Identification of key macrophage-related genes in systemic sclerosis–associated interstitial lung disease based on single-cell and bulk transcriptomic data

by Ting Zhao, Yulin Wang, Fu-an Lin

Systemic sclerosis–associated interstitial lung disease (SSc-ILD) is a major clinical challenge with no effective treatments. It is also the leading cause of death in patients with systemic sclerosis. Thus, understanding its underlying molecular mechanisms, particularly those related to macrophage-related gene functions, is critical to address this urgent medical need.

In this study, single-cell and transcriptomic data retrieved from a public database were analyzed to investigate the underlying molecular mechanisms of SSc-ILD. A series of comprehensive analyses was conducted, including cell–cell communication analysis, pseudotime trajectory analysis, and high-dimensional weighted gene co-expression network analysis, to identify pertinent genes linked to macrophage modules. Candidate genes were determined by intersecting differentially expressed genes (DEGs) with macrophage module genes. Subsequently, key genes were identified through protein–protein interaction (PPI) network analysis and gene expression validation. Various analytical procedures were used to evaluate the function of the key genes in the regulatory roles of SSc-ILD, including enrichment analysis, immune infiltration analysis, drug prediction, and molecular docking.

Of the 1515 DEGs and 400 macrophage module genes intersected, 50 candidate genes were identified. In particular, ARG2, ELF3, and NKX2–1 emerged as key genes through subsequent PPI network analyses and gene expression evaluations. Enrichment analyses revealed a notable co-enrichment of the lysosomal pathway with these key genes. Moreover, immune infiltration analysis revealed a strong negative correlation between NKX2–1 and monocytes, whereas ELF3 and ARG2 exhibited a positive association with activated dendritic cells. The molecular docking results showed that the binding energies of ARG2-SKA-111/cyclophosphamide and ELF3–voruciclib/cyclophosphamide were less than − 5 kcal/mol.

The findings of this study highlight the key roles of ARG2, ELF3, and NKX2−1 in macrophage-related mechanisms of SSc-ILD, providing insights into potential therapeutic targets. Further research is necessary to explore their functional implications in disease progression and treatment.

Barriers and Facilitators for Nurses to Manage Medication of Cancer Pain: A Qualitative Systematic Review of Healthcare Professionals’ Perspectives

ABSTRACT

Background

Improving global access to pain management medications for cancer patients remains a critical priority. Nurses are now understood to play an essential role in cancer pain medication management, yet the barriers and facilitators they encounter require urgent identification.

Objective

This systematic review aimed to identify the barriers and facilitators for nurses in managing cancer pain medication.

Design

This systematic review followed the Joanna Briggs Institute (JBI)'s guidelines for qualitative systematic reviews.

Methods

Eleven databases (PubMed, Web of Science, the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Scopus, OPENGREY.EU, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP) and SinoMed) were searched from their inception to 9th July 2025. Articles were evaluated for quality using JBI critical appraisal tools. Data extraction was performed according to JBI standardised protocols, and evidence synthesis was conducted using JBI meta-aggregation, which involved extracting findings, categorising them into thematic groups and synthesising them into comprehensive statements.

Results

Twenty-four qualitative studies were reviewed in the present study. Two synthesised findings regarding the barriers and facilitators for nurses in managing cancer pain medication were integrated: (1) Barriers for nurses to manage cancer pain medication were summarised into five categories: systemic barriers, resource barriers, knowledge and skills barriers, financial and cultural barriers and communication and psychological barriers; (2) Facilitators for nurses to manage cancer pain medication were summarised into three categories: nursing capacity building, supportive care environments and collaborative support systems.

Conclusions

Multilevel barriers impede nurse-led cancer pain management, necessitating policy reforms (e.g., tiered prescribing), investments in telehealth/training and culturally responsive interprofessional collaboration. Prioritising facilitators, capacity building, supportive environments and collaboration is vital to empower nurses in delivering equitable, evidence-based pain relief.

Impact

This review equips clinical managers and policymakers with evidence to implement policy and practice reforms, such as tiered prescribing and interprofessional collaboration, which are critical to empower nurses in delivering effective cancer pain management.

Registration

This systematic review was prospectively registered in PROSPERO prior to the initiation of the search (Registration ID: CRD42024570807).

Patient or Public Contribution

There was no patient or public contribution.