There are four members of the JAK family and seven of the STAT family in mammals. The JAK/STAT molecular pathway could be activated by broad hormones, cytokines, growth factors, and more. The JAK/STAT signaling pathway extensively mediates various biological processes such as cell proliferation, differentiation, migration, apoptosis, and immune regulation. JAK/STAT activation is closely related to growth and development, homeostasis, various solid tumors, inflammatory illness, and autoimmune diseases. Recently, with the deepening understanding of the JAK/STAT pathway, the relationship between JAK/STAT and the pathophysiology of fibrotic diseases was noticed, including the liver, renal, heart, bone marrow, and lung. JAK inhibitor has been approved for myelofibrosis, and subsequently, JAK/STAT may serve as a promising target for fibrosis in other organs. Therefore, this article reviews the roles and mechanisms of the JAK/STAT signaling pathway in fibrotic diseases.

Background: More and more trials have been conducted. We aimed to assess the efficacy and safety of different JAKinibs in RA. Methods: A systematic search of randomized controlled trials (RCTs) with JAKinib treatment in RA published in the Medline, Embase, and Cochrane databases up to May 2021 was performed. Results: 37 trials involving 15,174 patients were identified. Pooled analysis revealed that JAKinibs were associated with significant therapeutic improvement in RA patients as determined by ACR20 (RR = 2.03, 95% CI: 1.85 to 2.28) and HAQ-DI (MD = −0.31, 95% CI: −0.33 to −0.28) over placebo. Compared to placebo, JAKinib treatment was also associated with more adverse events (RR = 1.10, p < 0.001; RR = 1.29, p < 0.001; RR = 1.59, p = 0.02). Baricitinib and upadacitinib were related to more frequent adverse events (RR = 1.10; 95% CI: 1.01, 1.21; RR = 1.19; 95% CI: 1.11, 1.28) and infection (RR = 1.22; 95% CI: 1.09, 1.37; RR = 1.38; 95% CI: 1.22, 1.56), whereas only baricitinib was associated with more herpes zoster (RR = 3.15; 95% CI: 1.19, 8.33). Conclusions: JAKinibs were superior to placebo for improving signs, symptoms, and health-related quality of life in RA patients at short term, whereas the overall risk of adverse events and infections were greater with baricitinib and upadacitinib, and a higher risk of herpes zoster was only associated with baricitinib. More trials are needed to investigate the long-term safety.

Background: Interstitial lung disease (ILD) is a common pulmonary disease often associated with significant morbidity and mortality in patients with connective tissue diseases (CTD). Currently, no gold-standard therapies are available for CTD-ILD. Recently, several studies have proposed that rituximab (RTX) may be effective for the treatment of CTD-ILD.Objectives: This study aimed to systematically evaluate the efficacy and safety of RTX for the treatment of CTD-ILD.Methods: Studies were selected from PubMed, Embase, and Cochrane Library, up to 20 July 2022. Improvement and stable rates were extracted as the main outcomes and pooled using the weighted mean proportion with fixed or random-effects models, in case of significant heterogeneity (I² > 50%). Safety analysis was performed based on the adverse events reported in all of the studies.Results: Thirteen studies (312 patients) were included in the meta-analysis. The follow-up durations ranged from 6 to 36 months. The pooled improvement rate was 35.0% (95% CI: 0.277–0.442), while the pooled stable rate was 59.2% (95% CI: 0.534–0.656). Anti-synthetase syndrome associated with ILD [ASS-ILD, 48.1% (95% CI, 0.373–0.620)] and idiopathic inflammatory myopathies associated with ILD [IIM-ILD, non-ASS, 47.4% (95% CI, 0.266–0.846)] had higher improvement rates than the other types. A total of 106 adverse events associated with RTX or progressive ILD were reported among the 318 patients, 55.7% of which were mild. Among 19 deaths, 17 were due to ILD progression, one to severe pulmonary arterial hypertension, and one to Pneumocystis jirovecii infection.Conclusion: RTX, which exhibits a satisfactory safety profile, is an effective treatment option for CTD-ILD, even in patients who fail to respond to other therapies. Further randomized trials are needed to assess the efficacy of rituximab compared to other treatments for CTD-ILD.Systematic review registration: PROSPERO, identifier (CRD42022363403).

Background: Early reports highlighted unique features of COVID-19-associated ARDS. The combination of prone position (PP) and positive end-expiratory pressure (PEEP)-induced lung recruitment maneuver (LRM) has demonstrated efficacy in enhancing oxygenation and improving outcomes in patients with ARDS, but it remains unknown whether there is a difference between COVID-19 ARDS and non-COVID-19 ARDS. Method: This study is a secondary analysis of a previously conducted randomized controlled trial. Patients with moderate to severe ARDS were consecutively enrolled during the study period (June–December 2023). After initiation of PP, patients received a PEEP-induced LRM followed by 12 h of daily PP. The interventions were repeated at least three times over the subsequent 3 days. Clinical outcomes, respiratory mechanics, and electrical impedance tomography (EIT) results were evaluated. Results: Twenty-eight patients were included in the final analysis, half of whom were infected with COVID-19 (50%). The PEEP-induced LRM led to greater improvement in oxygenation among COVID-19 ARDS than non-COVID-19 ARDS (∆PaO₂/FiO₂ ratio 90.5 mmHg vs. 65.5 mmHg, p < 0.05). Based on EIT measurement, compared with the non-COVID-19 ARDS group, PEEP-induced LRM resulted in a greater increase in ventilation distribution, mainly in the dorsal regions of interest 4 (ROI 4) ventilation distribution (∆ROI4 4.5% vs. 1.0%, p = 0.01) and in dorsal regional ventilation (∆dorsal regional ventilation 10.0% vs. 5.5%, p = 0.04) in the COVID-19 ARDS group. Conclusions: Compared to typical ARDS, PEEP-induced LRM combined with PP may be more effective in enhancing oxygenation in COVID-19-related ARDS.

Background: Lung fibrosis is an abnormal repair process following injury response and characterized by fibroblasts activation and excessive extracellular matrix (ECM) deposition。Recent studies suggest Runt-related transcription factor 1 (RUNX1) involved in lung fibrosis. In this study we determined how RUNX1 influenced fibroblast.

Methods: RUNX1 was detected in IPF patients and bleomycin (BLM)-induced pulmonary fibrosis mice model. ECM were detected after adenovirus or silence RNA was used to overexpressed/inhibited Runx1 with or without RUNX1 inhibitor Ro5-3335 or TGF-β treatment. Fibroblasts proliferation, migration, and senescence were investigated. Runx1 inhibitor Ro5-3335 was also conducted in mice model.

Results: RUNX1 are increased in IPF patient samples and mice with bleomycin (BLM)-induced pulmonary fibrosis. In particular, higher levels of RUNX1 are related to worse lung function. Additionally, RUNX1 was highly identified in lung fibroblasts by scRNA-Seq analysis and confirmed in IPF tissue and BLM mice lung tissue by immunofluorescence staining. Further investigation showed RUNX1 promoted fibroblast differentiation and senescence, while having no effect on proliferation and migration (Figure 1). More importantly, Ro5-3335, a RUNX1 inhibitor, was effective at reversing established pulmonary fibrosis in vivo (Figure 2).

Conclusion: Runx1 plays a pivotal role in mediating fibroblast differentiation and senescence. Runx1 inhibitor Ro5-3335 might be a promising therapeutic approach for the treatment of pulmonary fibrosis.