Mediastinal lesions in children

The mediastinum is where thoracic lesions most frequently occur in young patients.The histological spectrum of diseases caused by the presence of several organs in the mediastinum is broad.Congenital lesions,infections,benign and malignant lesions,and vascular diseases are examples of lesions.Care should be taken to make the proper diagnosis at the time of diagnosis in order to initiate therapy promptly.Our task is currently made simpler by radiological imaging techniques.

Potassium dehydroandrographolide succinate regulates the MyD88/CDH13 signaling pathway to enhance vascular injuryinduced pathological vascular remodeling

Pathological vascular remodeling is a hallmark of various vascular diseases.Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction,which leads to pathological vascular remodeling.Potassium dehydroandrographolide succinate(PDA),a derivative of andrographolide,has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections.This study investigates the potential of PDA in regulating pathological vascular remodeling.The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice.Experimental approaches,including rat aortic primary smooth muscle cell culture,flow cytometry,bromodeoxyuridine(BrdU)incorporation assay,Boyden chamber cell migration assay,spheroid sprouting assay,and Matrigel-based tube formation assay,were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells(SMCs).Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions.The results revealed that PDA exacerbates vascular injury-induced pathological remodeling,as evidenced by enhanced neointima formation.PDA treatment significantly increased the proliferation and migration of SMCs.Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88(MyD88)expression in SMCs and interacted with T-cadherin(CDH13).This interaction augmented proliferation,migration,and extracellular matrix deposition,culminating in pathological vascular remodeling.Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling,mediated through the MyD88/CDH13 signaling pathway.

AB040.Single-cell transcriptomics identifies cell-specific signatures of pathological angiogenesis

Background:To treat vascular proliferative diseases,anti-VEGF therapies have shown systemic adverse effects attributable to the lack of selectivity between pathological and physiological angiogenesis.Thus,identifying the molecular mechanisms that are only specific to pathological cell types is crucial to develop better precision medicine.Methods:Here,we used different cell type enrichment approaches combined with single-cell RNA sequencing to define the transcriptomic changes within each retinal cell types in a mouse model of ischemic retinopathy.This retinal model develops pathological neovascularization(NV)in response to local hypoxia following oxygen-induced vessel obliteration(P7 to P12).The NV phenotype is characterized by the progressive appearance of vascular tufts resulting from misguided,abnormal proliferation of endothelial cells that we monitored at 3 consecutive time points-P12,P14 and P17(peak of NV).Results:By following the dynamic response to hypoxia,our experimental design reveals how pathological angiogenesis is specifically associated with significant metabolic adaptations in different subtypes of endothelial cells(i.e.,Tips vs Stalk cells).We also identify a pathological subtype of glial cells over-expressing VEGFA and pro-inflammatory IL-1 receptor subunits.This subtype of activated glial cells was targeted using selective IL1R antagonist treatment which reduced glial activation,inflammation,NV and promotes physiological angiogenesis,therefore improving tissue regeneration.Conclusions:Our results illustrate how analyzing cell type heterogeneity in tissues developing pathological angiogenesis allows establishing better targeting therapies to restore vascular integrity.

Effect of Liuweidihuang pill and Jinkuishenqi pill on inhibition of spontaneous breast carcinoma growth in mice

OBJECTIVE: To investigate the preventing and treating action of Liuweidihuang pill(LP) and Jinkuishenqi pill(JP) on spontaneous breast carcinoma in mice.METHODS: A model of spontaneous breast carcinoma was derived from 11.5-month-old female Kunming breeding mice following the delivery of several litters. The mice were randomly divided into five groups: model control group(C),Liuweidihuang pill high-dose group(LH; 4.6 g·kg1·d1),Liuweidihuang pill low-dose group(LL;2.3 g·kg1·d﹣1),Jinkuishenqi pill high-dose group(JH; 4.6 g·kg﹣1·d1) and Jinkuishenqi pill low-dose group(JL;2.3 g·kg﹣1·d﹣1). Cancer tissue volume was measured by water immersion. Histopathology was analyzed by hematoxylin and eosin staining. Vascular endothelial growth factor(VEGF),extracellular signal-regulated kinase(ERK) and cyclin D1 protein expression in cancer tissue was assayed by western blotting.RESULTS: Compared with the control group,cancer tissue volume and weight were lower in the LP and JP groups,and survival time was longer. The expression of VEGF,ERK and Cyclin D1 were inhibited in the LP and JP groups(P < 0.05),and cell differentiation was increased. Tumor weights and volumes and VEGF,ERK and Cyclin D1 expression in LL or LH were significantly lower than in JL and JH(P < 0.01).CONCLUSION: Both LP and JP could restrain cancer growth and promote cancer cell differentiation;moreover,LP was more effective than JP The likely mechanism of action was via inhibition of VEGF,ERK and cyclin D1.