Functional Involvement of ADRA1D in Cutaneous Melanoma Progression and Angiogenesis.

Cutaneous melanoma is a highly aggressive and malignant skin cancer, and its high recurrence rate and drug resistance increase the difficulty of treating advanced-stage patients. Studies have revealed that treatment via stimulation of alpha-1 adrenergic receptor (ADRA1) subtypes inhibits melanoma growth in mice. However, the associations between alpha-1D adrenergic receptor (ADRA1D) and cutaneous melanoma are poorly understood. Tissue specimens from 16 pairs of patients with a pigmented nevus and cutaneous melanoma were analyzed for ADRA1D expression using immunohistochemical staining. Western blotting and RT-qPCR were carried out in order to detect ADRA1D expression levels in melanoma cells and human epidermal melanocytes (HEMs), hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF) levels in HUVECS. A375 cells were transfected with a lentivirus overexpressing ADRA1D. Wound-healing, Transwell, and cell proliferation assays were utilized to identify the ADRA1D effect on the migration, invasion, and proliferation of the two groups of A375 cells in vitro. In order to evaluate the function of ADRA1D in vivo, a melanoma xenograft model was developed in immunodeficient mice. ADRA1D was low expressed in cutaneous melanoma tissues. Overexpression of ADRA1D inhibited the tubulation and migration of HUVECs in vitro. Overexpression of ADRA1D significantly decreased the HIF-1α and VEGF expression. Overexpression of ADRA1D inhibited the invasion and proliferation of A375 melanoma cells in vitro and reduced its angiogenesis in vivo. ADRA1D inhibits cutaneous melanoma growth and angiogenesis. It attenuates melanoma cell proliferation and invasion. Meanwhile, its anti-angiogenic effect is achieved by negatively regulating the HIF-1α/VEGF axis in melanoma tissue, thereby attenuating the growth of cutaneous melanoma and reducing the potential of metastasis.

Analysis of clinical features and inflammatory-related molecules with the disease in acute infectious urticaria.

Acute infectious urticaria, a subset of acute urticaria, with severe persistence wheals and systemic symptoms, response well to corticosteroids treatment in combination with antibiotics. The exact pathogenic mechanisms are not fully understood. In this study, we aim to analyze the different clinical features, compare the level of neutrophil activation, and investigate the expression of inflammatory related cytokine in patients with acute urticaria and acute infectious urticaria. Eighteen patients with acute infectious urticaria and eighteen patients with acute urticaria were included in this study. We analyzed the difference between the clinical features and the serum expressions of pro-inflammatory factors in the two groups, then examined the levels of inflammation-associated cytokines before and after treatment of acute infectious urticaria. Hematoxylin & eosin (HE) staining and immunohistochemistry (IHC) were used to further study the relationship between neutrophil and neutrophil-derived Myeloperoxidase (MPO) of lesions in the two groups. The expression levels of C-reactive protein (CRP), D-dimer, interleukin 6 (IL-6), IL-8 and chemokine ligand 8 (CCL8) in serum were significantly higher in acute infectious urticaria than acute urticaria. In acute infectious urticaria, the serum expression levels of CCL8 were significantly decreased after the treatment, a significant correlation observed between CRP levels and IL-6, both CCL8 and CRP were positively correlated with neutrophil granulocytes. Neutrophils infiltration were not observed by HE stains in two groups, but in IHC stains we found a positive expression of MPO in acute infectious urticaria lesions. Elevated neutrophil in the serum, which is associated with the levels of IL-8 & CCL8, and positively expressed MPO in lesions, may be involved in the pathogenic mechanism of acute infectious urticaria.

Classic Eosinophilic Pustular Folliculitis in an Immunocompetent Patient with Syphilis: Are They Related?

Eosinophilic pustular folliculitis (EPF) is a rare, chronic, non-infectious inflammatory skin disease. Although the pathogenesis of EPF is unknown, eosinophilic pustular folliculitis may be associated with human immunodeficiency virus (HIV) infection, malignancies or syphilis. Here, we report the first case of EPF associated with syphilis, indicating that syphilis and EPF are correlated with T-helper type 2 immune responses. A 48-year-old man gradually developed erythema and pustules on the face, neck. Physical examination revealed multiple infiltrative red patches and plaques on the face, neck with tiny pustules. Skin biopsy results revealed that the dermal follicular sebaceous gland unit was infiltrated by a large number of neutrophils and eosinophils, forming eosinophilic microabscesses. Therefore, the patient was diagnosed with EPF associated with syphilis and received drug treatment. After the treatment, the pustules markedly decreased, leaving behind pigmentation. Furthermore, the patient is still being followed up.

Clinical value of the prognostic nutritional index and red blood cell distribution width-to-albumin ratio for the prediction of severity of and mortality associated with Stevens-Johnson syndrome/toxic epidermal necrolysis.

The prognostic nutritional index (PNI) and red blood cell distribution width-to-albumin ratio (RAR) are considered to be related to the prognosis of disease severity. However, the role of these biomarkers in predicting Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) severity and mortality is unclear. The aim of the current study was to investigate the association of PNI and RAR with severity and mortality in individuals with SJS/TEN. Clinical data were retrospectively collected from 74 individuals with SJS/TEN and 74 healthy individuals, who were matched for age and sex during the same period. PNI, RAR, and other indicators were compared between individuals with SJS/TEN and healthy controls. The association of PNI and RAR with SJS/TEN severity was assessed using Spearman or Pearson correlation analyses. Individuals with SJS/TEN were categorized into two groups, either survivors or nonsurvivors. The correlation between PNI, RAR, and SJS/TEN mortality was analyzed using univariate and multivariate logistic regression. The predictive value of the previously mentioned indicators on the mortality of patients with SJS/TEN was assessed using receiver operating characteristic curve analysis. The RAR level of patients with SJS/TEN was greater than that of the control group (p < 0.05), whereas PNI was lower. In compliance with correlation analysis, RAR was positively correlated with SCORTEN (Score of Toxic Epidermal Necrolysis) and ABCD-10 (age, bicarbonate, cancer, dialysis, 10% body surface area) (p < 0.05), and PNI was negatively correlated (p < 0.05). RAR is a risk factor for death in patients with SJS/TEN, but an elevated PNI level is a protective factor for mortality. The best cutoff values of PNI and RAR for predicting death in patients with SJS/TEN were 31.375 (sensitivity, 84.7%; specificity, 80%) and 0.486 (sensitivity, 73.3%; specificity, 84.7%). These results underscore the potential clinical value of PNI and RAR as appropriate and meaningful biomarkers to assess the severity of SJS/TEN and the mortality associated with it.

Prediction of Diagnostic Gene Biomarkers Associated with Immune Infiltration for Basal Cell Carcinoma.

Purpose: Basal cell carcinoma (BCC) is a frequent tumor of the surface layer of skin or its accessories, and ranks first among the prevalence of skin cancer cases. However, its pathogenesis remains unclear. The purpose of this analysis was to scientifically evaluate the role of mRNAs in the occurrence and progression of BCC and further elucidate their underlying potential molecular mechanisms of action. Methods: Differentially expression genes (DEGs) between nineteen BCC cases and five controls which initiate from the GSE103439 and GSE7553 datasets were identified and the transcriptome sequencing information was obtained. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and Gene Ontology (GO) annotation were performed. Logistic regression (LASSO) and support vector machine (SVM) analyses were performed to identify candidate biomarkers obtained from protein-protein interaction (PPI) analysis. The tumor microenvironment comprising hub genes in BCC was investigated by immune infiltration analysis. The expression of two representative hub genes (KIF23 and NCAPG) was measured by qRT-PCR. Finally, the potential miRNAs and lncRNAs related to the hub genes were analyzed on relevant websites to obtain a ceRNA interaction network. Results: Twenty-seven DEGs were identified. Fifteen hub genes were screened in the protein-protein interaction network. These showed marked enrichment in the cell cycle and p53 signaling pathway. FGF20, KIF23, and NCAPG were identified as the diagnostic markers of BCC. Immune cell infiltration analysis suggested their significant association with T cells CD4 memory activated, macrophages M1, and natural killer (NK) resting cells. Two miRNAs and twelve lncRNAs were used to construct the lncRNA-miRNA-mRNA ceRNA network. Conclusion: FGF20, KIF23, and NCAPG are potential diagnostic markers of BCC. Our findings may shed new light on the molecular mechanisms underlying BCC occurrence.

Considering Computational Mathematics IGHG3 as Malignant Melanoma Is Associated with Immune Infiltration of Malignant Melanoma.

Malignant melanoma is one of the most threatening cancers to human health. Only 14% of patients with malignant melanoma have a remaining life span of 5 years. At present, there have been some studies looking for potential prognostic indicators of esophageal cancer from the level of genes and infiltrating immune cells, but there are still some problems that need to be resolved urgently. This paper proposes IGHG3 as the immune infiltration of malignant melanoma, which takes into account the computational mathematics. It aims to deduce the characteristics of immune cell infiltration in malignant melanoma and study the relationship between different immune cell infiltration characteristics and prognosis. The method in this article is to establish a computational mathematical model for the immunotherapy of melanoma, then study the method of identification of the affinity of the IGHG3 reagent, and finally obtain the gene expression of immune infiltration. The functions of these methods are, respectively, to predict the dynamic behavior of T cells with two different specificities through mathematical models and to test the matching degree of different concentrations of IGHG3 reagent with the human body. Then use the ssGSEA algorithm to obtain immune infiltration related data and calculate the difference between the weighted empirical cumulative distribution function of all genes in the effect of IGHG3 on melanoma that was carried out. The experimental results showed the computational mathematical method genome and all the remaining genes. In this study, a computational mathematical method to detect the IGHG3 gene expression had a significant inhibitory effect on A375 cells in the experimental group, and the knockdown efficiency reached 85.6%.

Successful treatment of tuberculosis verrucosa cutis with fester as primary manifestation with photodynamic therapy and anti-tubercular drugs.

Tuberculosis verrucosa cutis (TBVC) is a rare type of cutaneous tuberculosis, which often occurs in the body with good immunity to tuberculosis bacilli. It usually presents as a hyperkeratotic verrucous plaque with polygonal boarders but can mimic or evolved into other dermatosis such as verruca vulgaris, chromoblastomycosis, hyperkeratotic lupus vulgaris, hypertrophic lichen planus, or squamous cell carcinoma, leading to delayed diagnosis. Here, we reported that a 62-year-old patient diagnosed by TBVC with fester as primary manifestation. Photodynamic therapy combined with anti-tuberculosis drugs is an effective method to treat TBVC lesions with fester, and it may shorten the treatment cycle of anti-tuberculosis drugs.

Correlation of the detection rate of upper GI cancer with artificial intelligence score: results from a multicenter trial (with video).

BACKGROUND AND AIMS: The quality of EGD is a prerequisite for a high detection rate of upper GI lesions, especially early gastric cancer. Our previous study showed that an artificial intelligence system, named intelligent detection endoscopic assistant (IDEA), could help to monitor blind spots and provide an operation score during EGD. Here, we verified the effectiveness of IDEA to help evaluate the quality of EGD in a large-scale multicenter trial. METHODS: Patients undergoing EGD in 12 hospitals were consecutively enrolled. All hospitals were equipped with IDEA developed using deep convolutional neural networks and long short-term memory. Patients were examined by EGD, and the results were recorded by IDEA. The primary outcome was the detection rate of upper GI cancer. Secondary outcomes were part scores, total scores, and endoscopic procedure time, which were analyzed by IDEA. RESULTS: A total of 17,787 patients were recruited. The total detection rate of cancer-positive cases was 1.50%, ranging from .60% to 3.94% in each hospital. The total detection rate of early cancer-positive cases was .36%, ranging from .00% to 1.58% in each hospital. The average total score analyzed by IDEA ranged from 64.87 ± 16.87 to 83.50 ± 9.57 in each hospital. The cancer detection rate in each hospital was positively correlated with total score (r = .775, P = .003). Similarly, the early cancer detection rate was positively correlated with total score (r = .756, P = .004). CONCLUSIONS: This multicenter trial confirmed that the quality of the EGD result is positively correlated with the detection rate of cancer, which can be monitored by IDEA. (Clinical trial registration number: ChiCTR2000029001.).

Development and validation of prognostic nomogram in patients with nonmetastatic malignant melanoma: a SEER population-based study.

BACKGROUND: The condition of tumor recurrence and overall death can be worried in the progress of nonmetastatic malignant melanoma (NMMM). Our goal was to construct and validate a prognostic nomogram from a large population database, which is vital for physicians to predict the 3- and 5-year overall survival (OS) rates of patients with NMMM. METHODS: According to the Surveillance, Epidemiology, and End Results (SEER) program, patients were collected and randomly assigned into the training and validation cohorts. Several independent risk factors were identified based on the methods of univariable and multivariable cox hazards regression and were incorporated to develop a nomogram. The concordance index (C-index), the area under the receiver operating characteristics (AUC) curve and calibration plot were confirmed to assess predictive power of the nomogram. Decision curve analysis (DCA) was performed to measure nomogram for the clinical practice. RESULTS: A total of 66192 eligible patients, randomly assigned into 70% of training (n = 46 336) and 30% of validation cohorts (n = 19 856), were selected in this study. The selected independent factors were applied to develop a nomogram, and validated indexes indicated nomogram had a good discrimination ability. The C-index for OS rates was 0.817 (95% CI: 0.811-0.823) in training cohort and 0.817 (95% CI: 0.809-0.825) in validation cohort, respectively. The AUCs of 3- and 5-year OS rates were more than 0.79, and the calibration plots also showed a good power for the nomogram. DCA demonstrated that constructed nomogram can provide clinical net benefit. CONCLUSION: We constructed a novel nomogram that more accurately and comprehensively predict OS with nonmetastatic malignant melanoma patients, which is vital for clinician to improve individual treatment, make reasonable clinical decisions, and set appropriate follow-up strategies.