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Transferrin

OBJECTIVETo explore the roles of intracellular cholesterol metabolism in neuroendocrine (NE) differentiation of prostate cancer based on an androgen-independent prostate cancer NE cell model induced by androgen deprivation.

METHODSLNCaP cells were cultured in androgen-depleted medium, and NE phenotypes were identified by observing the changes in cell morphology, molecular markers (SgIII, NSE and CgA) and cell proliferation. The expression and distribution of cholesterol and Sg III were determined by immunofluorescence staining. The expressions of the key genes LDL-R, SREBP-1 and SREBP-2 involved in cholesterol synthesis and uptake were detected by semi-quantitative RT-PCR.

RESULTSThe LNCaP cells showed shrinking bodies and extending axons after androgen deprivation, and all the molecular markers, such as Sg III, NSE and CgA, significantly increased in a time-dependent manner, while the cell proliferation was obviously inhibited (P < 0.05). The cholesterol distribution in the LNCaP cells after NE differentiation presented remarkable aggregation at the axon terminals. However, there were no significant differences in the expression of cholesterol between the two types of cells, nor in the changes of the expressions of key genes LDL-R, SREBP-1 and SREBP-2 involved in cholesterol synthesis and uptake (P > 0.05).

CONCLUSIONTransient androgen depletion could successfully induce NE differentiation of LNCaP cells, and the intracellular cholesterol could re-distribute into axon terminals to enhance the formation of neurosecretory granules.

Androgens ; pharmacology ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; Cholesterol ; metabolism ; Humans ; Male ; Neurosecretory Systems ; metabolism ; Prostatic Neoplasms ; metabolism ; pathology ; Receptors, LDL ; metabolism ; Sterol Regulatory Element Binding Protein 1 ; metabolism ; Sterol Regulatory Element Binding Protein 2 ; metabolism

Attention deficit and hyperactive disorder(ADHD)is a chronic neurodevelopmental disorder characterized by inattention,hyperactivity-impulsivity,and working memory deficits.Social dysfunction is one of the major challenges faced by children with ADHD.It has been found that children with ADHD can't perform as well as typically developing children on facial expression recognition(FER)tasks.Generally,children with ADHD have some difficulties in FER,while some studies suggest that they have no significant differences in accuracy of specific emotion recognition compared with typically developing children.The neuropsychological mechanisms underlying these difficulties are as follows.First,neuroanatomically.Compared to typically developing children,children with ADHD show smaller gray matter volume and surface area in the amygdala and medial prefrontal cortex regions,as well as reduced density and volume of axons/cells in certain frontal white matter fiber tracts.Second,neurophysiologically.Children with ADHD exhibit increased slow-wave activity in their electroencephalogram,and event-related potential studies reveal abnormalities in emotional regulation and responses to angry faces when facing facial stimuli.Third,psychologically.Psychosocial stressors may influence FER abilities in children with ADHD,and sleep deprivation in ADHD children may significantly increase their recognition threshold for negative expressions such as sadness and anger.This article reviews research progress over the past three years on FER abilities of children with ADHD,analyzing the FER deficit in children with ADHD from three dimensions:neuroanatomy,neurophysiology and psychology,aiming to provide new perspectives for further research and clinical treatment of ADHD.

Purpose/Significance The establishment of a specialized database for children with attention deficit hyperactivity disorder(ADHD)aims to address the issues of low data usage efficiency caused by scattered and low-quality diagnostic data.Method/Process Based on clinical diagnostic data of children with ADHD from March 2020 to April 2024,natural language processing(NLP)techniques are utilized to realize the post-structuring of the data.Furthermore,standardization of the database is performed according to industry standards and treatment guidelines.Result/Conclusion The specialized database for children with ADHD is established,comprising data from 75 835 ADHD children and 280 000 clinical visits.This database supports various applications such as the analysis of basic character-istics of the ADHD population,prediction model construction,resource allocation optimization,and clinical pathway optimization.

Objective: To explore the feasibility of gender assignment in 46,XY disorders of sex development (DSD) with severe undermasculinisation mainly based on molecular diagnosis. Methods: A retrospective study of 45 patients of 46, XY DSD with severe undermasculinisation were admitted between November 2015 and October 2018 at Children′s Hospital, Zhejiang University School of Medicine. The initial social gender were all female, of whom the external genital manifestations were Prader 0 to 2; the degree of masculinity was scored using external masculinisation score (EMS); the position and development of the gonads were examined by ultrasound, cystoscopy and laparoscopy, also including assessing the development of the Wolffian tube and the Müllerian tube. The level and ratio of testosterone to dihydrotestosterone before and after hCG stimulation were evaluated for the function of Leydig cell and 5α-reductase-2. Gender role scales and sandbox games were used to assess gender role behavior. Genital sensitivity to androgen stimulation was assessed; A panel including 163 genes related to gender development were determined by second-generation sequencing in all 45 patients. Finally, a multidisciplinary team (MDT) makes a gender assignment after a comprehensive analysis mainly based on the molecular etiological diagnosis. Results: Thirty-nine out of 45 patients (87%) had an identifiable genetic etiology, and the remaining 6 (13%) were negative for genetic testing. Forty-five patients had EMS less than or equal to 3 points. Sexual psychological assessment was performed in 39 patients, with male dominance in 24 (62%) and female dominance in 15 (38%). The gender assignment was 23 cases (51%) for male and 19 cases (42%) for female, and 3 cases (7%) were not completely determined. Conclusions Molecular diagnosis provides a strong basis for appropriate gender assignment of 46, XY DSD children with severe undermasculinisation. Based on molecular diagnosis, each DSD should be analyzed by professional MDT to analyze the clinical symptoms/signs, gonadal development, gonad tumor risk, external genital morphology, sexual psychological assessment, potential fertility opportunities, parental views, Social and cultural factors, etc. make appropriate gender assignment.