods A total of 116 patients with HFrEF were randomly divided into combination group and control group,with 58 cases in each group.The control group was treated with sacubitril/valsartan,while the combi-nation group was treated with sacubitril/valsartan and creatine phosphate sodium.Both groups were continually treated for 8 weeks.The clinical efficacy,oxidative stress indicators,cardiac function indicators,vascular endothelial function indicators and myocardial injury indicators before treatment and at 4 and 8 weeks after treatment as well as the occurrence of adverse reactions were compared between the two groups.Results The total effective rate was 94.83％in the combination group,which was significantly higher than 81.03％in the control group(P＜0.05).At 4 and 8 weeks of treatment,the left ventricular end-systolic diameter(LVESD)and left ventricular end-diastolic diam-eter(LVEDD)in the combination group were significantly lower than those in the control group,while the left ventricular ejection fraction(LVEF)was significantly higher than that in the control group(P＜0.01);the thromboxane B2(TXB2)and endothelin-1(ET-1)levels in the combination group were significantly lower than those in the control group,while the vascular endothelial growth factor(VEGF)level was significantly higher than that in the control group(P＜0.01);the levels of car-diac troponin Ⅰ(cTnⅠ),heart-type fatty acid-binding protein(H-FABP)and N-terminal pro-brain natriuretic peptide(NT-proBNP)in the combination group were significantly lower than those in the control group(P＜0.01).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Sacubitril/valsartan combined with creatine phosphate sodium has a definite therapeutic effect in treating patients with HFrEF,which can regu-late the degree of oxidative stress,improve vascular endothelial function,and thus promote the re-covery of cardiac function.

AIM: To investigate the efficacy and safety of ZKY001 eye drops with different concentrations in the treatment of corneal epithelial defects(CED)after primary pterygium excision.METHODS: This was a multicenter, randomized, double-blinded, placebo-controlled phase II clinical trial. From March 15, 2022 to November 14, 2022, patients with primary pterygium who had undergone surgery were recruited from 12 tertiary hospitals across China. Using block randomization, 178 patients(178 eyes)were randomly assigned to 3 groups in a 1:1:1 ratio: 0.002% ZKY001 group(n=59), 0.004% ZKY001 group(n=59), and placebo group(n=60, receiving ZKY001 sham eye drops). Subjects in each group received 1 drop of the study drug 4 times per day for 4 d. The percentage of CED area recovery from baseline, the first complete healing time of CED area, the number of first complete healing cases of CED, and changes in visual analogue scale(VAS)scores for eye discomfort including eye pain, foreign body sensation, tearing and photophobia were observed.RESULTS: In terms of improvement in CED, there were no statistically significant differences among the three groups including the first healing time of CED, the percentage improvement in CED area compared to baseline, and the percentage of first healing cases at different follow-up visits(all P>0.05). Numerically, the first healing time of CED was shorter in the test groups compared to the placebo group(67.87±21.688 h for the 0.002% ZKY001 group, 61.48±22.091 h for the 0.004% ZKY001 group, and 68.85±20.851 h for the placebo group). On D1 morning, the percentage improvement in CED area compared to baseline was maximally different from the placebo group, and the numerical difference advantage was maintained at subsequent follow-up visits. The number of first healing cases in the CED area at different follow-up visits was higher in the test groups than the placebo group. In terms of improvement in ocular discomfort, the total VAS scores were lower in the test groups compared to the placebo group, mainly due to reductions in foreign body sensation and pain scores. At D3, the 0.004% ZKY001 group showed statistically significant improvement in foreign body sensation(P<0.017). In terms of safety, the overall incidence of adverse events was low(9.0%)and similar among groups.CONCLUSION: The use of ZKY001 eyedrops after primary pterygium surgery can safely improve the CED repair, and alleviate postoperative symptoms caused by CED.

Purpose/Significance To explore the establishment of a remote maternal and fetal monitoring system based on 5 G tech-nology in the obstetrics and gynecology hospital,and to provide references for the medical system to improve telemedicine and smart medi-cal care based on 5 G technology.Method/Process By utilizing the advantages of 5 G technology such as fast speed,wide spectrum and low delay,and combining services such as maternal and fetal monitoring,online education,remote consultation,artificial intelligence(AI),health data management,and medical green channel,the maternal and fetal monitoring database and the AI model of maternal and fetal monitoring are constructed,the remote maternal and fetal monitoring system is constructed,and fetal heart monitoring process is op-timized.Result/Conclusion It realizes the combination of maternal and fetal monitoring application in hospital and outside hospital,medical alliance applications,internet hospital applications and ambulance transfer process applications.

Objective:To evaluate the role of the SIRT1/FoxO1 signaling pathway in trilobatin-induced reduction of cerebral ischemia-reperfusion (I/R) injury in rats.Methods:Eighty clean-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 230-280 g, were divided into 4 groups ( n=20 each) using a random number table method: sham operation group (group S), cerebral I/R group (group CIR), trilobatin+ cerebral I/R group (group T) and trilobatin+ cerebral I/R+ SIRT1/FoxO1 signaling pathway inhibitor EX527 group (group E). The model of focal cerebral I/R injury was established by middle cerebral artery occlusion in anesthetized animals. Trilobatin 15 mg/kg was given by gavage twice a day for 3 consecutive days starting from 3 days before ischemia in T and E groups. EX527 5 mg/kg was intraperitoneally injected before each gavage in group E. Modified Longa scoring scale was used to assess neurological function at 24 h of reperfusion, then the rats were sacrificed and whole brain tissues were obtained for determination of cerebral infarct size (using TTC staining), apoptosis rate and level of reactive oxygen species (ROS) in the hippocampus (by flow cytometry), expression of SIRT1 and acetylated FOXO1 (Ac-FOXO1) (by Western blot) and contents of superoxide dismutase (SOD) and malondialdehyde (MDA) (by enzyme-linked immunosorbent assay) and for microscopic examination of pathological changes in the hippocampal CAI area after HE staining. Results:Compared with group S, Longa score, cerebral infarct size, apoptosis rate of hippocampal neurons, and levels of ROS and MDA were significantly increased, the content of SOD was decreased, the expression of SIRT1 was down-regulated, and the expression of Ac-FOXO1 was up-regulated in group CIR ( P<0.05). Compared with group CIR, Longa score, cerebral infarct size, apoptosis rate of hippocampal neurons, and levels of ROS and MDA were significantly decreased, the content of SOD was increased, the expression of SIRT1 was up-regulated, and the expression of Ac-FOXO1 was down-regulated in group T ( P<0.05). Compared with group T, Longa score, cerebral infarct size, apoptosis rate of hippocampal neurons, and levels of ROS and MDA were significantly increased, the content of SOD was decreased, the expression of SIRT1 was down-regulated, and the expression of Ac-FOXO1 was up-regulated in group E ( P<0.05). Conclusions:Trilobatin may inhibit oxidative stress responses and neuronal apoptosis in hippocampi by activating the SIRT1/FoxO1 signaling pathway, thus alleviating cerebral I/R injury in rats.

This paper summarizes the concept of telemedicine, the application of telemedicine in home-based palliative care for cancer patients, and the impact of telemedicine on cancer patients receiving home-based palliative care. This paper also provides suggestions for the application of telemedicine in home-based palliative care, aiming to provide a reference for the application of telemedicine in home-based palliative care for cancer patients in China.