OBJECTIVE To analyze the specific risks and long-term toxicities of four BCR-ABL1 tyrosine kinase inhibitors （TKIs）（imatinib， dasatinib， nilotinib， and bosutinib） in pediatric patients with hematological malignancies. METHODS Adverse drug event （ADE） reports submitted to the the United States FDA Adverse Event Reporting System （FAERS） from January 2012 to December 2024， with imatinib， dasatinib， nilotinib， and bosutinib as the primary suspect drugs， were collected. Data mining was performed using the reporting odds ratio method and proportional reporting ratio method. ADE terms were classified and summarized by system organ class （SOC） and preferred term （PT） according to the Medical Dictionary for Drug Regulatory Activities （MedDRA， version 26.0）. Meanwhile， the ADE reports were divided by age into the adult group （≥18 years） and the pediatric group （＜18 years） to compare the differences in ADE between the two groups. RESULTS A total of 1 512 pediatric ADE reports were included： 993 for imatinib， 391 for dasatinib， 112 for nilotinib， and 16 for bosutinib. Among the reported ADEs， the patients were mainly aged 12-＜18 years； the reports mainly originated from the United States， France， and Japan； and the primary indications were chronic myeloid leukemia and acute lymphoblastic leukemia. A total of 5 256 ADE signals were mined， among which 235 were positive signals， involving 1 103 PT across 27 SOC. The top five PT ranked by the number of positive signals were nausea， febrile neutropenia， abdominal pain， neutropenia， and anemia. The top two SOC were general disorders and administration site conditions， and gastrointestinal disorders. Compared with the adult group， the pediatric group had relatively higher proportions of events related to infections and infestations as well as blood and lymphatic system disorders. Pediatric long-term toxicity signals primarily included growth retardation， accompanied by signals related to endocrine system abnormalities and bone metabolism abnormalities. Specific signals included imatinib-associated septic shock， dasatinib-associated chylothorax， and nilotinib-associated electrocardiographic QT interval prolongation. CONCLUSIONS When pediatric patients use BCR-ABL1 TKIs， priority monitoring of infection risk and hematologic parameters is required， along with long-term follow-up of height， endocrine， and bone metabolism parameters. Targeted screening and management of drug-specific signals should be performed to ensure the long-term safety of pediatric medication.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta and the pathological accumulation ofα‑synuclein. Although extensive progress has been made in elucidating its pathogenesis, current therapeutic approaches remain largely symptomatic, and effective disease-modifying treatments are still unavailable. Increasing evidence indicates that PD is driven by the interaction of multiple pathological processes, including neuroinflammation, iron homeostasis dysregulation and ferroptosis, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, oxidative stress, and impaired protein homeostasis, which together contribute to neuronal vulnerability and degeneration. Fibroblast growth factors (FGFs) comprise a family of 22 ligands that play important roles in neural development, stress responses, metabolic regulation, and the maintenance of nervous system homeostasis. Recent studies have shown that several FGF family members, such as FGF1, FGF2, FGF9, and FGF21, exert neuroprotective effects in cellular and animal models of PD. These effects include the regulation of inflammatory responses, oxidative stress, iron homeostasis, cellular stress adaptation, and neuronal survival. Compared with therapeutic strategies targeting a single pathogenic pathway, FGFs appear to influence multiple disease-related processes, suggesting their potential relevance to the complex pathophysiology of PD. Experimental evidence indicates that altered FGF signaling may contribute to dopaminergic neuron dysfunction through the coordinated regulation of several interconnected mechanisms. FGFs have been reported to modulate neuroinflammation by affecting the activation of microglia and astrocytes, thereby influencing the inflammatory environment in the central nervous system. In addition, FGFs are involved in the regulation of iron homeostasis and ferroptosis, partly through antioxidant signaling pathways associated with NRF2, SLC7A11, and GPX4. Moreover, FGFs can alleviate ER stress and mitochondrial dysfunction by activating intracellular signaling pathways such as PI3K/AKT, AMPK-PGC-1α, as well as SIRT1-dependent programs, which support cellular energy metabolism and redox balance. Recent advances in single-cell and spatial transcriptomic studies further suggest that FGF signaling is not limited to neuron-intrinsic mechanisms but also involves interactions among different glial cell types. Altered FGF ligand-receptor communication between astrocytes and oligodendrocytes has been observed in PD models and is associated with increased susceptibility of dopaminergic neurons to oxidative stress and ferroptosis. These findings indicate that the biological effects of FGFs are influenced by cell type and disease stage and may vary under different pathological conditions. In this review, we summarize recent progress in understanding the roles of FGF family members in PD, with a focus on their involvement in iron homeostasis dysregulation and ferroptosis, neuroinflammation, cellular stress responses, and neuronal protection and regeneration. By integrating current evidence, this review aims to provide a clearer understanding of how FGFs participate in PD pathogenesis and to offer a theoretical basis for future studies exploring their potential value in disease-modifying therapeutic strategies.

Objective To investigate the expression of the histone deacetylase SIRT7 in glioma cells and its impact on epithelial-mesenchymal transformation(EMT),as well as its effects on proliferative,migratory and invasive capabilities of glioma cells.Methods Bioinformatics analysis was conducted on data from glioma patients in the Cancer Genome Atlas(TCGA)and the Chinese glioma Genome Atlas(CGGA)databases to explore the expression of SIRT7 gene in gliomas and its correlation with tumor grading,molecular characteristics and patient clinical prognosis.Glioma cells were randomly divided into control,SIRT7 knockdown,SIRT7 overexpression,drug treatment(10 μmol/L hydrochlorothiazide)and drug(10 μmol/L hydrochlorothiazide)+SIRT7 overexpression groups.The CCK-8 assay,cell scratch assay and Transwell assay were used to observe the effects of upregulating and downregulating SIRT7 expression on glioma cell proliferation,migration and invasion.RT-qPCR and Western blotting were employed to detect the effects of SIRT7 on the expression of neural cadherin(N-cadherin),Vimentin,E-cadherin,transforming growth factor-β(TGF-β),Ki-67,and Smad3 protein in glioma cells.Nude mouse tumor-bearing experiments were conducted to observe the effect of SIRT7 knockdown on glioma growth.Results Higher expression levels of SIRT7 gene were associated with poorer clinical prognosis(P＜0.0001).SIRT7 expression levels were significantly correlated with tumor grading and 1p19q coding status(P＜0.01).Compared with normal HA cells,glioma cells showed significantly increased SIRT7 expression levels(P＜0.01).CCK-8 assay results indicated that,compared with control group,the proliferation activity of glioma cells in SIRT7 knockout group was significantly decreased(P＜0.01),while SIRT7 overexpression group showed significantly increased proliferation activity(P＜0.01).EdU assay results showed that,compared with control group,the proportion of glioma cells in the proliferative stage was significantly decreased in SIRT7 knockdown group(P＜0.01),and significantly increased in SIRT7 overexpression group(P＜0.01).Western blotting results revealed that,compared with control group,the protein expression levels of TGF-β,Smad3,N-cadherin and Vimentin were significantly decreased in SIRT7 knockdown group(P＜0.01),while the expression level of E-cadherin protein was significantly increased(P＜0.05).SIRT7 overexpression group showed significantly increased protein expression levels of TGF-β,Smad3,N-cadherin and Vimentin(P＜0.05),and a significantly decrease in E-cadherin protein expression level(P＜0.05).Scratch assay results indicated that,compared with control group,the migration ability of cells in SIRT7 knockdown group and drug group was significantly decreased(P＜0.01),and SIRT7 overexpression group showed significantly increased cell migration ability(P＜0.05).Compared with drug group,drug+SIRT7 overexpression group exhibited significantly increased cell migration ability(P＜0.01).Transwell assay results showed that,compared with control group,the migration and invasion abilities of cells in SIRT7 knockdown group and drug group were significantly decreased(P＜0.01),and SIRT7 overexpression group exhibited significantly increased migration and invasion abilities(P＜0.01).Compared with drug group,drug+SIRT7 overexpression group showed significantly increased migration and invasion abilities(P＜0.01).Nude mouse tumor-bearing assay results indicated that the volume and weight of glioma in SIRT7 knockdown group were significantly reduced compared with control group(P＜0.01).Conclusions Glioma patients with high SIRT7 expression have poorer clinical prognosis.SIRT7 can regulate the TGF-β/Smad3 pathway to mediate EMT,promoting the proliferation and migration of glioma cells.SIRT7 knockdown can inhibit the growth of transplanted gliomas in nude mice.

Objective Understanding the population structure of mosquitoes in the drainage system of Minhang District,Shanghai,and exploring the physical prevention and control technology of mosquito traps with a Vazor mosquito repellent film in the drainage system.Methods A 500 mL water spoon was used to assist in visual inspection to investigate the breeding status of mosquito larvae in the drainage system.A carbon dioxide mosquito trap method was used to monitor adult mosquitoes around the ground drainage system,and the artificial hour method was used to monitor adult mosquitoes around the underground drainage system.Mosquito-repellent film was applied at a rate of 1 mL/m2 to the drainage system where mosquito larvae or pupae are found,and the breeding situation was observed and recorded.Results The positivity rate of mosquitoes breeding in the ground drainage system was 50%.The mosquito larvae in the drainage channels were primarily Aedes albopictus,whereas Ae.albopictus were primarily noted in the sewage wells.The proportions of Ae.albopictus and Culex pipiens pallens in the rainwater wells were similar,and the dominant mosquito species around the surface drainage system was Ae.Albopictus.The positive rate of mosquito breeding in the underground drainage system was 47%,with the dominant mosquito species being Cx.pipiens pallens(58.39%)followed by Ae.albopictus(41.6%).The dominant adult mosquito species around the drainage system were Cx.pipiens pallens(83%)followed by Ae.albopictus(11%).In terms of the effectiveness of mosquito-repellent water film,the mosquito breeding rates of the ground and underground drainage systems using mosquito-repellent water film decreased to 2.78%and 5%after 1 week of use,respectively,and then rebounded after the 3rd week.After a supplementary dose during the 5th week,the breeding rates returned to normal.No statistically significant differences were observed in the effect compared with the standard control group using 1%bisulfite granules;however,a statistically significant difference was noted compared with the blank control group without special treatment.Conclusions In the drainage system of Minhang District,Shanghai,mosquito breeding is severe,and variations exist in the dominant mosquito species in different environmental drainage facilities.The simultaneous use of mosquito-repellent films can effectively control mosquito breeding in drainage systems.

AIM To study the chemical constituents from Euphorbia humifusa Willd.and their in vitro anti-hepatoma activity.METHODS Silica gel,D101 macroporous adsorption resin and semi-preparative RP-HPLC were used for isolated and purified,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The anti-hepatocellular carcinoma activity was determined by MTT mothod.RESULTS Eighteen compounds were isolated and identified as 22-O-angeloyl-R1-barrigenol(1),dimethyl 3,3'-[oxybis(4,1-phenylene)](2E,2'E)-diacrylate(2),N-(3-methoxy-1,3-dioxopropyl)-D-tryptophan methyl ester(3),N-acetyltryptophan methyl ester(4),N-(methoxycarbonyl)-tryptophan methyl ester(5),(3β,5α,17β)-4,4,8,14-tetramethyl-18-norandrostane-3,17-diol(6),3β,18,19β-trihydroxylupane(7),pregnenolone(8),3-hydroxy-5,6-epoxy-7-megastigmen-9-one(9),dehydrovomifoliol(10),loliolide(11),2,2'-oxybis(1,4-di-tert-butylbenzene)(12),dibutyl phthalate(13),4-methoxycinnamic acid(14),3,4-dimethoxycinnamic acid(15),methyl 4-hydroxybenzoate(16),kaempferol(17),quercetin(18).The IC50 values of compounds 1,7 and 8 on HepG2 cells were(17.27±0.92),(19.11±2.14)and(7.53±1.09)μmol/L,respectively.CONCLUSION Compounds 1-16 are first isolated from this plant.Compounds 1,7 and 8 have anti-hepatoma activity.

Transfer-RNA derived small RNA(tsRNA),a re-cently discovered class of non-coding RNA,is produced by ma-ture tRNA or tRNA precursor through the mediation of specific endonucleases.By regulating gene expression at the transcrip-tional and post transcriptional levels and acting as an epigenetic regulator,tsRNA plays an important role in the physiological and pathological processes of many organisms.Therefore,it has gradually become a research hotspot in biomedicine and attracted widespread attention.Moreover,there is increasing evidence that tsRNA is involved in the occurrence and development of many neuropsychiatric diseases through participating in stress re-sponse,cell proliferation and apoptosis,neural development,synaptic plasticity,neuroinflammation and immune regulation,epigenetic regulation,RNA processing,and protein translation regulation.This article mainly discusses the generation,classifi-cation and biological functions of tsRNA,and elaborates on the role and possible mechanisms of tsRNA in neurodevelopment and neuropsychiatric disorders,thereby further revealing the poten-tial of tsRNA as a reliable biomarker and therapeutic target for neuropsychiatric disorders.

Objective To explore a deep learning-based automatic bone age estimation model for elbow joint X-ray images of Chinese Han adolescents and children and evaluate its performance.Methods A total of 943(517 males and 426 females)elbow joint frontal view X-ray images of Chinese Han ado-lescents and children aged 6.00 to<16.00 years were collected from East,South,Central and North-west China.Three experimental schemes were adopted for bone age estimation.Scheme 1:Directly in-put preprocessed images into the regression model;Scheme 2:Train a segmentation network using"key elbow joint bone annotations"as labels,then input segmented images into the regression model;Scheme 3:Train a segmentation network using"full elbow joint bone annotations"as labels,then in-put segmented images into the regression model.For segmentation,the optimal model was selected from U-Net,UNet++and TransUNet.For regression,VGG16,VGG19,InceptionV2,InceptionV3,ResNet34,ResNet50,ResNet101 and DenseNet121 models were selected for bone age estimation.The dataset was randomly split into 80%(754 samples)for training and validation for model fitting and hyperparameter tuning,and 20%(189 samples)as an internal test set to test the performance of the trained model.An additional 104 elbow joint X-ray images from the same demographic and age group were col-lected and used as an external test set.Model performance was evaluated by comparing the mean ab-solute error(MAE),root mean square error(RMSE),accuracies within±0.7 years(P±0.7 years)and±1.0 years(P±1.0 years)between the estimated age and the actual age,and by drawing radar charts,scat-ter plots,and heatmaps.Results When segmented with Scheme 3,the UNet++model achieved good segmentation performance with a segmentation loss of 0.000 4 and an accuracy of 93.8%at a learning rate of 0.000 1.In the internal test set,the DenseNet121 model with Scheme 3 yielded the best results with MAE,P±0.7 years and P±1.0 years being 0.83 years,70.03%,and 84.30%,respectively.In the external test set,the DenseNet121 model with Scheme 3 also performed best,with an average MAE of 0.89 years and an average RMSE of 1.00 years.Conclusion When performing automatic bone age estima-tion using elbow joint X-ray images in Chinese Han adolescents and children,it is recommended to use the UNet++model for segmentation.The DenseNet121 model with Scheme 3 achieves optimal per-formance.Using segmentation networks,especially that trained with annotation areas encompassing the full elbow joint including the distal humerus,proximal radius,and proximal ulna,can improve the ac-curacy of bone age estimation based on elbow joint X-ray images.

Objective To explore a deep learning network model suitable for bone age estimation using shoulder joint X-ray images in Chinese Han adolescents.Methods A retrospective collection of 1 286 shoulder joint X-ray images of Chinese Han adolescents aged 12.0 to<18.0 years(708 males and 578 females)was conducted.Using random sampling,approximately 80%of the samples(1 032 cases)were selected as the training and validation sets for model learning,selection and optimization,and the other 20%samples(254 cases)were used as the test set to evaluate the model's generalization ability.The original single-channel shoulder joint X-ray images and dual-channel inputs combining original images with segmentation labels(manually annotated shoulder joint regions multiplied pixel-by-pixel with original images,followed by segmentation via the U-Net++network to retain only key shoulder joint region information)were respectively input into four network models,namely VGG16,ResNet18,ResNet50 and DenseNet121 for bone age estimation.Additionally,manual bone age estimation was con-ducted on the test set data,and the results were compared with the four network models.The mean absolute error(MAE),root mean square error(RMSE),coefficient of determination(R2),and Pear-son correlation coefficient(PCC)were used as main evaluation indicators.Results In the test set,the bone age estimation results of the four models with dual-channel input of shoulder joint X-ray images outperformed those with single-channel input in all four evaluation indicators.Among them,DenseNet121 with dual-channel input achieved best results with MAE of 0.54 years,RMSE of 0.82 years,R2 of 0.76,and PCC(r)of 0.88.Manual estimation yielded an MAE of 0.82 years,ranking second only to dual-channel DenseNet121.Conclusion The DenseNet121 model with dual-channel input combined with original images and segmentation labels is superior to manual evaluation results,and can effectively estimate the bone age of Chinese Han adolescents.

OBJECTIVE: Baicalein has been reported to have wide therapeutic effects that act through its anti-inflammatory activity. This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy (SIC). METHODS: A thorough screening of a small library of natural products, comprising 100 diverse compounds, was conducted to identify the most effective drug against lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes. The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology. RESULTS: Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes. It exhibited a dose-dependent inhibitory effect on cell injury and inflammation. In the LPS-induced septic mouse model, baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits, inflammatory responses, and ferroptosis. Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit α (HIF1-α) is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury. By combining microRNA (miRNA) screening in LPS-treated myocardium with miRNA prediction targeting HIF1-α, we found that miR-299b-5p may serve as a regulator of HIF1-α. The reduction in miR-299b-5p levels in LPS-treated myocardium, compared to the control group, was reversed by baicalein treatment. The reverse transcription quantitative polymerase chain reaction, Western blotting, and dual-luciferase reporter gene analyses together identified HIF1-α as the target of miR-299b-5p in cardiomyocytes. CONCLUSION Baicalein mitigates SIC at the miRNA level, suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-α/ferroptosis pathway. Please cite this article as: Zhou WY, Du JK, Liu HH, Deng L, Ma K, Xiao J, Zhang S, Wang CN. Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway. J Integr Med. 2025; 23(5):560-575.
Flavanones/pharmacology* ; Animals ; MicroRNAs/genetics* ; Lipopolysaccharides ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Ferroptosis/drug effects* ; Mice ; Myocytes, Cardiac/metabolism* ; Signal Transduction/drug effects* ; Rats ; Male ; Mice, Inbred C57BL ; Cardiomyopathies/etiology* ; Cell Line ; Sepsis/complications*

OBJECTIVE: This study aimed to evaluate the relationships of white blood cell (WBC) count, platelet (PLT) count, and PLT-to-WBC ratio (PWR) with muscle mass in Chinese older adults. METHODS: This cross-sectional analysis involved 4,033 Chinese older adults aged ≥ 65 years from the Healthy Ageing and Biomarkers Cohort Study. Muscle mass and total skeletal muscle mass index (TSMI) were measured by bioelectric impedance analysis. WBC, PLT, and PWR were measured using standard methods. Multivariate linear regression was used to examine the associations of WBC count, PLT count, and PWR with TSMI. RESULTS: High WBC count, PLT count, and PWR were associated with low TSMI, with coefficients of -0.0091 (95% confidence interval [ CI]: -0.0142 to -0.0041), -0.0119 (95% CI: -0.0170 to -0.0068), and -0.0051 (95% CI: -0.0102 to -0.0001). The associations between the three inflammatory indices and TSMI were linear. Stratified analyses indicated that the relationship between inflammatory markers and TSMI was more evident in male participants and in individuals aged < 80 years than in their counterparts. CONCLUSION Elevated WBC count, PLT count, and PWR correlated with muscle mass loss. This study highlights the importance of regular monitoring of inflammatory markers as a potential strategy for the screening and management of sarcopenia in older adults.
Humans ; Aged ; Male ; Female ; China ; Leukocyte Count ; Cross-Sectional Studies ; Platelet Count ; Aged, 80 and over ; Muscle, Skeletal/anatomy & histology* ; Independent Living ; Blood Platelets ; Leukocytes ; Sarcopenia