Mediastinal and/or hilar lymphadenopathy (MHL) has become more frequently identified. Despite advances in endobronchial ultrasound (EBUS)-guided sampling, evidence on the optimal modality is lacking. This systematic review and network meta-analysis aimed to compare the diagnostic performance and safety of different EBUS-guided sampling methods in MHL. This study was performed on published studies reporting the diagnostic performance and complications of EBUS-guided transbronchial needle aspiration (EBUS–TBNA), EBUS-guided transbronchial mediastinal cryobiopsy (EBUS–TBMC), EBUS-guided transbronchial forceps biopsy (EBUS–TBFB) to sample MHL. The outcomes included the diagnostic yield, diagnostic sensitivity, negative predictive value and complications. A frequentist random-effects model was employed to rank the diagnostic performance and safety for network meta-analysis. Subgroup analysis was performed with stratification by disease. Twenty-two studies with 2357 patients were included. EBUS–TBMC had the highest diagnostic yield, at 88.0

Background Non-metastatic lymphadenopathy is challenging to diagnose. The comparative diagnostic performance of endobronchial ultrasound (EBUS)-guided transbronchial mediastinal cryobiopsy (TBMC) vs. EBUS-transbronchial needle aspiration (TBNA) remains debated. Methods This multicenter randomized trial was conducted in three hospitals. Patients with at least one mediastinal and/or hilar lesion of ≥1 cm in the short axis who required diagnostic bronchoscopy were included. The patients were randomized in a 1:1 ratio to receive either EBUS-TBNA followed by EBUS-TBMC (EBUS-TBNA-first group) or EBUS-TBMC followed by EBUS-TBNA (EBUS-TBMC-first group). The primary outcome was the diagnostic yields of EBUS-TBMC and EBUS-TBNA. Findings The overall diagnostic yield of EBUS-TBMC for non-metastatic lymphadenopathy was significantly higher than that of EBUS-TBNA for specific benign etiologies and lymphomas (97.1% vs. 79.9%, p < 0.001). In the subgroup analysis, EBUS-TBMC showed a higher sensitivity for sarcoidosis than EBUS-TBNA (98.0% vs. 82.7%, p < 0.001). All patients experienced grade 1 airway bleeding. Conclusions EBUS-TBMC demonstrated a higher diagnostic yield than EBUS-TBNA for non-metastatic lymphadenopathy in a cohort almost exclusively composed of sarcoidosis cases, with a good safety profile. EBUS-TBMC is a potential first-line diagnostic tool for non-metastatic lymphadenopathy. Funding This work was financially supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project (2024ZD0528900 and 2024ZD0528902 to G.H.).

Introduction Semirigid thoracoscopy plays an important role in the diagnosis of pleural diseases. However, its diagnostic performance remains unsatisfactory particularly in terms of the negative likelihood ratio. Therefore, more effective supplementary diagnostic tools are required. Probe-based confocal laser endomicroscopy (pCLE), which allows live tissue imaging at the cellular level, can discriminate between malignant and benign pleura during medical thoracoscopy. However, the clinical relevance of pCLE in pleural disease remains unclear. This protocol describes a randomised controlled trial that evaluates the additional diagnostic value of pCLE in diagnosing pleural diseases using semirigid thoracoscopy.Methods and analysis This study is a multicentre, parallel-group, randomised controlled trial that will be conducted at ten sites in China. A total of 158 adult patients with undiagnosed exudative pleural effusions will be enrolled and randomly allocated (1:1) to undergo either a conventional pleural biopsy (control group) or a pCLE-guided pleural biopsy (intervention group) via semirigid thoracoscopy. In the intervention group, a pCLE system will be applied during thoracoscopy to identify suspicious pleural areas for targeted biopsy. The primary outcome is the diagnostic yield of the procedure in patients with unknown causes of pleural effusion. Secondary outcomes include negative likelihood ratio, diagnostic sensitivity in specific diseases, procedural time, rate of adequate specimens for achieving molecular diagnosis and complications.Ethics and dissemination Ethics approval was obtained from the China-Japan Friendship Hospital Ethics Committee (2025-KY-018). Written informed consent will be obtained from all the participants. The findings will be disseminated through journal publications and conference presentations.Trial registration number NCT06741839.

Exudative pleural effusion of an unclear aetiology remains a diagnostic challenge. Ultrasonic elastography-guided pleural biopsy (UEPB) offers a higher diagnostic yield than conventional ultrasound-guided pleural biopsy; however, its role relative to semi-rigid thoracoscopy remains unclear. This trial is designed to determine whether UEPB is non‑inferior to semi-rigid thoracoscopy in diagnostic yield when used as the initial diagnostic procedure, and to further quantify the proportion of patients in whom semi-rigid thoracoscopy could be avoided by adopting a UEPB-first diagnostic strategy. In this multicentre, open-label, parallel-group, non-inferiority, randomised controlled trial conducted at five sites in China, 420 patients with exudative pleural effusion of unknown aetiology and negative cytology will be randomly assigned 1:1 to either initial UEPB (with semi-rigid thoracoscopy reserved for non-diagnostic cases) or immediate semi-rigid thoracoscopy. The primary outcome is the overall diagnostic yield of the allocated diagnostic strategy, defined as the proportion of participants in whom a specific histopathological diagnosis is stablished through the protocol-defined biopsy procedures within the allocated diagnostic pathway. A non-inferiority margin of − 5

OBJECTIVE:Long-term use of glucocorticoids, such as dexamethasone, often leads to glucocorticoid-induced muscle atrophy (GIMA), a condition associated with mitochondrial oxidative stress and abnormal activation of protein degradation pathways. Histone deacetylase 6 (HDAC6) is involved in cellular stress regulation, but its role in GIMA remains unclear. We investigated the protective effects of HDAC6 inhibition/loss-of-function against dexamethasone-induced muscle atrophy and its potential molecular mechanisms. METHODS:Using Hdac6 knockout (KO) mice and C2C12 myotube models, combined with the HDAC6-selective inhibitor ACY-1215, we evaluated the phenotype of dexamethasone-induced muscle atrophy. We performed transcriptomic sequencing, Western blotting, immunofluorescence assays, and measured oxidative stress markers including reactive oxygen species (ROS), malondialdehyde (MDA), and the reduced glutathione to oxidized glutathione disulfide ratio (GSH/GSSG). Mitochondria-specific parameters, including mitochondrial superoxide (MitoSOX), mitochondrial membrane potential (MT-1 and JC-1), mitochondrial biogenesis markers (PGC-1α and TFAM), and antioxidant enzymes (SOD2, GPx1, and GPx4), were assessed. To investigate the regulatory mechanism, we assessed Ucp3 mRNA abundance and UCP3 protein stability. We also performed UCP3 knockdown and overexpression experiments in C2C12 myotubes to determine the functional contribution of UCP3 to the protective effects of HDAC6 loss or inhibition. RESULTS:Hdac6 knockout or HDAC6 inhibition significantly attenuated dexamethasone-induced muscle atrophy, as evidenced by increased grip strength, restored muscle mass, enlarged muscle fiber diameter, and downregulated MuRF1/Atrogin-1 expression in mice. RNA-seq analysis identified DEX-responsive changes in redox-related pathways in Hdac6-deficient skeletal muscle, with Ucp3 among the DEX-responsive genes. Mechanistically, HDAC6 knockdown increased Ucp3 mRNA abundance without detectably altering UCP3 protein stability. This was accompanied by reduced mitochondrial superoxide, restored mitochondrial membrane potential, and increased expression of mitochondrial biogenesis markers and antioxidant enzymes. Importantly, UCP3 overexpression in C2C12 myotubes, without HDAC6 manipulation, was sufficient to attenuate dexamethasone-induced myotube atrophy. Functional rescue experiments showed that UCP3 knockdown reversed the antioxidant and anti-atrophic effects of HDAC6 knockdown. ACY-1215 attenuated dexamethasone-induced muscle atrophy in both mice and C2C12 myotubes. In C2C12 myotubes, UCP3 knockdown abolished the antioxidant and anti-atrophic effects of ACY-1215, demonstrating UCP3 dependence in the in vitro model. CONCLUSION:This study identifies UCP3-associated redox homeostasis as an important downstream mechanism linking HDAC6 inhibition to protection against dexamethasone-induced muscle atrophy. In C2C12 myotubes, UCP3 was required for the protective effects of HDAC6 knockdown and ACY-1215, whereas UCP3 overexpression was sufficient to attenuate dexamethasone-induced myotube atrophy. ACY-1215 also alleviated dexamethasone-induced muscle atrophy in mice, although the UCP3 dependence of this in vivo effect remains to be determined.

Introduction Sarcoidosis frequently involves intrathoracic lymph nodes and lung parenchyma and requires histological confirmation for diagnosis. Although endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is recommended for obtaining mediastinal samples, its diagnostic yield frequently necessitates additional transbronchial lung biopsy (TBLB) and/or endobronchial biopsy (EBB). EBUS transbronchial mediastinal cryobiopsy (EBUS-TBMC) can yield larger, well-preserved tissue samples than EBUS-TBNA alone. However, whether EBUS-TBMC alone is equivalent to conventional multimodal sampling (EBUS-TBNA combined with TBLB and/or EBB), and whether TBLB and EBB provide incremental diagnostic value when added to EBUS-TBMC, is still unclear.Methods and analysis In this study, 410 patients with suspected stage I/II sarcoidosis will be randomly assigned in a 1:1 ratio to either the EBUS-TBMC or EBUS-TBNA group. All participants will then undergo TBLB and EBB. The primary outcome will be the granuloma detection rate. The diagnostic sensitivity, negative predictive value and procedure-related complications will be selected for secondary outcomes. Statistical analysis will be performed using SPSS V.24.0, with non-inferior testing for the primary comparison.Ethics and dissemination Approval for this DETECTION-SAR-II trial was obtained by the China-Japan Friendship Hospital Ethics Committee (Ethics number: 2025-KY-075). Participants will be fully informed of objectives, protocol and potential risks of the study before enrolment and will provide written informed consent.Trial registration number NCT07246876.

INTRODUCTION:Undiagnosed exudative pleural effusions often require pleural biopsy for a definitive diagnosis. The optimal sampling method, particularly when medical thoracoscopy is compared with image-guided pleural biopsy, remains uncertain. METHODS:This systematic review and network meta-analysis included studies that reported on the diagnostic performance and safety of medical thoracoscopy and image-guided pleural biopsy approaches. The primary outcome of this study was diagnostic yield, and the secondary outcomes included other diagnostic parameters (e.g. sensitivity, negative likelihood ratio, and negative predictive value), post-procedure complications, and biopsy quality and number. A frequentist network meta-analysis was performed to compare and rank the diagnostic performance and safety of various pleural biopsy methods using a random-effects model. A subgroup analysis was performed according to the presence of pleural nodules or thickness and the type of biopsy needles used. RESULTS:An analysis of 64 studies involving 8744 patients revealed that rigid medical thoracoscopy had the highest diagnostic yield (95.0%), followed by cryobiopsy (93.1%), semirigid medical thoracoscopy (92.3%), and ultrasound elastography (UE)-guided biopsy (92.3%). Closed pleural biopsy had the lowest yield (75.1%). The current evidence is insufficient to establish the superiority of any biopsy method in terms of complications. The network meta-analysis ranked rigid medical thoracoscopy as having the highest overall diagnostic yield, closely followed by UE-guided biopsy, with no statistically significant differences between image-guided biopsy and rigid medical thoracoscopy. CONCLUSION:Closed pleural biopsy consistently has a low diagnostic yield and is not recommended as a first-line biopsy method for patients with undiagnosed exudative pleural effusions. Rigid medical thoracoscopy offers distinct clinical value for a complete visual inspection, large biopsies, and potential pleurodesis, particularly in suspected mesothelioma cases. The currently available evidence does not support the routine replacement of semirigid medical thoracoscopy with cryobiopsy. Computed tomography-guided biopsy may be preferred in cases involving thickening ≥10 mm or small target lesions. Conversely, ultrasound-guided biopsy may be appropriate for lesions measuring ≥3 mm with a clear acoustic window. UE-guided pleural biopsy shows promise as an emerging option, although the evidence is limited. In tuberculous pleurisy, medical thoracoscopy may offer higher diagnostic sensitivity in certain settings, particularly in high-prevalence areas. The current evidence is insufficient to establish a clear advantage for any biopsy method regarding the overall complication risk.

BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a severe and progressive disease with limited options for therapy. Mitsugumin 53 (MG53), a key factor involved in cell membrane repair, emerges as a protector in diverse disease models and cell injury. Although its role in pulmonary fibrosis is not well understood, this study focuses on exploring the function of MG53 in IPF and evaluating the therapeutic potential of recombinant MG53 protein. METHODS:Circulating MG53 levels were quantified in IPF patients and healthy controls. A pulmonary fibrosis model was induced in C57BL/6J mice using bleomycin (BLM), and the mice were then treated with either recombinant human MG53(rhMG53) or saline. In vitro, MLE-12 cells were subjected to TGF-β1 stimulation with or without rhMG53 to explore the affected mechanisms, with a focus on the TGF-β1/Smad signaling pathway and epithelial-mesenchymal transition (EMT). RESULTS:Circulating MG53 levels were significantly decreased in IPF patients and positively correlated with lung function parameters. Similarly, MG53 expression was decreased in the BLM-exposed mice lungs. Treatment with rhMG53 improved survival, attenuated weight loss, and enhanced pulmonary function in BLM-injured mice. Mechanistically, rhMG53 decreased TGF-β1 levels in bronchoalveolar lavage fluid and inhibited Smad2/3 phosphorylation both in vivo and in TGF-β1-stimulated MLE-12 cells. rhMG53 administration did not cause any signs of systemic toxicity. CONCLUSION:MG53 deficiency is associated with IPF severity, and supplementation with rhMG53 mitigates BLM-induced pulmonary fibrosis by preventing TGF-β1/Smad signaling and EMT. These findings highlight MG53 as a potential protein-based therapy and biomarker of pulmonary fibrosis.

Background Exudative pleural effusion often presents diagnostic challenges, with up to 25% of cases remaining undiagnosed after thoracentesis or closed pleural biopsy. Semi-rigid thoracoscopy is a widely used minimally invasive diagnostic method. However, its diagnostic yield is limited by small and superficial biopsy samples due to the lack of mechanical power, particularly in cases of thickened pleura or suspected mesothelioma. We had designed and developed a dual-function semi-rigid thoracoscope and semi-rigid forceps to improve sampling quality and depth. However, their diagnostic performance and safety, particularly compared with that of conventional semi-rigid thoracoscopy is still unclear. Methods This randomised controlled trial will enrol a total of 522 adults with exudative pleural effusions of unclear aetiology that remain undiagnosed after the initial investigations from 10 sites in China. Participants will be randomised (1:1:1) to undergo thoracoscopy using either a conventional semi-rigid thoracoscope (with flexible forceps) or a novel dual-function semi-rigid thoracoscope (with either semi-rigid forceps alone or a combination of flexible and rigid forceps). The primary outcome is diagnostic yield. Secondary outcomes include the biopsy success rate, incidence of procedure-related complications, biopsy specimen size and depth, histological interpretability, and adequacy of tissue for molecular marker analysis. Discussion We hypothesize that the dual-function semi-rigid thoracoscopy with semi-rigid forceps will achieve higher diagnostic yield than conventional semi-rigid thoracoscopy due to the larger and deeper sampling. If this hypothesis is validated, dual-function semi-rigid thoracoscopy could be a novel option for performing pleural biopsy for patients with unknown exudative pleural effusion. Trial registration This study has been registered at www.clinicaltrials.gov (ID: NCT06744725; Registration Date: 2024-12-19).

BACKGROUND:Sarcopenia, an important complication of chronic obstructive pulmonary disease (COPD), is significantly associated with increased mortality. Systemic inflammation is an important trigger of COPD-related skeletal muscle dysfunction. Calprotectin is a damage-associated molecular pattern involved in the inflammatory response, but its exact role and mode of action in COPD-related skeletal muscle dysfunction remain unclear. This study aimed to determine whether calprotectin is involved in COPD-related sarcopenia. METHODS:In this study, 235 patients with stable COPD were divided into the development (n = 117) and validation (n = 118) groups, and serum calprotectin concentrations were measured by enzyme-linked immunosorbent assays (ELISAs). Paquinimod, an oral calprotectin-specific inhibitor, was used to investigate the involvement of calprotectin in cigarette smoke (CS)-induced skeletal muscle dysfunction in vivo. RESULTS:Handgrip strength and quadriceps muscle strength, essential indicators of muscle strength, were negatively correlated with serum calprotectin levels (r = -0.367, p < 0.001; r = -0.409, p < 0.001). The 5-time sit-to-stand test results, which reflect endurance and physical strength, were positively correlated with serum calprotectin levels (r = 0.290, p = 0.006). Ultrasound measurement of the rectus femoris muscle revealed negative correlations of serum calprotectin levels with both muscle thickness (r = -0.448, p < 0.001) and cross-sectional area (r = -0.495, p < 0.001). Furthermore, serum calprotectin levels were significantly greater in patients with sarcopenia than in those without sarcopenia (90.09 ± 25.72 ng/mL vs. 59.56 ± 23.22 ng/mL, p < 0.001). Importantly, serum calprotectin levels could effectively predict sarcopenia in COPD patients in the development set (AUC = 0.811) and validation set (AUC = 0.805). In C57BL/6 mice with CS-induced muscle dysfunction, paquinimod (10 mg/kg/day) reduced CS-induced muscle mass loss (skeletal muscle weight 1.15% ± 0.09% vs. 1.33% ± 0.09%; p = 0.005) and increased the muscle cross-sectional area (1375 ± 536.9 μm2 vs. 2094 ± 470.2 μm2; p < 0.001). Paquinimod also reduced CS-induced muscle weakness, as indicated by increased grip strength (214.9 ± 31.38 g vs. 333.1 ± 34.93 g; p < 0.01). Paquinimod inhibited ubiquitin-proteasome system activity, reduced protein degradation marker levels, attenuated oxidative stress and increased antioxidant enzyme levels in CS-exposed mice. CONCLUSIONS:Serum calprotectin levels can be used to accurately predict sarcopenia in patients with COPD, and the calprotectin inhibitor paquinimod is a potential treatment for CS-induced skeletal muscle dysfunction.

INTRODUCTION:Transbronchial lung cryobiopsy (TBLC) is increasingly used to diagnose interstitial lung disease (ILD). However, the learning curve associated with this technique remains unclear. METHODS:This retrospective analysis included the first 100 patients suspected of having ILD for whom TBLC was performed by six physicians (three chief physicians and three attending physicians) across three centers in China. The diagnostic yield, procedural information, and complications were compared between consecutive groups of patients. Logistic regression was employed to analyze the median diagnostic yields across ten subgroups of operative experience, categorized in intervals of 10 patients, to delineate the learning curve. RESULTS:The overall multidisciplinary discussion (MDD)-based diagnostic rate for ILD after TBLC was 75% (450 of 600 procedures). The diagnostic yield increased with time. Learning curves revealed that chief physicians achieved proficiency after approximately 60 procedures and attending physicians after approximately 90. The sample biopsy was larger for chief physicians than for attending physicians (median, 19 mm2 vs. 15.25 mm2, p < 0.001). The complication rates were acceptable, with no significant difference between the chief and attending physicians over their first 100 procedures. CONCLUSION:TBLC is a safe and effective diagnostic approach for ILD, but operators require extensive training to achieve proficiency. Senior physicians reached competency earlier than junior colleagues (after several dozen procedures), underscoring the importance of structured training programs and standardized protocols for facilitating safe implementation.

Introduction Rigid thoracoscopy is an established diagnostic instrument for pleural diseases; however, it is limited by challenges related to manoeuvrability, patient comfort and operator learning curve. A novel dual-function semi-rigid thoracoscope with associated semi-rigid forceps has been engineered to integrate the diagnostic efficacy of rigid biopsy forceps with the ergonomic advantages of a semi-rigid system. The Dual-functIon Semi-rigid thoraCoscOpy Versus rigid thoracoscopy for the diagnosis of plEuRal disease trial was designed to evaluate whether this device achieves a diagnostic yield that is non-inferior to that of traditional rigid thoracoscopy.Methods and analysis This study is designed as a prospective, randomised, open-label, controlled, non-inferiority trial. A cohort of 92 patients presenting with undiagnosed exudative pleural effusion across five centres in China will be randomly allocated to undergo pleural biopsy using either a dual-function semi-rigid thoracoscope or a conventional rigid thoracoscope. The primary endpoint of the study is the diagnostic yield. The key secondary endpoints include procedural analgesic requirements, specimen quality, operator-assessed device performance, postprocedural pain and safety. A non-inferiority margin of 10% will be applied, with analyses conducted on both the intention-to-treat and per-protocol populations.Ethics and dissemination The study protocol was approved by the Ethics Committee of China-Japan Friendship Hospital (2026-KY-033). Written informed consent will be obtained from all participants before enrolment. The trial will be conducted in compliance with the Declaration of Helsinki and Good Clinical Practice guidelines. The results will be submitted for publication in a peer-reviewed journal.Trial registration number NCT07114783.

Rationale and objectives A direct comparison between endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), combined with endobronchial biopsy (EBB) and/or transbronchial lung biopsy (TBLB), and endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TBMC) for diagnosing sarcoidosis has not been conducted. The aim of the study was to evaluate whether EBUS-TBMC has the same or better diagnostic yield for sarcoidosis than EBUS-TBNA combined with standard bronchoscopic modalities (EBB and/or TBLB). Methods The records of patients with stage I/II sarcoidosis from four centres in China who underwent EBUS-TBMC or EBUS-TBNA combined with EBB and/or TBLB were retrospectively examined. Data on bronchoscopy examination records, pathological results of bronchoscopic biopsy modalities and postprocedural complications were collected. The outcomes were diagnostic yield and postprocedural complications. Measurements and main results A total of 438 patients were included in this study. Compared with EBUS-TBNA, EBUS-TBMC had greater diagnostic yield for sarcoidosis (95.1% versus 84.1%, p<0.001). The diagnostic yield of EBUS-TBNA combined with EBB and/or TBLB was greater than that of EBUS-TBNA alone. No significant differences in diagnostic yield were detected between EBUS-TBMC and EBUS-TBNA combined with EBB and/or TBLB or between EBUS-TBMC and EBUS-TBMC combined with EBB and/or TBLB. No major adverse complications related to the bronchoscopic procedure were observed. Conclusions EBUS-TBMC exhibited diagnostic yield equivalent to that of EBUS-TBNA combined with EBB and/or TBLB, and superior to that of EBUS-TBNA alone in stage I/II sarcoidosis. The addition of EBB and/or TBLB to EBUS-TBMC did not improve the diagnostic yield of EBUS-TBMC for sarcoidosis. EBUS-TBMC has the potential to reduce the need for EBB and TBLB.

Rationale Conventional bronchoscopy training often does not ensure lasting skill retention or adaptability to different anatomies, limiting real-world impact. This study used a digital-twin bronchoscopy simulator with various CT-derived bronchial tree models to better train novices. Objectives To explore training with various anatomically diverse bronchial tree models in novices' bronchoscopy performance. Methods 60 bronchoscopy-naive participants were randomly assigned to three groups (n=20 each): control (written instruction only), anatomic-uniformity (trained on one standard bronchial model) and anatomic-variety (trained on multiple patient-derived bronchial models). All participants performed two tests: test 1 on a standard model and test 2 on a new CT-derived model. Both tests were repeated 3 months later to assess skill retention. The primary comparison was between the anatomic-variety and anatomic-uniformity groups. Measurements and main results 60 participants completed tests 1 and 2. 55 returned at 3 months. In test 1, there were no significant differences between the anatomic-variety and anatomic-uniformity groups in diagnostic completeness (DC, 0 segments, p=0.576), structured progress (SP, 1 correct progression, p=0.091) and procedure time (31 s, p=0.831). In test 2, the anatomic-variety group had significantly higher DC (2.5 segments, p<0.001) and SP (9 progression, p<0.001) than the anatomic-uniformity group. At 3 months, the anatomic-variety group retained superior DC and SP scores in both tests despite slight declines. Conclusions Training with diverse anatomical models significantly enhanced bronchoscopy performance compared with repetitive practice on a single standardised model with partially maintained learning gains at 3 months.

Skeletal muscle atrophy is characterized by diminished muscle mass and function, which can arise from aging, nerve damage, and disease-related secondary atrophy. A central unresolved question is how these diverse stressors trigger common downstream mechanisms to cause sustained muscle deterioration. Here, we confirmed the role of cytosolic double-stranded RNA (dsRNA) in muscle atrophy across multiple murine models (aging, denervation and dexamethasone). Accumulated dsRNA released from damaged mitochondria aberrantly activated the innate immune sensor RIG-I signaling, triggering inflammation and muscle wasting. Moreover, adoptive transfer of mitochondrial dsRNA (mt-dsRNA) into healthy myotubes was sufficient to recapitulate the atrophic phenotype and activate RIG-I signaling. Furthermore, E3 ligase TRIM72 was identified as muscle-specific regulator of RIG-I signaling. TRIM72 attenuates the mt-dsRNA/RIG-I axis through two mechanisms. One is ubiquitinating RIG-I via interaction with its CARD domain to trigger degradation, the other is preserving mitochondria to prevent dsRNA leakage. Consequently, TRIM72 deficiency exacerbated atrophy while supplementation with recombinant TRIM72 (rhT72) improved muscle conditions and suppressed RIG-I signaling in vivo. In a clinic cohort, plasma TRIM72 level declined with muscle atrophy across multiple pathologies and rose with muscle recovery. Overall, our findings revealed mt-dsRNA/RIG-I axis as a key pathogenic pathway in muscle atrophy and identified TRIM72 as a key regulator and potential therapeutic agent.

The diagnosis of exudative pleural effusion is challenging. Although ultrasound-guided pleural biopsy (UGBx) is common, its effectiveness varies, especially in the absence of pleural abnormalities. New imaging techniques have been explored to improve UGBx outcomes, but the results remain inadequate. Recently, needle-based confocal laser endomicroscopy (nCLE) has been used to improve biopsy targeting and diagnostic yield through real-time cellular-level imaging; however, robust evidence is lacking. This trial aims to assess the diagnostic yield and safety of nCLE-assisted UGBx for unknown exudative pleural effusions. COLLABORATION-II is a multicenter randomized controlled study in China involving 324 participants across ten centers. Participants will be divided into two groups based on the ultrasound findings: Group 1 with pleural thickening (> 5 mm) and/or pleural nodularity, and Group 2 with thickness ≤ 5 mm and no nodularity. Each group will be randomly assigned to either the nCLE-assisted UGBx or UGBx arm at a 1:1 ratio, with a 12-month follow-up. The primary outcome is the overall diagnostic yield, while secondary outcomes include the biopsy success rate, diagnostic sensitivity for specific diseases, complication in incidence, and specimen characteristics, such as size, quality, interpretability, and adequacy for achieving molecular diagnosis. We hypothesize that the nCLE-assisted UGBx will achieve higher diagnostic yield than conventional UGBx by providing real-time, cellular-level visualization and targeted sampling of pathological areas. If this hypothesis is validated, nCLE-assisted UGBx could emerge as a novel and effective option for diagnosing patients with unknown exudative pleural effusion. This study has been registered at www.clinicaltrials.gov (Registration number: NCT07040241; Registration Date: 2025-06-26).

Introduction Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an established first-line technique for sampling mediastinal and/or hilar lymphadenopathy (MHL). However, its diagnostic accuracy is constrained by the procurement of small-volume specimens, which may not reliably capture the diagnostically relevant tissue. Needle-based confocal laser endomicroscopy (nCLE) provides real-time in vivo microscopic imaging and has the potential to facilitate targeted tissue acquisition. EBUS-guided transbronchial mediastinal cryobiopsy (EBUS-TBMC) can yield larger and better-preserved specimens; however, its availability is limited. This study aims to evaluate whether nCLE-assisted EBUS-TBNA is non-inferior to EBUS-TBMC for diagnostic yield for MHL. Methods and analysis The confocal laser endomicroscopy-assisted endobronchial ultrasound-guided needle aspiration (COLLABORATION III) trial is a prospective, multicentre, stratified, non-inferiority randomised controlled trial conducted across five centres in China. The study aims to enroll 640 adult participants presenting with unexplained MHL with a short-axis measurement ≥10 mm necessitating histopathological confirmation. Participants will be stratified based on the preprocedural likelihood of malignancy and randomised at a 1:1 ratio to undergo nCLE-assisted EBUS-TBNA or EBUS-TBMC. The primary endpoint is the overall diagnostic yield, defined as the proportion of procedures that obtain specimens sufficient for a definitive histological or cytological diagnosis, with a non-inferiority margin set at −10%. Secondary endpoints include diagnostic sensitivity for both malignant and benign conditions, rate of granuloma detection, procedure duration and incidence of adverse events. The primary analysis will be conducted on an intention-to-treat basis, supplemented by a per-protocol sensitivity analysis. Non-inferiority will be established if the difference in the diagnostic yield exceeds −10%. Ethics and dissemination The study protocol was approved by the Institutional Review Board of the China–Japan Friendship Hospital (2025-KY-388). Written informed consent will be required from all participants. These findings will be disseminated through peer-reviewed journal publications and conference presentations. Trial registration number COLLABORATION-III was prospectively registered at ClinicalTrials.gov (ID: NCT07040670 , Date: 2025–6-26).

Fibrotic interstitial lung diseases (ILDs), including idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF), are characterized by an irreversible decline in lung function and high mortality. While two approved antifibrotic therapies, nintedanib and pirfenidone, have been shown to alter the disease trajectory by slowing its progression, the disease remains incurable. This review summarizes current pharmacological treatments for fibrotic interstitial lung disease (f-ILD), mainly IPF and PPF; highlights novel antifibrotic targets such as the lysophosphatidic acid (LPA) receptor; outlines the therapeutic development pipeline; and discusses emerging strategies, including personalized medicine and early intervention.