Ferroptosis of chondrocytes is a significant contributor to osteoarthritis(OA),for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis.Here,we screen for anti-ferroptotic drugs in Food and Drug Administration(FDA)-approved drug library via a high-throughput manner in chondrocytes.We identified a group of FDA-approved anti-ferroptotic drugs,among which vitamin K showed the most powerful protective effect.Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix(ECM)degradation in chondrocytes.Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus(DMM)mouse model.Mechanistically,transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6(Gas6).Furthermore,exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase(AXL)/phosphatidylinositol 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)axis.Together,we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis,indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are common and critically important diseases of preterm infants. The common feature of both conditions is altered angiogenesis and pathological changes in the case of incomplete organ development. The interaction of multiple factors leads to abnormal angiogenesis, which not only increases the possibility of comorbidity of BPO and ROP, but also reveals the potential co-pathogenesis between the two. However, the specific mechanism of this angiogenic balance in the occurrence and development of BPD or ROP is still unclear, and there are no animal models to explore the pathogenesis of both diseases. At present, effective prevention measures for BPO and ROP are still lacking, and treatment methods mainly rely on drug therapy and surgery. In the future, more studies should be conducted to find common therapeutic targets for factors affecting angiogenesis, so as to provide better treatment options for BPD and ROP and improve the effectiveness of treatment.

Objective:To observe and analyze thyroxine levels in children with retinopathy of prematurity (ROP) and its effect on severe ROP.Methods:A retrospective clinical study. From January 2022 to December 2023, a total of 64 premature infants with severe ROP (ROP group), hospitalized in the Children's Hospital Affiliated to Zhengzhou University and with a gestational age ≤32 weeks, were included. According to a 1:2 ratio, 128 premature infants without ROP, matched for sex and gestational age, were selected as the control group. Thyroid function tests were performed 7 to 14 d after birth. The levels of thyroid-stimulating hormone, triiodothyronine, free triiodothyronine, thyroxine (T4), and free T4 (FT4) were compared and observed between the two groups. The quantitative data between groups were compared by independent samples t-test or Mann-Whitney U test; the count data were compared by χ2 test. Logistic regression was used to analyze the correlation between various variables and the occurrence of severe ROP. The predictive efficacy of the differential indicators was assessed by receiver operating characteristic (ROC) curve. Results:Compared with the control group, T4 and FT4 levels were significantly lower in children in the ROP group, and the difference was statistically significant ( t=2.572, 2.704; P=0.011, 0.008). The results of univariate logistic regression analysis showed that the Apgar scores at 1 and 5 minutes, as well as sepsis, T4, FT4, and bronchopulmonary dysplasia (BPD), were significantly associated with the occurrence of severe ROP ( P<0.05). The results of multivariate logistic regression analysis indicated that FT4 and BPD are independent risk factors for the occurrence of severe ROP ( P<0.05). The ROC curve analysis revealed that T4 had a sensitivity of 80.9% and specificity of 43.3%, while FT4 showed a sensitivity of 46.8% and specificity of 75.0%, with abnormal cutoff values set at 98.4 nmol/L for T4 and 15.65 pmol/L for FT4. Conclusions:The T4 and FT4 level of children with severe ROP are lower than that of children without ROP in the early postnatal period. The T4 and FT4 level in the early postnatal period may have a certain correlation with the occurrence of severe ROP.

Objective:A method was first established for determination simultaneously of 12 elements including B,Al,Si,As,Cd,Hg,Pb,Co,Ni,V,Cu and Sb in phloroglucinol injection,and investigate the elemental impuri-ty content of commercially available phloroglucinol injection.Methods:Samples were digested with microwave-as-sisted acid and determined by inductively coupled plasma chromatography(ICP-MS).Results:This method has a good linear relationship.The average recovery rate was range from 88.9％-100.4％.The repeatability RSD were range from 0.6％-5.8％,and the precision RSD were between 0.4％-8.1％.The methodological validation meets the requirements.B,Al,Si,As,Cd,Co,Ni,V,Cu were detected to varying degrees in 9 batches of sam-ples,and there were significant differences in content among different enterprises.The sources of elemental impuri-ties were deeply explored in combination with the production process,medicinal property and pharmaceutical packa-ging material.Conclusion:The new established method has strong specificity,high accuracy,reliable results,and can be used as a quality evaluation method for elemental impurities in phloroglucinol injection.

Objective:A method was first established for determination simultaneously of 12 elements including B,Al,Si,As,Cd,Hg,Pb,Co,Ni,V,Cu and Sb in phloroglucinol injection,and investigate the elemental impuri-ty content of commercially available phloroglucinol injection.Methods:Samples were digested with microwave-as-sisted acid and determined by inductively coupled plasma chromatography(ICP-MS).Results:This method has a good linear relationship.The average recovery rate was range from 88.9％-100.4％.The repeatability RSD were range from 0.6％-5.8％,and the precision RSD were between 0.4％-8.1％.The methodological validation meets the requirements.B,Al,Si,As,Cd,Co,Ni,V,Cu were detected to varying degrees in 9 batches of sam-ples,and there were significant differences in content among different enterprises.The sources of elemental impuri-ties were deeply explored in combination with the production process,medicinal property and pharmaceutical packa-ging material.Conclusion:The new established method has strong specificity,high accuracy,reliable results,and can be used as a quality evaluation method for elemental impurities in phloroglucinol injection.

Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are common and critically important diseases of preterm infants. The common feature of both conditions is altered angiogenesis and pathological changes in the case of incomplete organ development. The interaction of multiple factors leads to abnormal angiogenesis, which not only increases the possibility of comorbidity of BPO and ROP, but also reveals the potential co-pathogenesis between the two. However, the specific mechanism of this angiogenic balance in the occurrence and development of BPD or ROP is still unclear, and there are no animal models to explore the pathogenesis of both diseases. At present, effective prevention measures for BPO and ROP are still lacking, and treatment methods mainly rely on drug therapy and surgery. In the future, more studies should be conducted to find common therapeutic targets for factors affecting angiogenesis, so as to provide better treatment options for BPD and ROP and improve the effectiveness of treatment.

Objective:To observe and analyze thyroxine levels in children with retinopathy of prematurity (ROP) and its effect on severe ROP.Methods:A retrospective clinical study. From January 2022 to December 2023, a total of 64 premature infants with severe ROP (ROP group), hospitalized in the Children's Hospital Affiliated to Zhengzhou University and with a gestational age ≤32 weeks, were included. According to a 1:2 ratio, 128 premature infants without ROP, matched for sex and gestational age, were selected as the control group. Thyroid function tests were performed 7 to 14 d after birth. The levels of thyroid-stimulating hormone, triiodothyronine, free triiodothyronine, thyroxine (T4), and free T4 (FT4) were compared and observed between the two groups. The quantitative data between groups were compared by independent samples t-test or Mann-Whitney U test; the count data were compared by χ2 test. Logistic regression was used to analyze the correlation between various variables and the occurrence of severe ROP. The predictive efficacy of the differential indicators was assessed by receiver operating characteristic (ROC) curve. Results:Compared with the control group, T4 and FT4 levels were significantly lower in children in the ROP group, and the difference was statistically significant ( t=2.572, 2.704; P=0.011, 0.008). The results of univariate logistic regression analysis showed that the Apgar scores at 1 and 5 minutes, as well as sepsis, T4, FT4, and bronchopulmonary dysplasia (BPD), were significantly associated with the occurrence of severe ROP ( P<0.05). The results of multivariate logistic regression analysis indicated that FT4 and BPD are independent risk factors for the occurrence of severe ROP ( P<0.05). The ROC curve analysis revealed that T4 had a sensitivity of 80.9% and specificity of 43.3%, while FT4 showed a sensitivity of 46.8% and specificity of 75.0%, with abnormal cutoff values set at 98.4 nmol/L for T4 and 15.65 pmol/L for FT4. Conclusions:The T4 and FT4 level of children with severe ROP are lower than that of children without ROP in the early postnatal period. The T4 and FT4 level in the early postnatal period may have a certain correlation with the occurrence of severe ROP.

Objective:To identify potential therapeutic targets of chronic sinusitis with nasal polyps (CRSwNP) through proteomics screening of and verify its effectiveness experimentally.Methods:The nasal tissue samples were collected from patients undergoing surgical treatment in the Department of Otorhinolaryngology, Head and Neck Surgery in Yuhuangding Hospital of Yantai from June 2010 to December 2021, including 69 patients with CRSwNP and 39 patients in the control group. Tissue samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in data-independent acquisition (DIA) mode to find differentially expressed proteins. Bioinformatics tools were employed to analyze the functions of differentially expressed proteins. The expression of hematopoietic cell kinase (HCK) in nasal tissues of patients with CRSwNP was further confirmed by qPCR and western blot. The mouse model of CRSwNP was established and treated with HCK inhibitor. The levels of inflammatory factors IgE, IL-4 and IL-5 in serum of CRSwNP mice, both treated and untreated with HCK inhibitors, were detected by enzyme-linked immunosorbent assay (ELISA) across different experimental groups. The experimental data were analyzed by Graphpad Prism 9 software.Results:DIA analysis identified 1 850 differential proteins, including 760 up-regulated proteins and 1 090 down-regulated proteins. Weighted correlation network analysis (WGCNA) correlation analysis of phenotypic data such as cell count and CT score with the results of genomics indemnified 575 proteins of MEBrown module which intersected with 35 kinases further screened from 1 850 differential proteins, yielding eight protein kinases: HCK, SYK, PDK2, FGR, PRKCB, ROR1, CAMK1 and GRK6. qPCR showed that the expression of HCK in CRSwNP was significantly higher than that in the control group ( P<0.05). Further experiments in mice confirmed that the secretion of IgE, IL-4 and IL-5 in the serum of CRSwNP group was significantly higher than the control group (all P<0.05), indicating successful model establishment. The intervention of HCK significantly decreased the secretion of IgE, IL-4 and IL-5 in serum of mice (all P<0.05). Conclusion:The HCK inhibitor can reduce the inflammatory index of mice with CRSwNP, and HCK is a potential therapeutic target of CRSwNP.