RNA-based gene therapy has been widely used for various diseases, and extensive studies have proved that suitable delivery routes greatly help the development of RNA therapeutics. Identifying a safe and effective delivery system is key to realizing RNA therapeutics' clinical translation. Inhalation is a non-invasive pulmonary delivery modality that can enhance the retention of therapeutic agents in the lungs with negligible toxicity, thereby improving patient compliance. Inhaled RNA therapeutics are increasingly becoming an area of focus for researchers; however, only several clinical trials have explored inhaled delivery of RNA for pulmonary diseases. This review presents an overview of recent advances in inhaled delivery systems for RNA therapeutics, including viral and nonviral systems, highlighting state of the art regarding inhalation in the messenger RNA (mRNA) field. We also summarize the applications of mRNA inhalants in infectious and other lung diseases. Simultaneously, the research progresses on small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs), and different types of RNA are also discussed to provide new strategies for developing RNA inhalation therapy. Finally, we clarify the challenges inhaled RNA-based therapeutics face before their widespread adoption and provide insights to help advance this exciting field to the bedside.

Objective To investigate whether adjuvant therapy can bring survival benefits to patients with esophageal squamous cell carcinoma (ESCC) who have received neoadjuvant therapy plus esophagectomy. Methods Studies were identified by searching databases including PubMed, EMbase, Web of Science, The Cochrane Library and CNKI from inception to November 2022 to collect studies which conformed to the objective of this study. Clinical outcomes including overall survival (OS) and recurrence-free survival (RFS) were extracted from eligible studies after screening. RevMan 5.4 and Stata 14.0 were used to perform the meta-analysis. Results A total of 9 studies were selected including 1 340 patients. Compared with the neoadjuvant therapy plus surgery (NS) group, the neoadjuvant therapy plus surgery+adjuvant therapy (NS+A) group had no significant benefit in the OS [HR=0.88, 95%CI (0.75, 1.02), P=0.09], but had remarkable benefit in the RFS [HR=0.75, 95%CI (0.58, 0.97), P=0.03]. Subgroup analysis by nodal status showed that adjuvant therapy could improve the RFS of patients with node-positive disease. Prolonged OS was observed in the patients with both positive and negative nodes but not in the patients with only positive nodes. In terms of the subgroup analysis by prescription, it revealed that triple agents exhibited advantages in improving RFS but not OS. However, dual agents did not bring additional survival benefits to the NS+A group compared with the NS group. Subgroup analysis by adjuvant therapy indicated that neither postoperative chemoradiotherapy nor chemotherapy improved OS, whereas postoperative chemoradiation elongated RFS. Conclusion Adjuvant therapy can improve the prognosis of patients with ESCC after neoadjuvant therapy followed by esophagectomy.