Differences in clinical characteristics and lesion proteomics between inflammatory linear verrucous epidermal nevus and local verrucous epidermal nevus.

BACKGROUND: Verrucous epidermal nevus (VEN) are keratinocytic epidermal nevus that appear at birth or in early childhood. They exhibit a range of manifestations, depending on the patient's age. VEN are rarely encountered in clinical practice, and the systemic and comprehensive clinical characteristics of VEN have not been well investigated. Furthermore, the association between tandem mass tag (TMT)-based quantitative proteomics and the VEN phenotype is still unclear. OBJECTIVES: This study investigated the differences in the clinical characteristics and lesion proteomics between inflammatory linear VEN (ILVEN) and local VEN. METHODS: This retrospective study enrolled 125 patients with histopathologically diagnosed VEN who presented to our hospital between 2019 and 2021. We collected the clinical data of all patients with VEN using a self-designed questionnaire. The expression of proteins in VEN lesions was analyzed using TMT proteomics technology. RESULTS: In total, there were 125 patients with VEN that were evaluated, including 67 (53.60%) patients with local VEN and 58 (46.40%) with ILVEN. No significant differences were found in sex, onset age, and lesion location between patients with local VEN and those with ILVEN (all P > 0.05). Significant differences were found in the onset site and pruritus scores between patients with ILVEN and those with local VEN (all P < 0.05). According to the TMT proteomics results, 89 proteins were up or downregulated with at least 1.3-fold (upregulated: 38, downregulated: 51; P < 0.05) in ILVEN lesions relative to VEN lesions. The top 10 differentially expressed proteins between ILVEN and local VEN lesions were OGN, NT5C3A, ADD1, OLFML1, DHRS1, CALML5, SAMHD1, SFRP2, SPRR1B, and SERPINB13. The upregulated proteins are mainly involved in neutrophil activation, neutrophil-mediated immunity, and p53 signaling pathway (hsa04115). The downregulated proteins are mainly involved in cellular response to cytokine stimulus, cell adhesion, Th1 and Th2 cell differentiation. In total, based on the differentially expressed proteins between ILVEN and local VEN, five pathways that may be associated with the pathogenesis of inflammation, including CAMs (P = 0.006), Th1 and Th2 cell differentiation (P = 0.017), PPAR signaling pathway (P = 0.023), Th17 cell differentiation (P = 0.024), and p53 signaling pathway (P = 0.041). CONCLUSIONS: Clinical data of the patients revealed that ILVEN lesions presented with intense pruritus and inflammatory change. Differentially expressed proteins between ILVEN and local VEN are mainly involved in multiple inflammation related pathways associated with the pathogenesis mechanisms of pruritus. LIMITATIONS: The small sample size in clinical characteristic and proteomics study is one of the most significant limitations in our study. The inflammation associated proteins and signal pathways in the pathogenesis of pruritus in ILVEN is not explored. SIGNIFICANCE: In this study, we found the lesions of ILVEN patients presented with intense pruritus and inflammational change. A total of 89 proteins were up or downregulated with at least 1.3-fold (upregulated: 38, downregulated: 51; P < 0.05) in ILVEN lesions relative to VEN lesions. On the other hand, the etiology of itch in ILVEN mainly associated with inflammation, but the exact mechanisms was still unclear. We found the differentially expressed proteins between ILVEN and local VEN enriched five pathways that may be associated with the pathogenesis of inflammation and pruritus.

Neuroimaging Features, Follow-Up Analyses, and Comparisons Between Asymptomatic and Symptomatic Neurosyphilis.

INTRODUCTION: Many studies have explored the imaging characteristics of patients with neurosyphilis, but no systematic study has been made on the neuroimaging changes after anti-syphilitic treatment. The purpose of this study was to examine neuroimaging differences before and after treatment, comparing patients with asymptomatic and symptomatic neurosyphilis. METHODS: A total of 102 patients with neurosyphilis, including 60 cases of symptomatic neurosyphilis and 42 cases of asymptomatic neurosyphilis, were identified between December 2012 and June 2019. Their demographics, medical histories, serological tests of peripheral blood and cerebrospinal fluid, and especially neuroimaging features before and after anti-syphilitic treatment were collected and analyzed. RESULTS: The patients presented with variable clinical and neuroimaging features, including cerebral infarction or hemorrhage, atrophy, demyelination, arteritis, encephalitis, and hippocampal sclerosis. A total of 29 neuroradiological re-examinations were performed in 19 patients treated with anti-syphilitic medicine. The results indicated that some patients still presented neuroradiological progression after treatment, including 42.1% showing infarction lesions, 47.4% mild to severe brain atrophy, and 15.8% white matter demyelination. CONCLUSION: The clinical and neuroimaging features of neurosyphilis patients are diverse, and their follow-up neuroimaging continued to show progression even with standardized treatment.

Efficacy and safety of endovascular thrombectomy in mild ischemic stroke: results from a retrospective study and meta-analysis of previous trials.

BACKGROUND: Mechanical thrombectomy has been proven as a standard care for moderate to severe ischemic stroke with anterior large vessel occlusion (LVO); however, whether it is equally effective in mild ischemic stroke (MIS) is controversial. METHODS: In this retrospective study, a total of 177 Chinese patients presenting with MIS (NIHSS ≤8) and LVO between January 2014 and September 2017 from seven comprehensive stroke centers were identified. Odds of good outcome with endovascular thrombectomy versus medical treatment were obtained by logistic regression analysis and propensity-score matching method, and a meta-analysis pooled results from six studies (n = 733). RESULTS: Good outcome (mRS: 0-1) was 58.2% (46/79) in the thrombectomy and 46.9% (46/98) in the medical group, which showed no statistical significance before adjustment (P = 0.13; OR = 1.57, 95% CI: 0.86 to 2.86). The adjusted ORs of thrombectomy versus medical group were 3.23 (95% CI, 1.35 to 7.73; P = 0.008) by multivariable logistic analysis, 2.78 (1.12 to 6.89; P = 0.02) by propensity score matching analysis, and 3.20 (1.22 to 8.37; P = 0.01) by propensity score matching analysis with additional adjustments, respectively. Thrombectomy treatment did not result in excessive mortality or symptomatic intracranial hemorrhage after adjustments. The meta-analysis did not confirm the associations between good outcome and endovascular treatment. CONCLUSIONS: The current study indicates that endovascular thrombectomy is associated with good functional outcome in MIS patients with LVO, and without additional risk of symptomatic intracranial hemorrhage and mortality. Although the meta-analysis failed to demonstrate its superiority compared to medical treatment, randomized clinical trials are needed.

Three-dimensional visualization of the functional fascicular groups of a long-segment peripheral nerve.

The three-dimensional (3D) visualization of the functional bundles in the peripheral nerve provides direct and detailed intraneural spatial information. It is useful for selecting suitable surgical methods to repair nerve defects and in optimizing the construction of tissue-engineered nerve grafts. However, there remain major technical hurdles in obtaining, registering and interpreting 2D images, as well as in establishing 3D models. Moreover, the 3D models are plagued by poor accuracy and lack of detail and cannot completely reflect the stereoscopic microstructure inside the nerve. To explore and help resolve these key technical problems of 3D reconstruction, in the present study, we designed a novel method based on re-imaging techniques and computer image layer processing technology. A 20-cm ulnar nerve segment from the upper arm of a fresh adult cadaver was used for acetylcholinesterase (AChE) staining. Then, 2D panoramic images were obtained before and after AChE staining under the stereomicroscope. Using layer processing techniques in Photoshop, a space transformation method was used to fulfill automatic registration. The contours were outlined, and the 3D rendering of functional fascicular groups in the long-segment ulnar nerve was performed with Amira 4.1 software. The re-imaging technique based on layer processing in Photoshop produced an image that was detailed and accurate. The merging of images was accurate, and the whole procedure was simple and fast. The least square support vector machine was accurate, with an error rate of only 8.25%. The 3D reconstruction directly revealed changes in the fusion of different nerve functional fascicular groups. IN CONCLUSION: The technique is fast with satisfactory visual reconstruction.

Follow-up study identifies two novel susceptibility loci PRKCB and 8p11.21 for systemic lupus erythematosus.

OBJECTIVE: We have performed a large-scale replication study based on our previous genome-wide association study (GWAS) of SLE in the Chinese Han population to further explore additional genetic variants affecting susceptibility to SLE. METHODS: Thirty-eight single nucleotide polymorphisms from our GWAS were genotyped in two additional Chinese Han cohorts (total 3152 cases and 7050 controls) using the Sequenom Massarray system. Association analyses were performed using logistic regression with gender or sample cohorts as a covariate. RESULTS: Association evidence for rs16972959 (PRKCB at 16p11.2) and rs12676482 (8p11.21) with SLE was replicated independently in both replication cohorts (P < 0.05), showing high significance for SLE in combined all 4199 cases and 8255 controls of Chinese Han [rs16972959: odds ratio (OR) = 0.81; 95% CI 0.76, 0.87; P(combined) = 1.35 × 10(-9); rs12676482: OR = 1.26; 95% CI 1.15, 1.38; P(combined) = 6.68 × 10(-7)). PRKCB is related to the established SLE immune-related pathway (NF-κB) and 8p11.21 contains important candidate genes such as IKBKB and DKK4. IKBKB is a critical component of NF-κB and DKK4 is an inhibitor of canonical Wnt signalling pathway. Interestingly, PRKCB is required for recruiting IKBKB into lipid rafts, up-regulating NF-κB-dependent survival signal. CONCLUSIONS: Our findings provided novel insights into the genetic architecture of SLE and emphasized the contribution of multiple variants of modest effect. Further study focused on PRKCB, 8p11.21, should advance our understanding on the pathogenesis of SLE.

Human peripheral nerve-derived scaffold for tissue-engineered nerve grafts: histology and biocompatibility analysis.

Human acellular nerve grafts (ANGs) have been rarely used to construct tissue-engineered nerves compared to the animal-derived ANGs, and their potential clinical applications were relatively unknown. In this study, it was aimed to investigate the structure and components of a scaffold derived from human peripheral nerve and evaluate its biocompatibility. The human peripheral nerves were processed to prepare the scaffolds by chemical extraction. Light and electron microscopy were carried out to analyze scaffold structure and components. The analysis of cytotoxicity, hemolysis, and skin sensitization were performed to evaluate their biocompatibility. It was shown that Schwann cells and axons, identified by S-100 and neurofilament (NF) expression, were absent, and the scaffolds were cell-free and rich in collagen-I and laminin whose microarchitecture was similar to the fibrous framework of human peripheral nerves. It was revealed from biocompatibility tests that the scaffolds had very mild cytotoxicity and hemolysis, whereas skin sensitization was not observed. The constructed human peripheral nerve-derived scaffolds with well biocompatibility for clinical practice, which were cell-free and possess the microstructure and extracellular matrix (ECM) of a human nerve, might be an optimal scaffold for tissue-engineered nerve grafts in human.