Good Syndrome (GS) is a rare immunodeficiency disorder classically defined by the triad of thymoma, hypogammaglobulinemia, and recurrent infections. Cytomegalovirus (CMV) infection is the most frequently reported viral infection in patients with GS. This study aimed to characterize the clinical features and immunological alterations in patients with GS complicated by CMV infection. We conducted a retrospective cohort study of GS patients with or without CMV infection at Peking Union Medical College Hospital from January 2015 to December 2024. Logistic regression and COX proportional hazards regression model were employed to identify potential risk factors for CMV infection and prognostic factors of overall survival among GS patients. Among the 27 enrolled patients, 15 developed CMV infection: 1 presented with CMV pneumonia, 6 was clinically diagnosed with CMV pneumonia, 6 with isolated CMV DNAemia, 1 with CMV colitis, and 1 with CMV retinitis. Peripheral blood CD4 + T-cell counts were significantly lower in the CMV group than non-CMV group (156 [116–210] vs. 374 [200–443] cells/µL; P < 0.05). The CMV group exhibited a higher rate of glucocorticoid (GC) use, greater cumulative GC exposure prior to diagnosis, and higher frequencies of respiratory pathogen isolation and fungal infection compared with the non-CMV group. Multivariable logistic regression identified lower serum albumin (P = 0.012; OR, 0.743; 95

Sarcoidosis is a multisystem granulomatous disease that most commonly affects the lungs. 18F-2-fluoro-2-deoxyglucose (18F-FDG) PET/CT is a sensitive imaging modality for assessing of sarcoidosis. However, fasting before 18F-FDG PET/CT is generally required to improve image quality and diagnostic accuracy. In this context, our study aims to explore the utility of 68Ga-fibroblast activation protein inhibitors (68Ga-FAPI) PET/CT in sarcoidosis, with particular emphasis on lesion uptake patterns and intensity, as well as the correlation with disease activity. This is a prospective, single-center, observational study conducted at the Peking Union Medical College Hospital. Eight patients with newly diagnosed thoracic sarcoidosis were consecutively recruited for 68Ga-FAPI PET/CT between January 2024 and December 2024. The follow-up 68Ga-FAPI PET/CT imaging was scheduled 6–12 months after standard treatment. In addition, we retrospectively analyzed 18F-FDG PET/CT scans from 16 sarcoidosis patients. For both imaging groups, the maximum and mean standardized uptake values (SUVmax and SUVmean, respectively) and corrected lesion-to-background ratio (LBR) were calculated. 68Ga-FAPI PET/CT imaging detected FAPI-avid lesions in all 8 patients, including enlarged lymph nodes (8 patients, SUVmax = 7.78 ± 3.98, LBR = 7.4 ± 5.9), pulmonary infiltrates (6 patients, SUVmax = 5.35 ± 1.15, LBR = 10.4 ± 3.8), spleen nodules (2 patients) and hepatic nodules (1 patient). Following treatment, the follow-up 68Ga-FAPI PET/CT scans showed lesion shrinkage and decreased uptake parameters. However, some pulmonary lesions showed non-significant changes of SUV or LBR. Addtionally, the average SUVmax, SUVmean, and LBR for 68Ga-FAPI of lymph nodes tended to be lower than 18F-FDG uptake parameters in the retrospective cohort. 68Ga-FAPI PET/CT can be useful for evaluating both active and chronic granulomatous inflammation. It is also potentially valuable for determining disease extent, detecting occult disease, and monitoring treatment response in sarcoidosis.

Telomeres and telomerase have been extensively implicated in the cellular processes of aging and inflammation. Recent studies have shown that telomere length (TL), the shelterin complex, and telomerase dysfunction are closely related to non-malignant pulmonary diseases, including interstitial lung diseases (ILD), chronic obstructive pulmonary disease (COPD), and asthma. Short telomere defects with or without mutations in telomere maintenance genes and telomerase are relatively common, affecting the progression of non-malignant pulmonary diseases, explaining disease susceptibility, and revealing clinically relevant manifestations. In this review, we examine the biological characteristics and functions of telomeres and telomerase, and investigate the intricate relationship between changes in TL and mutations in telomerase genes in non-malignant pulmonary diseases after a detailed associated literature review. Subsequently, we focus on the clinical features of non-malignant pulmonary diseases related to dysfunctional telomeres/telomerase, as well as the potential molecular mechanisms underlying these associations, along with the current status of therapeutic interventions. Finally, we delineate current knowledge gaps and transformative opportunities in telomere biology research, with a focus on bridging molecular discoveries to clinical innovations for telomere-associated non-malignant pulmonary diseases, aiming to accelerate the development of precision diagnostic tools and mechanism-based therapeutics.

OBJECTIVE:To present a case of a non-human immunodeficiency virus (HIV)-infected patient with human cytomegalovirus (HCMV) viremia and severe Pneumocystis jirovecii (PJ) pneumonia. CASE REPORT:The patient was admitted in June 2024 for chronic dry cough and dyspnea. Sputum-targeted next-generation sequencing (tNGS) and blood pathogen metagenomic detection were used to identify concurrent infections of sputum HCMV and PJ, along with blood HCMV. The extensive treatment included intravenous ganciclovir, in conjunction with caspofungin and oral sulfamethoxazole, augmented by glucocorticoids and breathing assistance. After three weeks, the patient's oxygenation index markedly improved, accompanied by the significant resolution of imaging lesions, leading to patient discharge in June 2024. CONCLUSION:This case underscores the diagnostic efficacy of tNGS on several opportunistic infections for older people with several comorbidities.

Background:The likelihood of lung cancer in patients with pulmonary fibrosis is significantly increased, particularly the incidence of lung adenocarcinoma in areas affected by fibrosis, which is usually accompanied with epidermal growth factor receptor (EGFR) mutations. However, EGFR-tyrosine kinase inhibitor (TKI) can paradoxically induce or exacerbate pulmonary fibrosis as a serious adverse effect. Consequently, the use of EGFR-TKIs is approached with extreme caution in patients with lung cancer and co-existing interstitial lung disease, leading to a scarcity of clinical evidence regarding their application in individuals with both EGFR-mutated non-small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF). Case Description:This article reports a rare and instructive case of a patient with a pre-existing diagnosis of IPF who subsequently developed lung adenocarcinoma harboring an EGFR mutation during clinical follow-up. The patient was managed with a combination therapy of icotinib (an EGFR-TKI) and Pirfenidone (an anti-fibrotic agent). This therapeutic strategy resulted in effective control of the lung adenocarcinoma while maintaining relative stability of the underlying pulmonary fibrosis. The patient's eventual death was attributed to a severe coronavirus disease 2019 (COVID-19) infection, not to progression of cancer or pulmonary fibrosis. Conclusions:This report aims to enhance clinicians' understanding of pulmonary fibrosis complicated by lung cancer. Tumor molecular testing is also important in patients with NSCLC concurrent with IPF. Furthermore, it provides preliminary clinical evidence suggesting that, with careful monitoring and concomitant anti-fibrotic therapy, EGFR-TKIs like Icotinib may represent a viable treatment option for patients co-existing with IPF and EGFR-mutated NSCLC.

Pulmonary alveolar proteinosis (PAP) and pulmonary nocardiosis are relatively rare, their co-occurrence constitutes a clinically important comorbidity. Nocardia infection exhibits variable clinical manifestations, and carries a substantial risk of mortality in the absence of timely, pathogen-directed antimicrobial therapy. This study aims to summarize the clinical features of Nocardia infection in PAP patients. We present four confirmed cases of PAP complicated by Nocardia infection. These cases illustrate the distinct microbial species, disease courses and clinical outcomes. The duration of Nocardia infection among the four patients ranged from 3 months to over 2 years. All patients received anti-infection treatment guided by antimicrobial susceptibility testing (AST) results. Clinical outcomes included microbiological cure of infection, sustained clinical stability without progression, and all-cause mortality. In patients with PAP, the emergence of fever and new pulmonary opacities warrants strong clinical suspicion for Nocardia infection. Early initiation of pathogen-directed antimicrobial therapy is critical for infection control and enables subsequent PAP stabilization, clinical recovery, and the safe performance of whole-lung lavage.

Background:Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown etiology with poor prognosis. The currently approved antifibrotic drugs only decelerate functional decline and fail to reverse established fibrosis or extend survival. Binimetinib, a highly selective and noncompetitive MEK1/2 inhibitor, has been approved for clinical use in malignancies such as melanoma and non-small cell lung cancer. This study aims to evaluate the therapeutic effects of binimetinib on IPF and to explore its underlying mechanism. Methods:In this study, the antifibrotic effects and underlying mechanisms of binimetinib were evaluated both in vivo and in vitro. Results:In vivo, experiments demonstrated that binimetinib markedly ameliorated bleomycin-induced pulmonary fibrosis in mice, as evidenced by the reduction in hydroxyproline content (184.3±25.4 µg in bleomycin group vs. 94.6±9.8 µg in high-dose binimetinib group, P<0.001) and fibrotic area (14.8%±2.9% in bleomycin group vs. 5.4%±1.6% in high-dose binimetinib group, P<0.001). In vitro, binimetinib directly targeted the MEK/ERK signaling cascade and concurrently inhibited both the TGF-β/SMAD and TGF-β/non-SMAD pathways, thereby suppressing fibroblast proliferation, migration, activation, and extracellular matrix deposition. Furthermore, binimetinib attenuated the overall activation of pulmonary macrophages through inhibition of the JAK/STAT pathway. Conclusions:In summary, binimetinib exerted potent anti-inflammatory and antifibrotic effects by suppressing the activation of both fibroblasts and pulmonary macrophages, ultimately mitigating bleomycin-induced pulmonary fibrosis in mice.

Studies verifying the performance of antifibrotic drugs for the treatment of ANCA positive fibrotic ILD (ANCA-fILD) are lacking. This study assessed the clinical features of ANCA-fILD patients with or without add-on treatment with antifibrotic drugs. A retrospective study involving ANCA-positive patients treated from January 2012 to December 2023 at Peking Union Medical College Hospital was conducted, and a case‒control analysis was performed accordingly. A total of 105 ANCA-fILD patients were identified from 18,617 ANCA-positive patients treated from January 2012 to December 2023 at Peking Union Medical College Hospital; these patients were further divided into an add-on group (31 patients) and a non-add-on group (74 patients). On the basis of baseline FVC

To explore the risk of relapse after glucocorticoids (GCs) withdrawal in patients with stable Sjögren’s disease-associated interstitial lung disease (SjD-ILD). This was a single-center, retrospective cohort study conducted at Peking Union Medical College Hospital between February 2016 and January 2024. The study compared two treatment strategies for patients with stable SjD-ILD: GC withdrawal versus GC maintenance. The primary endpoint was to compare the relapse rates between the two groups over a 3-year follow-up period. The secondary endpoints included changes in pulmonary function, serological markers, and adverse events. A total of 134 patients were included in this study, with 61 in the GC withdrawal group and 73 in the GC maintenance group. Over the 3-year follow-up, 16 patients (27.93

OBJECTIVE:Severe steroid-resistant asthma (SSRA) is characterized by persistent neutrophilic airway inflammation and limited glucocorticoid efficacy. Dysregulated macrophage polarization toward the pro-inflammatory M1 phenotype contributes to SSRA pathogenesis. The voltage-gated potassium channel Kv1.3 regulates immune cell activation, but its role in asthma-related macrophage polarization remains unclear. METHODS:We analyzed KCNA3 (Kv1.3-encoding gene) expression in alveolar macrophages from asthma patients (GSE2125 dataset). An OVA/LPS-induced SSRA mouse model was established and treated with the Kv1.3 inhibitor Margatoxin (MgTX), clarithromycin (CLA), or dexamethasone (DEX). Airway hyperresponsiveness (AHR) and lung pathology were evaluated. Macrophage phenotypes and STAT signaling were analyzed by flow cytometry, immunofluorescence, and Western blotting. Bone marrow-derived macrophages (BMDMs) were polarized in vitro with or without MgTX. RESULTS:KCNA3 expression was significantly elevated in alveolar macrophages from asthma patients. In SSRA mice, MgTX and CLA outperformed DEX in reducing AHR, inflammation, and collagen deposition. Kv1.3 inhibition upregulated M2 markers (Arg-1, FIZZ1) and downregulated the M1 marker iNOS, and was associated with enhanced STAT3 phosphorylation (p-STAT3/STAT3 ratio increased ∼2.5-fold). In vitro, MgTX promoted BMDM M2 polarization through selective STAT3 activation without affecting STAT6. CONCLUSION:Kv1.3 negatively correlates with STAT3 pathway activity, suggesting a potential inhibitory role in macrophage M2 polarization, which may contribute to sustained inflammation in SSRA. Pharmacological Kv1.3 inhibition is associated with restored macrophage balance and STAT3 activation, highlighting its potential as a novel therapeutic target for steroid-resistant asthma.

Background:Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung disease. Crizotinib is an oral tyrosine kinase inhibitor (TKI), which has been widely used in the treatment of non-small cell lung cancer (NSCLC). Previous studies have demonstrated that crizotinib can inhibit downstream signaling pathways of anaplastic lymphoma kinase (ALK) in lung adenocarcinoma mouse, including pSTAT3, pAKT, and pERK, which also play an important role in the development and progression of pulmonary fibrosis. We conducted this study to investigate the antifibrotic efficacy of crizotinib in pulmonary fibrosis in vivo and in vitro, as well as exploring the potential mechanism further. Methods:Fibroblasts were stimulated with TGF-β1 and co-treated with crizotinib to evaluate its impact on fibroblast activation markers as well as main related proteins of signal pathways in vitro. Male C57BL/6 mice were administered bleomycin (BLM) established as in vivo model. We assessed lung function, micro-computed tomography (CT), hydroxyproline level, percentage of fibrotic areas and the expression of fibrotic factors to evaluate the effects of crizotinib on pulmonary fibrosis. Western blot was performed to identify our speculated hypothesis. Results:In vitro studies showed that crizotinib reduced the gene and protein expression levels of the fibronectin (Fn), Collagen 1 (Col-1) and α-smooth muscle actin (α-SMA), as well as exerting potential anti-fibrotic effects by inhibiting the activation and migration of fibroblasts. Additionally, the results of the in vivo studies demonstrated that crizotinib could improve lung dysfunction, pulmonary fibrosis lesions, area of full ventilation in CT, and the expression of fibrotic-associated factors in lung tissues of BLM-mice. Additionally, crizotinib inhibited the PI3K/AKT/mTOR, STAT3 and ERK signaling pathways, which play vital roles during pulmonary fibrosis. Conclusions:Through suppressing fibroblast proliferation and activation, crizotinib could alleviate pulmonary fibrosis in BLM induced mice. Crizotinib could inhibit the PI3K/AKT/mTOR, STAT3 and ERK signaling pathways. Crizotinib might be an emerging medication choice for patients with IPF.

Background: Idiopathic pulmonary fibrosis (IPF), a progressive fibrotic interstitial lung disease (ILD), has a poor prognosis, and effective drugs, including nintedanib and pirfenidone, are limited. Therefore, developing new drugs for treating pulmonary fibrosis is of the highest priority. The inhibition of cellular autophagy in lung fibroblasts is an important mechanism involved in pulmonary fibrosis, and the PI3K/Akt/ mTORC1 pathway is responsible for modulating the level of intracellular autophagy. As a result, copanlisib, a pan-class I PI3K inhibitor, has promise for preventing pulmonary fibrosis by ameliorating cellular autophagy. This study aimed to evaluate the effect and underlying mechanism of copanlisib in pulmonary fibrosis. Methods: In this study, we evaluated the antifibrotic effect of copanlisib by using a mouse model of bleomycin (BLM)-induced pulmonary fibrosis for in vivo experiments and mouse lung fibroblasts (Mlg cells) for in vitro experiments. Results: As a result, copanlisib markedly alleviated BLM-induced collagen deposition and improved pulmonary function and ventilation volume in vivo. In addition, both in vivo and in vitro experiments verified that copanlisib showed a dose-dependent association with reduced fibrotic activity and changes in autophagy markers consistent with increased activity. These effects were accompanied by the reduced phosphorylation of PI3K, Akt, and mTORC1, suggesting a potential mechanistic link between PI3K/mTOR inhibition and the observed therapeutic efficacy in these experimental settings. Conclusions: In conclusion, copanlisib is a promising candidate as a treatment for pulmonary fibrosis.

12016 Background: Checkpoint inhibitor pneumonitis (CIP) stands out as a remarkable complication during ICIs therapy. Severe CIP represents a potentially life-threaten immune-related adverse event (irAE) with limited evidence from clinical trials that guides therapeutic interventions. Ruxolitinib, a selective JAK1/2 inhibitor, effectively attenuates cytokine-release syndrome and show significant anti-fibrotic in mouse lung with BLM model. We conducted a multicenter, investigator-initiated, open-label, phase 2 randomized controlled trial to evaluate the efficacy and safety of add-on ruxolitinib for patients with severe CIP management with corticosteroids. Methods: Patients with malignant who were suffered from CTCAE grade (G) 3 or G4 CIP after ICIs therapy were screened. Enrolled CIP patients were randomly assigned 1:1 to control group (only glucocorticoids) or ruxolitinib group (glucocorticoids plus ruxolitinib). Initiated dosage of glucocorticoids was no less than prednisone 1 mg/kg/day (or same steroid equivalent dose) with subsequent tapering off. In ruxolitinib group, enrolled patients were add-on ruxolitinib (5 mg twice daily for 2 weeks, followed with 5 mg daily for 2 weeks). The primary end point was the proportion of patients with a prednisone daily dosage of no more than 10mg and improvement to G1 CIP at week 8. Continuous variables were analyzed using a mixed-effects model for repeated measures with treatment group, study visit and treatment-by-visit interaction. Results: From April 2023 to November 2025, a total of 60 eligible patients were recruited and randomly assigned to control group and ruxolitinib group. There were 52 cases of G3 CIP and 8 cases of G4 CIP. There were more patients in the ruxolitinib group improved to G1 CIP and received ≤prednisone 10mg daily at 8 th week than in the controlled group (20cases/66.7% vs 11cases/36.7%, p = 0.0379 ). This effect was more significant in the 2 nd and 4 th week. Two patients in ruxolitinib group and 4 patients in the control group died within eight weeks. The repeated measures analysis using a generalized linear mixed model demonstrated a significant overall treatment effect, ie. add-on ruxolitinib was associated with significantly higher odds of clinical improvement (adjusted OR = 5.12, 95% CI 1.06 - 24.64; p = 0.04). A total of 13 G3 or higher treatment-related AEs (TRAEs) occurred (7 cases in control group and 6 cases in ruxolitinib group), including 9 cases of infectious diseases. Conclusions: Add-on ruxolitinib for malignant patients with severe CIP management with glucocorticoids show with higher resolution rates and earlier response trends than only glucocorticoids treatment. And there were no different adverse events between them. Add-on ruxolitinib with glucocorticoids might be a promising proposed treatment for patients with severe CIP. Clinical trial information: NCT05899725 .

Hypersensitivity pneumonitis (HP) is characterized by bronchiolocentric inflammation and fibrosis. The characteristic pathological features include bronchiolocentric inflammation, peribronchiolar fibrosis, and the presence of poorly formed granulomas. Nerandomilast is a novel oral phosphodiesterase 4 (PDE4) inhibitor with good selectivity for PDE4B. PDE4 inhibitors (PDE4i) exhibit anti-inflammatory/antifibrotic properties, the efficacy of nerandomilast remains unexplored in HP. We selected macrophages and fibroblasts as effector cells for the inflammatory and fibrotic phases of HP in vitro. And we established in vivo HP models induced by saline extract of the cells of P. agglomerans (SE-PA). The results of the in vitro studies revealed that nerandomilast inhibited the expression of proinflammatory markers (i.e., CD86, iNOS, and IL-1β) of M1 macrophages by increasing CREB phosphorylation and inhibiting the NF-κB signaling pathway. Furthermore, nerandomilast reduced TGFβ1-induced fibroblast activation by inhibiting Smad and non-Smad signaling pathways. In vivo studies confirmed that nerandomilast could reduce the number of inflammatory cells in bronchoalveolar lavage fluid and the secretion of proinflammatory cytokines (such as IL-1β, IL-6, and TNF-α), lower the serum levels of the oxidative stress markers MPO and MDA, and inhibit the transcription of proinflammatory cytokines in lung tissue. Moreover, nerandomilast alleviated pulmonary fibrosis and pulmonary dysfunction in mice with HP induced by SE-PA. Our findings indicated that nerandomilast might attenuate inflammation and fibrosis in SE-PA-induced HP mice by regulating macrophage polarization and inhibiting fibroblast activation, which provides new insights for the clinical treatment of HP.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for various malignancies by demonstrating exceptional antitumor effects and significant improvement in patient survival. Despite their overt therapeutic advantages, ICIs also induce immune-related adverse events (irAEs). Of these, checkpoint inhibitor pneumonitis (CIP) represents a prominent manifestation of pulmonary toxicity following ICI therapy, with incidence rates ranging from 2.7 % to 20.0 %. Notably, a substantial proportion of CIP cases show severe manifestations, often leading to life-threatening complications, which emphasizes its clinical significance. Understanding the risk factors and potential pathogenetic mechanisms of CIP, combined with vigilant monitoring during immunotherapy, is pivotal for early detection and management of this condition. Proactive strategies for the timely identification, accurate diagnosis, and effective management of CIP are essential to optimize patient outcomes. However, several challenges persist in CIP management, including management of severe and refractory cases, determining the timing of ICI rechallenge after CIP, management of long-term chronic CIP, and mitigating secondary infections. In order to manage this potentially life-threatening irAE effectively, it is urgent to establish multi-disciplinary treatment (MDT) management, precision CIP management, and practical surveillance systems for CIP monitoring, diagnosis, and management and to call for prospective multi-center clinical trials.

Surgery resection would improve idiopathic pulmonary fibrosis (IPF) patients with early-stage lung cancer (LC). However, most associated studies were published from surgeons. Interstitial lung disease (ILD) physicians involved in perioperative management would be helpful for improving patients with idiopathic pulmonary fibrosis combined with lung cancer (IPF-LC). To enhance the understanding of the clinical characteristics presented by patients with IPF-LC who have undergone surgical resection, and to explore the factors linked to unfavorable prognosis, our ILD physicians conducted this study. We retrospectively examined clinical records of IPF-LC patients at Peking Union Medical College Hospital from January 2014 to December 2023.Data related to clinical manifestations and treatment methods were collected. Patients underwent routine follow-up through clinical assessments and telephone consultations. The demographic, clinical, and laboratory features of 12 surviving patients and 8 deceased patients were comparatively analysed. There were 30 males and 2 females, aged from 49 years to 82 years. Twenty-eight patients had a history of smoking. Twenty-five patients had at least one comorbidity and emphysema was the most common. IPF was diagnosed before LC in 8 patients but none of them were prescribed with anti-fibrotic medications. Twenty-four patients were simultaneously diagnosed with LC and IPF, and 7 of them were prescribed anti-fibrotic medications. After surgery, 27 patients were pathologically diagnosed with non-small cell lung cancer and 26 patients were classified as stage I or II lung cancer. During follow-up, 8 patients died, 12 patients lost follow-up and 12 patients survived. Among the 8 deceased patients, 5 patients died from acute exacerbation of IPF, one died from cancer progression and 2 died from surgical complications. The serum Cyfra211 level was higher and the lung cancer stage was more advanced in the non-survival group than in the survival group. Most of our IPF-LC patients were elderly males with a history of smoking and had at least one comorbidity. Most of them were diagnosed with IPF and LC simultaneously. However, only one fifth were prescribed with pirfenidone or nintedanib. Acute exacerbation of IPF was the main cause of death. Similar to the LC patients, higher serum Cyfra211 levels and more advanced lung cancer stages were associated with a poor prognosis for our enrolled IPF-LC patients. Not applicable.

Idiopathic pulmonary fibrosis (IPF) is a rare, chronic, and progressive interstitial lung disease characterized by an unclear etiology and pathogenesis. Current anti-fibrotic therapies frequently fall short in effectively halting disease progression. A critical aspect of IPF involves the role of macrophages, which exhibit distinct polarized phenotypes that significantly influence the initiation and progression of fibrosis within the lung immune microenvironment. Recent evidence highlights the importance of the JAK-STAT signaling pathway in regulating macrophage polarization, suggesting that its inhibition may offer a promising therapeutic strategy for IPF. In this study, Ruxolitinib, a JAK1/2 inhibitor that is approved for the treatment of myelofibrosis, was investigated for its effects on pulmonary fibrosis for the first time. The in vivo studies were conducted utilizing a bleomycin-induced pulmonary fibrosis model, and in vitro experiments were induced pro-inflammatory and pro-fibrotic macrophage polarization using LPS/IFN-γ and IL-4/13, respectively. Notably, our findings reveal that Ruxolitinib diminishes pro-inflammatory polarization, thereby promoting a more favorable pulmonary inflammatory microenvironment. Furthermore, Ruxolitinib inhibits fibrotic macrophage polarization, effectively curtailing myofibroblast activation and displaying clear anti-fibrotic effects. The underlying regulatory mechanism of Ruxolitinib is through inhibition of JAK1/2-mediated STAT signaling, which interrupts the pathways leading to the polarization of fibrotic macrophages and the activation of pro-inflammatory macrophages. Collectively, these results underline the potential of Ruxolitinib as a therapeutic option for IPF treatment, representing a pivotal advance in addressing a disease that has previously evaded effective pharmacological intervention.

Pneumocystis jirovecii pneumonia (PJP) is a common opportunistic infection. With the wide application of glucocorticosteroids and immunosuppressants, the incidence and mortality rates of PJP in connective tissue disease (CTD) patients with interstitial lung disease (ILD) are increasing. We retrospectively enrolled consecutive CTD-ILD patients with PJP in our center between January 2014 and December 2022. Cox regression models were constructed to explore prognostic factors in CTD-ILD-PJP patients. There were 159 CTD-ILD patients [60 (51, 68) years, 61.0