Background. Hepcidin antimicrobial peptide (HAMP) is a key factor in maintaining iron metabolism, which may induce ferroptosis when upregulated. However, its prognostic value and relation to immune infiltrating cells remains unclear. Methods. This study analyzed the expression levels of HAMP in the Oncomine, Timer and Ualcan databases, and examined its prognostic potential in KIRC with R programming. The Timer and GEPIA databases were used to estimate the correlations between HAMP and immune infiltration and the markers of immune cells. The intersection genes and the co-expression PPI network were constructed via STRING, R programming and GeneMANIA, and the hub genes were selected with Cytoscape. In addition, we analyzed the gene set enrichment and GO/KEGG pathways by GSEA. Results. Our study revealed higher HAMP expression levels in tumor tissues including KIRC, which were related to poor prognosis in terms of OS, DSS and PFI. The expression of HAMP was positively related to the immune infiltration level of macrophages, Tregs, etc., corresponding with the immune biomarkers. Based on the intersection genes, we constructed the PPI network and used the 10 top hub genes. Further, we performed a pathway enrichment analysis of the gene sets, including Huntington’s disease, the JAK-STAT signaling pathway, ammonium ion metabolic process, and so on. Conclusion. In summary, our study gave an insight into the potential prognosis of HAMP, which may act as a diagnostic biomarker and therapeutic target related to immune infiltration in KIRC.

BACKGROUND AND PURPOSE: This study explores the impact of stenosis degree on outcomes of stenting compared with medical therapy alone in patients with symptomatic intracranial artery stenosis. MATERIALS AND METHODS: Patients with a transient ischemic attack or nondisabling ischemic stroke, attributed to 70 to 99% stenosis of a major intracranial artery, were included. The patient cohort was drawn from the China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS) and the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS). The primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. RESULTS: Out of 806 patients, 92 patients (11%) met the primary outcome. As the degree of stenosis increased, the risk of the primary endpoint was significantly lower in the stenting group (R = -0.886, P = .03). For stenosis below or equal to 85%, stenting is worse than medical therapy given the high perioperative risk [13% vs. 8.0%, HR, 1.67, (95% CI, 1.04-2.67); P = .04]; at stenosis degree above 85%, stenting was preferred over medical therapy given the potential for better long-term prevention [14% vs. 21%, HR, 0.67, (95% CI, 0.29-1.56); P = .36]. CONCLUSIONS: Patients with higher degrees of stenosis are more likely to benefit from stenting. Patients with intracranial artery stenosis exceeding 85% may be the focus of future studies. If innovations in interventional techniques significantly reduce perioperative risk, the critical threshold of 85% as the degree of stenosis might be reconsidered. ABBREVIATIONS: CASSISS = China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis; SAMMPRIS = Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis; ICAS = Intracranial atherosclerotic arterial stenosis; WASID = Warfarin versus Aspirin for Symptomatic Intracranial Disease; VISSIT = Vitesse Intracranial Stent Study for Ischemic Stroke Therapy; PH = proportional hazards; HR = Hazard ratio

Introduction Cerebrovascular intervention is an excellent option to treat cerebrovascular diseases. Interventional access is a prerequisite and a foundation for cerebrovascular intervention, which is crucial to the success of an intervention. Although transfemoral arterial access (TFA) has become a popular and acceptable method of access for cerebrovascular angiography and intervention in clinical practice, it has some drawbacks that limit the usage in cerebrovascular interventions. Therefore, transcarotid arterial access (TCA) has been developed in cerebrovascular interventions. We aim to conduct a systematic review to compare the safety and efficacy of TCA with TFA for cerebrovascular intervention. Methods and analysis In this protocol, Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols were followed. PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials will be searched mainly from 1 January 2004, to the formal search date. Additionally, reference lists and clinical trial registries will be searched. We will include clinical trials with more than 30 participants, which reported the endpoints of stroke, death and myocardial infarction. Two investigators will independently select studies, extract data and assess bias risk. A standardised mean difference with 95% CI will be presented for continuous data, and a risk ratio with 95% CI will be presented for dichotomous data. On inclusion of sufficient studies, subgroup analysis and sensitivity analysis will be conducted. The funnel plot and Egger’s test will be used to assess publication bias. Ethics and dissemination As only published sources will be used in this review, ethical approval is not required. We will publish the results in a peer-reviewed journal. PROSPERO registration number CRD42022316468.

Background. Skin cutaneous melanoma is one of most aggressive type of cancers worldwide. Therefore, the identification of SKCM biomarkers is of great importance. FLG gene is one of the genes that encode proteins involved in epidermal formation. This was the first time to study the role of FLG in the prognosis and immune infiltrates of skin cutaneous melanoma. Methods. We downloaded the somatic mutation data of 471 SKCM patients from the Cancer Genome Atlas (TCGA) database and analyzed the mutation profiles with MafTools package. The expression of FLG and the overall survival in SKCM were analyzed by GEPIA. Additionally, univariate and multivariate Cox analyses were used to compare several clinical features with survival rates. We used TIMER to investigate FLG expression and collection of immune infiltration levels in SKCM, as well as cumulative survival in SKCM. Meanwhile, we also used CIBERSORT to investigate the association between FLG and cancer immune infiltration. In addition, gene set enrichment analysis (GSEA) was performed using the TCGA dataset. Furthermore, data from GEO and HPA was used to validate the results. Results. Single nucleotide polymorphism (SNP) happened more frequently than insertion or deletion, and CT was the most common of SNV in SKCM. We selected the first 15 mutated genes by analyzing 471 melanoma samples, and the prognosis analysis showed that only the high expression of mutated FLG gene was significantly correlated with the poor prognosis of SKCM. Multivariate Cox analysis showed that age, the worse tumor status, less lymph node metastasis, and FLG expression were independent factors for prognosis. Specifically, lower infiltration levels of B cell, CD8+ T cells, neutrophils, and dendritic cells correlated with poor survival outcomes in SKCM. GSEA revealed that FLG is closely related to cancer pathways and epidermal cell proliferation. In addition, the previous conclusions can be verified from external data from GEO and HPA. Conclusion. The discovery of mutant gene FLG as a biomarker of SKCM helps elucidate how changes in the immune environment promote the occurrence of cutaneous melanoma. Further analysis suggested that FLG might be a new predictor of SKCM prognosis.