BACKGROUND: Senescent human skin primary fibroblast (FB) models have been established for studying aging-related, proliferative, and inflammatory skin diseases. The aim of this study was to compare the transcriptome characteristics of human primary dermal FBs from children and the elderly with four senescence models. METHODS: Human skin primary FBs were obtained from healthy children (FB-C) and elderly donors (FB-E). Senescence models were generated by ultraviolet B irradiation (FB-UVB), D-galactose stimulation (FB-D-gal), atazanavir treatment (FB-ATV), and replication exhaustion induction (FB-P30). Flow cytometry, immunofluorescence staining, real-time quantitative polymerase chain reaction, co-culturing with immune cells, and bulk RNA sequencing were used for systematic comparisons of the models. RESULTS: In comparison with FB-C, FB-E showed elevated expression of senescence-related genes related to the skin barrier and extracellular matrix, proinflammatory factors, chemokines, oxidative stress, and complement factors. In comparison with FB-E, FB-UVB and FB-ATV showed higher levels of senescence and expression of the genes related to the senescence-associated secretory phenotype (SASP), and their shaped immune microenvironment highly facilitated the activation of downstream immune cells, including T cells, macrophages, and natural killer cells. FB-P30 was most similar to FB-E in terms of general transcriptome features, such as FB migration and proliferation, and aging-related characteristics. FB-D-gal showed the lowest expression levels of senescence-related genes. In comparisons with the single-cell RNA sequencing results, FB-E showed almost complete simulation of the transcriptional spectrum of FBs in elderly patients with atopic dermatitis, followed by FB-P30 and FB-UVB. FB-E and FB-P30 showed higher similarity with the FBs in keloids. CONCLUSIONS Each senescent FB model exhibited different characteristics. In addition to showing upregulated expression of natural senescence features, FB-UVB and FB-ATV showed high expression levels of senescence-related genes, including those involved in the SASP, and FB-P30 showed the greatest similarity with FB-E. However, D-galactose-stimulated FBs did not clearly present aging characteristics.
Humans ; Fibroblasts/drug effects* ; Cellular Senescence/physiology* ; Skin/metabolism* ; Child ; Transcriptome/genetics* ; Aged ; Ultraviolet Rays ; Cells, Cultured ; Galactose/pharmacology*

OBJECTIVE To systematically evaluate the efficacy and safety of oxcarbazepine(OXC) and carbamazepine(CBZ) in the treatment of vestibular paroxysmia(VP). METHODS Randomized controlled trials(RCTs) comparing OXC and CBZ in treating VP were searched in PubMed, Cochrane Library, Embase, Wanfang, CNKI, VIP, China Biomedical Literature Database(SinoMed), from the establishment of the database to April 2022. RevMan5.4 software was used to perform meta-analysis on outcomes including total effective rate, the dizziness handicap inventory(DHI) score, attack frequency, degree of vertigo, self-rating anxiety scale(SAS) score, self-rating depression scale(SDS) score and adverse reactions. The quality of evidence for each outcome was evaluated using GRADE standard. RESULTS A total of 6 RCTs were included with a total sample size of 425 cases, including 211 cases in the OXC group and 214 cases in the CBZ group. Meta analysis results showed that there was no significant difference in the total effective rate in treating VP[RR=1.04, 95%CI(0.90, 1.20), P=0.57] and the degree of vertigo[SMD=-0.80, 95%CI(-2.14, 0.54), P=0.24]; OXC group was lower than CBZ group in DHI score[MD=-8.81, 95%CI(-14.59, -3.03), P=0.003], attack frequency[SMD=-1.86, 95%CI(-3.32, -0.41), P=0.01], SAS score[MD=-7.77, 95%CI(-14.09, -1.46), P=0.02], SDS score[MD=-10.45, 95%CI(-15.36,-5.54), P<0.000 1] and had fewer adverse reactions[RR=0.43, 95%CI(0.29, 0.63), P<0.000 1]. GRADE evidence quality evaluation showed that the quality for the adverse reactions rate was low and the quality for the other index was very low. CONCLUSION Compared with CBZ, OXC has better effects on the frequency of vertigo attacks, quality of life, depression and anxiety and adverse reactions. However, the sample size of the current studies is small and the evidence is low-quality. Large-sample, high-quality RCTs are need to provide further evidence.

Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant genetic disorder characterized by distinctive craniofacial features, skeletal abnormalities and short stature;it is classified into three subtypes according to genetics and clinical manifestations. We report a Han Chinese family with 2 TRPS type III patients, the proband and his mother, with typical clinical presentation. There were also 3 ankylosing spondylitis (AS) patients in this family, the proband’s mother and 2 uncles. A missense mutation, c.2762G>A (p.Arg921Gln), in the transcriptional repressor GATA binding 1 (TRPS1) gene was detected in the proband and his mother. The association between TRPS and AS and the diagnostic criteria for TRPS are discussed.