Vascular homeostasis is a cornerstone for the normal operation of body tissues and organs,and it is closely related to the pathophysiological processes of cardiovascular and other systemic diseases.The maintenance of vas-cular homeostasis relies on a normal vascular microenvironment,and disturbances in this microenvironment are key factors in the development and progression of diseases.In recent years,significant progress has been made in the study of endo-thelial damage and hemodynamics in the pathogenesis of cervical spondylosis of vertebral artery type(CSA).However,these aspects represent only part of the vertebral artery microenvironment disorder and do not fully explain the pathogenesis of CSA.Therefore,this paper reviews endothelial dysfunction,abnormal vasomotor function of vascular smooth muscle,damage perception effects of the vascular adventitia,and matrix microenvironment disorders.The aim is to systematically elucidate the role of vascular microenvironment disorder in the pathological process of CSA,providing new perspectives for research into the disease's pathogenesis and therapeutic targets.

Vascular homeostasis is a cornerstone for the normal operation of body tissues and organs,and it is closely related to the pathophysiological processes of cardiovascular and other systemic diseases.The maintenance of vas-cular homeostasis relies on a normal vascular microenvironment,and disturbances in this microenvironment are key factors in the development and progression of diseases.In recent years,significant progress has been made in the study of endo-thelial damage and hemodynamics in the pathogenesis of cervical spondylosis of vertebral artery type(CSA).However,these aspects represent only part of the vertebral artery microenvironment disorder and do not fully explain the pathogenesis of CSA.Therefore,this paper reviews endothelial dysfunction,abnormal vasomotor function of vascular smooth muscle,damage perception effects of the vascular adventitia,and matrix microenvironment disorders.The aim is to systematically elucidate the role of vascular microenvironment disorder in the pathological process of CSA,providing new perspectives for research into the disease's pathogenesis and therapeutic targets.

Cancer toxin is a specific pathogenesis leading to the heterogeneity of breast cancer.The nature and virulence of the cancer toxin determine the differences in the heterogeneity of breast cancer,which can dynamically evolve over time and space,resulting in varying invasion abilities and characteristics of the tumor.Cancer cells in the primary lesion possess"toxicity"that targets specific organs for metastasis,and cancer toxins can influence the metastatic propensity of different types of breast cancer.Therefore,breast cancer treatment strategies based on the theory of cancer toxins emphasize the continuous eradication of the cancer toxin,focusing on differentiating its strength and nature,protecting unaffected areas first,identifying the state based on symptoms,and targeting accordingly to combat resistance arising from tumor heterogeneity.This article aims to provide a new theoretical basis for the treatment strategies of different types of breast cancer.

Objectives: . Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. Methods: . We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. Results: . A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. Conclusion . We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.

Objective To clone the full length cDNA sequence of HSPC016 gene, an aggregative growth related gene in dermal papilla cells (DPC). Analyze its characteristics and predict its biological function in the phase of growth and differentiation for DPC. Methods Rapid amplification of cDNA ends (RACE) technology was used for full length cDNA amplification. Bioinformtic methods were used to analyze the chromosome location, protein sequence, domain and possible biological function of the gene. Results Two isoforms of HSPC016 gene were obtained from DPC. They were 400bp and 493bp, respectively. The gene was mapped on chromosome 3 q21 31, and was conservative on evolution. HSPC016 protein had 64aa, belonged to PD053992 protein family; its functional domain was homologous to T2FA gene. Conclusion HSPC016 was a transcriptional modulatory gene. Its protein product may act as a subunit of a transcriptional complex and play a role on DPC growth and differentiation through modulating other genes' transcription within nucleus