Background: Combination therapy has become an attractive option in pulmonary arterial hypertension (PAH) treatment. The aim of this study was to investigate whether additional use of prostacyclin analogs could exert any additional benefits over background targeted therapies in PAH patients.Methods: Searches were performed on PubMed, Embase, and ClinicalTrials.gov from inception to 1 October 2021. Randomized controlled trials were included if patients had been treated with prostacyclin analog-containing combination therapy and compared with the use of other PAH-specific background therapies. The bias risk and statistical analysis of the enrolled studies were performed with RevMan 5.1. Sensitivity analysis and funnel plot were used to evaluate the stability and publication bias, respectively. PROSPERO registered number CRD42021284196.Results: Ten trials involving 1828 patients were included. Prostacyclin analog treatment was associated with greater improvement in clinical worsening (risk ratio [RR], 0.70; 95% confidence interval [CI], 0.57–0.86), 6-min walk distance (mean difference [MD], 37.17 m; 95% CI, 3.01–71.33 m), NYHA/WHO functional class (RR, 1.58; 95% CI, 1.21–2.05), mean pulmonary artery pressure (MD, −9.23 mmHg; 95% CI, −17.44 to −1.03 mmHg), and cardiac index (MD, 0.41 L/min/m²; 95% CI, 0.26–0.55 L/min/m²) than the control group. No significant differences in pulmonary vascular resistance (MD, −137.22 dyn·s/cm⁵; 95% CI, −272.61 to −1.84 dyn·s/cm⁵) and all-cause mortality (RR, 0.96; 95% CI, 0.57–1.61) were found between the prostacyclin analog group and control group. Of note, more adverse events (RR, 1.07; 95% CI, 1.02–1.13) occurred in the prostacyclin analog group but no significant increase in serious adverse events (RR, 1.25; 95% CI, 0.75–2.11).Conclusion: Additional prostacyclin analog treatment exerted benefits on clinical worsening, exercise capacity, functional class, mean pulmonary artery pressure, and cardiac index in PAH patients, but it was associated with overall risk of adverse events.Clinical Trial Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021284196, identifier CRD42021284196.

Baicalin (BA) is an active component of the natural plant Scutellaria baicalensis, which has been used over many years to treat inflammation and respiratory infections. In this study, the sepsis-induced acute lung injury (ALI) mouse model, network pharmacology and molecular docking were used to predict and explore the potential targets and signaling pathways of BA against ALI. The results showed that BA inhibited the major characteristics of ALI, including pathological changes, alveolar-capillary barrier dysfunction, increased inflammatory response and M1 macrophage polarization. Based on network pharmacology and molecular docking analyses, the PI3K/AKT/NF-κB pathway might be an important mechanism by which BA mitigated sepsis-induced ALI. Moreover, BA attenuated the phosphorylation of PI3K, AKT, IκB and NF-κB in the lung tissues of the ALI mice. In conclusion, this study demonstrated that BA ameliorated lung injury in mice, and depressed M1 macrophage polarization through inhibition of the PI3K/AKT/NF-κB pathway.

Autoimmune diseases often co-occur with interstitial lung disease (ILD), and ILD is associated with patient prognosis. Research has demonstrated a relationship between autoimmune diseases and ILD; however, the genetic basis underlying this connection is frequently overlooked. Linkage disequilibrium score regression and high-definition likelihood methods were applied to large-scale genome-wide association studies summary-level data sets to assess genetic correlations between 17 autoimmune disorders and ILD. Several functional annotations and tissue-specific analyses were performed to determine the influence of pleiotropic genes based on the pleiotropy analysis method under the compound null hypothesis method. Eight autoimmune disorders were revealed sharing genetic mechanisms with ILD. A total of 107 pleiotropic loci were identified at the genome-wide significance level (P < 5 × 10^–8), 18 of which had strong evidence of colocalization. Multiple potential pleiotropic genetic loci were identified, particularly the SMO gene located 7q32.1 locus. Pathway analysis determined in bound by FOXP3, T cell selection, and regulation of immune response. SNP- and gene-level tissue enrichment revealed that pleiotropic mechanisms play a critical role in spleen, whole blood, lung, and EBV-transformed lymphocytes. There are significant genetic correlations and potential causal mechanisms between autoimmune diseases and ILD. The findings of this study provide a deeper understanding of the genetic architecture of autoimmune diseases and ILD.