Human skin comprises stratified squamous epithelium and dermis with various stromal cells and the extracellular matrix (ECM). The basement membrane (BM), a thin layer at the top of the dermis, serves as a unique niche for determining the fate of epidermal stem cells (EpSCs) by transmitting physical and biochemical signals to establish epidermal cell polarity and maintain the hierarchical structure and function of skin tissue. However, how stem cell niches maintain tissue homeostasis and control wound healing by regulating the behavior of EpSCs is still not completely understood. In this study, a hierarchical skin proteome map is constructed using spatial quantitative proteomics combined with decellularization, laser capture microdissection, and mass spectrometry. The specific functions of different structures of normal native skin tissues or tissues with a dermatologic disease are analyzed in situ. Transforming growth factor-beta (TGFβ)-induced protein ig-h3 (TGFBI), an ECM glycoprotein, in the BM is identified that could enhance the growth and function of EpSCs and promote wound healing. Our results provide insights into the way in which ECM proteins facilitate the growth and function of EpSCs as part of an important niche. The results may benefit the clinical treatment of skin ulcers or diseases with refractory lesions that involve epidermal cell dysfunction and re-epithelialization block in the future.

Serology is the mainstay for syphilis treatment monitoring. Baseline rapid plasma reagin (RPR) titre, HIV status, and syphilis stage have been found to be associated with the time to serological response among syphilis patients. This study mainly aims to evaluate the time to serological response, and to identify factors affecting the serological outcome. Medical records of syphilis cases diagnosed in Peking Union Medical College Hospital (PUMCH) between 2008 and 2018 were retrospectively reviewed. Kaplan–Meier analysis was performed to evaluate the median time to serologic response and cumulative probability of serologic response over time according to different variables. Cox regression model was conducted to find factors associated with serological response. There were 984 patients diagnosed with primary, secondary, or latent syphilis cases and receiving injections of benzathine penicillin G (BPG) as initial treatment at the Peking Union Medical College Hospital (PUMCH) between 2008 and 2018. Finally, data on 571 patients, including 49 (8.6%) primary syphilis, 261 (45.7%) secondary syphilis, and 261 (45.7%) latent syphilis, were used for analysis. It took longer time to achieve serological response for subjects aged ≥45 years than younger individuals (89 days versus 58 days; p=0.008). Males achieved serological response more quickly than females (71 days versus 83 days; p = 0.011). There was a significant difference in the time to serological response according to different syphilis stages ( p < 0.001), with 55 days (95% CI, 43–67 days) for primary, 57 days (95% CI, 51–63 days) for secondary, and 117 days for latent syphilis. In addition, patients with lower baseline RPR titre had longer period to achieve serological response (252 days [95% CI, 129–375 days] for RPR titre ≤1:8, 78 days [95% CI, 63–93 days] for RPR titres from 1:16 to 1:32, and 53 days [95% CI, 49–57 days] for RPR titres ≥1:64, respectively; p<0.001). However, no significant difference in time to serological response to treatment was found according to HIV coinfection status. The result of multivariate Cox regression analysis showed that being older than 45 years with latent syphilis, HIV coinfection, or with baseline RPR titre ≤1:8 was associated with slow response. Among patients followed for at least 1 year or seroreverted, 128 (36.9%) had seroreverted within a year, and 219 (63.1%) still had a positive RPR after 1 year. For multiple logistical regression, being female and HIV coinfection were significantly associated with the failure of seroreversion (OR, 0.42 [95% CI, 0.26–0.68]; p <0.001). This study revealed that younger age, higher initial RPR titre, early syphilis stage, and HIV-negative status were associated with faster serological cure. Female sex, individuals with HIV coinfection, and latent syphilis were significantly associated with the failure of seroreversion.

Background Syphilis is a chronic sexually transmitted disease caused by infection with Treponema pallidum, which can invade various system organs, leading to clinical manifestations such as neurosyphilis, ocular syphilis, and cardiovascular syphilis and seriously endangering human health. Serofast status is a common outcome after syphilis treatment that presents an important clinical problem. At present, the etiology of serofast status remains unknown. Methods A systematic investigation of the microRNA (miRNA) expression profiles in peripheral blood mononuclear cells (PBMCs) of patients with serofast status or secondary syphilis and of healthy control subjects was conducted using small RNA-seq. The expression of miRNAs was further confirmed by real-time fluorescence quantitative PCR (qPCR) assays. Results The data reveal a specific miRNA expression profile that was displayed in cells from patients with serofast status. Known and novel predicted (np)-miRNAs were also identified and verified, such as miR-338-5p, np-miR-163, np-miR-128, np-miR-244, and np-miR-5, which together may be used as indicators for treatment evaluation. The functions of genes targeted by the miRNAs differentially expressed in serofast status patients were further analyzed; these genes were found to be involved in various biological functions, such as T-cell receptor signaling pathways, metabolism, and growth. Our study presents the first systematic landscape of miRNAs in PBMCs from patients with serofast status and proposes specific miRNAs linked with serofast status that merit further investigation as potential biomarkers. Conclusion Our results provide further evidence that serofast status is closely related to host immune function. Additionally, the miRNA expression profile in PBMCs of patients with serofast status generated by this work offers insight into the complex immune network in humans. We hope our results can inspire the development of new treatment options for patients with serofast status.